P ISSN 2148–4902 E ISSN 2536–4553
NORTHERN CLINICS OF ISTANBUL • İSTANBUL KUZEY KLİNİKLERİ NORTHERN CLINICS OF ISTANBUL • İSTANBUL KUZEY KLİNİKLERİ
Vol. 4 • No. 2 • Year 2017
Indexed in Web of Science, Emerging Sources Citation Index, PubMed and PubMed Central
Journal Abbreviation: North Clin Istanb
Positive effects of meal frequency and calorie restriction on antioxidant systems in rats • Orthorexia nervosa tendency among students of the department of nutrition and dietetics at a university in Istanbul • Evaluation of analgesic regimens in
Vol. 4 • No. 2 • Year 2017
total knee arthroplasty, retrospective study • Comparison of RIVA and infraclavicular block in forearm and hand surgery • Retrospective analysis of cases of intestinal invagination treated and followed-up at our clinic • The use of monocyte to HDL ratio
to predict postoperative atrial fibrillation after aortocoronary bypass graft surgery • A comparison of the effectiveness of amitriptilin and pregabalin treatment in fibromyalgia patients • Investigation of celiac disease followed by immune
thrombocytopenic purpura diagnosisin patients and comparison with literature • Determination of health workers’ level of knowledge about blood transfusion • Does antiaggregant administration lead to early diagnosis in proximal colon cancer?
• Ultrasound therapy in iliopsoas hematoma • Giant arachnoid granulation mimicking dural sinus thrombosis • A rare cause of respiratory distress and edema in neonate: Panhypopituitarism • An infrequent case of intussusception caused by gastrointestinal
stromal tumor in an adult patient • Coexistence of eruptive syringoma and bilateral nipple vitiligo: Could there be a common immunopathogenesis? • Acute gastric dilatation due to binge eating may be fatal • A rare involvement in Behcet’s Disease aneurysm
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INDEXED IN WEB OF SCIENCE, EMERGING SOURCES CITATION INDEX, PUBMED, PUBMED CENTRAL, TUBITAK TR INDEX, AND TURKIYE CITATION INDEX.
NORTHERN CLINICS OF ISTANBUL İSTANBUL KUZEY KLİNİKLERİ Editor-in-Chief
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NORTHERN CLINICS OF ISTANBUL İSTANBUL KUZEY KLİNİKLERİ YEAR 2017 VOLUME 4 NUMBER 2
p ISSN 2148 - 4902 e ISSN 2536 - 4553
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Press date: September 2017 Circulation: 1100 Type of publication: Periodical
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Northern Clinics of Istanbul (NCI) is a peer-reviewed journal published triannually by the Istanbul Northern Anatolian Association of Public Hospitals. Materials published in the Journal is covered by copyright ©2017 NCI. All rights reserved. This publication is printed on paper that meets the international standard ISO 9706:1994. National Library of Medicine recommends the use of permanent, acid-free paper in the production of biomedical literature.
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CONTENTS Vol. 4 • No. 2 • Year 2017 IV
Experimental ORIGINAL ARTICLES
INSTRUCTIONS FOR THE AUTHORS
109–116 Positive effects of meal frequency and calorie restriction on antioxidant systems in rats H. B. Savas, F. Gultekin, I. M. Ciris 117–123 Orthorexia nervosa tendency among students of the department of nutrition and dietetics at a university in Istanbul B. Karakus, S. Hidiroglu, N. Keskin, M. Karavus 124–130 Evaluation of analgesic regimens in total knee arthroplasty, retrospective study S. Tulgar, O. Selvi, O. Senturk, T. E. Serifsoy, S. Sanel, S. Meydaneri 131–140 Comparison of RIVA and infraclavicular block in forearm and hand surgery Z. Sarikaya, G. Turan, R. Cetiner, D. Subasi, G. Ozturk, A. Ozgultekin, O. Ekinci 141–144 Retrospective analysis of cases of intestinal invagination treated and followed-up at our clinic B. Barut, H. Yonder, K. B. Sarici, F. Ozdemir, V. Ince 145–150 The use of monocyte to HDL ratio to predict postoperative atrial fibrillation after aortocoronary bypass graft surgery A. I. Tekkesin, M. I. Hayiroglu, R. Zehir, C. Turkkan, M. Keskin, G. Cinier, A. T. Alper 151–159 A comparison of the effectiveness of amitriptilin and pregabalin treatment in fibromyalgia patients G. Acet, A. Kaya, S. Akturk, G. Akgol 160–164 Investigation of celiac disease followed by immune thrombocytopenic purpura diagnosisin patients and comparison with literature H. Sarbay, H. Kocamaz, M. Akin, B. Ozhan 165–172 Determination of health workers’ level of knowledge about blood transfusion A. Beyazpinar Kavaklioglu, S. Dagci, B. Oren 173–179 Does antiaggregant administration lead to early diagnosis in proximal colon cancer? U. Aday, E .Gundes, H. Ciyiltepe, D. A. Cetin, K. C. Deger, S. Gulmez, A. S. Senger, E. Bozdag
C A S E REPORTS
180–184 Ultrasound therapy in iliopsoas hematoma B. Bilir Kaya, A. Icagasioglu 185–187 Giant arachnoid granulation mimicking dural sinus thrombosis E. Ayaz, B. Atalay, B. Baysal, S. Senturk, A. Aslan 188–191 A rare cause of respiratory distress and edema in neonate: Panhypopituitarism F. Dursun, H. Kirmizibekmez, F. Metin 192–194 An infrequent case of intussusception caused by gastrointestinal stromal tumor in an adult patient M. M. Fersahoglu, A. T. Fersahoglu, N. E. Bulut, B. S. Anil Narin, S. Tezer 195–198 Coexistence of eruptive syringoma and bilateral nipple vitiligo: Could there be a common immunopathogenesis? S. Yasar, N. Doner, P. Gunes 199–202 Acute gastric dilatation due to binge eating may be fatal O. Dincel, M. Goksu
Original Image
203–204 A rare involvement in Behcet’s Disease: Carotid artery aneurysm H. S. Basbug, Y. Gunerhan, H. Gocer, K. Ozisik
INSTRUCTIONS FOR THE AUTHORS Northern Clinics of Istanbul
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Experimental
BIOCHEMISTRY
North Clin Istanb 2017;4(2):109–116 doi: 10.14744/nci.2017.21548
Positive effects of meal frequency and calorie restriction on antioxidant systems in rats Hasan Basri Savas,1 Fatih Gultekin,1 Ibrahim Metin Ciris2 Department of Medical Biochemistry, Alanya Alaaddin Keykubat University Faculty of Medicine, Antalya, Turkey
1
Department of Pathology, Suleyman Demirel University Faculty of Medicine, Isparta, Turkey
2
ABSTRACT OBJECTIVE: In living organisms, there is a balance between the oxidant and antioxidant systems. Reactive products continuously formed by exogenous and endogenous sources are rendered harmless by the antioxidant system. Oxidative stress is an etiological factor in aging and the development of various diseases. In the present study, the aim was to investigate the effects of meal frequency and calorie restriction on oxidant-antioxidant systems in rat serum and tissue. METHODS: Nine adult male Wistar Albino rats were used for the pilot study, and another 24 adult male Wistar Albino rats, also weighing 200 to 250 g each, were included in the main study. The rats were divided into 3 groups based on nutrition: the ad libitum group (AL) (n=8), the 2-meal group (TM) (n=8), and the 2-meal with calorie restriction group (TM-CR) (n=8). Following the 4-week pilot study, nutrition regulation was performed in all groups for 20 weeks, 7 days a week, with 60 minutes allotted per meal. Serum and tissues of rats were isolated at the end of the experiment. Total antioxidant status (TAS) and total oxidant status (TOS) were determined using the Erel method. Oxidative stress index (OSI) was calculated using the formula OSI = TOS/TAS. Liver tissue was examined histopathologically. Statistical analyses were performed using the IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA) program. RESULTS: There were significant differences between the AL and TM, and the AL and TM-CR groups in adipose tissue TOS and OSI, and between the AL and TM groups in the liver TAS of the rats (p<0.05). CONCLUSION: Calorie restriction and sparse meal frequency can increase the activity of antioxidants and can reduce oxidative stress. Thus, many diseases caused by oxidative stress may be prevented with the correct regulation of feeding. Keywords: Antioxidant status; caloric restriction; meal frequency; nutrition; oxidant status; rat.
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utrition is defined as the process by which organisms take in nutritional elements from the external environment and use them to facilitate
all functions of living [1]. The effect of nutrition on metabolism is a subject that has been examined by various researchers for years [2–6]. Studies investi-
A part of this study was previously presented at the “6th World Congress of Oxidative Stress, Calcium Signaling and TRP. 24–27 May 2016, Isparta, Turkey. (www.cmos.org.tr).’’ as an oral presentation entitled “The effects of meal frequency and calorie restriction on oxidant-antioxidant systems in rats.’’
Received: January 30, 2017 Accepted: May 05, 2017 Online: August 26, 2017 Correspondence: Dr. Hasan Basri SAVAS. Alanya Alaaddin Keykubat Universitesi Tip Fakultesi, Tibbi Biyokimya Anabilim Dali, Antalya, Turkey. Tel: +90 242 - 518 11 44 e-mail: hasan.savas@alanya.edu.tr © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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gating the effects of meal frequency on metabolism are now rather outdated, as they examined the effects on metabolic enzymes and hormones without investigating the antioxidant system [7–11]. It is well established that excessive energy intake in humans increases the risk of diabetes, cancer, and cardiovascular diseases. However, the effects of increased meal frequency on human health or life span are not clear [12]. Increased meal frequency in humans has been linked to hepatic steatosis, an increase in triglycerides, and obesity [13]. Calorie restriction in animals and humans is a 20% to 40% reduction in the intake of calories compared with feeding ad libitum [14, 15]. Oxidative stress, mitochondrial damage, inflammation, and changes in the structure of proteins-DNA play an important role among the factors that induce neurodegeneration. It is thought that decreased oxidative stress and stimulated neutrophil production may be part of a mechanism related to the reduction of neurodegenerative changes observed with calorie restriction [16–19]. Calorie restriction reduces oxidative stress and the production of oxidant agents [20]. Several other studies have also found that calorie restriction reduced oxidative stress [21–23]. Dubnov et al. conducted a study in which 60% calorie restriction was implemented for 40 days. As a result of the experiment, they found that calorie restriction reduced oxidative stress in various tissues [21]. It was also observed in another study that antioxidant capacity decreased and there was a reduction of lipid peroxidation and protein oxidation products in the group with calorie restriction [24]. One of the accepted theories is that mild calorie restriction reduces the damage caused by free radicals [25]. It has been reported that antioxidant activity increased and oxidative stress decreased with calorie restriction [26]. It was demonstrated in a study of rats that calorie restriction increased antioxidant activity in the serum and liver tissue homogenate in comparison with the control group [27]. There is a continuous production of free radicals in organisms as a result of the effects of oxygen on metabolic pathways and exposure to radiation, drugs, and harmful chemicals. These free radicals facilitate oxidative stress. Antioxidant system enzymes disarm
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these free radicals and ensure that balance is preserved in the organism and life is sustained. Increase in oxidative stress and deficiency in the antioxidant system result in the pathogenesis of more than 100 diseases [28]. In living organisms, there is a balance between the oxidant and antioxidant systems. Reactive products continuously formed by exogenous and endogenous sources are rendered harmless by the antioxidant system [28]. In the present study, the aim was to investigate the effects of meal frequency and calorie restriction on oxidant-antioxidant systems in rat serum and adipose, brain, and striated muscle tissues, the liver, and liver pathology. MATERIALS AND METHODS Animals A total of 33 male Wistar Albino rats weighing 200 to 250 g each were used in the experimental procedures. The ambient temperature and relative humidity of the room where the animals were housed was 21±1°C and 60±7%, respectively. The room was illuminated with artificial light in a 12hour dark/light cycle. The animals were allowed free access to tap water, but standard pellet food was consumed in a controlled environment. All studies were performed with the approval of the Suleyman Demirel University ethics committee for animal experiments (approval date: 21.05.2015; number: 21438139-172). Experimental design Before initiating the studies, all of the rats were exposed to a light/dark living cycle for a week. Darkness was provided for 12 hours overnight to encourage them to sleep at night and be active during the day. Each rat was housed in a standard Euro-type 2 small animal cage (Techniplast, S.p.A., Buguggiate, Italy). Pilot study The rats were divided into 3 groups based on nutrition: the ad libitum group (AL) (n=3), the 2-meal group (TM) (n=3), and the 2-meal with calorie re-
Savas et al., Positive effects of meal frequency and calorie restriction on antioxidant systems in rats
striction (20%) group (TM-CR) (n=3). In the first week, all groups were given 20 minutes of access to food at determined feeding times. Duration of access was increased gradually to 30 minutes in the second week, 45 minutes in the third week, and an hour in the fourth week. The amount of food consumed at feedings was determined by calculating the difference in the weight of the food in the cages before and after feeding. As a result of the 4-week preliminary study, the average amount of food a rat consumed in a day was determined. The ideal amount of time for the rats to consume the determined amount of food was found to be 1 hour. It was decided to provide the daily meals of the TM and TM-CR groups from 9:00 to 10:00 every morning and from 4:00 to 5:00 every evening. In the pilot study, it was found that the rats in the AL group consumed 0.062 g of food per gram of body weight. Based on this result, when the necessary calculations were made regarding the weight of the animals in the main study, it was calculated that the TM group and the TM-CR group should consume 20 and 16 g/day of food, respectively. Main study The rats were divided into 3 groups based on nutrition: ad libitum (AL) group (n=8), 2-meal (TM) group (n=8), and 2-meal with calorie restriction (20%) group (TM-CR) (n=8). The nutrition regulation was performed in all groups for 20 weeks, 7 days a week, with 60 minutes allotted per meal following the 4-week pilot study. The AL group was provided with a sufficient amount of food (ad libitum). The TM group was fed by dividing the amount calculated as daily food intake into 2 meals. The TM-CR group was fed by dividing the amount calculated as daily food intake reduced by 20% into 2 meals. The AL, TM, and TM-CR groups were all fed using the same standard food. There were no restrictions on water in any group. Anesthesia and preparation of blood and tissue samples After 20 weeks, blood samples were taken and rats were euthanized using 10% ketamine (Alfamine;
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Alfasan IBV, Woerden, The Netherlands) and 2% xylazine (Alfazine; Alfasan IBV, Woerden, The Netherlands) in anesthesia. Serum and tissue samples were isolated. Obtaining the serum The blood samples obtained were centrifuged at 3500 rpm for 8 minutes (Rotanta 460; Andreas Hettich GmbH & Co. KG, Tuttlingen, Germany) and serum was collected. Serum samples were divided into Eppendorf tubes (Eppendorf AG, Hamburg, Germany) and stored at -80 0C until the date of analysis (Daihan WiseCryo WUF; Daihan Scientific, Wonju-si, Gangwon-do, South Korea). Tissue homogenization Adipose, striated muscle, and liver tissue were weighed on assay balance (Scaltec SPB33; Scaltec Instruments GmbH, Goettingen, Germany) and homogenized by mixing with phosphate buffer at a ratio of 1/10 (Ultra-Turrax T25; Janke & Kunkel/IKA, Staufen im Breisgau, Germany and UW2070; Bandelin Electronic GmbH & Co. KG, Berlin, Germany). The homogenates were centrifuged for 10 minutes at +4 °C at 10,000 g. In the following stage, supernatants were stored at -80°C in the cryogenic freezer until they were tested. Total antioxidant status, total oxidant status, and oxidative stress index analyses Serum and tissue samples were thawed and mixed using a vortex-mixer (Labinco L 46; Labinco BV, Breda The Netherlands) for oxidant-antioxidant analysis. The serum total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were measured spectrophotometrically using modified Erel method and biochemical auto-analyzer (AU5800; Beckman Coulter, Inc., Brea, CA, USA) with TAS and TOS commercial kit (Rell Assay Diagnostics, Gaziantep, Turkey) [29, 30]. The TAS and TOS results in the serum were expressed in μmol Trolox Eq/L and μmol H2O2 Eq/L, respectively. The TAS and TOS results for the tissues were expressed via division by the protein value. OSI was calculated using the formula
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A
B
C
D
E
Figure 1. Animal experiment, total antioxidant status, total oxidant status, and pathological analyses. (A) Housing of the experimental animals. (B) Each rat was kept individually in a standard cage. (C) The auto-analyzer used for oxidantantioxidant analyses (AU5800; Beckman Coulter, Inc., Brea, CA, USA) and researcher. (D) The optical microscope and integrated camera system used in the histopathological analysis (BX51; Olympus Corp., Tokyo, Japan). (E) The microtome device used in the histopathological analysis (RM 2245; Leica Biosystems Nussloch GmbH, Wetzlar, Germany). OSI = TOS/TAS. The principle of TAS measurement is that antioxidants in the sample reduce the dark blue-green colored 2-2’-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical to a colorless, reduced form of ABTS. The change of absorbance at 660 nm is related to the total antioxidant level of the sample. The assay is calibrated with a stable antioxidant standard solution known as Trolox Equivalent, which is similar to vitamin E [29]. The principle of TOS measurement is that oxidants present in the sample oxidize the ferrous ion–chelator complex into ferric ion. The oxidation reaction is prolonged by enhancer molecules, which are abundantly present in the reaction medium. The ferric ion provides a colored complex with chromogen in an acidic medium. The color intensity, which can be measured spectrophotometrically, is related to the total amount of oxidant molecules present in
the sample. The assay is calibrated with hydrogen peroxide [30]. Histopathological examination Tissues used for histopathological examination were fixed in 10% neutral formalin after samples were symmetrically divided in half on a vertical axis down the middle. Following dehydration and paraffin inclusion procedure, the tissues were embedded into paraffin blocks. Slices in thickness of 4 to 5 μm were obtained from the paraffin blocks using a rotary microtome (RM 2245; Leica Biosystems Nussloch GmbH, Wetzlar, Germany). The slices were stained with hematoxylin-eosin. Following the staining procedure, all of the slices were examined under an optical microscope (BX51, Olympus Corp., Tokyo, Japan), evaluated, and photographed.
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Table 1. The total antioxidant-oxidant status and oxidative stress index values of the tissues Groups Serum TAS (μmol Trolox Eq/L) Serum TOS (μmol H2O2 Eq/L) Serum OSI Liver TAS (μmol Trolox Eq/gr prt) Liver TOS (μmol H2O2 Eq/gr prt) Liver OSI Striated muscle TAS (μmol Trolox Eq/gr prt) Striated muscle TOS (μmol H2O2 Eq/gr prt) Striated muscle OSI Adipose tissue TAS (μmol Trolox Eq/gr prt) Adipose tissue TOS (μmol H2O2 Eq/gr prt Adipose tissue OSI Brain TAS (μmol Trolox Eq/gr prt) Brain TOS (μmol H2O2 Eq/gr prt Brain OSI
AL Mean±SD 1.52±0.14 16.03±3.08 10.73±2.79 0.2±0.02 2.14±0.19 10.89±1.75 0.15±0.01 0.34±0.08 2.32±0.57 0.30±0.14 30.50±2.18 12.65±6.18 0.23±0.02 2.75±0.42 12.19±2.16
TM Mean±SD 1.74±0.31 14.40±5.07 8.23±2.08 0.22±0.01* 2.28±0.27 10.50±1.45 0.18±0.06 0.3±0.05 1.83±0.69 0.43±0.15 14.38±1.35* 3.75±1.60* 0.25±0.03 2.22±0.55 9.33±3.29
TM-CR Kruskal-Wallis Mean±SD p 1.69±0.26 14.65±5.86 8.63±2.76 0.21±0.01 2.20±0.21 10.39±1.32 0.18±0.02 0.34±0.11 1.89±0.45 0.50±0.23 13.69±1.73* 3.40±1.83* 0.25±0,03 2.40±0.51 10.01±2.91
0.239 0.05 0.294 0.041 0.344 0.898 0.111 0.57 0.116 0.122 <0.001 0.001 0.286 0.108 0.153
AL: Ad libitum; OSI: Oxidative stress index (TOS/TAS); SD: Standard deviation; TAS: Total antioxidant status; TM: Two meals; TM-CR: Two meals and calories restricted by 20%); TOS: Total oxidant status. * When compared with AL group, these were statistically significant (Mann-Whitney U; p<0.05).
The materials used in the animal experiment and for the histopathological and biochemical analyses and animal experiments are shown in Figure 1. Statistical analysis Statistical analyses were conducted using the IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA) program. The numerical data obtained were expressed as mean±SD. Since there was a small number of subjects in each group, the Kruskal-Wallis test, which is a nonparametric test, was used to compare the average TAS, TOS, and OSI values of the 3 groups. Chi-square test was used to statistically analyze the rat liver histopathology. RESULTS Findings on oxidative stress and antioxidant system The effects of meal frequency and calorie restriction
on TAS (μmol Trolox Eq/L), TOS (μmol H2O2 Eq/L), and OSI values in the serum of the rats were analyzed (mean±SD). There were significant differences between the AL and TM, and the AL and TM-CR groups in the adipose tissue, and between the AL and TM groups in the livers of the rats (Table 1). Results of the histopathological analysis of the rat livers At the end of the experiment, the rat livers were microscopically analyzed in terms of granularity, changes in hepatocyte array, fattening, inflammation, and fibrosis. No fattening of the liver, inflammation, or fibrosis was seen in the experimental animals. Granularity in hepatocytes and hepatocyte array disorders were noted in some liver samples (Figure 2). In the results of the analysis using the chi-square test, it was determined that the granularity and changes in hepatocyte organization were not statistically significant. No significant differences were found between groups in terms of the param-
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A
B
C
D
Figure 2. Histopathology of rat liver. (A) Rat liver. Normal histology. Hepatocyte array is normal (HE x40). (B) Mild disorder in hepatocyte array (HE x40). (C) Mild disorder in hepatocyte array and mild increase in cytoplasmic granularity. Normal (HE x200). (D) Noticeable disorder in hepatocyte array and noticeable increase in cytoplasmic granularity (HE x200).
eters analyzed. Examples of the microscopic images of the rat livers are shown in Figure 2. DISCUSSION The results of our study were consistent with the literature: TAS level increased significantly in the TM and TM-CR groups compared with the control group (p<0.05). Based on the analysis in terms of TOS and OSI, a decrease was seen in the TM and TM-CR groups in comparison with the control group. However, there was not a statistical significance, except in fat tissue. In the fat tissue, in terms of TOS and OSI levels, the TM and TM-CR groups showed significant decreases in comparison with the control group (p<0.05). The relationship between manner of feeding and antioxidant activity was demonstrated with a noticeable increase in antioxidant activity, which is the protective mechanism of the body against oxidative stress on the liver, one of the central organs of metabolism. As a result, it was seen that TM and TM-CR methods of feeding may be useful in reducing oxidative stress and increasing antioxidant activity, as previously demonstrated in the literature. In our study,
the TM-CR group was allowed to feed 2 times a day and subjected to a moderate level of calorie restriction (20%). It was determined that the TAS level in the liver of the TM group increased significantly in comparison to the AL group, while TOS and OSI levels in the fat tissue decreased significantly in the TM and TM-CR groups. Considering the oxidantantioxidant system results of the TM-CR group according to the literature, many studies have reported a reduction of oxidative activity with calorie restriction, which is in agreement with the results of our study [21â&#x20AC;&#x201C;27]. However, there are a limited number of studies reporting an increase in antioxidant activity with calorie restriction [26, 27]. The fact that not all studies implementing calorie restriction demonstrated an increase in antioxidant activity has been tied to the duration of implementation [27]. Increase in antioxidant activity with calorie restriction was observed in our study, which may be considered long-term in comparison to other reported studies [21â&#x20AC;&#x201C;27]. Moreover, the combined implementation of meal frequency and calorie restriction, and positive outcomes regarding the antioxidant system, increases the value of our study. Another important result of this study is that meal frequency implementation without calorie restriction, which has not been sufficiently investigated, was shown to have positive effects on the oxidant-antioxidant system. No harm to the liver was seen in the analysis of liver histopathology with respect to meal frequency or calorie restriction. The granulation and change in the hepatocyte array observed more in the TM and TM-CR groups was insignificant, and may be explained by increased metabolic activity and the increase in the number of organelles, such as granulated endoplasmic reticulum, that have an active role in metabolism. This study produced promising findings about the relationship between meal frequency and the antioxidant system, considering that there is a limited amount of data in the literature on this subject. The results of our study indicated that, like calorie restriction, reducing meal frequency probably strengthens the antioxidant system and reduces oxidative stress. Therefore, eating less and eating less frequently may be presented as an alternate protec-
Savas et al., Positive effects of meal frequency and calorie restriction on antioxidant systems in rats
tive treatment in the prevention of hundreds of diseases known to be related to oxidative stress [28– 30]. The amount and frequency of food intake are as important as the content. Future studies of longer duration, and even life-long observation studies regarding the effects on life span, the addition of the factor of sex, and groups combining nutrition and exercise, may lead to new findings and may confirm our results. Changes in the TAS, TOS, and OSI values in the TM and TM-CR groups were in the same direction as the AL group; the fact that most of these changes were statistically insignificant may be explained by the small number of subjects. Statistical significance might arise in studies with a larger number of subjects. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The study was supported by the Scientific Research Unit (SDÜ BAP) and Faculty Development Program (OYP Coordination Unit; SDÜ ÖYP) of Suleyman Demirel University (Project Numbers: SDÜ BAP 4476-ÖYP-D2-15) and ÖYP (ÖYP 05333-DR-12) unit). Authorship contributions: Concept – H.B.S., F.G.; Design – H.B.S., F.G.; Supervision – H.B.S., F.G.; Materials – H.B.S., F.G., I.M.C.; Data collection &/or processing – H.B.S., F.G., I.M.C.; Analysis and/or interpretation – H.B.S., F.G.; Literature search – H.B.S., F.G.; Writing – H.B.S., F.G., I.M.C.; Critical review – H.B.S., F.G.
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Orıgınal Article
PUBLIC HEALTH
North Clin Istanb 2017;4(2):117–123 doi: 10.14744/nci.2017.20082
Orthorexia nervosa tendency among students of the department of nutrition and dietetics at a university in Istanbul Betul Karakus, Seyhan Hidiroglu, Nese Keskin, Melda Karavus Department of Public Health, Marmara University Faculty of Medicine, Istanbul, Turkey
ABSTRACT OBJECTIVE: The aim of this study was to determine an orthorexia nervosa scale score for and evaluate orthorexic tendency among students of nutrition and dietetics according to various sociodemographic characteristics. METHODS: This cross-sectional study was carried out in May and June of 2016 among 208 students in the nutrition and dietetics department at a university in Istanbul. After receiving the approval of the university ethics committee, of a total of 300 students, 208 agreed to join the study. Participants completed a questionnaire related to individual characteristics and the ORTO-11 scale during a face-to-face interview. The ORTO-11 scale is a verified Turkish scoring system in which a low score indicates orthorexic tendency. The Mann-Whitney U test, independent samples t-test, Kruskal-Wallis test, and analysis of variance were used to assess the data. P<0.05 was accepted as statistically significant. RESULTS: Orthorexic tendency was significantly higher in males (p=0.050) and students who lived with their family (p=0.002). Mean ORTHO-11 scale score did not differ significantly between groups when the participants were grouped by parameters of smoking, alcohol consumption, chronic disease status, body mass index, diet observance, or use of nutritional supplement products. CONCLUSION: The orthorexic tendency was higher in men and in students who lived with their family. Additional assessment of individual eating habits, eating behavior, and personality characteristics would shed light on the reasons for the difference between gender groups. Qualitative studies should be carried out and possible confounding factors should be determined. Keywords: Eating behavior disorder; food choice; orthorexia.
B
ehavioral responses associated with the act of eating, manner or mode of eating, and patterns in the act guide the definition of eating behavior [1]. Eating behavior is influenced by individual percep-
tion, previous experiences, nutritional status, and social, demographic, and cultural conditions [2–4]. An eating disorder is a disease state in which disorders of eating attitude and behavior emerge as a
Received: February 10, 2017 Accepted: May 30, 2017 Online: August 26, 2017 Correspondence: Dr. Betul KARAKUS. Marmara Universitesi Tip Fakultesi, Basibuyuk Yerleskesi, Maltepe, Istanbul, Turkey. Tel: +90 216 - 421 22 22 e-mail: betmar@mynet.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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result of an impaired perception of body image, and the groups at greatest risk are thought to be adolescents and young women [1, 5]. Individuals with eating disorders experience an obsessive fear of being overweight, which increases the level of anxiety related to body image [5, 6]. Various forms of eating disorders have existed for a very long time; however, anorexia nervosa (AN), and bulimia nervosa have only recently been included in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [7]. The term orthorexia nervosa (ON) was first defined by Steven Bratman in 1997 as a form of AN. The term was derived from the Greek words â&#x20AC;&#x153;orthosâ&#x20AC;? (right, true) and orexia (appetite), and it is related to an obsession with healthy foods and nutrition [8, 9]. In a case of ON, typically, the individual excessively controls each meal, and failing to observe the planned dietary regime results in self-reproach and self-hatred [10, 11]. Orthorexic individuals pay extreme attention to eating healthy foods; they are very attentive to the contents of foods they purchase, and tend to be particular about the methods and tools used in the preparation of food [4, 12]. Many orthorexic individuals prefer to eat raw food. Mental stress caused by obsessive dietary habits may lead these individuals to refrain from consuming many foods and result in a loss of weight, as seen in the eating disorder of AN [13]. Healthy modifications to lifestyle and eating play a fundamental role in the prevention of various conditions, such as cardiovascular disease, cancer, osteoporosis, hypertension, and obesity [4, 13]. Concern about healthy nutrition is considered a psychiatric disorder when it transforms into an exaggerated effort to painstakingly comply with a healthy diet, a fixation that preoccupies the individual and creates problems in their social life [13]. Since a universal definition of ON has not yet been made and diagnostic criteria have not been established, the contributions of new studies to the literature are of great importance. It has been reported in some studies that ON is frequently present among female dieticians and that
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ON influences their decision to become a dietician [4, 14]. The objective of the present study was to determine ORTO-11 scores among university students of nutrition and dietetics and to evaluate their orthorexic tendency based on sociodemographic characteristics. MATERIALS AND METHODS Method and participants This cross-sectional study was conducted among undergraduate students of the department of nutrition and dietetics of a university located on the Anatolian side of Istanbul province in May and June of 2016. The ethics committee of Marmara University granted approval for the study (date: May 6, 2016) before the data collection process was initiated. Probability sampling was not performed, and an attempt was made to reach all 300 students in the department program. A total of 208 (70%) students were willing to participate in the study, and the data were collected in face-toface interviews using a questionnaire that inquired about individual characteristics and the ORTO11 scale. Questionnaire The questionnaire was used to collect sociodemographic characteristic data: height/weight (based on self-report), smoking status of the participants, use of alcohol or nutritional supplements, if they lived with their family, presence of any chronic disease in the student or their family, degree of satisfaction with their external appearance, and whether they had been on a diet to lose weight in the last 3 months. Body mass index (BMI) of the participants was calculated and World Health Organization (WHO) classification of nutritional status was applied. ORTO-11 scale Donini et al. introduced the ORTO-15 scale to assess ON in 2005, and subsequently also performed a validation study [14, 15]. ArusoÄ&#x;lu et al. narrowed the focus of the ORTO-15 scale, and created the
Karakus et al., Orthorexia Nervosa Tendency in students of Nutrition and Dietetics
Turkish ORTO-11 scale adaptation in 2006 [16]. This Likert-4 type scale contains 11 questions regarding selection, purchase, and preparation of food, as well as respondent behavior with respect to the consumption of food they evaluated as “healthy.” The responses “never,” “sometimes,” “often,” or “always” yield a score of 0 to 4 points for each question; a lower score indicates greater tendency toward ON [16]. The ORTO-15 scale has a cut-off point, while the ORTO-11 scale does not. Data analysis Quantitative data were analyzed using the MannWhitney U test, independent samples t-test, Kruskal-Wallis test, and analysis of variance. Chi-square and Fisher’s exact tests were used to assess qualitative data. P<0.05 was accepted as the level of statistical significance. RESULTS The study population consisted of 208 students (female: n=179, 86%; male: n=29, 24%) who volunteered to participate in the study. An equal number of students lived with their family or in a student residence (each: n=76; 36%). Of the entire group, 164 (79%) participants were nonsmokers, and 170 (82%) did not consume alcohol. Most (n=199; 96%) said that they did not have any chronic disease, though chronic disease was present in the family of 86 (41%) participants. Mean BMI of the participants was 20.9±2.6 kg/m2 according to the WHO classification of nutritional status, 162 (78%) of individuals were normal weight. In response to the question, “Are you pleased with your image in the mirror?” 62 (30%) said not at all/not pleased, and 166 (70%) said somewhat/very pleased. Most (n=159; 77%) of the participants had not been following a diet to lose weight within the last 3 months. In addition, 159 (77%) participants were not using nutritional supplements at all, while 36 (17%) participants said that they had used such products in the past. Thirteen participants were using nutritional supplements at the time of the interview. A summary of these characteristics is provided in Table 1.
