TJTES 2019-5 by KAREPUBLISHING

ISSN 1306 - 696X

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi

Karaboğa İ. p. 433

Volume 25 | Number 5 | September 2019

www.tjtes.org

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Recep Güloğlu Editors M. Mahir Özmen Kaya Sarıbeyoğlu Mehmet Eryılmaz Osman Şimşek Publication Coordinator Mehmet Eryılmaz Former Editors Ömer Türel, Cemalettin Ertekin, Korhan Taviloğlu Section Editors Anaesthesiology & ICU Güniz Meyancı Köksal, Mert Şentürk Cardiac Surgery Münacettin Ceviz, Murat Güvener Neurosurgery Ahmet Deniz Belen, Mehmet Yaşar Kaynar Ophtalmology Cem Mocan, Halil Ateş Ortopedics and Traumatology Mahmut Nedim Doral, Mehmet Can Ünlü Plastic and Reconstructive Surgery Ufuk Emekli, Figen Özgür Pediatric Surgery Aydın Yagmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu

www.tjtes.org

THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ President (Başkan) Vice President (2. Başkan) Secretary General (Genel Sekreter) Treasurer (Sayman) Members (Yönetim Kurulu Üyeleri)

Orhan Alimoğlu Mehmet Eryılmaz Ali Fuat Kaan Gök Gökhan Akbulut Osman Şimşek Münevver Moran Adnan Özpek

ISSUED BY THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ YAYIN ORGANI Owner (Ulusal Travma ve Acil Cerrahi Derneği adına Sahibi) Editorial Director (Yazı İşleri Müdürü) Managing Editor (Yayın Koordinatörü) Publication Secretary (Yayın Sekreteri) Emblem (Amblem) Correspondence address (Yazışma adresi) Tel Fax (Faks)

Kaya Sarıbeyoğlu Kaya Sarıbeyoğlu Mehmet Eryılmaz Kerem Ayar Metin Ertem Ulusal Travma ve Acil Cerrahi Dergisi Sekreterliği Şehremini Mah., Köprülü Mehmet Paşa Sok., Dadaşoğlu Apt., No: 25/1, 34104 Şehremini, İstanbul +90 212 - 531 12 46 - 588 62 46 +90 212 - 586 18 04

p-ISSN 1306-696x • e-ISSN 1307-7945 • Included in Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ, EBSCO ve TÜBİTAK ULAKBİM Türk Tıp Dizini’nde yer almaktadır.) Publisher (Yayımcı): KARE Yayıncılık (KARE Publishing) • www.kareyayincilik.com • Design (Tasarım): Ali Cangül • Graphics (Grafikler): Edibe Çomaktekin • Linguistic Editor (İngilizce Editörü): Suzan Atwood • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): September (Eylül) 2019 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

KARE P U B L I S H I N G

www.tjtes.org

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 25

Number - Sayı 5 September - Eylül 2019

Contents - İçindekiler

Deneysel Çalışma - Experimental Experimental Studies - DeneyselStudy Çalışma 427-432 An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture Çekal ligasyon ve puncture yöntemi uygulanan sıçanlarda ertapenem etkinliğinin gösterilmesi Göl Serin B, Köse Ş, Yılmaz O, Yıldırım M, Akbulut İ, Serin Senger S, Akkoçlu G, Diniz G, Serin S 433-439 Caffeic acid phenethyl ester ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt pulmonary contusion model Kafeik asit fenetil ester künt pulmoner kontüzyon modelinde pulmoner enflmasyon ve apoptozisi Nf-κβ aktivasyonunu azaltarak iyileştirir Karaboğa İ

Original Articles - Orijinal Çalışma 440-446 Same-admission laparoscopic cholecystectomy in acute cholecystitis: the importance of 72 hours and oxidative stress markers Akut kolesistitde laparoskopik kolesistektominin zamanlaması: İlk 72 saat ve oksidatif stres belirteçlerinin önemi Arslan Onuk ZA, Gündüz UR, Koç Ü, Kızılateş E, Gömceli İ, Akbaş SH, Bülbüller N 447-452 Evaluation of the compliance between EEG monitoring (Bispectral IndexTM) and Ramsey Sedation Scale to measure the depth of sedation in the patients who underwent procedural sedation and analgesia in the emergency department Acil serviste girişimsel sedasyon ve analjezi uygulanan hastalarda sedasyon derinliğini ölçmede EEG monitörizasyonu (Bispectral IndexTM) ile Ramsey Sedasyon Skalası’nın uyumluluğunun değerlendirilmesi Avcı S, Bayram B, İnanç G, Gören N, Öniz A, Özgören M, Neşe Çolak Oray 453-460 The value of hematological parameters in acute pancreatitis Akut pankreatitte hematolojik parametrelerin değeri Yarkaç A, Köse A, Bozkurt Babuş S, Ateş F, Örekici Temel G, Ölmez A 461-466 The effects of early physiotherapy on biochemical parameters in major burn patients: A burn center’s experience Majör yanıklı hastalarda erken dönem fizyoterapinin biyokimyasal parametreler üzerine etkisi: Bir yanık merkezi deneyimi Çınar MA, Bayramlar K, Erkılıç A, Güneş A, Yakut Y 467-473 The diagnostic value of serum urokinase-type plasminogen activator receptor in acute appendicitis Akut apandisitte serum ürokinaz-tipi plazminojen aktivatör reseptörünün tanısal değeri Aygün A, Günaydın M, Özozan ÖV, Cihan M, Karakahya M 474-478 Motor cycle spoke wheel injuries in children: A preventable accident Çocuklarda motosiklet ispitli tekerlek yaralanmaları: Önlenebilir bir kaza Naumeri F, Qayyum B, Cheema NI, Sohail M, Bashir MM 479-483 Fournier’s gangrene: Review of 36 cases Fournier gangreni: Otuz altı olgunun incelenmesi Çalışkan S, Özsoy E, Sungur M, Gözdaş HT Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

vii

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 25

Number - Sayı 5 September - Eylül 2019

Contents - İçindekiler 484-488 The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome Travmatik torakolomber bileşke yaralanmalı hastalarda steroidin nörolojik sonuçlar üzerine etkisi İlik MK, Keskin F, Erdi F, Kaya B, Karataş Y, Kalkan E 489-496 Correlation of pelvic fractures and associated injuries: An analysis of 471 pelvic trauma patients Pelvik kırıklar ve bağlantılı yaralanmaların ilişkisi: Pelvik travmalı 471 hastanın istatistiksel analizi Saydam M, Şahin M, Yılmaz KB, Tamam S, Ünlü G, Atilla A, Bilgetekin Y, Güneş Tatar İ, Demir P, Akıncı M 497-502 A comparative study of pneumomediastinums based on clinical experience Pnömomediastinumların klinik deneyimlere dayalı olarak karşılaştırılması Sapmaz E, Işık H, Doğan D, Kavaklı K, Çaylak H 503-509 Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar: A single-center retrospective study Fitobezoara bağlı akut mekanik intestinal obstrüksiyon için tedavi stratejilerinin tartışılması: Tek merkezli geriye dönük bir çalışma Gök AFK, Sönmez RE, Kantarcı TR, Bayraktar A, Emiroğlu S, İlhan M, Güloğlu R 510-513 Carcinoid tumors of appendix presenting as acute appendicitis Akut apandisit gibi bulgu veren apendiks karsinoid tümörleri Barut B, Gönültaş F 514-519 Ipsilateral hip pain and femoral shaft fractures: Is there any relationship? İpsilateral kalça ağrısı ve femur şaft kırıkları: Herhangi bir ilişki var mı? Özmanevra R, Demirkıran ND, Hapa O, Balcı A, Havıtçıoğlu H

Case Series - Olgu Serisi 520-526 Our experience with dermal substitute Nevelia® in the treatment of severely burned patients Ağır yanık hastalarının tedavisinde deri eşdeğeri Nevelia® deneyimimiz Yiğitbaş H, Yavuz E, Beken Özdemir E, Önen Ö, Pençe HH, Meriç S, Çelik A, Çelebi F, Yastı AÇ, Sapmaz T, Zilan A, Turan M

Case Reports - Olgu Sunumu 527-530 Unilateral ischaemic retinopathy and bilateral subdural haemorrhage in an infant with non-accidental injury: An ophthalmological approach Kazaya sonucu oluşmamış yaralı bebekte tel taraflı iskemik retinopati ve iki taraflı subdural kanama: Bir oftalmolojik yaklaşım Ee CL, Abdullah AAM, Samsudin A, Khaliddin N 531-534 Heterotopic mesenteric and omental ossification incidentally found in a patient with multiple abdominal surgical operations because of gunshot injury Ateşli silah yaralanması nedeniyle birden fazla abdominal cerrahi operasyon geçiren bir hastada rastlantısal olarak bulunan heterotopik mezenterik ve omental ossifikasyon Çelik SU, Şenocak R, Hançerlioğulları O

viii

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

EXPERIMENTAL STUDY

An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture Başak Göl Serin, M.D.,1 Şükran Köse, M.D.,2 Osman Yılmaz, M.D.,3 Mehmet Yıldırım, M.D.,4 İlkay Akbulut, M.D.,2 Süheyla Serin Senger, M.D.,2 Gülgün Akkoçlu, M.D.,2 Gülden Diniz, M.D.,5 Süha Serin, M.D.6 1

Department of Infectious Diseases and Clinical Microbiology, Hopa State Hospital, Artvin-Turkey

Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences Tepecik Training and Research Hospital, İzmir-Turkey

2 3

Department of Laboratory Animal Science, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

Department of General Surgery, University of Health Sciences Bozyaka Training and Research Hospital, İzmir-Turkey

Department of Pathology, University of Health Sciences Tepecik Training and Research Hospital, İzmir-Turkey

Department of Emergency Medicine, Urla State Hospital, İzmir-Turkey

ABSTRACT BACKGROUND: Intra-abdominal adhesions are still a major problem which is expected to be reduced by the provision of bacterial decontamination. Various antibiotics have been used to prevent the formation of adhesion in the septic abdomen. This study aims to investigate the efficacy of ertapenem in sepsis of rats induced by cecal ligation and puncture. METHODS: Twenty-eight Wistar rats were divided into four groups randomly. In all groups, bacterial peritonitis was created by cecal ligation and puncture method. Group 1 was considered as sham group. Groups 2, 3 and 4 were given, respectively, saline, a single dose of ertapenem and a dose of ertapenem intraperitoneally every day. Intra-abdominal adhesions were assessed seven days after surgery by histopathological examination. Microbiological examination was performed through the ascites obtained. TNF-α was measured from blood taken from rats. RESULTS: Adhesion score decreased significantly by the application of ertapenem (p<0.001) and fibrosis scores were found to be significantly lower (p=0.005). Among all groups, the relationship between the decrease in the number of colonies and antibiotics application was not statistically significant (p=0.109). No statistically significant difference was found between the group given a single dose of ertapenem and the group given multiple ertapenem (p=1). CONCLUSION: Peritoneal lavage with ertapenem appears to be effective in preventing the adhesion in the septic abdomen. As no difference was detected at the end of a single dose and multiple-dose administration of antibiotics in the adhesion scores, a single dose after surgery seems to be enough. The findings suggest that the results should be evaluated in a clinical trial. Keywords: Ertapenem; rat; sepsis.

INTRODUCTION Sepsis is an important cause of mortality and morbidity. Studies have shown that inflammatory mediators and cytokines are released during sepsis.[1] Increased cytokine levels have been shown to correlate with the severity and mortality of the sepsis.[2]

Intra-abdominal sepsis and peritoneal adhesions occur as a part of the anatomical and functional regeneration process after the damage created by micro-organisms and toxins. These adhesions are made up of fibrin deposits and occur during the initial stage of inflammation. Cytokines also play a role in the formation of these adhesions. Fibrin deposits and intraabdominal adhesions are thought to be less common with

Cite this article as: Göl Serin B, Köse Ş, Yılmaz O, Yıldırım M, Akbulut İ, Serin Senger S, et al. An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture. Ulus Travma Acil Cerrahi Derg 2019;25:427-432. Address for correspondence: Başak Göl Serin, M.D. Hopa Devlet Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Bölümü, Artvin, Turkey Tel: +90 466 - 351 40 17 / 2328 E-mail: bskgl87@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):427-432 DOI: 10.5505/tjtes.2018.26050 Submitted: 06.05.2018 Accepted: 05.12.2018 Online: 09.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

427

Göl Serin et al. An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture

a decrease in bacterial contamination and inflammation.[3] A previous study evaluated the potential effects of several antibiotics used intra-abdominally, and it was reported that the degree of adhesiveness was lower in the antibiotic-treated groups than in the saline-treated control group.[4] However, to our knowledge, to date, there has been no comparison made of the dosages and durations of antibiotics, which remained under-researched. The present study aimed to investigate the effects on the formation of adhesions and cytokine levels of ertapenem lavage administered at different doses and durations in an experimental abdominal sepsis model.

MATERIALS AND METHODS The present study was conducted with the approval of Dokuz Eylül University Animal Experiment Ethics Committee (İzmir, Turkey). This study was performed on 28 Wistar strain male rats, each aged six months and weighing 200–250 g. All the rats were housed in standard animal chambers and cages at a room temperature of 20–22° C in the Animal Laboratory of Dokuz Eylül University, with a relative humidity of 50–60% and at 12/12 hours dark/light cycle until the end of the experiment. The rats were fed with standard feed and water (ad libitum). During the experiment, the rats were weighed daily, and the feed per cage and water consumption were monitored.

Surgical Procedure The rats were anesthetized using 45 mg/kg ketamine and 5 mg/kg xylazine intraperitoneally. Uncontrolled sepsis was established in rats with a procedure of cecal ligation and puncture. The rats were fasted for 12 hours before the first operation. The anterior abdominal wall was cleaned with 10% povidone-iodine and shaved. With a 3 cm incision to the abdominal wall, the abdominal cavity was opened under sterile conditions. The cecum was identified and dissected without any damage to the vascularization. The cecum was then ligated with 4/0 silk suture from the proximal of the ileocecal valve. The cecum was punctured twice with 22 gauge needles in the antimesenteric (avascular) region. After completion of these procedures, the anterior abdominal wall was sutured with 3/0 silk suture. All rats underwent fluid replacement with subcutaneous administration of 5 ml sodium chloride, and postoperative analgesia of 5 mg/kg xylose was administered subcutaneously.

All rats were reopened under anesthesia seven days after the first operation, and the abdomens were reopened and examined.

Evaluation Methods 1) Ascites evaluation: The quantity of ascites in all groups was determined and measured in cc. Bacterial culture analysis was performed from the ascites collected from the rats before each application and at the end of the experiment. Specimens taken for aerobic culture were incubated at 35°– 37°C for 24–48 hours, on a medium of 5% sheep blood agar, chocolate agar, and eosin methylene blue (EMB) agar. Samples taken for anaerobic culture were cultivated in 5% sheep blood agar added to chocolate agar, EMB agar, kanamycin and vancomycin and incubated in a GasPak jar at 35°–37°C for 48–72 hours. 2) Adhesion scoring: After seven days, the rats were sacrificed with high-dose ether. The abdomens were opened, and the terminal ileum and cecum walls were excised along with the adhesions on their surfaces. Adhesion scoring was applied to the materials examined according to the Bothin et al. method[5] (Table 1). Each adhesion was scored with 1 point, and the total score was obtained. The ascites accumulated within the abdomen was then collected. Table 1. Adhesion scoring Scoring Description 0

No adhesion

One adhesion band from the omentum to the target

organ +1

One adhesion band from the omentum to the

abdominal scar

One adhesion band from the omentum to another

place +1

One adhesion band from adnexa/epididymis to the

target organ

One adhesion band from adnexa/epididymis to the

abdominal scar

One adhesion band from adnexa/epididymis to

another place

Any other adhesion band except for those described

above

The rats were randomly separated into four groups one day after the surgical procedure. The first group was accepted as the sham group. Abdominal lavage of 2 ml saline was administered to group 2 as the saline group. A single dose of ertapenem (15 mg/kg, Invanz, MSD, Turkey) was administered intraperitoneally to group 3 and the same dosage of ertapenem (15 mg/kg, Invanz, MSD, Turkey) was administered intraperitoneally once daily for seven days to group 4. 428

Adhesion of the target organ to the abdominal wall

Adhesion of the target organ to the abdominal scar

Adhesion of the target organ to the intestine

Adhesion of the target organ to the liver and spleen

Adhesion to any organ

*The target organ was the cecum.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Göl Serin et al. An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture

3) Histopathological evaluation: The tissues were fixed in formol, then, embedded in paraffin blocks after the followup period. Sections 4–5 micrometers in thickness were cut and routine hematoxylin eosin and tricorn staining was applied. Evaluation of the extent of inflammatory cell infiltration (early neutrophil, late plasma, and monocytic cell), maturation of granulation tissue, collagen deposition, fibrosis, re-epithelization and neovascularization of the sections was made under a light microscope by a pathologist. The Abramov histological scoring system was used for the evaluation.[6] Each parameter was evaluated independently. The Abramov system scoring is shown in Table 2. 5) Biochemical and molecular evaluation: Blood samples were taken from the vena cava at the end of the experiment. The serum was separated from the samples and stored at -80°C. TNF-alpha molecule was studied using enzyme-linked immunosorbent assay (ELISA). Rat ELISA kits (Biosource International Inc. Camarillo, CA) were used. 6) Statistical analysis: Data analyses were performed using SPSS 22.0 (IBM Corporation, Armonk, New York, USA) software. Conformity of the data to normal distribution was evaluated using the Shapiro-Wilk test. The Kruskal-Wallis H

test was used together with Monte Carlo simulation results in the comparison of independent groups with respect to variables, while the Miller (1966) test was used for the Post Hoc analyses. Spearman’s rho test was used to examine the correlations of variables with each other. The data were analyzed at a 95% confidence level and a value of p<0.05 was accepted as statistically significant.

Exclusion Criteria 1) Rats that lost 20% of body weight would be sacrificed by high dose ether and excluded from the experiment. 2) In the case of any rat which died before the completion of the experiment, the adhesion scoring would be applied.

RESULTS No rat died or lost more than 20% of its body weight during the experiment. The adhesion scores of the groups were determined as median 2.5 (range: 1–3) in group 1, 11.4 (range: 6–15) in group 2, 4.67 (range: 1–6) in group 3, and 2.5 (range: 1–3) in group 4. The adhesion scores of the groups are shown in Figure 1. At the end of the antibiotic treatment, the decrease in the adhesion score was statistically significant (p<0.001).

Table 2. Histological scoring system Amount of granulation

0) Absent

tissue, collagen deposit

1) Low

2) Medium

3) High

Re-epithelization

0) Absent

1) Partial

2) Completed, but immature and

weak

3) Completed, mature

Neovascularization

0) Absent

1) Presence of 1–5 veins in the

large and enlargement area (LEA)

2) Presence of 6–10 veins in the LEA

3) Presence of more than 10 veins

The numbers of micro-organisms and colonies isolated according to the culture results of ascites from the rats are shown in Table 3. The decrease in the number of colonies following antibiotic administration was not found to be statistically significant (p=0.109) (Table 4). All the isolated microorganisms were identified as sensitive to ertapenem. The histological scores of the groups are shown in Table 5. The relationships between the antibiotic treatment and collagen deposit, neovascularization, fibrosis, and inflammatory cell accumulation were statistically significant in all groups (p<0.05 for all). There was no significant difference between the adhesion and histological scores when group 3 and group 4 were compared with each other (p>0.05). When all the groups were evaluated, the TNF-α values were determined to be highest in group 2 and lowest in group 1.

in the LEA 0) Fibroblast absent

12.0

1) Minimal fibroblast

10.0

2) Moderate fibroblast

3) Heavy fibroblast

Inflammatory cell count

1) Neutrophil between 0–25,

macrophage

2) Neutrophil between 26–50,

macrophage

3) >51 neutrophil, macrophage

Adhesion Score

Fibrosis

8.0 6.0 4.0 2.0 0.0

Sham

Saline

Single dose

Multiple dose

Figure 1. The adhesion score distribution of the groups.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

429

Göl Serin et al. An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture

Table 3. Distribution of breeding micro-organisms Groups

Isolated micro-organism

Number of colonies

Number of rats with reproduction

Group 1

No Reproduction

Group 2

Coagulase negative staphylococci

102 1

–

a-hemolytic streptococcus

103 1

Haemophilusparainfluenzae

103/104 2

Enterococcus spp.

103 1

Corynebacterium spp.

104 1

Escherichia coli

103 1

Group 3

a-hemolytic streptococcus

101 1

Enterococcus spp.

Escherichia coli

101/103 2 101 1

Haemophilusparainfluenzae

104 1

Group 4

104 1

Coagulase negative staphylococci

Haemophilusparainfluenzae

Table 4. Comparison of colony numbers between groups Group

Number of colonies

Median (min-max)

Group 1 (n=7)

0 (0–0)

Group 2 (n=7)

100 (105–0)

Group 3 (n=7)

2,857.1 (103–0)

Group 4 (n=7)

1,428.6 (104–0)

Total (n=28)

104 1

between coagulation and the fibrinolytic system is disrupted in favor of coagulation. As a result, fibrin deposits form a matrix for the growth of fibrinocollagenous tissue. Thus, fibroblasts are stored in the extracellular matrix. If the matrix metalloproteinase proenzymes (MMP) break the extracellular matrix, this results in normal healing. If MMP is inhibited by tissue inhibitors, peritoneal adhesions occur.[7] Plasminogen-activator inhibitor (PAI) has been detected at high levels in peritoneal tissue and fluid during intra-abdominal infections, thereby inhibiting fibrinolysis.[8] Inflammatory exudate accumulating in bacte-

31.8 (105–0)

P-value 0.109

Tumor necrosis factor

350.00

299.71

300.00

The TNF-α levels of the groups are shown in Figure 2. The findings showed that there was a significant correlation between the TNF-α values and the adhesion score (p<0.05).

250.00 200.00

Adhesions occur as a result of the contact of two damaged peritoneum surfaces. Following a peritoneal injury, the balance

233.29

213.57

247.64

150.00 100.00 50.00 0.00

DISCUSSION

244.00

Multiple dose Saline

Sham

Single dose

Total

Figure 2. TNF-α values of the groups.

Table 5. Comparison of the histopathological scores between the groups Group

Collagen deposit

Neovascularization

Fibrosis

Inflammatory cell accumulation

Median (min-max)

Group 1 (n=7)

1.00 (1–1)

1.29 (2–1)

1.00 (1–1)

1.29 (2–1)

Group 2 (n=7)

1.86 (2–1)

2.43 (3–2)

2.00 (3–1)

2.57 (3–2)

Group 3 (n=7)

1.57 (2–1)

2.43 (3–2)

1.43 (2–1)

2.71 (3–2)

Group 4 (n=7)

1.71 (2–1)

2.29 (3–2)

1.71 (2–1)

2.14 (3–2)

Total (n=28)

1.54 (2–1)

2.13 (3–1)

1.52 (3–1)

2.22 (3–1)

P-value 0.010 0.001 0.005

430

<0.001

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Göl Serin et al. An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture

rial peritoneal injury gives rise to fibrin deposits and adhesions. [9] In addition, fibroblasts invading the infection site contribute to the formation of collagen deposits and fibrous adhesions.[10] Adhesion is the first step in colonization and is an important virulence factor. Antibiotics exhibit anti-adhesive effects by inhibiting the expression of adhesions on the bacterial cell surface or by causing modifications in protein expression in bacteria. As a result, antibiotics prevent micro-organisms from binding to the cell surface.[11] Ertapenem is a carbapenem with a broad spectrum of effects. It has a limited effect against Pseudomonas Aeruginosa and Acinetobacter species,[12] and is therefore not expected to affect the resistance profiles of bacteria such as Pseudomonas spp. and Acinetobacter spp. as other carbapenems do. Ertapenem was preferred in this study because it is thought that future use will be more widespread due to the rational use of antibiotics and increased antibiotic resistance over time. No systemic antibiotic was administered, but the local antibiotic effect was evaluated in this study. The potential side effects of systemic antibiotics are thought to be reduced by the use of local antibiotics. Peritoneal lavage, although previously attempted in the treatment of intra-abdominal infections and adhesions, does not have precise results. Various studies[4,13,14] have reported the use of saline, antibiotic and fibrinolytic agents given during peritoneal lavage. Today, there is no universally accepted peritoneal lavage method and solution. As a result of giving antibiotics with peritoneal lavage, both positive and negative results have been obtained on adhesions. In the peritonitis model performed by researchers,[15] the findings showed that administration of rifampicin with peritoneal lavage both reduced adhesions and improved survival. Similarly, in another study,[4] researchers applied peritoneal lavage with metronidazole, imipenem, ceftriaxone and cefazolin, and showed that cephalosporins and imipenem decreased adhesions in the septic abdomen. In contrast, some studies[16] determined that peritoneal lavage with cefazolin and tetracyclin increased abdominal adhesions in the thenon-septic abdomen. In another research[17] compared chloramphenicol, clindamycin, piperacillin, tobramycin, ceftriaxone, and imipenem with saline, and reported that more adhesions occurred in the antibiotic groups compared to the saline group. In the present study, a statistically significant reduction was detected in the adhesion score at the end of antibiotic administration (p<0.001). There was also a significant correlation between antibiotic administration and reduction of the histological score (collagen deposit, fibrosis, inflammatory cell accumulation, neovascularization) (p<0.005). Recent studies[18] showed that enteric bacteria and antigens increased adhesion formation after laparotomy. Epithelial repair and secondary wound healing, such as mesothelial regeneration, were seen to be affected by bacterial contamination. It has been thought that a reduction in bacterial contamination and decreased local and systemic inflammation will result in fewer fibrin deposits and intra-abdominal adhesions.[3] In Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

the present study, there was a high correlation between adhesion score and number of colonies (r=0.539, p=0.003). No statistically significant decrease was found in the number of colonies in any of the antibiotic-treated groups in the current study (p=0.109). These may be attributed to various reasons, such as the late delivery of the acid materials in the laboratory and the inability to produce bacteria due to the difficulty in producing anaerobic bacteria. Theoretically, agents that inhibit contact between the serosal surfaces for more than three days have the potential to inhibit the formation of adhesions.[19] In this study, a single dose of ertapenem was administered to one group, and multiple doses to the other group in the form of a single dose every day for seven days. As a result, a difference was observed between the two groups (single dose and multiple dose) in terms of the duration of antibiotic treatment and adhesion formation but not in respect of the histopathological evaluation (p>0.05). The findings obtained in this study suggest that in cases of surgically-treated peritonitis, irrigation with ertapenem may reduce the formation of adhesions. TNF-α is an important mediator that has a role in early inflammation and also involved in the formation of adhesions by being released from the mesothelial cells. In a previous rat model experiment, a high level of TNF-α was detected in the peritoneal fluid and serum, correlated with the severity of adhesions.[20] In the present study, a significant correlation was also found between TNF-α level and the adhesion score. For the findings of the current study to come into clinical use, some modifications need to be made in practice. No intravenous antibiotics were administered during this study, and only local antibiotics were used. Intraperitoneal antibiotherapy alone has been shown to inhibit the entire peritoneal bacterial reproduction, and although the effect was brief, it has been seen to continue if repeated at frequent intervals. [21] Another study showed that administration of antibiotic peritoneal lavage concomitantly with systemic antibiotics to patients in generalized peritonitis reduced mortality, morbidity, and length of hospital stay.[22] Therefore, in clinical practice, it can be considered that intraperitoneal antibiotic administration alone may not suffice, and it should be administered together with intravenous antibiotherapy. If the present study comes into clinical use, drainage may be required to perform intraperitoneal lavage. However, drainage may bring about serious complications that may require surgical intervention, such as wound infection, bleeding from the abdominal vessels, and, more rarely, intestinal obstruction and/or incarceration.[23] It is thought that rational antibiotic use and the use of single-dose intraperitoneal ertapenem during the surgical procedure may be beneficial and sufficient to reduce current surgical complications. Since intra-abdominal adhesions may cause chronic abdominal pain, infertility, and ileus at later stages, the current experiment may be considered to contribute to 431

Göl Serin et al. An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture

the literature. There is a need for further studies and clinical practice on this subject. Conflict of interest: None declared.

REFERENCES 1. Cinel I, Dellinger RP. Advances in pathogenesis and management of sepsis. Curr Opin Infect Dis 2007;20:345–52. 2. Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis 2000;181:176–80. 3. Bicalho PR, Mayrink CA, Fernandes F, Alvarenga DG, Nunes TA, Reis FA, et al. Chlorhexidine as a factor that promotes peritoneal adhesions in rats with induced peritonitis. Acta Cir Bras 2013;28:641–5. 4. Kayaoğlu HA, Ozkan N, Yenidoğan E, Köseoğlu RD. Effect of antibiotic lavage in adhesion prevention in bacterial peritonitis. Ulus Travma Acil Cerrahi Derg 2013;19:189–94. 5. Bothin C, Okada M, Midtvedt T, Perbeck L. The intestinal flora influences adhesion formation around surgical anastomoses. Br J Surg 2001;88:143–5. 6. Abramov Y, Golden B, Sullivan M, Botros SM, Miller JJ, Alshahrour A, et al. Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model. Wound Repair Regen 2007;15:80–6. 7. Arung W, Meurisse M, Detry O. Pathophysiology and prevention of postoperative peritoneal adhesions. World J Gastroenterol 2011;17:4545–53. 8. van Goor H, de Graaf JS, Grond J, Sluiter WJ, van der Meer J, Bom VJ, et al. Fibrinolytic activity in the abdominal cavity of rats with faecal peritonitis. Br J Surg 1994;81:1046–9. 9. van Goor H, Bom VJ, van der Meer J, Sluiter WJ, Bleichrodt RP. Coagulation and fibrinolytic responses of human peritoneal fluid and plasma to bacterial peritonitis. Br J Surg 1996;83:1133–5. 10. Thompson JN, Whawell SA. Pathogenesis and prevention of adhesion formation. Br J Surg 1995;82:3–5.

11. Lorian V, Ernst J. Effects of antibiotics on bacterial structure and their pathogenicity. Pathol Biol (Paris) 1987;35(10 Pt 2):1370–6. 12. Shah PM, Isaacs RD. Ertapenem, the first of a new group of carbapenems. J Antimicrob Chemother 2003;52:538–42. 13. Kirdak T, Uysal E, Korun N. Assessment of effectiveness of different doses of methylprednisolone on intraabdominal adhesion prevention. [Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2008;14:188–91. 14. Günaydın M, Güvenç D, Yıldız L, Aksoy A, Tander B, Bıçakcı Ü, et al. Comparison of substances used for prevention of intra-abdominal adhesions: an experimental study in rats. Turkiye Klinikleri J Med Sci 2012;32:337–45. 15. Jallouli M, Hakim A, Znazen A, Sahnoun Z, Kallel H, Zghal K, et al. Rifamycin lavage in the treatment of experimental intra-abdominal infection. J Surg Res 2009;155:191–4. 16. Rappaport WD, Holcomb M, Valente J, Chvapil M. Antibiotic irrigation and the formation of intraabdominal adhesions. Am J Surg 1989;158:435–7. 17. Sortini D, Feo CV, Maravegias K, Carcoforo P, Pozza E, Liboni A, et al. Role of peritoneal lavage in adhesion formation and survival rate in rats: an experimental study. J Invest Surg 2006;19:291–7. 18. Cahill RA, Wang JH, Redmond HP. Enteric bacteria and their antigens may stimulate postoperative peritoneal adhesion formation. Surgery 2007;141:403–10. 19. Gomel V, Urman B, Gurgan T. Pathophysiology of adhesion formation and strategies for prevention. J Reprod Med 1996;41:35–41. 20. Kaidi AA, Gurchumelidze T, Nazzal M, Figert P, Vanterpool C, Silva Y. Tumor necrosis factor-alpha: a marker for peritoneal adhesion formation. J Surg Res 1995;58:516–8. 21. Krukowski ZH, Al-Sayer HM, Reid TM, Matheson NA. Effect of topical and systemic antibiotics on bacterial growth kinesis in generalized peritonitis in man. Br J Surg 1987;74:303–6. 22. Khan BA, Hassan G, Shant MS, Kadri SM, Rather RA. Role of intraperitoneal antibiotic lavage in peritonitis. JK Science 2003;2:67–9. 23. Loh A, Jones PA. Evisceration and other complications of abdominal drains. Postgrad Med J 1991;67:687–8.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Çekal ligasyon ve puncture yöntemi uygulanan sıçanlarda ertapenem etkinliğinin gösterilmesi Dr. Başak Göl Serin,1 Dr. Şükran Köse,2 Dr. Osman Yılmaz,3 Dr. Mehmet Yıldırım,4 Dr. İlkay Akbulut,2 Dr. Süheyla Serin Senger,2 Dr. Gülgün Akkoçlu,3 Dr. Gülden Diniz,5 Dr. Süha Serin6 Hopa Devlet Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Kliniği, Artvin Sağlık Bilimleri Üniversitesi Tepecik Eğitim ve Araştırma Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Kliniği, İzmir Dokuz Eylül Üniversitesi Tıp Fakültesi, Laboratuvar Hayvanları Bilimi Anabilim Dalı, İzmir 4 Sağlık Bilimleri Üniversitesi Bozyaka Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İzmir 5 Sağlık Bilimleri Üniversitesi Tepecik Eğitim ve Araştırma Hastanesi, Patoloji Kiliniği, İzmir 6 Urla Devlet Hastanesi, Acil Tıp Kliniği, İzmir 1 2 3

AMAÇ: Karın içi yapışıklıklar halen önemli bir sorundur. Bakteriyel dekontaminasyon sağlanmasıyla karın içi yapışıklıkların azalacağı düşünülmektedir. Geçmişte çeşitli antibiyotikler septik karında adezyon formasyonunun önlenmesi için kullanılmıştır. Bu çalışmanın amacı çekal ligasyon ve puncture yöntemi ile sepsis modeli oluşturulan sıçanlarda ertapenem etkinliğinin gösterilmesidir. GEREÇ VE YÖNTEM: Çalışmada ağırlıkları 200–250 gr arasında değişen, erkek cinsi, 28 adet Wistar cinsi sıçan kullanıldı. Sıçanlar rastgele dört gruba ayrıldı. Tüm gruplarda çekal ligasyon ve puncture yöntemiyle bakteriyel peritonit oluşturuldu. Grup 1 sham grubu olarak kabul edildi; grup 2’ye serum fizyolojik (SF), grup 3’e ertapenem tek doz, grup 4’e ertapenem her gün günde bir doz intraperitoneal yolla verildi. Cerrahiden yedi gün sonra karın içi yapışıklıklar değerlendirildi, histopatolojik inceleme yapıldı, elde edilen asitesten mikrobiyolojik inceleme yapıldı. Sıçanlardan alınan kan örneklerinden TNF-α bakıldı. BULGULAR: Ertapenem uygulaması ile adezyon skoru anlamlı derecede azaldı (p<0.001) ve fibrozis skorları anlamlı derecede düşük olarak bulundu (p=0.005). Tüm gruplar arasında, antibiyotik uygulaması ile koloni sayısındaki azalma arasındaki ilişki anlamlı bulunmadı (p=0.109). Tek doz ertapenem verilen grup ile multipl (çok doz) ertapenem verilen grup arasında istatistiksel olarak fark saptanmadı (p=1). TARTIŞMA: Bu veriler ışığında septik karında, ertapenemle peritoneal lavajın adezyonu önlemede etkin olduğu görülmektedir. Tek doz ile çok doz antibiyotik uygulaması sonunda adezyon skorlarında fark saptanmadığından operasyon sonrası tek doz uygulamanın yeterli olabileceği düşünülmektedir. Sonuçların bir klinik çalışmada değerlendirilmesi gerektiği düşünülmektedir. Anahtar sözcükler: Ertapenem; sepsis; sıçan. Ulus Travma Acil Cerrahi Derg 2019;25(5):427-432

432

doi: 10.5505/tjtes.2018.26050

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

EXPERIMENTAL STUDY

Caffeic acid phenethyl ester ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt pulmonary contusion model İhsan Karaboğa, Ph.D. Department of Emergency and Disaster Management, Tekirdağ Namık Kemal University School of Health, Tekirdağ-Turkey

ABSTRACT BACKGROUND: Pulmonary contusion (PC) is an important life-threatening clinical condition characterized by lung injury and inflammation. Caffeic acid phenethyl ester (CAPE) is a biological agent with potent antioxidant and anti-inflammatory effects. This study aimed to investigate the potential effects of CAPE on tissue damage, nuclear factor kappa-beta (Nf-κβ) activity, inducible nitric oxide synthase (iNOS) synthesis, and pulmonary apoptosis in an experimental PC model. METHODS: Forty adult Wistar albino rats were used in this study and divided into four groups as follows: control, PC, PC + CAPE, and CAPE. CAPE was administered intraperitoneally for seven days following PC formation (10 µmol/kg, dissolved in dimethyl sulfoxide). Wet/dry weight ratio in lung tissue was determined. The pulmonary tissue was examined using hematoxylin–eosin and Masson’s trichrome histochemical staining and also by scanning electron microscopy. Nf-κβ and iNOS activities in the lungs were determined by the indirect immunohistochemical method. Pulmonary apoptosis was detected by the TUNEL method. RESULTS: Increased leukocyte infiltration score, pulmonary edema, alveolar damage, and increased Nf-κβ and iNOS activities were determined in the PC group. CAPE administration inhibited Nf-κβ and iNOS activities and pulmonary apoptosis. CONCLUSION: In this study, the findings showed that CAPE inhibited tissue damage by suppressing inflammatory mediators of Nfκβ and iNOS activities. Also, CAPE was found to be protective in the lung tissue and could be used as a therapeutic agent. Keywords: Apoptosis; inflammation; iNOS, Nf-κβ; pulmonary contusion.

INTRODUCTION Pulmonary contusion (PC) is the most important intrathoracic injury of blunt chest injuries that arises from falls or traffic accidents in children and adults.[1,2] PC is also the most important injury that triggers the local and systemic inflammatory response in multiple traumas.[3] Cytokines and other pro-inflammatory mediators released from macrophages and leukocytes, which are active after blunt chest trauma, cause inflammation of lung tissue.[4] Pulmonary edema, alveolar– capillary permeability, surfactant dysfunction, and ventilation– perfusion mismatch are known to be the consequences of PC.[5,6] No specific treatment option is available for patients with blunt chest trauma, which is a concern in emergency

medicine and trauma care and symptomatic treatment is generally administered.[4] Nuclear factor kappa-beta (Nf-κβ) is a transcription factor that has a central role in many biological processes, such as inflammation, apoptosis, and infections.[7,8] Activation of Nf-κβ induces inflammation by triggering the transcription of pro-inflammatory genes.[9] Recent studies reported that exposure to chest trauma caused Nf-κβ activation and increased the synthesis of pro-inflammatory cytokines, such as inducible nitric oxide synthase (iNOS) and interleukin-1 beta (IL-1β).[10,11] Chest trauma resulting in macrophage activation and increased pro-inflammatory cytokine synthesis induced apoptosis in pulmonary alveolar epithelial cells.[3,5]

Cite this article as: Karaboğa İ. Caffeic Acid Phenethyl Ester Ameliorates Pulmonary Inflammation and Apoptosis Reducing Nf-κβ Activation in Blunt Pulmonary Contusion Model. Ulus Travma Acil Cerrahi Derg 2019;25:433-439. Address for correspondence: İhsan Karaboğa, M.D. Namık Kemal Üniversitesi Sağlık Yüksekokulu, Acil Yardım ve Afet Yönetimi Bölümü, 59030 Tekirdağ, Turkey Tel: +90 282 - 250 31 19 E-mail: ihsankaraboga@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):433-439 DOI: 10.5505/tjtes.2018.51694 Submitted: 01.08.2018 Accepted: 04.12.2018 Online: 05.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

433

Karaboğa et al. CAPE ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt PC model

Caffeic acid phenethyl ester (CAPE), one of the most important biological components of propolis produced by worker bees, has strong anti-inflammatory and antiapoptotic effects. [12,13] Koksel et al.[14] (2006) demonstrated that CAPE suppressed antioxidative stress in the lung tissue and reduced inflammation in the lipopolysaccharide (LPS)-induced lung injury model in rats. The present study aimed to reveal the potential effects of CAPE on inflammation and apoptotic processes using light and scanning electron microscopic methods in the rat chest trauma model.

MATERIALS AND METHODS Experimental Design This study was performed at Tekirdag Namık Kemal University Application and Research Centre for Experimental Animals after obtaining permission from the local ethics committee (Permission number: 17/10/2017-7). Forty adult male (8-week-old) Wistar albino rats were divided into four groups as follows: control (n=10), PC (n=10), PC + CAPE (n=10), and CAPE. Chest trauma was created with the model previously described by Raghavendran et al.[15] (2005). CAPE treatment was applied to the chest trauma model and chest trauma + CAPE groups for seven days dissolved in dimethyl sulfoxide (10 µmol/kg, intraperitoneally). During the experimental period, the animals were kept under standard laboratory conditions (22±2°C; 60% humidity; 12/12 dark–light cycles) and fed ad libitum with the standard diet. At the end of the seventh day, the rats were anesthetized (ketamine–xylazine; 90–10 mg/kg) and sacrificed by drawing blood from the heart-opening through the midline. The left lung lobe was evaluated for edema and the right lung lobe for light and electron microscopic analysis.

Wet/Dry Weight Ratio The fresh left superior lobe from each rat was weighed quickly after sacrificing for the evaluation of pulmonary edema. Wet/ Dry (W/D) weight ratio was calculated by reweighing samples held for 24 h at 80°C according to a previous study.[16]

Histopathological Analysis Lung tissue specimens were fixed in 10% neutral formalin. After fixation, paraffin blocks were prepared using routine histological methods. Five-micrometer-thick sections were stained with hematoxylin–eosin (H&E) and Masson’s trichrome stains. Histopathological changes, such as alveolar edema, vascular congestion, hemorrhage, and leukocyte infiltrations, were assessed in lung tissue. Extravascular leukocyte counts were determined and scored in H&E-stained sections (0, no extravascular leukocytes; 1, <10 leukocytes; 2, 10–45 leukocytes; 3, >45 leukocytes) to determine the severity of inflammation.[17] The distribution of connective tissue and the thickening of the alveolar wall were confirmed by Masson’s trichrome staining in lung tissue. All histological examinations were performed using Olympus CX41 (Olympus, Japan) light 434

microscope and image analysis system (Kameram Gen 2.1 Image Analysis Software, Istanbul, Turkey).

Immunohistochemical Staining iNOS and Nf-κβ immunohistochemical markers were used for the indirect immunohistochemical method. Primer antibodies (iNOS: NB300-605; Nf-κβ: NB100-56055) were obtained from Novus Biologicals (Littleton, CO, USA). Biotinylated secondary antibody and streptavidin peroxidase (Ultra Vision Detection System-HRP kit, Thermo Scientific/Lab Vision, Fremont, CA, USA) were used according to the manufacturer’s instructions. Further, 3-amino-9-ethylcarbazole was used for iNOS staining, and 3,3’-diaminobenzidine chromogen was used for Nf-κβ staining to create contrast. Contrasting stains were made with Mayer’s hematoxylin. iNOS and Nf-κβ positive stained cell numbers were expressed as positive stained cells/mm2 for each group in lung tissue.

Apoptosis Apoptotic cells in the lung tissue were detected by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method (S7101 ApopTag Plus Peroxidase In Situ, Merck Millipore, Darmstadt, Germany). Apoptotic cells identified using intense brown nuclear staining were calculated as positive cells/mm2 for each group.

Scanning Electron Microscopy Analysis The specimens fixed in 2% 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffered glutaraldehyde solution overnight at 4°C were used for ultrastructural analysis of lung tissue. After fixation, the tissues were rinsed with 0.1 M HEPES and dehydrated with ethanol. They were dried using hexamethyldisilazane. The specimens were examined using scanning electron microscopy (SEM) (Quanta Feg 250, FEI, USA) at Tekirdag Namık Kemal University Scientific and Technological Research and Application Center.

Statistical Analysis Data were evaluated using the PASW Statistics 18.0.0 (SPSS Inc, IL, USA) statistical program. The numerical parameters of the groups were evaluated using a nonparametric test (Kruskal–Wallis), and the significance of the values obtained in the two-way comparison was measured using the Mann– Whitney U test. P-values <0.05 were considered statistically significant.

RESULTS Effects of CAPE On Pulmonary Architecture Histopathological changes in the lungs were assessed using H&E and Masson’s trichrome staining under a light microscope. Figure 1 shows the general tissue structure and infiltration score in H&E-stained lung sections. The control group exhibited a normal histological structure (Fig. 1a). Intense inUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Karaboğa et al. CAPE ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt PC model

(a)

(b)

(c)

(d)

(e)

(f)

2.5 2

1.5

6.00

Wet/dry weight ratio

Leukocyte inflammation scores

3.5

0.5 0

Control

PC+CAPE

CAPE

5.00 4.00 3.00

2.00 1.00 0

Control

PC+CAPE

CAPE

Figure 1. Effects of CAPE on pulmonary tissue. (a) Control, normal histological architecture. (b) PC, peribronchial and alveolar inflammation. (c) PC + CAPE, decreased inflammation in lung tissue. (d) CAPE, no histopathological change. (e) Lung leukocyte inflammation scores. (f) Effects of CAPE on W/D weight ratios (arrowhead; leukocyte infiltration, scale bar; 100 µm, H&E, *p<0.001 compared with the control group; **p<0.001 compared with the PC group).

flammatory cell infiltration was seen in the PC group (Fig. 1b). Inflammatory cell infiltration in the PC + CAPE group was attenuated compared with that in the chest trauma group (Fig. 1c). The CAPE group showed normal histological architectures similar to that in the control group (Fig. 1d). As shown in Figure 1e, CAPE treatment caused a significant reduction in the leukocyte infiltration score.

The W/D weight ratios determined as pulmonary edema size are shown in Figure 1f. The PC group showed increased W/D ratio compared with the control group (p<0.001). The CAPE-administered group exhibited significantly decreased W/D ratio compared with the PC group (p<0.001). No significant difference in W/D ratio was observed between the control and CAPE groups.

(a)

(b)

(c)

(d)

Figure 2. Masson’s trichrome–stained pulmonary tissue. (a) Control. (b) PC, increased edema and alveolar infiltration. (c) PC + CAPE, decreased infiltration. (d) CAPE group similar to the control group (Masson’s trichrome, scale bar; 100 µm).

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

435

Karaboğa et al. CAPE ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt PC model

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h) Figure 3. SEM analysis of pulmonary tissue. (a and b) Control, normal ultrastructural architecture. (c and d) PC, increased infiltration and alveolar degeneration. (e and f) PC + CAPE, decreased parenchymal infiltration and improved the alveolar structure. (g and h) CAPE, normal lung tissue (right panel, 200×; left panel, 1000×).

The findings of Masson’s trichrome staining revealed that the chest trauma caused thickened alveolar wall and edema or increased connective tissue in areas of inflammation on comparing the control and PC groups (Fig. 2a and 2b). In addition,

(b)

(d)

(e) iNOS hositive-stained cell/mm2

(a)

436

18 16 14 12 10 8 6 4 2 0

Masson’s trichrome staining showed evidence of decreased inflammation in the CAPE-treated group (Fig. 2c). SEM findings of lung tissue examined at different magnifica-

(c)

* Control

** PC+CAPE

CAPE

Figure 4. Immunohistochemical examination of nucleus-located Nf-κβ expression in lung tissue. (a) Control. (b) PC. (c) PC + CAPE. (d) CAPE. (e) Distribution of Nf-κβ-positive stained nuclei of groups (Immunperoxidase, arrows; Nf-κβ-positive cells, counterstain; Mayer’s hematoxylin, scale bar; 100 µm; *p<0.001 compared with the control group; **p<0.001 compared with the PC group).

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Karaboğa et al. CAPE ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt PC model

(b)

(d)

(e) Nf-κβ positive-stained cell/mm2

(a)

(c)

20 15 10 5 0

Control

tions are presented in Figure 3. SEM analysis results were consistent with the findings of H&E and Masson’s trichrome staining. Increased edema, infiltration, and alveolar disruption were found in the chest trauma group (Fig. 3c-d). Decreased pathological degeneration was detected in the PC + CAPE group, and the observations were consistent with the findings of the light microscopic examination (Fig. 3e-f).

(e) Apoptotic cell numbers/mm2

(d)

CAPE

The Nf-κβ immunohistochemical expression was observed as nuclear brown staining. A statistically significant decrease in the number of positively stained cells was noted in the group treated with CAPE despite the increase in the Nf-κβ immunohistochemical expression in the PC group (p<0.001, Fig. 5b and c). The control and CAPE groups were similar in

The immunohistochemical expression of iNOS is shown in Figure 4. The control group showed rare iNOS immunoreactivity in some alveolar epithelial cells (Fig. 4a). iNOS ex-

(b)

PC+CAPE

pression increased, especially in the areas of inflammation, in the PC group (Fig. 4b). Decreased expression was detected in the PC + CAPE group compared with the PC group (Fig. 4c). The CAPE group was similar to the iNOS expression control group (Fig. 4d). iNOS-positive staining cell counts of the groups are presented in Figure 4e.

Effects of CAPE on iNOS and Nf-κβ Immunoreactivity

(a)

Figure 5. Effects of iNOS activity of CAPE. (a) Control. (b) PC. (c) PC + CAPE. (d) CAPE. (e) Distribution of iNOS-positive cell numbers in groups (arrows, iNOS-positive cells; counterstain, Mayer’s hematoxylin; scale bar, 100 µm; *p<0.001 compared with the control group; **p<0.001 compared with the PC group).

(c)

35 30 25 20 15 10

5 0

Control

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

PC+CAPE

CAPE

Figure 6. Apoptotic cells in lung tissue. (a) Control, a few apoptotic cells. (b) PC, increased number of apoptotic cells in contused lung tissue. (c) Decreased number of apoptotic cells. (d) Rare apoptotic cells in lung tissue. (e) Distribution of apoptotic cells in groups (scale bar, 100 µm; arrows, TUNEL-positive stained apoptotic cells; *p<0.001 compared with the control group; **p<0.001 compared with the PC group).

437

Karaboğa et al. CAPE ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt PC model

terms of Nf-κβ immunohistochemical expression (Fig. 5a–e).

Effects of CAPE On Pulmonary Apoptosis The number of apoptotic cells in the lung tissue was determined by the TUNEL method, which marked the broken DNA ends. The findings are presented in Figure 6. An increased TUNEL-positive cell number was detected in the PC group compared with the control group (p<0.001, Fig. 6b and c). The apoptotic cell number showed a significant decline in the CAPE-treated group compared with the PC group (Fig. 6e). These results clearly demonstrated the potential antiapoptotic effects of CAPE in the lung tissue after chest trauma.

DISCUSSION PC is an important clinical problem accompanied by multiple traumas or chest trauma. PC affects the patients’ prognosis in emergency medicine.[18] One of the most important pathophysiological factors in PC that arises from blunt chest trauma is the progressive inflammatory response.[11,19] An excessive inflammatory response leads to increased alveolar–capillary permeability, leukocyte infiltration, edema, and respiratory distress.[20,21] Moreover, PC is associated with the increased pro-inflammatory cytokine release and alveolar cell apoptosis.[3,22] Thus, effective treatment is the most important issue in managing patients with PC and preventing complications. This study used different methods in the experimental PC model to demonstrate that CAPE supported tissue healing by suppressing inflammation in the lung tissue. Histopathological changes, such as infiltration, edema, and alveolar deterioration, in the pulmonary tissues of experimental PC models, have been revealed in many studies.[23,24] Sırmalı et al.[25] (2013) showed that CAPE inhibited tissue damage by its antioxidative action in the rat PC model. Consistent with the findings of the aforementioned study, CAPE improved lung tissue damage in the present study. In addition, histopathological changes in the lung tissue were also demonstrated in this study using the Masson’s trichrome stain. Moreover, SEM analysis results supported the findings. This novel study showed that CAPE inhibited apoptosis by reducing the pulmonary levels of pro-inflammatory mediators iNOS and Nf-κβ in the PC model. The Nf-κβ/Rel transcriptional family has a vital role in the inflammatory process because of the ability of pro-inflammatory genes to induce transcription.[26] Nuclear translocation of cytoplasmic complexes of Nf-κβ leads to the induction of pro-inflammatory cytokines, chemokines, adhesion molecules, and iNOS.[10] Nf-κβ has been reported to be overexpressed in many inflammatory diseases, such as inflammatory bowel diseases, asthma, multiple sclerosis, and rheumatoid arthritis.[7,26] Experimental studies demonstrated the role of Nf-κβ activation in pulmonary damage that arises from chest trauma. 438

Relja et al.[22] (2018) reported that increased Nf-κβ activation in the blunt chest trauma model was associated with local tumor necrosis factor-alpha (TNF-α) and leukocyte infiltration. Similarly, Wu et al.[27] (2013) showed that Nf-κβ increased in proportion to the level of systemic TNF-α and IL-1β in an experimental pulmonary contusion model. In the present study, increased Nf-κβ activation consistent with histopathological changes was demonstrated immunohistochemically. Nitric oxide (NO) is involved in biological functions, including inflammation in the lung. iNOS activity causes an increase in NO production in the lung.[28] NO combines rapidly with oxygen radical superoxide in the lungs, leading to the formation of highly toxic and reactive nitrogen species, such as peroxynitrite. [17] In PC models, damage to lung tissue is associated with NO, and iNOS activity inhibits tissue destruction and apoptosis. [29,30] The present study also showed that CAPE administration improved the tissue structure with decreasing iNOS activity and significantly reduced the number of apoptotic cells in the lungs. CAPE has been reported to suppress NO production and iNOS activity in different in vivo and in vitro models.[31–33]

Conclusions

In addition to the data obtained from a previous study reporting that CAPE inhibited oxidative stress and inhibited tissue damage,[25] this study used light and electron microscopic methods to demonstrate that CAPE reduced tissue damage by suppressing Nf-κβ and iNOS activity in the lung tissue. Therefore, CAPE can be used as a powerful anti-inflammatory agent to prevent tissue damage resulting from chest trauma and to suppress inflammation.

Acknowledgment This study was supported by Tekirdag Namık Kemal University, Scientific Research Projects Commission (NKUBAP.23. GA.18.160). Conflict of interest: None declared.