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Table 1. Distribution of participants according to characteristics Gender Female Male University class Year 1 Year 2 Year 3 Year 4 Residence With family Student housing Student hostel Alone Other Tobacco use Never smoked Quit smoking Current smoker Alcohol use Yes No Chronic disease Present Absent Chronic disease in the family Present Absent BMI group Underweight Normal Overweight Obese Are you pleased with your image in the mirror? Not at all pleased Not pleased Somewhat pleased Pleased Very pleased Are you on a diet? Yes No Nutritional supplement use Never used Used in the past I am still using Total BMI: Body mass index.
n %
179 86.1 29 13.9 32 75 56 45
15.4 36.1 26.9 21.6
76 36.5 50 24.0 76 36.5 3 1.4 3 1.4 164 78.8 17 8.2 27 13.0 38 18.3 170 81.7 9 4.3 199 95.7 86 41.3 122 58.7 32 15.4 163 78.4 11 5.3 2 1.0 4 1.9 10 4.8 48 23.1 122 58.7 24 11.5 43 20.7 165 79.3 159 76.4 36 17.3 13 6.3 208 100.0
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Table 2. ORTO-11 score according to characteristics Gender Female Male University class Year 1 Year 2 Year 3 Year 4 Residence With family Other Tobacco use Smoker Nonsmoker Alcohol use Yes No Chronic disease Yes No Chronic disease in the family Yes No Are you pleased with your image in the mirror?* Low High BMI group** Underweight/normal Overweight/obese On diet Yes No Nutritional supplement use Nonuser Past/present user
n
%
Mean
SD
p
179 86.1 28.9 3.7 0.050 29 13.9 27.4 3.4 32 75 56 45
15.4 36.1 26.9 21.6
29.4 28.9 29.1 27.4
3.8 3.3 3.0 4.6
0.13
76 132
36.5 63.5
27.7 29.3
3.8 3.5
0.002
181 27
87.0 13.0
27.5 28.9
4.2 3.5
0.07
38 170
18.3 81.7
29.5 28.5
3.4 3.7
0.18
9 199
4.3 95.7
30.4 28.6
3.4 3.7
0.1
86 122
41.3 58.7
29.0 28.5
3.7 3.7
0.5
62 146
29.8 70.2
29.2 28.5
2.6 4.0
0.4
195 13
93.8 6.3
28.8 27.6
3.6 4.1
0.38
43 165
20.7 79.3
29.5 28.5
3.5 3.7
0.15
159 49
76.4 23.6
28.6 29.1
3.6 3.8
0.4
SD: Standard deviation; *Low: I am not pleased at all/I am not pleased/I am somewhat pleased; High: I am pleased/I am a very pleased. **BMI: Body mass index.
The mean ORTO-11 scale score of all participants was 16.5Âą4.6 points. The distribution of ORTO-11 scores based on characteristics of the participants can be seen in Table 2. The mean ORTO11 score of male participants was significantly lower
than that of female participants (Table 2). When the participants were grouped based on smoking status, presence of chronic disease in the student or the family, and BMI, no significant difference was found in mean ORTO-11 score (Table 2).
Karakus et al., Orthorexia Nervosa Tendency in students of Nutrition and Dietetics
When the participants were divided into groups of those living with family members and another residence, examination of the ORTO-11 scores revealed that mean of those living at home (27.7) was significantly lower than the other group (29.3; p=0.002) (Table 2). The mean ORTO-11 score was 1 point higher among those who were observing a diet compared with those who didnâ&#x20AC;&#x2122;t, but the difference was not significant (p=0.15). The mean ORTO-11 score of the group who had not used nutritional supplements was 0.5 point lower than those who had previously used such products and current users, without a statistically significant difference between groups. Among the participants who were not very pleased with their image in the mirror, the mean ORTO-11 score of was 0.7 points higher than those who were very pleased, but there was no significant difference between groups (p=0.4) (Table 2). DISCUSSION The ORTO-11 scale score of students of a university department of nutrition and dietetics was calculated and analyzed based on sociodemographic data and characteristics of the respondents. The association between gender and tendency toward ON was examined, and it was observed that the male participants had a greater predisposition toward ON. Some studies [17â&#x20AC;&#x201C;21] have reported no significant association between gender and inclination toward ON, while in others [22, 23], the tendency was observed more often among men. Increased ON tendency among women has also been reported [24, 25]. Eating disorders are generally acknowledged to be more frequently seen among women [26]. However in our study, a lack of adequate data about the eating attitudes and behavior of the participants made it difficult to definitively determine the cause of this difference between gender groups. In one study conducted [25], the risk of ON was found to be 5-fold higher among individuals displaying an abnormal eating attitude compared with those with normal eating attitudes. Our subgroup analyses revealed that male participants more frequently consumed tobacco products (p=0.005) and alco-
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hol (p=0.021) compared with female respondents. Though unhealthy habits such as cigarette use were more frequently encountered in men, the greater tendency toward ON may be related to personality characteristics of the male participants. One of the important limitations of this study was our inability to use a standard scale to evaluate the personality characteristics of our participants. Furthermore, our study group consisted only of students of the department of nutrition and dietetics, and therefore our results may be different from those of a survey of the general population. Study participants living with their family were found to be significantly more predisposed toward ON in our analysis; however previous studies did not find a significant association between living conditions and tendency toward ON [23, 25] Subgroup analyses of our study group revealed that frequency of tobacco (p=0.052) and alcohol (p=0.003) use was 3 times lower in participants living with their family relative to other groups. Higher predisposition toward ON among individuals refraining from an unhealthy lifestyle seems to be a consistent finding. While observing healthy dietary habits should be encouraged, it becomes dangerous when it becomes an obsessive type of eating behavior. Individuals with this pathological focus will likely develop eating behavior that is not dependent on the place of residence [4, 10, 13]. Since this was a cross-sectional study, it was difficult to evaluate the causal relationship between residence environment and predisposition toward ON. As in previous studies [14, 24], a significant association between BMI and ON was not found in our research. In the aforementioned studies, the authors indicated that BMI was not a determinative factor for ON and that individuals demonstrating orthorexic behavior generally had a normal BMI. Another study found a significant correlation between extraordinary focus on external appearance, fear of being overweight, and a tendency toward ON [19]. Most (93.8%) of our study participants had a low/ normal BMI, which might have prevented us from distinguishing any such difference between groups. When participants were grouped according to use of tobacco products and alcohol, the ORTO-
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11 scores did not differ significantly between groups. No significant association was found between the presence of a chronic disease in the individual or in the family and the participants’ tendency toward ON. Another limitation of our study was the lack of a more detailed inquiry about eating attitude. Orthorexic trend is more frequently seen among individuals who follow a strict dietary regimen [24]. A significant correlation was not found between diet regimen, use of nutritional supplements, and tendency toward ON. This may be due to the small number of study participants who observed a diet plan or used nutritional supplement products. Conclusion and Recommendations In our study, the tendency toward ON was greater among men. Further evaluation of eating attitudes and eating behavior, as well as personality characteristics of the individuals, could add to our understanding of difference based on gender. Tendency toward ON was also more frequently detected in participants living with their family. Qualitative studies should be conducted to examine the association between living with family and inclination toward ON, and potential confounding factors should be identified. The ORTO-11 scale does not have a cut-off value, which may lead us to evaluate healthy behavior patterns as a pathological condition Therefore, validation and reliability studies of this scale should be performed. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – S.H, M.K.; Design B.K., N.K., M.K.; Supervision - M.K., S.H.; Funding – B.K., N.K., Materials – N.K., B.K.; Data Collection and processing – N.K., B.K..; Analysis and interpretation -N.K., B.K. ; Literature search N.K., B.K., M.K., S.H.; Writing – N.K., B.K., S.H., M.K.; Critical review – M.K., S.H..
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North Clin Istanb 2. Fairburn CG, Harrison PJ. Eating disorders. Lancet 2003;361:407–16. 3. Köster EP. Diversity in the determinants of food choice: A psychological perspective. Food Quality and Preference 2009;20:70–82. 4. Gezer C, Kabaran S. Beslenme ve diyetetik bölümü kız öğrencileri arasında görülen ortoreksiya nervosa riski. SDÜ Sağlık Bilimleri Dergisi 2013;4:14–22. 5. Özgen L, Kınacı B, Arlı M. Eating attitudes and behaviors of adolescents. Journal of Faculty of Educational Sciences 2012;45:229–47. 6. Bellodi L, Cavallini MC, Bertelli S, Chiapparino D, Riboldi C, Smeraldi E. Morbidity risk for obsessive-compulsive spectrum disorders in first-degree relatives of patients with eating disorders. Am J Psychiatry 2001;158:563–9. 7. Andersen A, Yager J. Eating disorders. In: Sadock BJ, Sadock VA, editors. Comprehensive Textbook of Psychiatry. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 2005–21. 8. Cartwright MM. Eating disorder emergencies: understanding the medical complexities of the hospitalized eating disordered patient. Crit Care Nurs Clin North Am 2004;16:515–30. 9. Mathieu J. What is orthorexia? J Am Diet Assoc 2005;105:1510– 2. 10. Bratman S, Knight D. Health Food Junkies. Newyork: Broadway Books; 2000. p. 210–9. 11. Brytek-Matera A, Rogoza R, Gramaglia C, Zeppegno P. Predictors of orthorexic behaviours in patients with eating disorders: a preliminary study. BMC Psychiatry 2015;15:252. 12. Catalina Zamora ML, Bote Bonaechea B, García Sánchez F, Ríos Rial B. Orthorexia nervosa. A new eating behavior disorder? Actas Esp Psiquiatr 2005;33:66–8. 13. Aldana SG, Greenlaw RL, Diehl HA, Salberg A, Merrill RM, Ohmine S, et al. Effects of an intensive diet and physical activity modification program on the health risks of adults. J Am Diet Assoc 2005;105:371–81. 14. Donini LM, Marsili D, Graziani MP, Imbriale M, Cannella C. Orthorexia nervosa: a preliminary study with a proposal for diagnosis and an attempt to measure the dimension of the phenomenon. Eat Weight Disord 2004;9:151–7. 15. Donini LM, Marsili D, Graziani MP, Imbriale M, Cannella C. Orthorexia nervosa: validation of a diagnosis questionnaire. Eat Weight Disord 2005;10:e28–32. 16. Arusoğlu G, Kabakçi E, Köksal G, Merdol TK. Orthorexia nervosa and adaptation of ORTO-11 into Turkish. Turk Psikiyatri Derg 2008;19:283–91. 17. Varga M, Thege BK, Dukay-Szabó S, Túry F, van Furth EF. When eating healthy is not healthy: orthorexia nervosa and its measurement with the ORTO-15 in Hungary. BMC Psychiatry 2014;14:59. 18. Brytek-Matera A, Donini LM, Krupa M, Poggiogalle E, Hay P. Orthorexia nervosa and self-attitudinal aspects of body image in female and male university students. J Eat Disord 2015;3:2. 19. Barnes MA, Caltabiano ML. The interrelationship between
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orthorexia nervosa, perfectionism, body image and attachment style. Eat Weight Disord 2017;22:177–184. 20. Dunn TM, Gibbs J, Whitney N, Starosta A. Prevalence of orthorexia nervosa is less than 1 %: data from a US sample. Eat Weight Disord 2017;22:185–92. 21. Aksoydan E, Camci N. Prevalence of orthorexia nervosa among Turkish performance artists. Eat Weight Disord 2009;14:33–7. 22. Fidan T, Ertekin V, Işikay S, Kirpinar I. Prevalence of orthorexia among medical students in Erzurum, Turkey. Compr Psychiatry 2010;51:49–54. 23. Özenoğlu A, Gökhan D. Üniversite Gençliğinde Yeme Bozukluğunun Yordayıcıları Olarak Benlik Saygısı ve Beslenme
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Eğitiminin Ortoreksiya Nervoza Gelişmesi Üzerine Etkisi. Bozok Tıp Dergisi 2015;5:5–14. 24. Arusoğlu G, Kabakçi E, Köksal G, Merdol TK. Orthorexia nervosa and adaptation of ORTO-11 into Turkish. Turk Psikiyatri Derg 2008;19:283–91. 25. Sanlier N, Yassibas E, Bilici S, Sahin G, Celik B. Does the rise in eating disorders lead to increasing risk of orthorexia nervosa? Correlations with gender, education, and body mass index. Ecol Food Nutr 2016;55:266–78. 26. Varga M, Dukay-Szabó S, Túry F, van Furth EF. Evidence and gaps in the literature on orthorexia nervosa. Eat Weight Disord 2013;18:103–11.
Orıgınal Article
ANESTHESIOLOGY&REANIMATION
North Clin Istanb 2017;4(2):124–130 doi: 10.14744/nci.2017.88598
Evaluation of analgesic regimens in total knee arthroplasty, retrospective study Serkan Tulgar,1 Onur Selvi,1 Ozgur Senturk,1 Talat Ercan Serifsoy,1 Selim Sanel,2 Sertac Meydaneri2 Department of Anesthesiology and Reanimation, Maltepe University Faculty of Medicine, Istanbul, Turkey
1
Department of Ortopedy and Travmatology, Maltepe University Faculty of Medicine, Istanbul, Turkey
2
ABSTRACT OBJECTIVE: Analgesic therapies have an immense role in early rehabilitation period after total knee arthroplasty (TKA) and multimodal approaches should be considered as the first choice of treatment. In this retrospective study, the aim was to evaluate the effectiveness of multimodal analgesic therapies for TKA, including femoral nerve block (FNB) and patient controlled analgesia (PCA). METHODS: The data of 79 patients who underwent TKA between January and December 2016 were retrospectively evaluated. In all, 63 patients met the inclusion criteria. Hemodynamic records and Visual Analogue Scale (VAS) pain scores for postoperative 0, 2, 4, 6, 9, and 12 hours were evaluated and patients were separated into 3 groups. Group 1: FNB with 0.25% bupivacaine, Group 2: FNB with 0.166% bupivacaine, and Group 3: No FNB. RESULTS: The average age of the patients was 64.3±14.9 years and average body mass index (BMI) was 32.5±5.3 kg/m2. There was no statistical difference between groups in age, gender, American Society of Anesthesiologists (ASA) classification of physical health scores, BMI, or anesthesia type (p<0.05). When VAS scores at postoperative time intervals were compared, there was a statistically significant difference between Group 1 and Group 2 (p>0.05). When difference between Groups 1 and 3 and Groups 2 and 3 were compared, the difference was statistically significant for VAS 0 (p>0.05). Additional analgesic use was highest in Group 3. CONCLUSION: This study demonstrated that FNB significantly decreases postoperative pain intensity and additional analgesia requirement in patients undergoing TKA. A concentration of 0.166% bupivacaine is as effective as a concentration of 0.25% when used as part of a multimodal analgesia regimen in TKA. Keywords: Analgesia; femoral block; knee arthroplasty.
P
ostoperative pain is a common complaint after total knee arthroplasty (TKA) [1]. Appropriate management of this postoperative pain is im-
portant during the early rehabilitation period [2]. Postoperative analgesia after TKA can be administered using several techniques, including intrave-
Received: January 26, 2017 Accepted: June 12, 2017 Online: August 25, 2017 Correspondence: Dr. Serkan TULGAR. Maltepe Universitesi Tip Fakultesi Hastanesi, Feyzullah Caddesi, No: 39, Maltepe, Istanbul, Turkey. Tel: +90 216 - 399 97 50 e-mail: serkantulgar.md@gmail.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
Tulgar et al., Evaluation of analgesic regimens in total knee arthroplasty, retrospective study
nous (IV) analgesics, neuraxial blocks, and peripheral nerve blocks [2–5]. The use of a femoral nerve block (FNB) in patients undergoing TKA has increased recently, as it allows for early rehabilitation, and decreases postoperative pain, the use of opioids, and the length of hospital stay [6–8]. Some authors have stated that FNB is the gold standard for analgesia in patients undergoing TKA [6, 9, 10]. If physically possible, it is advised to perform all peripheral nerve blocks under ultrasonographic guidance in order to increase safety and the success of the block [11–13]. However, when ultrasonography is not available, performance of peripheral nerve block using a traditional nerve stimulator (NS) is also a safe technique [14]. Studies evaluating the use of FNB in patients undergoing TKA in our country are scarce [15]. While patients traditionally received IV patientcontrolled analgesia (PCA) after TKA at our institute, FNB has been used as a component of multimodal analgesia for the last year. In this retrospective study, different modalities of postoperative analgesia administered to patients undergoing TKA at our institute were evaluated. MATERIALS AND METHODS After receiving institutional review board approval, the medical data of all patients who underwent TKA between January 1, 2016 and December 31, 2016 were retrospectively reviewed. Patient consent was not sought, as data were collected without patient identifiers. Patient files were reviewed, and patients with the following characteristics were excluded: patients who underwent neuraxial anesthesia, bilateral TKA, American Society of Anesthesiologists (ASA) classification of physical health status IV, emergency case, psychiatric or neurological pathology that would interfere with evaluation of pain, and those with missing data. PCA follow-up forms were used for documentation of pain; therefore, patients with missing PCA forms were also excluded. Patient age, gender, body mass index (BMI) plus peroperative
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and postoperative analgesia regimens were noted. All patients’ peroperative analgesia regimens were analyzed. Patients with analgesia regimen that differed from standard protocol as detailed below were also excluded. The routine perioperative analgesia protocol of the institute is as follows: 0.1 mg/ kg morphine, 1 g IV paracetamol, and 20 mg tenoxicam administered at least 1 hour before end of surgery. PCA is commenced in postanesthetic care unit (PACU). PCA included: 400 mg tramadol in 100 mL 0.09 sodium chloride solution to create 4 mg/ mL concentration of tramadol. PCA was set to deliver 10 mg infusion per hour plus 10 mg bolus with 20-minute lock time. PCA forms were completed in PACU and follow-up in wards included hourly recording of VAS score and hemodynamic parameters. Postoperatively, IV paracetamol 3x1g was ordered for all patients by the surgical team. All other drugs used for analgesia were noted on the PCA forms. These drugs were cross-checked with electronic orders. Intramuscular diclofenac was used as rescue analgesia in all patients with a VAS score over 4 and 50 mg IV meperidine was administered if VAS score remained above 4 after 2 hours. VAS scores were noted at 0, 2, 4, 6, 9, and 12 hours after the patient was transferred from PACU to ward. The maximum VAS score was noted for the respective time frame. For standardization, VAS evaluation until the 12th hour was used, as PCA was terminated at different times after that point. When the data were retrospectively reviewed, the patients were separated into 3 groups according to analgesia protocol: Group 1 (0.25% bupivacaine): Twenty mL of mixture containing 10 mL bupivacaine (Marcaine 0.5%; Hospira, Inc./Pfizer, Inc., New York, NY, USA) + 5 mL lidocaine (Aritmal 2%; Osel İlaç Sanayi ve Tic. A.Ş., Istanbul, Turkey) + 5 mL physiological saline. Group 2 (0.166% bupivacaine): A solution of 24 mL was prepared (8 mL bupivacaine [Marcaine 0.5%] + 5 mL lidocaine [Aritmal 2%] + 11 mL physiological saline) and of this mixture, 20 mL was injected for FNB. Group 3: No femoral block.
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Assessed for Eligibility (n=79) Excluded (n=16) Neuroaxial anesthesia (n=7) History of psychiatric drug use (n=2) PCA at different dosage (n=2) Early termination of PCA (n=2) Differing concentration of local anesthetic (n=2) Bilateral TKA (n=1) Entered into study (n=63)
Group 1 (n=22) FNB at 0.25% concentration
Group 2 (n=25) FNB at 0.166% concentration
Group 3 (n=16) No FNB
Figure 1. Flowchart of the study methodology. FNB: Femoral nerve block; PCA: Patient-controlled analgesia. The local anesthetic concentration and mixture preparation used was according to the preference of the anesthesiologist. In all cases where FNB was used, it was administered at the end of surgery under conscious sedation. A nerve stimulator (STIMPOD NMS 400; Xavant Technology, Silverton, Pretoria, South Africa) and an insulated Stimuplex (B. Braun Medical, Inc., Bethlehem, PA, USA) needle were used. Antiseptic solution was used to prepare the skin of the femoral area of the ipsilateral side of the TKA. An insulated 5-cm needle was inserted immediately lateral to the femoral artery at the femoral skin crease. After negative aspiration to check for blood, anesthetic agents were injected into the location where 0.25-0.5 mA twitch of the quadriceps muscle (lateral and medial branches) was observed. Statistical analysis SPSS for Windows, Version 16.0 (SPSS, Inc., Chicago, IL, USA) software was used for statistical analysis. Mean±SD was used for descriptive statistics. Ratios were compared using chi-square test. Qualitative data was compared using Fisher’s exact test. Continuous variables were compared using one-way analysis of variance with post hoc Tukey analysis. A p value of <0.05 was regarded as statistically significant.
RESULTS The medical files of 79 patients were retrospectively reviewed. Seven patients who underwent spinal or spinal-epidural anesthesia, 2 patients with a history of psychiatric drug use, 2 patients who used different dose of PCA, 2 patients with different concentration of local anesthetic agents, 2 patients with early termination of PCA due to technical issues, and 1 patient who underwent bilateral TKA were excluded from the study. The data of 63 patients (49 female, 14 male) were included in the study. Inclusion flowchart is provided in Figure 1. The average age of the study patients was 64.3±14.9 years and average BMI was 32.5±5.3 kg/m2. The age, gender, ASA score, BMI, anesthesia type, and surgical time for all groups can be seen in Table 1. Comparison of these data between groups revealed no statistically significant difference (p>0.05). When VAS scores at 0, 2, 4, 6, 9, and 12 hours were compared there was a statistically significant difference between groups. Post hoc analysis revealed no difference between Groups 1 and 2 at any time period. However, when difference between Groups 1 and 3 and Groups 2 and 3 were compared, the difference was statistically significantly for VAS 0 (p>0.05) and extremely significant for other VAS time frames (p<0.01).
Tulgar et al., Evaluation of analgesic regimens in total knee arthroplasty, retrospective study
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Table 1. Patient demographics
All patients (n=63)
Age (years) Male/female (n) ASA I/II/III (n) Average BMI kg/m2 Surgical time (minutes)
Group 1 (n=22)
64.37±14.91 49/14 10/25/28 32.50±5.37 126.8±15.9
Group 2 (n=26)
Group 3 (n=16)
p
68.59±7.66 63.60±15.90 59.75±19.56 0.188* 20/2 18/7 11/5 0.177** 0/10/12 5/10/10 5/5/6 0.079** 33.89±5.73 31.64±4.89 31.95±5.55 0.328* 127±14.5 122.6±16.3 125.8±17.2 0.616*
ASA: American Society of Anesthesiologists classification of physical health; BMI: Body mass index. *Analysis of variance; ** Fisher’s exact test probability.
Table 2. Average postoperative Visual Analogue Scale
pain score according to group
p
1
2 Groups
3
1
2 Groups
3
10 9 8 7 6 5 4 3 2 1 0
10 9 8 7 6 5 4 3 2 1 0
VAS score 4
2.77±1.15 2.84±0.94 4.44±1.96 <0.001 2.23±1.15 1.80±0.65 4.25±1.69 <0.001 1.68±1.08 1.60±0.65 3.62±1.10 <0.001 1.41±1.08 1.48±0.71 4.0±1.41 <0.001 1.64±1.04 1.40±0.81 4.25±1.39 <0.001 1.45±0.85 1.20±0.81 4.0±1.75 <0.001
1
2 Groups
3
VAS score 12
10 9 8 7 6 5 4 3 2 1 0
Group 3
VAS score 2
10 9 8 7 6 5 4 3 2 1 0
Group 2
VAS score 9
VAS score 6
VAS score 0
0 hour 2nd hour 4th hour 6th hour 9th hour 12th hour
Group 1
VAS score comparison between groups is shown in Table 2. VAS scores and SD are illustrated in Figure 2. Table 3 reports the postoperative analgesia protocol used by the orthopedics clinic in patients who required additional analgesia. There was an extremely significant statistical difference between groups when the use of additional anesthesia was analyzed. When compared to other groups, Group 3 had 104.2% more patients receiving additional analgesic, which was statistically significant. There was no difference between Groups 1 and 2.
1
2 Groups
3
10 9 8 7 6 5 4 3 2 1 0
10 9 8 7 6 5 4 3 2 1 0
1
2 Groups
3
1
2 Groups
3
Figure 2. Postoperative Visual Analogue Scale scores at postoperative time intervals according to group. Green represents the maximum 3rd quartile (3/4) and red represents the minimum first quartile (1/4). VAS: Visual Analogue Scale of pain.
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Table 3. Additional analgesia requirements of the patients by group
Group 1 (PD)
Group 2 (PD)
Group 3 (PD)
p
No additional analgesia Additional analgesia required Diclofenac Diclofenac and meperidine
16 (+27.3%) 6 (-36.4%) 3 3
18 (+26%) 7 (-34.7%) 5 2
2 (-78.1%) 14 (+104.2%) 5 9
<0.001
PD: Percentage deviation.
DISCUSSION In this study we retrospectively reviewed the data of patients who underwent TKA at our institute. Patients who had FNB administered were found to have less pain during the first postoperative 12 hours and required less analgesic agent. Bupivacaine at 0.25% and 0.166% concentrations was used. When the 2 groups with different concentrations were compared, there was no difference between patient VAS scores or additional analgesic requirement. The administration of peripheral nerve block under ultrasound (US) guidance is the safest and most accepted method. The authors do not claim that peripheral nerve stimulator (PNS) is as successful and safe as US guidance. The aim of this study was not to compare PNS with US, but to evaluate the use of different concentrations of bupivacaine in FNB. Postoperative analgesia in TKA patients has been the subject of much research. While epidural analgesia was once considered the criterion standard for TKA, this has now been replaced with FNB [9]. However, FNB may lead to some undesirable effects. The most important of these is FNBrelated quadriceps weakness [2, 16, 17]. It has been suggested that blocking the femoral nerve more distally within the adductor canal could help prevent this effect [4, 18, 19]. However, adductor canal block is an advanced nerve block technique that is performed using US guidance. In our institute, we prefer to use FNB, as it is easily performed using a PNS and US is not available. Although we did not routinely evaluate quadriceps weakness in our patients, no falls were reported in their files.
There are a limited number of studies regarding FNB use in TKA in our country. Sahin et al. [15] performed US-guided FNB using 40 mL of 0.5% bupivacaine after T12 regression of spinal anesthesia. Their study reported significant decrease in opioid consumption with sufficient and effective analgesia for up to 48 hours. In another study from our country, 20 mL of 0.25% bupivacaine was administered near the femoral nerve with US and/or PNS guidance followed by placement of a catheter. Continuous bupivacaine was administered at a concentration of 0.125% with sufficient postoperative analgesia observed [20]. They reported no difference in analgesia effectiveness, length, or procedure performance (time, success, etc.) between patients undergoing FNB with or without US guidance. These 2 studies differ from ours in design and objective. However, the concentration and volume of bupivacaine should be discussed. Sahin et al. used 40 mL of 0.5% bupivacaine, a larger volume and concentration compared with our study. Aytac et al. [20] used 0.25% of bupivacaine concentration. We were unable to find a study that used our low concentration of 0.166% bupivacaine as the single shot or initiation dose. All patients in our study had a single injection for FNB. Our findings have demonstrated effective analgesia at low volume and concentration. The success of FNB is dependent on numerous factors, including the concentration and volume of the local anesthetic. There are several studies comparing different concentrations of bupivacaine for FNB [21, 22]. In a randomized, double-blind study to determine the minimum effective concentration
Tulgar et al., Evaluation of analgesic regimens in total knee arthroplasty, retrospective study
of bupivacaine in US-guided FNB for knee meniscectomy, bupivacaine was administered at concentrations ranging from 0.15% to 0.35%. Effective concentration (EC) 50 and EC90 were found to be 0.160% and 0.271%, respectively [21]. The concentrations of bupivacaine used in our study were within this range. Many studies have evaluated the effectiveness of FNB or have compared it with another analgesia method in TKA. A large majority of these studies have reported the use of 0.25% bupivacaine for single dose FNB [3, 8, 15, 23, 24]. When the catheter was placed near the femoral nerve, bolus of 0.25% bupivacaine was followed by 0.125% concentration as a continuous infusion [20, 25–27]. Most studies report 0.25% concentration of bupivacaine as the single shot or initiation dose. We have demonstrated that a single injection FNB with bupivacaine concentrations of 0.166% and 0.25% administered as part of a multimodal analgesia regimen are just as effective. Our study has some limitations. The primary limitation is performing FNB without US guidance. Another is that the presence and duration of motor block, quadriceps weakness, and fall risk scores plus VAS scores after the 12th hour were unavailable from patient files. Determination of tramadol consumption in patients with tramadol PCA would have added value to the study. However, analysis of rescue analgesia use partially decreases the effect of this limitation. Although there was no statistical difference in the demographics and surgical time between groups, the study’s retrospective design means that the groups may not be similar with regard to surgical trauma and severity or degree of damage to the knee. A well-designed prospective study that takes all demographics and confounders into account is required for a better level of evidence. Conclusion This study has demonstrated that FNB used in addition to our routine clinical analgesia protocol significantly decreased postoperative pain intensity and additional analgesia requirement in patients
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who underwent TKA. A concentration of 0.166% bupivacaine was as effective as a concentration of 0.25% when used as part of multimodal analgesia regimen in TKA. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – S.T., O.S.; Design– S.T., O.S.; Supervision – S.T., T.E.S.; Materials – S.M., S.T., O.S., S.S.; Data collection &/or processing – S.M., S.S., S.T.; Analysis and/or interpretation – S.T. ; Literature search – S.T.; Writing – S.T.; Critical review – S.T., O.S.
REFERENCES 1. Specht K, Kjaersgaard-Andersen P, Pedersen BD. Patient experience in fast-track hip and knee arthroplasty--a qualitative study. J Clin Nurs 2016;25:836–45. 2. Li D, Tan Z, Kang P, Shen B, Pei F. Effects of multi-site infiltration analgesia on pain management and early rehabilitation compared with femoral nerve or adductor canal block for patients undergoing total knee arthroplasty: a prospective randomized controlled trial. Int Orthop 2017;41:75–83. 3. Shin HJ, Soh JS, Lim HH, Joo B, Lee HW, Lim HJ. In-plane three-step needle insertion technique for ultrasound-guided continuous femoral nerve block after total knee arthroplasty: a retrospective review of 488 cases. Korean J Anesthesiol 2016;69:587–91. 4. Joe HB, Choo HS, Yoon JS, Oh SE, Cho JH, Park YU. Adductor canal block versus femoral nerve block combined with sciatic nerve block as an anesthetic technique for hindfoot and ankle surgery: A prospective, randomized noninferiority trial. Medicine (Baltimore) 2016;95:e5758. 5. Kodaka M, Minayoshi H, Ichikawa J, Nishiyama K, Komori M. A Prospective, Randomized, Blinded Trial to Compare Continuous Epidural Block and Femoral Nerve Block for Total Knee Arthroplasty. J Anesth Clin Res 2014;05:410–5. 6. Tanikawa H, Sato T, Nagafuchi M, Takeda K, Oshida J, Okuma K. Comparison of local infiltration of analgesia and sciatic nerve block in addition to femoral nerve block for total knee arthroplasty. J Arthroplasty 2014;29:2462–7. 7. Sakai N, Inoue T, Kunugiza Y, Tomita T, Mashimo T. Continuous femoral versus epidural block for attainment of 120° knee flexion after total knee arthroplasty: a randomized controlled trial. J Arthroplasty 2013;28:807–14. 8. Emerson RH Jr, Barrington JW, Olugbode O, Lovald S, Watson H, Ong K. Femoral Nerve Block Versus Long-Acting Wound Infiltration in Total Knee Arthroplasty. Orthopedics 2016;39:e449–55. 9. Hadzic A, Houle TT, Capdevila X, Ilfeld BM. Femoral nerve block for analgesia in patients having knee arthroplasty. Anesthe-
130 siology 2010;113:1014–5. 10. Bauer MC, Pogatzki-Zahn EM, Zahn PK. Regional analgesia techniques for total knee replacement. Curr Opin Anaesthesiol 2014;27:501–6. 11. Ratnawat A, Bhati FS, Khatri C, Srinivasan B, Sangwan P, Chouhan DP. Comparative study between nerve stimulator guided technique and ultrasound guided technique of supraclavicular nerve block for upper limb surgery. Int J Res Med Sci 2016;4:2101–6. 12. Beaudoin FL, Nagdev A, Merchant RC, Becker BM. Ultrasound-guided femoral nerve blocks in elderly patients with hip fractures. Am J Emerg Med 2010;28:76–81. 13. Fredrickson MJ, Kilfoyle DH. Neurological complication analysis of 1000 ultrasound guided peripheral nerve blocks for elective orthopaedic surgery: a prospective study. Anaesthesia 2009;64:836–44. 14. Wang F, Liu LW, Hu Z, Peng Y, Zhang XQ, Li Q. Ultrasound and nerve stimulator guided continuous femoral nerve block analgesia after total knee arthroplasty: a multicenter randomized controlled study. Rev Bras Anestesiol 2015;65:14–20. 15. Sahin L, Korkmaz HF, Sahin M, Atalan G. Ultrasound-guided single-injection femoral nerve block provides effective analgesia after total knee arthroplasty up to 48 hours. Agri 2014;26:113–8. 16. Jaeger P, Nielsen ZJ, Henningsen MH, Hilsted KL, Mathiesen O, Dahl JB. Adductor canal block versus femoral nerve block and quadriceps strength: a randomized, double-blind, placebocontrolled, crossover study in healthy volunteers. Anesthesiology 2013;118:409–15. 17. Dong CC, Dong SL, He FC. Comparison of Adductor Canal Block and Femoral Nerve Block for Postoperative Pain in Total Knee Arthroplasty: A Systematic Review and Meta-analysis. Medicine (Baltimore) 2016;95:e2983. 18. Shah NA, Jain NP. Is continuous adductor canal block better than continuous femoral nerve block after total knee arthroplasty? Effect on ambulation ability, early functional recovery and pain control: a randomized controlled trial. J Arthroplasty 2014;29:2224–9.
North Clin Istanb 19. Memtsoudis SG, Yoo D, Stundner O, Danninger T, Ma Y, Poultsides L, et al. Subsartorial adductor canal vs femoral nerve block for analgesia after total knee replacement. Int Orthop 2015;39:673–80. 20. Aytaç Ş, Atalan G, Gülen G, Yılmaz H. Comparison of femoral nerve block by neurostimulator accompanied with ultrasound and without ultrasound in knee artroplsty. J Clin Anal Med 2015;6:208–11. 21. Moura EC, de Oliveira Honda CA, Bringel RC, Leal Pda C, Filho Gde J, Sakata RK. Minimum Effective Concentration of Bupivacaine in Ultrasound-Guided Femoral Nerve Block after Arthroscopic Knee Meniscectomy: A Randomized, DoubleBlind, Controlled Trial. Pain Physician 2016;19:E79–86. 22. Veneziano G, Tripi J, Tumin D, Hakim M, Martin D, Beltran R, et al. Femoral nerve blockade using various concentrations of local anesthetic for knee arthroscopy in the pediatric population. J Pain Res 2016;9:1073–9. 23. Hartmann FV, Novaes MR, Carvalho MR. Femoral nerve block versus intravenous fentanyl in adult patients with hip fractures a systematic review. Rev Bras Anestesiol 2017;67:67–71. 24. Alzeftawy AE, El-Daba AA. Cold bupivacaine versus magnesium sulfate added to room temperature bupivacaine in sonarguided femoral and sciatic nerve block in arthroscopic anterior cruciate ligament reconstruction surgery. Anesth Essays Res 2016;10:667–73. 25. Liu Q, Chelly JE, Williams JP, Gold MS. Impact of peripheral nerve block with low dose local anesthetics on analgesia and functional outcomes following total knee arthroplasty: a retrospective study. Pain Med 2015;16:998–1006. 26. Park CK, Cho CK, Lee GG, Lee JH. Optimizing dose infusion of 0.125% bupivacaine for continuous femoral nerve block after total knee replacement. Korean J Anesthesiol 2010;58:468–76. 27. C Wyatt M, Wright T, Locker J, Stout K, Chapple C, Theis JC. Femoral nerve infusion after primary total knee arthroplasty: a prospective, double-blind, randomised and placebo-controlled trial. Bone Joint Res 2015;4:11–6.
Orıgınal Article
ANESTHESIOLOGY&REANIMATION
North Clin Istanb 2017;4(2):131–140 doi: 10.14744/nci.2017.89421
Comparison of RIVA and infraclavicular block in forearm and hand surgery Zubeyir Sarikaya,1 Guldem Turan,2 Reyhan Cetiner,3 Dilek Subasi,3 Gulcin Ozturk,4 Asu Ozgultekin,3 Osman Ekinci3 Department of Anesthesiology and Intensive Care, Vakfikebir State Hospital, Trabzon, Turkey
1
Department of Anesthesiology and Intensive Care, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
2
Department of Anesthesiology and Intensive Care, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
3
Department of Anesthesiology and Intensive Care, Kozan State Hospital, Adana, Turkey
4
ABSTRACT OBJECTIVE: The aim of this study was to compare 2 techniques that are widely used in hand, wrist, and forearm: regional intravenous anesthesia (RIVA) and infraclavicular brachial block. METHODS: A total of 100 patients who were aged 18 to 85 years and who underwent hand, wrist, or forearm surgery of at least 30 minutes duration were included. RIVA was applied to Group 1 patients with administration of 40 mL of prilocaine (3 mg/kg). Ultrasonography-guided infraclavicular block was performed on Group 2 patients with 20 mL of 1% prilocaine. Several aspects of these 2 methods were compared, including length of time required to apply anesthesia, the analgesic effectiveness of the treatment during administration and in the peroperative and postoperative periods. RESULTS: The rate of mild and complete sensory loss was significantly higher in Group 2 at 10th and 15th minutes than in Group 1. The number scoring less than grade 2 using modified Bromage grading system in Group 2 was considerably greater than in Group 1. Processing time to apply the block was significantly longer in Group 1 compared with Group 2. CONCLUSION: It was determined that infraclavicular brachial block is superior to the RIVA method with respect to length of time required to administer and ease of application. Keywords: Infraclavicular brachial block; regional intravenous anesthesia; upper extremity surgery.
T
he use of regional anesthesia techniques in surgical procedures continues to evolve and become more popular. Regional anesthesia is preferred to general anesthesia in suitable patients
as a result of greater analgesic effectiveness in the pre- and postoperative periods, and lower peroperative morbidity, length of postoperative hospital stay, and cost.
Received: May 07, 2017 Accepted: July 04, 2017 Online: August 26, 2017 Correspondence: Dr. Guldem TURAN. Fatih Sultan Mehmet Egitim ve Arastirma Hastanesi, E 5 Bostanci, Isanbul, Turkey. Tel: +90 216 - 578 30 00 e-mail: gturanmd@yahoo.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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Regional intravenous anesthesia (RIVA) is a preferred form of regional anesthesia, particularly in surgery of the upper extremities, performed with the injection of anesthetic solution into a local vein that is blocked with a tourniquet. RIVA is often used due to features such as minimal postoperative complications, low cost, and ease of application. However, there are a number of disadvantages to RIVA as well, including the need for a large volume of local anesthesia and short duration of anesthesia after release of the tourniquet. Peripheral block applications have become more popular with the introduction of ultrasound (US) technology to the administration of anesthetic agents. As the anesthetic agent can be quickly and safely given to patients in US-guided peripheral block, the technique is now widely used in surgery that is of short duration on an extremity. The aim of this study was to compare these 2 methods of anesthesia applied in hand, wrist, and forearm surgery: ultrasound-guided infraclavicular brachial block and RIVA. MATERIALS AND METHODS This study was conducted after obtaining approval from ethics committee of Haydarpasa Numune Teaching and Research Hospital, making the required explanations about the study to the patients, and finally, obtaining their informed consent. A total of 104 patients who were examined either in the orthopedics or plastic surgery clinic (American Society of Anesthesiologists [ASA] physical status classification I-III and body mass index <35 kg/ m2) who underwent hand, wrist, or forearm surgery of minimum 30 minutes and maximum 180 minutes duration were initially included in this study. Patients were excluded from the study if there was local anesthetic allergy or local infection in the area where block was to be applied, coagulopathy, neurological deficit in the upper extremity, prominent psychiatric or cognitive disorder, substance abuse, previous clavicular fracture or pneumonectomy, pregnancy, pneumothorax, thrombophlebitis, arteriosclerotic vascular disease, Raynaudâ&#x20AC;&#x2122;s disease, arteriovenous fistula, scleroderma, sickle cell ane-
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mia, extensive burns, lacerations, or infection in the area to be operated on, or neuromuscular disease, such as myasthenia gravis, decompensated heart failure, or epilepsy. Non-cooperative, debilitated, or malnourished patients, and those with advanced liver dysfunction were also excluded from the study. Three patients who underwent RIVA procedure but needed an additional injection of local anesthetic agent due to development of pain at surgical site were also excepted. Moreover, 1 patient from Group 2 required general anesthesia and therefore was excluded from the study. Patients were divided into 2 equal groups by simple randomization programmed by computer. Following intravenous line insertion, standard monitoring (noninvasive blood pressure, electrocardiography, oxygen saturation) was performed and all patients were sedated with midozalam (0.03 mg/kg). Group 1 (RIVA) (n=50): Vessel access points were opened on the back of the hand of the extremity to be operated on and on contralateral arm with 22-G needle. Intravenous access on operated extremity was used for RIVA application, while crystalloid infusion and drug solution were delivered through the other. The upper part of the operated arm was wrapped with cotton and doublecuff tourniquet was put in place. Before injection of the anesthetic agent, the arm was firmly wrapped from fingertips to distal tourniquet with 10-cmwide elastic (Esmarch) bandage to drain the venous blood, and then proximal cuff tourniquet was inflated to 300 mmHg pressure. Elastic bandage was removed and arterial circulation was confirmed by palpating the radial artery. The pre-prepared drug was administered intravenously to the operated arm in 90 seconds and then vessel access was closed. Distal tourniquet was inflated 10 minutes after drug administration while proximal tourniquet was deflated. In the postoperative period, the tourniquet was deflated at intervals beginning 35 minutes after the injection. Prilocaine was used as local anesthetic (40 mL of 3 mg/kg). Group 2 (infraclavicular block) (n=50): The patientâ&#x20AC;&#x2122;s head was turned to the opposite side of block application. The area where the block would be applied was disinfected with 10% povidone, and
Sarikaya et al., Comparison of RIVA and infraclavicular block in forearm and hand surgery
local anesthesia (2% lidocaine, 20 mg/mL) was administered subcutaneously to region of peripheral nervous needle puncture. A peripheral nerve needle (21-G) with a length of 50-80 mm and linear probe (5-12 MHz) were used in block application. The probe was covered with a sterile, transparent cover, sterile gel was applied, and it was then sagittally placed 1 cm below the intersection of the clavicle and coracoid process. Twenty mL of 1% prilocaine was administered around the subclavian artery and lateral, posterior, and medial cords with aspiration every 5 mL in correlation with the US image (in-plane technique). Sensory examination was performed every 5 minutes for 30 minutes after application of the block. Motor function was examined every 10 minutes. The first 3 fingers and wrist dorsal area were used for sensory examination of the radial nerve, while the fifth finger was used for the ulnar nerve. The first 3 fingers and volar aspect of the wrist were used for sensory examination of the median nerve, and the lateral region of the forearm was used for comparison of the musculocutaneous nerve with the nerves of the opposite forearm. Pinprick sensation test was performed in both groups using a scale for sensation block, and a modified Bromage scale was applied for assessment of the motor block. The results were noted as numbness, moderate, or no sensory block in pinprick sensation test. Surgery commenced when an absence of sensation determined by pinprick test and a score of ≤2 on modified Bromage scale was confirmed. Additional administration of local anesthesia to operated area, need for application of a rescue block on the distal part of the infraclavicular region, or application of general anesthesia was accepted as failure. Rescue block was applied when 1 or 2 nerves could not be blocked. If more then 2 nerves could not be blocked, general anesthesia was used. The number of times an invasive attempt was needed for block and whether vessel puncture occurred were also noted. Process duration was defined in Group 1 (RIVA) as the period that started with application of the Esmarch bandage and ended with completion of the local anesthetic injection. In Group 2, (infraclavicular block) it was defined as the period
133
between the passage of the peripheric nerve stimulator needle through the cutaneous and subcutaneous layers and the complete injection of local anesthesia. In addition, systolic blood pressure, diastolic blood pressure, mean blood pressure (MBP), heart rate (HR), and level of peripheral oxygen saturation were checked every 5 minutes from the initiation of the nerve blockade to postoperative 20th minute and noted in order to monitor the hemodynamic state of patients. After the application of the blockade, patients were questioned as to comfort and satisfaction with the method of anesthesia application prior to undergoing surgery. They were also asked if they would prefer the same anesthetic method if another operation were necessary, and the responses were noted. Details of preoperative application of tourniquet, duration, and whether patients developed pain as a result were also recorded. Furthermore, the time patients needed first analgesic in the postoperative period was also noted. Finally, sensory and motor function examinations were performed at 2nd, 4th, 8th, and 24th hours, and early complications were recorded. Statistical analysis IBM SPSS Statistics for Windows, Version 21.0 (IBM Corp., Armonk, NY, USA) software was used for the analyses. Mean±standard error and ratios of value frequency were used for definitive statistical analysis of data. The distribution of variables was assessed with the Kolmogorov-Smirnov test. Independent samples t-test and Mann-Whitney U test were applied for the analysis of quantitative data. Both chi-square test and Fisher’s exact test (when chi-square test could not be used) were used to analyze qualitative data. A minimum of 15 patients per group was required for the comparison of blockade types to have 100% statistical power and 0.5% standard error. RESULTS One patient from Group 1 was converted to general anesthesia and 3 patients from Group 2 required additional local anesthesia due to pain that developed in the operated area. Therefore, these patients
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104 patients included in the study 4 patients were excluded
100 patients were assessed
50 USG-guided infraclavicular block
Unwanted conditions: One patient was required to have general anesthesia due to failure of nerve blockade
50 patients were included in the study
50 RIVA
Unwanted conditions: Three patients needed additional local anesthetic due to persistent pain in operated area during procedure
50 patients were included in the study
Figure 1. The flow chart of randomization. RIVA: Regional intravenous anesthesia. were excluded from the study (Figure 1). There was no significant difference between the groups in terms of mean age (Group 1: 38.6±16.6 years, Group 2: 36.3±14 years), weight (Group 1: 74.4±12.9 kg, Group 2: 77.2±15.4 kg), gender distribution (Group 1: 16 female/34 male, Group 2: 11 female/39 male), or ASA classification. There was no significant difference between Group 1 and Group 2 in the evaluation of pinprick sensation at the fifth minute. Percentage of moderate sensory block and numbness was significantly higher at both 10th and 15th minute in the patients of Group 2 compared with Group 1 (Table 1). A noteworthy increase was determined in the degree of complete blockade in all nerve function at 10th, 20th, and 30th minute in Group 2 in comparison with Group 1 using modified Bromage Score. There was no difference between groups in the duration of tourniquet or operation, presence of pain as a result of the tourniquet, ratio of tourniquet use, requirement for analgesic, or satisfaction of the surgeon with respect to the anesthetic method used. The duration of the process was notably longer in Group 1 than in Group 2. Moreover, the patients of Group 1 needed additional analgesic in the postoperative period significantly earlier then those of Group 2. Complete satisfaction with the method
of anesthesia was significantly lower in Group 1. The ratio of those who preferred the same method of local anesthesia for another operation was also substantially lower in Group 1 in comparison with patients in Group 2 (Table 2). The rate of regaining complete sensation (recovery) after sensory block at 2nd, 4th, and 8th hours was determined to be significantly higher in Group 1. However, there was no remarkable difference between the 2 groups in this rate at 24th hour (Table 3). In addition, patients were evaluated at 2nd, 4th, and 8th hours to determine the length of time required to recover motor function after the blockade. The results revealed that the ratio of hand and finger mobilization was significantly higher in Group 1 (p<0.05) (Table 4). MBP at the fifth minute was significantly higher in patients in Group 1 compared with Group 2 (p<0.05); however, there was no significant difference in values collected at other time points. HR measurement was similar between the 2 groups. DISCUSSION There are a number of advantages to the use of regional local anesthesia, including continued an-
Sarikaya et al., Comparison of RIVA and infraclavicular block in forearm and hand surgery
135
Table 1. Sensory block level Pinprick test
Time (minutes)
Degree of Group 1 Group 2 sensation
p
n % n %
5 10 15 5 10 15 5 10 15 5 10 15
1 2.0 5 10.0 0.092 48 96.0 45 90.0 1 2.0 0 0.0 21 42.0 44 88.0 0.000 29 58.0 6 12.0 0 0.0 0 0.0 44 89.8 50 100.0 0.020 3 6.1 0 0.0 2 4.1 0 0.0 1 2.0 5 10.0 0.092 48 96.0 45 90.0 1 2.0 0 0.0 21 42.0 44 88.0 0.000 29 58.0 6 12.0 0 0.0 0 0.0 45 90.0 50 100.0 0.022 3 6.0 0 0.0 2 4.0 0 0.0 1 2.0 5 10.0 0.092 48 96.0 45 90.0 1 2.0 0 0.0 21 42.0 44 88.0 0.000 29 58.0 6 12.0 0 0.0 0 0.0 45 90.0 50 100.0 0.022 3 6.0 0 0.0 2 4.0 0 0.0 2 4.0 6 12.0 0.140 47 94.0 44 88.0 1 2.0 0 0.0 21 42.0 44 88.0 0.000 29 58.0 6 12.0 0 0.0 0 0.0 45 90.0 50 100.0 0.022 3 6.0 0 0.0 2 4.0 0 0.0
N. musculocutaneus: Forearm and lateral armsensation deficiency
N. ulnaris: Hypothenar region- sensation deficiency
N. radialis: Dorsal region-sensation deficiency
N. medianus: Thenar region-sensation deficiency
Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block Numbness Moderate No sensory block
Chi-square test.
algesia into the postoperative period and earlier mobilization of the patient than is the case with
general anesthesia. Since the patient is conscious, they are able to respond and express any complaints
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Table 2. Characteristics of the procedures
Group 1
Mean±SE
n
%
Mean±SE
Group 2 n
p
%
Duration of process 4.1±1.3 2.2±1.3 Duration of tourniquet 50.7±19.2 52.9±17.2 Duration of operation 57.0±24.9 57.3±18.6 Use of tourniquet No 0 0.0 1 2.0 Yes 50 100.0 49 98.0 Tourniquet pain No 46 92.0 46 92.0 Yes 4 8.0 4 8.0 Time until requirement for first postoperative analgesic 9.8±12.6 337.0±168.7 Peroperative complications No 50 100.0 50 100.0 Yes 0 0.0 0 0.0 Postoperative side effects No 50 100.0 50 100.0 Yes 0 0.0 0 0.0 Patient satisfaction with analgesic agent application method Not satisfied 1 2.0 0 0.0 Moderately satisfied 6 12.0 0 0.0 Satisfied 43 86.0 50 100.0 Surgeon satisfaction with local anesthetic application method Not satisfied 2 4.0 4 8.0 Moderately satisfied 6 12.0 0 0.0 Satisfied 42 84.0 46 92.0 Would you choose the same method of local anesthetic application if another operation is required? No 7 14.0 0 0.0 Yes 43 86.0 50 100.0
0.000 0.343 0.395 1.000
1.000
0.000 –
–
0.006
0.218
0.006
SE: Standard error. Chi-square test (or Fisher’s exact test) / Mann-Whitney U test.
during the administration of anesthesia. Additionally, spontaneous respiration continues and airway reflexes are preserved [1]. For these and other reasons, with developments in advanced technology and modern local anesthetics, the use of regional anesthetic techniques has increased in recent years. Advances in the use of US imaging led to a gen-
eration of portable US units that have enabled enhanced use of regional local anesthesia. The achievement of nerve block increased while the ratio of complications decreased using US guidance [2, 3]. Hadzic et al. [4] compared general anesthesia with infraclavicular block in cases of hand surgery. They suggested that both the score of analgesia
Sarikaya et al., Comparison of RIVA and infraclavicular block in forearm and hand surgery
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Table 3. Rate of sensory recovery
Time (hours)
Do you feel the touch? 2nd hour No Moderate Yes 4th hour No Moderate Yes 8th hour No Moderate Yes 24th hour No Moderate Yes
Group 1
Group 2
p
n
%
n
%
0 0 50
0 0 100
43 5 2
86 10 4
0 0 50
0 0 100
20 20 10
40 40 20
0.000
0 0 50
0 0 100
5 7 38
10 14 76
0.000
0 0 50
0 0 100
1 0 49
2 0 98
0.315
0.000
Chi-square test.
Table 4. Rate of recovery of motor function
Time (hours)
Can you move your arm and fingers? 2nd hour No Moderate Yes 4th hour No Moderate Yes 8th hour No Moderate Yes 24th hour No Moderate Yes Chi-square test.
Group 1
Group 2
p
n
%
n
%
0 0 50
0 0 100
42 6 2
84 12 4
0 0 50
0 0 100
9 21 20
18 42 40
0.000
0 0 50
0 0 100
3 5 42
6 10 84
0.003
0 0 50
0 0 100
1 1 48
2 2 96
0.495
0.000
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was better and that postoperative analgesic was not needed with infraclavicular block. They further reported that local anesthesia was better in terms of earlier ambulation and had fewer side effects. In this study, we compared 2 methods that are frequently used in routine hand surgery: RIVA (Group 1) and US-guided infraclavicular brachial plexus block (Group 2). The aim of the research was to determine the most advantageous method of providing anesthesia in short-duration upper extremity surgery. The high success rate and ease of application observed led to a preference for infraclavicular block. Advantages to the use of US in regional anesthesia include direct visualization of nerves and anatomical structures, making it easy to localize and follow the needle. Imaging of the distribution of the local anesthetic also allows for reduced dose and fewer needle attempts, which increases patient comfort. However, many aspects of the use and development of US-guided regional anesthesia have not yet been completely clarified. These include ideal needle position for a secure, successful block, the number of injections required for each block, minimal volume of local anesthetics, and whether it is preferable to an alternative anesthetic method in a particular procedure [5–8]. Successful application of regional anesthetic method depends on parameters including compatible timing between duration of operation and local anesthesia, selection of appropriate regional anesthetic method for targeted surgery, and the experience of the surgeon [9]. Important issues to be considered in cases using either RIVA or peripheric block include not exceeding toxic dose of local anesthetic and remaining alert for hemodynamic complications that may develop. Research continues regarding reduction of the quantity and concentration of local anesthetic agents and determination of minimal volume and dose to avoid systemic effect. To improve the generation of sufficient anesthesia with low concentration and dose, various adjuvant drugs are added to local anesthetics. Numerous recent studies have examined the use of clonidine, morphine, meperidine,
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fentanyl, sufentanyl, tramadol, muscle relaxants, nonsteroid anti-inflammatory drugs, dexamethasone, magnesium, and other local anesthetics to promote the formation of sensory and motor block and improve the quality of anesthesia created with RIVA [10, 11]. As a result of being able to see the drug injection site, quality anesthesia can be generated with lower doses of local anesthetic in USguided infraclavicular block without requiring any additional drugs. In this study, we did not use any drug other than local anesthetic agent; prilocaine was used at volume of 40 mL (3 mg/kg) and 20 mL (1%) in Group 1 and Group 2, respectively. Local anesthetic agents used in regional anesthesia have some advantageous features, including prolonged and less toxic anesthetic effects [12]. The most commonly used agents in RIVA are lidocaine and prilocaine. Prilocaine is used at dose of 3–4 mg/kg at a concentration ranging between 0.15% and 2% in RIVA. This anesthetic agent is commonly used in RIVA because of its rapid absorption by tissues and quick metabolization, reducing plasma concentration. The duration of the anesthetic effect of prilocaine is longer than that of lidocaine [13]. The duration of all application processes in this study was recorded by a person who was not involved in the research. Processing time was considered to be the length of time between the entry of the needle into the skin and exit of the needle after injection of local anesthetic agent in Group 2. In Group 1, processing time began with application of the Esmarch bandage and continued until the injection of the local anesthetic agent was completed. Processing time was significantly greater in Group 1 (Group 1: 4.1±1.3 minutes, Group 2: 2.2±1.3 minutes; p<0.05). Gurkan et al. [14] and Uysal et al. [15] reported block processing time of brachial plexus by USguided infraclavicular approach of 24±1 minutes and 5.2 minutes, respectively, while it was 3 minutes in a study conducted by Dingemans et al. [16]. Our research yielded a processing time of 3.7±2.6 minutes. Due to the need to apply an additional analgesic agent, 3 patients were excluded from the study. One
Sarikaya et al., Comparison of RIVA and infraclavicular block in forearm and hand surgery
other individual was excluded as a result of conversion to general anesthesia. Recovery from sensory block was determined significantly earlier in Group 1 at 2nd, 4th, and 8th hour compared with Group 2 (p<0.05). However, there was no difference between groups 24th hour. Postoperative analgesic was required by patients in Group 1 due to the development of pain 1 to 2 minutes after release of the tourniquet. The length of time until the first analgesic requirement was longer in Group 2 (p<0.05). This condition provides a significant advantage in terms of patient satisfaction. Moreover, it is interesting to note that it is also gratifying to the surgeon. Evaluation of the length of time until full recovery from motor block and ratios of hand and finger movement ability were found to be significantly greater in Group 1 in comparison with Group 2 at 2nd, 4th, and 8th hours (p<0.05); however, this difference disappeared at 24th hour (p>0.05). Enhanced success ratio of achievement of block was seen in both groups (Group 1: 94.3%, Group 2: 98.03%). Sandhu et al. [17] described nearly 100% achievement with an application of local anesthetic around the neural cord with US guidance. There were no complications due to process in this study. Based on findings from magnetic resonance imaging, Neuburger et al. [18] suggested that infraclavicular block is a safe technique, although there is a risk for development of pneumothorax. Though this risk is small, pneumothorax is the most dangerous complication in infraclavicular brachial plexus block. An experienced surgeon should perform the block, complying with the rules and using suitable size nerve stimulator. The risk of pneumothorax is virtually eliminated in the application of the block with US guidance. Pneumothorax was not observed in any patient in our block groups. Vascular puncture is a complication that may be encountered in brachial plexus block due to the close proximity of blood vessels and nerves. Incidence of this complication is reduced with use of US. No vascular puncture or invasive process was observed in the present study. The rate of vascular injury complication in peripheral nerve block guid-
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ed by US was determined to be 0.4% in large series of retrospective and prospective applications [17, 19]. The rate of vascular injury in a study comparing neurostimulation with US was found to be significantly lower in the US group [20, 21]. Vascular puncture has been observed in US-guided infraclavicular block at rate of 0% to 7.5% [22–26]. In this study, we did not observe any side effects, toxicity, or complication during or after anesthesia in either group in terms of the application of local anesthetic agent. Both methods also demonstrated the effect of surgical anesthesia at the desired time. No pneumothorax, respiratory problems, or hematoma due to vascular puncture was found in subsequent patient controls. Although both methods are used for upper extremity surgery, we conclude that US-guided infraclavicular block may be preferred for greater postoperative patient comfort in short-duration upper extremity surgery, particularly hand, wrist, and forearm operations. Although conventional methods, including RIVA, may still be used successfully, we think that infraclavicular brachial block is better than other methods due to the low risk and low rate of complications, as well as ease of application with current improvements in technology. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – Z.S., G.T.; Design – Z.S., G.T.,O.E; Supervision – G.T., D.S., A.O., O.E.; Materials – Z.S., G.T., R.C.; Data collection &/or processing – Z.S., R.C., D.S., G.O.; Analysis and/or interpretation – Z.S., G.T., A.O., O.E.; Literature search – Z.S., G.T, G.O.; Writing – Z.S., G.T., O.E.; Critical review – G.T., A.O.,O.E.