REFERENCES 1. Ismail MF, al-Refaie RI. Chest trauma in children, single center experience. [Article in English, Spanish]. Arch Bronconeumol 2012;48:362–6. 2. Inan M, Ayvaz S, Sut N, Aksu B, Basaran UN, Ceylan T. Blunt chest trauma in childhood. ANZ J Surg 2007;77:682–5. 3. Seitz DH, Perl M, Mangold S, Neddermann A, Braumüller ST, Zhou S, et al. Pulmonary contusion induces alveolar type 2 epithelial cell apoptosis: role of alveolar macrophages and neutrophils. Shock 2008;30:537–44. 4. Türüt H, Ciralik H, Kilinc M, Ozbag D, Imrek SS. Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin on inflammatory and oxidant-antioxidant status after lung contusion in rats. Injury 2009;40:521–7. 5. Topcu-Tarladacalisir Y, Tarladacalisir T, Sapmaz-Metin M, Karamustafaoglu A, Uz YH, Akpolat M, et al. N-Acetylcysteine counteracts oxidative stress and protects alveolar epithelial cells from lung contusion-induced apoptosis in rats with blunt chest trauma. J Mol Histol 2014;45:463–71. 6. Cohn SM. Pulmonary contusion: review of the clinical entity. J Trauma

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Karaboğa et al. CAPE ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt PC model 1997;42:973–9. 7. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol 2018;18:309–24. 8. Matteucci C, Minutolo A, Marino-Merlo F, Grelli S, Frezza C, Mastino A, et al. Characterization of the enhanced apoptotic response to azidothymidine by pharmacological inhibition of NF-kB. Life Sci 2015;127:90–7. 9. Gross CM, Kellner M, Wang T, Lu Q, Sun X, Zemskov EA, et al. LPSinduced Acute Lung Injury Involves NF-κB-mediated Downregulation of SOX18. Am J Respir Cell Mol Biol 2018;58:614–24. 10. Ehrnthaller C, Flierl M, Perl M, Denk S, Unnewehr H, Ward PA, et al. The molecular fingerprint of lung inflammation after blunt chest trauma. Eur J Med Res 2015;20:70. 11. Ayvaz S, Aksu B, Karaca T, Cemek M, Tarladacalisir YT, Ayaz A, et al. Effects of methylene blue in acute lung injury induced by blunt chest trauma. Hippokratia 2014;18:50–6. 12. Akyol S, Ugurcu V, Altuntas A, Hasgul R, Cakmak O, Akyol O. Caffeic acid phenethyl ester as a protective agent against nephrotoxicity and/or oxidative kidney damage: a detailed systematic review. ScientificWorldJournal 2014;2014:561971. 13. Kus I, Colakoglu N, Pekmez H, Seckin D, Ogeturk M, Sarsilmaz M. Protective effects of caffeic acid phenethyl ester (CAPE) on carbon tetrachloride-induced hepatotoxicity in rats. Acta Histochem 2004;106:289–97. 14. Koksel O, Ozdulger A, Tamer L, Cinel L, Ercil M, Degirmenci U, et al. Effects of caffeic acid phenethyl ester on lipopolysaccharide-induced lung injury in rats. Pulm Pharmacol Ther 2006;19:90–5. 15. Raghavendran K, Davidson BA, Woytash JA, Helinski JD, Marschke CJ, Manderscheid PA, et al. The evolution of isolated bilateral lung contusion from blunt chest trauma in rats: cellular and cytokine responses. Shock 2005;24:132–8. 16. Kao MC, Yang CH, Sheu JR, Huang CJ. Cepharanthine mitigates proinflammatory cytokine response in lung injuryinduced by hemorrhagic shock/resuscitation in rats. Cytokine 2015;76:442–8. 17. Basaran UN, Ayvaz S, Aksu B, Karaca T, Cemek M, Karaboga I, et al. Desferrioxamine reduces oxidative stress in the lung contusion. ScientificWorldJournal 2013;2013:376959. 18. Boybeyi O, Bakar B, Aslan MK, Atasoy P, Kisa U, Soyer T. Evaluation of dimethyl sulfoxide and dexamethasone on pulmonary contusion in experimental blunt thoracic trauma. Thorac Cardiovasc Surg 2014;62:710–5. 19. Rocksén D, Gryth D, Druid H, Gustavsson J, Arborelius UP. Pathophysiological effects and changes in potassium, ionised calcium, glucose and haemoglobin early after severe blunt chest trauma. Injury 2012;43:632–7. 20. Aksu B, Ayvaz S, Aksu F, Karaca T, Cemek M, Ayaz A, et al. Effects of sphingosylphosphorylcholine against oxidative stress and acute

lung ınjury ınduced by pulmonary contusion in rats. J Pediatr Surg 2015;50:591–7. 21. Wang ND, Stevens MH, Doty DB, Hammond EH. Blunt chest trauma: an experimental model for heart and lung contusion. J Trauma 2003;54:744–8. 22. Relja B, Wagner N, Franz N, Dieteren S, Mörs K, Schmidt J, et al. Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagicshock via inhibition of NF-κB and HMGB1. Immunobiology 2018;223:310–8. 23. Wu XJ, Xia ZY, Wang LL, Luo T, Zhan LY, Meng QT, et al. Effects of penehyclidine hydrochloride on pulmonary contusion from blunt chest trauma in rats. Injury 2012;43:232–6. 24. Torun AC, Tutuncu S, Ustun B, Akdemir HU. A Study of the Therapeutic Effects of Resveratrol on Blunt Chest Trauma-Induced Acute Lung Injury in Rats and the Potential Role of Endocan as a Biomarker of Inflammation. Inflammation 2017;40:1803–10. 25. Sırmalı M, Solak O, Tezel C, Sırmalı R, Ginis Z, Atik D, et al. Comparative analysis of the protective effects of caffeic acid phenethyl ester (CAPE) on pulmonary contusion lung oxidative stress and serum copper and zinc levels in experimental rat model. Biol Trace Elem Res 2013;151:50–8. 26. Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J Clin Invest 2001;107:7–11. 27. Wu X, Song X, Li N, Zhan L, Meng Q, Xia Z. Protective effects of dexmedetomidine on blunt chest trauma-induced pulmonary contusion in rats. J Trauma Acute Care Surg 2013;74:524–30. 28. Ricciardolo FL, Sterk PJ, Gaston B, Folkerts G. Nitric oxide in health and disease of the respiratory system. Physiol Rev 2004;84:731–65. 29. Dolkart O, Amar E, Shapira S, Marmor S, Steinberg EL, Weinbroum AA. Protective effects of rosuvastatin in a rat model of lung contusion: Stimulation of the cyclooxygenase 2-prostaglandin E-2 pathway. Surgery 2015;157:944–53. 30. Kozan A, Kilic N, Alacam H, Guzel A, Guvenc T, Acikgoz M. The Effects of Dexamethasone and L-NAME on Acute Lung Injury in Rats with Lung Contusion. Inflammation 2016;39:1747–56. 31. Kart A, Cigremis Y, Karaman M, Ozen H. Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit. Exp Toxicol Pathol 2010;62:45–52. 32. Barlas FB, Erdoğan S. Caffeic acid phenethyl ester protects lung alveolar epithelial cells from cigarette smoke-induced damage. Turk J Med Sci 2015;45:534–41. 33. Shi Y, Guo L, Shi L, Yu J, Song M, Li Y. Caffeic Acid Phenethyl Ester inhibit Hepatic Fibrosis by Nitric Oxide Synthase and Cystathionine Gamma-Lyase in Rats. Med Sci Monit 2015;21:2774–80.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Kafeik asit fenetil ester künt pulmoner kontüzyon modelinde pulmoner enflmasyon ve apoptozisi Nf-κβ aktivasyonunu azaltarak iyileştirir Dr. İhsan Karaboğa Tekirdağ Namık Kemal Üniversitesi Sağlık Yüksekokulu, Acil Yardım ve Afet Yönetimi Bölümü, Tekirdağ

AMAÇ: Pulmoner kontüzyon (PC), akciğer hasarı ve enflamasyon ile karakterize, hayatı tehdit eden önemli bir klinik durumdur. Kafeik asit fenetil ester (CAPE), güçlü antioksidan ve anti-enflamatuvar etkileri olan biyolojik bir ajandır. Bu çalışmada, CAPE’nin deneysel PC modelinde doku hasarı, nükleer faktör kappa-beta (Nf-κβ) aktivitesi, indüklenebilir nitrik oksit sentaz (iNOS) sentezi ve pulmoner apoptozis üzerindeki etkileri araştırıldı. GEREÇ VE YÖNTEM: Çalışmada 40 yetişkin Wistar albino sıçanı kullanıldı ve dört gruba ayrıldı: Kontrol, PC, PC + CAPE ve CAPE. CAPE, PC oluşumunu takiben yedi gün boyunca intraperitonal olarak uygulandı (dimetil sülfoksit içinde çözülmüş 10 umol/kg). Akciğer dokusunda ıslak/kuru ağırlık oranı belirlendi. Pulmoner doku hematoksilen-eosin ve masson trikrom histokimyasal boyaması ile ve taramalı elektron mikroskobu ile incelendi. Akciğerlerdeki Nf-κβ ve iNOS aktiviteleri indirekt immünhistokimyasal yöntemle belirlendi. Pulmoner apoptozis, TUNEL yöntemi ile tespit edildi. BULGULAR: Pulmoner kontüzyon grubunda artmış lökosit infiltrasyon skoru, pulmoner ödem, alveoler hasar ve artmış Nf-κβ ve iNOS aktiviteleri tespit edildi. CAPE uygulaması Nf-κβ ve iNOS aktivitelerini ve pulmoner apoptozu azaltmaktadır. TARTIŞMA: Çalışmanın sonuçları, CAPE’nin Nf-κβ ve iNOS enflamatuvar mediatörlerini baskılayarak doku hasarını engellediğini ettiğini açıkça göstermektedir. Ayrıca, CAPE’nin akciğer dokusunda koruyucu olduğunu ve terapötik bir ajan olarak kullanılabileceğini göstermektedir. Anahtar sözcükler: Apoptozis; enflamasyon; indüklenebilir nitrik oksit sentaz; nükleer faktör kappa-beta; pulmoner kontüzyon. Ulus Travma Acil Cerrahi Derg 2019;25(5):433-439

doi: 10.5505/tjtes.2018.51694

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

439

ORIGIN A L A R T IC L E

Same-admission laparoscopic cholecystectomy in acute cholecystitis: the importance of 72 hours and oxidative stress markers Zinet Asuman Arslan Onuk, M.D.,1 Umut Rıza Gündüz, M.D.,2 Ümit Koç, M.D.,2 Esra Kızılateş, M.D.,1 İsmail Gömceli, M.D.,2 S. Halide Akbaş, M.D.,3 Nurullah Bülbüller, M.D.4 1

Department of Anesthesiology and Reanimation, University of Health Science, Antalya Training and Research Hospital, Antalya-Turkey

Department of General Surgery, University of Health Science, Antalya Training and Research Hospital, Antalya-Turkey

Department of Medical Biochemistry, Akdeniz University Faculty of Medicine, Antalya-Turkey

Department of General Surgery, Akdeniz University Faculty of Medicine, Antalya-Turkey

ABSTRACT BACKGROUND: This prospective randomized study aims to compare outcomes between immediate laparoscopic cholecystectomy (LC) and same admission delayed LC in patients with acute cholecystitis and also to investigate the relation between oxidative stress markers and complication rates in the patients with AC. METHODS: This study included 64 patients with AC who were randomly divided into two groups. Patients in Group 1 (n=32) were immediately administered LC, while in Group 2 (n=32) patients underwent transient LC following medical treatment. All patients were operated on their first hospitalization. RESULTS: No statistically significant differences were observed between the groups for the comparison of complications, conversion rates, or operation durations (p>0.05). The length of postoperative hospital stay was found to be significantly shorter in group 1 compared to group 2 (1.75 vs 2.93 days; p=0.024). Only the total antioxidant status result was significantly higher in group 1 (p=0.017), but the finding was not correlated with complications. CONCLUSION: LC for AC was performed during the first admission was found to be safe, even beyond 72 hours following symptom onset. Pre-operative oxidative stress markers did not correlate with the complication rates. Keywords: 72 hours; acute cholecystitis; oxidative stress; same admission.

INTRODUCTION Gallstone disease is one of the most common problems of the digestive tract. Autopsy reports have shown a prevalence of gallstones between 11% and 36%.[1] Many conditions are associated with an increased risk of developing gallstones, such as obesity, pregnancy, dietary factors, Crohn’s disease, terminal ileum resection, gastric surgery, hereditary spherocytosis, sickle cell disease, and thalassemia.[2] Most of the

patients remain asymptomatic throughout life, but some patients progress to a symptomatic stage. Symptomatic gallstone disease may present as acute or chronic cholecystitis, choledocholithiasis with or without cholangitis, gallstone pancreatitis, cholecystocholedochal fistula, cholecystoduodenal fistula leading to gallstone ileus, and gallbladder carcinoma.[3] Acute cholecystitis (AC) is a well-known complication of gallstone disease, and AC is a potentially life-threatening condi-

Cite this article as: Arslan Onuk ZA, Gündüz UR, Koç Ü, Kızılateş E, Gömceli İ, Akbaş SH, et al. Same-admission laparoscopic cholecystectomy in acute cholecystitis: the importance of 72 hours and oxidative stress markers. Ulus Travma Acil Cerrahi Derg 2019;25:440-446. Address for correspondence: Umut Rıza Gündüz, M.D. Sağlık Bilimleri Üniversitesi, Antalya Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Antalya, Turkey Tel: +90 242 - 249 44 00 E-mail: utg1@yahoo.com Ulus Travma Acil Cerrahi Derg 2019;25(5):440-446 DOI: 10.14744/tjtes.2019.17807 Submitted: 19.10.2018 Accepted: 09.01.2019 Online: 22.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

440

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Arslan Onuk et al. Same-admission laparoscopic cholecystectomy in acute cholecystitis

tion due to its related complications. Laparoscopic cholecystectomy (LC) was once considered a relative contraindication in the presence of AC because of increased morbidity and conversion rates.[4,5] Today, there are studies that have shown that LC is the most common treatment for AC, which is a result of improvements in the laparoscopic skills and experiences of medical teams.[6] However, there has been a lack of agreement regarding the timing of the operation for the treatment of AC. Oxidative stress responses, which are characterized by a balance between pro-oxidants and antioxidants, are an integral part of the response to surgical stress and the activation of inﬂammatory cells.[7,8] This prospective randomized study aimed to compare the clinical and surgical results of the LC, which was applied early (within 72 hours as of the symptoms’ onset) and delayed (72 hours later as of the symptoms onset), and to discuss the 72-hour rule’s importance in light of the literature. In this study, the secondary aim was to compare the oxidative stress response between early and late cholecystectomy patient groups, and then, evaluate the relationship between oxidative stress markers and complications in patients with AC.

MATERIALS AND METHODS Study Design and Patients This prospective, single-center study was conducted at the University of Health Science, Antalya Training and Research Hospital, in Turkey. Parallel patient groups were created, and the randomization of the groups was balanced (1:1). This study was approved by the institutional ethics committee at the University of Health Science, Antalya Training and Re-

Enrollment

search Hospital, in Turkey (#2012/029). The trial was conducted in accordance with the most recent version of the Declaration of Helsinki, and the results were presented according to the CONSORT guidelines. This study was registered with researchregistry.com (UIN: 2383). The diagnosis of AC was established on the basis of local (that is, Murphy’s sign, right upper quadrant pain) and systemic (that is, fever, elevated white blood cell, and/or C-reactive protein) signs of inflammation and confirmed by ultrasound according to Tokyo guidelines (TG13).[9] The abdominal ultrasound was performed by trained radiologists, and intraluminal pathologies and thickening of the gallbladder wall were recorded. The patient exclusion criteria were sepsis, immunosuppression, perforated cholecystitis, choledocholithiasis, cholangitis, acute pancreatitis, previous upper abdominal surgery, pregnancy, and patients who declined to participate in this study. Every patient provided a written informed consent before enrollment. Between January 2013 and December 2014, 293 patients were admitted for AC. After applying exclusion criteria (159 patients admitted 72 hours after the onset of symptoms, four patients with sepsis, two patients under immunosuppression, three patients with perforated cholecystitis, 14 patients with choledocholithiasis, 27 patients with acute pancreatitis, seven patients with previous upper abdominal surgery, one patient was pregnant, and 12 patients refused to participate in the study), 64 patients were included in this study (Fig. 1). Randomization was done by an assistant who was not involved in the enrolment or this study. Study assistant assigned randomly to early (group 1) or delayed (group 2) LC, by picking out

Assessed for eligibility (n=293)

Excluded (n=229) • Not meeting inclusion criteria (n=217) • Declined to participate (n=12) Randomized (n=64)

Allocated to Group 1 (n=32)

Allocation

• Received allocated intervention (n=32)

Allocated to Group 2 (n=32) • Received allocated intervention (n=32)

Follow-up Lost to follow-up (n=0)

Lost to follow-up (n=0)

Analysis Analysed (n=32)

Analysed (n=32)

Figure 1. CONSORT flow diagram.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

441

Arslan Onuk et al. Same-admission laparoscopic cholecystectomy in acute cholecystitis

of an opaque box and opening a sealed opaque randomization envelope. The details of the allocated groups (‘1’ or ‘2’) were given on cards contained in sealed opaque envelopes. All sealed opaque envelopes were previously prepared with a 1: 1 ratio, well-shuffled and put into a box by the dedicated study assistant. No blinding was performed. The early operation group was operated on within 72 hours of the onset of symptoms (32 patients), whereas the late operation group was operated on during the same hospital admission following initial treatment (4–6 days) (32 patients). Operations were performed by staff surgeons of our clinic who were experienced in laparoscopic and open surgery. All patients were treated with intravenous fluids, antibiotics, and analgesics.

Interventions In both groups, intravenous antibiotics (1 g of Ceftriaxone 2x1 and 500 mg of Metronidazole 4x1) were administered upon diagnosis of AC, according to TG13.9 Blood samples for the analysis of oxidative stress markers were collected before the operation. Blood specimens were centrifuged for 10 min at 2,000 g, the resulting serum was transferred to Eppendorf tubes, and the samples were stored at -80°C. The specimens were used to measure advanced oxidation protein products (AOPP), sulfhydryl groups (SG), total antioxidant status (TAS), and total oxidant status (TOS). All patients underwent general anesthesia. The anesthetic technique was standardized for all patients and consisted of balanced anesthesia. All patients were premedicated with diazepam 5 mg the night before surgery and with midazolam 0.03 mg/kg intravenously (IV) 10 minutes preoperatively. Anesthesia was induced with thiopental (5 mg/kg) and fentanyl (4 μg/kg). Vecuronium was used as a muscle relaxant (0.1–0.15 mg/kg). After tracheal intubation, anesthesia was maintained with a 50% air/oxygen mixture with desflurane at a concentration of 4% to 5%. Additional fentanyl and vecuronium were administered whenever necessary. The LC procedure used a standard four-port technique. A Hasson-type trocar was inserted at the periumbilical region for the laparoscope. Carbon dioxide was used for peritoneal insufflation, and abdominal pressure was maintained between 10 mmHg and 12 mmHg. Operator access ports of 10 mm and 5 mm in diameter were inserted into the epigastrium and the right hypochondrium, respectively. The fundus of the gallbladder was grasped with the forceps inserted via a 5-mm port placed at the right upper quadrant. If it were difficult to grasp the gallbladder due to inflammation and the thickness of the wall, gallbladder decompression would be performed using a Veress needle. If severe inflammation and adhesion were present, blunt dissection with a suction device was useful to provide a clear field, and the tissues were dissected safely. The cystic duct and cystic artery were dissected at Calot’s triangle. The critical view of safety established in each case, so intraoperative cholangiography was not performed. Total 442

cholecystectomy was performed for all patients. A drain was routinely inserted to the subhepatic area to assess intraperitoneal bleeding and bile leakage postoperatively. A pathological diagnosis was routinely performed to confirm AC. Demographics, clinical data, laboratory tests, ultrasonography (gall bladder wall thickness: 3 mm/>3 mm), and operative and postoperative variables (such as operation time, number of postoperative hospitalization days, intraoperative and postoperative adverse events, and rate of conversion to open cholecystectomy) were recorded for all of the patients. The primary evaluation criterion of this study was overall morbidity, which was defined as any adverse event that occurred from the time of diagnosis until the 30th postoperative day. The secondary outcome of this study was a comparison of the oxidative stress parameters (AOPP, SG, TAS, TOS, and OSI) between early and late cholecystectomy patient groups and whether there was an association with complications. According to our clinical experience, there is no clinical significance of the ‘early’ concept in acute cholecystitis patients. In addition, different time frames for early cholecystectomy are described in the current literature. This study is based on this hypothesis.

Oxidative Stress Markers Measurement of advanced oxidation protein products (AOPP) Spectrophotometric measurement of AOPP levels was performed with a V-Twin analyzer by Witko’s method.[10] The results are expressed in µmol/L.

Measurement of Sulfhydryl Groups (SG) Plasma sulfhydryl groups originated predominantly from plasma proteins, and they participate in the defense against oxidative stress. Measurement of total free sulfhydryl groups (serum–SH levels) was assayed according to the method of Ellman, as modified by Hu et al.[11,12] The SG amount was expressed in mol/L.

Measurement of Total Antioxidant Status of Serum (TAS) The total antioxidant status of the serum was determined using a novel spectrophotometric measurement method developed by Erel.[13] The results are expressed in µmol of Trolox equivalents/L.

Measurement of Total Oxidant Status (TOS) TOS of serum was determined using a novel spectrophotometric measurement method, as previously described by Erel. [14] The results are expressed in terms of the µmol hydrogen peroxide equivalent per liter (µmol of H2O2 Equiv/L).

Oxidative Stress Index (OSI) The ratio of TOS to TAS was accepted as the oxidative stress index (OSI). The OSI value was calculated according to the Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Arslan Onuk et al. Same-admission laparoscopic cholecystectomy in acute cholecystitis

following formula: OSI (arbitrary unit) = [(TOS, µmol of H equivalent/L) / (TAS, µmol of Trolox equivalent/L) x 100].

Statistical Analysis The study data were summarized with descriptive statistics (mean, SD, frequency, and percentage). The comparisons between study groups were performed using the Mann-Whitney U test for continuous variables and the Pearson chi-square test for categorical variables. The statistical level of significance was set to p<0.05. Data were analyzed with Statistical Package for Social Sciences (SPSS 21.0, Inc., Chicago, IL). We performed this study with 32 experimental subjects and 32 control subjects. According to post hoc power analysis, our data indicate that the true probability of exposure among group 2 is 0.281. The true probability of exposure among group 1 is 0.125. We can reject the null hypothesis that the exposure rates for group 2 and group 1 are equal with a probability (power) equal to 0.34. The probability of a type I error associated with the test of this null hypothesis is 0.05. We used an uncorrected chi-squared statistic to evaluate this null hypothesis (software: PS Power and Sample Size Calculations, Version 3.0).

RESULTS The median age of the patients was 53.6 (27–83) years. There were no differences between the study groups for age or sex distribution (p>0.05). Hypertension was the most common comorbidity in all patients. 17 patients (26.5%) had hypertension, 7 (10.9%) patients had diabetes, 4 patients (6.25%) had thyroid disease (Hashimoto’s Disease), and one patient (1.5%) had pulmonary disease (asthma) (Table 1). Comorbidities were also similar between groups (p>0.05). In laboratory findings, white blood cell, ALT, ALP, and direct bilirubin results were not different between groups (p>0.05), but AST, GGT, and total bilirubin results were significantly higher in the group one patient (p=0.002, p=0.001, p=0.001, respectively) (Table 2). In terms of oxidative stress markers, only TAS result were significantly higher in the group 1 patients (p=0.005); other oxidative stress results (AOPP, SG, TOS, and OSI) were not different between groups (p>0.05) (Table 3). There were similar ultrasonography characteristics in both groups; calculi in the gallbladder were detected in all of the patients, and the thickness of the gallbladder wall was increased in 10 (31.3%) and 8 (25.0%) patients in group 1 and group 2, respectively (p>0.05). Length of operation seemed to be shorter in group 2, but there were no significant differences in either group (mean 64.6 min in group 1 vs 50.7 min in group 2; p>0.05). Only one patient (in group 2) converted to open surgery, due to tissue adhesions and inflammation. Overall morbidity was similar in both groups. Postoperative complications were observed in four patients in group 1 (12.5%) and nine patients in group 2 (28.1%) (p>0.05). All complications (wound infection on trocar site, perihepatic fluid, a hematoma on trocar site, and Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Table 1. Clinical and demographic features of the patients

Group 1 Group 2 (n=32) (n=32)

Age (years), mean±SD

54.04±15.83

53.53±11.19

Sex ratio (female/male)

19/13

20/12

Hypertension

8 9

Diabetes mellitus

Thyroid disease

Pulmonary disease

–

ASA I

ASA II

ASA: American Society of Anesthesiologists; SD: Standard deviation.

Table 2. Laboratory results

Group 1 (n=32)

Group 2 (n=32)

Mean±SD Mean±SD WBC 8.89±3.83

8.09±2.55 0.573

AST 47.09±48.53 20.97±7.50 0.002ª ALT 62.88±80.71 22.34±12.55 0.055 ALP 112.25±143.89 68.31±21.35 0.129 GGT 126.91±202.61 38.96±81.49 0.001ª 0.98±0.57

0.50±0.22 0.001ª

DB 0.34±0.31

0.21±0.07 0.582

a Statistically significant (p<0.05). WBC: White blood cell; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyltransferase; TB: Total bilirubin; DB: Direct bilirubin; SD: Standard deviation.

Table 3. Oxidative stress markers results

Mean±SD Mean±SD p

AOPP 12.66±5.62 15.16±7.27 0.270 SG

389.89±111.58 441.07±247.71 0.711

TAS 1.61±0.24

1.41±0.25 0.017ª

TOS 8.75±5.39

11.26±8.69 0.635

OSI 0.55±0.33

0.78±0.56 0.203

a Statistically significant (p<0.05). AOPP: Advanced oxidation protein products; SG: Sulfhydryl groups; TAS: Total antioxidant status; TOS: Total oxidant status; SD: Standard deviation.

postoperative ileus) were grade I or grade II complications, according to the Clavien–Dindo classification,[15] so there was no need for any surgical or endoscopic interventions for complications. The mean postoperative length of stay was significantly shorter in group 1 (1.75 vs 2.93 days; p=0.001) (Table 4). 443

Arslan Onuk et al. Same-admission laparoscopic cholecystectomy in acute cholecystitis

Table 4. Surgical data and complications

Group 1 (n=32)

Increased gallbladder wall thickness (number of patients) Operative time (min.), mean±SD Post-operative hospital stay in days, mean±SD Complications (number of patients)

Group 2 (n=32)

0.578

64.69±34.50

50.78±17.92

0.178

1.75±1.41

2.93±1.83

0.024ª

Total=4

Total=9

0.120

Wound infection

2 3

Hematomac

1 2

Perihepatic fluid

Postoperative ileus

Statistically significant (p<0.05); bSuperficial infection on trocar site; cIn abdominal wall. SD: Standard deviation.

DISCUSSION When we evaluated the results of the AC in the emergency department of our hospital, we observed that the vast majority of the patients were operated on after a long length of time following medical treatment (6–8 week). A small number of patients undergo early surgical treatment, which we think is caused by the high number of emergency patients who are referred to our hospital. Separate admissions for medical and surgical treatments make the cost of treatment high and result in loss of days off work. Early surgical treatment in acute cholecystitis is the first option, but the treatment of late-onset patients is controversial. The present study, which is a prospective randomized controlled study, focused on surgical treatments of patients with AC during the first admissions even if more than 72 hours have elapsed since the onset of symptoms, and the predictive value of oxidative stress markers in terms of the complications of AC. To our knowledge, the present study is the first randomized controlled trial, including LC performed for AC patients in the same admission. An increased number of studies have pointed toward the importance of the timing of the operation for the treatment of AC. The rule of “72 hours after the symptoms” has been previously examined in retrospective studies,[16–18] and similar rates of postoperative complications and conversion to open surgery have been observed for both early and delayed patient groups beyond 72 hours of symptoms. The time limit for early LC is defined in some studies as the first 72 hours following symptom onset,[16–18] and in other studies, it is describe as the first 1 to 10 days.[19–23] Regardless of the timing of the concept of “early”, all of the above-mentioned studies showed that early LC was associated with a reduction in the length of stay, workdays lost, and costs without an increase in conversion or perioperative complications.[16–23] Another important issue in the delayed group (1–8 weeks) is gallstone-related morbidity during the waiting period for a cholecystectomy. [16–18,21,23] The most common morbidity is the non-resolution or recurrence of cholecystitis, which occurred in 18.3–29.5% 444

of patients.[23,24] According to a Cochrane review, the patients who experienced non-resolution of symptoms under initial conservative treatment or recurrence of symptoms during the waiting period necessitating an emergency LC with a high conversion rate of 45%.[23] In the present study, we found no signiﬁcant differences in postoperative complication, operation time or conversion rates whether LC had been performed at as soon as possible with AC or 72 hours after the symptoms had settled. When the same review is compared with our study, between early and late group results are similar in terms of complication, operation time, or conversion rates.[23] Moreover, the early LC strategy had the advantage of decreasing the overall hospital stay and the total duration of antibiotic therapy. Only one patient in the delayed LC group has had a conversion to open surgery. Maybe partial cholecystectomy could be performed instead of open surgery, but we did not perform partial cholecystectomy to prevent the equality of groups.[25] This low conversion rate is compatible with rates described in the literature in some retrospective or prospective studies.[16,17,24] In contrast, other retrospective studies that had relatively high patient volumes showed high conversion rates (19.7–25.2%), especially in the early LC patient group.[18,21] This could be explained by an experienced surgery team or centers.[24] There was no statistically significant difference in terms of operation time in both groups. These findings are similar to many studies in the literature, but in these studies, it was seen that the patients in the late group operated between 8 days and 12 weeks.[17,18,21–24] In one retrospective study, it is shorter in the early cholecystectomy group.[16] A meta-analysis study involving fifteen randomized controlled trials reported that the operative time in the early cholecystectomy group (seven days following symptom onset) was significantly longer.[22] In an inflammatory condition, such as AC, inflammatory cells (for example, granulocytes and mastocytes) are recruited to the site of inflammation, and they subsequently cause an increase in the uptake of oxygen and, thus, free radicals. Free radicals cause lipid peroxidation in cellular membranes, which results in increased permeability, interstitial edema, and more Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Arslan Onuk et al. Same-admission laparoscopic cholecystectomy in acute cholecystitis

inflammatory cell infiltration and activation. Activated inflammatory cells produce potent mediators, including metabolites of arachidonic acid, cytokines, and chemokines, which leads to more free radical production; this cascade may eventually cause cell death.[7,8] Nowadays, a variety of oxidative stress markers have been measured to reflect oxidative stress. The secondary aim of this study was to evaluate the association between complications of AC and oxidative stress markers, and for those measurements, we used AOPP, SG, TAS, TOS, and OSI. Only the TAS result was significantly higher in the early LC group, but we did not find any correlations between TAS levels and complications (p=0.936). The reason for these results may be the small number of patients in the study groups and similar complication rates between groups. On the other hand, this may be due to the collection of blood samples before surgery in both groups of patients. According to the results of this study, we suggest applying immediate cholecystectomy at first admission, regardless of when the symptoms start. There are some limitations to our study. The number of patients in this study was small because of the limited availability of the oxidative stress kit, and many patients with AC were not included in this study due to strict exclusion criteria. As a result of the study plan, the shortterm results were examined, and therefore, we do not have long-term results of this study. In conclusion, early LC for AC, even beyond 72 hours of symptom onset, is safe and is associated with similar overall morbidity and shorter total hospital stay compared with delayed LC. Performing LC as soon as possible without any time limit between the onset of symptoms and the operation may be recommended in the first admission. Conflict of interest: None declared.

REFERENCES 1. Brett M, Barker DJ. The world distribution of gallstones. Int J Epidemiol 1976;5:335–41. 2. Al-Jiffry BO, Shaffer EA, Saccone GT, Downey P, Kow L, Toouli J. Changes in gallbladder motility and gallstone formation following laparoscopic gastric banding for morbid obestity. Can J Gastroenterol 2003;17:169–74. 3. Attili AF, De Santis A, Capri R, Repice AM, Maselli S. The natural history of gallstones: the GREPCO experience. The GREPCO Group. Hepatology 1995;21:655–60. 4. Cameron JL, Gadacz TR. Laparoscopic cholecystectomy. Ann Surg 1991;213:1–2. 5. Phillips EH, Carroll BJ, Fallas MJ. Laparoscopically guided cholecystectomy: a detailed report of the first 453 cases performed by one surgical team. Am Surg 1993;59:235–42. 6. Menahem B, Mulliri A, Fohlen A, Guittet L, Alves A, Lubrano J. Delayed laparoscopic cholecystectomy increases the total hospital stay compared to an early laparoscopic cholecystectomy after acute cholecystitis: an updated meta-analysis of randomized controlled trials. HPB (Oxford) 2015;17:857–62.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

7. Misthos P, Katsaragakis S, Theodorou D, Milingos N, Skottis I. The degree of oxidative stress is associated with major adverse effects after lung resection: a prospective study. Eur J Cardiothorac Surg 2006;29:591–5. 8. Shimanuki T, Nakamura RM, diZerega GS. A kinetic analysis of peritoneal fluid cytology and arachidonic acid metabolism after abrasion and reabrasion of rabbit peritoneum. J Surg Res 1986;41:245–51. 9. Takada T, Strasberg SM, Solomkin JS, Pitt HA, Gomi H, Yoshida M, et al. TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci 2013;20:1–7. 10. Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 1996;49:1304–13. 11. Ellman G, Lysko H. A precise method for the determination of whole blood and plasma sulfhydryl groups. Anal Biochem 1979;93:98–102. 12. Hu ML, Louie S, Cross CE, Motchnik P, Halliwell B. Antioxidant protection against hypochlorous acid in human plasma. J Lab Clin Med 1993;121:257–62. 13. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112–9. 14. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103–11. 15. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–13. 16. Zhu B, Zhang Z, Wang Y, Gong K, Lu Y, Zhang N. Comparison of laparoscopic cholecystectomy for acute cholecystitis within and beyond 72 h of symptom onset during emergency admissions. World J Surg 2012;36:2654–8. 17. Gomes RM, Mehta NT, Varik V, Doctor NH. No 72-hour pathological boundary for safe early laparoscopic cholecystectomy in acute cholecystitis: a clinicopathological study. Ann Gastroenterol 2013;26:340–5. 18. Degrate L, Ciravegna AL, Luperto M, Guaglio M, Garancini M, Maternini M, et al. Acute cholecystitis: the golden 72-h period is not a strict limit to perform early cholecystectomy. Results from 316 consecutive patients. Langenbecks Arch Surg 2013;398:1129–36. 19. Ansaloni L, Pisano M, Coccolini F, Peitzmann AB, Fingerhut A, Catena F, et al. 2016 WSES guidelines on acute calculous cholecystitis. World J Emerg Surg 2016;11:25. 20. Bouassida M, Hamzaoui L, Mroua B, Chtourou MF, Zribi S, Mighri MM, et al. Should acute cholecystitis be operated in the 24 h following symptom onset? A retrospective cohort study. Int J Surg 2016;25:88–90. 21. Sánchez-Carrasco M, Rodríguez-Sanjuán JC, Martín-Acebes F, LlorcaDíaz FJ, Gómez-Fleitas M, Zambrano Muñoz R, et al. Evaluation of Early Cholecystectomy versus Delayed Cholecystectomy in the Treatment of Acute Cholecystitis. HPB Surg 2016;2016:4614096. 22. Lyu Y, Cheng Y, Wang B, Zhao S, Chen L. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: an up-to-date meta-analysis of randomized controlled trials. Surg Endosc 2018;32:4728–41. 23. Gurusamy KS, Davidson C, Gluud C, Davidson BR. Early versus delayed laparoscopic cholecystectomy for people with acute cholecystitis. Cochrane Database Syst Rev 2013;6:CD005440. 24. Roulin D, Saadi A, Di Mare L, Demartines N, Halkic N. Early Versus Delayed Cholecystectomy for Acute Cholecystitis, Are the 72 hours Still the Rule?: A Randomized Trial. Ann Surg 2016;264:717–22. 25. Sormaz İC, Soytaş Y, Gök AFK, Özgür İ, Avtan L. Fundus-first technique and partial cholecystectomy for difficult laparoscopic cholecystectomies. Ulus Travma Acil Cerrahi Derg 2018;24:66–70.

445

Arslan Onuk et al. Same-admission laparoscopic cholecystectomy in acute cholecystitis

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut kolesistitde laparoskopik kolesistektominin zamanlaması: İlk 72 saat ve oksidatif stres belirteçlerinin önemi Dr. Zinet Asuman Arslan Onuk,1 Dr. Umut Rıza Gündüz,2 Dr. Ümit Koç,2 Dr. Esra Kızılateş,1 Dr. İsmail Gömceli,2 Dr. S. Halide Akbaş,3 Dr. Nurullah Bülbüller4 Sağlık Bilimleri Üniversitesi, Antalya Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, Antalya Sağlık Bilimleri Üniversitesi, Antalya Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Antalya Akdeniz Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, Antalya 4 Akdeniz Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Antalya 1 2 3

AMAÇ: Bu ileriye yönelik randomize çalışmanın amacı; akut kolesistitli (AK) hastalarda, hemen yapılan laparoskopik kolesistektomi (LK) ameliyatı ile medikal tedavi altında geçiktirilerek yapılan LK ameliyatının sonuçlarını kıyaslamaktır. Ayrıca ameliyat öncesi serumda bakılan oksidatif stres belirteçleri ile komplikasyon oranları arasındaki ilgiyi ortaya koymaktır. GEREÇ VE YÖNTEM: Bu çalışmaya AK tanılı 64 hasta dahil edildi ve hastalar rastgele iki gruba ayırıldı. Grup 1’deki (n=32) hastalara hemen LK uygulanırken, grup 2’deki (n=32) hastalara medikal tedaviyi takiben geciktirilmiş LK uygulandı. Tüm hastalar ilk yatışlarında ameliyat edildi. BULGULAR: Her iki grup arasında, komplikasyon, konversiyon oranları ve operasyon süreleri açısından istatistiksel anlamlı fark yoktur (p>0.05). Ameliyat sonrası hastanede yatış süresi grup 1’de istatistiksel olarak anlamlı oranda daha kısa olarak belirlendi (1.75 ve 2.93 gün; p=0.024). Sadece total antioksidan durumu (TAS) belirteci, grup 1’de anlamlı olarak yüksek çıkmış (p=0.017) fakat bu durum komplikasyon oranları ile korele bulunmamıştır. TARTIŞMA: Akut kolesistitli hastalarda, semptomların başlangıcından itibaren 72 saatten fazla zaman geçmesine rağmen, ilk başvuruda kolesistektomi güvenli bulunmuştur. Operasyon öncesi serum oksidatif stres belirteçleri ile komplikasyon oranları arasında korelasyon kurulamamıştır. Anahtar sözcükler: 72 saat; akut kolesistit; ilk başvuru; oksidatif stres. Ulus Travma Acil Cerrahi Derg 2019;25(5):440-446

446

doi: 10.14744/tjtes.2019.17807

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

ORIGIN A L A R T IC L E

Evaluation of the compliance between EEG monitoring (Bispectral IndexTM) and Ramsey Sedation Scale to measure the depth of sedation in the patients who underwent procedural sedation and analgesia in the emergency department Sinem Avcı, M.D.,1 Başak Bayram, M.D.,2 Adile Öniz, M.D.,3 Murat Özgören, M.D.,3

Gonca İnanç, M.D.,3 Nurfer Gören, M.D.,2 Neşe Çolak Oray, M.D.2

Department of Emergency Medicine, Ankara Training And Research Hospital, Ankara-Turkey

Department of Emergency Medicine, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

Department of Biophysics, Dokuz Eylül University Faculty of Medicine, İzmir-Turkey

ABSTRACT BACKGROUND: This study aimed to investigate the compliance between electroencephalogram monitoring (Bispectral Index, BIS) and Ramsay Sedation Scale (RSS) to measure the depth of sedation in patients who underwent procedural sedation and analgesia (PSA) in an emergency department. This study also aimed to investigate the usefulness of this compliance for early diagnosis of complications. METHODS: A total of 54 consecutive patients during PSA in the emergency department were included in this study. The BIS and RSS scores at regular intervals and also all complications and interventions of these patients were evaluated. The compliance between the BIS and the RSS score was evaluated. The BIS scores of cases with complication and without complication were compared. RESULTS: The BIS and RSS scores exhibited a high correlation was detected between the average BIS and RSS scores at each time interval (r=-0.989, p<0.001). The BIS scores of the complicated and uncomplicated cases were different at 15 min after the procedure (p=0.019). The cases were divided into two groups according to the BIS scores <70 and ≥70; complication rates were higher in the BIS score <70 group during the procedure (p=0.037). CONCLUSION: In our study, a high correlation was detected between BIS monitoring and RSS scores. BIS monitoring for PSA can be used as a full-time, objective, and an alternative technique for person-dependent clinical scales and also as an indicator for early diagnosis of complications. Keywords: Bispectral index; emergency department; procedural sedation and analgesia; Ramsay Sedation Scale.

INTRODUCTION Procedural sedation and analgesia (PSA) is a common technique frequently used in emergency department (ED) practice. The aim of using PSA is to successfully perform ED interventions with minimal complication and optimum anal-

gesia. Following the depth of sedation is one of the main elements to provide a successful and safe PSA.[1,2] The Ramsay Sedation Scale (RSS), developed by Ramsay in 1974, was first used in the assessment of sedation levels of patients in intensive care units, and is still the most commonly used sedation scale in these units.[3,4] RSS is an international evaluation scale

Cite this article as: Avcı S, Bayram B, İnanç G, Gören N, Öniz A, Özgören M, et al. Evaluation of the compliance between EEG monitoring (Bispectral IndexTM) and Ramsey Sedation Scale to measure the depth of sedation in the patients who underwent procedural sedation and analgesia in the emergency department. Ulus Travma Acil Cerrahi Derg 2019;25:447-452. Address for correspondence: Sinem Avcı, M.D. Ankara Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, Ankara, Turkey Tel: +90 312 - 595 38 06 E-mail: sinem.avci_@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):447-452 DOI: 10.5505/tjtes.2018.32627 Submitted: 08.12.2017 Accepted: 24.12.2018 Online: 19.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

447

Avcı et al. Evaluation of the compliance between EEG monitoring and Ramsey Sedation Scale

not only in intensive care units but also in all cases requiring sedative and analgesic medications.[5,6] RSS had several disadvantages, such as being person-dependent, requiring dispensing of painful and verbal stimuli to patients for the evaluation, and reflecting only the moment of observation and not giving a continuous measurement. Moreover, the use of these scales at the time of treatment is difficult.[7] Bispectral Index (BIS) is a sedation follow-up method that presents instantaneous sedation levels as a quantitative data by analyzing electroencephalogram (EEG) signals by electrodes adhering to the forehead and temporal region, and with computer software.[8] The full-time objective monitoring method makes the sedation depth easy to follow. The reliability of BIS usage for sedation level follow-ups was proven in operating rooms and intensive care units. BIS monitoring can be used as an alternative method to the classical sleep-scoring system in studies and to follow up the sedation depth in the cases not requiring general anesthesia but requiring sedation, such as bronchoscopy, endoscopy, and dental interventions.[9–13] An objective, person-independent monitoring that can be evaluated by all health care professional increases the success and reliability of the PSA. However, the number of studies related to the use of BIS monitoring to follow up the depth of sedation is fewer, with varying results. Therefore, the success and reliability of the BIS monitoring in ED are still open to discussions. The primary aim of this study was to investigate the compatibility between EEG monitoring (BIS™) and RSS to follow up the sedation depth in the patients who undergo PSA in ED. The study also aimed to explore the usefulness of this technique for early diagnosis of complications.

MATERIALS AND METHODS Study Design This prospective, cross-sectional, analytical study was carried out in Dokuz Eylül University Faculty of Medicine, Department of Emergency Medicine after the approval of the ethics committee (163-GOA).

Study Population The patients who were more than 18 years of age and who underwent PSA because of an extremity fracture or dislocation in the emergency department between December 1, 2014, and May 1, 2015, were included in this study. Twenty four patients were excluded from this study (13 patients who were diagnosed with epilepsy, patients with suppressed conscious awareness before PSA (mentally retarded, GKS (Glasgow coma scale) ≤14, sequelae of cerebrovascular disease, dementia, intracranial mass, severe head trauma, history of psychotic disease), patients with conscious repressive drug/ illegal substance/alcohol intake, patients who had a significant airway obstruction problem (tumor, sleep apnea syndrome), patients who were pregnant, patients who were followed up 448

with an invasive or noninvasive mechanical ventilation, patients who had a skin lesion on their frontal area, patients who refused to participate in the study, and patients who used ketamine for sedation.

Study Protocol and Measurements All patients were monitored before the PSA, and the nasal oxygen was started at a flow rate of 2–4 L/min. Midazolam, propofol and midazolam–propofol combination were used as sedative drugs. The type and the amount of sedation or analgesic drug used were determined by the emergency medicine resident physician. The researchers had no interference with the monitoring of the patient before or during the procedure, or type/dose of the planned drugs, or time/way of doing the procedure. All the vital signs (blood pressure, pulse, respiratory rate, oxygen saturation, and fever) and GKS of the patient were measured by a physician every five min and recorded. The RSS and BIS scores of the patients were recorded at the basal level (before PSA), at the beginning of the procedure (start of the procedure), and at 5, 10, 15, and 20 min. One of the researchers was recorded RSS score, and other researcher monitored and recorded BSS scores. The BIS scores were blinded to the RSS data. The procedure physician performing the sedation and procedure were also blinded to the BIS and RSS scores. All complications and interventions that occurred during the procedure were recorded. The following situations were considered as complications: 1. Partial or complete airway obstruction 2. Hypoventilation apnea 3. Nausea–vomiting after the procedure, aspiration 4. Hypotension (systolic blood pressure <90 mm Hg) 5. Bradycardia (pulse <50 pulse/min) 6. Need for a rescue maneuver (head re-position maneuvers, jaw-thrust maneuvers, oral airway usage, antidote usage) 7. Need for NIMV(Noninvasive mechanical ventilation)/intubation 8. Epileptic seizure

Data Collection Instruments In this study, “RSS” and “BIS” were used as sedation depth measurement methods. In the BIS measurement, A-2000 BIS XP monitor (Aspect Medical System, MA, USA) was used (Fig. 1). The patients were monitored with Nihon Kohden Bedside Monitor BSM 3662 (Nihon Kohden Corporation Shinjuku, Tokyo, Japan) for vital signs and obtained data.

Statistical Analysis Data were recorded using Statistical Package for Social Sciences for Windows 19.0. The Mann-Whitney U test was utilized to evaluate the relationship between the presence of a complication, drug types and BIS/RSS scores. The comUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Avcı et al. Evaluation of the compliance between EEG monitoring and Ramsey Sedation Scale

6.00

5.00

RSS

4.00

3.00

2.00

1.00 40.00

50.00

60.00

70.00

80.00

90.00

100.00

BIS 100

BIS RSS

0 0.5 1

Figure 1. A-2000 BIS XP monitor.

plication rates and BIS groups (BIS score <70 and ≥70) were analyzed using Fisher’s Exact Test. The Pearson correlation analysis was performed to compare both the RSS and BIS results at each time interval. A score of p<0.05 was accepted as significant.

RESULTS This study included 54 patients who satisfied the inclusion criteria out of 78 patients who planned to undergo PSA and visited the ED because of an extremity fracture or dislocation between December 2014 and May 2015. A total of 35 females (64.8%) and 19 males (35.2%) were included in this study, and their average age was 57.4±15.7 (between 18 and 87 years). Midazolam (n=16, 30%), propofol (n=14, 26%), and midazolam–propofol combination (n=24, 44%) were used as sedatives. The analysis of BIS scores revealed a significant difference between drug types and BIS scores at 5, 15, and 20 min (p=0.035, 0.002, and 0.07, respectively). In the midazolam– propofol group, the average BIS score at 5 min was (79±9.8), and the BIS scores at 15 and 20 min were lower in the midazolam group compared with the other groups (81.1±11.1 vs 87.7±9.1). The time curve of the BIS and RSS measurements of the patients are shown in Figure 2. The lowest average BIS measurement occurred between the start and five min after the procedure, and then it increased with an increased slope between 15 and 20 min. Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

1.5 2

2.5

3 75 70

3.5 Basal

Start of procedure

5.min

10.min

15.min

20.min

Figure 2. Distribution of BIS and RSS measurements according to follow-up durations.

A high correlation was detected between the whole BIS and RSS scores at all measurements (r=−0.989, p<0.001). No significant correlation was observed between the basal BIS and RSS scores (r=0.336, p=0.016). A moderate correlation was noted between the BIS and RSS scores of these 54 patients at the start of the procedure and 5 and 15 min after the procedure (r=−0.634, −0.637, and −0.665, respectively), and a high-degree correlation was observed at the start of the procedure and 10 and 20 min after the procedure (r=−0.748 and −0.774, respectively) (Table 1). Complications developed in 16 patients in the present study. The most common complication was hypoventilation/apnea (18.5%). Additionally, hypotension developed in two patients (3.7%), and a simple airway maneuver was needed in four patients (7.4%). None of the patients required İnvasive/noninvasive mechanical ventilation. On comparing the relationship between BIS measurements and complications, the BIS measurement scores at all times in the complicated cases were found to be lower. The BIS scores of the complicated and uncomplicated cases were different at 15 min after the procedure (p=0.019) (Table 2). 449

Avcı et al. Evaluation of the compliance between EEG monitoring and Ramsey Sedation Scale

DISCUSSION

Table 1. Average BIS and RSS scores of the cases Duration

BIS

Average±SD Average±SD (min–max) (min–max)

Basal

97.2±1.4 1.91±0.2 -0.326

(90–98) (1–2)

Start of the

The present study demonstrated a high-degree correlation between BIS monitoring and RSS measurement. Several studies have investigated the compliance between BIS and clinical scales. Correlations have been determined at varying degrees in the published studies. In a study by Gill et al.,[14] a moderate correlation was detected between BIS and modified RSS in 37 adult patients in the ED. In this study, the best BIS score that distinguished moderate sedation level from deeper sedation level was found to be 80 (sensitivity 86%, specificity 94%). In this respect, to our knowledge, this was the only study that determined a threshold score for the desired sedation level. Similar to the present study, Agrawal et al.[15] also detected a high-grade correlation between BIS and modified RSS in 20 pediatric patients who underwent PSA. Since the present study was conducted with a large number of adult patients, it took the study by Agrawal et al. to another level. In the study by Yang et al.,[16] a weak correlation was detected between the RSS and BIS scores in 1766 patients who underwent minor interventions out-of-surgery room by providing moderate sedation with midazolam. No correlation was observed between the type of drug (midazolam, propofol, and their combinations) and the presence of complication in the present study, which was consistent with other similar studies.[9,16–19] According to the present study and other previous studies, the sedation level determined the risk of complication in PSA rather than the type or dose of the drug. It can be concluded that effective PSA monitoring reduces the risk of complications irrespective of the drug dose.

RSS Correlation

82.9±11.2

3.4±1

-0.634

procedure (42–98) (1–6) 5 min

82.1±8.9

(64–98) (2–6)

10 min

85.1±9.8

(60–98) (1–6)

15 min

3.8±0.9 3.3±1.2

87.8±10.1

2.8±1

(51–98) (1–6)

20 min

91.8±7.8

(68–98) (2–5)

2.4±0.7

-0.637 -0.748 -0.665 -0.774

BIS: Bispectral Index; RSS: Ramsay Sedation Scale; SD: Standard deviation.

The average age of patients with complications was 53.5±16, and patients without complications was 59.1±15.3 (p=0.236). No significant difference was observed between sex and drug type used and complication development (p=0.819 and 0.530, respectively). The patients were separated into two groups according to their BIS scores <70 and ≥70. The complication rates in the BIS score <70 group were found to be higher during the procedure (p=0.037).

No internationally accepted scale followed up the depth of sedation in ED procedures. Several studies are available that

Table 2. Relationship between BIS and RSS scores and the presence of a complication

With complication Without complication (n=16) (n=38)

Median

Min-Max

Median

Min-Max

Basal

Bispectral Index

94–98

90–98

0.227

Ramsay Sedation Scale

1–2

0.122

Start of the procedure

Bispectral Index

42–97

65–98

0.056

Ramsay Sedation Scale

1–6

2–5

0.471

5 min

Bispectral Index

64–90

83.5

65–98

0.122

Ramsay Sedation Scale

3–5

2–6

0.094

10 min

Bispectral Index

68–97

60–98

0.537

Ramsay Sedation Scale

1–5

2–6

0.243

15 min

Bispectral Index

68–98

51–98

0.019

Ramsay Sedation Scale

1–5

2–6

0.599

20 min

Bispectral Index

90.5

68–98

75–98

0.069

Ramsay Sedation Scale

2–5

2–4

0.005

BIS: Bispectral Index; RSS: Ramsay Sedation Scale; Min: Minimum; Max: Maximum.

450

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Avcı et al. Evaluation of the compliance between EEG monitoring and Ramsey Sedation Scale

used different clinical scales. In the study by Weaver et al.,[7] BIS compliance was investigated with two clinical scales [Observer’s Assessment of Alertness/Sedation scale (OAA/S) and Continuum of Depth of Sedation] in 75 patients who underwent PSA with propofol in the ED and found a moderate correlation between these two. Although different clinical scales were used in this study, the aforementioned two scales showed very similar compliance with each other. Many correlational studies are available on sedation scales in different areas where PSA is applied, such as endoscopy, bronchoscopy, and dental interventions, except in ED.[9,20,21] Bower et al.[20] found a moderate correlation in their study that investigated the compliance between OAS/S and BIS in 50 adult patients undergoing PSA-requiring endoscopy. In another study, OAS/S and BIS compliance were assessed in 25 patients who underwent a tooth extraction, and a high correlation was determined between these two variables.[21] In the present study, a high correlation between RSS and BIS scores in the reduction of painful extremity fracture or disclosure demonstrated that BIS real-time monitoring is a more effective and reliable method than RSS. Clinical scorings, such as RSS are practitioner related. Practitioner-independent objective monitoring, which can be interpreted by any health practitioner, is possible with BIS in the ED during sedation analgesia procedure. PSA complications are the most frightening complications for health practitioners. In current practice, patients are classically monitored with oxygen saturation, blood pressure, heart rate, and less often with the end-tidal CO2. All these parameters deteriorate only after the complication develops. No method predicts the development of complication just before or during the complication. In the present study, the patients who had low BIS scores at the start of the procedure had higher statistical complication rates. Although no statistical difference was noted at different time intervals after the start of the procedure, BIS scores of the patients who had complications were lower. Several studies reported that reliable PSA follow-up could be carried out by BIS monitoring. For example, the study by Yang et al.[16] showed that complications were lower (especially desaturation) in the group monitored with BIS. Also, Miner et al.[17] reported a significant difference between BIS scores of patients with and without complications. Moreover, more respiratory depression was observed in the patients who had a BIS score <70. In another randomized controlled study conducted by Miner et al.,[22] 48 patients were monitored using BIS, and 52 patients were monitored using classical methods were compared. Although similar sedation levels were detected in both groups, less respiratory depression was seen in the group monitored using BIS. These studies showed that BIS monitoring was effective for following the depth of sedation and blocking the complications. The most common and frightening complications in the PSA are deep-sedation-related respiratory complications and drug/procedure-related vital instability. Complication rates increase as the sedation depth increases. The present study presumed that possible complications might be predicted beforehand, as the depth Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

of sedation can be shown by BIS monitoring. The BIS score for predicting possible complications was determined as 70.8 in this study, as well as in previous studies.[14,17] Despite this evaluation, the number of cases in these studies was limited. Knowing the target BIS scores is important for determining the possible sedation levels and blocking the complications. Further studies are required to determine BIS scores that are appropriate for sedation, have no complications in different patient groups, and involve a large number of patients.

Limitations Since the researcher had no interference with the PSA plan of the patients, start time of the procedure, and type or amount of the drug, a standard drug type, and dose were not used in this study. Although most studies showed that the use of different agents does not affect the results of the complications, the drug variability may still affect the outcomes in different patients. Second, both the sedation level and BIS monitoring were affected by temperature, muscle spasm, sleep, and external stimuli (e.g. interventions of health care professionals, noise, and painful stimulus). Especially, many (and unpredictable) external stimuli in the emergency setting environment might have affected the results. Also, since the study population consisted of patients who underwent more painful interventions, it was difficult to provide the sedation depth. Third, the RSS is an individual-specific scale, and differences might exist between the evaluations of different researchers. This scale was first used in the assessment of sedation levels of patients in intensive care units and is still the most commonly used sedation scale in these units. This is why we used it in this study. Different results may be revealed when other scales are used in this study.

Conclusions A high-degree correlation was detected between the RSS and BIS scores evaluated in the patients undergoing PSA in ED. A significant relation was detected between the BIS scores at the start of the procedure and complications. BIS monitoring for PSA follow-ups in the ED can be used as a full-time, objective, and an alternative technique for person-dependent clinical scales and also as an indicator for early diagnosis of complications. Conflict of interest: None declared.

REFERENCES 1. Godwin SA, Burton JH, Gerardo CJ, Hatten BW, Mace SE, Silvers SM, et al; American College of Emergency Physicians. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med 2014;63:247–58.e18. 2. Brown TB, Lovato LM, Parker D. Procedural sedation in the acute care setting. Am Fam Physician 2005;71:85–90. 3. Overly FL, Wright RO, Connor FA, Jay GD, Linakis JG. Bispectral anal-

451

Avcı et al. Evaluation of the compliance between EEG monitoring and Ramsey Sedation Scale ysis during deep sedation of pediatric oral surgery patients. J Oral Maxillofac Surg 2005;63:215–9. 4. Bombacı E, Boztepe A, Çizen A, Çevik B, Çolakoğlu S, Yollu Atakan T. Bilinci kapalı yoğun bakım hastalarında bispektral indeks monitörizasyonu ile modifiye glasgow koma ve ramsay sedasyon skala puanları arasındaki ilişki. Bakırköy Tıp Dergisi 2005;1:90–4. 5. De Deyne C, Struys M, Decruyenaere J, Creupelandt J, Hoste E, Colardyn F. Use of continuous bispectral EEG monitoring to assess depth of sedation in ICU patients. Intensive Care Med 1998;24:1294–8. 6. Robinson BR, Berube M, Barr J, Riker R, Gélinas C. Psychometric analysis of subjective sedation scales in critically ill adults. Crit Care Med 2013;41(9 Suppl 1):S16–29. 7. Weaver CS, Hauter WH, Duncan CE, Brizendine EJ, Cordell WH. An assessment of the association of bispectral index with 2 clinical sedation scales for monitoring depth of procedural sedation. Am J Emerg Med 2007;25:918–24. 8. Akinci SB, Çelebioglu B. Bispektral indeks monitörizasyonu. Türk Yoğun Bakım Dergisi 2006;4:85–90. 9. Fruchter O, Tirosh M, Carmi U, Rosengarten D, Kramer MR. Prospective randomized trial of bispectral index monitoring of sedation depth during flexible bronchoscopy. Respiration 2014;87:388–93. 10. Jang SY, Park HG, Jung MK, Cho CM, Park SY, Jeon SW, et al. Bispectral index monitoring as an adjunct to nurse-administered combined sedation during endoscopic retrograde cholangiopancreatography. World J Gastroenterol 2012;18:6284–9. 11. Kocaaslan S, Öniz A, Özgören M. Bispektral indeks ışığında uyku elektrofizyolojisi. Turkiye Klinikleri J Med Sci 2009;29:1421–9. 12. Özgören M, Kocaaslan S, Önız A. Analysis of non-REM sleep staging with electroencephalography bispectral index. Sleep and Biological Rhythms 2008;6:249–55. 13. Ozgoren M, Bayazit O, Kocaaslan S, Gokmen N, Oniz A. Brain function

assessment in different conscious states. Nonlinear Biomed Phys 2010;4 Suppl 1:S6. 14. Gill M, Green SM, Krauss B. A study of the Bispectral Index Monitor during procedural sedation and analgesia in the emergency department. Ann Emerg Med 2003;41:234–41. 15. Agrawal D, Feldman HA, Krauss B, Waltzman ML. Bispectral index monitoring quantifies depth of sedation during emergency department procedural sedation and analgesia in children. Ann Emerg Med 2004;43:247–55. 16. Yang KS, Habib AS, Lu M, Branch MS, Muir H, Manberg P, et al. A prospective evaluation of the incidence of adverse events in nurse-administered moderate sedation guided by sedation scores or Bispectral Index. Anesth Analg 2014;119:43–8. 17. Miner JR, Biros MH, Heegaard W, Plummer D. Bispectral electroencephalographic analysis of patients undergoing procedural sedation in the emergency department. Acad Emerg Med 2003;10:638–43. 18. Rahman NH, Hashim A. Is it safe to use propofol in the emergency department? A randomized controlled trial to compare propofol and midazolam. Int J Emerg Med 2010;3:105–13. 19. Zed PJ, Abu-Laban RB, Chan WW, Harrison DW. Efficacy, safety and patient satisfaction of propofol for procedural sedation and analgesia in the emergency department: a prospective study. CJEM 2007;9:421–7. 20. Bower AL, Ripepi A, Dilger J, Boparai N, Brody FJ, Ponsky JL. Bispectral index monitoring of sedation during endoscopy. Gastrointest Endosc 2000;52:192–6. 21. Sandler NA, Sparks BS. The use of bispectral analysis in patients undergoing intravenous sedation for third molar extractions. J Oral Maxillofac Surg 2000;58:364–8; discussion 369. 22. Miner JR, Biros MH, Seigel T, Ross K. The utility of the bispectral index in procedural sedation with propofol in the emergency department. Acad Emerg Med 2005;12:190–6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Acil serviste girişimsel sedasyon ve analjezi uygulanan hastalarda sedasyon derinliğini ölçmede EEG monitörizasyonu (Bispectral IndexTM) ile Ramsey Sedasyon Skalası’nın uyumluluğunun değerlendirilmesi Dr. Sinem Avcı,1 Dr. Başak Bayram,2 Dr. Gonca İnanç,3 Dr. Nurfer Gören,2 Dr. Adile Öniz,3 Dr. Murat Özgören,3 Dr. Neşe Çolak Oray2 Ankara Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, Ankara Dokuz Eylül Üniversitesi Tıp Fakültesi, Acil Tıp Anabiim Dalı, İzmir 3 Dokuz Eylül Üniversitesi Tıp Fakültesi, Biyofizik Anabilim Dalı, İzmir 1 2

AMAÇ: Çalışmamızda girişimsel sedasyon ve analjezi uygulanan hastalarda sedasyon derinliğini takip etmede EEG monitörizasyonu (Bispectral Index™, BIS) ile ‘Ramsey Sedasyon Skalası’nın (RSS) uyumluluğunu ve gelişebilecek komplikasyonları tanımada kullanılabilirliğini belirlemeyi amaçladık. GEREÇ VE YÖNTEM: Çalışmamızda olguların belirli aralıklarla BIS ve RSS değerleri, gelişen komplikasyonlar ve yapılan müdahaleler değerlendirildi. BIS ve RSS değerlerinin uyumluluğu değerlendirildi. Komplikasyon görülen, görülmeyen olguların BIS değerleri karşılaştırıldı. BULGULAR: Tüm zaman dilimlerindeki BIS ve RSS değerlerinin ortalamaları karşılaştırıldığında aralarında yüksek derecede korelasyon saptandı (r=0.989, p<0.001). Komplikasyon görülen olgularda 15. dk’daki BIS değerleri arasında istatistiksel anlamlı bir fark vardı (p=0.018). Olgular BIS değeri <70 ve ≥70 olarak iki gruba ayrıldı. BIS <70 olan grupta daha fazla komplikasyon görüldü (p=0.037). TARTIŞMA: Çalışmamızda RSS ve BIS monitörizasyonu aralarında yüksek derecede korelasyon saptandı. BIS monitörizasyonu, GSA takibinde rutin ve kişi bağımlı klinik skalalara alternatif, objektif bir monitörizasyon yöntemi olarak güvenle kullanılabilir ve komplikasyonları erken tanımada öncül bir gösterge olabilir. Anahtar sözcükler: Acil servis; Bispectral İndeks; girişimsel sedasyon analjezi; Ramsey Sedasyon Skalası. Ulus Travma Acil Cerrahi Derg 2019;25(5):447-452

452

doi: 10.5505/tjtes.2018.32627

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

ORIGIN A L A R T IC L E

The value of hematological parameters in acute pancreatitis Akif Yarkaç, M.D.,1 Fehmi Ateş, M.D.,3

Ataman Köse, M.D.,2 Seyran Bozkurt Babuş, M.D.,2 Gülhan Örekici Temel, M.D.,4 Aydemir Ölmez, M.D.5

Şanlıurfa Bilecik State Hospi̇ tal Department of Emergency Medi̇ ci̇ ne, Şanlıurfa-Turkey

Department of Emergency Medicine, Mersin University Faculty of Medicine, Mersin-Turkey

Department of Gastroenterology, Mersin University Faculty of Medicine, Mersin-Turkey

Department of Biostatistics and Medical Informaticis, Mersin University Faculty of Medicine, Mersin-Turkey

Department of General Surgery, Mersin University Faculty of Medicine, Mersin-Turkey

ABSTRACT BACKGROUND: Acute pancreatitis (AP) is a common inflammatory disease in the emergency department (ED). This study aims to assess the role of CRP and hematologic parameters in mild/severe AP patients and biliary/nonbiliary AP at the time of admission to the ED. METHODS: 168 patients who were diagnosed as AP in the ED, and as a control group, 100 patients were included in this study. At the time of application to the ED, the demographic information (age, sex) and the amylase, lipase, CRP, hematological parameters (WBC, MPV, RDW, PLT, NLR) of all patients and the control group were recorded and compared. According to the etiology of the patients, the patients were divided into biliary and nonbilary AP groups and according to the severity, they were divided into mild and severe AP groups, then, the same parameters were evaluated. RESULTS: Significant differences were found out between WBC, CRP, NLR, MPV and PLT values between patient and the control group (p<0.001). The length of hospitalization and the parameters were not significant between the biliary and the nonbiliary group. Ranson and APACHE II scores were correlated with WBC, CRP and NLR. There was a statistically significant difference between the mild and severe AP groups in terms of duration of the hospital stay, CRP, WBC and NLR values (p=0.003 for CRP, p<0.001 for the others). In severe AP, the cut-off value of NLR was found to be 8.05, sensitivity %93.48, specificity %86.89 and AUC 0.937 (p<0.001). CONCLUSION: The use of parameters, such as WBC, CRP, and NLR, in combination with other diagnostic and prognostic tools in emergency service can provide convenience to clinicians at the time of admission and prognosis. Keywords: Acute pancreatitis; mean platelet volume; neutrophil-to-lymphocyte ratio; platelet count; red cell distribution width.

INTRODUCTION Acute pancreatitis (AP) is an important cause of abdominal pain, which is the most common complaint of emergency department (ED). Risk factors and the etiology of the disease affect the outcome of patients with AP.[1] Over 80% of the etiology of AP all over the world is gallstones and alcohol usage.[2] Some studies have reported that biliary AP is more severe and has higher mortality than alcoholic AP.[3] Diagnosis of AP was based on the presence of at least two of the

following three criteria: (1) Continuous abdominal pain (2) serum amylase and/or serum lipase level at least three times higher than the normal upper limit and (3) Characteristic findings on abdominal imaging.[4–7] Serum biomarkers, imaging studies and many scoring systems (Balthazar and early warning score (EWS), Atlanta, Ranson, APACHE score, Glasgow and Imrie scores) are widely used for the assessment of mortality and severity in acute pancreatitis. [4,8,9] Ranson score ≥3, APACHE II score ≥8, and Atlanta score

Cite this article as: Yarkaç A, Köse A, Bozkurt Babuş S, Ateş F, Örekici Temel G, Ölmez A. The value of hematological parameters in acute pancreatitis. Ulus Travma Acil Cerrahi Derg 2019;25:453-460. Address for correspondence: Ataman Köse, M.D. Mersin Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Mersin, Turkey Tel: +90 324 - 361 00 01 / 2011 E-mail: ataberk76@yahoo.com.tr Ulus Travma Acil Cerrahi Derg 2019;25(5):453-460 DOI: 10.5505/tjtes.2018.69857 Submitted: 17.09.2018 Accepted: 28.11.2018 Online: 05.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

453

Yarkaç et al. The value of hematological parameters in AP

≥1 suggests severe AP.[4,10,11] The majority of these scores are impractical for immediate use due to various reasons (such as follow-up, service intensities and need for further investigation). Investigations are underway for new rapid biomarkers to predict the seriousness of AP. Acute pancreatitis is an inflammatory disease that arises from inappropriate intrapancreatic activation of digestive enzymes, the infiltration of neutrophils and macrophages, and the necrosis of pancreatic tissue in its pathogenesis.[6] Platelet count (PLT), mean platelet volume (MPV), neutrophil/lymphocyte ratio (NLR) and red cell distribution width (RDW) and other hematological parameters have been extensively studied in clinical settings, such as critical diseases, pneumonia, acute appendicitis, cerebrovascular and cardiovascular diseases, defined as prognostic factor.[12–15] A complete blood count is a laboratory test with many parameters that can show the inflammatory state in the AP. The advantages of PLT, MPV, NLR, and RDW are that they are easily accessible, and they can be routinely performed in critical patients, including patients with severe AP.[5,7,10,11,16–18] There are studies evaluating the prognosis and mortality of severe AP regarding white blood cell (WBC), C-reactive protein (CRP), PLT, NLR and RDW parameters. However, the correlation between CRP, WBC and NLR and Ranson and APACHE II score system is very rare in the literature. This study was conducted to investigate the possible associations of these hematological parameters in patients with biliary and non-biliary AP and the prognostic value of mild and severe AP.

MATERIALS AND METHODS Study Design A total of 168 patients who were diagnosed with AP in the ED between 01.01.2014–31.07.2016, and as a control group, 100 patients with inclusion and exclusion criteria were included in this study. This study was approved by the Mersin University Clinical Research Ethics Committee (Reference number: 2017/110, dated 14/ 04/2017). The medical records of 168 patients who applied to the emergency department for AP were obtained and analyzed using the “Nucleus and Enlil Medical Information System.” All data were analyzed retrospectively. Demographic information (age, sex), amylase, lipase, CRP, hematological parameters (WBC, MPV, RDW, PLT, NLR) of the patient group and control group were recorded. The parameters of both groups were compared. Patients were divided into two groups according to pancreatitis etiology: biliary and non-biliary group. The ultrasonography (USG) findings of the patients were used to determine the etiology. Patients with acute cholecystitis, cholelithiasis and other biliary pathologies were accepted as biliary AP. The patient group with no evidence of stones in the gallbladder or biliary tract on ultrasonography was evaluated as normal and other causes of AP (e.g. hyperlipidemia, alcohol, idiopathic) were detected was defined as non-biliary AP. In addition, the distribution of diagnostic parameters according to the length of stay of AP patients was investigated. 454

All AP patients were divided into two types according to the severity of the disease: (1) mild AP and (2) severe AP. The severity of the illness was measured by Ranson, APACHE II and Atlanta scores at admission. Ranson score ≥3, APACHE II score ≥8, and Atlanta score ≥1 were categorized as severe AP.[4,10,11] The patients with the values below these scores were accepted as mild AP.

Laboratory Analysis The electrical impedance method was used in the analyzer (Beckman Coulter LH 780) after obtaining EDTA blood tuber for hemoglobin (Hb), leukocyte count, platelet count, MPV and RDW assay. Serum CRP levels were measured by turbidimetric method (Roche Cobas C 501). The normal reference values of the parameters in our study were Hemoglobin (11.7–16 g/dL), WBC (4.5–10 x103/µL), neutrophil count (1.5–6.7 x103/µL), lymphocyte count (1.5–4 x103/µL), platelet count 150–400 x103/µL), MPV (7.4–10.4 fL), RDW (11.6–14.8%) and serum CRP (0–5 mg/dL).

Exclusion and Inclusion Criteria Exclusion criteria consisted of heart failure, hematologic disease, malignancy, chronic infection, liver disease, vascular disease, infectious disease other than infection or pancreatitis, failure to access file information, and history of drug use that could affect hematological parameters. For the control group, there was also an exclusion criterion for any other serious illness other than these diseases. Patients included in this study were adults over 18 years of age, patients diagnosed with AP between 01/01/2014 and 31/07/2016, patients without medications can cause low platelet count or platelet dysfunction by affecting platelet count and volume, no infection or inflammatory disease, and control group patients over 18 years of age.

Statistical Analysis The Shapiro Wilks test was used for the correlation between the parameters and the corresponding normal scores in the biliary and non-biliary groups, that testing the normality of data. Normal distribution was not found to be appropriate for the subgroups. Median and percentage values were given as descriptive statistics of the parameters. The difference between the averages of the parameters was analyzed by MannWhitney U test. Receiver Operating Curve (ROC) analyses were performed to determine the cut-off points of continuous measurements. Cut-off, Area Under Curve (AUC) and p-values, sensitivity, selectivity, LR+ and LR- values are given as descriptive statistics. In addition, the separation power on the discrimination of a biliary and non-biliary group of related parameters was evaluated by ROC analysis. Statistical significance was taken as p<0.05.

RESULTS In our study, the mean age of 168 patients diagnosed with panUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Yarkaç et al. The value of hematological parameters in AP

Table 1. Values of CRP and hematological parameters of the patient (AP) and control group White blood cell count (x10 /µL) 3

C-reactive protein (mg/dL)

Control (n=100)

Acute pancreatitis (n=168)

Med [Q1–Q3]

9.3 [7.5–12.6]

11.25 [8.625–14.375]

<0.001

3 [1–12.75]

9.5 [3–30.5]

<0.001

Neutrophil lymphocyte ratio (x10 /µL)

3 [1–5]

5 [3–9]

<0.001

Mean platelet volume (fL)

8 [8–9]

9 [8–10]

<0.001

13 [13–15]

13 [13–14]

0.418

233.5 [195.5–284]

256 [207–307.75]

0.024

Red cell distribution width (%) Platelet count (x103/µL) Values are expressed as the Median (range).

Table 2. ROC analysis of CRP and hematological parameters in AP patients Parameters

Cut off

AUC (95% CI)

Sensitivity (95% CI)

Specificity (95% CI)

LR+ (95% CI)

LR- (95% CI)

CRP

0.687 [0.627–0.742]

73.81 [66.5–80.3]

58 [47.7–67.8]

1.76 [1.5–2.1]

0.45 [0.3–0.6]

0.0001

WBC

>11.5

0.631 [0.570–0.689]

47.62 [39.9–55.5]

73.00 [63.2–81.4]

1.76 [1.4–2.2]

0.72 [0.5–1.0]

0.0001

NLR

0.654 [0.594–0.711]

76.79 [69.7–82.9]

47.00 [36.9–57.2]

1.45 [1.2–1.8]

0.49 [0.4–0.7]

0.0001

PLT

>276

0.582 [0.521–0.642]

43.45 [35.8–51.3]

73.00 [63.2–81.4]

1.61 [1.3–2.0]

0.77 [0.5–1.1]

0.0202

MPV

0.685 [0.626–0.740]

69.05 [61.5–75.9]

62.00 [51.7–71.5]

1.82 [1.5–2.2]

0.50 [0.4–0.7]

0.0001

RDW

>15

0.529 [0.467–0.590]

89.29 [83.6–93.5]

20.00 [12.7–29.2]

1.12 [0.8–1.7]

0.54 [0.3–0.8]

0.4335

AP: Acute pancreatitis; ROC: Receiver operating curve; CI: Confidence interval; AUC: Area under the curve; WBC: White blood cell count; CRP: C-reactive protein; MPV: Mean platelet volume; NLR: Neutrophil lymphocyte ratio; RDW: Red cell distribution width; PLT: Platelet count.

WBC, CRP, NLR, MPV, RDW and PLT parameters of the patient (AP) and control group were compared. There was a statistically significant difference between CRP, WBC, NLR, MPV and PLT levels (p=0.024 for PLT, p<0.001 for others). There was no significant difference between the two groups in terms of RDW value (p=0.418), which is shown in Table 1. According to the results of ROC analysis in patients with AP, the cut-off value of CRP was 3, sensitivity was 73.81%, specificity was 58% and AUC was 0.687, p=0.001. The cut-off value of the WBC was 11.5, the sensitivities were 47.62%, the specificity was 73% and AUC=0.631, p=0.001. The cutoff value of NLR was 2, the sensitivities were 76.79%, the specificity was 47% and the AUC was 0.654, p=0.001. The cut-off value of PLT was 276, sensitivity 43.45%, specificity 73% and AUC=0.582, p=0.0202. The cut-off value of MPV was 8, the sensitivity was 69.05%, the specificity was 62% and Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

the AUC was 0.685, p=0.001. The ROC curve and analysis of CRP and other hematological parameters are shown in Table 2 and Figure 1. 100

Sensitivity

creatitis was 48.13±13.28, while the mean age of the control group was 43.95±19.31. There was no statistically significant difference between two groups in the mean age (p=0.058). Among 168 patients, 79 were male (47%) and 89 were female (53%). The number of women in the control group was 54 (54%), while the number of males was 46 (46%). There was no statistically significant difference regarding sex in both groups (p=0.871).

40 CRP MPV NLR PLT RDW WBC

100

100-Specificity

Figure 1. ROC curve of CRP and hematological parameters in AP patients according to the control group.

455

Yarkaç et al. The value of hematological parameters in AP

Table 3. Correlation of hematologic parameters with Ranson and APACHE II scores

Ranson

APACHE II

WBC

CRP

NLR

MPV

RDV

PLT

Ranson

Pearson Correlation

0.424

–

<0.001 <0.001 0.009 <0.001 0.300 0.019 0.469

0.421 0.200 0.628 0.080 0.181 0.056

APACHE II

Pearson Correlation

0.424

0.275

<0.001

–

<0.001 0.426 <0.001 0.920 0.506 0.891

0.062

0.412

0.008

0.052

-0.011

APACHE-II: Acute Physiology and Chronic Health Evaluation-II; WBC: White blood cell count; CRP: C-reactive protein; MPV: Mean platelet volume; NLR: Neutrophil lymphocyte ratio; RDW: Red cell distribution width; PLT: Platelet count.

Table 4. Demographic features and laboratory values in mild and severe AP patients

Mild AP (n=122, 72.6%)

Severe AP (n=46, 27.4%)

0.901

Sex, n (%)

Male

57 (46.7)

21 (45.7)

Female

65 (53.3)

25 (54.3)

Ultrasonography, n (%)

Nonbiliary

26 (21.3)

11 (23.9)

Biliary

96 (78.7)

35 (76.1)

Age, Mean±SD

47.45±12.46

50.39±15.71

0.258

9.51±1.24

9.79±1.29

0.195

1407.86±1330.86

1574.93±1103.96

0.449

10.646±3.398

14.792±4.691

<0.001

Mean platelet volume (fL), Mean±SD Amylase U/L, Mean±SD White blood cell count (x103/µL), Mean±SD Hospital stay (days), Median (range)

0.717

4 (3–5)

5 (4–9.25)

<0.001

1123,50 (677–1578)

1200 (945.5–2433.75)

0.237

C-reactive protein (mg/dL), Median (range)

7.70 (3.16–26.11)

17.15 (7.37–53.09)

0.003

Neutrophil lymphocyte ratio (x103/µL), Median (range)

4.16 (2.57–6.59)

13.95 (9.51–19.33)

<0.001

13.65 (12.9–14.5)

14.00 (13.28–15.05)

0.092

246.5 (208.5–308.25)

266 (199.5–306.5)

0.519

Lipase U/L, Median (range)

Red cell distribution width (%), Median (range) Platelet count (x103/µL), Median (range) AP: Acute pancreatitis; SD: Standard deviation.

The amylase, lipase, WBC, CRP, NLR, MPV, RDW, PLT values and duration of hospital stay of the biliary and non- biliary AP group were compared. The median value of the amylase in the biliary group was 1300 [569–2670], while the median value of the lipase was 1200 [846–2180]. The median value of the amylase in the non- biliary group was 370 [168.5–683.5], while the median value of the lipase was 811 [441.5–1181.5]. There was a statistically significant difference between both groups of amylase and lipase values (p<0.001). There was no statistically significant difference between the biliary and nonbiliary AP groups in duration of hospital stay and other parameters (WBC, CRP, NLR, MPV, RDW, PLT) (p>0.05). The relation of hematological parameters with Ranson and APACHE II scores in patients with acute pancreatitis was investigated. Correlation of Ranson score with APACHE II score (r=0.424, p<0.001), WBC (r=0.421, p<0.001), CRP 456

(r=0.200, p=0.009), NLR (r=0.628, p<0.001) and RDW (r=0.181, p=0.019) was determined. Correlation of the APACHE II score with the Ranson score (r=0.424, p<0.001), WBC (r=0.275, p<0.001) and NLR (r=0.412, p<0.001) was found (Table 3). A total of 122 (72.6%) patients (57 males and 65 females) with a mean age of 47.45±12.46 were found to have mild AP diagnosis according to the severity scores performed at the time of emergency department admission. The remaining 46 (27.4%) patients (21 males and 25 females) were diagnosed with severe AP and their mean age was 50.39±15.71. Of the patients with mild AP, 26 (21.3%) were non-biliary AP and 96 (78.7%) were biliary AP. 11 of the severe AP patients (23.9%) were non- biliary AP and 35 (76.1%) were biliary AP. A statistically significant difference was found between the mild and severe AP groups for the duration of hospital stay, CRP, Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Yarkaç et al. The value of hematological parameters in AP

Table 5. ROC analysis of CRP and hematological parameters in patients with severe AP compared to mild AP group Parameter

Cutoff

AUC [CI]

Sensitivity [CI]

0.0016

Specificity [CI]

LR+ [CI]

LR- [CI]

CRP

>6.63

0.647 [0.57–0.72]

80.43 [66.1–90.6]

45.90 [36.8–55.2]

1.49 [1.2–1.8]

0.43 [0.2–0.8]

WBC

>11700

0.781 [0.711–0.841]

<0.0001 76.09 [61.2–87.4]

67.21 [58.1–75.4]

2.32 [1.7–3.1]

0.36 [0.2–0.6]

NLR

>8.05

0.937 [0.89–0.97]

<0.0001 93.48 [82.1–98.6]

86.89 [79.6–92.3]

7.13 [4.5–1.3]

0.075 [0.03–0.2]

PLT

>253000

0.532 [0.454–0.61]

0.5330

63.04 [47.5–76.8]

51.64 [42.4–60.8]

1.3 [1.0–1.7]

0.72 [0.5–1.1]

RDW

>14.7

0.584 [0.506–0.660]

0.0905

39.13 [25.1–54.6]

79.51 [71.3–86.3]

1.91 [1.2–3.2]

0.77[0.6–1.0]

MPV

>9.4

0.592 [0.52–0.67]

0.0667

71.74 [56.5–84]

49.18 [40.0–58.4]

1.41 [1.1–1.8]

0.57 [0.4–0.9]

ROC: Receiver operating curve; AP: Acute pancreatitis; CI: Confidence interval; AUC: Area under the curve; WBC: White blood cell count; CRP: C-reactive protein; MPV: Mean platelet volume; NLR: Neutrophil lymphocyte ratio; RDW: Red cell distribution width; PLT: Platelet count.

WBC and NLR (p=0.003 for CRP, p<0.001 for others). No significant difference was found between the two groups for other parameters (p>0.05). This situation is shown in Table 4. According to ROC analysis results in severe AP patients, the cut-off value of CRP was 6.63, sensitivity 80.43%, specificity 45.90% and AUC 0.647, p=0.0016. The cut-off value of WBC was 11.7, sensitivity was 76.09%, specificity was 67.21%, and AUC was 0.781, p<0.0001. The cut-off value of NLR was 8.05, sensitivity was 93.48%, sensitivity was 86.89%, and AUC was 0.937, p<0.001. The ROC curve and analysis of CRP, WBC, NLR and other hematological parameters are shown in Table 5 and Figure 2. The median values of patients who were hospitalized for seven days and fewer than seven days were analyzed respectively. The median values were (19.5 [5.5–103.5] vs. 8 [3–26], p=0.033) for CRP, (14.15 [11375–16850] vs. 10.5 [8400–13900], p<0.001) for WBC, (8 [4–14.75] vs. 5 [2–8], 100

Sensitivity

40 MPV NLR PLT CRP WBC RDW

100

100-Specificity

Figure 2. ROC curve of CRP and haematological parameters in patients with severe AP.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

p=0.008) for NLR and (10 [9.25–11] vs. 9 [8–10] p=0.001) for MPV. However, there was no statistically significant difference between the amylase, lipase, RDW and PLT median values of the inpatients (p>0.05).

DISCUSSION It is important that the diagnostic tests for diagnosing and in the clinical evaluation of the prognosis of acute pancreatitis should be fast and simple, inexpensive and potentially widely available. Hematological parameters (WBC, NLR, MPV, RDW, PLT) and especially CRP have been studied in many cases, such as stroke, heart failure, pneumonia, pancreatitis and rheumatologic diseases. The elevation of CRP, WBC, NLR and RDW in such diseases and low PLT and MPV values are considered as poor prognostic indicators.[5,7,10–13,16–18] White blood cells, NLR, and CRP are usually prominent as indicators of acute inflammation.[8,19,20] High CRP value is often accepted as an important determinant of violence in AP. In particular, the CRP value measured within 48 hours from the onset of symptoms was found to be significant for the diagnosis of severe AP with 80–86% sensitivity and 61–84% specificity. CRP value within 48 hours from the onset of symptoms was found to be significant for necrotizing pancreatitis with specificity over 80%.[21] In a study by Khanna et al.,[9] CRP value was found to be 100% sensitive and 81.4% specific for the detection of pancreatic necrosis. The disadvantage of CRP as a marker is the late peaking (48–72 h) and non-specificity as an inflammatory marker. Similarly, the number of WBCs (12.2x103/L) at the time of admission in mild AP patients was significantly higher than that of healthy subjects (6.3x103/L).[16] In our study, CRP and WBC values were found higher in AP patients than the control group. In other studies, NLR was found to be higher in AP patients. [17,20] In a study conducted in our country, the cut-off value for NLR with 86% sensitivity and 88% specificity was found to be 2.81.[22] In another AP study, sensitivity for NLR 2.6 cutoff value was defined as 92.9% and specificity as 41.4%.[17] In our study, NLR was found to be high in AP patients (Cut-off value >2, sensitivity 76.79%, specificity 47% and AUC 0.654). NLR is significantly higher in cases with more severe cases, 457

Yarkaç et al. The value of hematological parameters in AP

A direct correlation of Ranson and APACHE II score with WBC, CRP and NLR was determined in our study. CRP, WBC and NLR values were higher in severe AP. Especially in severe AP, the sensitivity of NLR was 93.48%, specificity was 86.89% and AUC was 0.937 and cut-off value was 8. The most widely used clinical prognostic scores include Ranson criteria and APACHE II classification system. The two scoring systems are commonly used to identify patients with severe pancreatitis who have an increased risk of complications: Ranson’s criteria and APACHE II. A Ranson score ≥3, or an APACHE II score ≥8 indicates severe pancreatitis.[4,10,11] Limitations of Ranson’s criteria include a 48-hour time requirement for score determination and a lack of ability to reassess severity at later points during the hospitalization. The APACHE II scoring system allows determination of severity on admission and at any point during the hospital course; however, the complexity of scoring may limit its use. Therefore, it may be possible to predict AP prognosis much more easily with WBC, CRP, and NLR in patients with AP clinical, laboratory, and imaging findings. Some studies on acute pancreatitis have reported that the height of RDW is proportional to the severity of inflammation, and patients with high RDW values may have higher mortality. It has been reported that RDW can be used in evaluating acute pancreatitis severity with other scoring systems.[7,24] In another study, the RDW value (12.6±0.59) at admission in mild AP patients was significantly lower than that of healthy subjects (13.42±0.85). However, in the same study, RDW (14.4±1.06) was significantly higher in patients with severe AP than in healthy subjects.[16] In the study of Akbal et al.,[25] similar to our data, there was no significant difference between the healthy and the patient group and between the mild and severe AP for the RDW value. The RDW value was not meaningful in our work because it was only measured on admission to the hospital.

who died of AP. Generally, patients without thrombocytopenia showed good prognosis. Meanwhile, with the treatment of AP, platelet counts increased within just a few days.[11] In a case report, serious thrombocytosis, as well as thrombocytopenia, may be seen in AP.[27] On the contrary, another study found out that PLT and RDW were not effective in determining the mortality of AP cases within the first 48 hours.[18] In several studies, there were no significant differences between patients with AP and healthy groups in terms of PLT numbers at the time of admission.[16,17] The increase in MPV showing platelet activation has been described as an independent risk factor for different clinical situations in the literature.[28–30] In a study of AP, no difference was found between baseline and remission MPV levels in 24 AP patients. Compared with the healthy group, the MPV value at the time of admission was higher in the patient group.[25] Similarly, in another study, the number of MPV in AP patients was found to be significantly higher than in healthy individuals.[16] In all these studies, the findings suggest that the severity of systemic inflammation is related to platelet volume. In our study, the number of PLT and MPV values in the AP at the time of admission was higher than the control group, even though it was in the normal reference interval. There was no difference between the mild and severe AP groups regarding PLT number and MPV value. Biliary causes (64–70%) take place on the top and idiopathic causes (24–31%) are in the second place in some studies which were conducted in Turkey.[31,32] When the etiologies of these patients were examined in detail, gallstones were determined as 40%, idiopathic causes 25.6%, alcohol 22% and post-ERCP 3.9%.[2] In our study, 77.9% of the 168 patients with AP were classified as biliary AP, while 22.1% were classified as non-biliary AP. 23.9% of severe AP patients were nonbiliary AP and 76.1% were biliary AP. The data obtained in our study are consistent with the literature in this regard. In our study, no significant difference was found between CRP and hematological parameters (WBC, NLR, MPV, RDW, PLT) between biliary and non-biliary AP groups. In our country, Turkey, related to AP, Kara et al.[20] reported that the WBC is an important inflammatory mediator in the discrimination between the biliary and non-biliary AP, on the other hand, the sensitivity and specificity are low. In the same study, there were no significant differences between the biliary and nonbiliary groups in terms of PLT and NLR. In one study, serum CRP levels measured during admission did not show a significant difference between alcohol-dependent AP and biliary AP groups.[3] In the same study, levels of serum amylase and lipase were significantly higher in the biliary AP group than in the alcoholic AP group.[3] Similar to our study, Okuturlar et al.’s[5] study showed that the amylase and lipase values in the biliary AP group were higher than the nonbiliary AP group.

A study examining the condition of the platelets and remission of the disease showed that platelets were directly involved in the systemic inflammatory process and contributed to the formation of AP.[26] Median and mean platelet counts were significantly lower in patients with severe AP and in patients

The average length of stay in the hospital for acute pancreatitis patients was reported to be 4–14 days.[2,3,7,16] Thus, we admitted an average length of stay in hospital is 7-day in our study, and the relationship between CRP and hematologic parameters was evaluated. CRP, WBC, NLR and MPV values

especially in gastrointestinal cases (appendicitis and cholecystitis).[19] Azab et al.[8] reported that NLR was better than WBC, without anticipating the undesirable consequences of AP. This study also showed that 44.7 NLR cut-off value was determined as a simple indicator of AP severity. However, Binnetoğlu et al.[23] concluded that NLR was a controversial issue in determining the prognosis of AP, although the study reported that the NLR reported an increase in AP, especially in the first 48 hours. In a study of 146 patients by Suppiah et al.,[10] NLR was found to be significantly higher in patients with severe AP in the first three days than in the other patients. This study concluded that NLR elevation was significantly associated with severe AP for the first 48 hours after admission and was an independent negative prognostic marker in AP. In this study, sensitivity was 63–90% and specificity was 5–57%.

458

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Yarkaç et al. The value of hematological parameters in AP

were higher in patients with a stay over seven days, amylase, lipase, RDW, and PLT mean values were not statistically significant. CRP value was found to be 19.5 mg/dL on average in hospitalized patients over seven days. Cetin et al.[33] found out that 7th day CRP was associated with necrotizing pancreatitis with a sensitivity of 71% and specificity of 74% when the cut-off value was accepted as 10 mg/dL. In the study of Azab et al.,[8] the NLR level was significantly longer than in the hospital (average duration of stay 6.2 days). High WBC, CRP, NLR and MPV values in AP patients with a longer hospital length of stay (more than seven days) may be associated with the severity of inflammation in pancreatitis. Patients with severe AP in our study had a longer stay in the hospital and WBC, CRP, and NLR values of these severe AP patients were also higher. In conclusion, our study aimed to evaluate the value of parameters, such as CRP, WBC, NLR, MPV and PLT, in AP patients at the time of admission. Parameters, such as CRP, WBC, NLR, MPV and PLT, found significant in AP. The same parameters were not found to discriminate between the biliary and non-biliary AP groups. Amylase and lipase values were higher in biliary AP. WBC, CRP, NLR and MPV were higher in long-term hospitalised patients. The high level of these parameters can provide clues to that AP patients may stay longer in the hospital. This study revealed that the correlation between Ranson and APACHE II prognostic scoring systems and WBC, CRP, NLR values is new and important information. Sensitivity, specificity and AUC value of NLR are better, especially when predicting the severity of the disease. It may be possible to predict AP prognosis much more easily with WBC, CRP, and NLR in patients with AP clinical, laboratory, and imaging findings.

Limitations The most important limitations of our study are retrospective study and small sample sizes. However, long-term outcomes, complications, and mortality have not been studied. We should note that only one measurement of the evaluated parameters has been taken into account. In addition, acute changes in haematological parameters due to technical reasons, such as haemolysis and possible changes over time, have not been evaluated. Although close attention has been paid to time constraint between the first blood sampling and laboratory analysis when selecting patient groups, this issue may not be fully standardized given that this study is retrospective. Conflict of interest: None declared.

REFERENCES 1. Reid GP, Williams EW, Francis DK, Lee MG. Acute pancreatitis: A 7 year retrospective cohort study of the epidemiology, aetiology and outcome from a tertiary hospital in Jamaica. Ann Med Surg (Lond) 2017;20:103–8. 2. Nesvaderani M, Eslick GD, Vagg D, Faraj S, Cox MR. Epidemiology, ae-

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

tiology and outcomes of acute pancreatitis: A retrospective cohort study. Int J Surg 2015;23:68–74. 3. Cho JH, Kim TN, Kim SB. Comparison of clinical course and outcome of acute pancreatitis according to the two main etiologies: alcohol and gallstone. BMC Gastroenterol 2015;15:87. 4. Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101:2379–400. 5. Okuturlar Y, Soylu A, Dogan H, Cakmak S, Kirac Utku I, Oztosun B, et al. Mean platelet volume in patients with biliary and non-biliary acute pancreatitis. Int J Clin Exp Pathol 2015;8:2051–6. 6. Basnayake C, Ratnam D. Blood tests for acute pancreatitis. Aust Prescr 2015;38:128–30. 7. Şenol K, Saylam B, Kocaay F, Tez M. Red cell distribution width as a predictor of mortality in acute pancreatitis. Am J Emerg Med 2013;31:687– 9. 8. Azab B, Jaglall N, Atallah JP, Lamet A, Raja-Surya V, Farah B, et al. Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis. Pancreatology 2011;11:445–52. 9. Khanna AK, Meher S, Prakashetal S, Tiwary ST, Singh U, Srivastava A, et al. “Comparison of Ranson, Glasgow, MOSS, SIRS, BISAP, APACHE-II, CTSI Scores, IL-6, CRP, and procalcitonin in predicting severity, organ failure, pancreatic necrosis and mortality in acute pancreatitis,” HPB Surgery 2013, ArticleID367581, 10 pages. 10. Suppiah A, Malde D, Arab T, Hamed M, Allgar V, Smith AM, et al. The prognostic value of the neutrophil-lymphocyte ratio (NLR) in acute pancreatitis: identification of an optimal NLR. J Gastrointest Surg 2013;17:675–81. 11. Osada J, Wereszczynska-Siemiatkowska U, Dabrowski A, Dabrowska MI. Platelet activation in acute pancreatitis. Pancreas 2012;41:1319–24. 12. Hunziker S, Celi LA, Lee J, Howell MD. Red cell distribution width improves the simplified acute physiology score for risk prediction in unselected critically ill patients. Crit Care 2012;16:R89. 13. Makhoul BF, Khourieh A, Kaplan M, Bahouth F, Aronson D, Azzam ZS. Relation between changes in red cell distribution width and clinical outcomes in acute decompensated heart failure. Int J Cardiol 2013;167:1412–6. 14. Braun E, Domany E, Kenig Y, Mazor Y, Makhoul BF, Azzam ZS. Elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia. Crit Care 2011;15:R194. 15. Demirkol S, Balta S, Unlu M, Arslan Z, Cakar M, Kucuk U, et al. Neutrophils/lymphocytes ratio in patients with cardiac syndrome X and its association with carotid intima-media thickness. Clin Appl Thromb Hemost 2014;20:250–5. 16. Yao J, Lv G. Association between red cell distribution width and acute pancreatitis: a cross-sectional study. BMJ Open 2014;4:e004721. 17. İlhan M, İlhan G, Gök AF, Bademler S, Verit Atmaca F, Ertekin C. Evaluation of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and red blood cell distribution width-platelet ratio as early predictor of acute pancreatitis in pregnancy. J Matern Fetal Neonatal Med 2016;29:1476–80. 18. Gülen B, Sonmez E, Yaylaci S, Serinken M, Eken C, Dur A, et al. Effect of harmless acute pancreatitis score, red cell distribution width and neutrophil/lymphocyte ratio on the mortality of patients with nontraumatic acute pancreatitis at the emergency department. World J Emerg Med 2015;6:29–33. 19. Kucuk A, Erol MF, Senel S, Eroler E, Yumun HA, Uslu AU, et al. The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis. Korean J Intern Med 2016;31:386–91.

459

Yarkaç et al. The value of hematological parameters in AP 20. Kara H, Doğru A, Değirmenci S, Bayır A, Ak A, Kafalı ME, et al, Diagnostic value of neutrophil-to-lymphocyte ratio in emergency department patients diagnosed with acute pancreatitis. Cukurova Medical Journal 2016;41:55–60. 21. Neoptolemos JP, Kemppainen EA, Mayer JM, Fitzpatrick JM, Raraty MG, Slavin J, et al. Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study. Lancet 2000;355:1955–60. 22. Ergenc H. The role of neutrophil/lymphocyte and platete/ lymphocyte rates in the evaluation of acute pancreatitis severity. Sakarya Üniversitesi Tıp Fakültesi İç Hastalıkları Anabilim Dalı, Master Thesis, 2015, Sakarya. 23. Binnetoğlu E, Akbal E, Güneş F, Sen H. The prognostic value of neutrophil-lymphocyte ratio in acute pancreatitis is controversial. J Gastrointest Surg 2014;18:885. 24. Wang D, Yang J, Zhang J, Zhang S, Wang B, Wang R, et al. Red cell distribution width predicts deaths in patients with acute pancreatitis. J Res Med Sci 2015;20:424–8. 25. Akbal E, Demirci S, Koçak E, Köklü S, Başar O, Tuna Y. Alterations of platelet function and coagulation parameters during acute pancreatitis. Blood Coagul Fibrinolysis 2013;24:243–6. 26. Mimidis K, Papadopoulos V, Kotsianidis J, Filippou D, Spanoudakis E, Bourikas G, et al. Alterations of platelet function, number and indexes during acute pancreatitis. Pancreatology 2004;4:22–7.

27. Jiang L, Ding W, Zhang M. The progressive increase of the platelet count in a patient with acute severe pancreatitis. Am J Emerg Med 2017;35:191. e1–191.e2. 28. Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: methodological issues. Platelets 2002;13:301–6. 29. Bath P, Algert C, Chapman N, Neal B; PROGRESS Collaborative Group. Association of mean platelet volume with risk of stroke among 3134 individuals with history of cerebrovascular disease. Stroke 2004;35:622–6. 30. Huczek Z, Kochman J, Filipiak KJ, Horszczaruk GJ, Grabowski M, Piatkowski R, et al. Mean platelet volume on admission predicts impaired reperfusion and long-term mortality in acute myocardial infarction treated with primary percutaneous coronary intervention. J Am Coll Cardiol 2005;46:284–90. 31. Yardan T, Genç S, Baydın A, Nural MS, Aydın M, Aygün D. Evaluation of patients with acute pancreatitis in the emergency department. Fırat Medical Journal 2009;14:124–8. 32. Tamer A, Yaylacı S, Demirsoy H, Nalbant A, Genç A, Demirci H et al. Retrospective analyses of the acute pancreatitis. Sakarya M J 2011;1:17– 21. 33. Cetin P. Eryhtrocyte sedimentation rate, C-reactive protein and other laboratory parameters for the prediction of necrosis and severity in acute pancreatitis. İzmir. Ege Üniversitesi Tıp Fakültesi İç Hastalıkları Anabilim Dalı. [Master Thesis]. 2010.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut pankreatitte hematolojik parametrelerin değeri Dr. Akif Yarkaç,1 Dr. Ataman Köse,2 Dr. Seyran Bozkurt Babuş,2 Dr. Fehmi Ateş,3 Dr. Gülhan Örekici Temel,4 Dr. Aydemir Ölmez5 Şanlıurfa Bilecik Devlet Hastanesi, Acil Tıp Kliniği, Şanlıurfa Mersin Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Mersin Mersin Üniversitesi Tıp Fakültesi Gastroenteroloji Anabilim Dalı, Mersin 4 Mersin Üniversitesi Tıp Fakültesi, Biyoistatistik ve Tıbbi Bilişim Bölümü, Mersin 5 Mersin Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Mersin 1 2 3

AMAÇ: Akut pankreatit (AP), acil serviste sık görülen bir enflamatuvar hastalıktır. Bu çalışmanın amacı, acil servise başvuru sırasında biliyer ve nonbiliyer AP’li hafif ve şiddetli AP hastalarında C-reaktif protein (CRP) ve hematolojik parametrelerin rolünü değerlendirmektir. GEREÇ VE YÖNTEM: Kontrol grubu olarak 100 hasta ve acil serviste AP tanısı alan 168 hasta çalışmaya dahil edildi. Kontrol grubunun ve AP hastaların demografik bilgileri (yaş, cinsiyet), amilaz, lipaz, CRP, hematolojik parametreler (beyaz kan hücresi sayımı [WBC], ortalama trombosit hacmi [MPV], kırmızı hücre dağılım genişliği [RDW], trombosit sayımı [PLT], nötrofil-lenfosit oranı [NLR]) kaydedildi ve karşılaştırıldı. Hastalar, AP etiyolojisine göre biliyer ve nonbiliyer grup olarak ayrıldı. Hastalığın şiddetine göre, hafif ve şiddetli AP olarak iki grup oluşturuldu, aynı parametreler değerlendirildi. BULGULAR: Hasta ve kontrol grubu arasında WBC, CRP, NLR, MPV ve PLT değerleri arasında anlamlı fark bulundu (p<0.001). Ranson ve APECHE II skorlaması WBC, CRP ve NLR ile korele idi. Hafif ve şiddetli AP grupları arasında, hastanede yatış süresi, CRP, WBC ve NLR değerleri arasında istatistiksel olarak anlamlı bir fark vardı (CRP için p=0.003, diğerleri için p<0.001). Ciddi AP’de NLR’nin kestirim değeri 8.05, sensitivite %93.48, spesifite %86.89 ve AUC: 0.937 olarak bulundu (p<0.001). TARTIŞMA: Beyaz kan hücresi sayımı, CRP ve NLR gibi parametrelerin acil serviste diğer diagnostik ve prognostik araçlarla birlikte kullanılması, başvuru ve prognoz sırasında klinisyenlere kolaylık sağlayabilir. Anahtar sözcükler: Akut pankreatit; kırmızı hücre dağılım genişliği; nötrofil-lenfosit oranı; ortalama trombosit hacmi; trombosit sayısı. Ulus Travma Acil Cerrahi Derg 2019;25(5):453-460

460

doi: 10.5505/tjtes.2018.69857

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

ORIGIN A L A R T IC L E

The effects of early physiotherapy on biochemical parameters in major burn patients: A burn center’s experience Murat Ali Çınar, PT, Msc,1 Kezban Bayramlar, PT, PhD.,1 Ali Güneş, M.D.,2 Yavuz Yakut, PT, PhD.1

Ahmet Erkılıç, M.D.,2

Department of Physical Therapy and Rehabilitation, Hasan Kalyoncu University Faculty of Health Sciences, Gaziantep-Turkey

Department of General Surgery, 25 Aralık State Hospital, Burn Center, Gaziantep-Turkey

ABSTRACT BACKGROUND: This study sets out to investigate the effects of early physiotherapy on biochemical parameters in major burn patients. METHODS: Ten women (50%) and 10 men (50%) aged 21–47 years old were included in this study. Participants were divided into two groups: the first group was the treatment group and the second group was the control group. In the treatment group, patients were admitted to the physiotherapy programme from the first day they have been hospitalised, in addition to their routine treatment (e.g. medical, surgery), for four days per week. The physiotherapy programme consisted of parameters, such as early mobilisation and ambulatory training, chest physiotherapy, and both active and passive normal joint movement exercises. The days of treatment were determined as of Tuesday, Wednesday, Thursday and Friday. Patients could not be treated on a Monday because that was surgery day. The control group consisted of patients who could not receive physiotherapy due to various reasons. All patients included in this study were evaluated weekly for six weeks after admission to the hospital. Parameters, such as demographic information, characteristics of burn injury, C-reactive protein, fibronectin, transferrin and prealbumin, were evaluated. RESULTS: When the results obtained in this study were considered, there was a significant difference in favour of the treatment group for all biochemical parameters (p<0.05). From the second week, a significant increase was observed in prealbumin values in the treatment group (p<0.05). A significant increase was observed in fibronectin after the fourth week (p<0.05). CONCLUSION: We believe that early physiotherapy should be included in the treatment in major burns. Early physiotherapy may reduce the effects of hypermetabolic response after major burns. There is a need for multi-centered and broader studies. Keywords: Biochemical parameters; early physiotherapy; fibronectin; major burns; prealbumin.

INTRODUCTION Burn injury is one of the longest traumas based on the duration of both hospitalisation and rehabilitation periods and its role in causing severe mortality and morbidity.[1] The American Burn Association (ABA) defines major burns as second degree burns with a total body surface area (TBSA) greater than 25% in adults, second degree burns with TBSA greater than 20% in children and all third-degree burns with TBSA above 10%. All burns, including hands, face, eyes, ears, feet, perineal burns, inhalation burns, electrical burns and fractures, fall into the major burn category.[2]

Lipolysis, proteolysis, glycolysis, and high fever, as well as many hyperdynamic and hypermetabolic responses, are seen in burn patients who have greater than 20% of the TBSA affected. These hypermetabolic responses seen in burn patients lead to decreased lean muscle mass, delayed wound healing weakened the immune system and premature mortality.[3] In the first 24 hours after major burns, fluid accumulation in the interstitial space occurs due to increased vascular permeability, whereas decreased intravascular volume affects tissue perfusion if no intervention ensues. Cardiac output is reduced, all systems, especially the gastrointestinal and renal systems, are affected. Because of burn injury, electrolytes in

Cite this article as: Çınar MA, Bayramlar K, Erkılıç A, Güneş A, Yakut Y. The effects of early physiotherapy on biochemical parameters in major burn patients: A burn center’s experience. Ulus Travma Acil Cerrahi Derg 2019;25:461-466. Address for correspondence: Murat Ali Çınar, M.D. Hasan Kalyoncu Üniversitesi, Havaalanı Yolu Üzeri 8. km., Şahinbey, 27000 Gaziantep, Turkey Tel: +90 342 - 211 80 80 E-mail: muratali.cinar@hku.edu.tr Ulus Travma Acil Cerrahi Derg 2019;25(5):461-466 DOI: 10.5505/tjtes.2018.05950 Submitted: 10.06.2018 Accepted: 25.12.2018 Online: 20.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

461

Çınar et al. The effects of early physiotherapy on biochemical parameters in major burn patients

the body are also affected and can lead to cell death.[4] The role of rehabilitation in burn treatment is becoming increasingly important, especially for major burn patients who need long-term rehabilitation, a process that includes both acute and post-discharge periods.[5] Rehabilitation should begin from the first day when the patient lies in the hospital.

Table 1. Physiotherapy protocol Parameters of PT protocol

Early stage burn PT protocol

Duration of PT

45–60 min

Times per day

In the literature, various researchers investigated the potential effects of physiotherapy on blood values. For example, Aguiar et al.[6] reported that the exercise therapy protocol could be a strategy for reducing IL-6 levels patients with OA of the knee. Kisacik et al.[7] concluded that e multidimensional exercise program should be taken into consideration for ankylosing spondylitis patients due to its positive effects on level of biochemical parameters, such as ESR, CRP and IL6. In the other research, Ruiz-Castilla et al.[8] stated that biomarkers might be a useful tool to guide burn treatments and may also explain why some treatments succeed or fail in improving outcomes. In the same article, they emphasised that an investigation into biomarkers in severe burn patients is a key feature of translational medicine in this area of knowledge. However, few studies examined the effects of physiotherapy on biochemical parameters in burn patients.

How many times a week

PT on admission

From the first day

PT after grafting

Third day of grafting

Chest physiotherapy

Respiratory exercises according

to the state of affection

Exercise therapy

Active and passive ROM

exercises according to the

patient’s condition

Training of mobilization

From the first day

To contribute to the literature, the present study aims to investigate the effects of early physiotherapy on biochemical parameters in major burn patients.

Table 2. Times of treatment

MATERIALS AND METHODS

Monday

This study was carried out in 25 Aralık State Hospital Burn Center and Hasan Kalyoncu University, Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation between October 2016 and April 2017.

Wednesday

20 major burn patients (10 women, 10 men) were included in this study. The inclusion criteria were: • Age ≥18 years; • Major burn injury (according to ABA); • Conscious patients. Patients with inhalation injury, various chronic disorders, organ dysfunctions, infection in the burn wound or the bloodstream and sepsis were all excluded from this study.

Sunday

Nutrient types and diets were the same in all groups. All patients received similar standard medical care and treatment from the time of emergency admission and acute care of the burn injury until the time of discharge. In addition, types and numbers of clinical interventions, such as surgical debridement and grafting, were similar in all groups. All patients who were included in this study were assessed for six weeks from the first day of hospitalisation and taken to the treatment programme. C-reactive protein (CRP), fibronectin, transferrin and prealbumin biochemical values of patients in all groups were recorded weekly from the first day of hospitalisation. Measurements of biochemical parameters were performed in 462

and ambulation Appropriate anti-

From the first day

contracture positioning PT: Physiotherapy; ROM: Range-of-motion.

Days of treatment

Morning

Afternoon

Operation Operation

Tuesday Physiotherapy Wound dressing

Physiotherapy

Thursday Physiotherapy Friday

Wound dressing

Saturday

Wound dressing

Physiotherapy

25 Aralık State Hospital Laboratories. Both initial and weekly values of the measured parameters were recorded. Patients in the treatment group have been received to the physiotherapy programme on the four times a week schedule, in addition to their routine treatment (such as medical treatment and surgery) from the first day of their stay in the hospital. Details of the physiotherapy programme are shown in Table 1. The control group consisted of patients who could not receive physiotherapy due to various reasons. For example, some Syrian patients did not want to receive physiotherapy due to communication problems. Despite the interpreter, they refused to communicate. Thus, they could not have physiotherapy. Treatment days were determined as of Tuesday, Wednesday, Thursday and Friday (Table 2).

Ethics Approval and Consent to Participate Ethical approval was obtained from the Hasan Kalyoncu Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Çınar et al. The effects of early physiotherapy on biochemical parameters in major burn patients

University, Faculty of Health Sciences Ethics Committee. Patients were informed of the nature of this study, and consent form was signed. Patients were made aware of their rights to withdrawn from this research at any time.

Table 3. Properties of burn patients

Treatment group

Control group

30.1±8.3

33.3±10.6

Age, years (Mean±SD)

Statistical Analysis

(Min-Max)

The statistical software of Statistical Product and Service Solutions 22.0 (SPSS) for Windows was used for analysis. A value of p<0.05 was considered statistically significant. In the study, which was formed by groups of 10 people for six weeks, the power of this study was 91%, according to the prealbumin value.[9]

Sex, n (%)

Variables which were determined by numerical measurements were expressed as arithmetic averages and standard deviations (mean±SD) for descriptive analyses. A Kolmogorov Smirnov test was used to investigate the normal distribution of biochemical parameters in our study. A t-test was used because the data showed a normal distribution.

RESULTS A total of 20 patients, 10 females and 10 males, participated in this study. The ages of patients ranged from 21 to 47 years old. When burn injuries of patients were evaluated; 19 (95%) were found to have flame burns, and 1 (5%) were found to have electrical burns. Also, it was observed that both the treatment group and the control group had burn injury percentages varying between 30 and 55 (Table 3). When the CRP values of the groups were examined; CRP values were found to be above normal reference values in both groups. When the groups were compared with each other, there was a significant decrease in the CRP value only during the last week in the treatment group compared with the control group (p<0.05) (Table 4).