REFERENCES 1. Gürkan Y, Acar S, Solak M, Toker K. Comparison of nerve stimulation vs. ultrasound-guided lateral sagittal infraclavicular block. Acta Anaesthesiol Scand 2008;52:851–5. 2. Klaastad Ø, Smedby O, Thompson GE, Tillung T, Hol PK, Røtnes JS, et al. Distribution of local anesthetic in axillary brachial plexus block: a clinical and magnetic resonance imaging study. Anesthesiology 2002;96:1315–24. 3. Hadzic A, Arliss J, Kerimoglu B, Karaca PE, Yufa M, Claudio RE, et al. A comparison of infraclavicular nerve block versus gen-
140 eral anesthesia for hand and wrist day-case surgeries. Anesthesiology 2004;101:127–32. 4. Klaastad Ø, Smith HJ, Smedby O, Winther-Larssen EH, Brodal P, Breivik H, et al. A novel infraclavicular brachial plexus block: the lateral and sagittal technique, developed by magnetic resonance imaging studies. Anesth Analg 2004;98:252–6. 5. Heid FM, Jage J, Guth M, Bauwe N, Brambrink AM. Efficacy of vertical infraclavicular plexus block vs. modified axillary plexus block: a prospective, randomized, observer-blinded study. Acta Anaesthesiol Scand 2005;49:677–82. 6. Marhofer P, Greher M, Kapral S. Ultrasound guidance in regional anaesthesia. Br J Anaesth 2005;94:7–17. 7. Koscielniak-Nielsen ZJ, Rasmussen H, Hesselbjerg L, Nielsen TP, Gürkan Y. Infraclavicular block causes less discomfort than axillary block in ambulatory patients. Acta Anaesthesiol Scand 2005;49:1030–4. 8. Gürkan Y, Ozdamar D, Hoşten T, Solak M, Toker K. Ultrasound guided lateral sagital infraclavicular block for pectoral flap release. Agri 2009;21:39–42. 9. Brown DL. Brachial plexus anesthesia: an analysis of options. Yale J Biol Med 1993;66:415–31. 10. Kleinschmidt S, Stöckl W, Wilhelm W, Larsen R. The addition of clonidine to prilocaine for intravenous regional anaesthesia. Eur J Anaesthesiol 1997;14:40–6. 11. Turan A, Memiş D, Karamanlioğlu B, Güler T, Pamukçu Z. Intravenous regional anesthesia using lidocaine and magnesium. Anesth Analg 2005;100:1189–92. 12. Whiteside JB, Wildsmith JA. Developments in local anaesthetic drugs. Br J Anaesth 2001;87:27–35. 13. Sean JE, Vonda B, Cephas PS. Intravenous regional anesthesia: a reviev. Seminars in Anesthesia. Perioperative Medicine and Pain 1998;1:2–9. 14. Gürkan Y, Tekin M, Acar S, Solak M, Toker K. Is nerve stimulation needed during an ultrasound-guided lateral sagittal infraclavicular block? Acta Anaesthesiol Scand 2010;54:403–7. 15. Yarkan Uysal H, Acar HV, Tezer E, Ceyhan A, Dikmen B. Ultrasonography (us) guidance in infraclavicular block: comparison of us vs. us + neurostimulation in a prospective, randomised study. Journal of Anesthesia 2013;21:106–12. 16. Dingemans E, Williams SR, Arcand G, Chouinard P, Harris P, Ruel M, et al. Neurostimulation in ultrasound-guided infra-
North Clin Istanb clavicular block: a prospective randomized trial. Anesth Analg 2007;104:1275–80. 17. Sandhu NS, Manne JS, Medabalmi PK, Capan LM. Sonographically guided infraclavicular brachial plexus block in adults: a retrospective analysis of 1146 cases. J Ultrasound Med 2006;25:1555–61. 18. Neuburger M, Kaiser H, Uhl M. Biometric data on risk of pneumothorax from vertical infraclavicular brachial plexus block. A magnetic resonance imaging study. Anaesthesist 2001;50:511–6. 19. Sites BD, Spence BC, Gallagher JD, Wiley CW, Bertrand ML, Blike GT. Characterizing novice behavior associated with learning ultrasound-guided peripheral regional anesthesia. Reg Anesth Pain Med 2007;32:107–15. 20. Kapral S, Krafft P, Gosch M, Fleischmann D, Weinstabl C. Ultrasound imaging for stellate ganglion block: direct visualization of puncture site and local anesthetic spread. A pilot study. Reg Anesth 1995;20:323–8. 21. Liu FC, Liou JT, Tsai YF, Li AH, Day YY, Hui YL, et al. Efficacy of ultrasound-guided axillary brachial plexus block: a comparative study with nerve stimulator-guided method. Chang Gung Med J 2005;28:396–402. 22. Brull R, Lupu M, Perlas A, Chan VW, McCartney CJ. Compared with dual nerve stimulation, ultrasound guidance shortens the time for infraclavicular block performance. Can J Anaesth 2009;56:812–8. 23. Sauter AR, Dodgson MS, Stubhaug A, Halstensen AM, Klaastad Ø. Electrical nerve stimulation or ultrasound guidance for lateral sagittal infraclavicular blocks: a randomized, controlled, observer-blinded, comparative study. Anesth Analg 2008;106:1910–5. 24. Marhofer P, Sitzwohl C, Greher M, Kapral S. Ultrasound guidance for infraclavicular brachial plexus anaesthesia in children. Anaesthesia 2004;59:642–6. 25. Frederiksen BS, Koscielniak-Nielsen ZJ, Jacobsen RB, Rasmussen H, Hesselbjerg L. Procedural pain of an ultrasound-guided brachial plexus block: a comparison of axillary and infraclavicular approaches. Acta Anaesthesiol Scand 2010;54:408–13. 26. Vainionpää VA, Haavisto ET, Huha TM, Korpi KJ, Nuutinen LS, Hollmén AI, et al. A clinical and pharmacokinetic comparison of ropivacaine and bupivacaine in axillary plexus block. Anesth Analg 1995;81:534–8.
Orıgınal Article
GENERAL SURGERY
North Clin Istanb 2017;4(2):141–144 doi: 10.14744/nci.2017.19970
Retrospective analysis of cases of intestinal invagination treated and followed-up at our clinic Bora Barut,1 Huseyin Yonder,2 Kemal Baris Sarici,1 Fatih Ozdemir,1 Volkan Ince1 Department of General Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
1
Department of General Surgery, Derik State Hospital, Mardin, Turkey
2
ABSTRACT OBJECTIVE: The purpose of this study was to present data on the diagnosis, treatment, clinical course, and outcome of cases of intestinal invagination. METHODS: Data of 11 patients treated for intestinal invagination at one center between June 2009 and July 2015 were analyzed retrospectively in terms of demographic data, etiological factors, anatomical localization of invagination, admission complaints, physical examination findings, diagnostic imaging modalities used, postoperative complications, and hospital stay. RESULTS: Of the total, 9 (81.8%) patients were female and 2 (18.2%) were male. Nine (81.8%) cases occurred due to benign causes and 2 to malignant causes. One (9%) patient had jejunojejunal invagination, 5 (45.5%) had ileoileal invagination, and 5 (45.5%) had ileocecal invagination. Right hemicolectomy-ileotransversostomy was performed in 5 (45.5%) patients and segmental small bowel resection with end-to-end anastomosis in 6 (54.5%). CONCLUSION: Intestinal invagination is a rare cause of acute abdomen in adults that may have a variety of etiologies and therefore may present with different clinical pictures. Abdominal pain, nausea, and vomiting are the most common symptoms. The rate of accurate diagnosis is 30% to 35% using ultrasonography and 50% to 80% using computerized tomography. In adults, the preferred treatment is surgery. As malignant pathologies are responsible for some cases of invagination, oncological principles should be strictly observed in surgical treatment. Though a rare cause of acute abdomen and/or ileus in adults, invagination is a clinical condition that must be kept in mind in the differential diagnosis. Keywords: Acute abdomen; cecum; ileum; invagination; jejunum.
I
ntestinal invagination occurs when one part of the intestine folds into the proximal segment [1]. It is a relatively frequently seen clinical condition during childhood; however, it constitutes only 1% of all in-
testinal obstructions seen in adults. Ninety percent of the cases in children are idiopathic, while 90% of adult cases are related to an organic lesion caused by benign or malignant tumors [2]. Abdominal pain, nausea,
Received: March 19, 2017 Accepted: May 18, 2017 Online: August 26, 2017 Correspondence: Dr. Bora BARUT. Turgut Ozal Tip Merkezi̇ , Genel Cerrahi̇ Klinigi, 78712 Malatya, Turkey. Tel: +90 422 - 341 06 60 e-mail: borabarut@mynet.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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Table 1. Distribution of invagination etiology Etiology
Subgroup
n %
Malignant 18.2 Mucinous adenocarcinoma 1 Gastrointestinal stromal tumor 1 Benign 81.8 Lipoma 5 Polyp 3 Hemangioma 1
and vomiting are the most frequently seen symptoms [3]. The rate of accurate diagnosis of invagination using ultrasonography (US) and computed tomography (CT) ranges between 30% to 35% and 50% to 80%, respectively. The preferred treatment for invagination in the adult age group is surgery [4].
Figure 1. Intraoperative appearance of ileocecal invagination.
MATERIALS AND METHODS Demographic data, etiological factors, anatomical location of the invagination, admission complaints, findings of preoperative physical examination, diagnostic imaging modalities used, surgery performed, postoperative complications, and the length of hospital stay of 11 patients treated at one center between June 2009 and July 2015 with the indication of intestinal invagination were retrospectively examined. RESULTS The study population consisted of 9 (81.8%) female and 2 (18.2%) male patients with a mean age of 57 years (range: 27â&#x20AC;&#x201C;84 years). All of the patients were over 18 years of age. Intestinal invagination developed due to benign (n=9; 81.8%) and malignant (n=2; 18.2%) etiologies. Data regarding the etiology of invagination are summarized in Table 1. Jejunojejunal (n=1; 9%), ileoileal (n=5; 45.5%), and ileocecal (n=5; 45.5%) invaginations were detected in the study patients (Figures 1, 2). The patients were operated on as an emergency (n=9; 81.8%) and on elective (n=2; 18.2%) basis. In 8 (81.8%) of 9 patients who underwent emergency surgery, admis-
Figure 2. Intraoperative appearance of ileoileal invagination.
sion complaints included abdominal pain, nausea, vomiting, and inability to defecate or pass gas, and in remaining patient (10.2%) lower gastrointestinal (GIS) system bleeding was detected. In the 2 patients who were operated on under elective conditions, the primary complaints were abdominal pain, lassitude, and anemia. Diagnosis was established in the 1 (1.9%) patient with lower GIS bleeding using angiography, while 6 (60%) of the remaining 10 patients were diagnosed on the basis of US and/ or CT findings (Figure 3). All patients underwent surgery: right hemicolectomy-ileotransversostomy (n=5; 45.5%) or segmental resection of small bowel
Barut et al., Retrospective analysis of cases of intestinal invagination treated and followed-up at our clinic
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with end-to-end anastomosis (n=6; 54.5 %). Postoperatively, pneumonia (n=1; 9%), wound infection (n=1; 9%), and abdominal evisceration (n=1; 9%) developed. All patients were discharged with full recovery. Mean hospital stay was 8 days. Data of the cases are summarized in Table 2. DISCUSSION
Figure 3.
Preoperative computed tomography image of a patient with invaginated bowel segment (arrow).
Intestinal invagination in adults is a clinical condition rarely encountered by surgeons. Although the pathogenetic mechanisms of invagination are not precisely known, an intraluminal lesion or an irritating factor is believed to alter normal peristaltic movements, leading to the initiation of invagination [5]. In adults,
Table 2. Data of the cases Case Age (years)/ Location of Preoperative Type of Emergency/ Pathology Postoperative Length of gender the lesion imaging surgery elective complication hospitalization (days) 1 66/F Ileoileal US: Diagnosis (+) 2 67/F Ileoileal CT: Diagnosis (+) 3 21/F Ileocecal US: Diagnosis (+) 4 84/F Ileoileal CT: Diagnosis (+) 5 60/F Ileoileal USG: Normal 6 70/M Ileocecal CT: Diagnosis (+) 7 56/F Ileocecal US: Normal 8 49/M Ileocecal CT: Normal 9 74/F Ileocecal US: Normal 10 27/F Ileoileal CT: Diagnosis (+) 11 54/F Jejunojejunal Angiography: Diagnosis (+)
Segmental Emergency Mucinous small bowel adenocarcinoma resection Segmental Emergency Lipoma small bowel resection Right Emergency Lipoma hemicolectomy Segmental Emergency Inflammatory small bowel fibroid polyp resection Segmental Emergency Lipoma small bowel resection Right Elective Capillary hemicolectomy hemangioma Right Elective Polyp hemicolectomy laparoscopic Right Emergency Lipoma hemicolectomy Right Emergency Lipoma hemicolectomy Segmental Emergency Peutz- small bowel Jeghers resection polyp Segmental Emergency GIST small bowel resection
CT: Computed tomography; GIST: Gastrointestinal stromal tumor; F: Female; M: Male; US: Ultrasonography.
None
7
None
9
None
5
Pneumonia
11
None
7
None
8
None
5
Abdominal evisceration Wound infection None
9 11
None
10
5
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90% of invaginations manifest as a result of an organic lesion caused by benign or malignant tumors. Leiomyoma, adenoma, lipoma, Brunner cell hamartoma, hemangioma, adenomyoma, neurofibroma, desmoid tumor, and Meckel’s diverticulum are among the benign lesions that can cause invagination. Lymphoma, adenocarcinoma of the small bowel or colon, and metastatic malignant tumor are among the malignant lesions that most frequently cause invagination [6]. In all of our cases, an organic etiology was present, and consistent with the literature, we found malignant tumor in 2 (18.2%) and benign tumor in 9 (81.8%) patients. Invagination is classified as enteroenteric, colocolic, ileocolic, or ileocecal, according to anatomical location [7]. In enteroenteric and colocolic invagination, the affected small bowel and colonic segments telescope into another segment, while in ileocolic invagination, the terminal ileum passes through the ileocecal valve and infolds into the ascending colon. In ileocecal invagination, a segment of the terminal ileum is retained at the level of the ileocecal valve. However, it may be difficult to differentiate between ileocecal and ileocolic invagination intraoperatively. [8]. Abdominal pain, nausea, vomiting, rectal bleeding, alterations in bowel habits, and constipation are the most frequently seen complaints. The imaging modalities most frequently used in the diagnosis of invagination include plain or contrast-enhanced radiograph, abdominal US, and CT. The rate of accurate diagnosis ranges between 30% and 35% for US, while it rises to 50% to 80% when CT is used. [9]. In 10 of 11 patients in this study, US and/or CT were/ was used for preoperative imaging, and in 6 (60%) patients accurate diagnosis was made using radiological imaging modalities. A non-operative reduction procedure is a frequently applied treatment for invagination in children; however, since in most adult cases there is an underlying organic lesion with malignant potential, surgical resection is the primary method of treatment. During the process of reduction, because there is the possibility of seeding tumor cells in other foci and risk of procedural perforation, resection of the affected bowel segment should be conducted in compliance with oncological procedures [10, 11]. In conclusion, intestinal invagination is a rarely seen disease in adults that may manifest due to nu-
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merous etiological factors and may display a diverse clinical picture. It can present with manifestations of acute abdomen and/or ileus. In patients who present at emergency service with manifestations of acute abdomen and/or ileus, invagination must be considered in the differential diagnosis. Surgery is the preferred treatment for invagination in adults. Considering that the organic lesion responsible may be a malignant entity, oncological principles should be observed during resection. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – B.B, F.O; Desing – H.Y; Supervision – K.B.S; Materials and data collection – B.B, H.Y; Analysis – V.I; Writing – B.B; Litarature search – B.B, H.Y; Critical reiew – K.B.S, V.I.
REFERENCES 1. Chandra N, Campbell S, Gibson M, Reece-Smith H, Mee A. Intussusception caused by a heterotopic pancreas. Case report and literature review. JOP 2004;5:476–9. 2. Patrizi G, Di Rocco G, Giannotti D, Casella G, Casella Mariolo JR, Bernieri MG, et al. Double ileo-ceco-colic invagination due to right colon carcinoma: clinical presentation and management. Eur Rev Med Pharmacol Sci 2013;17:2267–9. 3. Gonzalez-Hernandez J, Garcia F. Cecal adenocarcinoma presenting as colonic intussusception in adulthood. Proc (Bayl Univ Med Cent) 2015;28:180–2. 4. Korkmaz Ö, Yılmaz HG, Taçyıldız İ, Baç B, Çevik S. Erişkinlerde Görülen İnvajinasyon Olgularının Değerlendirilmesi. Dicle Tıp Dergisi 2007;34:182–6. 5. Yakan S, Caliskan C, Makay O, Denecli AG, Korkut MA. Intussusception in adults: clinical characteristics, diagnosis and operative strategies. World J Gastroenterol 2009;15:1985–9. 6. Toso C, Erne M, Lenzlinger PM, Schmid JF, Büchel H, Melcher G, et al. Intussusception as a cause of bowel obstruction in adults. Swiss Med Wkly 2005;135:87–90. 7. Lu T, Chng YM. Adult intussusception. Perm J 2015;19:79–81. 8. Azar T, Berger DL. Adult intussusception. Ann Surg 1997;226:134–8. 9. Kaya F, Kızıltan R, Şit M, Yılmaz EE. İleoçekal İnvajinasyona Neden Olan İntestinal Non-Hodgkin Lenfoma: Olgu Sunumu. Abant Tıp Dergisi 2012;1:162–4. 10. Kannan U, Rahnemai-Azar AA, Patel AN, Gaduputi V, Shah AK. Jejunal Intussusception: A Rare Presentation of Carcinoid Tumor. Case Rep Surg 2015;2015:260697. 11. Barussaud M, Regenet N, Briennon X, de Kerviler B, Pessaux P, Kohneh-Sharhi N, et al. Clinical spectrum and surgical approach of adult intussusceptions: a multicentric study. Int J Colorectal Dis 2006;21:834–9.
Orıgınal Article
CARDIOLOGY
North Clin Istanb 2017;4(2):145–150 doi: 10.14744/nci.2017.53315
The use of monocyte to HDL ratio to predict postoperative atrial fibrillation after aortocoronary bypass graft surgery Ahmet Ilker Tekkesin,1 Mert Ilker Hayiroglu,1 Regayip Zehir,2 Ceyhan Turkkan,1 Muhammed Keskin,1 Goksel Cinier,1 Ahmet Taha Alper1 Department of Cardiology, Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Center Training and Research Hospital,
1
Istanbul, Turkey Department of Cardiology, Kosuyolu Cardiovascular and Thoracic Surgery Hospital Kartal, Istanbul, Turkey
2
ABSTRACT OBJECTIVE: Postoperative atrial fibrillation (POAF) is a frequent and serious complication after aortocoronary bypass graft (ACBG) surgery and one that, unfortunately, increases morbidity and mortality. Postoperative stroke, hemodynamic instability, renal failure, infection, need for inotropic agent and coronary unit are complications caused by POAF. Inflammation and oxidative stress are among several mechanisms that contribute to pathogenesis of POAF. Monocyte to HDL (M/H) ratio is a newly defined parameter of both inflammation and oxidative stress. In this study, M/H ratio was investigated as predictor of POAF after ACBG surgery. METHODS: Total of 311 patients who underwent ACBG surgery were included in the study. Blood samples for analysis of routine biochemistry and lipid panel were obtained from the patients on the morning of ACBG surgery after 12 hours of fasting. Patients were continuously monitored for occurrence of POAF throughout hospitalization. RESULTS: POAF was observed in 71 patients following ACBG operation. M/H ratio was significantly higher in POAF(+) group compared with POAF(-) group (p<0.001). Median age of POAF(+) patients was 62.0±10.1 years, which was significantly higher than mean age of POAF(-) patients. Other atrial fibrillation (AF) risk factors, such as hypertension, diabetes mellitus, smoking, and alcohol consumption, were similar between groups. Potassium level was statistically lower in POAF(+) group compared with POAF(-) group (p=0.01). CONCLUSION: M/H ratio is an indicator of inflammation and oxidative stress, both of which play important role in pathogenesis of AF. M/H ratio was found be statistically significantly higher in POAF(+) patients than in POAF(-) patients. Keywords: Atrial fibrillation; monocyte to high-density lipoprotein ratio; postoperative atrial fibrillation.
Received: December 24, 2016 Accepted: April 05, 2017 Online: August 26, 2017 Correspondence: Dr. Mert Ilker HAYIROGLU. Dr. Siyami Ersek Gogus ve Kalp Damar Cerrahisi Egitim ve Arastirma Hastanesi, Istanbul, Turkey. Tel: +90 216 - 542 44 44 e-mail: mertilkerh@yahoo.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
146
P
ostoperative atrial fibrillation (POAF) is one of the most common complications seen after cardiac surgery, and contributes to mortality and morbidity. Incidence of PAOF has been demonstrated to be 15% to 60% in studies [1–3]. POAF can lead to stroke, infection, need for inotropic agent, hemodynamic instability, and renal failure in postoperative patients. In the literature, development of POAF has been proven to increase acute renal failure and stroke incidence 4 to 5 times in postoperative patients [4]. For this reason, there is interest among clinicians in POAF pathophysiology and management, including search for parameters that may predict POAF in order to prevent its complications. Inflammation and oxidative stress are among several mechanisms contributing to pathogenesis of atrial fibrillation (AF). Leukocyte activation and subsequent release of various proinflammatory and pro-oxidant cytokines and chemokines lead to pathological structural and electrical remodeling in the left atria, which is considered to be important prerequisite for development of AF [5]. High-density lipoprotein (HDL) molecule exhibits anti-inflammatory and antioxidant properties via several pathways, including inhibiting transmigration of monocytes in response to oxidized low-density lipoprotein (LDL), expression of endothelial adhesion proteins, and promoting reverse transport of oxidized molecules [6]. Secondary to these protective effects, low HDL level has been associated with occurrence of AF [7]. Despite the fact that there are many studies evaluating M/H ratio, and particularly correlation with inflammation processes, to our knowledge there is no study examining M/H ratio and POAF. Presently described is investigation of relationship between M/H ratio and POAF. MATERIALS AND METHODS Total of 311 patients who underwent coronary artery bypass surgery between February 2015 and June 2015 were consecutively enrolled in the study. Patients who underwent additional cardiovascular surgeries (valvular surgery, aorta surgery, peripheral vascular surgery) were excluded. Patients with
North Clin Istanb
valvular heart disease, atrial arrhythmia history, renal failure, or on pacemaker rhythm were also excluded from the study. All patients participating in the study provided signed written consent. The study was approved by the Haydarpasa Numune Training and Research Hospital ethical committee. Baseline demographic parameters and related clinical information of the patients were recorded preoperatively. All patients underwent preoperative electrocardiogram (EKG) and demonstrated normal sinus rhythm. Transthoracic echocardiogram was also administered to all patients preoperatively by an expert in cardiac imaging. Blood samples were obtained from the patients on the morning of ACBG surgery after 12 hours of fasting for analysis of routine biochemistry and lipid panel. Samples for complete blood count analysis were collected in ethylenediamine tetraacetic acid anticoagulant tubes at the same time. Reference value for monocyte count in our laboratory was 2% to 10% of total white blood cells. Isolated coronary artery bypass surgery was performed on all patients. Daily EKG was included in monitored follow-up. Patients were divided into 2 groups based on development of AF during hospitalization period: POAF(+) and POAF(-). All data were evaluated by using IBM SPSS Statistics for Windows, Version 22.0. (IBM Corp., Armonk, NY, USA). Mean and SD were calculated for quantitative variables. Student’s t-test was used for normally distributed variables in both groups and Mann-Whitney U test was used for variables that were not normally distributed. Qualitative variables were evaluated with Pearson’s chi-square test with Yates’s continuity correction. Logistic regression model was applied to multivariate analysis to identify risk factors related to mortality. P value of <0.05 was accepted as statistically significant. RESULTS Total of 311 patients (mean age 60.1±8.7 years) who underwent isolated ACBG surgery between February 2015 and June 2015 were included in the present study. Patients (66.7% male) were divided
Tekkesin et al., The use M/H ratio to predict post-op AF after aortocoronary bypass graft surgery
147
Table 1. Demographic variables of the study population Parameters
Total (n=311) POAF(-) (n=240)
POAF(+) (n=71)
p
n % Mean±SD n % Mean±SD n % Mean±SD
Age (years) 60.1±8.7 59.5±8.2 62.0±10.1 0.041** Women 106 33.3 85 35.4 21 29.6 0.362 BMI 26.8±2.8 26.9±3.7 26.5±4.0 0.480 Diabetes mellitus 105 33.8 76 31.7 29 40.8 0.151 Hypertension 116 37.3 83 34.6 33 46.5 0.069 Alcohol consumption 43 13.8 31 12.9 12 16.9 0.393 Smoker 122 39.1 93 38.7 29 40.8 0.751 BMI: Body mass index; SD: Standard deviation.
Table 2. Echocardiographic and laboratory parameters Parameters
Total (n=311)
POAF(-) (n=240)
POAF(+) (n=71)
p
Left atrial diameter (cm) Left ventricular ejection fraction (%) Serum creatinine (mg/dL) Sodium (mEq/L) Potassium (mEq/L) Hemoglobin (g/dL) White blood cell (x109 /L) Monocyte (x109/L) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Monocyte/HDL ratio
3.91±0.38 55.01±8.32 1.16±0.42 139.24±2.71 4.40±2.04 13.62±6.95 7.15±1.11 370.12±47.17 111.41±26.55 41.76±4.56 8.95±1.46
3.91±0.40 55.04±8.33 1.16±0.40 139.26±2.55 4.34±0.59 13.70±7.88 7.13±1.11 359.12±43.13 109.93±25.28 42.40±4,08 8.52±1.17
3.93±0.38 54.92±8.34 1.18±0.48 139.18±3.21 4.10±0.33 13.35±1.48 7.20±1.13 407.32±41.05 116.40±30.11 39.59±5.37 10.41±1.40
0.653 0.921 0.771 0.838 0.01** 0.714 0.627 <0.001** 0.07 <0.001** <0.001**
HDL: High-density lipoprotein; LDL: Low-density lipoprotein.
into 2 groups, POAF(+) and POAF(-), according to development of AF during hospitalization period. In all, 71 patients (22.8%) had AF occurrence after ACBG surgery. Both groups were similar in terms of baseline characteristics, with exception of age. POAF(+) group proved to be statistically significantly older than POAF(-) group (p=0.041) (Table 1) Transthoracic echocardiography and laboratory data of our study groups are listed in Table 2. Potassium level was lower in POAF(+) group (p=0.01). Left
atrial diameter and ejection fraction were similar between groups. Multivariate Cox proportional hazards regression analysis revealed that M/H ratio (odds ratio [OR], 51.814; 95% confidence interval [CI], 11.479–233.865; p<0.01) and serum HDL level (OR,1.874; %95 CI, 1.402–2.505; p<0.01) were independent predictors of POAF in patients after ACBG surgery (Table 3). In receiver operating characteristic curve analysis of M/H ratio, area under curve was found to be 0.844.
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14.00
Table 3. Multivariate analysis of POAF risk factors
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Monocyte/HDL ratio LDL cholesterol HDL cholesterol WBC Monocyte Potassium
p
OR
95% CI
<0.01 51.814 11.479–233.865 0.117 1.010 0.998–1.022 <0.01 1.874 1.402–2.505 0.400 0.882 0.657–1.182 <0.01 0.934 0.901–0.969 0.045 0.487 0.241–0.984
Monocyte/HDL ratio
12.00 10.00 8.00 8 33
6.00 75
4.00
CI: Confidence interval; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; OR: Odds ratio; POAF: Postoperative atrial fibrillation; WBC: White blood cell.
Absent Present Postoperative atrial fibrillation
Figure 1.
Figure 1 presented the comparison of preoperative atrial fibrillation and monocyte/HDL ratio. Figure 2 presented the ROC analysis showed that the best cut-off value of monocyte/HDL raiot to predict post-operative atrial fibrillation was 8.55.
Comparison of preoperative atrial fibrillation and monocyte/HDL ratio. HDL: High-density lipoprotein.
Monocyte/HDL ratio ROC curve 1.0
0.8
In this prospective study, our aim was to examine and define correlation between M/H ratio and POAF occurrence. After ACBG surgery, patients with higher M/H ratio tended to develop POAF during hospitalization. To our knowledge, present report is the first in the literature illustrating relationship between M/H ratio and POAF in isolated ACBG patients. Pathogenesis of POAF is multifactorial and involves adrenergic activation, inflammation, atrial ischemia, electrolyte disturbances, and genetic factors [8]. Our study hypothesis originated with inflammation as pathogenesis of AF. Recent reports, including studies of atrial biopsies of patients with AF, have shown structural remodeling caused by inflammation and oxidative damage [9, 10]. Several risk factors for POAF have been identified, such as age older than 70 years, history of prior AF, male gender, left ventricular dysfunction, left atrial enlargement, diabetes, and obesity [8]. In our study, POAF(+) patients were statistically older than those in POAF(-) group. Other risk factors were found to be similar between study groups.
Sensitivity
DISCUSSION
0.6
0.4
0.2
0.0 0.0
0.2
0.4 0.6 Specifitity
0.8
1.0
Figure 2. ROC: Receiver operating characteristic. ROC Area under curve: 0.844; cut-off:8.55. Proinflammatory cytokines have been analyzed many times in connection with POAF correlation. Fontes et al. demonstrated that patients who developed POAF had greater degree of monocyte activation, which is dependent on higher CD11b expression [11]. Other proinflammatory parameters, such as neutrophil/lymphocyte ratio, have been found to be related to increased incidence of POAF [12]. In
Tekkesin et al., The use M/H ratio to predict post-op AF after aortocoronary bypass graft surgery
addition, C-reactive protein (CRP), an important indicator of inflammation in routine clinical practice, has been studied numerous times to determine correlation with POAF. Unsurprisingly, CRP was found to be statistically higher in POAF patients, which was supportive of inflammatory mechanism for occurrence of AF [13]. Interestingly, peak CRP level occurs on second or third day after operation, which is concurrent with peak incidence of POAF. Other inflammatory parameters involving interleukin (IL)-6, IL-8, IL-10, and vascular endothelial growth factor have also been demonstrated to be higher in AF patients [14]. Based on these studies, we elected to evaluate correlation of inflammatory parameter of M/H ratio to POAF, and found it to be exclusively significant. Dyslipidemia, which has been repeatedly demonstrated to be risk factor for atherosclerotic vascular disease and AF, as result of oxidative stress and inflammation, is also one of the main sources of POAF pathogenesis. Though there are conflicting studies [15], lower HDL has been considered risk factor for occurrence of AF. Lahoz-Tornos et al. examined HDL value in cardiac surgery patients and found low HDL to be predictor of AF [16]. Mechanism was considered to be secondary to anti-inflammatory and antioxidant functions of HDL. HDL executes its anti-inflammatory effects via several pathways. It inhibits adhesion of immune cells by reducing expression of activated endothelial adhesion molecules, and inhibits monocyte chemoattractant protein-1 molecule, which is chemokine for monocytes in response to LDL oxidation. In a study similar to ours, M/H ratio was used to investigate prediction of AF recurrence after successful cryoballoon-based catheter ablation. M/H was proven to be independent predictor of AF recurrence after cryoablation [17]. Like Canpolat et al., we demonstrated strong correlation between M/H ratio and POAF occurrence in isolated ACBG surgery patients. The present study had several limitations. First, it was single-center study with small sample size. Secondly, measurement of serum HDL and monocyte count at once may be insufficient to use as parameter. Thirdly, details of surgery, including on-
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pump, off-pump, and cross-clamp times, were not known and could have been independent factors in development of POAF. Finally, study population included isolated ACBG patients from short period of time. Conclusion Despite many investigations, POAF remains a serious factor for morbidity and mortality in ACBG surgery patients. M/H is a novel biomarker and shows strong correlation with POAF occurrence, based on inflammation and oxidative stress mechanisms. Increased M/H ratio will help clinicians predict POAF. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – M.I.H., A.I.T., R.Z.; Design – R.Z.; Supervision – A.T.A., C.T.; Materials – R.Z., G.C.; Data collection &/or processing – M.K., R.Z., C.T.; Analysis and/or interpretation – A.T.A., M.I.H.; Literature search – G.C., M.K.; Writing – A.I.T.; Critical review – A.T.H.