Female

Erkek

21–47 20–47 3 (30)

Percentage of burn, (Mean±SD) (Min-Max)

7 (70)

3 (30)

37.5±7.9

41.5±9.5

30–55

Type of burn n(%)

Flame

Electrical

10 (100)

9 (90) 1 (10)

SD: Standard deviation; Min: Minimum; Max: Maximum.

Table 4. CRP values CRP Reference range (0–0.5 mg/dL)

Treatment Control group group

Mean±SD Mean±SD

First day

12.57±8.16

0.694

0.496

9.89±9.07

1 week

17.89±7.92 25.19±10.63 -1.742

0.099

2nd week

16.26±7.01

16.37±5.23

-0.039

0.969

3 week

10.16±6.38

13.98±4.31

-1.566

0.135

4th week

9.29±4.61

11.92±4.60

-1.278

0.217

5 week

8.08±5.43

12.46±6.20

-1.682

0.110

6th week

4.94±3.22

12.85±7.20

-3.169 0.005*

P<0.05. CRP: C-reactive protein; SD: Standard deviation.

Table 5. Fibronectin values

Initial and weekly measurements of fibronectin values were evaluated in both groups. Fibronectin values in the control group were below reference values for all weeks. In the treatment group, fibronectin values were below reference values only at one and two weeks. When the groups were compared, there was a difference starting in the fourth week in favour of the treatment group (p<0.05) (Table 5). When initial and weekly measurements of transferrin values were evaluated in both groups, it was determined that transferrin values were observed below reference values in both groups for all weeks. When the groups were compared, it was observed that there was a significant difference in favour of the treatment group from the first week (p<0.05) (Table 6).

Fibronectin Treatment Reference range group (25–40 mg/dL)

Control group

Mean±SD Mean±SD

First day

30.05±7.14

-0.494

0.627

1 week

24.35±11.20 22.10±11.06 0.452

0.657

2nd week

20.40±13.08 19.25±9.06

0.229

0.822 0.131

31.52±6.13

3 week

27.72±13.42 19.60±9.15

1.582

4th week

39.44±10.10 18.13±8.95

4.993 <0.001*

5th week

40.15±10.91 16.74±9.52

5.113 <0.001*

6 week

40.33±10.66 13.93±6.39

6.714 <0.001*

P<0.05. SD: Standard deviation.

Initial and weekly measurements of prealbumin values were evaluated in both groups. It was determined that transferrin values were observed below reference values in both groups Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

for all weeks. However, prealbumin values in the treatment group were found to be slightly below reference values from 463

Çınar et al. The effects of early physiotherapy on biochemical parameters in major burn patients

Table 6. Transferrin values Transferrin Reference range (202-364 mg/dL)

Treatment group

Control group

Mean±SD Mean±SD

First day

109.07±29.68 102.40±42.14 0.409 0.687

1 week

89.86±26.85 66.70±13.69 2.430 0.026*

2nd week

110.43±28.95 70.73±19.04 3.623 0.002*

3rd week

124.37±36.10 71.32±21.85 3.976 0.001*

4th week

144.00±44.72 60.13±13.50 5.678 <0.001*

5 week

160.18±31.74 62.32±18.23 8.455 <0.001*

6th week

159.00±32.21 55.88±15.10 9.166 <0.001*

P<0.05. SD: Standard deviation.

Table 7. Prealbumin values Prealbumin Reference range (0.2-0.4 g/dL)

Treatment group

Control group

Mean±SD Mean±SD

First day

0.10±0.05

0.11±0.04

-0.540

0.596

0.05±0.03

0.03±0.01

3.141

0.006*

2nd week

0.07±0.03

0.03±0.02

3.417

0.003*

3 week

0.10±0.05

0.04±0.01

3.828

0.001*

4th week

0.12±0.07

0.03±0.01

4.069

0.001*

5 week

0.16±0.07

0.05±0.05

3.703

0.002*

6th week

0.17±0.06

0.05±0.03

5.319

<0.001*

P<0.05. SD: Standard deviation.

the fifth week. When the groups were compared, it was observed that there was a significant difference in favour of the treatment group from the first week (p<0.05) (Tablo 7).

DISCUSSION In major burn patients, the organ which modulates the inflammatory response in the acute phase is the liver increased glycogenolysis, hyperglycaemia and insulin resistance underlie the inflammatory process.[10] Also, CRP is used as a marker of the acute inflammatory condition. CRP is often used to monitor inflammation in burn patients during the acute phase.[11] There are many studies in the literature about the effects of exercise on low-grade chronic inflammation. For example, Beavers et al.[12] emphasised that walking exercises reduced the effects of chronic inflammation. In this study, CRP values were observed to be approximately 30 times higher than the reference range for six weeks in 464

Fibronectin is a marker that acts in all phases of wound healing and delays wound healing if it’s deficient. In particular, fibronectin levels in the plasma provide information about wound healing in the acute phase.[13] Studies in the literature demonstrate that fibronectin affects wound healing and also show the effects of both exercise and physiotherapy on wound healing. Especially in healthy individuals, walking exercises have been reported to be the most effective exercise in wound healing.[14,15] Similarly, Çınar et al.[16] stated that physiotherapy increases fibronectin levels in pilot studies in major burn patients.

1st week rd

both groups. Although CRP levels in the treatment group decreased significantly compared with the control group after the fifth week, it was observed that the reference interval was still 15 to 20 times higher than normal levels. Our findings suggest that physiotherapy in the acute phase alone is not sufficient to reduce CRP levels to normal levels. However, physiotherapy reduces the effects of the inflammatory response, which is due to the major burn in the acute phase.

In this study, fibronectin levels were observed at normal levels on the first day in both the treatment and control groups. It was quite remarkable that fibronectin values that had started to decrease at the beginning of the acute phase due to burn injury increased in the treatment group from the fourth week and reached normal values during the fifth week. Major burn patients experience too many surgical operations during their treatment, which is grafting surgery. Therefore, patients need to devote a period to good wound healing. Thus, we believe that physiotherapy in the early period will positively affect wound healing of patients, may contribute to the success of graft operations and thus decrease the mortality of patients. In addition, delayed wound healing can lead to the formation of hypertrophic scarring in patients.[17] Our findings suggest that early physiotherapy will shorten the wound healing period and prevent hypertrophic scar tissue formation. Fibronectin values above the reference range may be indicative of poor wound healing or excessive scar tissue formation. [18] Also, to us it is not clinically meaningful that fibronectin values are slightly above the reference range in the treatment group in the sixth week. Transferrin is a glycoprotein which is synthesised in the liver and can be affected by all the trauma that affects the liver. This biomarker, which controls iron concentrations of cells, also reduces inflammation and is directly linked to the immune system. Because transferrin is an acute-phase protein, it is characterised by severe reductions in the early period after major trauma.[19] In the literature, to our knowledge, no studies related to the relationship between physiotherapy and transferrin has been found. Pouramir et al.[20] reported that long-term exercise may drain iron deposits and cause Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Çınar et al. The effects of early physiotherapy on biochemical parameters in major burn patients

serious problems analogous to the effects of exercise on iron ions in healthy subjects. In another study, it has been shown that long-term exercise in healthy individuals may have a negative effect on transferrin.[21] Although in the literature it is argued whether transferrin and exercise may have a negative relationship, transferrin values of the patients in our treatment group were observed to be higher than of the patients in the control group from the first week. At the sixth week, our findings suggest that the highest level of transferrin in the treatment group is at a reasonable level clinically, even though it is below the reference range. Our findings suggest that physiotherapy is directly effective as the reason for the rise in transferrin. Our findings suggest that physiotherapy affects iron concentration indirectly by reducing the effects of the hypermetabolic response due to the burn. This indirect reduction in the effects of the hypermetabolic response has a positive impact on transferrin levels. In particular, the suppression of the immune system affects the transferrin value negatively. Iron deposits decrease due to inflammation and impairment of liver function in major burn patients. Our findings suggest that physiotherapy may have increased the level of transferrin because of both the reduction of inflammation and the positive effects on liver function. Thus, physiotherapy is necessary in addition to nutrition and medical treatment in the acute phase. Prealbumin (also known as transthyretin) has often been used to assess the effects of protein-energy malnutrition (PEM) or any dietary on protein levels. Raguso et al.[22] have emphasised that types of nutrition in intensive care patients may differ in prealbumin levels. Türkmen et al.[23] used prealbumin as a biochemical marker in their study of PEM in children. However, in the same study, the findings showed that this parameter alone was not enough. Prealbumin values may be affected by types of nutrition. Therefore, only enteral-fed patients were included in this study. Although the prealbumin value has been used as a nutritional indicator, it has begun to be used to follow the clinical course of patients who have had major trauma in recent years. Prealbumin levels in burn patients are thought to be directly related to both the clinical course of the disease and the mortality of the patient.[24] A study that is investigating the effects of exercise on prealbumin has not been found in the current literature. Studies on prealbumin levels in intensive care and burn patients do not include an evaluation of the efficacy of physiotherapy on prealbumin.[25] In our study, when prealbumin levels of the treatment group were compared with the control group, there was a significant increase in the treatment group from the second week. Our findings suggest that this increase in the acute phase is Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

very positive for the clinical course of the disease. Early physiotherapy increases both protein metabolism and decreases mortality in patients.

Conclusion Further studies should be conducted with more patients and as a multi-centred study to provide new insights into the literature. Our findings suggest that the physiotherapy programme should be started at the earliest possible time in patients with major burn injuries. In addition to routine treatments, there must be a physiotherapy programme to reduce the effects of the hypermetabolic response due to burn injury. Conflict of interest: None declared.

REFERENCES 1. Pazar B, İyigün E, Şahin İ. Determination of subacute and chronic period sleep quality in burn patients. [Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2016;22:489–94. 2. Edlich RF, Larkham N, O’Hanlan JT, Berry R, Hiebert J, Rodeheaver GT, et al. Modification of the American Burn Association injury severity grading system. JACEP 1978;7:226–8. 3. Mandell SP, Gibran NS. Early Enteral Nutrition for Burn Injury. Adv Wound Care (New Rochelle) 2014;3:64–70. 4. Gillenwater J, Garner W. Acute Fluid Management of Large Burns: Pathophysiology, Monitoring, and Resuscitation. Clin Plast Surg 2017;44:495–503. 5. Chinese Burn Association; Chinese Association of Burn Surgeons, Cen Y, Chai J, Chen H, Chen J, Guo G, Han C, et al; Chinese Burn Care and Rehabilitation Association. Guidelines for burn rehabilitation in China. Burns Trauma 2015;3:20. 6. Aguiar GC, Do Nascimento MR, De Miranda AS, Rocha NP, Teixeira AL, Scalzo PL. Effects of an exercise therapy protocol on inflammatory markers, perception of pain, and physical performance in individuals with knee osteoarthritis. Rheumatol Int 2015;35:525–31. 7. Kisacik P, Unal E, Akman U, Yapali G, Karabulut E, Akdogan A. Investigating the effects of a multidimensional exercise program on symptoms and antiinflammatory status in female patients with ankylosing spondylitis. Complement Ther Clin Pract 2016;22:38–43. 8. Ruiz-Castilla M, Roca O, Masclans JR, Barret JP. Recent advances in biomarkers in severe burns. Shock 2016;45:117–25. 9. Portney LG, Watkins MP. Foundations of Clinical Research: Application to Practice. 3rd ed. Prentice Hall; 2009. 10. Jeschke MG, Boehning DF, Finnerty CC, Herndon DN. Effect of insulin on the inflammatory and acute phase response after burn injury. Crit Care Med 2007;35(9 Suppl):S519–23. 11. Luzzani A, Polati E, Dorizzi R, Rungatscher A, Pavan R, Merlini A. Comparison of procalcitonin and C-reactive protein as markers of sepsis. Crit Care Med 2003;31:1737–41. 12. Beavers KM, Brinkley TE, Nicklas BJ. Effect of exercise training on chronic inflammation. Clin Chim Acta 2010;411:785–93. 13. Lenselink EA. Role of fibronectin in normal wound healing. Int Wound J 2015;12:313–6. 14. Natiella JR, Burch L, Fries KM, Upton LG, Edsberg LE. Analysis of the collagen I and fibronectin of temporomandibular joint synovial fluid and discs. J Oral Maxillofac Surg 2009;67:105–13.

465

Çınar et al. The effects of early physiotherapy on biochemical parameters in major burn patients 15. Zhou W, Liu GH, Yang SH, Mi BB, Ye SN. Low-intensity treadmill exercise promotes rat dorsal wound healing. J Huazhong Univ Sci Technolog Med Sci 2016;36:121–6. 16. Çınar MA, Bayramlar K, Erkılıç A, Güneş A, Yakut Y. Effect of early physiotherapy on fibronectin level in major burn patients: a pilot study. J Exerc Ther Rehabil 2017;4:105–10. 17. Deitch EA, Wheelahan TM, Rose MP, Clothier J, Cotter J. Hypertrophic burn scars: analysis of variables. J Trauma 1983;23:895–8. 18. Cohen C, Leal MF, Belangero PS, Figueiredo EA, Smith MC, Andreoli CV, et al. The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study. Clinics (Sao Paulo) 2016;71:325–31. 19. Sal E, Yenicesu I, Celik N, Pasaoglu H, Celik B, Pasaoglu OT, et al. Relationship between obesity and iron deficiency anemia: is there a role of hepcidin? Hematology 2018;23:542–8. 20. Pouramir M, Haghshenas O, Sorkhi H. Effects of Gymnastic Exercise on the Body Iron Status and Hematologic Profile. Iranian Journal of Medical Sciences 2014;29:140–1.

21. Beard J, Tobin B. Iron status and exercise. Am J Clin Nutr 2000;72(2 Suppl):594S–7S. 22. Raguso CA, Dupertuis YM, Pichard C. The role of visceral proteins in the nutritional assessment of intensive care unit patients. Curr Opin Clin Nutr Metab Care 2003;6:211–6. 23. Türkmen S, Güvenen G, Erkal S, Heral Y, Akyüz S. The serum total protein, albumin, transferrin, prealbumin and retinol-binding protein Levels in patients with protein-energy malnutrition. İstanbul Med J 1999;1:15– 20. 24. Yang HT, Yim H, Cho YS, Kim D, Hur J, Kim JH, et al. Serum transthyretin level is associated with clinical severity rather than nutrition status in massively burned patients. JPEN J Parenter Enteral Nutr 2014;38:966–72. 25. Yang HT, Yim H, Cho YS, Kim D, Hur J, Kim JH, et al. Prediction of clinical outcomes for massively-burned patients via serum transthyretin levels in the early postburn period. J Trauma Acute Care Surg 2012;72:999–1005.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Majör yanıklı hastalarda erken dönem fizyoterapinin biyokimyasal parametreler üzerine etkisi: Bir yanık merkezi deneyimi Dr. Murat Ali Çınar,1 Dr. Kezban Bayramlar,1 Dr. Ahmet Erkılıç,2 Dr. Ali Güneş,2 Dr. Yavuz Yakut1 1 2

Hasan Kalyoncu Üniversitesi Sağlık Bilimleri Fakültesi, Fizyoterapi ve Rehabilitasyon Anabilim Dalı, Gaziantep 25 Aralık Devlet Hastanesi, Yanık Merkezi, Genel Cerrahi Kliniği, Gaziantep

AMAÇ: Bu çalışma, majör yanıklı hastalarda erken dönem fizyoterapinin biyokimyasal parametreler üzerine etkisini araştırmak amacıyla planlandı. GEREÇ VE YÖNTEM: Çalışmaya, yaşları 21–47 arasında değişen 10 kadın (%50), 10 erkek (%50) toplam 20 hasta alındı. Çalışmaya alınan hastalar, tedavi ve kontrol gurubu olmak üzere iki gruba ayrıldı. Tedavi grubundaki hastalar, hastaneye yattıkları ilk günden itibaren rutin tedavilerine (tıbbi, cerrahi vs.) ek olarak haftada dört gün olmak üzere fizyoterapi programına alındı. Fizyoterapi programı; erken mobilizasyon ve ambulasyon eğitimi, pulmoner fizyoterapi, aktif ve pasif normal eklem hareketi egzersizleri gibi parametreleri içermekteydi. Tedavi günleri salı, çarşamba, perşembe ve cuma günü olarak belirlendi. Pazartesi ameliyat günü olduğundan hastalara tedavi yapılamadı. Kontrol grubu, çeşitli nedenlerden dolayı fizyoterapi alamayan hastalardan oluşturuldu. Çalışmaya dahil edilen tüm hastaların hastaneye yatışlarından itibaren altı hafta boyunca haftalık olarak değerlendirmeleri yapıldı. Değerlendirmede demografik bilgiler, yanık hasarının özellikleri, C-reaktif protein, fibronektin, transferrin ve prealbumin gibi parametrelere bakıldı. BULGULAR: Çalışmadan elde edilen sonuçlara bakıldığında; tüm biyokimyasal parametrelerde tedavi grubu lehine anlamlı olduğu gözlendi (p<0.05). Prealbuminde tedavi grubunda ikinci haftadan itibaren anlamlı bir yükselme görüldü (p<0.05). Fibronektinde de tedavi grubunda dördüncü haftadan itibaren anlamlı bir artış gözlendi (p<0.05). TARTIŞMA: Erken fizyoterapi yanık tedavisinin önemli bir parçasıdır. Majör yanık sonrası görülen hipermetabolik cevabın etikisinin azaltılmasında, erken dönem fizyoterapinin etkili olabileceği görüşündeyiz. Ancak çok merkezli ve daha geniş çalışmalara ihtiyaç vardır. Anahtar sözcükler: Biyokimyasal parametreler; erken fizyoterapi; fibronektin; majör yanıklar; prealbumin. Ulus Travma Acil Cerrahi Derg 2019;25(5):461-466

466

doi: 10.5505/tjtes.2018.05950

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

ORIGIN A L A R T IC L E

The diagnostic value of serum urokinase-type plasminogen activator receptor in acute appendicitis Ali Aygün, M.D.,1 Mücahit Günaydın, M.D.,2 Ömer Vefik Özozan, M.D.,3 Murat Cihan, M.D.,4 Murat Karakahya, M.D.5 1

Department of Emergency Medicine, Ordu University Faculty of Medicine, Ordu-Turkey

Department of Emergency Medicine, Giresun University Faculty of Medicine, Giresun-Turkey

Department of General Surgery, Istinye University Hospital, İstanbul-Turkey

Department of Biochemistry, Ordu University Training and Research Hospital, Ordu-Turkey

Department of General Surgery, Ordu University Faculty of Medicine, Ordu-Turkey

ABSTRACT BACKGROUND: To measure serum uPAR levels in patients operated with a preliminary diagnosis of acute appendicitis (AA) and to investigate whether these parameters can be used as a biochemical marker in the diagnosis of AA. METHODS: Patients aged 18 or over, presenting to the emergency department between May and December 2018 and operated with a diagnosis of AA were enrolled. This study included 84 patients with surgical pathology results compatible with AA (Group A), 26 patients with surgical pathology results were not compatible with AA (Group B) and 55 healthy control groups. Serum uPAR levels were measured from venous blood samples taken at admission. RESULTS: Mean uPAR levels were 4.53±3.47 ng/mL in the Group A, 1.13±1.63 ng/mL in the Group B and 0.80±1.21 ng/mL in the control group. Serum uPAR levels differed statistically significantly from Group A in Group B and the control group, (p<0.05). CONCLUSION: uPAR was found to be significantly higher in the AA patients compared to the control group and patients with surgically determined non-AA pathologies. uPAR can be used as an aid in the diagnosis of acute appendicitis. Keywords: Abdominal pain; acute appendicitis; adult; inflammation; urokinase-type plasminogen activator receptor.

INTRODUCTION Acute appendicitis (AA) is the principal cause of acute abdomen in patients presenting to the emergency department due to abdominal pain.[1,2] Morbidity and mortality increase if AA is diagnosed late. Perforated appendix and associated peritonitis, intra-abdominal abscess, sepsis, and ileus can develop in the event of late diagnosis.[3] History, physical examination, an increase in blood inflammatory parameters, and clinical experience occupy an important place in diagnosis. Although radiological imaging methods, such as ultrasound (USG) and computerized tomography (CT), are used in the differential diagnosis of other pathologies causing pain in the

right lower quadrant, negative surgical pathology results are encountered at a rate of 10–30% in patients operated with a preliminary diagnosis of AA.[2,4–6] Clinicians, therefore, require new research to reduce increasing malpractice suits and negative appendectomy rates. Studies have, therefore, shown a relation between AA and biochemical parameters showing acute inflammation, such as white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin.[2,4] The pathophysiology of AA is associated with mucosal impairment caused by invasive infection and inflammation.[7] Infiltration of the intestinal wall by activating neutrophils occurs following invasion by intraluminal bacteria of the appendix wall

Cite this article as: Aygün A, Günaydın M, Özozan ÖV, Cihan M, Karakahya M. The diagnostic value of serum urokinase-type plasminogen activator receptor in acute appendicitis. Ulus Travma Acil Cerrahi Derg 2019;25:467-473. Address for correspondence: Ali Aygün, M.D. Ordu Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Ordu, Turkey Tel: +90 452 - 225 01 85 E-mail: dr_aliaygun@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):467-473 DOI: 10.14744/tjtes.2019.55623 Submitted: 01.06.2019 Accepted: 25.06.2019 Online: 21.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

467

Aygün et al. The diagnostic value of serum uPAR in AA

with an impaired mucosal barrier.[8] Degradation of the extracellular matrix is important for neutrophil invasion of tissue in the inflammatory response. One study showed immunoreactive urokinase-type plasminogen activator (uPA), involved in the conversion of plasminogen to plasma, in inflamed appendix tissue.[9] Plasmin leads to leukocytes passing the tissue barrier by reducing pericellular matrix proteins. Urokinase-type plasminogen activator receptor (uPAR, CD 87) is a glycosylphosphatidylinositol-anchored protein with high uPA receptor affinity. In addition to serving as a binding point on the cell surface, uPAR also facilitates leukocyte adhesion and migration.[10] Rijneveld et al.[11] determined that uPA and uPAR exhibit immune functions more by activating other defense cells than through fibrinolytic effects. Following an inflammatory stimulus, uPAR and proteases, such as chymotrypsin and phospholipase, facilitate leukocyte adhesion and migration, and activated neutrophils release the chemotactically active soluble form of uPAR from the cell surface into the circulation. With its direct chemotactic effect, uPAR facilitates the production of additional anti-inflammatory cells (generally neutrophils and macrophages) and the mobilization of hematopoietic stem cells in order to overcome bacterial invasion.[12] This study was planned to measure serum uPAR levels in patients operated with a preliminary diagnosis of AA and to investigate whether these parameters can be used as a biochemical marker in the diagnosis of AA.

MATERIALS AND METHODS This study was conducted after Ordu University Medical Faculty Clinical Research Ethical Committee approval (decision No. 2018/61). Patients aged 18 or over, presenting to the emergency department of a tertiary hospital between May and December 2018, and operated with a diagnosis of AA were enrolled. We planned to exclude patients with a nonAA focus of infection, acute coronary syndrome, hemorrhagic stroke, cerebrovascular disease, liver failure, acute pulmonary edema, cardiopulmonary arrest, acute mesenteric ischemia, or pulmonary thromboembolism, pregnant patients, subjects with acute trauma, or for whom consent to participate was not granted by the patient or relatives. We also intended to exclude patients for whom data deficiencies were determined at the end of the study period. Healthy volunteers aged over 18 with no disease and presenting to hospital for a check-up and agreeing to participate were included as the control group in this study. The clinical and demographic characteristics, symptoms, physical examination findings, Alvarado scores, WRP and CRP values, all abdominal USG and CT imaging results, and postoperative pathology results of the patients included in this study were recorded onto study forms. We planned to measure the serum uPAR values of the patient group and the control group. Patients with surgical pathology results compatible with AA were assigned into Group A, and patients 468

with surgical pathology results not compatible with AA were assigned into Group B.

Analysis of Biochemical Parameters Venous blood specimens were collected at the time of presentation. Blood specimens were drawn into a serum separator tube until the vacuum was filled. Tubes with separator gel were used for serum collection, and tubes containing potassium-EDTA were used for a blood count. Plasmas were separated by centrifugation for 10 min at 3000 rpm and were stored -80 ºC. Serum CRP levels were studied spectrophotometrically on a closed system with a Cobas 600 series c501 modular analyzer in our laboratory. Blood WBC levels were collected with results obtained with an XN-1000 device in our laboratory. uPAR levels in human blood serum were determined using a Cloud Clone (USCNK) (Wuhan, China) enzyme-linked immunosorbent assay (ELISA) kit in line with the manufacturer’s instructions. uPAR levels in specimens were calculated as ng/mL.

Statistical Analysis Statistical software was used for data analysis. Descriptive express was expressed as number and percentage for categorical variables and mean, standard deviation (SD), minimum (min), and maximum (max) for numerical variables. Compatibility with normal distribution was assessed using the KolmogorovSmirnov test. The t-test was used for two-way comparisons of normally distributed parameters, and the Mann-Whitney U test for non-normally distributed parameters. One-way analysis of variance (ANOVA) was used to compare normally distributed variables between three groups, and the Kruskal-Wallis test for non-normally distributed parameters. When significance was determined with the ANOVA test, two-group comparisons were performed using Turkey’s test if the group were homogeneous, or with Tamhane’s test if they were not homogeneous. The Mann-Whitney U test with Bonferroni correction was used for two-way comparisons when significance was determined using the Kruskal-Wallis test. Correlation coefficients and statistical significances were determined using Pearson’s test for normally distributed variables and Spearman’s test for non-normally distributed variables. The decision-determining characteristics of serum uPAR values in predicting the diagnosis of appendicitis were examined using Receiver Operating Characteristics (ROC) curve analysis. The sensitivity, specificity, positive predictive and negative predictive values were calculated for significant threshold values. At area under the curve (AUC) analysis, type 1 error levels less than 5% were interpreted as the statistically significant diagnostic value of the test. Statistical significance was set at p<0.05.

RESULTS One hundred ten patients aged 18 or over, presenting to the emergency department with abdominal pain and operated Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Aygün et al. The diagnostic value of serum uPAR in AA

with a diagnosis of AA were included in this study. The control group consisted of 55 healthy volunteers. Twenty-five patients could not be included in this study due to insufficient data. Following examination of the postoperative surgical pathology results of the patients operated with a diagnosis of AA, although pathology compatible with AA was determined in 84 cases (Group A), non-AA histopathological results were obtained in 26 (Group B) patients. Histopathological examination of the Group B patients revealed normal appendix vermiformis tissue in 15 cases, mesenteric lymphadenitis in six, ovarian cyst hemorrhage in three, and diverticulitis in two. Distributions of the patient groups’ age, sex, Alvarado score and clinical characteristics are shown in Table 1. CT

was the most commonly employed diagnostic imaging modality in the emergency department among the cases enrolled in the study. CT was performed on 75 Group A patients but not on the other nine. CT imaging was reported to be compatible with AA in 18 of the patients in Group B, and four patients were operated although CT imaging was not reported to be compatible with AA (Table 1). The patient groups’ mean WBC, CRP and uPAR values were compared. Serum uPAR levels differed statistically significantly from Group A in Group B and the control group. No significant difference was observed between the serum uPAR levels of Group B and the control group (Table 2).

Table 1. The groups’ demographic characteristics Characteristics

Group A Group B Control (n=84) (n=26) (n=55)

Sex, n (%)

Male

60 (71.4)

11 (42.3)

35 (63.6)

Female

24 (28.6)

15 (57.7)

20 (36.4)

38.8±18.9

33.2±13.7

27.7±10.8

Age, mean±SD (min-max)

(18–93) (18–62) (18–64)

Time to onset of symptoms (hours),

14.5±13.6

9.9±9.8

mean±SD (min-max)

(1–72)

(2–48)

Alvarado score mean±SD (min-max)

6.8±1.6

5.0±1.8

(3–10) (3–9)

– –

Right lower quadrant tenderness, n (%)

Yes

81 (96.4)

26 (100.0)

–

3 (3.6)

0 (0.0)

–

Leukocytosis, n (%)

Yes

68 (81.0)

10 (38.5)

–

16 (19.0)

16 (61.5)

–

Pain migration, n (%)

Yes

50 (59.5)

10 (38.5)

–

34 (40.5)

16 (61.5)

–

Lack of appetite, n (%)

Yes

43 (51.2)

9 (34.6)

–

41 (48.8)

17 (65.4)

–

Nausea-vomiting, n (%)

Yes

50 (59.5)

13 (50.0)

–

34 (40.5)

13 (50.0)

–

Rebound, n (%)

Yes

51 (60.7)

12 (46.2)

–

33 (39.3)

14 (53.8)

–

Body temperature >37.3, n (%)

Yes

17 (20.2)

2 (7.7)

–

67 (79.8)

24 (92.3)

–

Left shift in neutrophils, n (%)

Yes

64 (76.2)

12 (46.2)

–

20 (23.8)

14 (53.8)

–

USG imaging, n (%)

Positive

13 (15.5)

5 (19.2)

–

Negative

7 (8.3)

1 (3.8)

–

Not performed

64 (76.2)

20 (76.9)

–

CT imaging, n (%)

Positive

75 (89.3)

18 (69.2)

–

Negative

0 (0.0)

4 (15.4)

–

Not performed

9 (10.7)

4 (15.4)

–

Min: Minimum; Max: Maximum; USG: Ultrasonography; CT: Computerized tomography; SD: Standard deviation.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

469

Aygün et al. The diagnostic value of serum uPAR in AA

Table 2. Comparison of patient group blood white blood cell, C-reactive protein and uPAR levels Characteristic

Group Aa Group Bb Controlc p (n=84) (n=26) (n=55)

Mean±SD Mean±SD Mean±SD

White blood cell (cells/mm3) 14.096±3898 9953±2261 7391±1621

<0.001α

a,b

C-reactive protein (mg/L)

3.61±4.22

1.30±1.93

<0.001γ, a,c<0.001γ, b,c<0.001γ

0.16±0.17

<0.001β =0.001δ, a,c<0.001δ, b,c<0.001δ

a,b

uPAR (ng/mL)

4.53±3.47

1.13±1.63

0.80±1.21

<0.001β <0.001δ, a,c<0.001δ, b,c=0.439δ

a,b

α According to ANOVA test; βAccording to Kruskal Wallis test; γAccording to Post Hoc Tamhane’s testi; δAccording to Bonferroni-corrected Mann-Whitney U test. uPAR: Urokinase-type plasminogen activator receptor; SD: Standard deviation.

Table 3. The sensitivity and specificity percent of uPAR in diagnosing acute appendicitis uPAR (ng/mL)

Sensitivity (95% Cl)

Specificity (95% Cl)

+LR

-LR

PPV (%)

NPV (%)

>1.08

90.4% (82.4–95.8)

76.9% (56.4–91.0)

3.92

0.12

92.7

71.4

>1.5

82.1% (72.3–89.6)

84.6% (65.1–95.6)

5.34

0.21

94.5

59.5

>5.88

33.3% (23.4–44.5)

96.1% (80.4–99.9)

8.67

0.69

96.6

30.9

uPAR: Urokinase-type plasminogen activator receptor; +LR: Positive likelihood ratio; -LR: Negative likelihood ratio; PPV: Positive predictive value; NPV: Negative predictive value; Cl: Confidence interval.

The mean uPAR value of the AA patients with Alvarado scores less than 5 (n=17) was 1.92±4.06, compared to 4.06±3.24 in the AA patients (n=93) with Alvarado scores of 5 or more serum. The difference was statistically significant (p=0.018). The area under the curve (AUC) at ROC analysis performed to measure the diagnostic value of serum uPAR in patients was 0.88 (p<0.001, 95% confidence interval [CI] 0.80–0.97) (Fig. 1). AUC at ROC analysis performed for WBC was 0.83 (p<0.001, 95% CI 0.74–0.92), and 0.70 at ROC analysis for CRP (p<0.001, 95% CI 0.59–0.81). Analysis of correlation ROC Curve

1.0

Source of the Curve uPAR WBC CRP Reference Line

Sensitivity

0.8 0.6 0.4 0.2 0.0 0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 1. ROC analysis chart performed to measure the diagnostic value of WBC, CRP and uPAR in patients with acute appendicitis.

470

levels between uPAR values and WBC and CRP values revealed significant relations (r values 0.63 and 0.59, respectively) (p<0.001 for both). The sensitivity and specificity of uPAR in the diagnosis of appendicitis were calculated and are shown in Table 3. The specificity of uPAR in the diagnosis of appendicitis increased as uPAR values in patients’ plasma increased (Table 3).

DISCUSSION Activation of the uPA/uPAR system plays a key role in chemotaxis and inflammatory cell infiltration at the start of the inflammatory reaction.[13] In addition, the uPA system is also a key factor in cell migration, tissue remodeling, wound healing, inflammation, angiogenesis, tumor invasion, and metastasis. [14,15] uPAR (CD87) is a cellular receptor for uPA and is released from several cells, including leukocytes, and endothelial and malignant cells.[15,16] uPAR contributes to the conversion to plasmin of plasminogen, which leads to the proteolysis of matrix proteins, and the migration of leukocytes to the relevant region in the event of infection of inflammation.[15,17] Serum uPAR levels have been shown to increase in many inflammatory pathologies, such as sepsis, non-septic systemic inflammatory response (SIRS), pneumonia, pancreatitis, and intestinal inflammation.[12,18–23] Additionally, an increase in serum concentrations of the soluble form of uPAR has been shown to reflect activation of the immunological system and the severity of inflammatory diseases.[24,25] Kolber et al.[25] observed a significant increase in serum uPAR concentrations Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Aygün et al. The diagnostic value of serum uPAR in AA

from the first day of onset of symptoms of acute pancreatitis. That study also determined a significant correlation between uPAR and the neutrophil to lymphocyte ratio and reported that uPAR was associated with the severity of acute pancreatitis. AA is an inflammation that frequently occurs as a result of the invasion of the appendix by micro-organisms and obstruction of the lumen. An increase in inflammatory cells as a cytokine response to inflammation and an increase in biochemical inflammation values are observed.[26] Chan et al.[27] analyzed serum soluble uPAR in the extracted intestinal segments of patients with necrotizing enterocolitis, and also in blood studied simultaneously. This revealed a close relation between impairment of the intestinal mucosa barrier and increased uPAR levels in blood. Grøndahl-Hansen et al.[9] reported negative uPA immunostaining in normal appendix tissue and positive immunostaining in acute inflamed appendix tissue. Solberg et al.[28] reported increased uPA staining in perforated and non-perforated appendix biopsies compared to normal appendix tissue biopsies. Oztan et al.[15] determined a significant increase in serum uPAR levels in perforated and non-perforated cases among pediatric appendicitis patients compared to a healthy control group. They also reported sensitivity for AA in children of 85.7%, specificity of 84.3%, and an AUC of 0.90 at a uPAR cut-off value greater than 2.2 ng/mL. We also determined a significant difference in uPAR levels between adult AA patients and healthy controls (p<0.05), with an increase in serum uPSR levels in patients identified as AA-positive in terms of postoperative histopathology, in agreement with the previous literature. At the same time, we determined that the uPAR levels of patients with histopathology negative in terms of AA increased less than the levels of positive patients. We, therefore, think that uPAR levels increase in appendix inflammation in a manner compatible with its role in the inflammatory response. WBC and CRP are the inflammatory markers most commonly used in the diagnosis of AA. Several studies have investigated the diagnosis of AA with these parameters. Based on the results of those studies, WBC has been reported to exhibit a sensitivity of 67–97.8% and specificity of 31.9–90.8% in the diagnosis of AA, with NPV between 77.9% and 82% and PPV between 42% and 91.8%.[2,15,29] Yu et al.[30] performed a systemic review and meta-analysis to determine the diagnostic accuracy of CRP, WBC and procalcitonin in AA patients and reported a wide range of sensitivity (39–73%) and specificity (58–97%) values for CRP. They reported large differences between CRP cutoff values in studies, and that CRP had the largest area under the ROC curve, followed by WBC and procalcitonin. Correlation analysis in our study revealed that uPAR exhibited a good level of correlation with WBC and CRP. This suggests that the diagnostic value of uPAR in AA will increase when used together with WBC and CRP. Although AA is one of the most common surgical pathologies, difficulties continue to be experienced in diagnosis unUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

der emergency conditions. Clinical scoring systems are employed in addition to clinical findings in diagnosis. The most commonly employed scoring system in the diagnosis of AA is the Alvarado score.[26] The Alvarado scoring system relies on systemic symptoms, physical examination findings, and laboratory values. Alvarado scores of 4 or lower indicate a low probability of appendicitis, while surgery is recommended in all cases with scores ≥7.[31,32] However, prospective studies have reported that the Alvarado score alone cannot be used as a diagnostic test.[33,34] The Alvarado scores of the patients included in our study were recorded. We determined the significant difference between serum uPAR levels in patients with Alvarado scores above and below 5, suggesting a higher probability of AA in patients with high Alvarado scores and serum uPAR levels. Although history, physical examination, and Alvarado score occupy an important place in the diagnosis of AA, general surgeons currently employ imaging techniques in diagnosis due to increasing malpractice suits. Abdominal CT is a radiological methodology with high evidential value at differential diagnosis of AA and pathologies, causing right lower quadrant pain. Although the question of which radiological imaging technique should be employed is still the subject of debate, several studies have reported that CT is more reliable in the diagnosis of AA.[29] CT was also the most commonly used method in the diagnosis of AA in the present study. However, negative laparotomy results were encountered in 18 of the 93 patients with results compatible with AA at CT examination. Since atypical presentations are possible in patients presenting due to the right lower quadrant pain, we think that rather than using blood infective parameters of imaging techniques alone in the diagnosis of AA, use should be made of all findings obtained by correlating them with one another. In conclusion, the sensitivity and specificity levels of uPAR in the diagnosis of adult AA are compatible with previous studies investigating inflammatory parameters in AA patients. uPAR was significantly higher in the AA patients compared to the control group and patients with surgically determined non-AA pathologies. We think that serum uPAR values can be used as an assistant test in the diagnosis of adult AA patients.

Limitations The first limitation of this study is the relatively low number of patients. In addition, time to presentation to the emergency department after the onset of symptoms in AA patients is a variable and given that this leads to differences in patients’ serum uPAR levels is another limitation.

Acknowledgements This study was supported by the Ordu University Scientific Research Foundation (Project Number: HD-1803), Ordu, Turkey. We thank Dr. Volkan Karabacak for their help in this study. 471

Aygün et al. The diagnostic value of serum uPAR in AA

Compliance with Ethical Standards: None of the authors had any financial or personal relationships with other individuals or organizations that might inappropriately influence their work during the submission process. Informed consent: Informed consent was obtained from all individual participants included in this study. Conflict of interest: None declared.

REFERENCES 1. Sevim Y, Namdaroglu OB, Akpınar MY, Ertem AG. The diagnostic value of Neutrophil Lymphocyte ratio in acute appendicitis. Sakarymj 2014;4: 78–81. 2. Aygun A, Katipoglu B, İmamoglu M, Demir S, Yadigaroglu M, Tatli O, et al. Diagnostic value of plasma pentraxin-3 in acute appendicitis. J Invest Surg 2019;32:143–8. 3. Saraç M, Bakal Ü, TartarT, Kazez A. The role of the doctors in perforated appendicitis. Firat Med J 2014;19:126–9. 4. Mengücük ME, Ayten R, Bülbüller N, Gödekmerdan A, Başbuğ M, Mungan İ. Role of C-reactive protein, procalsitonin and neopterin in the diagnosis of acute appendicitis. Firat Med J 2010;15:40–3. 5. Gökçe AH, Aren A, Gökçe FS, Dursun N, Barut AY. Reliability of ultrasonography for diagnosing acute appendicitis. [Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2011;17:19–22. 6. Binnebösel M, Otto J, Stumpf M, Mahnken AH, Gassler N, Schumpelick V, et al. Acute appendicitis. Modern diagnostics-surgical ultrasound. [Article in German]. Chirurg 2009;80:579–87. 7. Carr NJ. The pathology of acute appendicitis. Ann Diagn Pathol 2000;4:46–58. 8. Tsuji M, Puri P, Reen DJ. Characterisation of the local inflammatory response in appendicitis. J Pediatr Gastroenterol Nutr 1993;16:43–8. 9. Grøndahl-Hansen J, Kirkeby LT, Ralfkiaer E, Kristensen P, Lund LR, Danø K. Urokinase-type plasminogen activator in endothelial cells during acute inflammation of the appendix. Am J Pathol 1989;135:631–6. 10. Del Rosso M, Margheri F, Serratì S, Chillà A, Laurenzana A, Fibbi G. The urokinase receptor system, a key regulator at the intersection between inflammation, immunity, and coagulation. Curr Pharm Des 2011;17:1924–43. 11. Rijneveld AW, Florquin S, Bresser P, Levi M, De Waard V, Lijnen R, et al. Plasminogen activator inhibitor type-1 deficiency does not influence the outcome of murine pneumococcal pneumonia. Blood 2003;102:934–9. 12. Backes Y, van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, et al. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Med 2012;38:1418–28. 13. Zeng M, Chang M, Zheng H, Li B, Chen Y, He W, et al. Clinical value of soluble urokinase-type plasminogen activator receptor in the diagnosis, prognosis, and therapeutic guidance of sepsis. Am J Emerg Med 2016;34:375–80. 14. Montuori N, Visconte V, Rossi G, Ragno P. Soluble and cleaved forms of the urokinase-receptor: degradation products or active molecules? Thromb Haemost 2005;93:192–8. 15. Oztan MO, Aksoy Gokmen A, Arslan FD, Cakir E, Sayan A, Abay E, et al. Diagnostic value of serum urokinase-type plasminogen activator receptor in children with acute appendicitis. Pediatr Emerg Care 2018. [Epub ahead of print]

472

16. Renckens R, Roelofs JJ, Florquin S, van der Poll T. Urokinase-type plasminogen activator receptor plays a role in neutrophil migration during lipopolysaccharide-induced peritoneal inflammation but not during Escherichia coli-induced peritonitis. J Infect Dis 2006;193:522–30. 17. Sitrin RG, Pan PM, Harper HA, Todd RF 3rd, Harsh DM, Blackwood RA. Clustering of urokinase receptors (uPAR; CD87) induces proinflammatory signaling in human polymorphonuclear neutrophils. J Immunol 2000;165:3341–9. 18. Wu XL, Long D, Yu L, Yang JH, Zhang YC, Geng F. Urokinase-type plasminogen activator receptor as a predictor of poor outcome in patients with systemic inflammatory response syndrome. World J Emerg Med 2013;4:190–5. 19. Koch A, Voigt S, Kruschinski C, Sanson E, Dückers H, Horn A, et al. Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients. Crit Care 2011;15:R63. 20. Donadello K, Scolletta S, Covajes C, Vincent JL. suPAR as a prognostic biomarker in sepsis. BMC Med 2012;10:2. 21. Kolber W, Kuśnierz-Cabala B, Dumnicka P, Maraj M, Mazur-Laskowska M, Pędziwiatr M, et al. Serum Urokinase-Type Plasminogen Activator Receptor Does Not Outperform C-Reactive Protein and Procalcitonin as an Early Marker of Severity of Acute Pancreatitis. J Clin Med 2018;7pii: E305. 22. Genua M, D’Alessio S, Cibella J, Gandelli A, Sala E, Correale C, et al. The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation. Gut 2015;64:589–600. 23. Wrotek A, Jackowska T. The role of the soluble urokinase plasminogen activator (suPAR) in children with pneumonia. Respir Physiol Neurobiol 2015;209:120–3. 24. Lipinski M, Rydzewska-Rosolowska A, Rydzewski A, Cicha M, Rydzewska G. Soluble urokinase-type plasminogen activator receptor (suPAR) in patients with acute pancreatitis (AP) - Progress in prediction of AP severity. Pancreatology 2017;17:24–9. 25. Kolber W, Kuśnierz-Cabala B, Maraj M, Kielar M, Mazur P, Maziarz B, et al. Neutrophil to lymphocyte ratio at the early phase of acute pancreatitis correlates with serum urokinase-type plasminogen activator receptor and interleukin 6 and predicts organ failure. Folia Med Cracov. 2018;58:57–74. 26. Cesur Ö, Benli AR, Koyuncu M. Analyses of laboratory tests in cases with appendicitis in childhood. Konuralp Tıp Dergisi 2016;8:5–8. 27. Chan KY, Leung FW, Lam HS, Tam YH, To KF, Cheung HM, et al. Immunoregulatory protein profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in preterm infants. PLoS One 2012;7:e36977. 28. Solberg A, Holmdahl L, Falk P, Willén R, Palmgren I, Ivarsson ML. Tissue proteolysis in appendicitis with perforation. J Surg Res 2011;169:194–201. 29. Yildirim O, Solak C, Koçer B, Unal B, Karabeyoğlu M, Bozkurt B, et al. The role of serum inflammatory markers in acute appendicitis and their success in preventing negative laparotomy. J Invest Surg 2006;19:345–52. 30. Yu CW, Juan LI, Wu MH, Shen CJ, Wu JY, Lee CC. Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis. Br J Surg 2013;100:322–9. 31. Konan A, Hayran M, Kılıç YA, Karakoç D, Kaynaroğlu V. Scoring systems in the diagnosis of acute appendicitis in the elderly. Ulus Travma Acil Cerrahi Derg 2011;17:396–400. 32. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64. 33. Ohmann C, Yang Q, Franke C. Diagnostic scores for acute appendicitis. Abdominal Pain Study Group. Eur J Surg 1995;161:273–81. 34. Macklin CP, Radcliffe GS, Merei JM, Stringer MD. A prospective evaluation of the modified Alvarado score for acute appendicitis in children. Ann R Coll Surg Engl 1997;79:203–5.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Aygün et al. The diagnostic value of serum uPAR in AA

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisitte serum ürokinaz-tipi plazminojen aktivatör reseptörünün tanısal değeri Dr. Ali Aygün,1 Dr. Mücahit Günaydın,2 Dr. Ömer Vefik Özozan,3 Dr. Murat Cihan,4 Dr. Murat Karakahya5 Ordu Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Ordu Giresun Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Giresun İstinye Üniversitesi Hastanesi, Genel Cerrahi Anabilim Dalı, İstanbul 4 Ordu Üniversitesi Eğitim ve Araştırma Hastanesi, Biyokimya Laboratuvarı, Ordu 5 Ordu Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ordu 1 2 3

AMAÇ: Acil servise sağ alt kadran ağrısı ile başvuran erişkin hastalarda serum ürokinaz-tipi plazminojen aktivatör reseptörü (uPAR) düzeylerini ölçmek ve bu parametrenin akut apandisit (AA) tanısında bir biyokimyasal belirteç olup olamayacağını araştırmayı planladık. GEREÇ VE YÖNTEM: Çalışmaya Mayıs 2018–Aralık 2018 tarihleri arasında acil servise başvuran ve AA tanısı konularak ameliyat edilen 18 yaş ve üzeri hastalar dahil edildi. Çalışmaya AA (Grup A) ile uyumlu cerrahi patoloji sonuçları olan 84 hasta, AA (Grup B) ile uyumlu olmayan cerrahi patoloji sonuçları olan 26 hasta ve 55 sağlıklı kontrol grubu dahil edildi. Hastalardan başvuru anında alınan venöz kan örneklerinden serum uPAR seviyeleri ölçüldü. BULGULAR: Grup A’da ortalama uPAR düzeyleri 4.53±3.47 ng/mL, Grup B’de 1.13±1.63 ng/mL ve kontrol grubunda 0.80±1.21 ng/mL idi. Grup A hastaların serum uPAR düzeyinin Grup B ve kontrol grupların serum uPAR düzeyleri ile karşılaştırılmasında istatiksel olarak anlamlı fark bulundu (p<0.05). TARTIŞMA: uPAR, AA hastalarında kontrol grubu ve cerrahi olarak AA dışı patoloji saptanan hastalara göre anlamlı olarak yüksek bulundu. Serum uPAR değerleri erişkin hastalarda AA tanısında yardımcı tetkik olarak kullanılabilir. Anahtar sözcükler: Akut apandisit; erişkin; inflamasyon; karın ağrısı; ürokinaz-tipi plazminojen aktivatör reseptörü. Ulus Travma Acil Cerrahi Derg 2019;25(5):467-473

doi: 10.14744/tjtes.2019.55623

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

473

ORIGIN A L A R T IC L E

Motor cycle spoke wheel injuries in children: A preventable accident Fatima Naumeri, M.D.,1 Bilal Qayyum, M.D.,1 Nadeem Ilahi Cheema, M.D.,1 Muhammad Sohail, M.D.,2 Muhammad Mustehsan Bashir, M.D.2 1

Department of Paediatric Surgery, King Edward Medical University, Lahore-Pakistan

Department of Plastic Surgery, King Edward Medical University, Lahore-Pakistan

ABSTRACT BACKGROUND: The incidence of motorcycle-induced spoke wheel injury is on the rise in our set up. These injuries range from minor soft tissue laceration to extensive crush injuries. This study aimed to evaluate the mechanism, characteristics, incidence and management of wheel spoke injuries. METHODS: Data of all children admitted to Pediatric Surgery Emergency from January 2014 to December 2017, presenting with wheel spoke injuries were analyzed. Incidence, mechanism and characteristics of injury, along with management plan, were noted. The outcomes were assessed by evaluating patients in follow up. RESULTS: Total study patients were 120, with an incidence of 21.7%. Mean age was 8.03Âą2.28 years. There were 101male patients and nine female patients. All patients were passengers and were sitting astride. Most of the patients were wearing shoes, and hindfoot area of the right foot was mainly involved. Grade 2 injury was seen in 55 (45.8%) and Grade 3 in 55 (45.8%) patients. Flap was needed in 27(22.5%) patients. All patients were mobile at the time of the follow-up. CONCLUSION: We noted the rising incidence of entrapment injuries; however, we had a satisfactory outcome in our patients using different management techniques. We recommend the implementation of safety protocols to avoid such catastrophic injuries. Keywords: Child; entrapment; foot injuries; motorcycle; spoke injuries.

INTRODUCTION Motorcycle injuries are one of the major causes of road traffic accidents in urban and suburban areas of developing countries like Pakistan.[1] The incidence of motorcycle-induced spoke wheel injuries (i.e. the feet of the rider getting trapped in the rotating spokes of the wheel of a motorcycle) is increasing in our part of the world because of lack of safety protocols and children are the main victims.[2] The spectrum of spoke wheel injury ranges from minor soft tissue laceration to extensive crush injury with tendon and bony involvement to subtotal amputations, mainly involving heel and ankle sites.[2â&#x20AC;&#x201C;4] Management of the spoke wheel injuries is often challenging and is based on the location and grade of injury. Oestern and

Tscherne classification (grade 0 to 3) is the most commonly used grading system to determine the extent of tissue damage. Management may involve multiple surgeries, including debridement of dead and devitalized tissues, repair of tendons, fracture fixation, skin grafting and flaps to salvage the limbs.[3,4] Our study objective was to evaluate the mechanism, characteristics, incidence and management of wheel spoke injuries. A previous study conducted in Pakistan in 2004 showed that children predominantly presented with spoke wheel injuries due to bicycles.[5] Our study shows the alarming trend of all children presenting after spoke wheel injuries due to the mo-

Cite this article as: Naumeri F, Qayyum B, Cheema NI, Sohail M, Bashir MM. Motor cycle spoke wheel injuries in children: A preventable accident. Ulus Travma Acil Cerrahi Derg 2019;25:474-478. Address for correspondence: Fatima Naumeri, M.D. House#93, Block-P, Phase-1, Defence Housing Authority, 54000 Lahore, Pakistan Tel: +92 4299211129 / 511 E-mail: fatimanaumeri@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):474-478 DOI: 10.14744/tjtes.2019.04052 Submitted: 28.10.2018 Accepted: 23.01.2019 Online: 22.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

474

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Naumeri et al. Motor cycle spoke wheel injuries in children

torcycle. The rationale of this study was to determine the injury mechanism and thus emphasize preventive measures based on its mechanism.

MATERIALS AND METHODS All the study protocols were approved by the Institutional Review Board. Medical records of all children presenting in Department of Pediatric Surgery, from January 2014 to December 2017, after entrapment injury to the foot due to wheel spokes, were reviewed. Children with polytrauma were excluded from this study. Informed consent was taken from parents. Demographic details (age and gender), mechanism and characteristics of injury (e.g. side of the foot, location of injury and severity of the injury, type of footwear at time of accident and relation of foot position with wheel, time from injury to presentation), laboratory data and X- ray findings of patients were noted. Management plan and outcome (mobility according to age) were noted. Treatment was administered according to the location and severity of injury based on Oestern and Tscherne classification.[3,4] â&#x20AC;&#x153;Grade 0 little or no injury to soft tissue Grade 1 Minor abrasion Grade 2 Local damage to skin or muscle Grade 3 Extensive damage to soft tissue and underlying structuresâ&#x20AC;? Parents were counselled regarding treatment modalities and their likely complications. The treatment employed included wound debridement, dressings and splint, skin graft and flap coverage or combination. Antibiotics were prescribed depending on the severity of injury and culture reports. In all patients, the wound was thoroughly washed and dressed in antibacterial cream. The limb was splinted with below-knee plaster of Paris slab and kept elevated. Treatment was continued for two to three weeks for Grade 1 injury patients till wound healed. In patients with moderate to severe injury (Grade 2 and 3), dead and necrotic tissue was debrided under anaesthesia. The wound was inspected regularly, and if required, repeat debridement was performed. Split thickness skin graft harvested from the thigh was applied to well-granulated wounds over non-weight- bearing areas. The graft was applied in close contact with a recipient bed with three-layered dressing. Grafted part of the limb was immobilised. The first dressing was changed on day five. Massage with steroid cream and compression garments were started after graft maturation, three to four weeks postoperatively. Patients with grade 3 injury were managed at the plastic surgery department. Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

After debridement in severe injury patients, VAC therapy was also used. A controlled negative pressure to wound was applied in cyclical fashion using the VAC device to remove blood or serous fluid. The application was repeated after three days and continued till wound was ready for further management. Flap coverage was performed for wounds with an exposed, fractured bone, ruptured tendons and/or weight-bearing area. Ruptured tendons were repaired using proline 4/0, and fractures were fixed by the orthopedic surgeon with the help of wires and screws. Skin defect was covered by the flap. Division and insetting of the flap were performed at three weeks interval. Reverse Sural Flap: Under general anaesthesia, the patient was placed in a prone position, and the trajectory of the lesser saphenous vein and the sural nerve was marked by drawing a line starting from the middle of the popliteal fossa to the posterior side of the lateral malleolus. Perforators were marked with hand-held Doppler. A tourniquet was used in all cases, but the lower limb was not previously emptied of blood; the perforators and plexuses can be seen better. The cutaneous island to be transferred was drawn on the middle third of the leg. The pivot point of the pedicle was kept 5 to 7 cm above the lateral malleolus. The procedure was started by incision at the top of the skin island, to locate the sural nerve and lesser saphenous vein. The sural nerve and the lesser saphenous vein were ligated proximally. The dissection was carried from proximal to distal, including deep fascia and vascular pedicle preserving the lower medial and lateral perforators. The pedicle width was kept 3 cm, and the flap was rotated 180 degrees and transposed to cover the defect without tension. Donor area was covered with a split-thickness skin graft. Medial Plantar Flap: This sensate fascia-cutaneous flap was raised from non- weight-bearing region of same foot and based on the medial plantar vessels. Flap was raised under Tourniquet control. Axis of the flap was drawn as a line from medial calcaneum to great toe metatarsal head. Flap was incised and raised from lateral to medial until the intermuscular septum with its perforators was seen and then dissection was carried out from the other side. Abductor Hallucis retracted medially to expose the medial plantar artery and nerve and the distal end of the vessels were divided. Flap was elevated with the vessel and septum, leaving the medial plantar nerve behind and was transposed to cover the defect. The donor site was skin grafted. Patients were mobilized usually six weeks after surgery and followed for one year postoperatively. Data were entered in SPSS 23. Mean and standard deviation of quantitative data (age) was recorded. Frequency and percentages of qualitative data (e.g. gender, the position of the foot, type of footwear, injury grade, treatment modality, and mobility) were calculated. Association of injury grade and need for flap were analyzed with age, gender, type of footwear, position and area of foot involved using logistic re475

Naumeri et al. Motor cycle spoke wheel injuries in children

(a)

(b)

Figure 1. (a) Grade-III injury in a patient. (b) Grade-II injury in a patient with partial tendoachilles tear. Treatment 2.50%

1.67%

13.33%

Repair plus graft Wound dressings

7.50%

30.83%

Repair of vessel/ herve/tendon Skin graft Flap rotation

41.67%

2.50%

Repair plus graft Skin graft plus flap

Figure 2. Different treatment modalities.

gression. The need for flap with a grade of injury was also analyzed using the Pearson chi-square test. P-value of less than 0.05 was taken as statistically significant.

RESULTS Patients admitted to the Department of Pediatric Surgery during the study period after trauma were 553, out of which patients admitted after spoke wheel injuries were 120 (21.7%). Mean age was 8.03Âą2.28 years. 101 (84.2%) were

(a)

male and 19 (15.8%) were female. All patients (100%) had suffered injuries as passengers of motorcycle and were sitting astride. The foot was trapped in the front-wheel in eight (6.7%) patients and back wheel in 112 (93.3%) patients. Fiftythree (44.2%) were wearing chappal, 63 (52.5%) were wearing shoes and 4 (3.3%) were wearing no footwear. The right foot was involved in 93 (77.5%) patients, and the left foot was involved in 27 (22.5%) patients. Forefoot was involved in 2 (1.7%) patients, midfoot in 5 (4.2%), hindfoot in 84 (70%), forefoot and midfoot in 4 (3.3%) patients and hindfoot with the midfoot in 25 (20.8%) patients. 108 (90%) patients presented within a day of the injury and only 12 (10%) patients presented late. Grade 1 injury was seen in 10 (8.3%) patients. Grade 2 injury was seen in 55 (45.8%) and Grade 3 in 55 (45.8%) patients. Figure 1a and b show different grades of injuries in patients. Treatment modalities are summarized in Figure 2. Flap was needed in 27 (22.5%) patients. Reverse sural artery flap was done in 23 patients, while four patients underwent medial plantar artery flap. There were no complications, like flap necrosis or graft rejection. Follow up after one year confirmed that all children were mobile, though some children had difficulty in climbing stairs. Outcome after skin grafting and flap can be seen in Figure 3a and b.

(b)

Figure 3. (a) Satisfactory outcome noted after skin grafting in patient with grade-II injury. (b) Satisfactory outcome noted after flap repair in patients with grade-III injury.

476

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Naumeri et al. Motor cycle spoke wheel injuries in children

There was no association between the need for flap and age, gender, type of footwear, position and area of foot involved. Similarly, there was no association between the grade of injury and age, gender, type of footwear, position and area of foot involved. However, we found a significant association between the need for flap and injury grade (p-value 0.0001).

DISCUSSION Since first reported in 1948, spoke wheel injuries are on the rise and its reported incidence is 4.3% of all trauma patients. [6] Road traffic accidents data from Thailand alone showed that almost 70% of the morbidity and mortality in children (less than 15 years of age) was due to motorcycle injuries.[1] In Pakistan, there has been a 400% increase in motorcycles in the last decade, and our study showed the alarming trend of children presenting after spoke wheel injuries due to a motorcycle, instead of a bicycle.[7] Incidence was 21.7% of all trauma patients presenting in our emergency. Reason of such a high incidence in our setup is no age limitation on riding, lack of wheel guards and footrests and overloading. Traffic regulations in developed countries prohibit children younger than seven years to ride motorcycles.[6,8] Our study showed that the right foot was more commonly involved and the area most susceptible was hindfoot, which is similar to other studies, as on left side chain guards act as a protection.[6,8] Literature suggests that wearing shoes help in decreasing the severity and incidence of spoke wheel injuries, but in our study, footwear did not help in reducing the severity. [6] Boys of age group 2-6 years were more commonly affected, which is consistent with other studies in the literature.[8,9] Motorcycles cause high energy trauma, so children are unlikely to present after grade 1 injury.[6] In our study, only 8.3% of children presented with grade 1 injury. Higher the grade, likelihood of multiple debridement increased. We noted that treatment and prognosis were directly related to a grade of injury. Grade 2 injury has an early time of presentation.[6,8] We admitted these patients and after initial debridement, re-evaluated all in 48 hours. No wound was primarily stitched on day of admission as vascularity is compromised.[4] Tendons were repaired and fractures stabilized if needed. Graft was done with or without the application of VAC in cases of soft tissue injuries. In grade 3 injury, the flap was performed in the plastic surgery department. As foot does not have adequate muscle and sole needs to bear weight, we preferred local flaps as our primary choice.[10] Choice of the flap also depended on defect size and site.[6,10] The most common used flap was reverse sural flap which has dependable blood supply with a preserved lesser saphenous vein.[6,11] The medial plantar flap was also performed as it is specialized glabrous skin and is perfect for the reconstruction of heel defects. Although microvascular surgery and other flaps have also been used in these injuries, we did not require these in our study. We did Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

not have any case of flap necrosis or any other complications. In follow up, good weight-bearing was noted. We did not calculate healing time, and although we followed up, detailed psychological or motor examination was not undertaken. A study conducted on long term follow up showed 14% had behavioural problems and mean healing time was markedly increased in grade three injuries.[9] Implementation of safety protocols, use of protective gear, guards on the wheel can help in prevention.[12,13]

Conclusion We noted a rising incidence of these entrapment injuries; however, we had a satisfactory outcome in our patients using different management techniques. We recommend the implementation of safety protocols to avoid such catastrophic injuries. Conflict of interest: None declared.

REFERENCES 1. World Health Organization, Regional Office for South-East Asia. (2015). Child development and motorcycle safety. Available at: http:// www.who.int/iris/handle/10665/173782. Accessed August 2, 2019. 2. Rathinam C, Nair N, Gupta A, Joshi S, Bansal S. Self-reported motorcycle riding behaviour among school children in India. Accid Anal Prev 2007;39:334–9. 3. Gupta HK, Shrestha R. Bicycle-spoke injuries of the foot and ankle: A prospective study. J Coll Med Sci-Nepal 2014;9:36–9. 4. Agarwal A, Pruthi M. Bicycle-spoke injuries of the foot in children. J Orthop Surg (Hong Kong) 2010;18:338–41. 5. Safdar CA. Bicycle and motorcycle spoke injuries in children as passengers. J Coll Physicians Surg Pak 2005;15:802–4. 6. Zhu YL, Li J, Ma WQ, Mei LB, Xu YQ. Motorcycle spoke injuries of the heel. Injury 2011;42:356–61. 7. Hamza A. Motorcycle production in Pakistan reaches nearly 2m per annum. Daily Times [newspaper on the internet]. Available from: http:// dailytimes.com.pk/93038/motorcycle-production-in-pakistan-reachesnearly-2m-per-annum/. Accessed August 2, 2019. 8. Agu TC. Motorcycle spokes entrapment foot injuries: Prevalence, and pattern of presentation in a private orthopedic and trauma centre, Southeast Nigeria–A 10-year retrospective analysis. Afr J Trauma 2017;6:6–10. 9. Sturms LM, van der Sluis CK, Snippe H, Groothoff JW, ten Duis HJ, Eisma WH. Bicycle spoke injuries in children: accident details and consequences. [Article in Dutch]. Ned Tijdschr Geneeskd 2002;146:1691–6. 10. Vlastou C. Alternatives in soft tissue reconstruction of the ankle and foot. Acta Orthop Scand Suppl 1995;264:27–30. 11. Farooq HU, Ishtiaq R, Mehr S, Ayub S, Chaudhry UH, Ashraf A. Effectiveness of Reverse Sural Artery Flap in the Management of WheelSpoke Injuries of the Heel. Cureus 2017;9:e1331. 12. Mak CY, Chang JH, Lui TH, Ngai WK. Bicycle and motorcycle wheel spoke injury in children. J Orthop Surg (Hong Kong) 2015;23:56–8. 13. Solagberu BA, Ofoegbu CK, Nasir AA, Ogundipe OK, Adekanye AO, Abdur-Rahman LO. Motorcycle injuries in a developing country and the vulnerability of riders, passengers, and pedestrians. Inj Prev 2006;12:266–8.

477

Naumeri et al. Motor cycle spoke wheel injuries in children

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Çocuklarda motosiklet ispitli tekerlek yaralanmaları: Önlenebilir bir kaza Dr. Fatima Naumeri,1 Dr. Bilal Qayyum,1 Dr. Nadeem Ilahi Cheema,1 Dr. Muhammad Sohail,2 Dr. Muhammad Mustehsan Bashir2 1 2

Kral Edward Tıp Üniversitesi, Çocuk Cerrahisi Anabilim Dalı, Lahore-Pakistan Kral Edward Tıp Üniversitesi, Plastik Cerrahi Anabilim Dalı, Lahore-Pakistan

AMAÇ: Motosiklet kullanımının neden olduğu ispitli tekerlek yaralanmasının görülme sıklığı artmaktadır. Bu yaralanmalar küçük yumuşak doku laserasyonundan yoğun ezilme yaralanmalarına kadar uzanır. Bu çalışmanın amacı ispitli tekerlek yaralanmalarının mekanizmasını, özelliklerini, insidansını ve tedavisini değerlendirmektir. GEREÇ VE YÖNTEM: Çocuk cerrahisi acil servisinde Ocak 2014–Aralık 2017 tarihleri arasında başvuran, ispitli tekerlek yaralanmaları ile başvuran tüm çocukların verileri analiz edildi. Tedavi planıyla birlikte yaralanma insidansı, mekanizması ve özellikleri kaydedildi. Takipteki hastalar değerlendirilerek sonuç değerlendirildi. BULGULAR: Çalışmaya alınan toplam hasta sayısı 120, yaralanmanın insidansı ise %21.7 idi. Yaş ortalaması 8.03±2.28 yıl idi. Yüz bir adet yaralı erkek hasta mevcuttu. Hastalar ve yolcular motosiklete ata biner gibi oturuyorlardı. Hastaların çoğu ayakkabı giyiyordu ve esasen sağ ayağın arka kısmı yaralanmıştı. Elli beş (%45.8) hastada ikinci ve 55 (%45.8) hastada üçüncü derece yaralanma görüldü. Yirmi yedi hastada (%22.5) flep kullanılması gerekti. Tüm hastalar ayaktan takip edildi. TARTIŞMA: Bu tuzaklanma yaralanmalarının insidansının arttığına dikkat çekmekle birlikte farklı tedavi teknikleri kullanarak hastalarımızda tatmin edici sonuçlar aldık. Bu kadar feci yaralanmaları önlemek için güvenlik protokollerinin uygulanmasını öneriyoruz. Anahtar sözcükler: Ayak yaralanması; çocuk; ispitli tekerlek yaralanması; motosiklet; tuzaklanma. Ulus Travma Acil Cerrahi Derg 2019;25(5):474-478

478

doi: 10.14744/tjtes.2019.04052

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

ORIGIN A L A R T IC L E

Fournier’s gangrene: Review of 36 cases Selahattin Çalışkan, M.D.,1 Emrah Özsoy, M.D.,2 Hasan Tahsin Gözdaş, M.D.4

Mustafa Sungur, M.D.,3

Department of Urology, Kanuni Sultan Süleyman Training and Research Hospital, İstanbul-Turkey

Department of Urology, Haydarpaşa Numune Training and Research Hospital, İstanbul-Turkey

Department of Urology, Hitit University Çorum Erol Olçok Training and Research Hospital, Çorum-Turkey

Department of Infectious Disease and Clinical Microbiology, Abant İzzet Baysal University Faculty of Medicire, Bolu-Turkey

ABSTRACT BACKGROUND: Fournier’s gangrene (FG) is a very rare disease in daily urological practice. Despite medical improvements, mortality in FG is still high. Early diagnosis is very important to reduce additional instrumentations and mortality. In this study, we aimed to present the characteristics of the patients with Fournier’s gangrene followed in two centers during ten years period. METHODS: The medical records of patients with FG were reviewed retrospectively. The patient characteristics, causative pathogens, laboratory findings and treatment modalities were evaluated. RESULTS: A total of 36 FG cases admitted between January 2008 and February 2018 were included in this study, consisting of 35 male patients, and one female patient with a mean age of 59.27±12.91 years. The mean duration of hospital stay was 19±10.44 days. The most common predisposing factor was diabetes mellitus, which was found in 28 patients. Malignancy was detected in three patients; prostate cancer in two patients and chronic lymphoblastic leukemia in one patient. Two patients had liver cirrhosis, and one patient had Behcet’s disease and psoriasis. The microbiological agent was isolated from a wound culture in nine patients. After urgent surgical debridement, daily dressing with nitrofurazone (Furacin) was done. Additional debridement was conducted when necessary. Orchiectomy was performed in 10 patients; two of them underwent bilateral orchiectomy. One patient died because of sepsis on the seventh day of hospital admission. CONCLUSION: FG is a life-threatening urological emergency with a high mortality rate. Treatment with broad-spectrum antibiotics and urgent surgery is pivotal for the prevention of mortality. Keywords: Fournier’s gangrene; morbidity; mortality; necrotizing fasciitis.

INTRODUCTION Fournier’s gangrene (FG) is a rare, life-threatening disease characterised by rapidly progressive necrotizing fasciitis of the perianal and genitourinary area and usually affects men. [1] The incidence was reported to be 1,6–3/100.000 with a 10/1 male predominance.[2] The disease was firstly reported by Baurienne in 1764.[3] He presented the case of a 45-yearold man with scrotal gangrene and suggested radical surgical debridement of all the infected and necrotic tissues. After 119 years, Jean-Alfred Fournier, a venereologist, reported

five previously healthy young male with progressive gangrene of the penis and scrotum in 1883.[4] Since this description of Fournier, the classical patient profile has been changed.[5] Fournier’s gangrene has been shown to be associated with several comorbidities and affects both genders, either young patients or elder ones as well. There are some predisposing factors for FG, such as diabetes mellitus, alcoholism, atherosclerosis, peripheral arterial disease, trauma, tissue injury, malnutrition, immunosuppression, HIV infection, liver disease and leukemia.[6] These predispos-

Cite this article as: Çalışkan S, Özsoy E, Sungur M, Gözdaş HT. Fournier’s gangrene: Review of 36 cases. Ulus Travma Acil Cerrahi Derg 2019;25:479-483. Address for correspondence: Selahattin Çalışkan, M.D. Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, İstanbul, Turkey Tel: +90 212 - 404 15 00 E-mail: dr.selahattin@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):479-483 DOI: 10.14744/tjtes.2019.30232 Submitted: 10.10.2018 Accepted: 09.01.2019 Online: 20.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

479

Çalışkan et al. Fournier’s gangrene

ing factors are related to poor prognosis and high mortality. Although the overall mortality rate is nearly 20–40%, it can be as high as 70–80% if the patient presents with sepsis. This study aims to present the characteristics of 36 cases of FG followed in two medical centers during the ten years period.

MATERIALS AND METHODS The patients who were diagnosed with FG and followed in two medical centers (Haydarpaşa Numune Training and Research Hospital and Çorum Erol Olçok Training and Research Hospital) between January 2008 and February 2018 were reviewed retrospectively. The patients who had missing data were excluded from this study. The clinical presentation, age, gender, surgical and medical treatments were recorded. The predisposing factors, hospitalization period and laboratory results were analyzed. After starting broad-spectrum antibiotics, all patients underwent urgent surgery with wide debridement. The data were expressed as mean+standard deviation, median and percentage values using MedCalc statistical software demo version 17.6 (Ostend, Belgium, 2017).

RESULTS There were 36 patients in the present study. Among these patients; 35 (97.2%) were male, and one (2.8%) was female. The mean age of the patients was 59.27±12.91 years, and the hospitalization period was 19±10.44 days. The diagnosis of FG was made by the characteristic clinical picture. The most common symptom was swelling (Fig. 1). The most common predisposing factor was diabetes mellitus, which was found

in 28 patients. Malignancy was detected in three patients; prostate cancer in two patients and chronic lymphoblastic leukemia in one patient. Two patients had liver cirrhosis, and one patient had Behcet’s disease and psoriasis. Table 1 shows the patient characteristics and predisposing factors. Primary antimicrobial regimens were as follows: cefazolin+ gentamicin+metronidazole, ceftriaxone+metronidazole, imipenem, piperacillin/tazobactam+teicoplanin and meropenem+vancomycin. Antimicrobial treatment was revised according to culture antibiogram result of isolated microorganism. The microbiological agent was isolated from wound culture in nine patients: Escherichia coli in one patient, E.coli and Corynebacterium in two patients, E.coli and Candida albicans in two patients, Actinomyces turicensis in one patient, Bacteroides fragilis in one patient, methicillin-resistant Staphylococcus aureus in two patients. Laboratory results of the patients are summarized in Table 2. After urgent surgical debridement, daily dressing with nitroTable 1. Characteristics of the patients

Results

Number of the patients

100

Male

97.2

Female

2.8

Mean±SD

Age (years)

59.27±12.91

Hospital stay (days)

19±10.44

Clinical symptoms Swelling

21 58.33

Erythema

18 50

Purulent collection

44.4

Pain

14 38.9

Fever

5 13.9

Comorbidities

Diabetes mellitus

Malignancy

Liver cirrhosis

Other

77.7

3 8.3 2

5.5

2 5.5

Additional surgery Orchiectomy

Figure 1. Scrotal oedema in a patient with Fournier’s gangrene.

480

Suprapubic tube placement

10 27.80 3

8.33

Mortality

1 2.77

Reconstruction

31 100

Primary closure

67.75

Flap techniques

22.6

Graft techniques

9.67

SD: Standard deviation.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Çalışkan et al. Fournier’s gangrene

Table 2. Laboratory test results of the patients Laboratory tests

Results

White blood count (*1000/mm3), mean±SD CRP (mg/dL), median (range) Hematocrit (%), mean±SD

37.29±8.48

Leukocytosis (>10.000/mm3), n (%)

34 (94.4)

Fever (>38 °C), n (%)

5 (13.9)

Kidney injury (Cr >1.2 mg/dL) n,% Albumin (<4 g/dL), n (%)

16.69±5.54 21.88 (0.6–520)

13 (36.11) 32 (96.96)

Microbiological organism in wound cultures, n (%)

Escheriscia coli (E.coli)

1 (11.1)

E.coli and Corynebacterium

2 (22.2)

E.coli and Candida albicans

2 (22.2)

Actinomyces turicensis

1 (11.1)

Bacteroides fragilis

1 (11.1)

Methicillin resistant Stafilococcus aureus

2 (22.2)

SD: Standard deviation.

furazone (Furacin) was done (Fig. 2). Additional debridement was conducted if necessary. Orchiectomy was performed in 10 patients; two of them underwent bilateral orchiectomy. One patient died because of sepsis on the seventh day of hospital admission.

DISCUSSION Fournier’s gangrene is one of the urological emergencies and characterized by progressive necrotizing fasciitis of the external genitalia and perineum.[7] The annual incidence of this

Figure 2. Dressing with nitrofurazone after urgent surgical debridement.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

disease is 1.6 per 100.000 in male patients, and the incidence increases with aging. Although pediatric cases are very rare, some pediatric cases have been reported from countries with limited sources in which poor hygiene is prevalent among immunocompromised children.[8] The peak incidence is seen after 50 years of age.[7] Fournier’s gangrene is frequently diagnosed in males, but it may affect both genders in every age groups.[9] The reason for the lower prevalence in female patients can be explained by the simple drainage of the female perineum through the vaginal way. Another reason for the low prevalence in women is that most of the articles were reported by urology clinics, which led to males being overreported. The authors from urology clinics reported the rate of females as 0–5% in their studies.[5,10] In contrast, studies from the other clinics reported that the female patients composed 56% and 28.8% of the whole patients.[9,11] In our study, the mean age of the patients was 59 years, and 97% of the patients were male. The diagnosis of FG is usually made by physical examination. [9] The clinical presentation is variable depending on the infection stage, comorbidities and general health status of the patients.[12] Tenderness, erythema, swelling and pain are the main symptoms. The patients can present with fever, malaise, local discomfort, purulent collection and sepsis.[13] The differential diagnosis includes many diseases, such as cellulitis, acute epididymitis, orchitis, strangulated hernia, scrotal abscess, balanitis, herpes infection, pyoderma gangrenosum, polyarteritis nodosa, warfarin necrosis and ecthyma gangrenosum.[6] Radiological examinations, such as X-rays, ultrasonography, computed tomography and magnetic resonance imaging techniques, may be helpful in the diagnosis when the diagnosis is uncertain.[12] The ultrasonographic finding is thickened scrotal tissue due to inflammation and edema. Computed tomography is superior to radiography and ultrasonography, which shows soft tissue thickening, inflammation, abscesses and subcutaneous gas. Magnetic resonance imaging is expensive and time-consuming, which may cause a delay in the treatment. We diagnosed FG in our patients based on the characteristic clinical picture. We did not use radiological imaging. Most of the patients presented with swelling and erythema in this study. Pathophysiologically, bacterial infection results in obliterating endarteritis, ischemia and eventually tissue necrosis.[13] There are some predisposing factors, such as age, hypertension, chronic renal disease, obesity, hepatic diseases, alcoholism, congestive heart failure, peripheral vascular disease, smoking, immunosuppression, acquired human immunodeficiency syndrome, cachexia, diabetes mellitus and malnutrition.[12–14] Some scoring systems were developed for the diagnosis and prognosis of FG.[12] The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) scoring system includes age, gender, potassium, sodium, creatinine, platelet, C-reactive protein, leukocyte, hemoglobin and glucose. The Fournier Gangrene Severity Index (FGSI) predict the prognosis with some pa481

Çalışkan et al. Fournier’s gangrene

rameters, including body temperature, heart rate, respiratory rate, sodium, potassium, creatinine, bicarbonate, leukocyte and hematocrit values. FG is a polymicrobial infection of necrotizing soft tissues.[12] E. coli is the most common pathogen. Other bacterial pathogens are Streptococcus, Bacteroides, Enterobacter, Staphylococcus, Enterococcus, Corynebacterium, Klebsiella and Pseudomonas. This necrotizing soft tissue infection can be categorized into four groups based on the microbiological agent. • Type 1 (polymicrobial) is the most common type and consists of more than 50% of the infections. There is synergistic action of aerobic, anaerobic and facultative anaerobic bacteria (E.coli, Pseudomonas and Bacteroides) and usually affects immunocompromised patients. • Type 2 (monomicrobial) can be more aggressive than type 1. Group A beta-hemolytic streptococcus is the most common agent. • Type 3 is responsible for less than 5% of the infections and associated with Vibrio species or gram-negative bacteria. Crepitus because of the gas production is a common clinical finding. • Type 4 (fungal) is due to Candida spp and Zygomycetes, which is usually seen in immunocompromised patients after trauma. Effective resuscitation, broad-spectrum antibiotherapy and wide surgical debridement of necrotic tissues is the cornerstone of the treatment.[9] Preoperative findings are lack of bleeding due to the thrombosis of the vessels, grey discoloration due to necrosis, edematous fluid and the absence of tissue resistance during dissection.[12] All necrotic tissues must be debrided until the bleeding of the healthy tissues was detected. In our study, all of the patients underwent early surgical debridement after starting empiric antibiotherapy. There are some poor prognostic factors; delay in the treatment, primary anorectal disease, female gender, advanced age, diabetes mellitus, multiple organ failure and high FGSI scores.[9] The mortality rate is still as high as 16–50% despite the modern diagnostic and treatment modalities. There are some limitations to the current study. Firstly, this study includes a limited number of patients with a retrospective design. The lack of FGSI is the other limitation, and our study demonstrated data from only two medical centers that limit the results.

482

Fournier’s gangrene is one of the rare urological diseases which has a high mortality rate. Early diagnosis and treatment with broad-spectrum antibiotics and surgical debridement are very important to decrease the mortality. Conflict of interest: None declared.

REFERENCES 1. Althunayyan S, Karamitosos E. Fournier’s gangrene in an obese female in third trimester of pregnancy. Saudi Med J 2018;39:415–8. 2. Taylor GM, Hess DV. Fournier gangrene: a rare case of necrotizing fasciitis of the entire right hemi-pelvis in a diabetic female. Oxf Med Case Reports 2018;2018:omx094. 3. Baurienne H. Sur une plaie quisest terminee par la sphacele de la scrotum. J Med Chir Pharm 1764;20:251–6. 4. Fournier JA. Jean-Alfred Fournier 1832-1914. Gangrène foudroyante de la verge (overwhelming gangrene). Sem Med 1883. Dis Colon Rectum 1988;31:984–8. 5. Ferretti M, Saji AA, Phillips J. Fournier’s Gangrene: A Review and Outcome Comparison from 2009 to 2016. Adv Wound Care (New Rochelle) 2017;6:289–95. 6. Kuzaka B, Wróblewska MM, Borkowski T, Kawecki D, Kuzaka P, Młynarczyk G, Radziszewski P. Fournier’s Gangrene: Clinical Presentation of 13 Cases. Med Sci Monit 2018;24:548–55. 7. Sorensen MD, Krieger JN, Rivara FP, Broghammer JA, Klein MB, Mack CD, et al. Fournier’s Gangrene: population based epidemiology and outcomes. J Urol 2009;181:2120–6. 8. Bakshi C, Banavali S, Lokeshwar N, Prasad R, Advani S. Clustering of Fournier (male genital) gangrene cases in a pediatric cancer ward. Med Pediatr Oncol 2003;41:472–4. 9. Yücel M, Özpek A, Başak F, Kılıç A, Ünal E, Yüksekdağ S, et al. Fournier’s gangrene: A retrospective analysis of 25 patients. Ulus Travma Acil Cerrahi Derg 2017;23:400–4. 10. Yanaral F, Balci C, Ozgor F, Simsek A, Onuk O, Aydin M, et al. Comparison of conventional dressings and vacuum-assisted closure in the wound therapy of Fournier’s gangrene. Arch Ital Urol Androl 2017;89:208–11. 11. Chia L, Crum-Cianflone NF. Emergence of multi-drug resistant organisms (MDROs) causing Fournier’s gangrene. J Infect 2018;76:38–43. 12. Voelzke BB, Hagedorn JC. Presentation and Diagnosis of Fournier Gangrene. Urology 2018;114:8–13. 13. Dos-Santos DR, Roman ULT, Westphalen AP, Lovison K, Spencer Neto FAC. Profile of patients with Fournier’s gangrene and their clinical evolution. [Article in English, Portuguese]. Rev Col Bras Cir 2018;45:e1430. 14. Hsu JM, Chen M, Weng CH, Tseng JS. Fournier’s Gangrene: Clinical Characteristics in the Elderly. International Journal of Gerontology 2014;8:162–5.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Çalışkan et al. Fournier’s gangrene

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Fournier gangreni: Otuz altı olgunun incelenmesi Dr. Selahattin Çalışkan,1 Dr. Emrah Özsoy,2 Dr. Mustafa Sungur,3 Dr. Hasan Tahsin Gözdaş4 Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, İstanbul Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, İstanbul Hitit Üniversitesi Çorum Erol Olçok Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, Çorum 4 Abant Izzet Baysal Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Bolu 1 2 3

AMAÇ: Fournier gangreni (FG) günlük üroloji pratiğinde çok nadir görülen bir hastalıktır. Tıbbi gelişmelere rağmen, FG’de mortalite hala yüksektir. İlave girişimlerin ve mortalitenin düşürülmesi için erken tanı çok önemlidir. Bu çalışmada, on yıl süresince iki merkezde izlenen FG’li hastaların özelliklerini sunmayı amaçladık. GEREÇ VE YÖNTEM: Fournier gangrenli hastaların tıbbi kayıtları geriye dönük gözden geçirildi. Hastaların özellikleri, etken patojenler, laboratuvar bulguları ve tedavi yaklaşımları değerlendirildi. BULGULAR: Ocak 2008–Şubat 2018 tarihleri arasında başvuran 35’i erkek ve biri kadın olmak üzere toplam 36 FG olgusu çalışmaya alındı. Hastaların yaş ortalaması 59.27±12.91 idi. Hastanede kalış süresi ortalama 19±10.44 gündü. En sık predispozan faktör 28 hastada bulunan diyabetes mellitus idi. İki hastada prostat kanseri ve bir hastada kronik lenfoblastik lösemi olmak üzere üç hastada malignite saptandı. İki hastada karaciğer sirozu ve bir hastada da Behçet hastalığı ve sedef hastalığı vardı. Dokuz hastanın yara kültüründen mikrobiyolojik etken izole edilmiştir. Acil cerrahi debridman sonrası nitrofurazone (Furacin) ile günlük pansuman yapıldı. Gerektiğinde ilave debridman gerçekleştirildi. On hastaya orşiektomi uygulandı, bunlardan ikisi iki taraflı orşiektomi idi. Bir hasta hastaneye başvurusunun yedinci gününde sepsis nedeniyle kaybedildi. TARTIŞMA: Fournier gangreni yüksek mortalite oranı ile hayatı tehdit edici bir ürolojik acildir. Geniş spektrumlu antibiyotikler ve acil cerrahi müdahale mortaliteyi önlemektedir. Anahtar sözcükler: Fournier gangreni; morbidite; mortalite; nekrotizan fasiit. Ulus Travma Acil Cerrahi Derg 2019;25(5):479-483

doi: 10.14744/tjtes.2019.30232

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

483

ORIGIN A L A R T IC L E

The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome Mustafa Kemal İlik, M.D.,1 Fatih Keskin, M.D.,2 Fatih Erdi, M.D.,2 Bülent Kaya, M.D.,2 Yaşar Karataş, M.D.,2 Erdal Kalkan, M.D.2 1

Department of Neurosurgery, Farabi Hospital, Konya-Turkey

Department of Neurosurgery, Necmettin Erbakan University Meram Faculty of Medicine, Konya-Turkey

ABSTRACT BACKGROUND: In this study, we aim to evaluate the potential effects of methylprednisolone on the neurological outcome of spinal cord injury (SCI) patients with thoracolumbar junction (T10-L1) spine fractures. METHODS: The data from 182 SCI patients who sustained a thoracolumbar junction spine fracture were operated by us between September 2008 to January 2015 were analysed retrospectively. The patients were divided into two groups: Group 1 underwent methylprednisolone treatment in conjunction with early surgical intervention, while group 2 underwent only early surgical intervention without methylprednisolone treatment. American Spinal Injury Association (ASIA) motor index scores of the patients were evaluated and compared with statistical methods at admission and at the first-year follow-up. RESULTS: The main follow-up period was 14.4±1.4 months in group 1 and 13.6±1.7 months in group 2. Initial and last follow-up ASIA scores of the patients were similar between groups (p>0.05), but the complication rate was significantly high in group 1 (p<0.05). CONCLUSION: The findings showed that steroids have no significant beneficial effects on the neurological outcome but have significant side effects and leads to increased complication rate in SCI patients. Keywords: Methylprednisolone; spinal cord injury; thoracolumbar junction; treatment.

INTRODUCTION Although spinal cord injury (SCI) is a serious and common health problem, the effective management of these types of injuries remains controversial. Mechanical compression, impact and shear injuries cause a primary SCI which initiates a cascade of deleterious pathological processes and leads to secondary neurological tissue destruction. Both primary and secondary injury mechanisms give rise to subsequent neurological deterioration.[1] Surgical procedures, such as decompression and stabilization of the spine, are primarily intended to prevent increased pressure within the spinal canal and to restore normal spinal alignment. Although decompression of the spinal cord is fundamental, it may not prevent the spinal cord from secondary injury.[1]

The prevention and treatment of secondary spinal injury remain controversial in spite of several experimental and clinical studies.[2–6] Currently, steroid treatment after SCI remains a viable option although some studies reported that steroids might not be beneficial and actually increase the overall rate of complications and even may bring about death.[7–10] The primary aim of the present study is to evaluate the potential effects of intravenous methylprednisolone treatment on the neurological outcome of SCI patients which have thoracolumbar junction spine fractures.

Cite this article as: İlik MK, Keskin F, Erdi F, Kaya B, Karataş Y, Kalkan E. The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome. Ulus Travma Acil Cerrahi Derg 2019;25:484-488. Address for correspondence: Mustafa Kemal İlik, M.D. Farabi Hastanesi, Nöroşirürji Bölümü, Kosova Mah., Veysel Karani Cad., Ebru Sok., No: 14, Konya, Turkey Tel: +90 332 - 221 44 44 E-mail: mkilik@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):484-488 DOI: 10.5505/tjtes.2018.86721 Submitted: 19.03.2017 Accepted: 05.12.2018 Online: 05.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

484

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

İlik et al. The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome

MATERIALS AND METHODS The medical records and patient charts of our 182 SCI patients who were sustained an injury at the thoracolumbar junction (T10-L1) between September 2008 and January 2015 were analyzed retrospectively. All of these patients were isolated SCI patients who were operated by us within 24 hours after the development of traumatic SCI. The patients who had additional injuries, such as head trauma, thorax trauma, visceral organ injury, or an unstable clinical-biochemical profile, were excluded from the study group in this research. In our clinic, we routinely started methylprednisolone treatment to SCI patients according to the NASCIS II protocol[2] until 2011, but then we gave up this medication after novel findings that indicated severe side effects of methylprednisolone treatment.[11] The patients divided into two groups: In group 1, there were 95 patients (60 male and 35 female) who received methylprednisolone treatment in conjunction with early surgical intervention. In group 2, there were 87 patients (56 male, 31 female) who underwent only early surgical intervention without methylprednisolone treatment. All patients in this study were admitted to our clinic within eight hours after the development of traumatic SCI. The methylprednisolone treatment was administered to group 1 patients according to the NASCIS II protocol.[2] Briefly, methylprednisolone was intravenously administered

in a bolus dose (30 mg/kg) and then in maintenance dose was administered as (5.4 mg/kg/h) over 23 hours. All patients were operated by the same experienced spinal surgery team and underwent rehabilitation at the same physical medicine and rehabilitation center. All patients underwent a neurological examination during their admission at our emergency service, and their neurological status was categorized into classes A–D according to the criteria established by the American Spinal Injury Association (ASIA) motor index score. Patients with an ASIA motor index score of E were excluded from this study. All patients were re-evaluated at the last follow-up and their initial and the last follow-up ASIA scores were compared. Demographic data, initial and the last follow-up ASIA scores, performed surgical procedures were summarized in Table 1.

Surgical Treatment We aimed to maintain the stability and decompression of the spinal cord in a standard manner in all patients. Eightyeight patients in group 1 operated with a posterior approach, four patients operated with an anterior approach, and three patient from group 1 operated by a combined posterior/anterior approach. Eighty-two patient from group 2 operated with a posterior approach, two patient from group 2 operated with an anterior approach, and three patients operated with a combined posterior/anterior approach. The decom-

Table 1. Demographic data of the patients, initial and first year follow-up ASIA scores and surgical methods

Group I

Group II

Mean age (years)

38.2±9.4 (mean)

36.6±8.3 (mean)

21–62 (ranging)

18–60 (ranging)

Gender

60 male (63%)

56 male (65%)

35 female (37%)

31 female (35%)

Initial ASIA scores

28 ASIA A

26 ASIA A

36 ASIA B

33 ASIA B

20 ASIA C

18 ASIA C

11ASIA D

10 ASIA D

Last follow-up ASIA scores

22 ASIA A

20 ASIA A

32 ASIA B

29 ASIA B

20 ASIA C

17 ASIA C

13 ASIA D

11 ASIA D

Surgical methods

8 ASIA E

10 ASIA E

88 posterior approach

82 posterior approach

4 anterior approach

2 anterior approach

3 posterior+anterior approach

ASIA: American spinal injury association motor index score.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

485

İlik et al. The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome

pression and fusion procedures were conducted in a standard manner for all patients. Spinal decompression was achieved via discectomy, corpectomy, osteotomy and total laminectomy. Transpedicular screws and cages were used in conjunction with autografts and allografts to establish stabilization and fusion. In group 1, eight dural tears occurred during surgery, which were repaired by primary saturation with fibrin glue. In group 2, the dural tear occurred in seven patients, which were repaired as group 1. After surgery, all patients were fitted with a thoracolumbar brace for eight weeks and referred to the same rehabilitation center within the shortest time interval. All patients in this study underwent rehabilitation at the same physical medicine and rehabilitation center according to their neurological status. At the last follow-up, all patients were re-evaluated, and their neurological status was assessed according to ASIA classification. During the follow-up period, some complications, such as decubitus ulcers, deep vein thrombosis, urinary tract infections, were developed in both groups. Encountered complications were summarized in Table 2. The patients with decubitus ulcers were consulted with plastic reconstructive surgery and after adequate treatment, their decubitus ulcers resolved. Deep vein thrombosis, gastrointestinal bleeding, and uriner tract infection were treated with medical treatment. Table 2. Prevalence and rate of complications in these series Complications

Group 1 (n=24, 25%)

Group 2 (n=5, 6%)

Deep vein thrombosis

Uriner tract infection

Gastrointestinal bleeding

Decubitus ulcers

Mortality did not occur in these series.

Statistical Analysis Statistical analysis was performed using Independent Sample t-Tests and Paired Sample t-Tests with SPSS 18.0 for Windows. A p-value <0.05 was considered to indicate statistical significance.

RESULTS In this study, two groups of the patients were comparable in terms of the number, age and sex. The mean time interval between the trauma and operation was not statistically significant (p<0.05) among the groups and 14.6±4.3 hours in group 1 and 13.3±3.5 hours in group 2. ASIA scores of the patients were similar between groups at admission and the one- year follow-up examination without any significant statistically difference (p>0.05). Mean complication rate was statistically significantly high in group 1 who underwent steroid treatment after surgery (p=0.01). The results obtained in this study were summarized in Table 3.

DISCUSSION SCI is a severe public health problem. Neuronal injury occurs via primary and secondary injury mechanisms during SCI.[12,13] Primary injuries that arise from compression, impact, and shear initiate secondary processes that result in damage characterized by inflammation, ischemia, edema, electrolyte disturbances, free oxygen radicals, apoptosis, and demyelination.[12–16] Primary injury tends to be unavoidable following a trauma, but if the secondary injuries can be blocked or mitigated, then, the neurological function may be spared or treated.[16] Various experimental pharmacological agents have been used over the past 30 years to prevent secondary injury in various animal studies but, of these agents, only methylprednisolone has been widely used in daily clinical practice.[3–5,17–19] Exper-

Table 3. Neurological state initial and the last follow-up in both groups

Changes in ASIA scores

Group I

ASIA A-B (n=4) ASIA A-C (n=2) ASIA B-C (n=6) ASIA B-D (n=2)

ASIA C-D (n=5) ASIA C-E (n=3) ASIA D-E (n=5)

Group II

ASIA A-B (n=3) ASIA A-C (n=3) ASIA B-C (n=4) ASIA B-D (n=3)

ASIA C-D (n=6) ASIA C-E (n=2) ASIA D-E (n=8)

Improvement (%)

Unchanged (n)

Total (n)

28.4

33.3

ASIA: American spinal injury association motor index score.

486

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

İlik et al. The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome

imental studies have demonstrated that methylprednisolone reduces inflammation, attenuates the production of free radicals, and decreases lipid peroxidation. Additionally, methylprednisolone increases Na+/K+-ATPase activity and promote local blood supply and perfusion.[20–23] Methylprednisolone shows some neuroprotective effects due to its antioxidant properties. Methylprednisolone decreases tumor necrosis alpha synthesis, increases blood flow to the spinal cord, decreases calcium accumulation, decreases posttraumatic axonal injury and lipid peroxidation.[24] We should note that although methylprednisolone has some beneficial effects, it also has significant side effects,[25] particularly high dose methylprednisolone after SCI increases the risk of wound infection, pneumonia, sepsis, gastrointestinal hemorrhage, pulmonary injury and may lead to even death.[25,26] Among the clinical trials that aimed to evaluate the NASCIS II and NASCIS III protocols, Bracken et al.[2–5] reported that methylprednisolone treatment improved neurological function but increased the probability of infection. However, other clinical studies indicated that the NASCIS II protocol did not produce any beneficial effects on neurological function.[27–29] In our clinic, we routinely started methylprednisolone treatment to SCI patients according to the NASCIS II protocol[2] until 2011, but then we gave up this medication after novel findings that indicated severe side effects of methylprednisolone treatment.[15] In this study, we evaluate the potential effects of intravenous methylprednisolone treatment on the neurological outcome of SCI patients which have thoracolumbar junction spine fractures. According to our results, steroids have no significant beneficial effects on the neurological outcome of SCI patients but have significant side effects and leads to increased complication rates. The primary limitation of the present study is its retrospective nature. However, the findings obtained in this study may contribute to the awareness about the significant side effects of steroids in this patient group.

Conclusion Steroids have no significant beneficial effects on the neurological outcome of SCI patients but have significant side effects and lead to increased complication rates. Conflict of interest: None declared.

REFERENCES 1. Dusart I, Schwab ME. Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J Neurosci 1994;6:712–24.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

2. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 1990;322:1405– 11. 3. Bracken MB, Shepard MJ, Collins WF Jr, Holford TR, Baskin DS, Eisenberg HM, et al. Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study. J Neurosurg 1992;76:23–31. 4. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 1997;277:1597–604. 5. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, et al. Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury randomized controlled trial. J Neurosurg 1998;89:699–706. 6. Bydon M, Lin J, Macki M, Gokaslan ZL, Bydon A. The current role of steroids in acute spinal cord injury. World Neurosurg 2014;82:848–54. 7. Hurlbert RJ, Hadley MN, Walters BC, Aarabi B, Dhall SS, Gelb DE, et al. Pharmacological therapy for acute spinal cord injury. Neurosurgery 2013;72:93–105. 8. Merola A, O’Brien MF, Castro BA, Smith DA, Eule JM, Lowe TG, et al. Histologic characterization of acute spinal cord injury treated with intravenous methylprednisolone. J Orthop Trauma 2002;16:155–61. 9. Rabchevsky AG, Fugaccia I, Sullivan PG, Blades DA, Scheff SW. Efficacy of methylprednisolone therapy for the injured rat spinal cord. J Neurosci Res 2002;68:7–18. 10. Suberviola B, González-Castro A, Llorca J, Ortiz-Melón F, Miñambres E. Early complications of high-dose methylprednisolone in acute spinal cord injury patients. Injury 2008;39:748–52. 11. Ito Y, Sugimoto Y, Tomioka M, Kai N, Tanaka M. Does high dose methylprednisolone sodium succinate really improveneurological status in patient with acute cervical cord injury?: a prospectivestudy about neurological recovery and early complications. Spine (Phila Pa 1976) 2009;34:2121–4. 12. Rowland JW, Hawryluk GW, Kwon B, Fehlings MG. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus 2008;25:E2. 13. Tator CH. Update on the pathophysiology and pathology of acute spinal cord injury. Brain Pathol 1995;5:407–13. 14. Park SJ, Oh IS, Kwon JY, Ha KY. The effect of irradiation and methylprednisolone in spinal cord injured rats. Spine (Phila Pa 1976) 2011;36:434–40. 15. Taoka Y, Okajima K. Role of leukocytes in spinal cord injury in rats. J Neurotrauma 2000;17:219–29. 16. Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991;75:15–26. 17. Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, Silten RM, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA 1984;251:45–52. 18. Kwon BK, Okon E, Hillyer J, Mann C, Baptiste D, Weaver LC, et al. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma 2011;28:1545–88. 19. Olsson Y, Sharma HS, Nyberg F, Westman J. The opioid receptor antag-

487

İlik et al. The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome onist naloxone influences the pathophysiology of spinal cord injury. Prog Brain Res 1995;104:381–99. 20. Braughler JM, Hall ED. Correlation of methylprednisolone levels in cat spinal cord with its effects on (Na+ + K+)-ATPase, lipid peroxidation, and alpha motor neuron function. J Neurosurg 1982;56:838–44. 21. Braughler JM, Hall ED. Lactate and pyruvate metabolism in injured cat spinal cord before and after a single large intravenous dose of methylprednisolone. J Neurosurg 1983;59:256–61. 22. Hall ED. Neuroprotective actions of glucocorticoid and nonglucocorticoid steroids in acute neuronal injury. Cell Mol Neurobiol 1993;13:415– 32. 23. Jones TB, McDaniel EE, Popovich PG. Inflammatory-mediated injury and repair in the traumatically injured spinal cord. Curr Pharm Des 2005;11:1223–36. 24. Hall ED, Springer JE. Neuroprotection and acute spinal cord injury: a

reappraisal. NeuroRx 2004;1:80–100. 25. Hurlbert RJ. The role of steroids in acute spinal cord injury: an evidencebased analysis. Spine (Phila Pa 1976) 2001;26:S39–46. 26. Khan MF, Burks SS, Al-Khayat H, Levi AD. The effect of steroids on the incidence of gastrointestinal hemorrhage after spinal cord injury: a casecontrolled study. Spinal Cord 2014;52:58–60. 27. Felleiter P, Müller N, Schumann F, Felix O, Lierz P. Changes in the use of the methylprednisolone protocol for traumatic spinal cord injury in Switzerland. Spine (Phila Pa 1976) 2012;37:953–6. 28. Pointillart V, Petitjean ME, Wiart L, Vital JM, Lassié P, Thicoipé M, et al. Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 2000;38:71–6. 29. Short DJ, El Masry WS, Jones PW. High dose methylprednisolone in the management of acute spinal cord injury - a systematic review from a clinical perspective. Spinal Cord 2000;38:273–86.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Travmatik torakolomber bileşke yaralanmalı hastalarda steroidin nörolojik sonuçlar üzerine etkisi Dr. Mustafa Kemal İlik,1 Dr. Fatih Keskin,2 Dr. Fatih Erdi,2 Dr. Bülent Kaya,2 Dr. Yaşar Karataş,2 Dr. Erdal Kalkan2 1 2

Farabi Hastanesi, Nöroşirürji Kliniği, Konya Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Nöroşirürji Anabilim Dalı, Konya

AMAÇ: Bu çalışmada metilprednizolonun torakolomber bileşke (T10-L1) kırıkları ile beraber spinal kord yaralanması olan hastalarda nörolojik sonuçlarına etkisi değerlendirildi. GEREÇ VE YÖNTEM: Eylül 2008–Ocak 2015 ayları arasında torakolomber bileşke kırığı nedeniyle ameliyat ettiğimiz 182 hastanın bilgileri geriye dönük olarak değerlendirildi. Hastalar iki gruba ayrıldı. Grup 1; erken cerrahi ile beraber metilprednizolon tedavisi uygulanan grup iken, Grup 2; metilprednizolon tedavisi verilmeyen sadece erken cerrahi uygulanan gruptu. Hastaların ilk başvuruda ve son muayene kayıtlarına göre motor indeks skorları Amerikan Spinal Yaralanma Birliği (ASIA) skalasına göre değerlendirildi. Sonuçlar istatistiki olarak karşılaştırıldı. BULGULAR: Grup 1’de ortalama takip süresi 14.4±1.4 iken Grup 2’de 13.6±1.7 idi. Hastaların başlangıçta ve son muayene kayıtlarında ASIA skorları benzerdi (p>0.05). Komplikasyon oranı ise Grup 1’de belirgin şekilde yüksekti (p<0.05). TARTIŞMA: Bulgularımıza göre spinal kord yaralanması olan hastalarda steroidin nörolojik sonuçlar üzerine belirgin faydalı etkisi yoktur ve yan etkisiyle komplikasyon oranını arttırmaktadır. Anahtar sözcükler: Metilprednizolon; spinal kord yaralanması; tedavi; torakolomber bileşke. Ulus Travma Acil Cerrahi Derg 2019;25(5):484-488

488

doi: 10.5505/tjtes.2018.86721

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

ORIGIN A L A R T IC L E

Correlation of pelvic fractures and associated injuries: An analysis of 471 pelvic trauma patients Mehmet Saydam, M.D.,1 Mutlu Şahin, M.D.,1 Kerim Bora Yılmaz, M.D.,1 Selim Tamam, M.D.,1 Gökhan Ünlü, M.D.,2 Atıl Atilla, M.D.,2 Yenel Bilgetekin,2 M.D., İdil Güneş Tatar, M.D.,3 Pervin Demir, M.D.,4 Melih Akıncı, M.D.1 1

Department of General Surgery, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara-Turkey

Department of Orthopaedics, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara-Turkey

Department of Radiology, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara-Turkey

Department of Medical Biostatistics, Yıldırım Beyazıt University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: In most respects, the vast majority of pelvic injuries is not of a life-threatening status, but co-presence of other injuries needs to be diagnosed. This study aims to evaluate associated pelvic and extra-pelvic visceral organ injuries of the patients with closed pelvic fractures. METHODS: This retrospective study was conducted with 471 adult patients who had been admitted to our Emergency Service with the diagnosis of pelvic fractures. Type of fractures, accompanying visceral organ injuries, the demographic data, type of operation, mortality rates were recorded and analysed statistically. RESULTS: The rate of operations carried out by the general surgery clinic or other surgical clinics in each type of fracture according to AO classification did not differ (p=0.118). In patients with A2, A3 and B1 types of fractures, the operation rate of general surgery clinic did not show a significant difference. However, most of the patients who had extrapelvic surgery were in the mild severity pelvic trauma, such as AO A2 and A3. A total of 31 patients were ex-patients, 17 of whom had AO-A2 type of fractures. The findings showed that there was a significant difference between abdominal ultrasonography outcome that was normal and non-orthopedic surgery types (p<0.001). There was no significant difference between the types of surgery performed and Abdominal CT outcome, which was normal (p=0.215). CONCLUSION: In the management of patients with pelvic fractures irrespective of its type or grade, the findings suggests that greater attention should be paid to not to overlook the associated injuries. Early blood and imaging tests are encouraged after the patient’s hemodynamic status is stabilized. Keywords: Associated injuries; pelvic fractures; trauma.

INTRODUCTION The initial management of the pelvic injury is still challenging because of its blurred and heterogeneous nature. An immediate evaluation is crucial to avoid possible suffering from polytrauma. Pelvic fractures usually arise from high-kineticenergy, such as motor vehicle accidents and falls from heights,

in young population and as a consequence of associated injuries. The prognosis of pelvic trauma is likely to be related to the severity of these injuries.[1] In the elderly population with osteoporosis, they are usually caused by low-energy trauma, such as simple falls.

Cite this article as: Saydam M, Şahin M, Yılmaz KB, Tamam S, Ünlü G, Atilla A, et al. Correlation of pelvic fractures and associated injuries: an analysis of 471 pelvic trauma patients. Ulus Travma Acil Cerrahi Derg 2019;25:489-496. Address for correspondence: Mehmet Saydam, M.D. Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, 06110 Ankara, Turkey Tel: +90 312 - 596 20 00 E-mail: msaydam2008@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):489-496 DOI: 10.5505/tjtes.2018.72505 Submitted: 21.05.2018 Accepted: 19.12.2018 Online: 02.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

489

Saydam et al. Correlation of pelvic fractures and associated injuries

The mortality rate varies from 4% to 15%.[2,3] The mortality rates and the associated complications, such as neurologic, thoracic and abdominal conditions, increase with associated trauma.[4,5] The present study aimed to evaluate pelvic fractures regarding their type and severity and also assess the possible correlation between the type of pelvic injuries and the associated injuries. Moreover, the present study demonstrated the analysis and comparison of various data, such as age, mechanism and type of injury AO/OTA (The American Orthopaedic Foundation and Orthopaedic Trauma Association), emergency interventions, imaging, definitive treatment by either orthopaedic and other disciplines, hospitalization time, and morbidity and mortality rates.

MATERIALS AND METHODS This retrospective study was approved by Local Ethics Committee and was conducted between January 2012 and December 2017 with 471 adult patients (≥18) who were admitted to the University of Health Sciences, Emergency Service of Diskapi Education and Research Hospital because of the diagnosis of pelvic fractures with or without other injuries. Patients who had a pelvic fracture were identified with the use of the International Classification of Diseases, Ninth Revision (ICD-9) codes 806.6, 806.7, 808.2, 808.3, 808.4, and 808.5, which include all open and closed fractures of the sacrum, ischium, ilium, pubis, pelvic ring, and acetabular area. The age, sex, cause of injury (traffic accident, Industrial accident, fall from height, be trapped under wreckage, assault), type of treatments whether surgical or non-surgical, Abdominal CT (Computerized Tomography) and USG (Ultrasonography) findings, all of the interventions and operations, including orthopaedic and other clinics, e.g. general surgery, neurosurgery, urology, cardiothoracic surgery, additional organ injuries, surgery during the surgical procedure findings and patient survival results, hospitalization days were assessed and recorded. Patients under the age of 18 were excluded from this study. The pelvic fractures were reclassified by an experienced orthopedist with AO/OTA classification (Table 1, Table 2).

Table 1. The revised AO/OTA classification (2018) Stable ring

61-A1

Innominate bone, avulsion

61-A2

Innominate bone, direct blow

61-A3

Transverse sacrum/coccyx

Partially stable ring

61-B1

Open book

61-B2

Lateral compression injury

61-B3

Bilateral partial posterior arch

Unstable ring

61-C1

Unilateral complete posterior disruption

61-C2

C1 with contralateral B injury

61-C3

Bilateral C1 injuries

AO/OTA: The American Orthopaedic Foundation and Orthopaedic Trauma Association.

Table 2. Acetabular fractures (AO classification) 62 The AO system incorporates the concepts of the Letournel classification Type A

Partial articular, involving only one of two colums

A1: Posterior wall fracture

A2: Posterior column fracture

A3: Anterior wall or column fracture

Type B

Partial articular, involving a transverse component

B1: Pure transverse fractures

B2: T-Shaped fractures

B3: Anterior column and posterior hemitransverse

Type C

Complete articular fravtures, both columns

C1: High variety, extending to the iliac crest

C2: Low variety, extendirg to the anterior border of

the ilium

C3: Extension into the sacroiliac joint

AO: The American Orthopaedic Foundation.

After classification, the correlation and the co-occurrence between severity of pelvic trauma and extrapelvic associated injuries and the correlation between pelvic trauma and mortality were analyzed. Moreover, the analysis was performed to find out whether mortality arose from pelvic trauma or associated trauma. The correlation between the results of imaging techniques, whether positive or negative and rates of operation was also analyzed.

Statistical Analysis Distribution of the numerical variables was evaluated using the Shapiro-Wilk test. The median and minimum and maximum values were used to represent the variables determined to have non-Gaussian distribution, as well as the descriptive 490

statistics of discrete variables. The percentage values and number (n) were given for categorical variables. Pearson’s chi-square test was used to compare the distribution of the results of USG, CT, and operation types according to fracture classification type. Spearman’s rho correlation coefficient was used to examine the relationship between USG, CT, and the day of admission and classification. In the case of meaningful correlation, when the correlation coefficient was between the range of 0.00–0.19, it was determined as “no relationship”, values between range of 0.20–0.39 was determined as “low relationship”, values between range of 0.40–0.69 was determined as “intermediate relationship”, valUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Saydam et al. Correlation of pelvic fractures and associated injuries

ues between range of 0.70–0.89 was determined as “high relationship”, and finally values between range of 0.90–1.0 was determined as “very strong relationship”. IBM SPSS Statistics for Windows version 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp) and MS-Excel 2007 (Microsoft Corporation, Redmond, WA, USA) were used for statistical analysis and calculations. P<0.05 was considered as statistically significant.