REFERENCES 1. Tsai YT, Lai CH, Loh SH, Lin CY, Lin YC, Lee CY, et al. Assessment of the Risk Factors and Outcomes for Postoperative Atrial Fibrillation Patients Undergoing Isolated Coronary Artery Bypass Grafting. Acta Cardiol Sin 2015;31:436–43. 2. Bohatch Júnior MS, Matkovski PD, Di Giovanni FJ, Fenili R, Varella EL, Dietrich A. Incidence of postoperative atrial fibrillation in patients undergoing on-pump and off-pump coronary artery bypass grafting. Rev Bras Cir Cardiovasc 2015;30:316–24. 3. Rostagno C, Blanzola C, Pinelli F, Rossi A, Carone E, Stefàno PL. Atrial fibrillation after isolated coronary surgery. Incidence, long term effects and relation with operative technique. Heart Lung Vessel 2014;6:171–9. 4. Barbieri LR, Sobral ML, Gerônimo GM, Santos GG, Sbaraíni E, Dorfman FK, et al. Incidence of stroke and acute renal failure in patients of postoperative atrial fibrillation after myocardial revascularization. Rev Bras Cir Cardiovasc 2013;28:442–8. 5. Psychari SN, Apostolou TS, Sinos L, Hamodraka E, Liakos G, Kremastinos DT. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am J Cardiol 2005;95:764–7. 6. Barter PJ, Baker PW, Rye KA. Effect of high-density lipoproteins on the expression of adhesion molecules in endothelial cells. Curr Opin Lipidol 2002;13:285–8. 7. Watanabe H, Tanabe N, Yagihara N, Watanabe T, Aizawa Y,
150 Kodama M. Association between lipid profile and risk of atrial fibrillation. Circ J 2011;75:2767–74. 8. Morady FP, Zipes D. Atrial Fibrillation: Clinical Features, Mechanisms and Management. In: Braunwald E, Bonow RO. editors. Braunwald’s heart disease : a textbook of cardiovascular medicine. 9th ed. Philadelphia: Saunders; 2012. p. 825–35. 9. Frustaci A, Chimenti C, Bellocci F, Morgante E, Russo MA, Maseri A. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997;96:1180–4. 10. Guo Y, Lip GY, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol 2012;60:2263–70. 11. Fontes ML, Mathew JP, Rinder HM, Zelterman D, Smith BR, Rinder CS; Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Atrial fibrillation after cardiac surgery/ cardiopulmonary bypass is associated with monocyte activation. Anesth Analg 2005;101:17–23. 12. Gibson PH, Cuthbertson BH, Croal BL, Rae D, El-Shafei H, Gibson G, et al. Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 2010;105:186–91.
North Clin Istanb 13. Li T, Sun ZL, Xie QY. Meta-analysis Identifies Serum C-Reactive Protein as an Indicator of Atrial Fibrillation Risk After Coronary Artery Bypass Graft. Am J Ther 2016;23:e1586–e1596. 14. Li J, Solus J, Chen Q, Rho YH, Milne G, Stein CM, et al. Role of inflammation and oxidative stress in atrial fibrillation. Heart Rhythm 2010;7:438–44. 15. Díaz-Peromingo JA, Albán-Salgado A, García-Suárez F, Sánchez-Leira J, Saborido-Froján J, Iglesias-Gallego M. Lipoprotein(a) and lipid profile in patients with atrial fibrillation. Med Sci Monit 2006;12:CR122–5. 16. Lahoz-Tornos Á, Vilchez-Aguilera JA, Hernandez-Romero D, Romero-Aniorte AI, Orenes-Piñero E, Jara-Rubio R, et al. [HDL cholesterol and high-sensitive troponin T as predictive biomarkers of atrial fibrillation after heart surgery]. Arch Cardiol Mex 2015;85:111–7. 17. Canpolat U, Aytemir K, Yorgun H, Şahiner L, Kaya EB, Çay S, et al. The role of preprocedural monocyte-to-high-density lipoprotein ratio in prediction of atrial fibrillation recurrence after cryoballoon-based catheter ablation. Europace 2015;17:1807– 15.
Orıgınal Article
PT&R
North Clin Istanb 2017;4(2):151–159 doi: 10.14744/nci.2017.61687
A comparison of the effectiveness of amitriptilin and pregabalin treatment in fibromyalgia patients Gunseli Acet,1 Arzu Kaya,2 Semra Akturk,3 Gurkan Akgol2 Department of Physical Medicine and Rehabilitation, Malatya Training and Research Hospital, Malatya, Turkey
1
Department of Physical Medicine and Rehabilitation, Firat University Faculty of Medicine, Elazig, Turkey
2
Department of Physical Medicine and Rehabilitation, Inonu Univesity Faculty of Medicine, Malatya, Turkey
3
ABSTRACT OBJECTIVE: The present study is a comparison of the effectiveness of amitriptyline and pregabalin on the symptoms of fibromyalgia patients. METHODS: A total of 71 female patients aged ≥18 years were included in this study. The patients were divided into 2 groups. Pregabalin (n=36) or amitriptyline (n=35) treatment was initiated at daily oral dose of 450 mg and 25 mg, respectively for the indicated number of patients. The patients were evaluated at the start of treatment and at the end of 12 weeks. The Fibromyalgia Impact Questionnaire, Fatigue Severity Scale, Modified Fatigue Impact Scale, Hospital Anxiety Depression Scale, Nottingham Health Profile, Mini Mental State Test, and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were administered to all study participants. Pain at all tender points was measured using a pressure algometer. RESULTS: Significant improvement was observed in both groups after 12 weeks of treatment (p<0.05). Percent change in LANSS was greater in the pregabalin group compared with the amitriptyline group. Tender point pressure pain thresholds and total myalgic score improved significantly in both groups (p<0.05); however higher percentage change in these parameters was achieved in the amitriptyline group when compared with the pregabalin group (p<0.05). CONCLUSION: Both drugs improved pain, fatigue, sleep disorder, disability, psychological evaluation, and cognitive function; however, amitriptyline was more effective at reducing experimentally measured pain than neuropathic pain. According to these results, preference for pregabalin may be recommended in fibromyalgia patients whose primary complaint is neuropathic pain. Keywords: Amitriptyline; fibromyalgia; neuropathic pain; pregabalin; pressure pain threshold.
Received: March 20, 2017 Accepted: July 04, 2017 Online: August 26, 2017 Correspondence: Dr. Semra AKTURK. Turgut Ozal Tip Merkezi, Fiziksel Tedavi ve Rehabilitasyon Klinigi 1. Kat, Malatya, Turkey. Tel: +90 422 - 341 06 60 e-mail: semrakayakturk@hotmail.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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F
ibromyalgia syndrome (FMS) is a chronic, extra-articular, rheumatic syndrome characterized by widespread musculoskeletal system pain and tender points at specific anatomical points [1]. Its prevalence ranges between 2% and 7% in the population [2]. Although trauma, infection, autoimmune, genetic, endocrinological, and emotional factors have been emphasized in the etiology of FMS, its exact etiology is still not known [3, 4]. Abnormalities in central mechanisms may explain its etiopathogenesis. Sleep disorders, psychological function, disorders in pain modulation, biochemical changes in the central nervous system, and neuroendocrinological dysfunction play roles in abnormalities of central mechanisms [5–8]. Abnormalities in the mechanisms of tryptophan, which is a serotonin precursor, are seen in these patients. As a neuropeptide, substance P is a primary nociceptive afferent modulator, and plays a role in the regulation of immune functions. In FMS patients, plasma substance P level is within normal limits; however, the level in cerebrospinal fluid was found to be 3 times higher than that of normal control subjects [9]. A pharmacological agent that completely resolves all symptoms and ensures complete well-being is not yet available for patients with fibromyalgia. Treatments are most frequently targeted at symptoms using non-standardized methods [10]. Depression medications, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin, and noradrenalin reuptake inhibitors have been demonstrated to be effective at reducing pain, depression, and fatigue in patients with fibromyalgia [11]. Tricyclic antidepressants are believed to be effective in fibromyalgia treatment by influencing the reuptake of amines, such as serotonin and epinephrine, by inducing the production of endogenous opioids, and regulating central motor activity, thereby improving symptoms of depression. Amitriptyline is an important member of this class of antidepressants. Its analgesic mechanism has not been fully explained yet; however, it has been demonstrated to have greater effectiveness in providing relief for patients with fibromyalgia than selective serotonin reuptake inhibitors, independent of its antidepressant effects. It has been proposed that the inhibition of noradrenaline
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reuptake, N-Methyl-D-aspartic acid receptor antagonism, and the blockade of muscarinic receptors and ion channels may contribute to the analgesic effect of amitriptyline [12–14]. It has been demonstrated in various studies that pregabalin is effective in the treatment of fibromyalgia [15–17]. In 2007, it was the first medicine approved by the US Food and Drug Administration for fibromyalgia treatment. It exerts its effect by binding to alpha-2 delta subunits of voltage-sensitive calcium channels and slowing the entry of calcium into neurons It does not interact with benzodiazepine or gamma-aminobutyric acid (GABA)-A and GABA-B receptors. Since it does not bind to these receptor sites, it also does not interact with other antiepileptics, antidepressants, or analgesics, and it can be used safely in drug combinations [16]. The aim of this study was to compare the effectiveness of amitriptyline, with established efficacy in patients with fibromyalgia, with that of pregabalin, the use of which in the treatment of fibromyalgia has become increasingly prevalent in recent years. MATERIALS AND METHODS The present study was approved by the Fırat University Faculty of Medicine ethics committee and was conducted in accordance with the Declaration of Helsinki. Written, informed consent was obtained from all participants. Among admissions to Fırat University Hospital Physical Medicine and Rehabilitation outpatient clinic, a total of 71 female patients aged ≥18 years (mean age: 39.2±8.96 years in the amitriptyline group and 36.5±6.68 years in the pregabalin group) having predominantly neuropathic pain pattern diagnosed as FMS based on the diagnostic criteria of the American College of Rheumatology were included in this study. Patients who had previously been operated on for lumbar herniated disc, those who had recently received physical therapy, or pregabalin or antidepressant treatment within the previous 2 months, patients with inflammatory or malignant diseases, pregnant patients, cases with severe psychological disorders or systemic disease were not enrolled in the study.
Acet et al., A comparison of the effectiveness of amitriptilin and pregabalin treatment in fibromyalgia patients
Demographic data (age, gender, marital status, socioeconomic status, type of employment, educational level, smoking/alcohol use, body mass index) of the patients were recorded. All participants underwent systemic examination and laboratory assessment of complete blood count, routine biochemical analysis, erythrocyte sedimentation rate, rheumatoid factor, C-reactive protein level, presence of Brucella, and thyroid function was performed. Body mass index was measured using Tanita BC418MA scale with Segmental Body Composition Analyzer (Tanita Corp., Tokyo, Japan). The patients were randomly divided into 2 groups. Pregabalin (n=36) or amitriptyline (n=25) therapy was initiated at daily 150 mg and slowly increased to 450 mg oral dose, and 10 mg to 25 mg, respectively, in the indicated number of patients. The patients were evaluated monthly over the course of 3-month treatment for effects using the Visual Analogue Scale (VAS) for pain, assessment of sleep quality, and side effects of the treatment. At baseline and at the conclusion of 12 weeks, clinical evaluations were performed in both groups using several measurement tools. Functional evaluation was performed with the Fibromyalgia Impact Questionnaire (FIQ), impact of fatigue on daily activities was measured with the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS), quality of life was assessed with the Nottingham Health Profile (NHP), risk for anxiety and depression was evaluated with the Hospital Anxiety Depression Scale (HADS), cognitive function was measured with the Mini Mental State Examination (MMSE), neuropathic pain was gauged using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), and a global scoring of severity of pain estimated separately by the patient and the physician using the VAS. VAS and sleep quality evaluations were performed at 4-week intervals. Pressure pain threshold (PPT) measurements were taken from tender points (18 points), and control points (3 points: midpoint of the forehead; distal one-third dorsal aspect of the dominant forearm, and nail of the thumb of the dominant hand) before and after the treatment using a manual algometry device (Force Dial model FDK 40 Push
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Pull Force Gage; Wagner Instruments, Riverside, CT, USA). Pressure was applied with 1 kg increase per second. Skin temperature was measured using Scantemp Pro 440 infrared thermometer (Cardinal Health, Inc., Dublin, OH, USA). The FIQ was administered to measure the health status of the patients. This disease-specific measure of global health status has been validated for a Turkish population with FMS [18]. The FIQ is a 10-item, self-administered test that measures physical function, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well-being. As score approaches maximum total of 100 it indicates more severe symptoms and disability. The FSS is the most frequently used questionnaire to evaluate the effect of fatigue on daily activities. Validation and reliability studies for Turkish version were performed by Armutlu et al. The scale consists of 9 statements, each of which is scored between 1 (I donâ&#x20AC;&#x2122;t agree at all), and 7 (I strongly agree). The FSS score is the average value of score for all 9 statements. A higher score reflects a more severe state of fatigue [19, 20]. The HADS is a self-assessment scale used to determine risks for, level of, and changes in severity of anxiety and depression. It comprises a total of 14 questions, 7 related to anxiety and 7 concerning depression. Health-related quality of life of the patients was evaluated with the NHP, which contains 38 items in 6 domains related to level of energy (3 items), pain (8 items), emotional reactions (9 items), sleep (5 items), physical mobility (8 items), and social isolation (5 items). Items in each domain are assigned a weight; the total score for each domain is 100; a score of 0 indicates good subjective health status, while 100 indicates poor subjective health status. Total NHP total score is obtained by averaging the 6 domain scores. The LANSS scale evaluates symptoms of neuropathic pain and responsiveness to treatment. Sensitivity and specificity in the discrimination between neuropathic and non-neuropathic pain have been evaluated in a local patient population [21]. Functions of orientation, registration, attention
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Table 1. Comparison of parameters in the amitriptyline group Parameters
Before treatment
After treatment (3 months)
p
VAS-pain 7.77±1.65 3.37±1.76 0.00 FIQ-pain 7.72±1.71 3.56±1.82 0.00 FIQ-morning fatigue 8.32±1.34 3.39±2.31 0.00 FSS 5.77±1.04 4.14±1.28 0.00 NHP-fatigue 91.86±23.68 33.55±37.92 0.00 NHP pain 66.22±26.29 24.64±15.46 0.00 FIQ-anxiety 6.15±2.54 1.25±1.79 0.00 FIQ-depression 5.81±2.68 1.29±1.66 0.00 NHP-physical activity 34.51±28.18 8.55±14.18 0.00 NHP-sleep 54.46±33.70 11.84±16.45 0.00 NHP-social isolation 26.41±37.13 7.1413±13.28 0.001 NHP-emotional reaction 10.97±19.75 2.15±3.88 0.005 HADS-depression 8.94±2.90 6.94±1.96 0.000 HADS-anxiety 10.17±2.06 8.20±1.90 0.000 FIQ: Fibromyalgia Impact Questionnaire; FSS: Fatigue Severity Scale; HADS: Hospital Anxiety and Depression Scale; NHP: Nottingham Health Profile; VAS: Visual Analogue Scale.
and calculation, recall, and language are measured with the MMSE questionnaire, which consists of 11 questions and has a total possible score of 30 points. Score <24 points indicates cognitive impairment [22–24]. Statistical analysis Statistical analyses were performed using SPSS for Windows, Version 15.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were used to summarize the distribution of patient and control group demographic characteristics. For intragroup comparisons of measurements performed at baseline and after 12 weeks of therapy, parametric Student’s t-test was used. McNemar’s test was used for intragroup comparisons of rates, and intergroup comparisons were performed using parametric Student’s ttest. For intergroup comparisons of measurements with ordinal and nominal variables, chi-square test was used. Pairwise comparisons of multiple measurements were assessed with Student’s t-test, with a limit of significance of 0.016 (0.05/number of comparisons [n=3] = 0.016). For other comparisons, limit of significance was accepted as p=0.05.
RESULTS A total of 66 patients (amitriptyline group, n=32; pregabalin group, n=34) completed the study. No significant intergroup difference was found with respect to age, body mass index, or level of formal education (p>0.05). Pre- and post-treatment measurements of VAS and MFIS physical, cognitive, and psychosocial function subscale scores were significantly different in the amitriptyline group (Group 1) (p=0.00). NHP, FIQ, and VAS scores of the patients in the amitriptyline group are provided in Table 1. A significant difference was seen in post-treatment LANSS score, or measurement of anxiety and depression parameters of the patients in Group 1 (p<0.05). No significant difference was found between pre- and post-treatment MMSE scores or sum of 3 PPT control point scores (p>0.05). In the pregabalin group, significant differences were observed in the patient self-assessment and the physician’s global evaluation (VAS) of the patient, and in the pain subscale scores of the NHP and FIQ (p<0.05). Group scores are provided in
Acet et al., A comparison of the effectiveness of amitriptilin and pregabalin treatment in fibromyalgia patients
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Table 2. Comparison of parameters in the pregabalin group Parameters
Pre-treatment
Post-treatment (3 months)
p
VAS 8.04±1.44 4.27±1.83 0.000 NHP-pain 72.70±21.14 30.20±15.85 0.000 FIQ-pain 7.91±1.65 4.50±1.80 0.000 NHP-pain 78.37±35.32 34.44±38.21 0.000 FIQ-fatigue 8.33±1.72 4.14±1.64 0.000 FIQ-morning fatigue 8.04±2.10 3.67±1.78 0.000 NHP-physical activity 38.57±25.59 16.53±20.51 0.000 NHP-sleep 33.60±35.64 10.72±18.73 0.000 NHP-social isolation 12.06±19.97 5.54±18.46 0.071 NHP-emotional reactions 5.60±11.09 2.80±9.82 0.174 HADS-depression 8.36±2.63 7.02±2.08 0.000 HADS-anxiety 9.41±1.93 7.26±1.60 0.000 FIQ-anxiety 5.94±2.94 1.67±1.95 0.000 FIQ-depression 4.91±3.076 1.60±1.74 0.000 MFIS-physical function 21.80±6.54 14.32±5.04 0.000 MFIS-cognitive function 21.91±7.85 14.73±5.66 0.000 FIQ: Fibromyalgia Impact Questionnaire; FSS: Fatigue Severity Scale; HADS: Hospital Anxiety and Depression Scale; MFIS: Modified Fatigue Impact Scale; NHP: Nottingham Health Profile; VAS: Visual Analogue Scale.
Table 3. Comparison of pretreatment and post-treatment clinical parameters between the amitriptyline and pregabalin groups
Parameters
Pre-treatment
Amitiriptyline (n=35)
Pregabalin (n=36)
p
Post-treatment
Amitiriptyline (n=32)
VAS 7.42±1.67 8.04±1.44 * 4.26±1.93 NHP-pain 66.22±26.29 72.70±21.14 * 24.64±15.46 FIQ-pain 7.72±1.71 7.91±1.65 * 3.56±1.82 MFIS-pf 21.22±6.66 21.80±6.54 * 14.62±4.46 NHP-fatigue 91.86±23.68 78.37±35.32 * 33.55±37.92 FIQ-fatigue 8.41±1.62 8.3333±1.72 * 3.9375±1.79 NHP-pa 34.51±28.18 38.57±25.59 * 8.55±14.18 HADS-depression 8.94±2.90 8.36±2.63 * 6.94±1.96 HADS-anxiety 10.17±2.06 9.41±1.93 * 8.20±1.90 MMSE 24.82±3.15 25.44±2.96 * 25.56±3.25
Pregabalin (n=34)
p
4.27±1.83 * 30.20±15.85 * 4.50±1.80 0.04 14.32±5.043 * 34.44±38.21 * 4.14±1.64 * 16.53±20.51 * 7.02±2.08 * 7.26±1.60 0.031 26.32±2.55 *
*p˃0.05. FIQ: Fibromyalgia Impact Questionnaire; FSS: Fatigue Severity Scale; HADS: Hospital Anxiety and Depression Scale; MFIS: Modified Fatigue Impact Scale; MMSE: Mini Mental State Examination; NHP: Nottingham Health Profile; pa: Physical activity; pf: Physical function; VAS: Visual Analogue Scale.
Table 2. Pre- and post-treatment LANSS neuropathic pain scale scores were significantly different
in the pregabalin group (p=0.00). A significant difference was also found in pre- and post-treatment
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Table 4. Percent change in tender point and total myalgic scores between groups Pregabalin (n=36)
P
-0.197±0.14 (-0.61–0.09) -0.160±0.13 (-0.58–0.06)
-0.098±0.12 (-0.47–0.17) -0.079±0.11 (-0.44–0.16)
0.005 0.012
DISCUSSION In the present study we observed that the effects of both pregbalin and amitriptyline were similar with respect to effectiveness on pain, fatigue, sleep disorders, disability, psychological factors, and cognitive function; however, amitriptyline was more effective at relieving experimental pain, while pregabalin was
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Pregabalin
di so rd er s Di zz in es s Dy sp ep sia
total PPT score of tender points and total myalgic score (p<0.05). A significant intergroup difference was seen in post-treatment assessments of the FIQ pain subscale, and the HADS anxiety measurement score (p<0.05). Pre- and post-treatment VAS and NHP pain subscale score was not significantly different between groups (p>0.05). Pre- and post-treatment NHP, FIQ, modified fatigue impact scale and VAS scores are presented in Table 3. No significant difference was found between pre- and post-treatment LANSS score (p>0.05), while the percent change was significantly different between groups (p<0.05); a greater degree of improvement was seen in the pregabalin group compared with the amitriptyline group. In the tender point pressure and total myalgic score percent change, however, there was a significant difference between the groups in favor of the amitriptyline group (p<0.05) (Table 4). No significant intergroup difference was found in the rate of pre- and post-treatment symptoms associated with FMS (p>0.05). The most frequently reported side effects of all patients in both groups were dizziness and sleep disorders. Dizziness was more frequently seen in the pregabalin group (Figure 1). Changes over time in side effects experienced and VAS scores can be seen in Table 5.
p
Percent change tender point score Percent change total myalgic score
Amitriptyline (n=35)
Sl ee
Parameters
10–15
15–20
Figure 1. Side effects of pregabalin and amitriptyline. more helpful for neuropathic pain. Since fibromyalgia patients describe widespread clinical manifestations, an overlap with neuropathic pain has been suggested. Hyperalgesia, allodynia, and paresthesia seen in neuropathic pain can also be observed in FMS. In almost all of these patients, impairment of central pain mechanism, neuroendocrinological abnormalities, and abnormal activation in the nociceptive domain of the brain are seen. These multiple abnormalities strongly suggest that fibromyalgia is a neuropathic pain syndrome [25, 26]. A serotonin deficiency proposed in the etiology of FMS may account for the pain and sleep disorders observed, which are important features of this syndrome [27]. Most frequently, antidepressants are used in the treatment of fibromyalgia, and among them the tricyclic antidepressant amitriptyline is most often administered. Generally, the analgesic effects of tricyclic antidepressants are accepted to be an acute effect independent of antidepressant effects, and only require a low dose [28]. Gabapentin, which is an anticonvulsant also used to treat neuropathic pain, was compared with amitriptyline, and both drugs were found to be ef-
Acet et al., A comparison of the effectiveness of amitriptilin and pregabalin treatment in fibromyalgia patients
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Table 5. Assessment of side effects and VAS (pain and sleep) changes in the groups at first, second, and third month Parameters
First month
Second month
Third month
Amitiriptyline Pregabalin Amitiriptyline Pregabalin Amitiriptyline Pregabalin % % % % % %
Sleep disorders 17.1 5.6 15.2 2.7 8.3 2.7 Dizziness 5.7 16.7 5.7 13.8 2.8 6.2 Dyspepsia 0 2.8 0 2.8 0 2.8 Cardiac disorders 0 0 2.8 0 2.8 0 Sleep+cardiac disorders 5.7 0 5.7 0 5.7 0 Dizziness+dyspepsia+sleep disorders 0 5.6 0 5.6 0 5.6 Pregabalin VAS (pain) Pregabalin VAS (sleep) Amitiriptyline VAS (pain) Amitiriptyline VAS (sleep)
p
p
p
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
VAS: Visual Analogue Scale.
fective in pain management. Gabapentin was found to be more effective on paroxysmal stabbing pain [29]. The effect of pregabalin on chronic pain syndromes has been reported to be comparable to that of gabapentin [14]. A study of 529 patients with fibromyalgia investigated the effect of pregabalin on pain, fatigue, and quality of life. Daily dose of 150 mg, 300 mg, and 450 mg pregabalin was compared with a placebo, and at the end of 8 weeks of treatment, a decrease in all painful sensations was reported in all of the pregbalin groups. It was reported that in patients using daily dose of 450 mg pregabalin, painful sensations decreased more dramatically compared with the other groups, and at daily dose of 300 mg and 450 mg, sleep quality and fatigue improved markedly relative to the placebo group [16]. In our study, in both the pregabalin and amitriptyline groups, considerable improvement was seen in parameters of pain; however, the percent of change, which indicated decrease in the severity of pain, did not differ significantly between groups. The present study included patients with prominent neuropathic complaints. The LANSS was used to evaluate
neuropathic pain pattern. LANSS scores improved significantly in both the amitriptyline and pregabalin group, yet intergroup comparisons revealed greater improvement in the pregabalin group. Morning fatigue is found in 75% to 80% of patients with fibromyalgia [30â&#x20AC;&#x201C;32], though severity varies. A similar percentage of patients complains of poor sleep or sleep disorders [33]. Antidepressants demonstrate important effects on sleep quality and the fatigue seen in FMS [1]. An important difference in the NHP sleep subscale scores was observed with respect to restless sleep in both amitriptyline and pregabalin users. Neither treatment was superior in terms of improvement in sleep problems or morning fatigue. In another study performed to investigate the effect of pregabalin on anxiety disorders, effectiveness in the short term was demonstrated relative to placebo. Pregabalin was also found to be more effective in patients who partially responded to atypical antipsychotic drug quetiapine [34]. In our study, we observed comparable, favorable effects for both pregabalin and amitriptyline on anxiety and depression in patients with fibromyalgia.
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The most important side effects of pregabalin are somnolence and dizziness. They are typically observed within the first 1 to 2 weeks of starting the drug therapy, and are more marked among the elderly [17, 35]. Among the most frequently seen side effects of tricyclic antidepressants are anticholinergic effects, such as dry mouth and constipation, and postural hypotension, sedation, and weight gain [36]. In our study, consistent with literature findings, the most frequently seen side effects of pregabalin users were dizziness (8.5%) and sleep disorders (2.8%); however, none of the patients discontinued the treatment due to these side effects. In the amitriptyline group, the most frequent side effects were sleep disorders (8.5%) and dizziness (2.8%). Dizziness was more common in the pregabalin group than the amitriptyline group. Generally, tolerance developed in 2 to 3 weeks, and these complaints decreased at control visits. In our study, PPTs and skin temperature were measured at all fibromyalgia control and tender points using an algometer and an infrared thermometer, respectively. In both the amitriptyline and pregabalin groups, control point scores did not change after treatment relative to baseline, while tender point and total myalgia scores improved in both groups. Tender point PPTs, which are considered a laboratory (experimental) assessment of pain, decreased more dramatically in the amitriptyline group after the treatment. The main limitation of this study is the small number of participants and the inability to prolong the follow-up period due to strict exclusion criteria of the study. In conclusion, based on the data we gathered in this study, we can say that neither drug is superior in terms of effectiveness on systemic symptoms of myalgia. However, we can state that amitriptyline is more effective in decreasing experimental pain, whereas pregabalin is more effective in relieving neuropathic complaints. Accordingly, a preference for pregabalin may be recommended for FMS patients primarily complaining of neuropathic pain. Conflict of Interest: None declared.
North Clin Istanb Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – G.Acet, A.K. Data collection &/or processing – G.A; Analysis and/or interpretation – G.Acet; Writing – S.A.
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15. White KP, Harth M. Classification, epidemiology, and natural history of fibromyalgia. Curr Pain Headache Rep 2001;5:320– 9. 16. Crofford LJ, Rowbotham MC, Mease PJ, Russell IJ, Dworkin RH, Corbin AE, et al; Pregabalin 1008-105 Study Group. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005;52:1264–73. 17. Calandre EP, Morillas-Arques P, Rodriguez-Lopez CM, RicoVillademoros F, Hidalgo J. Pregabalin augmentation of quetiapine therapy in the treatment of fibromyalgia: an open-label, prospective trial. Pharmacopsychiatry 2007;40:68–71. 18. Sarmer S, Ergin S, Yavuzer G. The validity and reliability of the Turkish version of the Fibromyalgia Impact Questionnaire. Rheumatol Int 2000;20:9–12. 19. Mancuso CA, Rincon M, Sayles W, Paget SA. Psychosocial variables and fatigue: a longitudinal study comparing individuals with rheumatoid arthritis and healthy controls. J Rheumatol 2006;33:1496–502. 20. Anton HA, Miller WC, Townson AF. Measuring fatigue in persons with spinal cord injury. Arch Phys Med Rehabil 2008;89:538–42. 21. Yucel A, Senocak M, Kocasoy Orhan E, Cimen A, Ertas M. Results of the Leeds assessment of neuropathic symptoms and signs pain scale in Turkey: a validation study. J Pain 2004;5:427–32. 22. Çapacı K, Hepgüler S. Fibromyalgia Syndrome: Diagnosis and Treatment. Ege J of Physical Med and Reh 1999;5:73–82. 23. Crofford LJ. The relationship of fibromyalgia to neuropathic pain syndromes. J Rheumatol Suppl 2005;75:41–5. 24. Arnold LM, Goldenberg DL, Stanford SB, Lalonde JK, Sandhu HS, Keck PE Jr, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum 2007;56:1336–44. 25. Staud R, Domingo M. Evidence for abnormal pain processing in fibromyalgia syndrome. Pain Med 2001;2:208–15. 26. Martínez-Lavin M, López S, Medina M, Nava A. Use of the
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Orıgınal Article
CHILD HEALTH&DISEASES
North Clin Istanb 2017;4(2):160–164 doi: 10.14744/nci.2017.07279
Investigation of celiac disease followed by immune thrombocytopenic purpura diagnosis in patients and comparison with literature Hakan Sarbay,1 Halil Kocamaz,2 Mehmet Akin,1 Bayram Ozhan3 Department of Pediatric Hematology and Oncology, Pamukkale University Faculty of Medicine, Denizli, Turkey
1
Department of Pediatric Gastroenterology, Pamukkale University Faculty of Medicine, Denizli, Turkey
2
Department of Pediatric Endocrinology, Pamukkale University Faculty of Medicine, Denizli, Turkey
3
ABSTRACT OBJECTIVE: Celiac disease (CD) and Immune thrombocytopenic purpura (ITP) may occur together as a result of similar autoimmune mechanisms. The aim of this study was to assess the frequency of CD in a group of ITP patients and in the literature. METHODS: A total of 29 patients in Pamukkale University Faculty of Medicine Hospital Pediatric Hematology and Oncology Department with ITP were included in the study. Test was performed for the antibodies related to CD. Positive result for celiac antibodies was confirmed with biopsy. The results were compared with the literature. RESULTS: Of the study group, 13 patients (44.8%) were female and 16 (55.2%) were male. The mean age was 7.2±4.7 years and mean platelet count at the time of admission was 13,440±11,110/mm3 (range: 2000-41,000/ mm3). Twelve patients (41.4%) were diagnosed as acute ITP, 6 patients (20.7%) as persistent ITP, and 11 patients (37.9%) as chronic ITP, according to the duration of thrombocytopenia. Antibody positivity was detected in 1 patient. Histological evaluation was compatible with CD. Results were compared with studies regarding the prevalence of CD in the population. No significant difference was found. CONCLUSION: Although it is not necessary to perform CD test in every case of ITP, the presence of differential diagnosis of CD is important to prevent unnecessary treatment, especially in ITP patients with growth retardation or malabsorption findings. Keywords: Autoimmunity; celiac disease; immune thrombocytopenic purpura.
I
mmune thrombocytopenic purpura (ITP) is the most frequent cause of sudden onset thrombocytopenia in healthy children. In children, it usually emerges after an infection or a vaccination. It is an
acquired disease, coursing with thrombocytopenia developing as an outcome of a decrease in the lifespan of platelets caused by autoantibodies formed against platelets [1, 2].