RESULTS In the analysis of the patient files, 50.3% (n=237) of the patients included in this study were male and 49.7% (n=234) were female (Table 3). The most common cause of trauma was traffic accidents (66.8%, n=314) and the second common cause was fall from height (24.6%, n=116) (Table 3). There were 47 (10.0%) patients with AO-A1, 246 (52.2%) with AO-A2 and 88 patients (18.6%) with acetabulum (Table 3). The median age of the patients aged between 18 and 94 years was found to be 48 (IQR=40) (Table 3). There were 464 patients known to be hospitalized. A total of 217 patients were hospitalized at least one day. There was no relationship between the AO OTA classification type and the day of hospitalization (p=0.118). One hundred fifty-five (32.9%) of the patients underwent surgery (Table 4). The major part of the patients with AO-

A1 type fracture (87.2%) was not operated. Four of AO-A1 (8.5%) patients underwent an orthopaedic surgery, and two of them (4.3%) had a neurosurgery (Table 5). Distribution of the type of surgery according to classification was statistically significant (χ2=95.717; p<0.001). Significant differences were found in the distributions of the patients with orthopeadic surgery in the classifications (χ2=78.368; p<0.001), but no significant difference was found in the distribution of other operations (χ2=15.622; p=0.075). As a result of the bilateral comparisons, the proportion of the patients who had only orthopedic surgery in the class of acetabulum (40.9%) was higher than the patients who had orthopedic surgery at type AO-A1 and AO-A2. The proportion of patients with orthopedic surgery in the AO-A1 type was lower than the patients with orthopedic surgery in the AO-B1, AO-B3, AO-C1, AO-C2 types. Type of surgical treatments was summarized in Table 6. The rate of “general surgery and other surgical clinics” operations in each type of fracture according to AO classification did not differ (χ2=12.833; p=0.118). In AO-A2, AO-A3 and AO-B1 types, the rate of application of general surgery was similar. 6.9% (n=17) of the patients with AO-A2 who died. Five (7.7%) of the AO-A2 patients who had surgery, and 12 (6.6%) of the AO-A2 patients who did not have surgery died. There was no statistical relationship between the classification and the mortality rates between nor survival and having

Table 3. Distribution of the individuals in specified variable groups Variables

n %

Variables

n %

AO classification (n=471)

Gender (n=471) Male

237 50.3

Acetabulum

Female

234 49.7

Type of trauma (n=471)

18.6

10.0

246 52.2

4.7

2.8

Industrial accident

7.4

Traffic accident

314

66.8

8.1

Fall from height

116

24.6

0.6

Industrial accident/fall from height

0.2

1.7

0.4

1.1

0.6

0.2

Be trapped under wreckage

Assault

Abdominal CT (n=471)

Abdominal USG (n=471)

Normal

114 24.2

Free fluid

9.8

Organ injury

5.1

Free fluid with organ injury

7.0

1.9

Not applied

254

53.7

37.4

Age (n=471), median (min-max)

Normal

233 49.5

Free fluid

10.8

Organ injury

0.4

Free fluid with organ injury

Not applied

176

48 (18–94)

AO: The American Orthopaedic Foundation; USG: Ultrasonography; CT: Computerized tomoghrapy.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

491

Saydam et al. Correlation of pelvic fractures and associated injuries

Table 4. Operation and survival distribution of the patients Variables

n %

Variables

n %

1,3: (orthopeadic surgery+urology)

1.1

None

316 67.1

1,3,4: (orthopeadic+plastic surgery+urology)

0.2

Present

155 32.9

1,5: (orthopeadic+neurosurgery)

0.4

1,6: (orthopeadic+cardiovascular surgery)

0.2

2,3: (general surgery+urology)

0.2

2,3,6: (general surgery+urology+

cardiovascular surgery)

0.2

Operation

Type of operation

0: Absent

316

67.1

1: Orthopaedic surgery only

117

24.8

2: General surgery only

0.8

3: Urologyonly

0.4

5: Neurosurgery only

1.3

4: Plastic surgery only

6: Cardiovascularsurgery only

1,2: (orthopeadic+general surgery)

2.3

1,2,3: (orthopeadic+general surgery+urology)

0.4

1,2,3,6: (orthopeadic+general surgery+

urology+cardiovascular surgery)

1,2,4: (orthopeadic+general surgery+

plastic surgery)

1 1

None

316 67.1

Orthopaedic surgery only

117

24.8

General surgery with or without other clinics

4.5

Orthopaedic surgery with other clinics

1.9

Urology

2 0.4

Neurosurgery

6 1.3

Survival

0.2 0.2

Yes

440 93.4

Exitus

31 6.6

Table 5. Distribution of type of surgery according to AO/ATO Classification Surgery None Orthopaedic Acetabulum

46 (52.3)

36 (40.9)

General surgery and the others

Orthopaedic and the others

Urology

Neurosurgery

2 (2.3)

3 (3.4)

–

1 (1.1)

41 (87.2)

4 (8.5)

–

2 (4.3)

181 (73.6)

46 (18.7)

12 (4.9)

3 (1.2)

2 (0.8)

19 (86.4)

–

3 (13.6)

–

4 (30.8)

7 (53.8)

2 (15.4)

–

24 (65.8)

9 (23.7)

1 (2.6)

3 (7.9)

–

3 (100.0)

–

7 (87.5)

–

1 (12.5)

–

5 (100.0)

–

1 (100.0)

–

AO/OTA: The American Orthopaedic Foundation and Orthopaedic Trauma Association.

operated (Table 7). Ten of the 31 patients who died due to multi-trauma were operated by the other surgical branches plus with the orthopaedic department. All of the patients who could not be operated were unable to survive because of the severe head and neck and thoracic pathologies. The distribution of USG results according to AO classification was given in Table 8. There was no statistically significant correlation between USG, abdominal CT results and AO/ 492

ATO classification (p=0.514 and p=0.313, respectively). Eight (21.1%) of abdominal USG outcomes were normal in patients undergoing non-orthopedic surgery. It was determined that there was a significant difference between abdominal USG outcome, which was normal and non-orthopedic surgery types (χ2=16.505; p<0.001). There was no significant difference between the types of surgery performed and abdominal CT outcome which was normal (χ2=3.079; p=0.215). The distribution of surgeries which were performed according to the results of Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Saydam et al. Correlation of pelvic fractures and associated injuries

Table 6. Type of surgical treatment Surgery

n %

Surgery

n %

Pelvic surgery only

14.4

Liver surgery+non-operative orthopedic treatment

0.6

Extremity surgery only

1.1

Liver+renal surgery+non-operative

0.2

Pelvic+extremity surgery

6.8

orthopedic treatment

Extremity+non-operative orthopedic treatment

2.5

Colorectal+pelvic surgery

0.4

Spleen+pelvic+extremity surgery

0.2

Spleen+renal+pelvic+extremity surgery

0.2

Negative laparatomy+pelvic+extremity surgery

0.2

Spleen+pelvic surgery

0.4

Negative laparatomy+extremity surgery

0.2

Spleen+pelvic+extremity surgery

0.4

Liver+bladder+major vascular+pelvic surg

0.2

Spleen surgery+non-operative orthopedic treatment

0.2

Liver+major vascular+pelvic+extremity surgery

0.2

Diaphragm+extremity surgery+non-operative

0.2

Liver+spleen+bladder

1 0.2

orthopedic treatment

Liver+spleen+renal surgery+non-operative

Bladder+pelvic surgery

1.1

Bladder+pelvic+extremity surgery

0.2

Bladder surgery+non-operative orthopedic

0.4

0.2

orthopedic treatment Liver+diaphragm surgery+non-operative

0.4

treatment

orthopedic treatment Liver+pelvic surgery

Liver+spleensurgery+non-operative

2 0.4

Renal+extremity surgery+non-operative

0.2

orthopedic treatment Orthopaedical nonoperative treatment

orthopedic treatment

320 67.9

Table 7. Exitus rates according to classification and surgery Classification

Non-operative treatment

Operative treatment

Total

Survival Exitus Survival Exitus Survival Exitus

Acetabulum

45 (97.8)

1 (2.2)

40 (95.2)

2 (4.8)

85 (96.6)

3 (3.4)

41 (100.0)

–

6 (100.0)

–

47 (100.0)

–

169 (93.4)

12 (6.6)

60 (92.3)

5 (7.7)

229 (93.1)

17 (6.9)

19 (100.0)

–

3 (100.0)

19 (86.4)

3 (13.6)

4 (100.0)

–

8 (88.9)

1 (11.1)

12 (92.3)

1 (7.7)

19 (76.0)

6 (24.0)

12 (92.3)

1 (7.7)

31 (81.6)

7 (18.4)

–

3 (100.0)

–

3 (100.0)

–

8 (100.0)

–

8 (100.0)

–

5 (100.0)

–

5 (100.0)

–

1 (100.0)

–

1 (100.0)

–

297 (94.0)

19 (6.0)

143 (92.3)

12 (7.7)

440 (93.4)

31 (6.6)

Total

the abdominal CT and ultrasonography are detailed in Table 9. The distribution of the abdominal CT scan is given in Table 8.

DISCUSSION Many trauma victims sustaining pelvic fractures are treated conservatively, although the pelvic injury is generally a description of severe injury, mandating a comprehensive investigation for the existence of associated injuries, mainly intra-abdominal injuries. However, the correlation between the severity of pelvic fractures and the incidence of associated abUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

dominal injuries is not clear.[6] In our study, the presentation of the extrapelvic injuries was not correlated with the AO classification, which measures pelvic trauma severity. Most of the patients in this study were in class A2, and the majority of the mortalities with any type of surgery performed were in this class. Nevertheless, AO-A2 may be named as a moderate injury type according to AO classification. Under normal circumstances, we would expect to find more surgery and mortality rates in the upper-level injuries before this study had been formed. 493

Saydam et al. Correlation of pelvic fractures and associated injuries

Table 8. The Distribution of USG and CT results according to the AO/ATO classification

AO/ATO Classification

Acetabulum A1 A2

A3 B1 B2 B3 C1 C2 C3

Abdominal USG (n=471), n (%)

Normal

43 (18.5)

Free fluid

9 (17.6)

Organ injury

25 (10.7) 117 (50.2) –

26 (51.0)

13 (5.6)

4 (1.7) 23 (9.9)

4 (7.8)

4 (7.8) 6 (11.8) 2 (3.9)

1 (50.0) – – –

2 (22.2)

–

4 (1.7)

–

– 1 (50.0) – – – – –

Free fluid+organ injury

1 (11.1)

–

n/a

34 (19.3)

22 (12.5) 101 (57.4)

4 (2.3)

1 (11.1) 1 (11.1) 1 (11.1) 1 (11.1) 1 (11.1)

12 (10.5) 58 (50.9)

4 (3.5) 2 (4.3)

8 (4.5)

–

3 (1.7)

–

3 (2.6) 10 (8.8) 1 (0.9)

2 (1.8)

3 (2.6)

–

2 (4.3) 6 (13.0) 1 (2.2)

2 (4.3)

–

Abdominal CT (n=470), n (%)

Normal

21 (18.4)

Free fluid

5 (10.9)

2 (2.2)

Organ injury

6 (25.0)

–

8 (33.3)

1 (4.2)

4 (16.7) 2 (8.3)

1 (4.2)

–

Free fluid+organ injury

4 (12.1)

–

19 (57.6)

4 (12.1)

2 (6.1)

–

1 (3.0)

–

1 (3.0)

n/a

51 (20.2)

34 (13.4) 134 (53.0)

11 (4.3)

2 (0.8) 18 (7.1)

–

2 (0.8)

1 (0.4)

–

27 (58.7)

AO/OTA: The American Orthopaedic Foundation and Orthopaedic Trauma Association; USG: Ultrasonography; CT: Computerized tomoghrapy.

Table 9. The distribution of surgeries performed according to results of the abdominal CT and abdominal ultrasonography Operation None Orthopaedic

General surgery and the other clinics

Orthopaedic and the other clinics

Urology

Neurosurgery

Abdominal USG

Negative

156 (67.0)

69 (29.6)

1 (0.4)

3 (1.3)

–

4 (1.7)

Positive

160 (67.2)

48 (20.2)

20 (8.4)

6 (2.5)

2 (0.8)

Abdominal CT

Negative

72 (63.2)

35 (30.7)

1 (0.9)

2 (1.8)

–

4 (3.5)

Positive

243 (68.3)

82 (23.0)

20 (5.6)

7 (2.0)

2 (0.6)

USG: Ultrasonography; CT: Computerized tomoghrapy.

The most common mechanism of injury leading to pelvic fractures is a motor vehicle accident (MVA) and fall from heights. [7,8] The rising incidence of road traffic crashes is the most important public health problem in civil society. The two most common causes of trauma in our study were these two mechanisms, which were around 90%. Depending on the position of a pedestrian or fallen person, the pelvis, hip, thighs or legs were usually affected at the first contact, and the extrapelvic structures, mostly intraabdominal solid organs, are affected by the real-time blast effect. Among abdominal injuries in pelvic trauma patients liver is the most commonly injured organ as reported in the literature.[9,10] In patients with complex pelvic fractures, the spleen is found to be the second most frequently injured solid organ 494

followed by the liver.[11,12] In our study, the incidence of liver and splenic injuries were in accordance with the literature, which followed by kidney and bladder injury. Contrary to our work, among adults with pelvic fractures and associated intraabdominal solid organ injuries, there was a clear correlation between the severity of pelvic fractures and the grade of the splenic or hepatic injuries according to most of the studies in the literature. Higher pelvic fracture mostly argues a more severe injury, possibly explaining the higher grade of the associated abdominal organ injuries. A study that included 126 patients with severe pelvic trauma (AO classification type B or C) revealed that the most common extrapelvic lesions were thoracic injuries in 56.4% and severe head injuries (GCS <8) in 33.3%.[13] However, among children, such a correlation was not observed. Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Saydam et al. Correlation of pelvic fractures and associated injuries

In our study, no relationship was found between AO classifications and abdominal CT outcomes. There was a significant false-negative rate in abdominal USG outcomes. However, USG is still the imaging modality of choice for the detection of blunt abdominal trauma, and positive ultrasonographic findings can be used as a risc factor when planning new algorithms in the management of the patient although it has shortcomings in the demonstration of hollow viscus injury.[14,15] On the other hand, given that USG is an operator-dependent imaging modality, and in emergency conditions where the patient cooperation is not expected, it may have low sensitivity rates, especially when performed by the physician other than radiologists. Therefore, in suspected cases, if the condition stabilizes, it is absolutely necessary to evaluate the patient with abdominal CT. Initial assessment of trauma patients using CT has resulted in shorter triage times and intensive care unit stays, as well as an overall reduction in ventilation requirements and organ failure rates. [16] Abdominopelvic CT is considered the optimal imaging examination in polytrauma patients.[17] The drawbacks of the modality could be the utilization of ionizing-radiation and the potentially nephrotoxic contrast agents. It is important to use CT always with the right indications.[18] A small percentage of traumatic injuries may not be identified or fail to be manifest in the initial CT, resulting in delayed manifestations of abdominal trauma. This may lead to subsequent readmission, delayed management, and more severe medical complications. Investigating the frequency, cause, and type of delayed abdominal injuries helps raise the awareness of radiologists and emergency physicians to traumatic injuries that may indicate delayed presentation.[19] Several publications showed the mortality rates after pelvic fracture and associated injuries, and the mortality rates ranged from 7.6% to 19%.[20,21] In our study, the mortality rate was 6.6%. The strategies aimed to decrease the risk of death after pelvic fracture were described in many studies in the literature.[22,23] Although there was no correlation between death rates and pelvic fracture severity and types of operations in our study, almost all of the patients who died had multi-trauma. In this case, the literature confirms that the most common cause of death after pelvic fracture was associated injuries. For example, although there were patients in the literature who died due to intrapelvic hemorrhage after pelvic fracture, our patients usually died due to intracranial hemorrhage and additional multiorgan trauma. Severe pelvic trauma management often requires a strategy different than regular approaches like removing an organ or tightening a vessel. Some specific interventions, such as reapproximation of bony structures, damage control resuscitation, assessment for associated injuries, and triage of investigations, as well as multimodality hemorrhage control (external fixation, preperitoneal packing, angioembolization, REBOA [resuscitative endovascular balloon occlusion of the aorta]) by multidisciplinary trauma specialists (general surUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

geons, orthopedic surgeons, endovascular surgeons/interventional radiologists) can be lifesaving.[24] Our work has some limitations. First of all, we could not reach the Injury Severity Score (ISS) data. We may have reached more effective results if we could have examined the associated traumas in the presence of these scores with the AO classification. However, when a patient with pelvic trauma arrives, we should be alerted not to overlook the underlying problem, even if the condition is stable and pelvic injury is moderate. Another limitation of our study is the patient population, which includes only adult patients. Thus, we should highlight that when various published studies are reviewed, it is emphasized that the clinical condition of children with pelvic trauma may be different with blurred findings compared to the adults.[25]

Conclusion Mortality and morbidity rates are mainly affected by associated injuries, rather than the severity of the pelvic fracture itself according to this study. Recent guidelines confirm that further chest and abdominal evaluation for referring pelvic fractures is recommended, regardless of the pelvic fracture severity. In the management of patients with pelvic fractures, greater attention should be paid to the associated injuries. Early CT imaging is suggested after the patient is hemodynamically stabilized. Conflict of interest: None declared.

REFERENCES 1. Cordts Filho Rde M, Parreira JG, Perlingeiro JA, Soldá SC, Campos Td, Assef JC. Pelvic fractures as a marker of injury severity in trauma patients. [Article in English, Portuguese]. Rev Col Bras Cir 2011;38:310–6. 2. Arvieux C, Thony F, Broux C, Ageron FX, Rancurel E, Abba J, et al. Current management of severe pelvic and perineal trauma. J Visc Surg 2012;149:e227–38. 3. Cullinane DC, Schiller HJ, Zielinski MD, Bilaniuk JW, Collier BR, Como J, et al. Eastern Association for the Surgery of Trauma practice management guidelines for hemorrhage in pelvic fracture--update and systematic review. J Trauma 2011;71:1850–68. 4. Demetriades D, Karaiskakis M, Toutouzas K, Alo K, Velmahos G, Chan L. Pelvic fractures: epidemiology and predictors of associated abdominal injuries and outcomes. J Am Coll Surg 2002;195:1–10. 5. Eastridge BJ, Burgess AR. Pedestrian pelvic fractures: 5-year experience of a major urban traumacenter. J Trauma 1997;42:695–700. 6. Holden CP, Holman J, Herman MJ. Pediatric pelvic fractures. J Am Acad Orthop Surg 2007;15:172–7. 7. Demetriades D, Karaiskakis M, Velmahos GC, Alo K, Murray J, Chan L. Pelvic fractures in pediatric and adult trauma patients: are they differentinjuries? J Trauma 2003;54:1146–51. 8. Leonard M, Ibrahim M, Mckenna P, Boran S, McCormack D. Paediatric pelvic ring fractures and associated injuries. Injury 2011;42:1027–30. 9. Shweiki E, Klena J, Wood GC, Indeck M. Assessing the true risk of abdominal solid organ injury in hospitalized ribfracture patients. J Trauma 2001;50:684–8.

495

Saydam et al. Correlation of pelvic fractures and associated injuries 10. Demetriades D, Karaiskakis M, Toutouzas K, Alo K, Velmahos G, Chan L. Pelvic fractures: epidemiology and predictors of associated abdominal injuries and outcomes. J Am Coll Surg 2002;195:1–10. 11. Pajenda GS, Seitz H, Mousavi M, Vécsei V. Concomitant intra-abdominal injuries in pelvic trauma. [Article in German]. Wien Klin Wochenschr 1998;110:834–40. 12. Lunsjo K, Tadros A, Hauggaard A, Blomgren R, Kopke J, Abu-Zidan FM. Associated injuries and not fracture instability predict mortality in pelvic fractures: a prospective study of 100 patients. J Trauma 2007;62:687–91. 13. Siegmeth A, Müllner T, Kukla C, Vécsei V. Associated injuries in severe pelvic trauma. [Article in German]. Unfallchirurg 2000;103:572–81. 14. Shojaee M, Faridaalaee G, Yousefifard M, Yaseri M, Arhami Dolatabadi A, Sabzghabaei A, et al. New scoring system for intra-abdominal injury diagnosis after blunt trauma. Chin J Traumatol 2014;17:19–24. 15. Güneş Tatar İ, Yılmaz KB, Ergun O, Balas Ş, Akıncı M, Deryol R, et al. The effect of clinical, laboratory and radiologic results on treatment decision and surgical results in patients admitted to the emergency department with blunt abdominal trauma due to traffic accident. [Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2015;21:256–60. 16. Wurmb TE, Frühwald P, Hopfner W, Keil T, Kredel M, Brederlau J, et al. Whole-body multislice computed tomography as the first line diagnostic tool in patients with multiple injuries: the focus on time. J Trauma 2009;66:658–65. 17. Soto JA, Anderson SW. Multidetector CT of blunt abdominal trauma. Radiology 2012;265:678–93.

18. Gunes Tatar I, Aydin H, Kizilgoz V, Yilmaz KB, Hekimoglu B. Appropriateness of selection criteria for CT examinations performed at an emergency department. Emerg Radiol 2014;21:583–8. 19. Elbanna KY, Mohammed MF, Huang SC, Mak D, Dawe JP, Joos E, et al. Delayed manifestations of abdominal trauma: follow-up abdominopelvic CTin posttraumatic patients. Abdom Radiol (NY)k 2018;43:1642–55. 20. Blackmore CC, Jurkovich GJ, Linnau KF, Cummings P, Hoffer EK, Rivara FP. Assessment of volume of hemorrhage and outcome from pelvic fracture. Arch Surg 2003;138:504–8. 21. Starr AJ, Griffin DR, Reinert CM, Frawley WH, Walker J, Whitlock SN, et al. Pelvic ring disruptions: prediction of associated injuries, transfusion requirement, pelvic arteriography, complications, and mortality. J Orthop Trauma 2002;16:553–61. 22. Agolini SF, Shah K, Jaffe J, Newcomb J, Rhodes M, Reed JF 3rd. Arterial embolization is a rapid and effective technique for controlling pelvic fracture hemorrhage. J Trauma 1997;43:395–9. 23. Smith W, Williams A, Agudelo J, Shannon M, Morgan S, Stahel P, et al. Early predictors of mortality in hemodynamically unstable pelvis fractures. J Orthop Trauma 2007;21:31–7. 24. Skitch S, Engels PT. Acute Management of the Traumatically Injured Pelvis. Emerg Med Clin North Am 2018;36:161–79. 25. Swaid F, Peleg K, Alfici R, Olsha O, Givon A, Kessel B; Israel Trauma Group. A comparison study of pelvic fractures and associated abdominal injuriesbetween pediatric and adult blunt trauma patients. J Pediatr Surg 2017;52:386–9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Pelvik kırıklar ve bağlantılı yaralanmaların ilişkisi: Pelvik travmalı 471 hastanın istatistiksel analizi Dr. Mehmet Saydam,1 Dr. Mutlu Şahin,1 Dr. Kerim Bora Yılmaz,1 Dr. Selim Tamam,1 Dr. Gökhan Ünlü,2 Dr. Atıl Atilla,2 Dr. Yenel Bilgetekin,2 Dr. İdil Güneş Tatar,3 Dr. Pervin Demir,4 Dr. Melih Akıncı1 Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Ortopedi Kliniği, Ankara Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Radyoloji Kliniği, Ankara 4 Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Medikal Biyoistatistik Bölümü, Ankara 1 2 3

AMAÇ: Pelvik yaralanmaların büyük çoğunluğu yaşamı tehdit etmemesine rağmen, ilişkili yaralanmaların heterojen doğası sebebiyle, açıklığa kavuşmasına ihtiyaç vardır. Bu çalışmanın amacı, kapalı pelvik travmalı hastalarda ilişkili pelvik ve ekstra pelvik organ yaralanmalarını araştırmaktır. GEREÇ VE YÖNTEM: Bu geriye dönük çalışma, acil servise pelvik kırık tanısı ile başvuran 471 erişkin hasta ile yapıldı. Kırık tipi, eşlik eden viseral organ yaralanmaları, demografik veriler, operasyon şekli, mortalite oranları kaydedildi ve istatistiksel olarak analiz edildi. BULGULAR: AO sınıflamasına göre genel cerrahi kliniği veya diğer cerrahi klinikler tarafından yapılan operasyonların oranı istatistiksel olarak farklılık göstermemiştir (p=0.118). A0-A2, A3 ve B1 kırık tiplerinde, genel cerrahi kliniğinin operasyon oranı anlamlı bir farklılık göstermemiştir. Bununla birlikte, ekstrapelvik cerrahi geçiren hastaların çoğu AO A2 ve A3 gibi hafif şiddetteki pelvik travmalı hastalardı. Toplamda 31 hasta hayatını kaybetti, bunların 17’si AO-A2 tipi kırığı olan hastalardı. Ortopedi dışı ameliyat olanlar ile normal abdominal ultrasonografi sonuçları arasında anlamlı bir fark olduğu saptandı (p<0.001). Yapılan tüm tip ameliyatlar ve normal abdominal bilgisayarlı tomografi sonuçları arasında (p=0.215) anlamlı bir fark yoktu. TARTIŞMA: Pelvis kırığı olan hastaların yönetiminde, türüne ya da evresine bakılmaksızın, ilişkili yaralanmaların gözden kaçırılmamasına dikkat edilmelidir. Hastanın hemodinamik durumu stabilize edildikten sonra erken kan ve görüntüleme testleri yapılmalıdır. Anahtar sözcükler: İlişkili yaralanmalar; pelvik kırıklar; travma. Ulus Travma Acil Cerrahi Derg 2019;25(5):489-496

496

doi: 10.5505/tjtes.2018.72505

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

ORIGIN A L A R T IC L E

A comparative study of pneumomediastinums based on clinical experience Ersin Sapmaz, M.D.,1 Hakan Işık, M.D.,1 Deniz Doğan, M.D.,2 Kuthan Kavaklı, M.D.,1 Hasan Çaylak, M.D.1 1

Department of Thoracic Surgery, Gülhane Training and Research Hospital, Ankara-Turkey

Department of Pulmonology, Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: Pneumomediastinum (PM) is the term which defines the presence of air in the mediastinum. PM has also been described as mediastinal emphysema. PM is divided into two subgroups called as Spontaneous PM (SPM) and Secondary PM (ScPM). METHODS: A retrospective comparative study of the PM diagnosed between February 2010 and July 2018 is presented. Forty patients were compared. Clinical data on patient history, physical characteristics, symptoms, findings of examinations, length of the hospital stay, treatments, clinical time course, recurrence and complications were investigated carefully. Patients with SPM, Traumatic PM (TPM) and Iatrogenic PM (IPM) were compared. RESULTS: SPM was identified in 14 patients (35%). In ScPM group, TPM was identified in 16 patients (40%), and IPM was identified in 10 patients (25%). On the SPM group, the most frequently reported symptoms were chest pain, dyspnea, subcutaneous emphysema and cough. CT was performed to all patients to confirm the diagnosis and to assess the possible findings. All patients prescribed prophylactic antibiotics to prevent mediastinitis. CONCLUSION: The present study aimed to evaluate the clinical differences and managements of PMs in trauma and non-trauma patients. The clinical spectrum of pneumomediastinum may vary from benign mediastinal emphysema to a fatal mediastinitis due to perforation of mediastinal structures. In most series, only the SPM was evaluated in many aspects, but there are fewer studies comparing the evaluation and management of traumatic and non-traumatic PMs. The patients with TPM who have limited trauma to the thorax and who do not have mediastinal organ injury in their imaging studies can be followed up and treated like SPM patients who do not have mediastinal organ injury, and both have good clinical course. Keywords: Mediastinal emphysema; mediastinitis; spontaneous pneumomediastinum; traumatic pneumomediastinum.

INTRODUCTION Pneumomediastinum (PM) is a term that defines the presence of air in the mediastinum. PM has also been described as mediastinal emphysema.[1] The entity was first described by Laenek in 1827.[1] PM is divided into two subgroups called Spontaneous PM (SPM) and Secondary PM (ScPM). The ScPM group is made up of the combination of Traumatic PM (TPM) and Iatrogenic PM (IPM) groups (Fig. 1).

SPM is an uncommon, self-limiting condition that often presents with sudden onset of symptoms, including chest pain, neck pain, dyspnea or signs of subcutaneous emphysema. SPM is classified as free air in the mediastinum without any traumatic or iatrogenic cause.[2] However, in many reports, the term SPM has been allowed even when a possible triggering factor is identified.[1–3] Triggering factors, such as asthma,

Cite this article as: Sapmaz E, Işık H, Doğan D, Kavaklı K, Çaylak H. A comparative study of pneumomediastinums based on clinical experience. Ulus Travma Acil Cerrahi Derg 2019;25:497-502. Address for correspondence: Ersin Sapmaz, M.D. Gülhane Eğitim ve Araştırma Hastanesi, Göğüs Cerrrahisi Anabilim Dalı Başkanlığı, Ana Bina, 6. Kat, Etlik, Ankara, Turkey Tel: +90 312 - 304 51 71 E-mail: esapmaz@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):497-502 DOI: 10.14744/tjtes.2019.03161 Submitted: 29.11.2018 Accepted: 20.05.2019 Online: 22.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

497

Sapmaz et al. A comparative study of pneumomediastinums based on clinical experience

Pneumomediastinum

Secondary pneumomediastinum

Iatrogenic

Spontaneous pneumomediastinum

Traumatic

Figure 1. Classification of PM.

vomiting, Valsalva maneuver, drugs, exercise, or severe cough, may be associated with SPM.[2] SPM is generally benign and self-limiting condition, presenting in young adults exposed to a sudden pressure change within the thoracic cavity.[4,5] In ScPM, there is a specific responsible pathologic event such as trauma, surgery and damage of the aerodigestive tract. This study aims to investigate the presenting features, similarities or differences for clinical management of SPM, IPM and TPM, and identify the required follow up time of hospitalized adult patients who were treated between January 2010 and July 2018.

MATERIALS AND METHODS A retrospective comparative study of the PM diagnosed between January 2010 and July 2018 is presented. The confirmation of PM (free air in the mediastinum) was made via chest X-ray and thorax computed tomography (CT). Clinical data on patient history, physical characteristics, symptoms, and findings of examinations, length of the hospital stay, treatments, clinical time course, recurrence and complications were investigated carefully. This study was approved by the institutional board review at our institution. Patients with SPM, TPM and IPM were compared. Only adult patients (>18 years) included in this study. Patients who had no history of trauma or medical intervention, subcutaneous emphysema or the presence of clinical picture consistent with PM were counted as SPM. Only the blunt thoracic trauma with PM who did not require thoracotomy and the integrity of the thorax was protected patients were included in this study and classified as TPM. PM after major thoracic surgeries, such as sternotomy, thoracotomy, or tracheal surgery, was excluded from IPM group in this study.

reported symptoms were chest pain in 43% (6 of 14) and dyspnea in 43% (6 of 14), followed by subcutaneous emphysema in 29% (4 of 14) and cough in 21% (3 of 14). Pneumothorax was present in 21% of patients (3 of 14) upon admission. The pneumothorax in each patient needed to be treated by chest tube and evident both on the chest x-ray and chest CT scan (Table 1). Average recovery time for these patients was 5.2 days (3 to 9 days). One patient (7%) needed tube insertion to the mediastinum. Recovery time for this patient was five days. One or more preexisting lung disorders were identified in four patients (29%). Two patients (14%) had evidence of cryptogenic organizing pneumonia, and two patients (14%) had evidence of lung cancer. Esophagoscopy was performed to three (21%) patients and two of them had both esophagoscopy and fiberoptic bronchoscopy (7%). None of the patients had mediastinal organ injury. One of the patients (7%) who had both esophagoscopy and fiberoptic bronchoscopy scanning had six times of recurrence. There were no in-hospital deaths. Patients with PM who did not fulfill the criteria previously defined for SPM were considered to have ScPM. This group consisted of 10 (25%) IPM patients and 16 (40%) TPM patients. In ScPM group, pneumothorax was present in 46% of patients (12 of 26) and all needed to be treated by a chest tube. Average recovery time for these patients was 6.6 days (3 to 15 days). Mediastinal chest tube insertion required in 12% (3 of 26) of the patients. Average recovery time for these patients was 5.3 days (5 to 10 days). Nineteen percent of the patients (5 of 26) were male. Average recovery time for ScPM group was 6.2 days (range 2 to 15). The mortality rate was 12% (3 of 26). IPM was identified in 10 patients (25%). IPM group included patients in whom PM developed as a result of tracheostomy procedure in 30% (3 of 10), after endoscopy in 30% (3 of 10), Table 1. SPM, clinical findings on presentation Clinical findings

Chest pain

Dyspnea

6 43

Subcutaneous emphysema

Cough

3 21

Neck swelling

Pneumothorax

3 21

According to the inclusion and exclusion criteria previously defined, 40 patients included in this study. SPM was identified in 14 patients (35%). All of the patients were male.

Dysphagia

2 14

Pneumorrhachis

1 7

Tingling in hands

On the SPM group, the clinical presentations were identified according to the patientâ&#x20AC;&#x2122;s complaints and physical examinations recorded to the medical records. The most frequently

Incidentally

1 7

RESULTS

498

SPM: Spontaneous pneumomediastinum.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Sapmaz et al. A comparative study of pneumomediastinums based on clinical experience

after ERCP procedure in 20% (2 of 10), after a dental procedure in 20% (2 of 10). Pneumothorax was present in 30% of the patients (3 of 10) and all needed to be treated by a chest tube. Average recovery time for these patients was eight days (4 to 15 days). Mediastinal chest tube insertion was required in 20% (2 of 10) of the patients. Average recovery time for these patients was 7.5 days (5 to 10 days). Sixty percent of the patients (6 of 10) were male. Mortality rate was 20% (2 of 10). TPM was identified in 16 patients (40%). The patients whose integrity of the thorax was protected were included in this group. Pneumothorax was present in 56% of patients (9 of 16) and all of them required chest tube insertion. Average recovery time for these patients was six days (three to 10 days). One patient died due to organ failure (kidney failure and sepsis), which was not related to TPM. One patient (6%) required substernal tube insertion. Recovery time of this patient was six days. Two patients had Fiberoptic Bronchoscopy screening and no mediastinal organ injury was found. Ninetyfour percent of the patients (15 of 16) were male. The treatment/follow-up periods for SPM, IPM and TPM cases were 6.0±1.8, 6.7±3.6 and 5.8±2.3 days, respectively and were not statistically significant (p=0.687). The patients’ discharge is planned according to patients’ clinical and radiological improvement and observing the decrease of pneumoderma. The age of SPM, IPM and TPM cases were 34±17, 49.1±24 and 39.9±15.6, respectively, and the difference was not statistically significant (p=0.159). This is thought to be due to an insufficient number of patients. CT was performed to all patients to confirm the diagnosis and to assess the possible findings. A typical chest CT of PM was shown in Figure 2. In the SPM and TPM group, the oral

Figure 2. A typical chest CT image of a PM case.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

intake of patients with suspected mediastinal organ injury was discontinued until the results of the patients were examined. Only the patients underwent mediastinal drainage for worsening subcutaneous emphysema with severe respiratory distress. Prophylactic antibiotics were given to all patients in order to prevent mediastinitis.

DISCUSSION The main purpose of this study is to evaluate the clinical differences and managements of PMs in trauma and non-trauma patients. The clinical spectrum of PM may vary from benign mediastinal emphysema to a fatal mediastinitis due to perforation of mediastinal structures (i.e. esophageal perforation). In most series, only the SPM was evaluated in many aspects,[2–4,6,7] but we should note that there are fewer studies that have compared the evaluation and management of traumatic and non-traumatic PMs.[8,9] The pathogenesis of spontaneous pneumomediastinum was first described by Macklin.[10] The pathophysiology is based on a pressure gradient between the alveolus and the lung interstitium. This pressure gradient may lead to alveolar rupture and the consequent flow of air into the interstitium. Once the air is in the lung interstitium, it flows towards the hilum and the mediastinum along a pressure gradient between the lung periphery and the mediastinum.[4,11] Crepitus heard with the heartbeat on chest auscultation, the pathognomonic sign of spontaneous pneumomediastinum, known as Hamman’s[12] sign, which was described by Hamman in 1939. There were no Hamman’s sign on the physical examination of our patients. SPM without any other complications has a benign clinical course. Recurrence is very rare and if an accompanying complication exists, it can cause death. SPM often presents with chest pain, dyspnea and subcutaneous emphysema. These findings were also seen in our patients and consistent with most of the other authors’ observations.[2,4,7] SPM has been associated with some triggering factors, including cough, asthma, inhaled drug use, interstitial lung disease, physical exercise, respiratory infection and lung cancer. Kouritas et al. reviewed in their paper that some authors exclude patients from the SPM group if there is any causative factor for PM.[1] However, in our and other studies,[3,4,7] the patients with triggering factors were included in SPM group if there was no surgery, trauma or other iatrogenic factors. Chalumeau et al.[13] noted that exclusion PNMD with a pulmonary disease from SPM had no clinical value. Dionísio et al.[7] found that 88.9% of patients had a triggering factor. We believe that when a patient with SPM was evaluated with detailed anamnesis, physical examination and laboratory tests for suspicious triggering factor, the patient can be found to have any triggering factor. 499

Sapmaz et al. A comparative study of pneumomediastinums based on clinical experience

Recurrence is very rare. Caceres et al.[9] reported no recurrence in 79% of the patients in the follow-up period of one to ten years and found a few case reports for recurrence in the literature. In our study, one of the patients in the SPM group had six times of recurrence. The patient had both esophagoscopy and fiberoptic bronchoscopy scanning and no pathological finding was found. After a detailed investigation, we learned that he was a soldier and was rested for a while after PM. He was abusing this situation by forcing himself to do the Valsalva maneuver. Three patients had pneumothorax requiring a tube thoracostomy and one patient required substernal tube insertion. Esophagoscopy was performed to three patients and two of them had both esophagoscopy and fiberoptic bronchoscopy but no additional findings like esophageal and tracheobronchial ruptures were detected. The main issue is to determine any suspicious underlying complications, especially esophageal perforation. Most of the authors describe highrisk factors for such patients. Younger age elevated white blood cells as a sign of inflammation and pleural effusion are considered high-risk factors for further diagnostic workup. [2,4] Gupta et al.[14] stated that spontaneous perforation of the esophagus had a much higher mortality rate when comparing other etiologies of esophageal perforation, such as traumatic or iatrogenic factors. Observation can be enough for patients with no severe symptoms or inflammatory signs.[3] The mean hospital stay for the SPM group was 5.2 days. Hospitalization times were reported between 1.8 days and 8.56 days in the most series.[4] The potential complications, such as pneumothorax or tension pneumomediastinum, can occur in the first 24–48 hours of admission, so we suggest that the patients should be hospitalized for at least 24–48 hours. In our study, one patient required tube mediastinotomy 24 hours after admission. Tube mediastinotomy was performed due to the patient’s persistent pneumomediastinum and subcutaneous emphysema resulting in respiratory distress. He had no pneumothorax and also required dermal needle puncture. Tube mediastinotomy and dermal needle puncture can be used safely to decrease the pneumoderma and mediastinal pressure to avoid respiratory distress and possible tracheal membrane collapse. None of our patients developed tracheal membrane collapse. Our clinical observations for hospital stay shows concordance with Takada’s[3] study. We think that the follow-up of outpatients without hospitalization as applied by Ebina et al.[4] should be limited by some criteria. Some authors found it unnecessary or avoid using prophylactic antibiotics in SPM patients,[3,4] but we used prophylactic antibiotics in our SPM patients routinely. The use of prophylactic antibiotics may vary depending on the complication of the patients during hospital follow-up. 500

Many studies have shown that the chest X-ray is not sufficient to diagnose alone. In the literature, the rate at which X-rays cannot be diagnosed varies between 5% and 33%[3,6,9] and computed tomography has become the gold standard and considered as a routine diagnostic modality for diagnosing the PM.[1,9] All of our patients had computed tomography imaging on admission to the emergency department. One patient in the SPM group had pneumorrhachis on admission which, is seen very rare in the literature.[15] Traumatic pneumomediastinum was first described by Laennec in 1819 in a 4-year-old boy who was run over by a dung cart.[8,16] The most common mechanism of injury in patients with pneumomediastinum is known to be blunt trauma. [8] Sixteen patients diagnosed PM after blunt trauma in our study. Nine patients (56%) required tube thoracostomy due to accompanying pneumothorax. One patient required (6%) tube mediastinotomy. One patient (6%) with multiple organ injuries died from another organ injury (kidney failure and sepsis). All patients diagnosed with thorax CT. There was no pleural effusion on radiographic scans. All patients used prophylactic antibiotics. In the majority of the blunt traumas, Valsalva maneuver was triggered. The severity of the trauma and Valsalva maneuver determine possible complications. However, multi-organ injuries due to blunt traumas that affect other body systems, even though the integrity of the rib cage is not impaired, should be considered separately due to the inability to predict complications that may develop outside of pneumomediastinum. In our series, we found that uncomplicated blunt injuries limited to thorax can be managed like uncomplicated SPM patients. Chest CT scan was not required for patients with isolated blunt thoracic trauma with no symptom or sign. Chest X-ray was efficient for the first evaluation for these patients. However, chest CT scan is required for patients who had unexplained severe chest pain, subcutaneous emphysema, dyspnea, and pleural effusion, evident air in the mediastinum at the chest X-ray or white cell increase in blood count. These patients should be followed for at least 24–48 hours in terms of subsequent pneumothorax and additional late complications. Prophylactic antibiotic use should be case sensitive. During hospitalization, we think that there is no need for prophylactic antibiotic use if there is no pleural effusion, no pneumothorax on the chest radiography and no white cell increase in blood count. Banki et al. showed in their study that most studies with blunt traumatic PM had less mediastinal organ injury than penetrating trauma. They also stated that pneumothorax was not associated with mediastinal organ injury,[8] which is similar to our study. Ebina et al.[4] included minor traumas to their study as SPM and they stated that pneumomediastinum with major trauma, such as penetrating injury, was considered secondary pneumomediastinum. However, minor trauma, such as falling on Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Sapmaz et al. A comparative study of pneumomediastinums based on clinical experience

one’s hips, can trigger a strong Valsalva maneuver, creating high intrathoracic pressure. Therefore, pneumomediastinum with minor trauma has the same mechanism as SPM. In the light of this information, we could not find any significant difference between uncomplicated SPM and TPM patients. Blunt traumas that do not disrupt the thorax integrity of this type can be accepted as SPM group and can be treated like SPM patients.

results. Although recurrence is very rare, patients with SPM who have recurrence should be examined in more detail to find underlying diseases. Long-term follow-up is not required for uncomplicated PM patients. Conflict of interest: None declared.

REFERENCES

IPM diagnosed in 10 patients who had a different type of medical intervention. Two patients in the IPM group had a history of the dental procedure. Cases of pneumomediastinum after dental procedures are very rare and still present in the literature as case reports. Two of all IPM patients (20%) were due to gastrointestinal system procedures. One patient was due to gastric surgery and the other patient was due to ERCP and both of them died. The clinical management of IPM is a completely different entity. The main problem with these patients is diseases/causes. In these patients, PM often remains an innocent complication. In many clinical scenarios, the physician needs to be focused on the main issue. Therefore, patient management in such patients should be patient-based.

1. Kouritas VK, Papagiannopoulos K, Lazaridis G, Baka S, Mpoukovinas I, Karavasilis V, et al. Pneumomediastinum. J Thorac Dis 2015;7:S44−9.

Limitations

7. Dionísio P, Martins L, Moreira S, Manique A, Macedo R, Caeiro F, et al. Spontaneous pneumomediastinum: experience in 18 patients during the last 12 years. J Bras Pneumol 2017;43:101−5.

Our study has some limitations. First, this is a retrospective observational study, so we could not prove the causes and effects, and our study might have lacked the power to detect complications. Second, we have limited and incomplete follow up data. Third, the criteria for hospitalization depend on attending physician. Fourth, the reason for using prophylactic antibiotics was undescribed.

Conclusion The patients with TPM who have limited trauma to the thorax and who do not have mediastinal organ injury in their imaging studies can be followed up and treated like SPM patients who do not have mediastinal organ injury, and both have good clinical course. The most common clinical presentations are chest pain, dyspnea and subcutaneous emphysema. TPM patients with associated injuries and SPM patients who have additional imaging findings, such as pneumothorax or pleural effusion, should be treated according to their clinical findings. In many patients, a chest x-ray is not sufficient to detect PM, and every suspected case should be evaluated with a CT scan. We recommend that patients should be observed for at least 24-48 hours to avoid delayed posttraumatic complications in uncomplicated TPM and SPM patients. Although antibiotic use is optional, it will be appropriate to decide according to the patient’s imaging and blood analysis

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

2. Potz BA, Chao LH, Ng TT, Okereke IC. Clinical Significance of Spontaneous Pneumomediastinum. Ann Thorac Surg 2017;104:431–5. 3. Takada K, Matsumoto S, Hiramatsu T, Kojima E, Watanabe H, Sizu M, et al. Management of spontaneous pneumomediastinum based on clinical experience of 25 cases. Respir Med 2008;102:1329−34. 4. Ebina M, Inoue A, Takaba A, Ariyoshi K. Management of spontaneous pneumomediastinum: Are hospitalization and prophylactic antibiotics needed? Am J Emerg Med 2017;35:1150–3. 5. Natsuki K, Fumihiro O, Yuichi K, Keisuke I, Yoshie K. Comparison of Spontaneous and Secondary Pneumomediastinum. J Respir Med Lung Dis 2017;2:1022. 6. Iyer VN, Joshi AY, Ryu JH. Spontaneous pneumomediastinum: Analysis of 62 consecutive adult patients. Mayo Clin Proc 2009;84:417−21.

8. Banki F, Estrera AL, Harrison RG, Miller CC 3rd, Leake SS, Mitchell KG, et al. Pneumomediastinum: Etiology and a guide to diagnosis and treatment. Am J Surg 2013;206:1001–6. 9. Caceres M, Ali SZ, Braud R, Weiman D, Garrett HE Jr. Spontaneous Pneumomediastinum: A Comparative Study and Review of the Literature. Ann Thorac Surg 2008;86:962−6. 10. Macklin C. Transport of air along sheaths of pulmonic vessels from alveoli to mediastinum. Arch Intern Med (Chic) 1939;64:913−26. 11. Macklin MT. Macklin CC. Malignant interstitial emphysema of the lungs and mediastinum as an important occult complication in many respiratory diseases and other conditions: interpretation of the clinical literature in the light of laboratory experiment. Medicine (Baltimore) 1944;23:281−358. 12. Hamman L. Spontaneous mediastinal emphysema. Bull Johns Hopkins Hosp 1939;64:1–21. 13. Chalumeau M, Le Clainche L, Sayeg N, Sannier N, Michel JL, Marianowski R, et al. Spontaneous pneumomediastinum in children. Pediatr Pulmonol 2001;31:67−75. 14. Gupta NM, Kaman L. Personal management of 57 consecutive patients with esophageal perforation. Am J Surg 2004;187:58–63. 15. Karabacak K, Genc G, Gundogdu G, Bakir A. Recurrent spontaneous pneumomediastinum and pneumorrhachis accompanied by Raynaud’s phenomenon. Turkish J Thorac Cardiovasc Surg 2013;21:1086–9. 16. Laennec R. A treatise on diseases of the chest and on mediate auscultation. New York: Samuel Wood Sons; 1830.

501

Sapmaz et al. A comparative study of pneumomediastinums based on clinical experience

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Pnömomediastinumların klinik deneyimlere dayalı olarak karşılaştırılması Dr. Ersin Sapmaz,1 Dr. Hakan Işık,1 Dr. Deniz Doğan,2 Dr. Kuthan Kavaklı,1 Dr. Hasan Çaylak1 1 2

Gülhane Eğitim ve Araştırma Hastanesi, Göğüs Cerrahisi Anabilim Dalı, Ankara Gülhane Eğitim ve Araştırma Hastanesi, Göğüs Hastalıkları Anabilim Dalı, Ankara

AMAÇ: Pnömomediastinum (PM) mediastende hava varlığını tanımlayan terimdir. Ayrıca mediastinal anfizem olarakta tanımlanmıştır. PM, spontan PM (SPM) ve sekonder PM (ScPM) olarak adlandırılan iki alt gruba ayrılır. GEREÇ VE YÖNTEM: Şubat 2010 ve Temmuz 2018 arasında tanı konulan PM’nin karşılaştırmalı geriye dönük bir çalışması sunuldu. Kırk hasta karşılaştırıldı. Hasta öyküsü, fiziksel özellikleri, semptomları, muayene bulguları, hastanede kalış süresi, tedavileri, klinik süreci, nüks ve komplikasyonları ile ilgili klinik veriler dikkatli bir şekilde araştırıldı. SPM, travmatik PM (TPM) ve iyatrojenik PM (IPM) olan hastalar karşılaştırıldı. BULGULAR: SPM 14 hastada (%35) tespit edildi. ScPM grubunda; 16 hastada (%40) TPM, 10 hastada (%25) iyatrojenik PM tespit edildi. SPM grubunda en sık bildirilen semptomlar göğüs ağrısı, dispne, subkütanöz amfizem ve öksürük idi. Tanıyı doğrulamak ve olası bulguları değerlendirmek için tüm hastalara BT uygulandı. Tüm hastalara mediastiniti önlemek için profilaktik antibiyotik reçete edildi. TARTIŞMA: Bu çalışmanın temel amacı, travma ve travma dışı hastalardaki PM’lerin klinik farklılıklarını ve yönetimini değerlendirmektir. Pnömomediastinumun klinik spektrumu, benign mediastinal anfizemden mediastinal yapıların perforasyonu nedeniyle ölümcül bir mediastinite kadar değişebilir. Birçok çalışmada sadece SPM pek çok açıdan değerlendirilmiştir, ancak travmatik ve travmatik olmayan PM’lerin değerlendirmesini ve yönetimini karşılaştıran daha az çalışma vardır. Sadece toraks bölgesine sınırlı travma geçiren ve görüntüleme çalışmalarında mediastinal organ hasarı olmadığı gösterilen TPM’li hastalar, mediastinal organ yaralanmasına sahip olmayan SPM hastalar gibi takip ve tedavi edilebilir. Anahtar sözcükler: Mediastinal amfizem; mediastinit; spontan pnömomediastinum; travmatik pnömomediastinum. Ulus Travma Acil Cerrahi Derg 2019;25(5):497-502

502

doi: 10.14744/tjtes.2019.03161

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

ORIGIN A L A R T IC L E

Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar: A single-center retrospective study Ali Fuat Kaan Gök, M.D.,1 Recep Erçin Sönmez, M.D.,2 Tarık Recep Kantarcı, M.D.,1 Adem Bayraktar, M.D.,1 Selman Emiroğlu, M.D.,1 Mehmet İlhan, M.D.,1 Recep Güloğlu, M.D.1 1

Department of General Surgery, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

Department of General Surgery, İstanbul Medeniyet University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: This study aims to discuss management strategies regarding phytobezoar induced ileus based upon clinical results. METHODS: In the present study, between December 2012 and December 2018, a total of 25 patients who were diagnosed with phytobezoar were evaluated retrospectively. Patients who had acute mechanical intestinal obstruction due to phytobezoars at different segments of gastrointestinal (GI) tract were included in this study. The clinical data (such as clinical findings, laboratory results, radiological evaluations, treatment methods) of the patients were examined. RESULTS: Twenty five patients were included in this study. Of the 25 patients, 13 were women (52%). The median age was 60 (31–84) years, and the overall median length of the stay was 7 (2–28) days. Previous abdominal surgery had been recorded for 13 patients (72%). Two patients (8%) were followed up conservatively, whereas 20 (80%) patients had needed surgical intervention. One (4%) patient underwent surgery for distal ileal obstruction due to the pieces of bezoar that crumbled with previous endoscopic intervention. Three of the patients had complications, such as surgical site infection, wound dehiscence and paralytic ileus in the postoperative period. There were no differences between milking and gastrotomy/enterotomy groups according to the length of stay and postoperative complications. One patient died on the 13th postoperative day due to multi-organ failure. The mortality rate was 4%. CONCLUSION: Phytobezoars, which are common with many other different surgical entities, can be located at any segment of the gastrointestinal tract and may cause obstruction, strangulation and/or even perforation. Contrast-enhanced CT scan must be performed in case of suspicion and to rule out any other causes of acute mechanical intestinal obstruction. Conservative and endoscopic procedures may be useful for selected patients, but the surgical treatment may be needed for the vast majority of the patients with phytobezoar. The surgery is safe for phytobezoar if the enterotomy site is chosen wisely. Keywords: Ileus; non-operative management; phytobezoar; surgery.

INTRODUCTION Bezoars, although present mostly at the gastroduodenal segment, is defined as the formation of a mass in non-absorbable materials at any part of the gastrointestinal (GI) tract.[1] This formation may occur within weeks, months or even years depending on etiology and patients may present with nonspecific physical findings, such as colic abdominal pain, dis-

tention, nausea, which occur mostly due to an obstruction in the GI tract.[2] Because of these features that can mimic many other surgical entities, the differential diagnosis should be made accordingly. Bezoars are often present in the form of ‘trichobezoar, phytobezoar, pharmacobezoar or lactobezoar’. Besides occurring mostly due to endocrine disorders like hypothyroidism

Cite this article as: Gök AFK, Sönmez RE, Kantarcı TR, Bayraktar A, Emiroğlu S, İlhan M, et al. Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar: A single-center retrospective study. Ulus Travma Acil Cerrahi Derg 2019;25:503-509. Address for correspondence: Ali Fuat Kaan Gök, M.D. İstanbul Üniversitesi İstanbul Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Çapa, İstanbul, Turkey Tel: +90 212 - 414 20 00 / 32319 E-mail: afkgok@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):503-509 DOI: 10.14744/tjtes.2019.24557 Submitted: 25.02.2019 Accepted: 05.08.2019 Online: 22.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

503

Gök et al. Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar

(e.g. autoimmune, post-thyroidectomy), previous abdominal surgery (e.g. peptic ulcer surgery, tumor surgery, bariatric surgery), GI motility disorders (e.g. chronic intestinal pseudoobstruction, neurogenic motility disorders), they are more frequent in patients having eating disorders or in patients who are diabetic.[3] Different treatment methods have been described regarding its management. Although the approach may differ according to the clinical status of the patient, mostly used regimens, such as N-acetylcysteine (NAC), papain, metoclopramide, cellulase enzyme preparations, ‘diet Coca-Cola™’, are preferred in the first stage, and surgical interventions are chosen for cases where endoscopic intervention and conservative treatment fails.[4]

MATERIALS AND METHODS Study Design Medical records of the patients were evaluated retrospectively between December 2012 and December 2018. The patients with acute mechanical intestinal obstruction (AMIO) caused by phytobezoar were included in this study. Patient characteristics, including age, admission white blood cell count (WBC), history of previous abdominal surgery, any known comorbidities, drug usage, history of consuming ‘persimmon’ specifically, previous history of hospital admission due to phytobezoar, diagnostic modalities, endoscopic intervention, and surgical procedure reports were obtained from the medical records.

Diagnosis of Bezoar Abdominal examination was performed according to the patient’s anamnesis. After that, routine blood tests for AMIO were carried out, such as whole blood count, biochemistry tests (glucose, creatinine, electrolyte values, C- reactive protein), and the plain abdominal X-rays were obtained. A contrast-enhanced (oral/iv/rectal) abdominal computerized tomography (CT) scan was performed to rule out the other reasons for AMIO. Intravenous (IV) contrast-enhanced abdominal CT scan was performed after confirming creatinine values less than 1.4 mg/dL. The CT scan was performed with oral and rectal water-soluble contrast only if the creatinine level was higher than 1.4 4 mg/dL. The mass that outlined by the bowel wall and presented internal gas bubbles was considered the characteristic mottled appearance of bezoar (Fig. 1). CT scan findings, such as the level of obstruction according to the location of phytobezoar in the GI tract, any fluid collection, and/or perforation were recorded.

Treatment Patients having nausea and abdominal distention were decompressed with nasogastric (NG) catheterization. Oral intake was stopped. Parenteral fluids and proton-pump inhibitors (PPIs) were given. Coca-Cola™ (330 mL/six times a 504

Figure 1. Showing phytobezoar located at jejunoileal segment causing intestinal obstruction.

day) were given for conservative treatment via either oral or NG tube after GI decompression. Parenteral fluids were ordered according to serum electrolyte levels on the following day of admission. The physical and laboratory findings recorded according to abdominal examinations were performed routinely every day during hospitalization. Daily plain abdominal X-rays and routine laboratory tests were obtained to monitor the severity of the obstruction. The NG tube was removed, and oral fluid regimen was given when the symptoms of the obstruction began to recover (such as gas outlet and/or defecation, and disappearance of air-fluid levels on the plain abdominal X-ray). The patients who got well with the conservative treatment were discharged for out-patient control. The patients who did not get well or deteriorated underwent surgery after 72 hours of the conservative treatment. The milking procedure (crumbling the bezoar with fingers gently and milking through the ileocaecal valve without gastrotomy and/or enterotomy) was the first preferred option for the surgical treatment. Gastrotomy and/or enterotomy were performed to remove the bezoar if the milking procedure was failed. The preferred enterotomy site was the collapsed and healthy distal bowel segment after the obstruction to make a safe intestinal repair. The patients with a bezoar located at the upper GI tract underwent upper GI endoscopic intervention to reduce the size of bezoar and/or to remove the bezoar if possible using an endoscopic snare and/or basket catheter.

Statistical Analysis

Data analysis was performed using Statistical Software for Social Sciences (SPSS), version 23 for Windows (IBM Corporation, Armonk, New York). The Chi-squared test or Fisher’s exact test was used to compare categorical variables. Student’s t-test was used to analyze normally distributed variables, and the non-parametric Mann-Whitney U test was used for the analysis of non-normally distributed values. Statistical significance was considered at p<0.05. Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Gök et al. Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar

In this study, approval of the local institutional review board was not needed because of the retrospective nature of the present study. Only the patient database was evaluated for study parameters and therefore informed consent was not obtained from the patients.

Besides, 12 (48%) patients included in the present study had no history of previous abdominal surgery. Five (20%) of them had dental problems, such as denture teeth and/or missing teeth, and four (16%) of them were being treated for psychiatric disorders.

RESULTS

Table 1. Demographic findings

Of the 25 patients, 13 (52%) were female, 12 (48%) were male. The median age was 60 (31–84) years, and the overall median length of the stay was 7 (2–28) days. Abdominal distention and tenderness were the most common symptoms recorded during the physical examination at the admission (n=17, 68%). Median WBC and CRP values found as 10650 μL and 50.4 mg/L, respectively.

Total (n=25)

18–40

The most common comorbidities were diabetes mellitus and dental problems. Thirteen patients (52%) had previous abdominal surgery. Seven (25%) patients in this group had a history of gastric surgery (Table 1).

40–65

13 52

>65

9 36

A phytobezoar was detected that causes GI obstruction at the gastroduodenal segment and jejunoileal segment respectively in 8 (32%) and 17 (68%) patients according to radiological evaluations (Fig. 1). Two (8%) patients had multiple bezoars at both gastroduodenal and jejunoileal segments (Fig. 2a, b).

Gender

Female

Male

12 48

Age (years) 12

Previous abdominal surgery Yes

13 52

Peptic ulcus

Gastrectomy (distal subtotal or

antrectomy) BTV + pyloroplasty

BTV + gastroenterostomy

1 1

Gastric neuroendocrine tumor

Two patients (8%) were got well according to physical findings and laboratory tests (decrement of acute phase reactants such as CRP and WBC count) underwent contrast-enhanced CT scan again for control evaluations. The control CT scans showed that phytobezoars which were located at the upper GI tract migrated distally and crumbled into smaller parts, as well as ileus-like findings such as dilated bowel loops, thickening of the bowel wall, findings of mesenchymal heterogenicity which indicated that inflammations were regressed spontaneously unlike the previous CT scan.

(distal subtotal gastrectomy)

Diabetes mellitus

Twelve patients (48%) had a history of ‘persimmon’ consumption according to their anamnesis. Within this group, five (20%) of them had no previous abdominal surgery and any known comorbidity that may cause phytobezoar induced GI tract obstruction (Fig. 3).

Missing teeth or denture teeth

Psychiatric disorders

Ischemic coronary disease

Chronic pulmonary disease

(a)

(b)

Sigmoid colon tumor (anterior resection)

Hysterectomy

Laparoscopic right nephrectomy

Whipple’s procedure

Bezoar

2 12 48

Comorbidities

Hypothyroidism

2 8

Chronic kidney disease

Previous admission for bezoar Yes

12 48

Twice

Once

13 52

Persimmon consumption

Figure 2. Showing multipl bezoars at both gastroduodenal (a) and jejunoileal segments (b).

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Yes

12 48

13 52

BTV: Bilateral truncal vagotomy.

505

Gök et al. Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar

Table 2. Type of treatment and complications Total (n=25)

Conservative Successful

2 8

Endoscopic interventions

Failure

Successful

Number of endoscopies

Failure

Surgery

Milking

Gastrotomy

Enterotomy

Gastrotomy and enterotomy

Figure 3. The appearance of ‘phytobezoar’ reaching 10 cm long which was taken out by enterotomy.

Complications

5 20 1

Distal ileal obstruction due to the

pieces of bezoar that crumbled with

previous endoscopic intervention

Wound dehiscence

Superficial surgical site infection

Postoperative ileus

1 1

Upper GI endoscopy was performed for 11 (44%) patients who had phytobezoars located at the upper GI tract according to CT evaluations. Three of them treated successfully with endoscopic interventions (Fig. 4a-d). Within this group, the surgical intervention was required for eight patients due to lack of clinical improvement despite conservative and endoscopic treatment (Fig. 5). The failure rate of endoscopic treatment was 72% (Table 2). Twenty (80%) patients underwent surgery. Of these, 11 (44%) patients underwent the milking procedure without gastrotomy and/or enterotomy. Enterotomy was performed for five patients and gastrotomy was performed for three patients. Gastrotomy and enterotomy were performed for only one patient to remove bezoars located at different segments of the GI tract (Table 2). There were no differences between milking and gastrotomy/enterotomy groups according to the length of stay and postoperative complications (Table 3). One (4%) patient underwent surgery for distal ileal obstruction due to the pieces of bezoar that crumbled with previous endoscopic intervention. Three patients had complications, such as surgical site infection, wound dehiscence and para506

(b)

(c)

(d)

Mortality

(a)

Figure 4. A gastric bezoar case treated successfully with endoscopic intervention. The full size of the bezoar (a), reducing the size of the bezoar with snare and basket catheter (b), Second endoscopic intervention 48 hours later to reduce the size of the size of the bezoar (c), removing the bezoar with a snare (d).

Total n=25 Conservative treatment n=2 (8%)

Endoscopic intervention n=11 (44%)

Discharghe n=3 (12%)

Failure n=8

Surgery n=20 (80%)

Milking n=11 (44%)

Gastrotomy Enterotomy n=9 (36%)

Figure 5. The clinical course of the bezoar cases.

lytic ileus, in the postoperative period. One patient died on the 13th postoperative day due to multi-organ failure. The mortality rate was 4%.

DISCUSSION The present study aims to discuss the diagnostic process and treatment options for patients with phytobezoar. The findings from our study showed that the vast majority of patients Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Gök et al. Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar

Table 3. Comparing outcomes according to the surgery types

Total (n=20)

Milking (n=11, 55%)

Gastrotomy/enterotomy (n=9, 45%)

10 (4–41)

10 (4–14)

14 (5–41)

0.603

Wound dehiscence

0 (0%)

1 (11%)

0.257

Superficial surgical site infection

0 (0%)

1 (11%)

0.257

Postoperative ileus

1 (9%)

0 (0%)

0.257

Length of stay

with phytobezoar underwent surgery. Our findings suggest that conservative and endoscopic procedures may be useful for selected patients. Also, our study showed that surgery for phytobezoar is safe if the enterotomy site is chosen carefully. Along with the discovery of etiological factors related to the formation of bezoars, conservative treatment had become to gain more weight progressively beginning from the early 1960s when before that period surgery was the mainstay of treatment.[5–7] By contrast, most of the patients (80%) in our study group required surgery. The first and most important step considering the management of the disease is to make the diagnosis accurately. Detailed physical examination, the assistance of radiological modalities (plain abdominal X-ray and contrast-enhanced CT) and endoscopic procedures are of utmost importance to accomplish accurate diagnosis.[8] The findings of abdominal examination can mimic many different abdominal pathologies as previously mentioned, which mostly include abdominal distention, nausea, vomiting, the absence of GI outlet.[9] The patients in the present study had similar complaints. Certain etiological factors come forward, such as the patients with a history of previous abdominal surgery, especially patients who had gastric surgery before (notably peptic ulcer surgery involving vagotomy+/-pyloroplasty such as Billroth I/ II) related with increased risk of bezoar formation due to deterioration of peristaltism according to recent literature.[10,11] Also, bariatric surgery (such as sleeve gastrectomy, gastric bypass, duodenal switch) and tumor surgery are the other common predisposing factors.[12] Phytobezoars may lead to obstruction, stricture, entero-enteric fistula, bleeding, or perforation within the lumen depending on the level at which it occurs.[13] Seven patients (28%) in our study had a history of gastric surgery due to different causes. In the past years, peptic ulcer surgery had given its way to conservative treatments since the use of medical agents, such as proton-pump inhibitors, H2-receptor antagonists, and mucosal barrier-protective agents.[14] Interpretation of our findings is that the long-term results of previously done procedures performed with vagotomy (truncal or selective) had reflected in the present-day with this ‘phytobezoar formation’. Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Bezoar formation is more common for people having disorders, such as hypothyroidism, diabetes mellitus, chronic idiopathic intestinal pseudo-obstruction, and psychiatric disorders, accompanied by eating disorders due to the disruption of intestinal motility.[15] In recent studies, it has been claimed that absorption and peristalsis are impaired due to an increase in levels of Glucagon-Like Peptide-1 (GLP-1) for patients with diabetes mellitus, and it has been accused in the formation of bezoar.[16] In this study, two patients had a history of thyroid hormone replacement due to total thyroidectomy. Also, six patients were diagnosed with diabetes mellitus. It is difficult to claim that these disorders are related in the retrospective evaluation, but the conclusion that can be reached on the basis of the literature is given that these comorbidities may have caused greatly to the formation of phytobezoar. And of course, the control and regular follow-up of these patients with endocrine disorders are of great importance in terms of their impact. Unlike ingestion of non-nutrient substances, such as metal, hair (also known as Rapunzel Syndrome) in some patients with psychiatric disorders, consumption of high fiber content may also cause phytobezoar formation.[17] Recent studies showed that persimmon consumption is frequently being blamed for phytobezoar occurrence in our region. The persimmon, mostly consumed in the northern region of Turkey, contains protein, fat, carbohydrates, iron, vitamins and high fiber. The high fiber content of persimmon makes it difficult to digest with gastric acid and this could lead to the formation of phytobezoar and obstruction in any part of the gastrointestinal tract in time.[18,19] In our study, 12 (48%) patients had a history of persimmon consumption recently. In this group, five patients had no predisposing factor, such as previous abdominal surgery or an eating disorder, except the persimmon consumption. Another interesting feature related to one of these patients is the detection of a newly emergent phytobezoar recorded on admission CT scan that disappeared on the control CT scan, which was obtained ten days later. The formation and disappearance of phytobezoar in such a short period of time are very rare according to our research in literature. Coca-Cola™ treatment for bezoar cases has been frequently mentioned in recent studies.[20] According to the theory, 507

Gök et al. Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar

NaHCO3 and CO2 molecules inside the mass cause dissection process that lead to the dissolution of smaller particles. [21,22] On the other hand, it has been published in many scientific reports that these disintegrating small parts can lead to re-obstruction of a distal bowel segment.[23,24] However, it is frequently preferred because of its low cost and simple applicability.[25] We administered the coke either by oral or nasogastric tube. Some patients tolerated this procedure well, and there were no problems recorded, but most of the patients (92%) underwent additional procedures such as endoscopy and/or surgery according to our study. In our institution, conservative and minimally invasive approaches are preferred at first stage. Based on CT findings, we performed endoscopic interventions for patients who had phytobezoars located at the upper GI tract. Successfully endoscopic procedure rate was 28%. In spite of this, we had to perform surgical intervention as a last resort for the patients whose clinical condition did not improve. Twenty (80%) patients underwent surgery in our study group. Successful results can be achieved without requiring bowel resection by using the milking method and enterotomy. There was no evidence of a statistically significant negative effect of gastrotomy/enterotomy comparing to the milking procedure only on postoperative complications (Table 3). The key point for surgery without complications is to make enterotomy at the distal and healthy bowel segment. This could make the enterotomy site safer. In our study, we tried to summarize our institution’s experience on patients with phytobezoar, but this study has some limitations, such as small sample size, retrospective design and well not documented physical examination findings.

Conclusion Phytobezoars which are common with many other different surgical entities can be located at any segment of the gastrointestinal tract and may cause obstruction, strangulation and/or even perforation. The patients’ anamnesis should be taken accurately, including any comorbidities, previous surgery, eating habits, consumption of persimmon. Detailed physical examination and laboratory tests must be performed according to the clinical condition. Contrast-enhanced CT scan must be performed in case of suspicion and to rule out any other causes of acute mechanical intestinal obstruction. Conservative and endoscopic procedures might be useful for selected patients, but the surgical treatment may be needed for the vast majority of the patients with phytobezoar. The surgery is safe for phytobezoar if the enterotomy site is chosen wisely. It must be kept in mind that this study was only conducted on a small group of patients retrospectively. Further prospective studies are needed to determine the best treatment option for patients with phytobezoar. Conflict of interest: None declared. 508

REFERENCES 1. Mihai C, Mihai B, Drug V, Cijevschi Prelipcean C. Gastric bezoars-diagnostic and therapeutic challenges. J Gastrointestin Liver Dis 2013;22:111. 2. Iwamuro M, Okada H, Matsueda K, Inaba T, Kusumoto C, Imagawa A, et al. Review of the diagnosis and management of gastrointestinal bezoars. World J Gastrointest Endosc 2015;7:336–45. 3. Prieto-Aldape MR, Almaguer-García FI, Figueroa-Jiménez SE, Fernández-Díaz O, Mora-Huerta JA, González-Ojeda A. Relapsing massive metal bezoar: a case report. J Med Case Rep 2009;3:56. 4. Eng K, Kay M. Gastrointestinal bezoars: history and current treatment paradigms. Gastroenterol Hepatol (N Y) 2012;8:776–8. 5. Chun J, Pochapin M. Gastric Diospyrobezoar Dissolution with Ingestion of Diet Soda and Cellulase Enzyme Supplement. ACG Case Rep J 2017;4:e90. 6. Ladas SD, Kamberoglou D, Karamanolis G, Vlachogiannakos J, Zouboulis-Vafiadis I. Systematic review: Coca-Cola can effectively dissolve gastric phytobezoars as a first-line treatment. Aliment Pharmacol Ther 2013;37:169–73. 7. Koulas SG, Zikos N, Charalampous C, Christodoulou K, Sakkas L, Katsamakis N. Management of gastrointestinal bezoars: an analysis of 23 cases. Int Surg 2008;93:95–8. 8. Ho TW, Koh DC. Small-bowel obstruction secondary to bezoar impaction: a diagnostic dilemma. World J Surg 2007;31:1072–8; discussion 1079–80. 9. Eisenberg RL, Levine MS. Miscellaneous abnormalities of the stomach and duodenum. In: Gore RM, Levine MS, editors. Gastrointestinal Radiology, 3rd ed. Philadelphia, USA: Saunders; 2008: p. 679–706. 10. Pinto D, Carrodeguas L, Soto F, Lascano C, Cho M, Szomstein S, et al. Gastric bezoar after laparoscopic Roux-en-Y gastric bypass. Obes Surg 2006;16:365–8. 11. Dirican A, Unal B, Tatli F, Sofotli I, Ozgor D, Piskin T, et al. Surgical treatment of phytobezoars causes acute small intestinal obstruction. Bratisl Lek Listy 2009;110:158–61. 12. Ben-Porat T, Sherf Dagan S, Goldenshluger A, Yuval JB, Elazary R. Gastrointestinal phytobezoar following bariatric surgery: Systematic review. Surg Obes Relat Dis 2016;12:1747–54. 13. Andrus CH, Ponsky JL. Bezoars: classification, pathophysiology, and treatment. Am J Gastroenterol 1988;83:476–8. 14. Eisner F, Hermann D, Bajaeifer K, Glatzle J, Königsrainer A, Küper MA. Gastric Ulcer Complications after the Introduction of Proton Pump Inhibitors into Clinical Routine: 20-Year Experience. Visc Med 2017;33:221–6. 15. Sanders MK. Bezoars: from mystical charms to medical and nutritional management. Pract. Gastroenterol 2004;28:37–50. 16. Nauck MA. Glucagon-like peptide 1 (GLP-1) in the treatment of diabetes. Horm Metab Res 2004;36:852–8. 17. Naik S, Gupta V, Naik S, Rangole A, Chaudhary AK, Jain P, et al. Rapunzel syndrome reviewed and redefined. Dig Surg 2007;24:157–61. 18. Şahin M, Bülbüloğlu E. Fitobezoara Bağlı Mekanik İnce Barsak Obstrüksiyonu: Vaka Takdimi. Turgut Özal Tip Merkezi Dergisi 1996;3:121–3. 19. Ersan Y, Yavuz N, Yüceyar S, Çiçek Y, Ergüney S, Karataş A, et al. Cerrahi tedavi gerektiren mide bezoarları. Cerrahpaşa J Med 2005;36:128–33. 20. Lee HJ, Kang HG, Park SY, Yi CY, Na GJ, Lee TY, et al. Two cases of phytobezoars treated by adminsitration of Coca-Cola by oral route. [Article in Korean]. Korean J Gastroenterol 2006;48:431–3. 21. Lu L, Zhang XF. Gastric Outlet Obstruction-An Unexpected Complication during Coca-Cola Therapy for a Gastric Bezoar: A Case Report and

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Gök et al. Discussing treatment strategies for acute mechanical intestinal obstruction caused by phytobezoar Literature Review. Intern Med 2016;55:1085–9.

2008;134:e1–2.

22. Ha SS, Lee HS, Jung MK, Jeon SW, Cho CM, Kim SK, et al. Acute intestinal obstruction caused by a persimmon phytobezoar after dissolution therapy with Coca-Cola. Korean J Intern Med 2007;22:300–3. 23. Yen HH, Chou KC, Soon MS, Chen YY. Electronic clinical challenges and images in GI. Migration of a gastric bezoar. Gastroenterology

24. Chen HW, Chu HC. Migration of gastric bezoars leading to secondary ileus. Intern Med 2011;50:1993–5. 25. Kramer SJ, Pochapin MB. Gastric phytobezoar dissolution with ingestion of diet coke and cellulase. Gastroenterol Hepatol (N Y) 2012;8:770– 2.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Fitobezoara bağlı akut mekanik intestinal obstrüksiyon için tedavi stratejilerinin tartışılması: Tek merkezli geriye dönük bir çalışma Dr. Ali Fuat Kaan Gök,1 Dr. Recep Erçi̇ n Sönmez,2 Dr. Tarık Recep Kantarcı,1 Dr. Adem Bayraktar,1 Dr. Selman Emi̇ roğlu,1 Dr. Mehmet İlhan,1 Dr. Recep Güloğlu1 1 2

İstanbul Üniversitesi İstanbul Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Istanbul

AMAÇ: Bu çalışmanın temel amacı, fitobezoarın neden olduğuı ileus ile ilgili klinik sonuçlara dayanan tedavi stratejilerini tartışmaktır. GEREÇ VE YÖNTEM: Aralık 2012 ve Aralık 2018 yılları arasında fitobezoar tanısı alan toplam 25 hasta geriye dönük olarak değerlendirildi. Farklı seviyelerde gastrointestinal (GI) tıkanıklığa yol açmış fitobezoarlara bağlı akut mekanik bağırsak obstrüksiyonu olan hastalar çalışmaya alındı. Hastaların klinik verileri (klinik bulgular, laboratuvar sonuçları, radyolojik değerlendirmeler, tedavi yöntemleri) değerlendildi. BULGULAR: Çalışmaya 25 hasta dahil edildi. Yirmi beş hastanın 13’ü kadındı (%52). Ortanca yaş 60 (31–84) yıldı ve toplam ortanca kalış süresi yedi (2–28) gündü. On üç hastada (%72) geçirilmiş abdominal cerrahi olduğu tespit edildi. İki hasta (%8) konservatif olarak takip edildi, 20 (%80) hastaya cerrahi müdahale gerekti. Bir hastaya (%4) önceki endoskopik girişim ile parçalanan bezoar parçaları yüzünden oluşan distal ileal obstrüksiyon nedeniyle cerrahi girişim uygulandı. Ameliyat sonrası dönemde hastaların üçünde cerrahi alan enfeksiyonu, yara ayrılması ve ameliyat sonrası ileus gibi komplikasyonlar geliştiği saptandı. Sadece milking yapılan grup ile gastrotomi/enterotomi grupları arasında hastanede yatış süresi ve ameliyat sonrası komplikasyonlar açısından fark olmadığı saptandı. Bir hasta ameliyat sonrası 13. günde çoklu organ yetersizliği nedeniyle öldü. Mortalite oranı %4 olarak saptandı. TARTIŞMA: Fitobezoar kaynaklı akut mekanik bağırsak tıkanıklığı ile başvuran seçilmiş olgularda konservatif yaklaşım uygulanarak, önemli cerrahi müdahale gerekmeksizin uygun klinik iyileşme sağlanabilir. Ancak konservatif tedaviye yanıt alınamayan olgularda cerrahi tedavi mutlaka göz önünde bulundurulmalıdır. Enterotomi yapılan bağırsak segmentinin dikkatlice seçilmesi güvenli cerrahi için önemlidir. Anahtar sözcükler: Cerrahi; fitobezoar; ileus; konservatif tedavi. Ulus Travma Acil Cerrahi Derg 2019;25(5):503-509

doi: 10.14744/tjtes.2019.24557

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

509

ORIGIN A L A R T IC L E

Carcinoid tumors of appendix presenting as acute appendicitis Bora Barut, M.D.,

Fatih Gönültaş, M.D.

Department of General Surgery, İnönü University Faculty of Medicine, Malatya-Turkey

ABSTRACT BACKGROUND: We aim to present the data of patients who underwent appendectomy due to acute appendicitis, and incidental carcinoid tumor was detected on pathology. METHODS: Retrospective analysis of the patient charts between January 1999 and September 2018 were performed. RESULTS: 2778 appendectomy was performed due to acute appendicitis. Appendiceal carcinoid tumor was detected in 12 (0.43%) patients. Eight patients were (66.7%) female. Median age 37.5 years (range: 21–60). The median tumor size was 0.7 cm (range: 0.1–2.5). No perforation was detected. Eleven patients underwent appendectomy, and one patient had right hemicolectomy. The median followup period was 41.5 months (range: 22–49). There were no recurrences. CONCLUSION: Appendix carcinoid tumors are quite rare, usually asymptomatic and diagnosed incidentally on histopathological examination after appendectomy. The treatment of carcinoid tumors of the appendix is directly related to the tumor size, localization, presence of lymphovascular and mesoappendix invasion, mitotic activation rate and level of Ki67. Thus, it is important to follow the histopathological results after appendectomy. The prognosis of appendix carcinoid tumors is very good if the appendix is non-perforated. Keywords: Acute appendicitis; appendectomy; carcinoid tumor.

INTRODUCTION Primary appendix neoplasm is a rare pathology found in 0.51% of all appendectomy specimens. Carcinoid tumors represent more than 50% of appendix neoplasms that demonstrate no specific clinical presentation and present as acute appendicitis. They are usually diagnosed incidentally after appendectomy. Most carcinoid tumors are located at the tip of the appendix, and they are usually less than1 cm but rarely larger than 2 cm in diameter.[1,2] In the present study, we reported a series of 12 appendiceal carcinoid tumors detected after emergency appendectomy at our clinic.

MATERIALS AND METHODS Patients who had undergone appendectomy for acute appendicitis at Inonu University, Department of General Surgery between January 1999 and September 2018 were reviewed retrospectively. Patients with a diagnosis of carcinoid tumor

were analysed. Age, gender, symptoms, physical examination findings, follow-up times of the patients, preoperative abdominal ultrasonography findings, the indication for operation and the type of the operation were evaluated. Location of the tumor, tumor diameter, depth of invasion, histopathological cell type, mitotic activation rate and level of Ki67 of the tumor were defined.

Statistical Analysis For statistical evaluation, descriptive analysis was used. For homogenous distributions, we used mean and standard deviation, and for heterogeneous distributions we preferred median and range.

RESULTS During the study period, a total of 2778 patients underwent an emergency appendectomy. The patients who underwent

Cite this article as: Barut B, Gönültaş F. Carcinoid tumors of appendix presenting as acute appendicitis. Ulus Travma Acil Cerrahi Derg 2019;25:510-513. Address for correspondence: Bora Barut, M.D. İnönü Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Malatya, Turkey Tel: +90 422 - 341 06 60 / 6402 E-mail: borabarut@mynet.com Ulus Travma Acil Cerrahi Derg 2019;25(5):510-513 DOI: 10.5505/tjtes.2018.99569 Submitted: 19.11.2018 Accepted: 27.12.2018 Online: 22.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

510

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Barut et al. Carcinoid tumors of appendix presenting as acute appendicitis

appendectomy in addition to other operations were excluded from this study. Twelve of which (0.43%) were found to have histological evidence of carcinoid tumor of the appendix. These 12 patients comprised 4 (33.3%) males and 8 (66.7%) females, with a median age of 37.5 years (range, 21–60 years). All patients presented with clinical and radiological appendicitis. Ten patients had localized (right lower quadrant) pain, and the other two patients had generalized pain. Tenderness and rebound were detected in the right lower quadrant in all patients. Ultrasonography (USG) was used as radiological imaging. Demographic data, symptoms, physical examination findings, follow-up time of patients, and preoperative abdominal ultrasonography findings and the indication for operation are summarized in Table 1. Histologically, in 10 (83.4%) patients tumors were located at the tip of the appendix, in one patient it was in the middle, and the other one was at the base of the appendix, with a median diameter of 0.7 cm (range: 0.1–2.5 cm). While in 4 (33.3%) patients, the mesoappendix was invaded. Submucosal involvement was demonstrated histologically in six (50%) patients and the invasion of muscularis propria was detected in the other two (16.7%) patients. Mitotic index and Ki67 levels were <2 in all patients. Open appendectomy was performed in all patients. In one

patient, who had a diameter of 2.5 cm tumor and mesoappendix invasion, right hemicolectomy was performed in the second operation. In this patient, cecal tumor infiltration was detected on histopathological examination. The other two patients with a tumor diameter of 1.2 and 1 cm who had mesoappendix invasion did not accept right hemicolectomy. In these two patients, the follow-up time without recurrences or metastasis was 22 and 42 months, respectively. The median follow-up period was 41.5 months (range: 22–49). The histopathologic results and operation types of patients were summarized in Table 2.

DISCUSSION Appendiceal tumors are rare clinical condition and rarely associated with the manifestation of clinical symptomatology. Thus, they are detected incidentally either during surgery or generally after pathological examination of a resected appendix specimen. The most often type of appendiceal malignancy is a carcinoid tumor that accounts for about 60% of all appendiceal tumors. The incidence of appendiceal carcinoid tumor is 0.30%–2.27% in patients undergoing an appendectomy.[3] In this study, none of the patients had a suspicion of appendix carcinoid tumor preoperatively and the incidence of appendiceal carcinoid tumor was 0.43% in patients who underwent an emergency appendectomy.

Table 1. Demographic, clinical, radiological findings and follow-up time of patients No Age Gender Symptoms 1

Female

Localized pain, anorexia,

Preoperative diagnosis

Preoperative radiology (USG)

Follow-up time (month)

Accute appendicitis

nausea and vomoting

Female

Localized pain, anorexia

Accute appendicitis

Male

Localized pain, anorexia,

Accute appendicitis

Female

nausea and vomoting Localized pain, anorexia, nausea and vomoting

Male

Localized pain, anorexia

Accute appendicitis

Male

Genaralized, anorexia,

Accute appendicitis

nausea and vomoting

Genaralized, anorexia,

Female

nausea and vomoting Localized pain, anorexia

Female

Localized pain, anorexia

Accute appendicitis

Female

Localized pain, anorexia,

Accute appendicitis

nausea and vomoting

Male

Localized pain, anorexia

Accute appendicitis

Female

Localized pain, anorexia,

Accute appendicitis

nausea and vomoting

USG: Ultrasonography.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

511

Barut et al. Carcinoid tumors of appendix presenting as acute appendicitis

Table 2. The histopathologic results and operation types of patients No Pathology 1

Classical carcinoid tumor

Tumor Depth of invasion Tumor size localizations (cm)

Mitosis

Ki67

Operation type

Tip

Submucosa

1.3

Open appendectomy

Classical carcinoid tumor

Tip

Muscularis propria

0.2

Open appendectomy

Classical carcinoid tumor

Middle

Submucosa

0.5

Open appendectomy

Classical carcinoid tumor

Tip

Submucosa

0.4

Open appendectomy

Classical carcinoid tumor

Tip

Submucosa

0.1

Open appendectomy

Classical carcinoid tumor

Tip

Submucosa

0.7

Open appendectomy

Classical carcinoid tumor

Base

Mesoappendix

2.5

Right hemicolectomy

Classical carcinoid tumor

Tip

Submucosa

0.5

Open appendectomy

Classical carcinoid tumor

Tip

Mesoappendix

0.8

Open appendectomy

Classical carcinoid tumor

Tip

Mesoappendix

1.0

Open appendectomy

Classical carcinoid tumor

Tip

Mesoappendix

1.2

Open appendectomy

Classical carcinoid tumor

Tip

Muscularis propria

1.3

Open appendectomy

The median age (37.5 years) of the patient in our study is in agreement with a report of a consecutive series of 1570 appendectomies, where the mean age of appendiceal carcinoid tumor patients was 42.2 years.[4] Appendiceal carcinoid tumors are generally diagnosed more often among female than in male patients.[5–7] Similar to these studies, our study showed that the female to male ratio was 2:1. Most of the appendiceal carcinoid tumor is located at the tip of the appendix, and majority of the cases are smaller than 1 cm. The malign potential of carcinoid tumors is directly related to tumors size, and metastasis is very rare for the tumors smaller than 1 cm.[8] In the present study, the tumors were localized at the tip of the appendix at a rate of 83.4% with a median diameter of 0.7 cm (range: 0.1–2.5). Generally, appendiceal carcinoid tumors are asymptomatic, difficult to diagnose because of no classic symptoms specifically attributed to a tumor, presented as acute appendicitis and incidentally found on histopathological examination.[9,10] In our study, also all patients were diagnosed with acute appendicitis preoperatively, however, appendiceal carcinoid tumor was detected on histopathological examination. The prognosis and treatment of appendiceal carcinoid tumors are associated with tumor size and location, depth of invasion, mitotic and Ki67 index, presence of perineural and lymphovascular invasion. The tumor with a diameter >2 cm is rare (<10%), but has up to 40% risk for systematic dissemination. In these tumors, right hemicolectomy should be performed. [11] Because of the long-term risk of recurrence, right hemicolectomy should also be considered in carcinoids 1–2 cm in size, if the following factors are present: involvement of the mesoappendix, demonstrable angioinvasion, apparent high proliferative index and Ki67 level, tumor located at the base 512

of the appendix with positive margins, and in younger patients with positive lymph nodes. If tumor size <1 cm, appendectomy is enough for a cure.[12,13] In the present study, in seven patients who had <1 cm tumor size and in 2 patients had >1 cm tumor size without mesoappendix invasion. Thus, appendectomy was performed. In one patient with 2.5 cm tumor and mesoappendix invasion, right hemicolectomy was performed, but two patients with >1 cm tumor and mesoappendix invasion did not accept right hemicolectomy. However, in these two patients, no recurrence or metastasis was not detected during followup of 22 and 42 months, respectively. In conclusion, this study reports the frequency and outcomes of incidentally detected appendiceal carcinoid tumors in patients who underwent appendectomy for clinically suspected acute appendicitis. Appendiceal carcinoid tumor is a rare clinical entity and usually presented as acute appendicitis and generally diagnosed incidentally on histopathological examination. Small appendiceal carcinoid tumors (<1 cm) have an excellent prognosis after an appendectomy, while those >2 cm require hemicolectomy. Hemicolectomy should be considered in carcinoid tumors 1–2 cm in size if the mesoappendix is involved, angioinvasion is demonstrable, a high proliferative index and Ki67 level is apparent, and tumors are located at the base of the appendix with positive margins. Thus, the results of the histopathological examination are so important for deciding on additional surgical treatment and providing curative resection. Our results represent incidental carcinoid tumors, therefore; the stage of the disease was rather early, and the results were good without a major operation. Therefore, early diagnosis and low threshold for appendectomy in any individual from any age group are essential to obtain a cure. Conflict of interest: None declared. Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Barut et al. Carcinoid tumors of appendix presenting as acute appendicitis

REFERENCES

docrinology 2012;95:135–56.

1. Coşkun H, Bostanci O, Dilege ME, Mihmanli M, Yilmaz B, Akgün I, et al. Carcinoid tumors of appendix: treatment and outcome. Ulus Travma Acil Cerrahi Derg 2006;12:150–4. 2. Abdelaal A, El Ansari W, Al-Bozom I, Khawar M, Shahid F, Aleter A, et al. Frequency, characteristics and outcomes of appendicular neuroendocrinetumors: A cross-sectional study from an academic tertiary care hospital. Ann Med Surg (Lond) 2017;21:20–4. 3. Yilmaz M, Akbulut S, Kutluturk K, Sahin N, Arabaci E, Ara C, et al. Unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis. World J Gastroenterol 2013;19:4015–22. 4. Sandor A, Modlin IM. A retrospective analysis of 1570 appendiceal carcinoids. Am J Gastroenterol 1998;93:422–8. 5. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26:3063–72. 6. Pape UF, Perren A, Niederle B, Gross D, Gress T, Costa F, et al; Barcelona Consensus Conference participants. ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas. Neuroen-

7. Saylam B, Küçük ÖK, Düzgün AP, Özer MV, Coşkun F. Carcinoid tumor of the appendix: report on ten cases. Eur J Trauma Emerg Surg 2011;37:491–3. 8. Cakar E, Bayrak S, Bektaş H, Colak Ș, Guneyi A, Sevinc MM, et al. Carcinoid tumor of the cecum presenting with acute appendicitis: a case report. Chirurgia (Bucur) 2015;110:171-4. 9. Alemayehu H, Snyder CL, St Peter SD, Ostlie DJ. Incidence and outcomes of unexpected pathology findings after appendectomy. J Pediatr Surg 2014;49:1390–3. 10. Akbulut S, Tas M, Sogutcu N, Arikanoglu Z, Basbug M, Ulku A, et al. Unusual histopathological findings in appendectomy specimens: a retrospective analysis and literature review. World J Gastroenterol 2011;17:1961–70. 11. Moris D, Tsilimigras DI, Vagios S, Ntanasis-Stathopoulos I, Karachaliou GS, et al. Neuroendocrine Neoplasms of the Appendix: A Review of the Literature. Anticancer Res 2018;38:601–11. 12. Parkes SE, Muir KR, al Sheyyab M, Cameron AH, Pincott JR, Raafat F, et al. Carcinoid tumours of the appendix in children 1957-1986: incidence, treatment and outcome. Br J Surg 1993;80:502–4. 13. Stinner B, Rothmund M. Neuroendocrine tumours (carcinoids) of the appendix. Best Pract Res Clin Gastroenterol 2005;19:729–38.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisit gibi bulgu veren apendiks karsinoid tümörleri Dr. Bora Barut, Dr. Fatih Gönültaş İnönü Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Malatya

AMAÇ: Bu çalışmanın amacı, kliniğimizde akut apandisit tanısıyla apendektomi yapılan ve histopatolojik inceleme sonucunda apendiks karsinoid tümörü tespit edilen hastalara ait verilerimizi sunmaktır. GEREÇ VE YÖNTEM: Ocak 1999–Eylül 2018 tarihleri arasında akut apandisit ön tanısı ile apendektomi yapılan hastalar içinden histopatolojik olarak apendiks karsinoid tümörü tespit edilen hastaların sonuçları geriye dönük olarak incelendi. BULGULAR: Bu tarihler arasında toplam 2778 hastaya akut apandisit tanısı ile apendektomi yapıldı. On iki (%0.43) hastada apendiks karsinoid tümörü tespit edildi. Dört (%33.3) hasta erkek, sekiz (%66.7) hasta ise kadındı. Medyan yaş 37.5 yıl (21–60) idi. Medyan tümör çapı 0.7 cm (0.1–2.5) idi. Hiçbir hastada perfore apandisit gözlenmedi. On bir (%91.7) hastaya sadece apendektomi yapılırken, bir (%8.3) hastaya sağ hemikolektomi yapıldı. Medyan takip süresi 41.5 ay (22–49) olup hiçbir hastada nüks izlenmedi. TARTIŞMA: Apendiks karsinoid tümörleri oldukça nadir görülürler. Genellikle semptomsuz seyreder. Tanı çoğunlukla akut apandisit nedeniyle apendektomi yapıldıktan sonra histopatolojik incelenme sonucu, insidental olarak konulur. Apendiks karsinoid tümörlerinin tedavisi tümör boyutu, yerleşim yeri, lenfovasküler ve mezoapendiks invasyon varlığı, mitotik aktivasyon oranı ve Ki67 seviyesi ile doğrudan ilişkili olduğundan patoloji sonuçlarının takip edilmesi son derece önemlidir. Anahtar sözcükler: Akut apandisit; apendektomi; karsinoid tümör. Ulus Travma Acil Cerrahi Derg 2019;25(5):510-513

doi: 10.5505/tjtes.2018.99569

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

513

ORIGIN A L A R T IC L E

Ipsilateral hip pain and femoral shaft fractures: is there any relationship? Ramadan Özmanevra, M.D.,1 Nihat Demirhan Demirkıran, M.D.,2 Onur Hapa, M.D.,3 Ali Balcı, M.D.,4 Hasan Havıtçıoğlu, M.D.3 1

Department of Orthopaedics and Traumatology, University of Kyrenia Faculty of Medicine, Kyrenia-TRNC

Department of Orthopaedics and Traumatology, Kütahya University of Health Sciences Evliya Çelebi Training and

Research Hospital, Kütahya-Turkey 3

Department of Orthopaedics and Trauma Surgery, Dokuz Eylul University Faculty of Medicine, İzmir-Turkey

Department of Radiology, Dokuz Eylul University Faculty of Medicine, İzmir-Turkey

ABSTRACT BACKGROUND: High-energy traumas are common occurrences worldwide. The rate of overlooked neck fractures in polytrauma cases is also high. Previous studies have shown that articular hip pathologies, particularly neck fractures, are associated with fractures of the femoral shaft. This study sets out to describe cases of intra-articular hip pathology following traumatic femoral shaft fracture. Thus, the present study aims to investigate the relationship between ipsilateral hip pain and femoral shaft fractures. METHODS: Patients who were diagnosed with a fracture of the femur shaft and who were operated on (intramedullary fixation or plate) were included in this study. Patients with pathologic fractures, femoral neck fractures, femoral intertrochanteric fractures, or pelvic fractures were excluded. Patients with at least six months of follow-up and who were capable of independent walking without support were grouped according to AO/OTA fracture classification. Patients were questioned for deep anterior groin pain, and physical examination tests and hip imaging (X-ray and MR arthrography) were performed by calling patients with the indicated complaints. RESULTS: The presence of labral tears were noted in two patients. The incidence of osseous bump of the femoral neck identified by MR arthrography (MRA) was found in three of 16 hips. Assessment of the presence of gluteal tendinosis or tear and herniation pit identified three of 16 hips. The presence of osteophytes was noted in one patient. MRA identified three of 16 hips with more than one type of intra-articular pathology. Two patients with an osseous bump of the femoral neck were also diagnosed with additional hip pathology as herniation pit. CONCLUSION: Anterior groin pain in patients with a history of femoral shaft fracture is not always related to implants. Orthopedic surgeons should become suspicious in cases of intra-articular hip pathology in patients who have persistent hip pain after severe lower extremity trauma. Keywords: Femoral shaft; femur fracture; hip pathology; intra-articular; MR arthrography.

INTRODUCTION High-energy trauma causes concurrent ipsilateral hip fractures and occurs in 1–6% of fractures of the femoral shaft. [1–3] The clearer deformity and shaft fracture pain usually cover the femoral neck fracture in the same extremity, and make diagnosis and treatment of these fractures diffi-

cult. The rate of overlooked femoral neck fracture in polytrauma cases varies from 19% to 50%;[2,4–6] however, with the growing awareness and advances in scanning, this rate is declining.[7,8] Severe complications, such as femoral head osteonecrosis, make it even more important to diagnose and treat these injuries as early as possible. Khanna et al.[9] investigated intra-articular hip pathologies associated with

Cite this article as: Özmanevra R, Demirkıran ND, Hapa O, Balcı A, Havıtçıoğlu H. Ipsilateral hip pain and femoral shaft fractures: is there any relationship? Ulus Travma Acil Cerrahi Derg 2019;25:514-519. Address for correspondence: Ramadan Özmanevra, M.D. Girne Üniversitesi, Dr. Suat Gunsel Hastanesi, 99320 Girne, KKTC Tel: +90 392 - 444 99 39 E-mail: rozmanevra@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):514-519 DOI: 10.5505/tjtes.2018.52543 Submitted: 19.09.2018 Accepted: 19.12.2018 Online: 05.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

514

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Özmanevra et al. Ipsilateral hip pain and femoral shaft fractures: is there any relationship?

acute hip traumas in their prospective case series and they found a high incidence of ipsilateral injuries, such as labral tears (93%), osteochondral lesions (49%) and intra-articular step-off (38%). Based on the findings previous studies obtained, we predict that patients with femoral shaft fractures may also have unilateral intra-articular pathologies that may not be noticed at initial evaluation. Particularly in patients who have complaints of anterior groin pain with a history of femoral shaft fracture, we think that this pain may be due to intra-articular hip pathologies that develop after trauma. Conventional radiographs may be inadequate for diagnosing these injuries (such as FAI, chondral injury, labral tear,) and MR arthrography has been proven to be a gold standard in recent studies. [10–13] Therefore, we set out to investigate intra-articular hip pathologies of patients who developed deep anterior groin pain in follow-up after femoral shaft fracture surgery, using physical examination X-rays and MR arthrography. Patients who were diagnosed with a fracture of the femoral shaft and who had been operated on (intramedullary fixation or plate) were included in this study. Patients with pathologic fractures, femoral neck fractures, femoral intertrochanteric fractures, or pelvic fractures were excluded. Patients with at least six months of follow-up and who were capable of independent walking without support were grouped according to AO/OTA fracture classification. Patients were questioned for deep anterior groin pain, and physical examination tests and hip imaging (X-ray and MR arthrography) were performed by calling patients with the indicated complaints. The research question of our study was ‘what is the frequency of unnoticed ipsilateral hip joint injuries following femoral shaft fractures?’. Our hypothesis was ‘after femur shaft fractures, ipsilateral intraarticular hip pathologies are seen, and the diagnosis is frequently overlooked at initial evaluation.’ This study aims to describe cases of intra-articular hip pathologies following traumatic femoral shaft fracture. We aimed to evaluate the correlation between intra-articular hip pathologies and femoral shaft fractures.

MATERIALS AND METHODS Patients who were diagnosed with a fracture of the femur shaft and who had been operated on (intramedullary fixation or plate application) were included in this study. Patients with pathologic fractures, femoral neck fractures, femoral intertrochanteric fractures, or pelvic fractures were excluded. Patients with at least six months of follow-up and who were capable of independent walking without support were grouped according to AO/OTA fracture classification. Patients were questioned for deep anterior groin and hip pain. Physical examination tests and hip imaging (X-ray and MR arthrography) were performed by calling patients with the indicated complaints. For this purpose, ethical approval Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

was obtained. This study was supported by the Scientific Research Project Unit of Dokuz Eylul University. A retrospective review was performed to identify 145 patients who had undergone femoral shaft fracture surgery within the previous six months. Twenty-five patients with persistent groin pain or limping following fixation of an ipsilateral femoral shaft fracture were reported. A written report was prepared by asking the patient about the pain or limping via telephone. Sixteen of the patients agreed to visit the hospital for examination. All patients reported groin pain that was not present before the surgery. All patients signed an informed consent form. The diagnosis was verified based on clinical examination findings and tests. X-rays (Pelvis AP, 45° modified Dunn lateral radiographs, false profile) and MRI arthrography (MRA) were applied to the included patients. Following the MR imaging, the joint injection was performed. Patients were placed on a fluoroscopic table for a hip puncture, and internal rotation was maintained using a bolster under the knees with both feet taped together. A direct anterior or anterolateral approach to the hip was used. Intraarticular needle position was documented by injecting a small amount of iodinated contrast material. After confirming the intraarticular position, Gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ) was injected. Objective assessment was performed at the radiology department. Data were collected, which included the assessment of labral tears, subchondral cysts, ligamentum teres tears, labral/paralabral cysts, acetabular bone edema, fibrocystic changes of the femoral head/neck, rim fracture, osseous bump of the femoral neck, chondral lesions, osteophytes, transverse ligament tears, bursitis, avascular necrosis, adductor longus tendinosis, gluteal tendinosis or tear, femoral bony abnormalities and herniation pit. Mean, standard deviation, median lowest, highest, frequency and ratio values were used in descriptive statistics of the data. The distribution of variables was measured with the Kolmogorov-Simirnov test. Mann-Whitney U test was used for quantitative independent data analysis. Chi-square test was used for the analysis of qualitative independent data, and Fischer test was used when the chi-square test conditions were not provided. SPSS 22.0 program was used in the analysis.

RESULTS Sex distribution consisted of six women and ten men. The average age of the patients was 37.8 years (range 18–81). The average time from trauma to study was 28.3 months. Four of the patients were applied plate and 12 patients were applied intramedullary nail. The presence of labral tear was noted in two patients (Fig. 1). The incidence of an osseous bump of the femoral neck iden515

Özmanevra et al. Ipsilateral hip pain and femoral shaft fractures: is there any relationship?

Table 1. Patients’ demographics and detected hip pathologies

Age

Min–Max Median Mean±SD n 18–81

27.0

37.8±20.6

Sex

Female

37.5

Male

10 62.5

Fracture type Figure 1. The MRI and X-rays of a patient with labral tear.

Oblique

2 12.5

Transvers

14 87.5

Operation type

Plate

Intramedullary nail

Alfa angle (degree)

29–78

41.5

43.9±11.4

24–46

35.5

35.3±5.8

25.0

12 75.0

Lateral center edge angle (degree) Labral tear Figure 2. The MRI and pelvis AP postoperative 2nd day of the patient showed gluteal tendinosis.

(–)

14 87.5

(+)

12.5

Osseous bump of the femoral neck (–)

13 81.3

(+)

3 18.8

Osteophytes

(–)

15 93.8

(+)

6.3

Gluteal tendinosus or tear

Figure 3. The MRI and X-ray of the patient with herniation pit.

tified by MRA was three of 16 hips. In the assessment of the presence of gluteal tendinosis or tear (Fig. 2) and herniation pit, three of 16 hips were identified (Fig. 3). The presence of osteophytes was noted in 1 patient. MRA identified three of 16 hips as having more than one type of intra-articular pathology (Table 1). Two patients with osseous bump of the femoral neck were also diagnosed with additional hip pathology as herniation pit. Fifty percent of hips were diagnosed radiologically with intra-articular pathology (Table 1). Overlooked femoral neck fracture was not detected. The average alfa angle which was measured was 43,9 and lateral centre edge angle was 35,3. No significant difference was found between the pathologies and angles of the hip in comparison with fracture types (p>0.05) (Table 2). No difference was found between the types of operations performed (p>0.05) (Table 3). 516

(–)

13 81.3

(+)

3 18.8

Herniation pit

(–)

13 81.3

(+)

18.8

Min: Minimum; Max: Maximum; SD: Standard deviation.

DISCUSSION Our study revealed an ipsilateral hip pathology in half of the patients with hip and deep groin pain after femoral shaft fracture, regardless of fracture type or treatment modality. The source of persistent hip pain during the recovery period in patients with traumatic femoral shaft fracture is not always obvious. In some patients, it is present despite appropriate healing of the fracture. Implant removal may be recommended in some cases, but this is not always successful.[14] The causes of persistent symptoms can be multifactorial. The probability of an intra-articular hip pathology is often neglected. With the high-energy injuries, the possibility of complaints depends on both femoral shaft fracture and pathology of the hip joint reUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Özmanevra et al. Ipsilateral hip pain and femoral shaft fractures: is there any relationship?

Table 2. The comparison of fracture types

Fracture type-Oblique

Mean±SD

Fracture type-Transvers

Median

Mean±SD

Median

Alfa angle (degree)

58.0±28.3

58.0

41.9±7.3

41.5

0.524m

Lateral center edge angle (degree)

39.0±5.7

39.0

34.7±5.9

35.0

0.340m

Labral tear (–)

2 100

12 85.7

(+)

0.0

14.3

1.000X²

Osseous bump of the femoral neck (–) 1 50.0 12 85.7 0.350X² (+) 1 50.0 2 14.3 Osteophytes

(–)

100

92.9

1.000X²

(+)

0.0

7.1

Gluteal tendinosus or tear (–)

2 100

11 78.6

1.000X²

(+) 0 0.0 3 21.4 Herniation pit

(–)

100

78.6

(+)

0.0

21.4

1.000X²

Mann-Whitney U test; X²Chi-square test (Fischer test). SD: Standard deviation.

Table 3. The comparison of operation types

Operation type-Plate

Mean±SD

Operation type-IMN Median

Mean±SD

p Median

Alfa angle (degree)

51.0±18.7

44.0

41.6±7.5

41.5

0.504m

Lateral center edge angle (degree)

37.8±3.6

36.5

34.4±6.3

33.5

0.208m

Labral tear (–) 3 75.0 11 91.7 0.450X²

(+)

25.0

8.3

Osseous bump of the femoral neck (–) 3 75.0 10 83.3 1.000X² (+) 1 25.0 2 16.7 Osteophytes

(–)

75.0

100.0

(+)

25.0

0.0

0.250X²

Gluteal tendinosus or tear (–) 3 75.0 10 83.3 1.000X² (+) 1 25.0 2 16.7 Herniation pit

(–)

100

75.0

(+)

0.0

25.0

0.529X²

Mann-Whitney U test; X²Chi-square test (Fischer test). IMN: Intramedullary nail; SD: Standard deviation.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

517

Özmanevra et al. Ipsilateral hip pain and femoral shaft fractures: is there any relationship?

mains unclear.[15,16] These pathologies may lead to persistent hip pain and disability. Femoral shaft fractures arise from considerable trauma, so these patients often have other injuries given that common comorbid injuries femoral neck fracture and soft tissue damage of the knee are both documented in the literature.[17,18] Burnett et al.[19] concluded that when a femoral shaft fracture occurs, significant attention has not been paid to the possibility of a soft tissue injury of the hip. This may be due in part to the initial severity of the trauma, as well as general pain related to the fracture or its fixation, complicating the diagnosis of labral pathology. In our study, we detected at least one type of intraarticular pathology in half of the patients with femoral shaft fracture and hip pain after a fracture. Three of these patients had more than one articular pathology. Orthopedic surgeons should become suspicious of labral pathology in patients who have persistent hip pain after severe lower extremity trauma. MRI arthrography is more specific and more sensitive than conventional MRI. Studies have shown that MRI arthrography is the most definitive and reliable diagnostic tool to confirm the presence of a labral tear.[20–22] In patients with ipsilateral hip joint complaints, evaluation of the hip with MRI arthrography after completing clinical and radiographic examination may be required. Intraarticular hip pathology can be confirmed by performing hip arthroscopy, and hip arthroscopy may also help to eliminate the source of pain. High energy trauma can subluxate or dislocate adjacent joints and cause significant intra-articular trauma. Similar entities have also been shown in the knee. Several studies have documented ligamentous knee damage in conjunction with femoral fractures.[23,24] Our patient group consisted of patients with femoral shaft fractures after high energy trauma. Only two of our patients had an oblique fracture. However, no significant difference was found between fracture type and intraarticular pathologies. Twelve patients were treated with IMN and four patients received plate application in our study group. No significant difference was found between operation types and intraarticular pathologies. None of the patients underwent implant removal because of pain. Removal of the implant is most commonly applied in patients with persistent hip pain following ORIF of a femoral shaft fracture. Implant removal successfully alleviates pain in many cases, but studies documented cases in which pain was not relieved. Dodenhoff et al. reported the incidence of residual femoral pain in 80 patients who were treated for traumatic femoral fracture with a Grosse-Kempf nail. Seventeen patients had the nail removed due to pain, and of these, six (35%) patients continued to experience the pain. This result suggests that if the pain is not resolved after implant removal, consideration should be given to soft 518

tissue and intra-articular pa-thology of the adjacent joints. Magnetic resonance imaging provides highly sensitive and accurate resolution of the labrum and associated tissue, making it an effective tool for identifying the location and magnitude of a labral tear.[14] In our study, eight of the sixteen patients presented intraarticular hip pathologies with persistent hip and groin pain after femoral shaft fracture. We found a correlation between femoral shaft fracture and intra-articular hip pathologies. One of the limitations of our study is the amount of included patients. The number of patients is insufficient to detect the frequency of the ipsilateral hip joint injuries following femoral shaft fractures. The weakness of this study is that it was a retrospective study. However, the study is enhanced by the use of a blinded musculoskeletal radiologist to quantify the pathologic findings from the imaging to provide valuable insights into the literature. We hope further investigations may lead to insightful information about this research topic.

Conclusions In conclusion, intra-articular hip pathologies can be detected in patients who have femoral shaft fractures. Anterior groin and hip pain in patients with a history of femoral shaft fracture are not always related to implants. Orthopedic surgeons should become suspicious of intra-articular hip pathology in patients who have persistent hip pain after severe lower extremity trauma. It should be kept in mind that intraarticular injuries other than femur neck fracture may develop with the femoral shaft fracture. Conflict of interest: None declared.

REFERENCES 1. Abalo A, Dossim A, Ouro Bangna AF, Tomta K, Assiobo A, Walla A. Dynamic hip screw and compression plate fixation of ipsilateral femoral neck and shaft fractures. J Orthop Surg (Hong Kong) 2008;16:35–8. 2. Swiontkowski MF. Ipsilateral femoral shaft and hip fractures. Orthop Clin North Am 1987;18:73–84. 3. Zettas JP, Zettas P. Ipsilateral fractures of the femoral neck and shaft. Clin Orthop 1981;160:63–73. 4. Swiontkowski MF, Hansen ST Jr, Kellam J. Ipsilateral fractures of the femoral neck and shaft. A treatment protocol. J Bone Joint Surg Am 1984;66:260–8. 5. Bennett FS, Zinar DM, Kilgus DJ. Ipsilateral hip and femoral shaft fractures. Clin Orthop Relat Res 1993;296:168–77. 6. Delaney WM, Street DM. Fracture of femoral shaft with fracture of neck of same femur; treatment with medullary nail for shaft and Knowles pins for neck. J Int Coll Surg 1953;19:303–12. 7. Lawson E, Madougou S, Chigblo P, Quenum G, Ouangré A, Tidjani F, et al. Ipsilateral proximal and shaft femoral fractures. Chin J Traumatol 2017;20:155–7. 8. Yang KH, Han DY, Park HW, Kang HJ, Park JH. Fracture of the ipsilateral neck of the femur in shaft nailing. The role of CT in diagnosis. J Bone Joint Surg Br 1998;80:673–8.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Özmanevra et al. Ipsilateral hip pain and femoral shaft fractures: is there any relationship? 9. Khanna V, Harris A, Farrokhyar F, Choudur HN, Wong IH. Hip arthroscopy: prevalence of intra-articular pathologic findings aftertraumatic injury of the hip. Arthroscopy 2014;30:299–304. 10. Chan YS, Lien LC, Hsu HL, Wan YL, Lee MS, Hsu KY, et al. Evaluating hip labral tears using magnetic resonance arthrography: a prospective study comparing hip arthroscopy and magnetic resonance arthrography diagnosis. Arthroscopy 2005;21:1250. 11. Toomayan GA, Holman WR, Major NM, Kozlowicz SM, Vail TP. Sensitivity of MR arthrography in the evaluation of acetabular labral tears. AJR Am J Roentgenol 2006;186:449–53. 12. Petersilge CA, Haque MA, Petersilge WJ, Lewin JS, Lieberman JM, Buly R. Acetabular labral tears: evaluation with MR arthrography. Radiology 1996;200:231–5. 13. Leunig M, Werlen S, Ungersböck A, Ito K, Ganz R. Evaluation of the acetabular labrum by MR arthrography. J Bone Joint Surg Br 1997;79:230– 4. 14. Dodenhoff RM, Dainton JN, Hutchins PM. Proximal thigh pain after femoral nailing. Causes and treatment. J Bone Joint Surg Br 1997;79:738–41. 15. Milenković S, Mitković M, Saveski J, Micić I, Stojiljković P, Stanojković M, et al. Avascular necrosis of the femoral head in the patients with posterior wall acetabular fractures associated with dislocations of the hip. [Article in Serbian]. Acta Chir Iugosl 2013;60:65–9. 16. Giannoudis PV, Kontakis G, Christoforakis Z, Akula M, Tosounidis T, Koutras C. Management, complications and clinical results of femoral head fractures. Injury 2009;40:1245–51.