Received: January 13, 2017 Accepted: April 19, 2017 Online: August 26, 2017 Correspondence: Dr. Hakan SARBAY. Pamukkale Universitesi Tip Fakultesi, Cocuk Hematoloji ve Onkoloji Bilim Dali, Denizli, Turkey. Tel: +90 258 - 296 60 00 e-mail: drhakansarbay@hotmail.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
Sarbay et al., Investigation of celiac disease in patients with ITP
Celiac disease (CD) is an immunological disease induced by intolerance of the small bowel to gluten. Growth retardation and chronic diarrhea are the most frequently seen manifestations [3]. In addition to the typical findings of malabsorption, many autoimmunological disorders may accompany the disease, or there may be extraintestinal findings, such as growth retardation, developmental delay, impaired hepatic function, skin manifestations, osteoporosis, or hematological disorders [4, 5]. As a result of having similar autoimmune mechanisms, in some publications, CD has been reported as a risk factor for ITP [6]. The aim of this article was to evaluate the frequency of CD in a group of patients and compare the results with literature data. MATERIALS AND METHODS A total of 29 patients with a diagnosis of ITP whose follow-up and treatment were ongoing at the Department of Pediatric Hematology and Oncology of the Pamukkale University Faculty of Medicine were included in the study. CD manifestations, and anti-endomysial antibody (EMA), tissue transglutaminase antibody (tTG), and immunoglobulin A (IgA) levels were evaluated. Age, gender, platelet count at the time of admission, and duration of thrombocytopenia were recorded. Based on the duration of the disease, thrombocytopenia was classified as acute (<3 months), persistent (3–12 months), or chronic (>12 months) thrombocytopenia. EMA and tTG positivity was confirmed with endoscopic examination and histological analyses. The results were compared with literature data. The study was approved by the ethics committee of Pamukkale University (2017/01–10.01.17). Written, informed consent was obtained from the parents of all patients. Statistical analyses All descriptive statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA). Fisher chisquare test was used for the comparison of categorical variables.
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RESULTS Thirteen female (44.8%) and 16 male (55.2%) patients with a collective mean age of 7.2±4.7 years (range: 7 months-17 years) were included in the study. Mean platelet count at admission was 13,440±11,110/mm3 (range: 2000– 41,000 mm3). The type of ITP was classified based on the duration of thrombocytopenia as acute (n=12; 41.4%), persistent (n=6; 20.7%), or chronic (n=11; 37.9%). Clinical and laboratory characteristics of the patients are provided in Table 1. Examination for the presence of CD revealed tTG IgA: 24.1 U/mL (<20 U/mL) and EMA positivity in 1 patient, a 9-year-old female with weight of 22 kg (3–10 percentile) and height of 118 cm (<3 percentile). Some notable laboratory parameters were as follows: white blood cell count: 6360/mm3, hemoglobin: 11.4 g/dL, platelet count: 28,000/mm3, aspartate aminotransferase: 174 IU/L, alanine aminotransferase: 193 IU/L, lactate dehydrogenase: 914 U/L, ferritin: 42 ng/ mL, iron: 38 ug/dL, total iron binding capacity: 300 ug/dL, vitamin B12: 284 pg/mL, folate: 9.9 ng/mL, prothrombin time: 12.1 seconds, partial thromboplastin time: 28 seconds, international normalized ratio: 1.08, free thyroxine: 1.39 ng/dL, and thyroid stimulating hormone: 3.21 uIU/mL. In addition to thrombocytopenia, the patient had impaired liver function and growth retardation. On peripheral smear, no atypical cells or blast cells were seen, and an average of 2 platelets were noted in every microscopic field of view. Histopathological examination of bone marrow aspiration biopsy specimen revealed an increase in the number of immature-mature megakaryocytes without any blast cells. The patient underwent endoscopic biopsy with the initial diagnosis of CD, and histopathological analysis revealed the presence of severe mucosal injury, villous atrophy, increase in the number of intraepithelial lymphocytes, and cryptic hyperplasia (Figure 1). Histopathological diagnosis was reported as consistent with Stage 3c CD based on modified Marsh classification. No treatment was administered due to the lack of
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North Clin Istanb
Table 1. Characteristic features of the study participants Patient Gender Age no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Female Female Female Female Male Male Male Male Male Female Male Male Male Male Male Female Female Female Male Female Female Female Female Male Female Male Male Male Male
9 years 15 years 8 years 9 years 4 years 7 months 2 years 4 years 10 years 6 years 16 years 3 years 4 years 10 years 1 year 15 years 9 years 5 years 3 years 8 months 6 years 9 years 10 years 17 years 7 years 3 years 4 years 8 years 12 years
Platelet count Duration of tTG Ig A level Ig A level 3 (/mm ) thrombocytopenia (U/mL) (mg/dL) 28,000 11,000 31,000 7000 1000 16,000 24,000 25,000 20,000 21,000 2000 3000 9000 15,000 11,000 2000 9000 3000 4000 41,000 2000 29,000 15,000 29,000 4000 15,000 1000 2000 10,000
5 months 1 month 17 months 2 months 1 month 6 months 1 month 1 month 6 months 1 month 18 months 1 month 8 months 3 years 1 year 1 month 2 years 1 month 4 years 18 months 6 months 6 months 1 month 5 years 2 years 1 month 2 months 4 years 18 months
24.2 2.94 5.2 1.19 0.99 0.96 0.45 1.66 0.74 0.65 0.89 1.13 3.1 1.69 0.89 2.06 1.04 2.1 1.72 3.2 1.39 1.55 4.44 3.12 4.97 2.17 3 1.39 1.2
420 48 301 74 38 36 42 44 90 106 148 149 47 253 86 71 105 162 67 72 168 80 142 99 93 33 138 217 113
Type
Persistent Acute Chronic Acute Acute Persistent Acute Acute Persistent Acute Chronic Acute Persistent Chronic Chronic Acute Chronic Acute Chronic Chronic Persistent Persistent Acute Chronic Chronic Acute Acute Chronic Chronic
Ig A: Immunoglobulin A; tTG: tissue transglutaminase.
any finding of active bleeding and platelet count greater than 10,000/mm3. The patient was started on a gluten-free diet. One month later, platelet count had risen to 87,000/mm3. At fifth month of dietary therapy, platelet count of the patient was within normal limits. In our study, the frequency of CD observed in our ITP patients was not significantly different from the results of previously performed studies related to the incidence of CD (Table 2).
DISCUSSION In cases of CD, generally, the clinical findings become manifest due to intestinal mucosa injury and resultant malabsorption [7]. As a result of deficient intestinal absorption, and as an autoimmune disease, various hematological symptoms can be seen in CD. Treatment-resistant iron deficiency is the most frequently seen hematological disorder seen in atypical CD [7, 8]. In addition to iron deficiency,
Sarbay et al., Investigation of celiac disease in patients with ITP
Figure 1. Histopathological examination of the biopsy material of the patients revealed villous atrophy, increase in the intraepithelial number of lymphocytes, and cryptic hyperplasia. folic acid, and vitamin B12 deficiencies may be also seen [7]. In a study performed in our country, 21 of 22 patients diagnosed as CD, iron deficiency anemia was detected. Among them, 7 also had vitamin B12 deficiency, and folic acid deficiency was observed in 1 patient [9]. In CD, apart from anemia, leukopenia and thrombocytopenia may develop due to vitamin B12 and folic acid deficiencies, and immune cytopenias, such as ITP, can develop via different autoimmune mechanisms [8]. Concomitancy between CD and ITP was first described in 1988, and studies performed have demonstrated the presence of similar autoimmune
163
mechanisms in the pathogenesis of both diseases [10]. It has been determined that the native immune system is important in the pathogenesis of CD, and that toll-like receptors (TLRs) also play a key role [11]. Zanoni et al. [12] demonstrated that in some cases of CD, tTG antibodies induce TLR4 activation. Presumably, TLR4 expression in platelets leads to thrombocytopenia [13]. CD is a frequently seen disease in the community; however, diagnosis can be overlooked due to its multivariant symptoms [14]. In a study performed in our country that screened 20,190 children, CD prevalence was detected at 0.47% [15]. Demirçeken et al. performed a study of tTG antibodies among healthy children aged 2 to 18 years who presented at the hospital, and found a prevalence of CD of 1% [16]. In another study performed in Turkey, CD was detected in 11 of 1263 children [17]. Cilleruelo et al. [18] evaluated 1291 newborns, and antibody positivity was found in 19 cases; 15 were diagnosed as CD based on histopathological evaluation of biopsy specimen. Prevalence of CD was found to be 1.1%. As an outcome of our study, among 29 ITP patients, antibody positivity and histopathological diagnosis of CD was detected in 1 patient. A significant difference was not found when our results were compared with literature data. In cases of ITP associated with CD cited in the literature, an increase in platelet count to normal limit within an average of 1 year was observed with gluten-free diet and without the need for intravenous immunoglobulin or steroid treatment [19].
Table 1. Comparison of our results with results of other studies
Number of patients with CD
Number of patients without CD
Total number of patients
Frequency %
1 95 10 11 15
28 20,095 990 1252 1276
29 20,190 1000 1263 1291
3.4 0.5 1 0.8 1.1
Present study Dalgıç et al. Demirçeken et al. Ertekin et al. Cilleruelo et al. p<0.05 significant; CD: Celiac disease.
p
p=0.129 p=0.271 p=0.239 p=0.301
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In our patient, platelet count 1 month after initiation of gluten-free diet was 87,000/mm3, and at 5 months, value was normal. In conclusion, ITP is one of the atypical findings of CD that may accompany CD due to a similar autoimmunme mechanism. Although investigation for CD is not required in every case diagnosed as ITP, in ITP patients with developmental retardation or malabsorption, considering CD in the differential diagnosis is important so as to prevent unnecessary treatment. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – H.S.; Design – H.S.; Supervision – H.S., H.K., M.A., B.O.; Materials – H.S.; Data collection &/or processing – H.S.; Analysis and/or interpretation – H.S.; Literature search – H.S.; Writing – H.S.; Critical review – H.S., H.K., M.A., B.O.
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Orıgınal Article
NURSING SERVICES
North Clin Istanb 2017;4(2):165–172 doi: 10.14744/nci.2017.41275
Determination of health workers’ level of knowledge about blood transfusion Aysegul Beyazpinar Kavaklioglu,1 Selma Dagci,2 Besey Oren3 Department of Research and Development, Balikesir Public Hospitals Association, Balikesir, Turkey
1
Department of Gastroenterology, Umraniye Training and Research Hospital, Istanbul, Turkey
2
Department of Midwifery, University of Health Sciences Faculty of Health Sciences, Istanbul, Turkey
3
ABSTRACT OBJECTIVE: This study was conducted to determine the knowledge level of healthcare workers about blood transfusion. METHODS: The study was conducted between October 1, 2015 and November 2, 2015 with 100 healthcare personnel working in a training and research hospital. A survey consisting of 19 questions based on the literature was prepared and administered. In addition to descriptive statistical methods (frequency), Fisher’s exact chi-square test and Yates’ correction for continuity were used to compare qualitative data. Significance was assessed at p<0.05. RESULTS: Of the total, 52% of the participants were ≤29 years of age and 94% were women. In all, 71% were nurses and 42% had been working at the hospital for 2 to 5 years. Seventy-nine percent indicated that they had been trained in blood and blood product transfusion, 86% stated that transfusions were performed to replace deficient blood volume, and 95% responded that blood was to be requested by a physician, and 97% indicated that informed consent of the patient should be obtained for a blood transfusion. In all, 78% of respondents identified crossmatching as the final check for ABO compatibility. With respect to blood unit quality, 90% of the respondents stated that they would return blood if the label could not be read and 98% would reject the product if the integrity of the blood bag was compromised or of the blood had a cloudy or foamy appearance. In the event of a patient experiencing fever and shock, 96% of the survey participants indicated that they would consider that it could be a reaction to a blood transfusion. The need to confirm the patient’s identity and the type of blood products was corroborated by 91%, and 85% agreed that no other medication should be added to the blood to be transfused. Furthermore, 88% of the study participants approved of continuous training regarding the transfusion of blood and blood products. CONCLUSION: According to the results of this research, while the knowledge of the healthcare professionals surveyed was adequate, standardization was lacking. In this respect, it may be advisable to conduct further studies on blood transfusion practices, and to provide additional in-service training to ensure patient safety and avoid medical errors. Keywords: Blood; education; health worker; nurse; transfusion.
Received: January 31, 2017 Accepted: June 22, 2017 Online: August 26, 2017 Correspondence: Selma DAGCI. Saglik Bilimleri Universitesi, Umraniye Egitim ve Arastirma Hastanesi, Istanbul, Turkey. Tel: +90 216 - 632 18 18 e-mail: selma.dagci@gmail.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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lood transfusion is an essential component of modern medical care [1, 2]. It has been reported that every year, 80 million units of blood are collected, and that a blood transfusion is performed every second [2]. According to 2006 government data 1,137,000 units of blood were transfused in Turkey in 1 year [3]. The objectives of healthcare services are the protection of and improvement in the health of the individual and the community, to treat the sick, and to do what is possible to provide for a healthy life. Healthcare professionals responsible for providing services should approach patients bearing in mind the principle of “First, do no harm.” Errors that occur in the provision of healthcare may directly result in the death or the deterioration of the health of a patient [4]. Mistakes can be avoided through good practices. Patient safety is a critically important issue in improving the quality of healthcare services [5]. Important errors that adversely affect patient safety include inadequate identity confirmation, lack of effective communication with the patient, prescription errors, nosocomial infections, premature termination of the patient’s treatment, patient falls, development of pressure sores, not evaluating risk factors, and surgery performed on the wrong side [6]. Inappropriate behavior of healthcare providers, lack of professional proficiency, and negligence while performing their duties may have an adverse effect on the patient [6]. While healthcare services benefit society, there is also risk in the complex merging of processes related to providing healthcare services, technological developments, and human factors [7, 8]. Blood transfusion and nursing care When performing a blood transfusion, nurses must pay attention to 4 basic elements: appropriate blood, correct patient, proper procedure, and right timing [9]. Nurses assume various roles and responsibilities in all stages of the process of a blood transfusion. It is important for the nurse to closely observe the
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Table 1. Distribution of sociodemographic characteristics of the respondents Age ≤29 years 30–39 years 40–49 years Gender Female Male Profession Nurse Midwife Medical assistant Emergency medical technician Length of time working at the hospital 0–1 year 2–5 years 6–10 years 11–20 years ≥21 years
n
%
52 35 13
52 35 13
94 6
94 6
71 27 1 1
71 27 1 1
8 42 19 21 10
8 42 19 21 10
patient for any complications that may develop. Vital signs must be checked before, during, and after any transfusion at appropriate intervals. The early determination of a complication developing during transfusion and prompt initiation of treatment are important safety considerations [10]. Blood and blood products are used to improve the clinical status of many patients and to save lives [11, 12]. Human errors that disrupt the proper execution of blood transfusions largely occur as a result of failure to comply with the relevant blood transfusion procedures [13]. These errors are mostly preventable. Mistakes related to blood transfusions may occur both within and outside of the blood bank. The present study was conceived and planned due to the serious need for additional research concerning the knowledge level of healthcare workers related to blood transfusion. MATERIALS AND METHODS The study population consisted of 100 individu-
Beyazpinar Kavaklioglu et al., Determination of health workers’ level of knowledge about blood transfusion
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Table 2. Distribution of responses to questions concerning blood transfusion
n
Previously received training on blood transfusion Yes No Who requests a blood transfusion? Physician Nurse Is informed consent of the patient obtained for blood transfusion? Yes No When do you attach the patient ID crossmatch barcode? At the time of transfusion When the blood bag is transported from the service I don’t attach, I don’t know Tubes with ID barcode labels on them are kept ready until the time of transfusion When is a blood product rejected? Cloudy, foamy appearance of the blood Blood bag integrity is compromised Inappropriate blood storage conditions in the unit Label information is illegible None of the above No response If you encounter a problem with a blood product before performing a transfusion, who do you inform first? Blood center The physician in charge Charge nurse Director of health services
als who were working at a training and research hospital located on the Anatolian side of Istanbul. The necessary permission was obtained from the institution where the research was performed before the investigation was initiated. Study data were collected between January 10, 2015 and February 11, 2015 in face-to-face interviews. A survey consisting of 19 questions, prepared according to literature information was used to collect the relevant data. Descriptive statistical methods (frequencies) were used to present study data, and qualitative data were compared using Fisher’s exact chi-square test with Yates’ correction for continuity. Statistical significance was set at p<0.05.
%
79 79 21 21 95 5
95 5
97 97 3 3 75 1 4 20
75 1 4 20
90 98 86 98 3 2
90 98 86 98 3 2
39 56 2 1
39 56 2 1
RESULTS Of the study population, 52 patients (52%) were aged ≤29 years, 94 (94%) were female, 71 (71%) were nurses, and 42 (42%) participants had been working at the hospital for 2 to 5 years (Table 1). The survey results indicated that 79 (79%) participants had received training about the transfusion of blood and blood products, 86% (n=86) of respondents indicated that transfusions were performed to replace deficient blood volume, 95% (n=95) of participants replied that blood and blood products were to be requested by a physician, and 97% (n=97) of the participants agreed with the need to obtain the informed consent of patients for trans-
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Table 3. Distribution of responses to additional questions concerning blood transfusion Symptoms suggesting blood transfusion reaction
n
%
Rash Fever Burning or tingling sensation along IV route Dark-colored urine Sudden fluctuation in blood pressure Shock Agitation Bleeding None of the above Do you think there is a need for training about the transfusion of blood and blood products? Yes No
84 84 96 96 50 50 20 20 84 84 96 96 31 31 15 15 – –
88 88 12 12
fusion. Seventy-eight (78%) participants described crossmatching test as the final step to ensure ABO compatibility (Table 2). Ninety-eight percent of the participants indicated that they would return blood if the integrity of the blood bag was compromised or if the label was illegible, and 90 (90%) participants indicated that they would also decline donated blood with a cloudy or foamy appearance. Furthermore, 96 (96%) participants stated that they would consider reaction to blood transfusion in the event of development of fever or shock in the patient. Of the 100 participants, 91 affirmed necessity to confirming patient identity using hospital ID bracelet and the blood product, and 85 (85%) respondents rejected the addition of any drug to the blood. Eighty-eight (88%) participants agreed with the necessity for continuous training on blood and blood products (Table 3). No statistically significant difference was found in the distribution of responses to the questions between those who received or did not receive training on blood transfusions (p>0.05). DISCUSSION Blood transfusion is a complex, multidisciplinary, and multi-stage process. Since any erroneous or in-
complete step may lead to a fatal clinical outcome, every step must be performed according to procedural guidelines. Verifications before transfusion are very important to minimize risk and avoid error. The most frequent cause of hemolytic transfusion reaction is misidentification of either the blood unit to be transfused or the recipient. Among the required steps for safe transfusion, accurate identification of the patient and the blood sample are of crucial significance. Matching the identity bracelet of the patient and the ID barcode of the blood or blood product is essential. Hijji et al. performed a study with 49 nurses and reported that 29% of the nurses confirmed ABO compatibility of blood bag and ID bracelet, while 4% checked the patient ID bracelet, blood bag, blood request form, and the information recorded in the patient observation form [14]. Gurkan et al. indicated in their study that the expiration date of blood and blood products was checked, while Bayraktar et al. found lack of relevant control. Sahin et al. also concluded that there was insufficient knowledge about crossmatching of blood and blood products [15, 16]. Siegenthaler et al. reported transfusion reaction due to lack of inspection of the expiration date [17]. Seventy-six percent of the healthcare professionals who participated in our study agreed that pre-transfusion procedure should consist of 2 healthcare professionals confirming and recording the identity of the patient, type of blood or blood product, serial number, quantity of blood product to be transfused, duration of the transfusion, expiration date, blood group, serological crossmatch, and physician’s request form and instructions before transfusion. Our study results also indicated that most healthcare professionals confirmed ABO compatibility by comparing the personal identifying information of the patient with that on the label on the blood product. Before initiating a blood transfusion, in order to avoid any error and to ensure ABO compatibility, the expiration date of the blood product, the results of crossmatching, and tests for diseases as AIDS and hepatitis B, the patient’s file number, and physician’s instructions should be examined. Since hemolytic reaction developing as a result of inadequate observance of pre-transfusion safeguards constitutes the
Beyazpinar Kavaklioglu et al., Determination of health workers’ level of knowledge about blood transfusion
most important cause of transfusion-related deaths, attention to these measures has the utmost importance [15, 18]. Early recognition of complications occurring during or as a result of a blood transfusion requires the close observance of the nurse before, during, and after the transfusion. In the study conducted by Lahlimi et al., it was reported that of 42 nurses, 40% had incomplete information about potential post-transfusion reactions [19]. Blood transfusion reactions are classified as acute or delayed reaction [15, 18]. Blood transfusions are an important cause of morbidity and mortality. Therefore, it is very important that nurses can recognize a blood transfusion reaction and know the measures to be taken in response [15, 18]. Though each blood reaction manifests differently, they have some common symptoms. Most frequently seen manifestations include a fever, chills, shivering, nausea and vomiting, tachycardia, dyspnea, cyanosis, low back pain, chest pain, urticaria, erythema, a burning sensation along the transfused vein, headache, dizziness, hypotension, and hematuria [15, 18]. In our survey, in response to the question, “What symptoms suggest a blood transfusion reaction?” 55% of the participating healthcare workers selected lower back/chest pain, 84% said rash, 96% indicated presence of a fever, and 84% noted sudden fluctuation in blood pressure. Importantly, this result demonstrates that more than 50% of our participants knew the most frequently encountered complications of a blood transfusion. A study performed by Sazama et al. stated that a nurse’s lack of attention to manifestations of patient reaction and continuation of administration of a blood transfusion led to the death of a patient [20]. Encouragingly, the staff participating in our study knew of nearly all (96%) of these manifestations. Bayraktar et al. found that fever and shivering were the most frequently known symptoms of blood transfusion reaction among nurses [15]. This result is consistent with that of our study. Monitoring vital signs and symptoms during the pre-transfusion period facilitates the determination
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of any transfusion reaction. In a study performed by Faukaneli et al., it was indicated that the risk of overlooking a transfusion reaction exists in 10% of patients due to failure to record patient vital signs and symptoms during the pre-transfusion period [21]. The patient should be observed directly for the first 15 minutes after the initiation of a blood transfusion and checked thereafter at intervals (every 15 minutes). In their study, Taylor et al. reported that vital signs and symptoms of patients were observed in 88% of cases [22]. The Hijji et al. study of 49 nurses reported that 35% observed their patients at bedside for the first 15 minutes of the transfusion. A smaller percentage of the nurses monitored pulse rate (35%) and body temperature (32%) of their patients throughout the first 15 minutes of the blood transfusion [23]. In our study, in the category of “What information about transfusion is true?” a multiple choice question, “At what time points is the transfusion patient to be checked on?” (before beginning transfusion, at 30 minutes, at every hour during transfusion, at termination of the transfusion, 4 hours after termination of the transfusion) was responded to correctly by 45% of the participants. This suggests that there is a lack of compliance with blood transfusion follow-up directions at the training and research hospital where this investigation was conducted. A blood bag must be without any hole or leak, and should not contain hemolyzed blood or coagulum. In a study entitled “Improving the process of blood transfusion at a public hospital in the Turkish Republic of Northern Cyprus” by Erkoc et al., the authors reported that after providing transfusion nurses with pocket-sized information about the implementation of transfusion, the majority of nurses checked for the presence of hemolysis (90.4%) and clotting (90.9%) in plasma, and holes or leaks in blood bags (91.8%) [24]. Bayraktar et al. also found that nurses did not verify the safety of blood bags. In our survey, participants responded to the multiple choice question of “When should blood or a blood product be rejected?” as follows: when the blood has a cloudy or foamy appearance (90%), when the integrity of the
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blood bag is compromised (90%), when the label information on the blood bag cannot be read (98%), and when blood storage conditions are not safe (86%). The majority of survey participants (93%) knew the conditions under which a blood product should be returned. The flow rate of a unit of transfused blood should be adjusted to the duration of the transfusion (maximum 4 hours). If a transfusion were to last more than 4 hours, bacteria can grow in blood secondary to increased room and blood temperature. Prolonged transfusion may also lead to the development of hemolysis [15, 18]. A question on this topic was answered correctly by 32% of the nurses in the study of Bayraktar et al. and 61.6% of the nurses in a study conducted by Benli et al. [15, 18]. In our study, 90% of the participants responded to the question, “For how long may a transfusion be given?” by choosing the answer “whole blood and erythrocyte suspension are to be delivered within 4 hours.” This was consistent with the result of the Benli study. In the literature, it has been stated that the first step in the prevention of the improper implementation of transfusion is to draw blood from the right patient and to ensure correct labeling [25]. At least 2 identifiers are recommended for the proper identification of the patient; these should not include the patient’s room number or bed number [26]. There is no study from Turkey in the literature reporting taking a blood sample for pre-transfusion testing from the wrong patient as a result of misidentification of the patient; however, this may be a result of inadequate reporting of errors. Many relevant studies from other countries have been shared [25]. In a study performed by Chiaroni, et al., the authors indicated that in some cases, patients were not correctly identified because of similarities in name, surname, birth date, etc. In another study, inability to correctly identify name, surname, birth date, and gender of a patient led to a blood sample being drawn from the wrong patient [27]. Lumadue et al. found cases of mislabeling of samples as a result of the incorrect name, surname, or hospital ID number assigned to the patient.
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Lundy et al. determined that blood tubes had been sent to the laboratory without personal identifying information on the label in 17% of cases studied. Personal ID information should be written on the label of the blood tube to be used when blood is drawn in order to eliminate the possibility of an empty tube being used for the sample of another patient or the ID label of another patient being mistakenly affixed to the tube [28, 29]. A total of 75 healthcare professionals participating in our study responded to the question “When do you put the barcode for crossmatching on the tube?” with the response “at the time blood sample is taken.” Putting a label with the patient information barcode on the tube at the time of blood collection will prevent cases of misidentification and help to ensure patient safety [28, 29]. In various studies it has been established that nurses did not know enough about complications that may occur in a blood transfusion or the signs of potential complication [18, 30], and did not monitor patients [15, 16], yet they knew to terminate blood transfusion promptly in the event complications did arise [18, 30] and did so [16]. There are studies from abroad in the literature that report mortality and serious morbidity as an outcome of improper blood transfusion [19]. Studies performed in Turkey have indicated that the attending physician was informed about the development of complications related to blood transfusion [15, 16]. In the present study, it was also observed that the respondents knew to terminate a transfusion when complications developed. Nearly all (99%) of the participants replied to a multiple choice item in our survey regarding the procedures to be followed in cases of suspected blood transfusion reaction with “I immediately stop the transfusion.” This correlates with the high level of awareness of transfusion reactions reflected in other survey questions. Limitations of the study: Since the data of this survey are limited to the responses given by healthcare professionals working at a training and research hospital, the results cannot be generalized.
Beyazpinar Kavaklioglu et al., Determination of health workers’ level of knowledge about blood transfusion
CONCLUSION An evaluation of the data indicated that the knowledge level of the healthcare professionals interviewed about blood transfusion was above average. Nonetheless, continuation of in-service training about blood transfusion is recommended. Our data revealed that 60.8% of the respondents replied to the question, “If you discover a problem with a blood product before you administer a transfusion, who do you inform first?” with “the physician in charge.” This response suggests that during subsequent training sessions the participants should be advised to contact the blood center when any problem is detected in transfusion blood products. There was no statistically significant difference in the distribution of the responses given by participants who had received training and those who had not (p>0.05). The results of our research demonstrate that the likelihood these healthcare professionals would make a medical error related to blood transfusion was low. Quality assurance work that is ongoing in the hospital where this research was conducted and in-service training aimed at patient safety and minimizing errors likely contributed to this result. Based on the evaluation of the results, the following recommendations are offered to provide healthcare professionals with adequate information about blood transfusion, and to put this information into practice: • Provide nursing staff with well-planned, useful, continuous in-service training and perform regular follow-up of the effectiveness of these training sessions; • In order to make in-service training effective and practicable, as well as to minimize errors, the transfusion procedure should be standardized; • Standardization of transfusion procedure training should include diagrams illustrating the proper method of providing blood transfusion and explain possible side effects that may occur; and • Blood transfusion committees should oversee proper implementation of these recommendations.
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Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – A.B., S.D., B.O.; Design – A.B., S.D., B.O; Materials – A.B., S.D., B.O; Data Collection – S.D., B.O., A.B.; Analysis – S.D., B.O., A.B; Literatüre Search – S.D., B.O., A.B; Writing – S.D., A.B., B.O.; Critical Rewiew – S.D., A.B., B.O.
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172 ve Uygulamaları, Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü, Doktora Tezi. Ankara: 1994. 16. Gürkan A. İstanbul ili genel cerrahi kliniklerinde kan ve kan ürünlerinin kan bankasından alınması, saklanması, kullanılması ve yeniden değerlendirilmesi ile ilgili uygulamaların saptanması. Marmara Enstitüsü Sağlık Bilimleri Enstitüsü Cerrahi Hastalıkları Hemşireliği Anabilim Dalı. İstanbul: 1998. 17. Siegenthaler MA, Schneider P, Vu DH, Tissot JD. Haemovigilance in a general university hospital: need for a more comprehensive classification and a codification of transfusion-related events. Vox Sang 2005;88:22–30. 18. Benli, S. Hemşirelerin ve Hemşirelik Öğrencilerinin Kan Transfüzyonuna Yönelik Bilgi Düzeylerinin Saptanması. Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü, Yüksek Lisans Tezi. Konya: 1996. 19. Lahlimi FZ, Tazi I, Sifsalam M, Bouchtia M, Mahmal L. Assessment of transfusion practice: assessing nurses’ knowledge in transfusion medicine at Mohamed VI Hematology and Oncology Center of Marrakesh, Morocco. Transfus Clin Biol 2015;22:12–6. 20. Linden JV, Paul B, Dressler KP. A report of 104 transfusion errors in New York State. Transfusion 1992;32:601–6. 21. Faukaneli D, Boralessa H, Murphy M, Taylor C, et al. National comparative audit of blood transfusion: 2008 bedside transfusion re-audit. 2009. Available at: http://hospital.blood.co.uk/ media/26876/nca-2008_bedside_transfusion_audit_report_-_ st_elsewheres.pdf. Accessed August 22, 2017. 22. Taylor CJ, Murphy MF, Lowe D, Pearson M. Changes in practice
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Orıgınal Article
GENERAL SURGERY
North Clin Istanb 2017;4(2):173–179 doi: 10.14744/nci.2017.80148
Does antiaggregant administration lead to early diagnosis in proximal colon cancer? Ulas Aday, Ebubekir Gundes, Huseyin Ciyiltepe, Durmus Ali Cetin, Kamuran Cumhur Deger, Selcuk Gulmez, Aziz Serkan Senger, Emre Bozdag Department of Gastroenterology Surgery, Kosuyolu High Speciality Training and Research Hospital, Kartal, Istanbul, Turkey
ABSTRACT OBJECTIVE: Cancers of the proximal colon are often diagnosed in advanced stages with iron deficiency anemia and nonspecific symptoms. Aspirin and clopidogrel are commonly used antiaggregant agents for various clinical conditions. The aim of this study was to investigate the effects of antiaggregant medication on the early diagnosis of proximal colon cancer. METHODS: Cases of colon cancer patients who had received curative surgical procedures between January 1, 2013 and July 31, 2016 were retrospectively reviewed. The clinical and pathological results of patients who had used antiaggregant drugs were compared to those who had not. RESULTS: During the studied period, 246 colorectal cancer patients underwent curative surgical procedures. Of the 67 patients with proximal colon cancer who were included in the study, 27 (40.3%) had taken antiaggregant medication. The mean age of the antiaggregant group was 67.1 years (range: 34–88 years), while it was 58.3 years (range: 34–83 years) for the non-antiaggregant group; the difference between the 2 groups was statistically significant (p=0.03). A pathological evaluation revealed that 74.1% of the antiaggregant group was in the early stages (Stage I/II: 7/13), while 42.5% of the non-antiaggregant group was in the early stages (Stage I/II: 2/15); the difference was statistically significant (p=0.011). CONCLUSION: Antiaggregant medication has a positive effect on diagnosing proximal colon cancer at early stages. Patients using aspirin or clopidogrel should undergo a complete colonoscopic evaluation in the presence of gastrointestinal tract bleeding or newly developed anemia. Keywords: Antiaggregant medication; early stage; proximal colon cancer.