17. Tornetta P 3rd, Kain MS, Creevy WR. Diagnosis of femoral neck fractures in patients with a femoral shaft fracture. Improvement with a standard protocol. J Bone Joint Surg Am 2007;89:39–43. 18. Dickson KF, Galland MW, Barrack RL, Neitzschman HR, Harris MB, Myers L, et al. Magnetic resonance imaging of the knee after ipsilateral femur fracture. J Orthop Trauma 2002;16:567–71. 19. Burnett RS, Della Rocca GJ, Prather H, Curry M, Maloney WJ, Clohisy JC. Clinical presentation of patients with tears of the acetabular labrum. J Bone Joint Surg Am 2006;88:1448–57. 20. Byrd JW, Jones KS. Diagnostic accuracy of clinical assessment, magnetic resonance imaging, magnetic resonance arthrography, and intra-articular injection in hip arthroscopy patients. Am J Sports Med 2004;32:1668– 74. 21. Kelly BT, Williams RJ 3rd, Philippon MJ. Hip arthroscopy: current indications, treatment options, and management issues. Am J Sports Med 2003;31:1020–37. 22. Freedman BA, Potter BK, Dinauer PA, Giuliani JR, Kuklo TR, Murphy KP. Prognostic value of magnetic resonance arthrography for Czerny stage II and III acetabular labral tears. Arthroscopy 2006;22:742–7. 23. Emami Meybodi MK, Ladani MJ, Emami Meybodi T, Rahimnia A, Dorostegan A, Abrisham J, et al. Concomitant ligamentous and meniscal knee injuries in femoral shaft fracture. J Orthop Traumatol 2014;15:35– 9. 24. Moore TM, Patzakis MJ, Harvey JP Jr. Ipsilateral diaphyseal femur fractures and knee ligament injuries. Clin Orthop Relat Res 1988;232:182– 9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İpsilateral kalça ağrısı ve femur şaft kırıkları: Herhangi bir ilişki var mı? Dr. Ramadan Özmanevra,1 Dr. Nihat Demirhan Demirkıran,2 Dr. Onur Hapa,3 Dr. Ali Balcı,4 Dr. Hasan Havıtçıoğlu3 Girne Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Girne-KKTC Kütahya Sağlık Bilimleri Üniversitesi Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Kütahya Dokuz Eylül Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İzmir 4 Dokuz Eylül Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, İzmir 1 2 3

AMAÇ: Yüksek enerjili travmalar dünya çapında yaygın karşılaşılan olaylardır. Politravma olgularında gözden kaçan boyun kırıklarının oranı da yüksektir. Daha önce yapılan çalışmalar artiküler (eklem içi) kalça patolojilerinin, özellikle de boyun kırıklarının femoral şaft kırıkları ile ilişkili olduğunu göstermiştir. Bu çalışmanın amacı travmatik femoral şaft kırığını takiben eklem içi kalça patolojisi olgularını tanımlamaktır. Bu çalışmanın araştırma sorusu “Femur şaft kırıklarından sonra femur boynu kırılmayan hastaların kalça eklemlerinde ne oluyor?” dur. GEREÇ VE YÖNTEM: Femur şaft kırığı tanısı konan ve ameliyat edilen hastalar (intramedüller fiksasyon veya plak uygulaması) çalışmaya alındı. En az altı ay takip edilen ve desteksiz bağımsız yürüme yeteneğine sahip hastalar AO/OTA kırık sınıflamasına göre gruplandırıldı. Hastalara derin anterior kasık ağrısı soruldu ve belirtilen şikayetleri olan hastalar aranarak fizik muayene ve kalça görüntüleme (X-ray ve manyetik rezonans artrografi [MRA]) yapıldı. BULGULAR: İki hastada labral yırtık tespit edildi. MRA ile femur boynu osseöz bump 16 kalçadan üçünde bulundu. Gluteal tendinosis veya gözyaşı ve herniasyon pit (çukurunun) varlığının değerlendirilmesi, 16 kalçadan üçünde tespit edilmiştir. Bir hastada osteofit varlığı belirlendi. MRA ile, 16 kalçadan üçünde birden fazla tipte intra-artiküler (eklem içi) patoloji tanımlandı. Femur boynu osseöz bumpı olan iki hastaya da herniasyon pit olarak ek kalça patolojisi tanısı konuldu. TARTIŞMA: Femur şaft kırığı öyküsü olan hastalarda kasık önü ağrısı her zaman implantlarla ilişkili değildir. Ortopedik cerrahlar, şiddetli alt ekstremite travması sonrası kalıcı kalça ağrısı olan hastalarda eklem içi kalça patolojilerinden şüphelenmelidirler. Anahtar sözcükler: Eklemiçi; femur kırığı; femur şaft; kalça patolojisi; manyetik rezonans artrografi. Ulus Travma Acil Cerrahi Derg 2019;25(5):514-519

doi: 10.5505/tjtes.2018.52543

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

519

CAS E SERI ES

Our experience with dermal substitute Nevelia® in the treatment of severely burned patients Hakan Yiğitbaş, M.D.,1 Erkan Yavuz, M.D.,1 Evrim Beken Özdemir, M.D.,1 Önder Önen, M.D.,1 Halime Hanım Pençe, M.D.,2 Serhat Meriç, M.D.,1 Atilla Çelik, M.D.,1 Fatih Çelebi, M.D.,1 Ahmet Çınar Yastı, M.D.,3 Tansel Sapmaz, M.D.,4 Aydın Zilan, M.D.,1 Mustafa Turan, M.D.1 1

Department of General Surgery, Health Sciences University Bağcılar Training and Research Hospital, İstanbul-Turkey

Department of Biochemistry, Health Sciences University Faculty of Medicine, İstanbul-Turkey

Department of General Surgery, Health Sciences University Ankara Numune Training and Research Hospital, Ankara-Turkey

Department of Histology and Embryology, Health Sciences University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: This research aims to retrospectively evaluate the effectiveness and safety of dermal substitute (DS), Nevelia®, for the treatment of severely burned patients. METHODS: Twenty severely burned patients were enrolled in this study between May 2017 and May 2018. After escharotomy of the wound, the treatment protocol was applied following a two-step procedure –DS implantation followed by split-thickness skin graft (STSG) application. Need for surgery, complications, hospitalisation duration and overall survival were analysed. RESULTS: Mean age was 40.1±4 (18–86) years old; female/male: 5/15. Mean burn surface area was 50.1%±2 (25–96). Two patients died under hospital treatment due to the severity of their burn trauma and comorbidities. For the rest of the cases, STSG was performed after Nevelia® at mean 21.2 days. No complications due to Nevelia® were detected. The patients were discharged with a mean total recovery of 55.2±4 days. CONCLUSION: This study showed that Nevelia® can be used safely and effectively in severely burned patients with low complication rates and short hospital stay. Keywords: Dermal substitute; eschar management; major burn.

INTRODUCTION The principle of care in managing severely burned patients is primarily focused on survival. The main issues in the first hours are resuscitation and haemodynamics. After 48 hours, septic problems and eschar management eventually become a critical issue. The insufficiency of skin graft donor sites in severely burned patients is one of the major problems in the management of these patients. Dermal substitutes (DS) are becoming an important part of burn care with an increasing interest. In the acute phase of

burn treatment, the use of DS ameliorates functional and aesthetic long-term results. DS are bio-matrices that perform the functions of the cutaneous dermal layer, including protecting the subcutaneous tissue from physical factors, acting as a barrier against infections and reducing scarring. DS, which act like matrices or scaffold and support tissue buildup, boost wound healing consequently.[1,2] The structure of DS provides flexibility and better scar tissue formation. In both acute and chronic stages, DS has a large part in healing fullthickness skin defects[3] and advanced scar quality.[4]

Cite this article as: Yiğitbaş H, Yavuz E, Beken Özdemir E, Önen Ö, Pençe HH, Meriç S, et al. Our experience with dermal substitute Nevelia® in the treatment of severely burned patients. Ulus Travma Acil Cerrahi Derg 2019;25:520-526. Address for correspondence: Hakan Yiğitbaş, M.D. Sağlık Bilimleri Üniversitesi Bağcılar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 440 40 00 / 3389 E-mail: drhyigitbas@yahoo.com.tr Ulus Travma Acil Cerrahi Derg 2019;25(5):520-526 DOI: 10.14744/tjtes.2019.24358 Submitted: 06.04.2019 Accepted: 05.08.2019 Online: 23.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

520

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Yiğitbaş et al. Our experience with DS Nevelia® in the treatment of severely burned patients

Nevelia® (Symatese Aesthetics, Lyon, France) is made from specific native collagen with a large fibrous proportion to preserve cell adhesion signals and mechanical structure to support regeneration. In vitro test demonstrate an optimised colonisation as fibroblasts recognise collagen fibres. Nevelia® is indicated for dermal regeneration in cases involving skin loss, particularly in burns and trauma. This bi-layer matrix is usually used in combination with a thin split-thickness skin graft (STSG) to recreate skin resembling the normal one in terms of function and appearance. This research describes our experience in using Nevelia® for the treatment of severely burned patients.

rescence Imaging System (Novodaq, Stryker, US), burn depth was measured. According to the patient’s clinical state and tolerance, viable and healthy dermis were protected. Chemical eschar debridement and reepithelisation procedures were performed. In burn areas that were not too deep, self-healing procedures were followed. In areas with a third-degree burn, early eschar excision protocol was used. Then, Nevelia® was applied to the escharotomy areas.

MATERIALS AND METHODS

Nevelia® was applied on the burn area using ApposeTM Single-Use Skin Stapler (Medtronic, MN, USA) and was dressed with antimicrobial materials. The dressing was changed every two days. Integration of the Nevelia® to the tissues was observed during this time.

This retrospective case series study was approved by the Health Sciences University, Bağcılar Education and Research Hospitals’ Ethics Committee. This study included patients who were admitted to a burn care unit with severe fullthickness burn wounds [Total Body Surface Area (TBSA) ≥25%] between May 2017 and May 2018. Their need for surgery, complications, hospitalisation duration and overall survival were analysed. TBSA percentage and TBSA with Nevelia® surface were measured using the Lund and Browder chart.[5]

The subsequent delamination of Nevelia® (silicone leaf removal) and the timing of split-thickness skin graft application were determined on a case-to-case basis according to the availability and physiological well-being of the subject. Re-harvesting from the same donor site was necessary for some patients. Therefore, the state of re-epithelialization of the skin graft donor site was very important for them. Once delaminated, the surface of the neodermis was refreshed by dermabrasion before meshed STSG was applied and the dressing was performed.

Burn patients were categorised according to a specific clinical burn management protocol designed to stabilise them within 48 to 72 hours. Later, using the SPY® Infrared Fluo-

The thickness of harvest and mesh ratio of the STSG was determined clinically on each occasion by donor site availability, and the need for the second harvest from the same

(a)

(b)

(e)

(f)

(c)

(d)

(g)

(h)

Figure 1. Case 1: 23 years old man (Subject 9), burned on 90% of his TBSA following a work accident. (a) The right and left limbs and the trunk were burned and underwent fascial excision. (b, c) Fasciotomy lines. No residual dermal element was left. (d, e) Nevelia® cut to shape and applied with staples. (f) Vascular invasion and collagen deposition complete by Day 20. (g, h) The autograft appearance 90 days after application over the integrated Nevelia® neo-dermis.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

521

Yiğitbaş et al. Our experience with DS Nevelia® in the treatment of severely burned patients

(a)

(d)

(b)

(e)

(c)

(f)

Figure 2. Case 2: 28 years old woman (Subject 19), burned on 60% of her TBSA following a house accident. (a, b) The right and left limbs and the trunk were burned and underwent fasciotomy and tangential excision. (c, d) Nevelia® cut to shape and applied with staples. Vascular invasion and collagen deposition complete by Day 20. (e, f) The autograft appearance 6 and 12 days respectively after grafting.

donor areas was anticipated. In this study, all grafts applied over Nevelia® were either applied as fenestrated sheet graft (over the dorsum of hands) or meshed 1,5–3, at all other sites. Skin grafts were dressed according to our previous standard of care, typically with paraffin gauze overlaid with saline and antibacterial-soaked gauze secured with crepe bandages. Dressings were changed with graft check at four days and then twice weekly until completely healed. Photographic records were taken at every intervention (Figs. 1, 2). The punch biopsy specimens of representative areas were taken at various intervals for culture. All subjects received standard physiotherapy scar treatment, which included compression garment therapy.

RESULTS Patient Characteristics Twenty adult patients aged between 18 and 86 years old (mean age 40.1±4) shown in Table 1 were enrolled in this study. Five out of 20 patients were female. Burn incidents had occurred mostly at work and home (45% and 40%, respectively). Seventy percent of the patients were in a closed area and were exposed to inhalation injuries. Full-thickness burn wounds covered 25%–96% of TBSA with a mean surface of 50.1%±2%. The mean surface receiving Nevelia® was 8.25%±1% of TBSA (on third-degree burn area). 522

Nevelia® application The colonisation of Nevelia® and mean duration time for the STSG acceptance was 21.2±3 days. Other than two integration failure, no adverse event or complications related to the use of Nevelia® were seen. Patients were discharged with a mean recovery of 55.2±4 days (Table 2). Among the 20 patients, failure was seen in two patients who had DS Nevelia®. These two cases had burn wound in 92% and 96% of their TBSA with multiple comorbidities. The clinical status of these two patients was critical, and they died from their injuries. Their wound healing was poor, probably because of multiorgan insufficiency.

DISCUSSION Patients with severe full-thickness burn wounds require artificial materials due to the deprivation of sufficient donor tissue. Identifying efficient, safe and cost-effective skeleton materials can be stressful. Autologous skin graft is the most preferred material in burn wound coverage; however, especially in extensive full-thickness burn wounds, having limited donor sites can complicate the process. Another distressing point is the presence of donor tissue morbidities regarding having additional wounds and scars. This issue required various skin substitutes for the treatment of acute full-thickness burn wounds.[6] Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Yiğitbaş et al. Our experience with DS Nevelia® in the treatment of severely burned patients

Table 1. Subject demographics and mechanisms of burn injury Subject Age Gender Burned areas Mechanisms of burn injury No. 1

Male

Lower limbs

The explosion of Liquid Petroleum Gas

(LPG) bottle. Enclosed space,

inhalation injury.

% TBSA burn

DS area/ TBSA (%)

Male

Lower limbs

Working place fire with petrol indoors.

Male

Lower limbs and trunk

Working place fire with petrol indoors.

Male

Female

Enclosed space, inhalation injury.

Upper limbs, lower

Working place fire.

limbs and trunk

Enclosed space, inhalation injury.

Head, upper limbs,

Heroin intoxication. House fire started

lower limbs and trunk

by cigarette falling into the carpet.

Female

Enclosed space, inhalation injury.

Lower limbs and trunk

House fire secondary to LPG oven.

Male

Enclosed space, inhalation injury.

Lower limbs and trunk

Working place fire.

Enclosed space, inhalation injury.

Male

Upper limbs and trunk

Garden fire explosion.

Male

Upper/lower limbs, trunk

Working place fire with the explosion

Male

of the water boiler.

Upper/lower limbs, trunk

Self-immolation with petrol indoors.

Male

Enclosed space, inhalation injury.

Upper/lower limbs

Working place fire with gasoline and motor oil.

Enclosed space, inhalation injury.

Upper/lower limbs,

Working place fire with gasoline.

trunk

Enclosed space, inhalation injury.

Lower limbs

Bonzai intoxication. House fire started by cigarette

Male

falling into the carpet. Enclosed space, inhalation injury.

Male

Upper/lower limbs, trunk

Working place burn with high voltage electricity.

Male

Upper limb, trunk

Bonzai intoxication. House fire started by

cigarette falling into gasoline.

Female

Upper limb, trunk

House fire secondary to deodorant gas.

Male

Upper/lower limbs

Working place fire secondary to the electrical fault.

Male

Upper limb, trunk

Enclosed space, inhalation injury. Alcohol intoxication. House fire started by cigarette

falling into the carpet. Enclosed space, inhalation injury

Alcohol intoxication. House fire started by cigarette

Female

Upper limb, trunk

Female

falling into the carpet. Enclosed space, inhalation injury

Upper/lower

Suicide attempt by opening the home natural gas.

limbs, trunk

Home fire secondary to electrical spark.

At present, there are numerous DS products available commercially. Most of these products have been extensively tested and examined in both pre-clinical and clinical settings.[7–10] In the last 1-year period, we have applied Nevelia® to several escharotomy areas of some of our severely burned patients. Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Enclosed space, inhalation injury.

Many of the present biocompatible DS can mimic the basic properties of the extracellular matrix in human skin by providing some structural integrity, elasticity and vascular bed. It reduces evaporative water loss, and the exudation of proteinrich fluids prevents wound desiccation and suppress micro523

Yiğitbaş et al. Our experience with DS Nevelia® in the treatment of severely burned patients

Table 2. The number of days for the DS integration, tpe length of stay, adverse events suffered by each subject, classified as those related to the burn injury and its pathophysiological evolution, and those related to the DS Subject Total Failure Comorbidities/ Burn-related AE No. days of of DS clinically DS to integration relevant integrate situation 1

–

Hypertension

Lower airway inhalation

Length of stay (days)

Result

Discharged with recovery

injuries, Pneumonia

–

Discharged with recovery

–

Hypertension

–

Discharged with recovery

–

Discharged with recovery

Failure of DS

Drug abuse

Significant lower airway inhalation injuries

Death

125

Discharged with recovery

integration in

Pneumonia

one of six areas.

Pseudomonas, Acinetobacter, candida

Acute renal injury requiring dialysis

ileus, abdominal compartment syndrome,

–

Alzheimer,

Pneumonia

hypertension

Pseudomonas, Acinetobacter in the

wound, candida in the blood

Small graft breakdowns on the trunk and lower limb

–

Discharged with recovery

–

Kidney transplant

Lower airway inhalation injuries

Discharged with recovery

Death

Discharged with recovery

(5 years ago)

Significant wound healing delay

Pseudomonas, acinetobacter in the wound,

Significant lower airway inhalation injuries,

–

Pneumonia, ventilation support.

Ileus, abdominal compartment syndrome,

Pseudomonas, Acinetobacter in the wound

Significant lower airway inhalation injuries,

Failure of DS

–

integration in

pneumonia, ventilation support.

one of six areas.

Abdominal compartment syndrome,

open abdomen by Bogota bag Acute

–

renal injury requiring dialysis Significant lower airway inhalation injuries, pneumonia.

–

Discharged with recovery

–

Drug abuse

–

Discharged with recovery

–

Discharged with recovery

–

Discharged with recovery

–

Discharged with recovery

–

Discharged with recovery

–

Alcoholism.

Lower airway inhalation injuries

Discharged with recovery

–

Discharged with recovery

Lower airway inhalation injuries, pneumonia,

Discharged with recovery

Child a cirrhosis

due to alcohol.

–

Drug abuse and alcoholism. Alcoholism

524

she needed mechanical ventilation support.

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Yiğitbaş et al. Our experience with DS Nevelia® in the treatment of severely burned patients

bial proliferation. However, these products lack the epithelial layer, and in most cases, the use of such products will generally be followed by the inoculation of the split-thickness skin autograft for permanent coverage in a two-step procedure. We applied a split-thickness skin autograft after a mean of 21.4 days from the application of Nevelia®.

and dermal regeneration when compared with that of Integra. The study also showed that Nevelia® revealed more pronounced angiogenesis against Integra®, which was evaluated with α-SMA immunohistochemistry.[10] In the present study, we found good integration and wound healing process with Nevelia®.

In severe burns, various options are available after the clinicians perform early escharotomy. These options include allograft usage, DS, keratinocyte autoculture or antimicrobial dressing material application. Allograft usage may pose problems because of rejection and infection. Antimicrobial dressing material application generally does not provide the patient with enough protection from bacteraemia. Keratinocyte autoculture has not progressed to qualify for routine clinical usage.

Conclusion

Identifying a successful material that will be helpful during the eschar management period is very important. In recent years, DS has played important roles in burn treatment protocols. After escharotomy, an effective DS is very helpful in building a protection cover for the body. If DS is effective, then, the survival percentage of the patient increases. There is still a possibility of harvest morbidity that may be inadequate in donor sites in wide burn areas. As indicated in the literature,[11] the use of Nevelia® allows us to harvest thinner split-thickness skin autografts and thus donor sites heal faster. These materials are also helpful in improving the elasticity of the skin after split-thickness skin graft application. Despite the potential and need for DS, further research is required to strengthen the scientific evidence of the potential impacts and to develop new technologies and products.[12,13] However, these substitutes have significant limitations when used in the presence of infections or full-thickness defects. [14] In our case series, integration failed only in two of the 20 cases. These two cases had burn wound in 92% and 96% of their TBSA and had many comorbidities. Their clinical status was critical, and they died from their injuries. Their wound healing was poor, probably due to multiorgan insufficiency. DS appear as a key research strategy to improve sufficient scaffolds to obtain long-lasting and scarred artificial skin for stem cells, regenerative medicine applications and tissue engineering.[15,16] Integra® Dermal Regeneration Template (Integra Life Science, NJ, USA) is a widely used for covering excised full-thickness burn wounds and has proven to be particularly valuable in patients with large burns and limited autograft donor sites.[11,17] Integra® consists of the following two layers: a DS made of porous bovine collagen and chondroitin-6sulfate glycosaminoglycan and an epidermal substitute made of a synthetic silicone polymer. The dermal layer serves as a matrix for infiltration by fibroblasts and other cells from the wound bed. De Angelis B et al. reported that Nevelia® had early regenerative properties in epidermal proliferation Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

The findings of the present study provide favourable results of incorporating Nevelia® in our daily practice for the treatment of severely burned patients. Authors conclude that Nevelia® is safe as well as easy to use. Additionally, graft loss over Nevelia® is unusual. Conflict of interest: None declared.

REFERENCES 1. Lee KH. Tissue-engineered human living skin substitutes: development and clinical application. Yonsei Med J 2000;41:774–9. 2. Pham C, Greenwood J, Cleland H, Woodruff P, Maddern G. Bioengineered skin substitutes for the management of burns: a systematic review. Burns 2007;33:946–57. 3. van der Veen VC, van der Wal MB, van Leeuwen MC, Ulrich MM, Middelkoop E. Biological background of dermal substitutes. Burns 2010;36:305–21. 4. Hodgkinson T, Bayat A. Dermal substitute-assisted healing: enhancing stem cell therapy with novel biomaterial design. Arch Dermatol Res 2011;303:301–15. 5. Lund CC, Browder NC. The estimation of areas of burns. Surg Gynecol Obstet 1944;79:352–8. 6. Oravcová D, Koller J. Currently available skin substitutes. Cas Lek Cesk 2014;153:7–12. 7. Supp DM, Boyce ST. Engineered skin substitutes: practices and potentials. Clin Dermatol 2005;23:403–12. 8. Shevchenko RV, James SL, James SE. A review of tissue-engineered skin bioconstructs available for skin reconstruction. J R Soc Interface 2010;7:229–58. 9. Hansbrough JF, Franco ES. Skin replacements. Clin Plast Surg 1998;25:407–23. 10. De Angelis B, Orlandi F, Fernandes Lopes Morais D’Autilio M, Scioli MG, Orlandi A, Cervelli V, et al. Long-term follow-up comparison of two different bi-layer dermal substitutes in tissue regeneration: Clinical outcomes and histological findings. Int Wound J 2018;15:695–706. 11. Heimbach D, Luterman A, Burke J, Cram A, Herndon D, Hunt J, et al. Artificial dermis for major burns. A multi-center randomized clinical trial. Ann Surg 1988;208:313–20. 12. Shahrokhi S, Arno A, Jeschke MG. The use of dermal substitutes in burn surgery: acute phase. Wound Repair Regen 2014;22:14–22. 13. Philandrianos C, Andrac-Meyer L, Mordon S, Feuerstein JM, Sabatier F, Veran J, et al. Comparison of five dermal substitutes in full-thickness skin wound healing in a porcine model. Burns 2012;38:820–9. 14. McGuigan FX. Skin substitutes as alternatives to autografting in a wartime trauma setting. J Am Acad Orthop Surg 2006;14(10 Spec No.):S87-9. 15. Bloemen MC, van Leeuwen MC, van Vucht NE, van Zuijlen PP, Middelkoop E. Dermal substitution in acute burns and reconstructive surgery: a 12-year follow-up. Plast Reconstr Surg 2010;125:1450–9.

525

Yiğitbaş et al. Our experience with DS Nevelia® in the treatment of severely burned patients 16. Ziegler UE, Debus ES, Keller HP, Thiede A. Skin substitutes in chronic wounds. [Article in German]. Zentralbl Chir 2001;126 Suppl 1:71–4. 17. Heimbach DM, Warden GD, Luterman A, Jordan MH, Ozobia N,

Ryan CM, et al. Multicenter postapproval clinical trial of Integra dermal regeneration template for burn treatment. J Burn Care Rehabil 2003;24:42–8.

OLGU SERİSİ - ÖZET OLGU SUNUMU

Ağır yanık hastalarının tedavisinde deri eşdeğeri Nevelia® deneyimimiz Dr. Hakan Yiğitbaş,1 Dr. Erkan Yavuz,1 Dr. Evrim Beken Özdemir,1 Dr. Önder Önen,1 Dr. Halime Hanım Pençe,2 Dr. Serhat Meriç,1 Dr. Atilla Çelik,1 Dr. Fatih Çelebi,1 Dr. Ahmet Çınar Yastı,3 Dr. Tansel Sapmaz,4 Dr. Aydın Zilan,1 Dr. Mustafa Turan1 Sağlık Bilimleri Üniversitesi Bağcılar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Sağlık Bilimleri Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, İstanbul Sağlık Bilimleri Üniversitesi Ankara Numune Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara 4 Sağlık Bilimleri Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, İstanbul 1 2 3

AMAÇ: Bu araştırma, ağır yanık hastalarının tedavisinde deri eşdeğeri, Nevelia®’nın etkinliğini ve güvenliğini geriye dönük olarak değerlendirmeyi amaçlamaktadır. GEREÇ VE YÖNTEM: Mayıs 2017–Mayıs 2018 tarihleri arasında çalışmamıza 20 ağır yanıklı hasta alındı. Eskarektomiden sonra yara tedavi protokolü iki aşamalı bir prosedürle uygulandı. Deri eşdeğeri implantasyonunu kısmi kalınlıkta deri grefti takip etti. Ameliyat ihtiyacı, komplikasyonlar, hastanede kalış süresi ve genel sağkalım analiz edildi. BULGULAR: Yaş ortalaması 40.1±4 (18–86), kadın/erkek: 5/15 idi. Ortalama yanma yüzey alanı %50.1±2 (dağılım, 25–96) idi. Yanık travmalarının ve yandaş hastalıklarının ciddiyeti nedeniyle iki hasta kaybedildi. Olgularda greft, Nevelia®’uygulamasından ortalama 21.2 gün sonra yapıldı. Nevelia® kaynaklı herhangi bir komplikasyon gelişmedi. Hastalar ortalama 55.2±4 günde taburcu edildi. TARTIŞMA: Bu çalışma Nevelia®’nın düşük komplikasyon oranları ve kısa hastanede yatış süresi ile ağır yanık hastalarında güvenli ve etkili bir şekilde kullanılabileceğini göstermiştir. Anahtar sözcükler: Ağır yanık; eskar yönetimi; deri eşdeğeri. Ulus Travma Acil Cerrahi Derg 2019;25(5):520-526

526

doi: 10.14744/tjtes.2019.24358

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

CA S E R EP O RT

Unilateral ischaemic retinopathy and bilateral subdural haemorrhage in an infant with non-accidental injury: An ophthalmological approach Chye Li Ee, M.D.,1 Azlindarita Aisyah Mohd Abdullah, MOph,2 Amir Samsudin, MOph, PhD,1 Nurliza Khaliddin, MOph1 1

Department of Ophthalmology, Malaya University Faculty of Medicine, Kuala Lumpur-Malaysia

Department of Ophthalmology, Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh, Selangor-Malaysia

ABSTRACT Non-accidental injury (NAI) is not an uncommon problem worldwide, which leads to significant morbidity and mortality in infants.The presence of retinal or subdural haemorrhages, or encephalopathy with injuries inconsistent with the clinical history is highly suggestive of NAI. In this study, we report on a case of a a 3-month-old infant who presented to the casualty department with a very sudden onset of recurrent generalised tonic-clonic seizures. There was no history of trauma or visible external signs. She was found to have bilateral subdural haemorrhages and atypical unilateral ischaemic retinopathy. Retinal photocoagulation was performed with subsequent resolution of vitreous and retinal haemorrhages. However, visual recovery in that eye remained poor. The findings showed that a high index of suspicion of NAI is required in infants with intracranial haemorrhage and unilateral retinal haemorrhages. Keywords: Infant; ischaemic retinopathy; non-accidental injury; subdural haemorrhage; unilateral retinal haemorrhage.

INTRODUCTION Non-accidental injury (NAI) is a growing public health problem in the world. In the United States, the annual incidence is estimated to be approximately 35 cases per 100,000 infants in the first year of life.[1] Infants are most commonly affected, with lower frequency in children older than three years of age.[2] In this study, we report an unusual presentation of NAI, in the form of unilateral ischaemic retinopathy and bilateral subdural haemorrhages.

CASE REPORT A 3-month-old infant girl with normal development was brought to the casualty department with three episodes of tonic-clonic seizures. There was no history of falls or head trauma. She was being cared by a baby-sitter when she first

developed the seizures. Computed tomography showed subdural haemorrhage bilaterally, with both sides requiring burr holes and drainage surgery (Fig. 1). The ophthalmological evaluation revealed a vitreous haemorrhage, as well as preretinal and intra-retinal haemorrhages with peripheral vascular sheathing in the left eye (Fig. 2). Fundus examination of the right eye was normal. There was no bruising on the head or body, and systemic examination was otherwise normal. She was admitted to the paediatric intensive care unit after the initial decompression surgery. Serological investigations for syphilis, rubella, toxoplasma cytomegalovirus and herpes virus were negative, and there were no organisms cultured from her cerebrospinal fluid sample. Skeletal survey was normal. Serial eye examinations were conducted during the hospital stay, but the view

Cite this article as: Ee CL, Abdullah AAM, Samsudin A, Khaliddin N. Unilateral ischaemic retinopathy and bilateral subdural haemorrhage in an infant with non-accidental injury: An ophthalmological approach. Ulus Travma Acil Cerrahi Derg 2019;25:527-530. Address for correspondence: Chye Li Ee, M.D. Department of Ophthalmology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur - Malaysia Tel: +60379492060 E-mail: eechyeli@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):527-530 DOI: 10.5505/tjtes.2018.57059 Submitted: 05.09.2018 Accepted: 05.11.2018 Online: 06.08.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

527

Ee et al. Unilateral ischaemic retinopathy and bilateral subdural haemorrhage in an infant with NAI

were signs of ischaemia with generalised peripheral neovascularisation, areas of pre-retinal haemorrhage and vascular sheathing of the left eye. An aqueous tap was sent for cytomegalovirus and syphilis PCR, which came back negative. After obtaining consent from the parents, pan-retinal photocoagulation was performed to ablate the ischaemic retina to reduce vascular endothelial growth factor drive and to treat the neovascularisation. The parents were informed that the treatment was not to restore vision but instead to prevent future complications, such as rubeotic glaucoma and the development of a painful blind eye.

Figure 1. Computed tomography showing bilateral fronto-parietaltemporal chronic subdural haemorrhage.

of the left fundus was obscured by the vitreous haemorrhage. Six weeks later, an examination under anaesthesia (EUA) was performed. The vitreous haemorrhage cleared up, but there

(a)

A second EUA with additional laser ablation was performed on the left eye two weeks after the first EUA as there was residual neovascularisation with peripheral pre-retinal haemorrhages. A week following the second retinal photocoagulation, she developed esotropia and a relative afferent pupil defect in her left eye. The fundus examination five months after the initial presentation revealed a pale optic disc with fibrovascular proliferation both nasally and superotemporally (Fig. 3).

DISCUSSION Clinical distinction between non-accidental and accidental injuries in infants is challenging. According to Maguire et al.,[3]

(b)

Figure 2. Fundus photo of the left eye showing (a) diffuse vitreous haemorrhage obscuring details of optic disc and retina at the time of presentation, and (b) extensive pre-retinal and intra-retinal haemorrhages nasal to the optic disc, and along the superotemporal and inferotemporal arcades a month after presentation.

(a)

(b)

Figure 3. Fundus photo of the left eye three months post panretinal photocoagulation showing optic disc pallor with fibrovascular proliferation and traction (a) nasal to the optic disc, and (b) along the superotemporal arcade.

528

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Ee et al. Unilateral ischaemic retinopathy and bilateral subdural haemorrhage in an infant with NAI

presence of subdural haemorrhage, retinal haemorrhage, apnoea or rib fractures are highly suggestive, although not exclusive to NAI. Cutaneous bruises of varying colours and long bone fractures at different stages of healing also increase the likelihood of NAI. However, the absence of visible external injuries or fractures does not exclude the possibility of NAI, such as in this infant. A meticulous history, detailed physical examination, as well as exclusion of possible organic causes (e.g. osteogenesis imperfecta and clotting abnormalities) are the key points in diagnosing NAI. Retinal haemorrhages are the most common ocular manifestation of NAI and are found in up to 85% of cases.[4] Other ophthalmic signs of NAI include periorbital haematoma, subconjunctival haemorrhage, subluxated or dislocated lens, retinal dialysis or detachment, and intraocular haemorrhage. When associated with a head injury, it is most often due to inflicted, rather than accidental injury, especially in infants less than 1-year old. Retinal haemorrhages in NAI are usually bilateral, multi-layered and extend to the periphery, unlike in the case described above, which presented with only unilateral retinal haemorrhages.[5] These haemorrhages are likely to be due to repetitive acceleration-deceleration forces causing vitreomacular traction, raised intracranial pressure, increased central venous pressure, hypoxia, or coagulopathies. [6] Seizures alone are unlikely to bring about retinal haemorrhages, with a likelihood of less than 1%.[7] The most common site of retinal haemorrhages is near to the ora serrata (40%), followed by the disc and macula (20%).[5] In this case, the bleeding occurred at the peripheral, as well as macula areas of the retina. Buys et al.[8] carried out a prospective study involving 79 children under the age of 3 years with head injuries. They found out that 75 children who sustained accidental head injuries due to falls from height did not have any retinal haemorrhages. However, retinal haemorrhages were present in all four children with NAI. This finding correlates well with the results we obtained from our infant in the present study, who most likely had a non- accidental injury rather than a fall. Other possible causes of retinal haemorrhages in infants include accidental head injury, Purtscher retinopathy, coagulopathy, retinopathy of prematurity, intracranial vascular malformation and infections, which should be excluded before the diagnosis of NAI.[9] Pathogens, such as herpes simplex virus, cytomegalovirus, toxoplasmosis, Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus spp., Brucella spp. and Candida albicans, have been reported to be associated with retinal haemorrhages. These retinal haemorrhages are often bilateral, with concomitant signs of systemic infection. Agrawal et al.[10] reported that children with infection and sepsis often showed fewer than five haemorrhages per

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

fundus. An infectious aetiology is highly unlikely to be the cause of unilateral ischaemic retinopathy in this case, as evidenced by negative serological, as well as aqueous culture and PCR results. Biochemical investigations in this patient were also unremarkable, excluding the possibility of coagulopathy as the cause of retinal haemorrhages and subdural haemorrhage. Tyagi et al.[11] published three cases of unilateral retinal haemorrhages in NAI. They described spontaneous and complete resolution of intraocular haemorrhages in all the infants but with consequent poor vision in two of them due to the associated optic nerve and occipital lobe injury. The infant in our case also had poor visual prognosis given the optic atrophy and relative afferent pupillary defect. Unilateral retinal haemorrhages do not exclude the possibility of NAI, although the latter is commonly associated with bilateral involvement. The presence of retinal haemorrhages and subdural haemorrhage in children strongly suggest NAI. However, other causes of retinal haemorrhages should be ruled out first due to significant social and legal implications. Maintaining an appropriate differential diagnosis could minimise the likelihood of misdiagnosis of child abuse. Conflict of interest: None declared.

REFERENCES 1. Joyce T, Huecker MR. Pediatric Abusive Head Trauma (Shaken Baby Syndrome). Treasure Island (FL): StatPearls Publishing; 2019. 2. Watts P; Child maltreatment guideline working party of Royal College of Ophthalmologists UK. Abusive head trauma and the eye in infancy. Eye (Lond) 2013;27:1227–9. 3. Maguire S, Pickerd N, Farewell D, Mann M, Tempest V, Kemp AM. Which clinical features distinguish inflicted from non-inflicted brain injury? A systematic review. Arch Dis Child 2009;94:860–7. 4. Kivlin JD, Simons KB, Lazoritz S, Ruttum MS. Shaken baby syndrome. Ophthalmology 2000;107:1246–54. 5. Aryan HE, Ghosheh FR, Jandial R, Levy ML. Retinal hemorrhage and pediatric brain injury: etiology and review of the literature. J Clin Neurosci 2005;12:624–31. 6. Levin AV. Retinal hemorrhage in abusive head trauma. Pediatrics 2010;126:961–70. 7. Mei-Zahav M, Uziel Y, Raz J, Ginot N, Wolach B, Fainmesser P. Convulsions and retinal haemorrhage: should we look further? Arch Dis Child 2002;86:334–5. 8. Buys YM, Levin AV, Enzenauer RW, Elder JE, Letourneau MA, Humphreys RP, et al. Retinal findings after head trauma in infants and young children. Ophthalmology 1992;99:1718–23. 9. Kaur B, Taylor D. Fundus hemorrhages in infancy. Surv Ophthalmol 1992;37:1–17. 10. Agrawal S, Peters MJ, Adams GG, Pierce CM. Prevalence of retinal hemorrhages in critically ill children. Pediatrics 2012;129:e1388–96. 11. Tyagi AK, Willshaw HE, Ainsworth JR. Unilateral retinal haemorrhages in non-accidental injury. Lancet 1997;349:1224.

529

Ee et al. Unilateral ischaemic retinopathy and bilateral subdural haemorrhage in an infant with NAI

OLGU SUNUMU - ÖZET

Kaza sonucu oluşmamış, yaralı bebekte tel taraflı iskemik retinopati ve iki taraflı subdural kanama: Bir oftalmolojik yaklaşım Dr. Chye Li Ee,1 Dr. Azlindarita Aisyah Mohd Abdullah,2 Dr. Amir Samsudin,1 Dr. Nurliza Khaliddin1 Malaya Üniversitesi Tıp Fakültesi, Göz Hastalıkları Bölümü, Kuala Lumpur-Malezya Universiti Teknologi MARA Tıp Fakültesi, Göz Hastalıkları Bölümü, SG Buloh, Selangor-Malezya

Kaza sonucu oluşmayan yaralanma (KSOY) dünya ölçeğinde sık görülmeyen bir sorun olup bebeklerde önemli morbidite ve mortaliteye yol açmaktadır. Klinik öyküyle uyumlu olmayan retina veya subdural kanamaların veya ensefalopatinin varlığı yüksek olasılıkla KSOY’yi düşündürür. Bu çalışmada acil servise çok hızlı başlangıçlı yinelenen generalize tonik-klonik nöbetlerle gelen üç aylık bir bebeği raporluyoruz. Travma öyküsü veya dışardan görünür belirti yoktu. Kız bebekte iki taraflı subdural kanamalar ve atipik tek taraflı iskemik retinopati saptanmıştır. Retinal fotokoagülasyon uygulaması sonucu vitröz ve retina kanamalarının kaybolduğu görülmüştür. Ancak bu gözde görme pek geri dönmemiştir. Bulgular, intrakranyal kanama ve tek taraflı retina kanamaları olan bebeklerde yüksek olasılıkla KSOY’den kuşkulanılması gerektiğini göstermiştir. Anahtar sözcükler: İnfant; iskemik retinopati; kaza sonucu oluşmamış yaralanma; subdural kanama; tek taraflı retina kanaması. Ulus Travma Acil Cerrahi Derg 2019;25(5):527-530

530

doi: 10.5505/tjtes.2018.57059

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

CA S E R EP O RT

Heterotopic mesenteric and omental ossification incidentally found in a patient with multiple abdominal surgical operations because of gunshot injury Süleyman Utku Çelik, M.D.,

Rahman Şenocak, M.D.,

Oğuz Hançerlioğulları, M.D.

Department of General Surgery, Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT Heterotopic mesenteric and/or omental ossification is an uncommon bone-like lesion located inside the abdominal cavity. Its etiology is unclear, but most of the patients with this rare disease had a history of a blunt or penetrating abdominal trauma or multiple surgical operations owing to surgical complications. Heterotopic mesenteric and/or omental ossification may be asymptomatic or may present with symptoms of bowel obstruction or cause a severe complication, such as bowel perforation. Due to its rarity, intra-abdominal ossification may sometimes be overlooked or misdiagnosed. However, the surgeon should be aware of this unusual condition, particularly in patients with a previous surgical history. In this study, we present a case of heterotopic mesenteric and omental ossification incidentally found in a 41-year-old man with multiple abdominal surgical operations because of a gunshot injury. Keywords: Abdominal injuries; heterotopic ossification; mesentery; omentum.

INTRODUCTION Heterotopic ossification describes bone formation at an abnormal anatomic location, usually in non-skeletal soft tissues because of a systemic or inflammatory condition.[1] This benign reactive process of mature bone formation occurs in response to a variety of clinical settings, including neurogenic, genetic, posttraumatic, and postsurgical.[2] Heterotopic mesenteric and/or omental ossification is an uncommon bone-like lesion located inside the abdominal cavity that arises from trauma, intra-abdominal infection, or surgery.[1,3,4] Heterotopic bone-like formation is generally found not only in the mesentery but also in the mesoappendix, omentum, peritoneal surfaces, or laparotomy scars.[3,5,6] Due to its rarity, the data are limited to case studies, and the true incidence of this reactive process remains unclear.[6] In clinical settings, patients with mesenteric or omental ossification can be asymptomatic or may present with chronic abdominal pain, discomfort, or intestinal obstruction.[7] We herein report a

rare case of heterotopic mesenteric and omental ossification incidentally found in a 41-year-old male patient with multiple abdominal surgical operations because of a gunshot injury.

CASE REPORT A 41-year-old man who underwent multiple abdominal surgical operations after gunshot injury was admitted to our clinic for ileostomy closure. The patient had no other significant past medical history and no family history. His surgical history was notable for emergency right nephrectomy, right hemicolectomy with end ileostomy, and applications of intra-abdominal vacuum-assisted closure therapy 15 months before admission. Physical examination was unremarkable except for a large incisional hernia following midline laparotomy and ileostomy. Laboratory studies were also unremarkable. Preoperative computed tomography (CT) scan of the abdomen/pelvis revealed multiple linear branching radiopaque

Cite this article as: Çelik SU, Şenocak R, Hançerlioğulları O. Heterotopic mesenteric and omental ossification incidentally found in a patient with multiple abdominal surgical operations because of gunshot injury. Ulus Travma Acil Cerrahi Derg 2019;25:531-534. Address for correspondence: Süleyman Utku Çelik, M.D. Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Etlik, 06010 Ankara, Turkey Tel: +90 312 - 304 20 00 E-mail: s.utkucelik@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(5):531-534 DOI: 10.5505/tjtes.2018.44014 Submitted: 22.10.2018 Accepted: 27.10.2018 Online: 29.10.2018 Copyright 2018 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

531

Ă&#x2021;elik et al. Heterotopic mesenteric and omental ossification

(b)

(a)

Figure 1. CT shows high-attenuation linear density and ossification within the omentum (a) and mesentery (b).

density and ossification within the mesentery and omentum, as well as a herniation of the intra-abdominal contents through an abdominal wall defect (Fig. 1). A midline laparotomy was required for the restoration of intestinal continuity and to close the end ileostomy. Extensive adhesions between adjacent bowel loops requiring adhesiolysis and several mesenteric, omental, and peritoneal sharp bone fragments were seen during the surgical procedure (Fig. 2). In addition, a long dagger-like bone fragment extending from the xiphisternal joint along the vertical midline abdom-

inal incision was released (Fig. 3). There was no evidence of intraluminal invasion related to these bone-like lesions. After removal of these sharp bone fragments from the abdominal wall, omentum, and small bowel mesentery; ileostomy was closed, and bowel continuity was restored. Finally, the ventral incisional hernia was repaired using a polypropylene mesh. Pathological examination of the excised bone-like lesions revealed dense organized lamellar bone trabeculae in fibroadipose connective tissue. There was also no cellular atypia or evidence of malignancy. The clinical and pathological findings were compatible with heterotopic ossification. The patient had an uneventful recovery and was discharged on postoperative day 7.

DISCUSSION

Figure 2. Ossified bone fragment encountered in the abdominal cavity.

(a)

(b)

Heterotopic ossification, which is defined as the development of lamellar bone outside the skeletal system, is a rare condition.[1â&#x20AC;&#x201C;3] Intra-abdominal heterotopic bone formation is also extremely rare and specifically found in the mesentery, omentum, and peritoneum. In addition, this benign process may occur in abdominal incision sites.[1,5,8] The etiology is unclear although it is thought to occur through an endochondral pathway without clear gene mutations causing hereditary conditions of heterotopic ossification.[1] Some authors also hypothesized that bone fragments of the symphysis pubis or

(c)

Figure 3. (a) Dagger-like bone fragment extending from the xiphisternal joint along the vertical midline abdominal incision; (b) heterotopic bone formation in the omentum; (c) heterotopic ossification in the mesentery.

532

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

Çelik et al. Heterotopic mesenteric and omental ossification

xiphoid are inoculated into the abdominal cavity or the incision site during the surgical intervention, and the seeding of periosteal or perichondrial cells leads to bone formation. [7,9,10] The time interval between predisposing factor and diagnosis may be as early as one month, which is contrary to the thought that the ossification occurs over the years.[10–12] In this case, because heterotopic ossification was found incidentally and did not cause a complication, it was difficult to know the time interval between the first surgical operations and diagnosis. However, the bone-like structures were realized 15 months after the first surgical interventions. To our knowledge, there are fewer than 50 cases of intraabdominal heterotopic ossification reported in the relevant literature.[3,4] There is a striking male predominance (as high as 10:1) with an average age at diagnosis of 50 years.[3,6,10,13] Patients afflicted with heterotopic mesenteric and/or omental ossification commonly present with nonspecific abdominal symptoms, or, as in this case, it may be incidentally found during a laparotomy.[4,6,10] Bowel obstruction and intestinal perforation associated with bone-like lesions located inside the abdominal cavity were also presented in a few cases.[7,10,11] An abdominal CT scan can be helpful in the diagnosis of intra-abdominal heterotopic ossification, but the preoperative diagnosis is usually quite difficult.[8,14] On CT scan, the lesions appear as multiple branching, and linear opacities with a welldefined cortex containing internal trabecular ossifications, and this finding is nearly always depicted as contrast extravasation from the bowel lumen.[3,15] The differential diagnosis for heterotopic mesenteric ossifications includes dystrophic calcification, foreign material, calcified abdominal cysts, extraskeletal osteosarcoma, or other osseous malignancies. [8,13,16] However, accurate diagnosis can only be achieved with a histopathological examination.[3] Conservative management should be the initial strategy for treating heterotopic mesenteric ossification, especially in asymptomatic patients. In case of the failure of conservative treatment, a disease-related complication, or the possibility of a malignancy, a surgical approach is inevitable.[3,11,13] Complete excision is recommended if feasible. However, it should be noted that intra-abdominal ossifications are benign bone-like lesions with no malignant potential, and aggressive resections may be significantly associated with increased morbidity and mortality.[4,17] Although recurrence is relatively rare, some pharmacologic agents, including non-steroidal anti-inflammatory drugs, diphosphonates, cimetidine, or even prophylactic local radiotherapy, have been used to prevent recurrence following resection.[8,10,11,14,16] In the present case, intra-abdominal heterotopic ossification was found incidentally during closure of the temporary ileostomy 15 months after the first surgical interventions. These bone-like fragments were most likely result of the multiple laparotomies, serial washouts and debridements, and applications of intra-abdominal vacuum-assisted closure therUlus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5

apy. In the literature, most of the patients afflicted heterotopic mesenteric ossification had a history of an abdominal trauma, such as gunshot wounds, stab injury, or high-speed motor vehicle collision, or multiple surgical operations, due to surgical complications.[3,4,8,14–17] Interestingly, some patients had also a history of intra-abdominal vacuum-assisted closure therapy, as in this case.[3,8,10,11] In conclusion, due to the rarity of these lesions, it is difficult to blame one factor as the cause of heterotopic mesenteric ossification. However, the surgeon should be aware of this unusual condition, particularly in patients with a previous surgical history. In clinical settings, it should not be forgotten that these bone-like lesions are benign with no malignant. Therefore, if it is difficult to resect all ossified tissue, partial excision should be considered not to cause a complication. Although this case report describes only one patient, there is a need for cumulative evidence for the clinical features and optimal management strategies for this unusual condition. Conflict of interest: None declared.

REFERENCES 1. Amalfitano M, Fyfe B, Thomas SV, Egan KP, Xu M, Smith AG, et al. A case report of mesenteric heterotopic ossification: Histopathologic and genetic findings. Bone 2018;109:56–60. 2. Garcia RA, Demicco EG, Klein MJ, Schiller AL. Bones, Joints and Soft Tissue. In: Strayer DS, editor. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 7th ed. Philadelphia: Wolters Kluwer Health; 2015. p. 1305–80. 3. Torgersen Z, Osmolak A, Bikhchandani J, Forse AR. Ectopic bone in the abdominal cavity: a surgical nightmare. J Gastrointest Surg 2013;17:1708–11. 4. Como JJ, Yowler CJ, Malangoni MA. Extensive heterotopic mesenteric ossification after penetrating abdominal trauma. J Trauma 2008;65:1567. 5. Reynoso J, Christensen D, Latifi R. Heterotopic mesenteric ossification as a cause of persistent enterocutaneous fistula: overview of the literature and addition of a new case. Eur Surg 2012;44:285–90. 6. Hogan NM, Caffrey E, Curran S, Sheehan M, Joyce MR. Heterotopic ossification of the abdominal wall. Int J Surg Case Rep 2012;3:489–91. 7. Wang Y, Stanek A, Grushka J, Fata P, Beckett A, Khwaja K, et al. Incidence and factors associated with development of heterotopic ossificationafter damage control laparotomy.Injury 2018;49:51–5. 8. Merrell JJ, Sadro CT, Chew FS. Heterotopic Mesenteric Ossification after Blunt Abdominal Trauma and Multiple Surgical Operations. Radiol Case Rep 2015;3:243. 9. Obeid A, Sarhane K, Berjaoui T, Abiad F. Heterotopic intra-abdominal ossification in a complex ventral hernia defect. J Wound Care 2014;23:S5–9. 10. Lao VV, Lao OB, Figueredo E. Postoperative Bowel Perforation due to Heterotopic Ossification (Myositis Ossificans Traumatica): A Case Report and Review of the Literature. Case Rep Gastrointest Med 2011;2011:908514. 11. Hashash JG, Zakhary L, Aoun EG, Refaat M. Heterotopic mesenteric ossification. Colorectal Dis 2012;14:e29–30. 12. Shi X, Zhang W, Nabieu PF, Zhao W, Fu C. Early postoperative heterotopic omental ossification: report of a case. Surg Today 2011;41:137–40. 13. Patel RM, Weiss SW, Folpe AL. Heterotopic mesenteric ossification: a distinctive pseudosarcoma commonly associated with intestinal obstruc-

533

Çelik et al. Heterotopic mesenteric and omental ossification tion. Am J Surg Pathol 2006;30:119–22. 14. Honjo H, Kumagai Y, Ishiguro T, Imaizumi H, Ono T, Suzuki O, et al. Heterotopic mesenteric ossification after a ruptured abdominal aortic aneurism: case report with a review of literatures. Int Surg 2014;99:479– 84. 15. Hicks CW, Velopulos CG, Sacks JM. Mesenteric calcification following

abdominal stab wound. Int J Surg Case Rep 2014;5:476–9. 16. Baker JC, Menias CO, Bhalla S. Bone in the belly: traumatic heterotopic mesenteric ossification. Emerg Radiol 2012;19:429–36. 17. Sapalidis K, Strati TM, Liavas L, Kotidis E, Koletsa T, Tsiompanou F, et al. Heterotopic mesenteric ossification of ileostomy - “intraabdominal myositis ossificans”.Rom J Morphol Embryol 2016;57:277–81.

OLGU SUNUMU - ÖZET

Ateşli silah yaralanması nedeniyle birden fazla abdominal cerrahi operasyon geçiren bir hastada rastlantısal olarak bulunan heterotopik mezenterik ve omental ossifikasyon Dr. Süleyman Utku Çelik, Dr. Rahman Şenocak, Dr. Oğuz Hançerlioğulları Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara

Heterotopik mezenterik ve/veya omental ossifikasyon, karın boşluğunda görülen kemik benzeri bir lezyondur. Bu nadir rastlanan klinik tablonun etiyolojisi belirsizdir, ancak bu hastaların çoğunda künt veya penetran abdominal travma veya cerrahi komplikasyonlar nedeniyle çoklu cerrahi girişim öyküsü vardır. İntraabdominal heterotopik ossifikasyon semptomsuz olabileceği gibi bağırsak tıkanıklığı semptomlarına veya bağırsak perforasyonu gibi ciddi bir komplikasyona neden olabilir. Kemikleşme benzeri oluşumlar, nadir görülmesi nedeniyle, bazen gözden kaçabilmekte ya da yanlış teşhis edilerek intraabdominal malignite veya opak kaçağı ile karıştırılabilmektedir. Bu sebeple cerrahlar, bu olağandışı tabloyu özellikle daha önceden geçirilmiş bir abdominal cerrahi öyküsü olan hastalarda akıllarında bulundurmalıdır. Bu yazıda, ateşli silah yaralanması nedeniyle çok sayıda abdominal cerrahi işlem geçiren 41 yaşında bir erkek hastada rastlantısal olarak karşılaşılan heterotopik mezenterik ve omental ossifikasyon olgusunu sunuyoruz. Anahtar sözcükler: Heterotopik ossifikasyon; karın yaralanmaları; mezenter; omentum. Ulus Travma Acil Cerrahi Derg 2019;25(5):531-534

534

doi: 10.5505/tjtes.2018.44014

Ulus Travma Acil Cerrahi Derg, September 2019, Vol. 25, No. 5