C
olorectal malignancies occur frequently and are the fourth most common cause of malignancyrelated mortality in the world. It is estimated that 2.2 million new diagnoses and 1.1 million mortality
cases will develop annually by 2030 [1]. The application of early screening programs has resulted in a significant reduction in the rate of colorectal cancerrelated mortality [2– 4]. The use of colonoscopy as
Received: February 02, 2017 Accepted: May 08, 2017 Online: August 26, 2017 Correspondence: Dr. Ulas ADAY. Kartal Kosuyolu Yuksek Ihtisas Egitim ve Arastirma Hastanesi, Gastroenteroliji Cerrahi Klinigi, Kartal, Istanbul, Turkey. Tel: +90 216 - 500 15 00 e-mail: ulasaday@gmail.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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a screening tool has proven to be the gold standard of tumor detection because it enables the removal of premalignant lesions by polypectomy and renders pathological diagnosis possible [5]. Aspirin and clopidogrel are the antiaggregant agents most frequently administered to patients with, most notably, cardiac pathologies, or to those who have experienced cerebrovascular events or peripheral arterial diseases [6–8]. Gastrointestinal tract bleeding is one of the most significant side effects of antiaggregant use [6, 7]. Lower gastrointestinal tract bleeding and the related anemia are prominent symptoms of colorectal cancer that enable early-stage diagnosis [9, 10]. The increase in the prevalence of proximal colon cancer, aggressive behavior due to tumor biology, the failure to detect tumor in colonoscopy, and late diagnosis lead to an increase in mortality rates [5, 11, 12]. This retrospective study compared the clinical and pathological results of proximal colon cancer (transverse and right colon) patients who had undergone curative surgical procedures based on whether antiaggregant agents had been administered. The effects of antiaggregant administration on proximal colon cancer staging were also evaluated. MATERIALS AND METHODS Cases of patients with colorectal cancer who had undergone curative surgical procedures at our clinic between January 1, 2013 and July 31, 2016 were retrospectively reviewed. Patients with proximal colon (cecum, ascending colon, hepatic flexura, or transverse colon-localized) tumors were included in the study, while those with rectum, splenic flexura, descending or sigmoid colon cancers were excluded. Moreover, patients who had surgical procedures for synchronous or metachronous tumors, who had been on anticoagulants, or who had received palliative interventions were excluded from the study. Patient data were collected from hospital records and final pathology results. Each patient’s age, gender, indications for colonoscopy, antiaggregant use, and duration of hospitalization were recorded, in addition to the laboratory
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parameters analyzed at the time of diagnosis and the tumor, node, and metastasis (TNM) staging of the tumor. Colonoscopy requests were divided into 2 groups: those that were related to bleeding conditions and those that were not. Bleeding-related conditions were defined as hematochezia, melena, positive fecal occult blood test (FOBT) results, and iron deficiency anemia. Conditions unrelated to bleeding were defined as abdominal pain, changes to defecation habits, weight loss, loss of appetite, obstructive findings, incidental findings by radiological evaluation, and findings resulting from colon cancer screening procedure. Anemia was defined as hemoglobin (Hb) level lower than 12 g/dL in females and lower than 13 g/dL in males. The pathological evaluation in this study was performed using the seventh edition of the American Joint Committee on Cancer TNM staging system [13]. Stages I and II were considered early stage, while stages III and IV were considered advanced stage. The duration of hospitalization was defined as the period from surgery to discharge, while early mortality was defined as mortality within the first 30 days after surgery. Study patients were divided into 2 groups: those who used antiaggregant agents (aspirin or clopidogrel) and those who did not. The clinical, laboratory and pathological results of each group were compared. Statistical analysis IBM SPSS Statistics for Windows, Version 21.0 (IBM Corp., Armonk, NY, USA) computer software was used for the statistical analyses of the data collected. Continuous variables were assessed using the Kolmogorov–Smirnov normality test. The data collected from the patients included in the study were given as mean, SD, and percentage, as appropriate. The Mann-Whitney U test was used for non-normally distributed data, while the Student’s t-test was performed for normally distributed data for comparisons between the groups. Categorical groups were compared with the chi-square test. A p-value of less than 0.05 was considered statistically significant.
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Table 1. Clinical characteristics of the patients Age (Mean±SD) Sex (male/female) Those with bleeding-related symptoms (%) Aspirin Clopidogrel Dual therapy Hb value at the time of diagnosis (g/dL±SD) Patients with anemia (n=57) Male (Hb<13 mg/dL) Female (Hb<12 mg/dL) Duration of hospitalization (days±SD)
Antiaggregant Yes (n=27)
Antiaggregant No (n=40)
67.1±11.1 58.3±12.0 14/13 22/18 18 (66.7%) 19 (47.5%) 9 – 8 – 10 – 9.3±1.8 10.2±2.3 12 (21.1%) 13 (22.8%) 11.3±6.8
16 (28.1%) 16 (28.1%) 9.2±3.7
p
0.03* 0.80 0.122
0.141
0.147
Hb: Hemoglobin; SD: Standard deviation. *p˂0.05.
RESULTS Between January 1, 2013 and July 31, 2016, a total of 246 patients underwent curative colorectal cancer surgery at our clinic. Of these tumors, 77 (31.3%) were localized in the rectum, 88 (35.8%) in the distal colon, and 71 (28.8%) in the proximal colon. Ten patients had synchronous or metachronous tumors. Of the patients with proximal colon cancer, 67 were included in the study. Three patients were excluded from the study due to warfarin use, while 1 was excluded due to missing data. The average age of the patients was 61.8 years (range: 34–88 years), and 31 patients (46.3%) were female. Antiaggregant agents were administered to 27 patients (40.3%) in the group; 40 patients (59.7%) did not receive such treatment. The mean age of the antiaggregant and non-antiaggregant groups was 67.1 years (range: 34–88 years) and 58.3 years (range: 34–83 years), respectively; the difference between the groups was statistically significant (p=0.03). While 8 of the antiaggregant patients used only clopidogrel and 9 used only aspirin, 10 used a combination of both. In both groups, colonoscopy request was most commonly caused by bleeding-related conditions; it was observed in 18 (66.7%) antiaggregant group patients and in
19 (47.5%) non-antiaggregant group patients. Abdominal pain was the second most common symptom in both groups; it was seen in 5 antiaggregant group patients and in 18 non-antiaggregant group patients. The mean Hb value at the time of diagnosis was 9.3±1.8 g/dL in the antiaggregant group and 10.2±2.3 g/dL in the non-antiaggregant group, but the difference was not found to be statistically significant (p=0.14). The demographic, clinical, and laboratory characteristics and results of the 2 groups have been summarized in Table 1. Pathological evaluation revealed that 20 (74.1%) patients in the antiaggregant group had early-stage cancer (Stage I/II: 7/13), while 17 (42.5%) patients in the non-antiaggregant group had early-stage cancer (Stage I/II: 2/15); the difference between the groups was found to be statistically significant (p=0.01). The mean number of excised lymph nodes in the antiaggregant group was 19.6 (range: 7–33 lymph nodes), while it was 24.9 (range: 11–59 lymph nodes) in the non-antiaggregant group, and the difference between the groups was statistically significant (p=0.02). The mean number of positive lymph nodes was 0.55 (range: 0–7 lymph nodes) and 1.95 (range: 0–23 lymph nodes) in the antiaggregant and non-antiaggregant groups, respectively
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(Table 2). The difference between the 2 groups was found to be statistically significant (p=0.006). The mean duration of hospitalization was 11.3 days (range: 6–37 days) in the antiaggregant group and 9.2 days (range: 5–20 days) in the non-antiaggregant group; there was no statistically significant difference between the groups (p=0.147). The number of patients in the antiaggregant group receiving monotherapy (either aspirin or clopidogrel) was 17, while 10 patients received dual therapy (aspirin and clopidogrel) (Table 3). Neither had a statistically significant effect on early-stage diagnosis (p=0.201).
proximal colon cancer incidence has increased over the course of the last decades [1, 2, 12, 14]. Proximal colon cancer has a poorer prognosis than left colon cancer because of the greater incidence of poor differentiation, tumors containing a mucinous component, late-stage diagnosis, and the advanced age of patients [11, 12, 15]. While anemia and non-specific symptoms are predominant in proximal colon cancer, symptoms related to changes in defecation habits, fresh rectal bleeding, mucoid discharge, and obstruction are more frequent in distal colon and rectum cancers [16]. Symptoms associated with hemorrhage (including melena, fresh rectal bleeding, iron deficiency anemia, and FOBT positivity) are witnessed in three-quarters of colorectal cancer patients. Early-stage diagnosis rates particularly increase when fresh rectal bleeding and melena are predominant [17, 18]. However, diagnosis is usu-
DISCUSSION Colorectal cancers account for the third most common type of cancer in the world, and the rate of
Table 2. Comparison of the pathological results between groups
Antiaggregant Antiaggregant Yes (n=27) No (n=40)
n % n %
Stage Early stage (I/II) Late stage (III/IV) The number of excised lymph nodes (Mean±SD) The number of metastatic lymph nodes [Median (Min.–Max.)]
20 74.1 7 25.9 19.6±6.3 0 (0–7)
17 42.5 23 57.5 24.9±9.5 1 (0–23)
p
0.011* 0.020* 0.006*
SD: Standard deviation; Min: Minimum; Max: Maximum. *p<0.05.
Table 3. The effects of single or dual antiaggregant administration on staging
Early stage (I/II) n=20
Late stage (III/IV) n=7
n
%
n
Antiaggregant treatment Monotherapy Dual therapy
14 6
51.9 22.2
3 4
SD: Standard deviation; Min: Minimum; Max: Maximum. *p<0.05.
p
%
11.1 14.8
0.201
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ally delayed and the survival rate is negatively affected by the presence of non-specific symptoms, such as iron deficiency anemia, abdominal pain, fatigue, and weight loss [18, 19]. The inclusion of colonoscopy in the screening program has led to more early diagnoses of colorectal cancers and has enabled polypectomy of premalignant lesions, resulting in a significant reduction in mortality rates. Pathologies in the proximal colon can be missed because of contamination, incomplete colonoscopy, and the fact that the adenomas observed in the proximal colon are often sessile-flat type; this results in delayed diagnosis and impaired prognosis [3, 4, 5, 20]. Antiaggregant agents are frequently and increasingly administered to patients with cardiac pathologies, stroke, and peripheral arterial diseases, and they have proven to be significantly beneficial to patient outcomes. Bleeding in the gastrointestinal tract is one of the side effects of these agents. Antithrombotic agents, especially when used as dual therapy, cause rising FOBT positivity and may lead to early diagnosis of digestive system malignancies by increasing bleeding from polyps or tumors [6, 7]. Gastrointestinal tract bleeding may be life-saving, as it often leads to early diagnosis, but it increases the false positivity rates for FOBT and causes an increase in negative colonoscopy rate [6, 9, 21]. In patients with cardiac and peripheral arterial disease, gastrointestinal system (especially colorectal) malignancies are more common than in the general population. This has been associated with accompanying characteristics like diabetes, obesity, and smoking, rather than antiaggregant agents [22]. Clopidogrel prevents platelets from sticking to each other and indirectly blocks angiogenesis and mucosal healing by binding to plateletsâ&#x20AC;&#x2122; adenosine diphosphate receptors. This leads to the prolonged bleeding of polyps and ulcerated malignant lesions, beginning with the early stage [22, 23]. As with aspirin and warfarin, clopidogrel should be discontinued according to clinical suitability before the FOBT evaluation due to this bi-directional effect [24]. Bleeding caused by the use of aspirin is directly proportional to the dose administered. Most colorectal cancers develop in polyps. Aspirin reduces the rate of cancer incidence by inhibiting cyclo-
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oxygenase-2 (COX-2) in low doses (less than 300 mg IN) and COX-1 in high doses, thereby blocking a polypâ&#x20AC;&#x2122;s progression. Rothwell et al. [25] reported that long-term, regular low-dose aspirin intake reduced the incidence and mortality rates of colorectal cancer, which was more pronounced in right colon cancer cases. Diagnosis is often delayed in the presence of anemia and nonspecific symptoms. In a study of 768 patients, Alexiusdottir et al. [16] reported that rectal bleeding and changes in bowel habits were more frequent in left colon tumors, which leads to earlierstage diagnosis. The authors also stated that anemia and other general symptoms were more frequent in right colon cancers leading to later-stage diagnosis [16]. Hreinsson et al. [17] reported a similar result: warfarin administration contributed to early-stage diagnosis by causing pronounced bleeding, whereas aspirin did not cause this effect [17]. Our center predominantly treats patients with cardiac and vascular pathologies. These pathologies are therefore present in a significant proportion of our patients who undergo surgical procedures of the gastrointestinal tract. This is also true of our patients who receive endoscopic and colonoscopic procedures. Twenty-seven (40.2%) of 67 proximal colon cancer patients who underwent curative surgery and were included in this study were taking antiaggregant agents. In our country, colorectal cancer screening programs are not at a sufficient level to cover the entire population. Generally, colonoscopic evaluations are performed only in the presence of symptoms or within the screening schedule. In our study, bleeding-related symptoms and the resulting anemia were the most common reasons for colonoscopic evaluation in both groups. Although the distribution of symptoms was similar in both groups, we believe that the rate of early-stage diagnosis was higher in the antiaggregant group (Stage I/II, 74.1%; p=0.011) because those patients were regularly monitored by physicians due to their cardiac or vascular pathologies. The prognoses and survival rates for cancers of the colon differ depending on the localization. The general view is that proximal colon cancer patients have a lower survival rate; however, there are several studies
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that document no difference in the survival rate for right colon cancer or that demonstrate a better rate [8, 12, 14, 20]. Benedix et al. [20] reported in their 28,797-patient study that, although the rate of early diagnosis in descending and ascending colon cancers was higher than 50%, the rate was lower in splenic flexura and cecal cancer. This may be explained in cecal cancer cases by prolonged stool transit time, prolonged stool exposure, a failure to detect tumor by colonoscopy, and a greater presence of poorly differentiated tumor types with aggressive prognosis; the reason is not clear in splenic flexura cancer cases [11, 20]. Weiss et al. [14] found that right colon cancer was more prevalent in the elderly and in female patients, and that advanced stage and poor differentiation characteristics were predominant. The authors, however, reported that there was no overall difference in 5-year mortality, but the mortality rate for stage II right colon cancer patients was found to be lower. In a study of 91,416 patients, Warschkow et al. [12] reported survival rate of right and left cancers following a mean follow-up of 38 months. Their results revealed that the prognosis and survival rate were better for stage I and II right colon cancer than for those of left colon cancer, while they proved to be similar for both in stage III. The authors’ study opened up new discussions about the issue. There are limitations to our work, including its retrospective structure, the limited number of patients, the absence of an evaluation of survival rate, a lack of comparison with the distal colon, and the lack of comparison between different localizations of the proximal colon. However, this study allows for the comparison of those who use antiaggregant agents with those who do not by forming a homogeneous group of proximal colon cancer cases. Conclusion The frequency of the administration of antiaggregant agents has been on the rise. Anemia due to gastrointestinal tract bleeding caused by these agents may be a sign of early-stage proximal colon cancer. The use of aspirin or clopidogrel has a positive effect on early-stage diagnosis of proximal colon cancer. Concerned clinicians should pay careful attention to newly diagnosed anemia in patients undergoing
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antiaggregant treatment, and patients should receive colonoscopic and endoscopic evaluations. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – U.A., E.G., H.C., D.A.C.; Design – U.A., E.G., D.A.C., E.B.; Supervision – K.C.D., S.G., E.B., A.S.S.; Materials – A.S.S., S.G., E.B.; Data collection &/or processing – U.A., E.G., D.A.C., H.C., E.B., A.S.S., S.G., KCD; Analysis and/or interpretation – U.A., E.G., K.C.D., E.M.; Literature search – U.A., E.G., H.C., D.A.C., S.G., E.B.; Writing – U.A., E.G., H.C; Critical review – E.B., K.C.D., S.G.
REFERENCES 1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017;66:683–91. 2. Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi RE, Corcione F. Worldwide burden of colorectal cancer: a review. Updates Surg 2016;68:7–11. 3. Jacob BJ, Moineddin R, Sutradhar R, Baxter NN, Urbach DR. Effect of colonoscopy on colorectal cancer incidence and mortality: an instrumental variable analysis. Gastrointest Endosc 2012;76:355-64.e1. 4. Pan J, Xin L, Ma YF, Hu LH, Li ZS. Colonoscopy Reduces Colorectal Cancer Incidence and Mortality in Patients With Non-Malignant Findings: A Meta-Analysis. Am J Gastroenterol 2016;111:355–65. 5. Matsuda T, Ono A, Kakugawa Y, Matsumoto M, Saito Y. Impact of screening colonoscopy on outcomes in colorectal cancer. Jpn J Clin Oncol 2015;45:900–5. 6. Ishizaka N, Sakamoto A, Fujishiro M, Nagai R, Koike K. Gastrointestinal malignancies and cardiovascular diseases-non-negligible comorbidity in an era of multi-antithrombotic drug use. J Cardiol 2011;58:199–207. 7. Sakamoto A, Fujishiro M, Koike K, Nagai R, Ishizaka N. The prevalence of malignant neoplastic and non-malignant gastrointestinal lesions in cardiology inpatients. J Cardiol 2013;61:181–5. 8. Kirshtein B, Ariad S, Mizrahi S, Man S, Walfisch S. Rectal bleeding and previous anticoagulant treatment in patients with colorectal cancer do not predict outcome. Tech Coloproctol 2007;11:121–6. 9. Norton SA, Armstrong CP. Lower gastrointestinal bleeding during anticoagulant therapy: a life-saving complication? Ann R Coll Surg Engl 1997;79:38–9. 10. Symeonidis D, Koukoulis G, Christodoulidis G, Mamaloudis I, Chatzinikolaou I, Tepetes K. Impact of antiplatelet treatment on colorectal cancer staging characteristics. World J Gastrointest Endosc 2012;4:409–13. 11. Benedix F, Meyer F, Kube R, Gastinger I, Lippert H. Right-and
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left-sided colonic cancer - different tumour entities. Zentralbl Chir 2010;135:312–7. 12. Warschkow R, Sulz MC, Marti L, Tarantino I, Schmied BM, Cerny T, et al. Better survival in right-sided versus left-sided stage I - III colon cancer patients. BMC Cancer 2016;16:554. 13. Edge S, Byrd DR, Compton CC, Fritz AG, Greene F, Trotti A. AJCC Cancer Staging Manual. 7th ed. New York: Springer-Verlag; 2010. 14. Weiss JM, Pfau PR, O’Connor ES, King J, LoConte N, Kennedy G, et al. Mortality by stage for right-versus left-sided colon cancer: analysis of surveillance, epidemiology, and end resultsMedicare data. J Clin Oncol 2011;29:4401–9. 15. Powell AG, Wallace R, McKee RF, Anderson JH, Going JJ, Edwards J, et al. The relationship between tumour site, clinicopathological characteristics and cancer-specific survival in patients undergoing surgery for colorectal cancer. Colorectal Dis 2012;14:1493–9. 16. Alexiusdottir KK, Möller PH, Snaebjornsson P, Jonasson L, Olafsdottir EJ, Björnsson ES, et al. Association of symptoms of colon cancer patients with tumor location and TNM tumor stage. Scand J Gastroenterol 2012;47:795–801. 17. Hreinsson JP, Jonasson JG, Bjornsson ES. Bleeding-related symptoms in colorectal cancer: a 4-year nationwide populationbased study. Aliment Pharmacol Ther 2014;39:77–84. 18. Thompson MR, Asiimwe A, Flashman K, Tsavellas G. Is earlier referral and investigation of bowel cancer patients presenting with rectal bleeding associated with better survival? Colorectal
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Dis 2011;13:1242–8. 19. Alexiusdottir KK, Snaebjornsson P, Tryggvadottir L, Jonasson L, Olafsdottir EJ, Björnsson ES, et al. Colon cancer: association of histopathological parameters and patients’ survival with clinical presentation. APMIS 2013;121:901–7. 20. Benedix F, Schmidt U, Mroczkowski P, Gastinger I, Lippert H, Kube R; Study Group Colon/Rectum Carcinoma (Primary Tumor). Colon carcinoma-classification into right and left sided cancer or according to colonic subsite?-Analysis of 29,568 patients. Eur J Surg Oncol 2011;37:134–9. 21. Johannsdottir GA, Onundarson PT, Gudmundsdottir BR, Bjornsson ES. Screening for anemia in patients on warfarin facilitates diagnosis of gastrointestinal malignancies and pre-malignant lesions. Thromb Res 2012;130:e20–5. 22. Chan AO, Jim MH, Lam KF, Morris JS, Siu DC, Tong T, et al. Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease. JAMA 2007;298:1412–9. 23. Cryer B. Reducing the risks of gastrointestinal bleeding with antiplatelet therapies. N Engl J Med 2005;352:287–9. 24. Sawhney MS, McDougall H, Nelson DB, Bond JH. Fecal occult blood test in patients on low-dose aspirin, warfarin, clopidogrel, or non-steroidal anti-inflammatory drugs. Dig Dis Sci 2010;55:1637–42. 25. Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010;376:1741–50.
Case Report
PT&R
North Clin Istanb 2017;4(2):180–184 doi: 10.14744/nci.2016.73644
Ultrasound therapy in iliopsoas hematoma Basak Bilir Kaya,1 Afitap Icagasioglu2 Departmant of Physical Medicine and Rehabilitation, Goverment of Health Siyami Ersek Training and Research Hospital,
1
Istanbul, Turkey Departmant of Physical Medicine and Rehabilitation, Medeniyet University Goztepe Training and Research Hospital,
2
Istanbul, Turkey
ABSTRACT Warfarin is a commonly used anticoagulant agent that can have life-threatening complications, such as severe bleeding, which then require cessation of the treatment. Due to the widespread use of this therapy in recent years, incidences of its hemorrhagic complications have also increased significantly. In hemodynamically stable patients, it is possible to adopt conservative treatment strategies, such as ultrasound (US) therapy as an alternative. US is a physical therapy modality widely used in musculoskeletal disorders, but there is little evidence about its effectiveness for hemorrhagic complications because of the limited number of studies on this subject at present. A 77-yearold male who had been under oral anticoagulant therapy for 6½ years presented at the clinic with complaints of severe pain and numbness in the anterolateral thigh. US evaluation revealed iliopsoas hematoma. US treatment, administered as a physical therapy modality, resulted in faster resorption of the hematoma than expected. The patient fully recovered from clinically observed pain, meralgia paresthetica, and reduced patellar reflex. Keywords: Hematoma; ultrasound; warfarin.
I
liopsoas hematoma occurring during anticoagulant use is a rare entity generally seen in patients who are using heparin or warfarin [1, 2]. Iliopsoas hematoma may manifest with various symptoms. In the early stage, pain localized in the lumbar and inguinal regions may occur, while in advanced cases, lumbar plexus neuropathy, massive bleeding, and hemorrhagic shock can be seen [3]. In some cases, direct hemorrhagic pathology may not come to mind [3]. The aim of this case presentation was to raise awareness of iliopsoas hematoma, which should be considered in patients who present with the frequently encountered complaints of thigh
pain, meralgia paresthetica, or femoral neuropathy. It was also a goal to draw attention to the accelerating effect of ultrasound (US) therapy on hematoma resorption in hemodynamically stable patients. US is a frequently used technology in the diagnosis and treatment of medical conditions [4]. It is also very often preferred among physical treatment modalities [4]. Its indications for use for the musculoskeletal system include muscle relaxation, and relief of edema and pain [5]. Although in vitro studies have demonstrated physiological effects of US on live tissue, there is scarce in vivo evidence available about its effects on soft tissue [5]. In a recent study
Received: September 18, 2015 Accepted: September 29, 2016 Online: August 26, 2017 Correspondence: Dr. Basak BILIR KAYA. Dr. Siyami Ersek Gogus Kalp ve Damar Cerrahisi Egitim ve Arastirma Hastanesi, Istanbul, Turkey. Tel: +90 216 - 542 44 44 e-mail: basakbilir@gmail.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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in mice, cutaneous stimulation with US was demonstrated to increase fibroblast migration through the activation of the calcium/calmodulin-dependent protein kinase II/T-cell lymphoma invasion and metastasis 1/Ras-related C3 botulinum toxin substrate 1 (Rac1) pathway, and to decrease wound healing time in diabetic and aged mice at a rate of 30% [6]. Speed evaluated the therapeutic use of US on soft tissue, and indicated that the thermal effects of US included an increase in blood flow and a mild pro-inflammatory response [5]. Its non-thermal effects include cavitation and acoustic microstreaming [5]. As a consequence of such thermal and nonthermal effects, an increase in fibroblastic activity and protein synthesis, increased blood flow, tissue regeneration, and bone healing can be expected [5]. The frequency of therapeutic US is between 0.75 and 3 MHz. Lower frequencies penetrate deeper, but focus on the target tissue with less precision. A frequency of 1 MHz is absorbed at depth of between 3 and 5 cm [7], and is appropriate for deeper tissues (i.e., the psoas muscle). Intermittent use of US increases its non-thermal effects, and a subsequent increase in microfluidity with an ensuing acceleration of fibrinolysis occurs [8, 9]. This effect might presumably hasten resorption of iliopsoas hematoma. Use of diagnostic US in a patient with a spontaneous iliopsoas hematoma and therapeutic use of US in a rectus sheath hematoma have been reported in the literature [2, 10]. However, to our knowledge, no publication of the use of US in the treatment of an iliopsoas hematoma has been presented in the literature.
gery and postoperative warfarin treatment was reinitiated at 5 mg, and 7.5 mg on alternate days, based on the recommendation of the department of cardiology. He had no history of bleeding diasthesis or alcohol use, and his coagulation parameters tested no more than 1 month earlier were reportedly under control and within therapeutic limits. Cardiovascular examination results of the patient were as follows: ambulatory blood pressure: 110/70 mmHg and heart rate: 80 bpm with 2/6 systolic murmur heard over cardiac apex. Locomotor system examination revealed a 30 x 20 mm, firm, tender mass, and hypoesthesia were detected on the left medioanterior region of the thigh. Femoral stretch test positivity and decreased patellar tendon reflex were observed in the right thigh. The patient had a score of 8 on 10-point Visual Analogue Scale (VAS) of pain. Some notable biochemical parameters were: bilirubin: 2.0 mg/dL (0.1–1.2 mg/dL), indirect bilirubin: 1.6 mg/dL (0.1–0.8 mg/dL), white blood cell count: 4000/mm3 (4000–11000/mm3), hemoglobin: 14.1 g/dL (11.0–18.0 g/dL), hematocrit: 40.6% (40–52%), platelet count: 150,000/ mm3 (150,000–400,000/mm3), prothrombin time: 31.8 seconds (11–15.5 seconds), activated partial thromboplastin time: 29.3 seconds (24–40 seconds), and international normalized ratio (INR): 2.67 (0.67–1.25) (Table 1). Since the patient had claustrophobia, US was preferred as an imaging modality. Superficial tissue US was performed and revealed a 31.1x20.4x14.2 mm hypoechoic mass, which was evaluated as consistent with organized, residual hematoma (Figure 1). Since hemoglobin level and hemodynamic data of the patient were stable and there was no life-threatening bleeding, his oral anticoagulant treatment was not discontinued. US therapy was thought to be a potential treatment for hematoma resorption. As the patient was hemodynamically stable and the mass lesion was ultrasonographically consistent with organized hematoma, 2 days after the diagnosis, US treatment was initiated. Treatment site was determined based on US findings of heterogeneous isoechoic mass (30.8x11.3x8.3 mm) surrounded by calcific hyperechoic images (Figure 2). In order to benefit from non-thermal effects, intermittent US treatment was preferred. The patient was informed about the emergency case of bleeding, and told that
CASE REPORT A 77-year-old male patient presented at the clinic with complaints of thigh pain and loss of sensation on the lateral aspect of his thigh. The patient had been using oral anticoagulants for 6½ years following aortic valve replacement and with the diagnoses of left ventricular systolic dysfunction, 3+ mitral valve insufficiency, and pulmonary hypertension. In 2004, he had gone to emergency service with complaints of headache and dizziness, and oral warfarin treatment was discontinued as result of diagnoses of subarachnoidal hematoma and bilateral frontoparietal subdural hematoma. The hematomas were surgically resolved by the department of neurosur-
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Figure 1. Pretreatment ultrasonographic findings.
Figure 2. Posttreatment ultrasonographic findings.
Table 1. Findings Physical examination Ultrasonographic findings Vital findings Laboratory results
Firm, solid, tender mass measuring 30 x 20 mm in the medioanterior aspect of the femoral region Hypoesthesia of the midlateral aspect of the femoral region Femoral stretch test Left side: positive Visual analogue scale (VAS) pain score VAS 8 Patellar tendon reflex Left side: decreased Hypoechoic mass measuring 31.1x20.4x14.2 mm, consistent with organized hematoma Blood pressure 110/70 mmHg Heart rate 80 bpm Findings on auscultation 2/6 systolic murmur heard over cardiac apex Bilirubin 2.0 mg/dL (0.1–1.2 mg/dL) Indirect bilirubin 1.6 mg/dL (0.1–0.8 mg/dL) White blood cell count 4000/mm3 (4000–11000/mm3) Hemoglobin 14.1 g/dL (11.0–18.0 g/dL) Hematocrit 40.6% (40–52%) Platelet count 150,000/mm3 (150,000–400,000/mm3) Prothrombin time 31.8 seconds (11–15.5 seconds) Activated partial thromboplastin time 29.3 seconds (24–40 seconds) International normalized ratio 2.67 (0.67–1.25)
VAS: Visual Analogue Scale
if his thigh pain increased or his health state deteriorated, he was to request emergency service. Restriction of physical activity during the treatment process was also recommended. US therapy was organized as a total of 15 sessions over a period of 3 weeks, once a day, 5 days a week. The dose of intermittent US applied was 1 W/cm2 for 5 minutes with probe light emission area of 5 cm2. The probe was applied with circular movements and with the aid of a lubri-
cating gel. No complication due to US therapy was observed. Flank pain regressed from VAS 8 to VAS 2. On physical examination, patellar reflex returned to normal. Femoral stretch test was negative on the left side, which had previously yielded positive result. Sensory examination of the previously hypoesthetic area on the lateral side of the thigh demonstrated normoesthesia. On control examination performed 4 months later, VAS score was 0 with normal sen-
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sory perception, and during US examination no hematoma formation was observed.
is organized, that is, after detection of a mostly hypoechoic mass on US, and coagulation parameters are brought within therapeutic limits (INR=2– 3.5), US therapy may be initiated [10]. As reported in the literature, a patient whose heparin treatment had been discontinued because of the presence of an iliac hematoma exited as a result of myocardial infarction [14]. Therefore, since discontinuation of anticoagulant therapy also constitutes a risk for the patient, hemodynamically stable patients can be closely followed-up without termination of anticoagulant therapy. We also believe that in appropriately selected cases, conservative treatment of an iliopsoas hematoma should be conducted by a specialist in physical therapy and rehabilitation in close collaboration with the primary specialist and a radiologist who will monitor the anticoagulant treatment of the patient. Randomized controlled studies to be performed in the future may help us formulate protocols to guide us concerning the use of US for the resorption of hematomas.
DISCUSSION In cases of hematoma, the ability to decrease resorption time is important. In a case presented by Berna et al., the authors followed-up the resorption process of a rectus sheath hematoma treated conservatively without the application of US, and observed spontaneous hematoma resorption nearly 3 months later [11]. They indicated that that during this process of resorption there was a risk of the hematoma becoming infected [11–13]. Therefore, decreasing the resorption time of a hematoma will enable a much faster improvement in the clinical state of the patient and decrease the possibility of infection. When a patient presents with thigh pain, iliopsoas hematoma should be kept in mind [14]. For the diagnosis of hematoma, US or computed tomography may be used [10]. The treatment alternative selected is dependent on the hemodynamic stability of the patient, and for hemodynamically unstable patients, a surgical alternative may be preferred [15]. However, in stable patients, conservative treatment alternatives may be evaluated. Among these alternatives, as a modality of physical therapy, US can be considered. However, very few publications are currently available indicating that US accelerates the processes of soft tissue regeneration and hematoma resorption [5]. Recently, a study on mice demonstrated that US activated the Rac 1 pathway, leading to a migration of fibroblasts, and also shortened the wound healing process by 30% [6]. In the present case, we also think that US sped up resorption of hematoma, as rapid clinical improvement of the patient was observed sooner than anticipated. Devcic-Kuhar et al. demonstrated that US increased in vitro thrombolysis mediated by plasminogen and tissue-type plasminogen activator [16]. The acceleration of hematoma resorption in our patient was consistent with these data. Berna et al. recommended proceeding with intermittent US therapy after the acute phase of a hematoma had terminated, due to the risk of hemorrhagic complications [10]. Nevertheless, despite the concern about a higher risk of recurrent bleeding in a newly formed hematoma, in some studies in the literature it has been stated that once a hematoma
Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – B.B.K.; Design – B.B.K.; Supervision – A.I.; Materials – B.B.K.; Data collection &/or processing – B.B.K.; Analysis and/or interpretation – B.B.K.; Literature search – B.B.K., A.I.; Writing – BBK; Critical review – A.I.
REFERENCES 1. Sasson Z, Mangat I, Peckham KA. Spontaneous iliopsoas hematoma in patients with unstable coronary syndromes receiving intravenous heparin in therapeutic doses. Can J Cardiol 1996;12:490–4. 2. Sharma D, Saker R, Govind A. Emergency department ultrasound diagnosis of spontaneous iliopsoas haemorrhage in a patient on warfarin. BMJ Case Rep 2013;2013. pii: bcr2013201291. 3. Qanadli SD, El Hajjam M, Mignon F, Bruckert F, Chagnon S, Lacombe P. Life-threatening spontaneous psoas haematoma treated by transcatheter arterial embolization. Eur Radiol 1999;9:1231–4. 4. Warden SJ, McMeeken JM. Ultrasound usage and dosage in sports physiotherapy. Ultrasound Med Biol 2002;28:1075–80. 5. Speed CA. Therapeutic ultrasound in soft tissue lesions. Rheumatology (Oxford) 2001;40:1331–6. 6. Roper JA, Williamson RC, Bally B, Cowell CA, Brooks R, Stephens P, et al. Ultrasonic Stimulation of Mouse Skin Reverses
184 the Healing Delays in Diabetes and Aging by Activation of Rac1. J Invest Dermatol 2015;135:2842–51. 7. Gann N. Ultrasound: Current concepts. Clin Manage 1991;11:64–9. 8. Francis CW, Onundarson PT, Carstensen EL, Blinc A, Meltzer RS, Schwarz K, et al. Enhancement of fibrinolysis in vitro by ultrasound. J Clin Invest 1992;90:2063–8. 9. Harpaz D, Chen X, Francis CW, Marder VJ, Meltzer RS. Ultrasound enhancement of thrombolysis and reperfusion in vitro. J Am Coll Cardiol 1993;21:1507–11. 10. Berná-Serna JD, Sánchez-Garre J, Madrigal M, Zuazu I, BernáMestre JD. Ultrasound therapy in rectus sheath hematoma. Phys Ther 2005;85:352–7. 11. Berná JD, Garcia-Medina V, Guirao J, Garcia-Medina J. Rectus sheath hematoma: diagnostic classification by CT. Abdom Imaging 1996;21:62–4.
North Clin Istanb 12. Fusato G, Vidali M, Zuccarotto D, Rodighiero D. Hematomas of the abdominal rectus muscle. Minerva Chir 1993;48:107–13. 13. Moreno Gallego A, Aguayo JL, Flores B, Soria T, Hernández Q, Ortiz S, et al. Ultrasonography and computed tomography reduce unnecessary surgery in abdominal rectus sheath haematoma. Br J Surg 1997;84:1295–7. 14. Piazza I, Girardi A, Giunta G, Pappagallo G. Femoral nerve palsy secondary to anticoagulant induced iliacus hematoma. A case report. Int Angiol 1990;9:125–6. 15. Egger B, Schweizer W, Wagner HE. Acute abdomen in abdominal wall hemorrhage in anticoagulation. Helv Chir Acta 1992;59:399–402. 16. Devcic-Kuhar B, Pfaffenberger S, Gherardini L, Mayer C, Gröschl M, Kaun C, et al. Ultrasound affects distribution of plasminogen and tissue-type plasminogen activator in whole blood clots in vitro. Thromb Haemost 2004;92:980–5.
Case Report
RADIOLOGY
North Clin Istanb 2017;4(2):185â&#x20AC;&#x201C;187 doi: 10.14744/nci.2017.93063
Giant arachnoid granulation mimicking dural sinus thrombosis Ercan Ayaz, Basak Atalay, Begumhan Baysal, Senem Senturk, Ahmet Aslan Department of Radiology, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey
ABSTRACT Arachnoid granulations (AG) are composed of dense, collagenous connective tissue that includes clusters of arachnoid cells. They tend to invaginate into the dural sinuses, through which cerebrospinal fluid enters the venous system. AG are most commonly seen at the junction between the middle and lateral thirds of the transverse sinuses near the entry sites of the superficial veins. Presently described is the case of a 21-year-old female who presented at the clinic with recurrent headaches. Magnetic resonance (MR) imaging revealed a 3.5-cm lesion, which extended from confluens sinuum through the superior sagittal sinus. The lesion had created a scallop-shaped area of erosion in the neighboring occipital bone. To exclude sinus thrombosis, MR venography was performed, which displayed a maintained venous flow around the lesion. Headaches were treated symptomatically with medical therapy. Giant AG can be misdiagnosed as dural sinus thrombosis. MR imaging combined with MR venography is the most useful diagnostic tool to differentiate giant AG from dural sinus thrombosis. Keywords: Arachnoid granulation; dural sinus thrombosis; magnetic resonance venography; Pacchionian granulation.
A
rachnoid granulations (AG) are tufts of arachnoid villi, often invaginated into the dural sinuses, through which cerebrospinal fluid (CSF) enters the venous system [1]. It is thought that hypertrophy occurs in some of the arachnoid villi in response to increasing CSF volume and pressure, forming macroscopic lobulated AG [2]. There is wide variability in site, number, size, and morphology. They routinely measure a few millimeters in size, but may grow to fill and dilate the dural sinuses. They can expand to the inner table of the skull. They frequently have a close relationship to the bridging veins that penetrate the dural venous sinuses. These structures form weak areas in the dura, through which perivascular arachnoid extrusion can occur [3]. They are often discovered as an
incidental finding in the transverse and posterosuperior sagittal sinus, though rarely, they have been reported to cause symptoms from venous hypertension secondary to partial sinus occlusion [1]. This report is a description of the case of a patient with recurrent episodes of moderate headache whose brain magnetic resonance (MR) imaging revealed incidental giant AG involving the confluens sinuum and extending through the superior sagittal sinus. CASE REPORT A 21-year-old female patient presented at the hospital with recurrent headaches. Neurological examination revealed normal findings. Brain MRI was per-
Received: April 24, 2015 Accepted: February 27, 2017 Online: August 26, 2017 Correspondence: Dr. Ercan AYAZ. Dr. Erkin Caddesi, Goztepe Egitim ve Arastirma Hastanesi, Radyoloji Klinigi, Kadikoy, Istanbul, Turkey. Tel: +90 216 - 566 40 00 e-mail: ercan_ayaz@yahoo.com Š Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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B
Figure 1.
(A) Axial T1-weighted image shows hypointense, lobulated contour lesion (arrow) within the confluens sinuum; (B) Axial T2-weighted image demonstrates lesion is hyperintense relative to brain parenchyma.
formed and showed a 3.5-cm lesion, which extended from the confluens sinuum through the superior sagittal sinus. The lesion was hypointense relative to the brain on T1-weighted image (WI), hyperintense relative to the brain on T2-WI (Figure 1), with banded lower signal, most likely representing collagenous connective tissue and complete suppression on fluid-attenuated inversion recovery sequences. The lesion had caused a scallop-shaped area of erosion in the neighboring occipital bone (Figure 2). Due to the bony erosion and singularity, the lesion was identified as AG. To exclude sinus thrombosis, MR venography was recommended. The patient requested a scan without contrast agent; therefore, non-contrast 2-dimensional time-of-flight (TOF) MR venography was performed. It was observed that there was maintained venous flow around the lesion (Figure 3). The left jugular and left transverse veins were hypoplasic. The headaches were treated symptomatically with medical therapy. DISCUSSION AG are composed of dense collagenous connective tissue that includes clusters of arachnoid cells in a delicate network within the vascular space filled with CSF from the contiguous subarachnoid
Figure 2.
Sagittal T2-weighted image indicates hyperintense lesion (arrow) extending from confluens sinuum through the superior sagittal sinus and scallop-shaped area of erosion in the neighboring bone.
Figure 3. Sagittal magnetic resonance venography maximum intensity projection image revealing obvious venous flow, which divided into 2 channels around filling defect (arachnoid granulation), and joined distally. space. This cell layer is continuous with the underlying arachnoid membrane [4]. Growth of arachnoid membrane-like projections into the dural sinus was first described by Pacchioni in 1705 [5]. These projections are called arachnoid villi or AG, depending on size. Arachnoid villi are microscopic, whereas AG are macroscopic structures. CSF is synthesized and produced by the choroid plexus, where it circulates to the subarachnoid space and eventually returns to the venous blood via AG. AG
Ayaz et al., Giant arachnoid granulation mimicking dural sinus thrombosis
have wide variability in location, number, size, and morphology. Occasionally, AG can extend partly up to the inner table of the skull as foveolae granulations, and even expand into the diploic space, and eventually involve the outer table, mimicking malignant osteolytic lesion [6]. It has been proposed that some AG increase in number and size with age in response to increasing CSF volume and pressure [1]. AG are most commonly seen at the junction between the middle and lateral thirds of the transverse sinuses (92%) near the entry sites of the superficial veins [7]. The clinical significance of AG is uncertain. Although giant AG are often discovered as an incidental finding in the transverse and posterior superior sagittal sinus, rarely, they cause symptoms of increased intracranial pressure as result of venous hypertension secondary to partial sinus occlusion. Typically, regardless of size, AG were diagnosed by identifying intra-AG fluid revealed as CSF-like attenuation on computed tomography (CT) and parallel CSF signal intensity on all MRI sequences, which was the conventional diagnostic criterion for AG. It was thought that identification of AG could be facilitated by a characteristic appearance: round or oval shape, well-defined outline, and homogenous intensity. Presence of an adjacent cortical vein can be considered an additional supportive element [7]. In the differential diagnosis of a mass within the dural sinus, many diseases, including meningioma, inclusion tumor, sinus cavernoma, and meningocele, can be excluded by characteristic imaging findings. It is particularly important to differentiate AG from dural sinus thrombosis, which may cause a fatal outcome and requires an immediate approach. Thrombosis usually involves an entire segment of a sinus or multiple sinuses, and can extend to the cortical veins, whereas AG produce focal, well-defined, nodular defects in the sinuses. Typical MRI finding of dural sinus thrombosis is a clot in the sinus that is iso- to hyperintense on T1-WI and hyperintense on T2-WI. A key MRI feature of giant AG is a nonenhancing lesion with central linear enhancement and surrounding blood flow on contrast enhanced MR venography. Thrombus within the sinus may show contrast enhancement and venous flow occlusion. Focal central linear enhancement in the arachnoid nodule may represent extension of the
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endothelium-lined venous sinuses into the fissure of the granulation [6]. The conventional TOF MR venography technique, which does not require the use of a paramagnetic contrast agent, has evolved as a reliable and clinically accepted method for assessment of the venous system [8]. However, this technique has limitations: it is susceptible to pulsatility, in-plane saturation effects, and spin dephasing when laminar flow is disturbed [8]. In conclusion, it should be kept in mind that giant AG may be misdiagnosed as dural sinus thrombosis, which requires immediate approach. Before diagnosing focal, nodular defect in the sinuses as thrombosis, giant AG should be considered as a differential diagnosis. MRI and contrast-enhanced MRI venography are the most useful diagnostic tools to differentiate giant AG from dural sinus thrombosis. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – B.B.; Design – B.A.; Supervision – S.S.; Materials – B.A., E.A.; Data Collection – E.A.; Analysis – B.A., B.B.; Literature Search – E.A.; Writing – E.A.; Critical Review – S.S, A.A.
REFERENCES 1. Kan P, Stevens EA, Couldwell WT. Incidental giant arachnoid granulation. AJNR Am J Neuroradiol 2006;27:1491–2. 2. Lu CX, Du Y, Xu XX, Li Y, Yang HF, Deng SQ, et al. Multiple occipital defects caused by arachnoid granulations: Emphasis on T2 mapping. World J Radiol 2012;4:341–4. 3. Haybaeck J, Silye R, Soffer D. Dural arachnoid granulations and “giant” arachnoid granulations. Surg Radiol Anat 2008;30:417–21. 4. Brunori A, Vagnozzi R, Giuffrè R. Antonio Pacchioni (1665-1726): early studies of the dura mater. J Neurosurg 1993;78:515–8. 5. Choi HJ, Cho CW, Kim YS, Cha JH. Giant arachnoid granulation misdiagnosed as transverse sinus thrombosis. J Korean Neurosurg Soc 2008;43:48–50. 6. Leach JL, Jones BV, Tomsick TA, Stewart CA, Balko MG. Normal appearance of arachnoid granulations on contrast-enhanced CT and MR of the brain: differentiation from dural sinus disease. AJNR Am J Neuroradiol 1996;17:1523–32. 7. Haroun AA, Mahafza WS, Al Najar MS. Arachnoid granulations in the cerebral dural sinuses as demonstrated by contrastenhanced 3D magnetic resonance venography. Surg Radiol Anat 2007;29:323–8. 8. Ayanzen RH, Bird CR, Keller PJ, McCully FJ, Theobald MR, Heiserman JE. Cerebral MR venography: normal anatomy and potential diagnostic pitfalls. AJNR Am J Neuroradiol 2000;21:74–8.
Case Report
PEDIATRICS
North Clin Istanb 2017;4(2):188â&#x20AC;&#x201C;191 doi: 10.14744/nci.2016.47450
A rare cause of respiratory distress and edema in neonate: Panhypopituitarism Fatma Dursun,1 Heves Kirmizibekmez,1 Fazilet Metin2 Department of Pediatric Endocrinology, Umraniye Training and Research Hospital, Istanbul, Turkey
1
Department of Neonatology, Erdem Hospital, Istanbul, Turkey
2
ABSTRACT Clinical presentation of hypopituitarism may be variable in the neonate. Symptoms are generally nonspecific, ranging from absent to severe, and even life-threatening, due to adrenocorticotrophic hormone deficiency. Presently described is a case of unexplained respiratory distress and edema in a neonate. Initial screening revealed panhypopituitarism. Respiratory distress improved after replacement treatment with hydrocortisone and thyroxine. Keywords: Neonate; panhypopituitarism; respiratory distress.
C
ongenital hypopituitarism (CH) in the neonate, which manifests as deficiency in 1 or more pituitary hormones, can present with a highly variable phenotype, either as isolated hypopituitarism or with associated developmental defects, such as ocular, midline, and genital abnormalities [1]. Neonates may manifest with nonspecific clinical symptoms, such as poor feeding, hypoglycemia, prolonged neonatal jaundice, and lethargy, as consequence of combined pituitary hormone deficiencies, or may be initially asymptomatic, but at risk for developing pituitary hormone deficiencies over time. Adrenocorticotrophic hormone deficiency is associated with increased risk of neonatal death [1]. Early diagnosis of CH in absence of any obvious external malformations is often difficult during neonatal period as a result of nonspecific clinical presentation. In a case of clinical appearance as sepsis and circulatory disorder in neonate with negative acute phase
reactants and no response to antimicrobial treatment, CH should be suspected. Presently described is a case of a newborn diagnosed as CH with severe respiratory distress and generalized edema, but no specific symptom like hypoglycemia. Significant clinical improvement was observed after initiation of hormone replacement treatment. CASE REPORT A male newborn was transferred to the intensive care unit due to respiratory distress. He was born at 37th gestational week by cesarean section to a 42-year-old mother who had gestational diabetes. His general appearance was poor. Tachycardia, tachypnea, respiratory distress, hypotonia, hypoactivity, and generalized edema were present. He had facial dysmorphic findings and micropenis. Clinical findings are summarized in Table 1.
Received: August 23, 2015 Accepted: April 26, 2016 Online: August 26, 2017 Correspondence: Dr. Fatma DURSUN. Umraniye Egitim ve Arastirma Hastanesi, Istanbul, Turkey. Tel: +90 216 - 632 18 18 e-mail: fatmadursun54@yahoo.com Š Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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Table 1. Clinical features of the patient Clinical findings
1st day
3rd day
7th day
10th day
15th day
Physical examination 3750 3800 3650 3800 Weight (g) 3740 (>90th p.) Height (cm) 53 (>90th p.) Head circumference (cm) 38 (>90th p.) General appearance Poor. Generalized Enteral feeding, Poor feeding, Vomiting Edema and edema, particularly no hypoglycemia, vomiting, ceased and respiratory in the scalp. generalized hypotonia generalized distress Anterior fontanel: edema, no hypoactivity, edema disappeared, 4x4 cm, sagittal weight loss ongoing edema diminished enteral suture open no weight loss feeding Dysmorphic features Prominent forehead, low-set ears, flat nose, highly-arched palate Respiratory system Tachypnea, Tachypnea, retractions retractions Abdomen Normal External genitalia Testes: 1 mL/1 mL, Penile length: 2x1 cm Laboratory findings Blood gases pH: 7.17 pH: 7.33 pH: 7.23 pH: 7.36 pH: 7.37 HCO3: 21 HCO3 :2 HCO3: 18 HCO3: 24 HCO3: 25 pO2: 0.79 pO2: 0.60 pO2: 0.79 pO2: 0.78 pO2: 64 pCO2: 79 pCO2: 36 pCO2: 50 pCO2: 34 pCO2: 33 CRP (mg/dL) 0.3 (N <0.5) 0.4 0.5 1.3 0.3 Glucose (mg/dL) 45/50/92 94 79 70 94 Sodium (mEq/L) 135 129 135 122 139 Potassium (mEq/L) 3.5 3.9 4.9 4.1 5.2 TSH (mIU/mL) 6.15 (N: <5) 13 16 1.42 Free-T4 (ng/dL) 0.64 (N: >0.8) 0.6 0.73 1.29 Baseline cortisol (Âľg/dL) 0.44 30th min. cortisol (Âľg/dL) 4.5 LH (mIU/mL) 0.6 FSH (mIU/mL) 2.45 Total testosterone (ng/mL) 0.01 Treatment and progress Respiratory support Intubation CPAP Intubation Intubation Extubation (mechanical (mechanical (mechanical ventilation, surfactant) ventilation) ventilation) Medication Ampicillin+ Ampicillin+ Hydrocortisone Hydrocortisone Hydrocortisone gentamicin gentamicin (10 mg/m2/day) (10 mg/m2/day) (10 mg/m2/day) L-thyroxine L-thyroxine L-thyroxine (8 mcg/kg/day) (8 mcg/kg/day) (8 mcg/kg/day) vancomysin+ vancomysin+ meropenem meropenem CPAP: Continuous positive airway pressure; CRP: C-reactive protein; FSH: Follicle-stimulating hormone; L-thyroxine: Levothyroxine; LH: Luteinizing hormone; P: Percentile; N: Normal; T4: Thyroxine.
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Tracheal intubation was performed soon after hospitalization. Intratracheal surfactant was administered, since severe respiratory acidosis, clinical and radiological findings, and being the infant of diabetic mother suggested diagnosis of respiratory distress syndrome. Broad-spectrum antibiotics were prescribed. Umbilical catheterization was required, since peripheral venous puncture was prohibited by severe edema. Respiratory functions began to improve on third day, and continuous positive airway pressure was well tolerated at end of 72nd hour after surfactant treatment. Enteral feeding was also well tolerated, and no hypoglycemic attack was detected during follow-up. However, generalized edema did not diminish, expected weight loss was not observed, poor feeding, vomiting, hypoactivity, and hypotonia became apparent, and mechanical ventilation was again necessary on 7th day. Metabolic screening was normal. Portal, splenic, renal Doppler investigations, and echocardiography were normal. Laboratory analyses revealed central hypothyroidism with low free-thyroxine (T4) and slightly elevated thyroid-stimulating hormone (TSH) level. Hyponatremia was present, while potassium levels were all normal (Table 1). Baseline cortisol level was 0.44 µg/dL. Low-dose adrenocorticotropic hormone test (with 1 µg intravenous Synacthen; Mallinckrodt Specialty Pharmaceuticals Ireland Ltd., Dublin, Ireland) was performed and 30th minute cortisol level was 4.5 µg/dL, supporting diagnosis of secondary adrenal insufficiency. Glucocorticoid replacement with hydrocortisone and thyroid hormone replacement with levothyroxine were initiated. Vomiting and hyponatremia receded, and edema was significantly improved on the third day of treatment. He was extubated on the 15th day, and there was no need for supplemental oxygen on 23rd day. Gonadotrophic hormone levels were below levels expected in mini-puberty stage. DISCUSSION Clinical presentation of hypopituitarism in the neonate varies, ranging from absent to severe, nonspecific symptoms. Pituitary hormone deficiencies, especially adrenocorticotropic hormone deficiency, may be life-threatening in severely ill patients [1–3]. Diagnosis of hypopituitarism must be based on clinical grounds, especially when hypoglycemia,
prolonged jaundice, micropenis, or midline alterations are found in neonatal period. Neonatal presentation may be mistaken for sepsis, which can present with similar clinical features of hypothermia, hypoglycemia, lethargy, and poor feeding [4]. Hypoglycemia, which is most common finding of CH, was not present in our patient, suggesting that it is not essential. Whenever central hypothyroidism is detected in a patient, accompanying anterior pituitary hormone deficiencies should be considered, since 78% of patients with central hypothyroidism have been found to have another pituitary hormone deficiency. Central hypothyroidism is characterized by low free-T4 level with discordantly normal or mildly elevated TSH level [5]. Hyponatremia may be present even if mineralocorticoid synthesis is adequate, since cortisol is needed for free-water excretion action of anti-diuretic hormone. Due to its effect on the stabilization of blood pressure, cortisol deficiency also may lead to hemodynamic instability and even shock [6]. Micropenis, which may arise from gonadotropin deficiency or growth hormone deficiency, might be another important finding of hypopituitarism in male infants [7]. The underlying cause of hemodynamic instability in the present patient was CH. Severe edema and respiratory distress did not improve with conventional therapies. Dramatic clinical response to hormone replacement treatment was observed. Unexplained edema and respiratory distress in a neonate and associated with dysmorphic findings suggesting midline defect and hypogenitalia should bring CH to mind. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – F.M.; Design – F.M.; Supervision – F.M.; Materials – F.M.; Data collection &/or processing – F.M., H.K.; Literature search – F.M.; Writing – F.M., H.K.; Critical review – F.M.
REFERENCES 1. Filges I, Bischof-Renner A, Röthlisberger B, Potthoff C, Glanzmann R, Günthard J, et al. Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4. Pediatrics 2012;129:529–34.
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2. Scommegna S, Galeazzi D, Picone S, Farinelli E, Agostino R, Bozzao A, et al. Neonatal identification of pituitary aplasia: a lifesaving diagnosis. Review of five cases. Horm Res 2004;62:10–6. 3. Vallette-Kasic S, Brue T, Pulichino AM, Gueydan M, Barlier A, David M, et al. Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations. J Clin Endocrinol Metab 2005;90:1323–31. 4. Lammoglia JJ, Eyzaguirre F, Unanue N, Román R, Codner E, Cassorla F, et al. Congenital hypopituitarism: report of 23 cases.
191 Rev Med Chil 2008;136:996–1006. 5. van Tijn DA, de Vijlder JJ, Verbeeten B Jr, Verkerk PH, Vulsma T. Neonatal detection of congenital hypothyroidism of central origin. J Clin Endocrinol Metab 2005;90:3350–9. 6. Geffner ME. Hypopituitarism in childhood. Cancer Control 2002;9:212–22. 7. Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab 2005;90:3122–7.
Case Report
GENERAL SURGERY
North Clin Istanb 2017;4(2):192â&#x20AC;&#x201C;194 doi: 10.14744/nci.2015.53825
An infrequent case of intussusception caused by gastrointestinal stromal tumor in an adult patient Mehmet Mahir Fersahoglu,1 Ayse Tuba Fersahoglu,1 Nuriye Esen Bulut,1 Burcu Seher Anil Narin,2 Sinan Tezer1 Department of General Surgery, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
1
Department of Radiology, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
2
ABSTRACT Intussusception may occur anywhere in the gastrointestinal system. Unlike its idiopathic childhood counterpart, it is uncommon during adult life and a definitive cause is usually found; almost half of cases develop with malignancy. Gastrointestinal stromal tumors (GIST) originate from interstitial Cajal cells of the gastrointestinal tract. They more frequently occur in the stomach and small intestines, and often grow extraluminally, making it unlikely to cause an obstruction or bleeding. Presently described is an unusual instance of ileo-ileal intussusception due to GIST. Keywords: Intussusception; stromal tumor.
I
ntussusception is an entity that develops as a telescopic intubation of a proximal intestinal segment into a distal segment, and rarely (1%), may cause a mechanical obstruction in any region of the gastrointestinal system. In childhood, idiopathic etiology is typical, while in almost all adult patients, an etiological factor can be demonstrated. In nearly half of adult cases, intussusception develops secondary to a malignancy [1, 2]. Symptoms of mechanical obstruction due to intussusception can occur acutely, or it may develop in an intermittent, chronic form secondary to spontaneous resolution of telescoped bowel segments and re-invagination over time. Gastrointestinal stromal tumors (GIST)
originating from Cajal cells, which assume the task of a pacemaker in the interstitial area, may occasionally lead to intussusception [3]. Since GISTs have a tendency to grow into extraluminal space, they rarely invaginate. Currently described is an infrequently encountered case of intussusception secondary to GIST, which represents 0.4 % of all gastrointestinal tumors. CASE REPORT A 64-year-old male patient presented at the outpatient clinic of general surgery with complaints of abdominal pain, frequent belching, and weight loss for
Received: October 15, 2015 Accepted: December 08, 2015 Online: August 26, 2017 Correspondence: Dr. Mehmet Mahir FERSAHOGLU. Fatih Sultan Mehmet Egitim Arastirma Hastanesi, Genel Cerahi Klinigi, Istanbul, Turkey. Tel: +90 216 - 578 30 00 e-mail: fersahoglu@yahoo.com Š Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
Fersahoglu et al., An infrequent case of intussusception caused by gastrointestinal stromal tumor in an adult patient
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Figure 2. Macroscopic appearance of invaginated ileal Figure 1. Computed tomography image of invaginated
loop.
ileal segment.
previous 3 to 4 months. The patient indicated that he had occasional episodes of nausea without vomiting, but no problem with defecation. His personal history did not reveal any known disease or malignant disease in his family history. On physical examination, the only remarkable abdominal finding was minimal tenderness in the right lower quadrant. Digital rectal examination findings were also unremarkable. Serum biochemical and hematological parameters were within normal limits (white blood cell count: 7700 K/uL, hemoglobin: 12.8 g/dL, alanine aminotransferase: 10 IU/L, aspartate aminotransferase: 13IU/L). Plain abdominal radiographs were unremarkable. Abdominal computed tomographs (CT) obtained to clarify reason for the tenderness localized in the lower abdominal quadrant revealed a mass lesion interpreted as plastron appendicitis in the area of the cecum or invagination (Figure 1). No abnormal finding was detected during colonoscopic or gastroscopic examination performed to detect intraluminal pathology. Laparoscopic exploration revealed invaginated bowel segments 30 cm proximal to the terminal ileum. However, due to the presence of diffuse adhesions, laparotomy was performed. The bowel segment was excised en bloc, and intestinal continuity was achieved with side-to-side ileo-ileal anastomosis (Figures 2, 3). The postoperative period was uneventful and the patient was discharged on postoperative fifth day. After completion of histopathological analysis, the patient was diagnosed as GIST, and he is currently monitored by the oncology clinic (tumor diameter: 8x5x5 cm; mitotic activity: decreased [5/50
Figure 3. Stromal tumor that caused invagination. BBA]; proto-oncogene c-Kit: >50% ++ staining intensity. The lesion did not stain with CD34, smooth muscle actin, or desmin. S100: less than 10% of the cells were stained; Ki-67 score: low [1%]). DISCUSSION More than 90% of GISTs are seen in people aged >40 years. Although it is more frequently seen in men compared with women, incidence does not differ according to geographic region or ethnicity. [3]. It may cause bleeding or gastrointestinal symptoms. When it reaches a large size, in 20% of cases, intussusception can be seen, secondary to pain, palpable mass, and obstruction [4]. Intussusception that develops with the infolding of a proximal bowel segment into a distal segment is rarely seen in adult patients. Symptoms are typically nonspecific, including recurrent abdominal pain, nausea, and vomiting. In half of these patients, the lead point of telescopic infolding is malignant [2].
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In nearly one-third of patients, preoperative diagnosis can be made based on history and physical examination combined with imaging modalities [5]. On ultrasonograph, telescopic multilayered intestinal wall may be visualized as a “bull’s eye” or a “target sign.” (Figure 1). Definitive diagnosis can be made based on intraoperative findings; however, oral or intravenous contrast-enhanced abdominal CT yields the most accurate result [6]. Usually, GISTs grow exophytically to the peripheral tissues and do not lead to the development of intussusception. However, since they retain the possibility –though rarely – like a pedunculated or sessile polyp, as was seen in this case, they can induce intussusception [7, 8]. Histological differentiation of GIST tumor from intestinal mesenchymal tumor can be achieved with CD117 staining or demonstration of the presence of proto-oncogene c-Kit. A newly developed oral formulation of a selective thyrosine kinase inhibitor with small molecular structure, imatinib, has enabled the prevention of recurrent GISTs during the postoperative period. Before the introduction of imatinib treatment, surgical excision was the only treatment modality, but recurrence rate remained high [9]. When adjuvant imatinib was administered to high-risk patients following surgical excision of GIST, a marked prolongation of survival time was observed when compared with placebo [10, 11]. Based on these results, the use of imatinib as an adjuvant treatment in high-risk patients after surgical resection of GIST was approved by US Food and Drug Administration (FDA) in 2008, and the European Medicines Agency (EMA) in 2009. In a recent randomized Phase III study that included 400 high-risk GIST patients, imatinib treatment for 3 years provided statistically significant improvement over 1-year imatinib treatment (recurrence-free survival: 65.6% vs 47.9%; p<0.001 and overall survival: 92% vs 81.7%; p<0.02) [12]. Based on these outcomes, concurrently, both the FDA and the EMA advised that adjuvant treatment be maintained for 36 months in high-risk patients. Since spread to regional lymph nodes is rarely seen, segmental resection is a sufficiently acceptable intervention in surgical procedure targeting the tumor, rather than peritumoral resection. Conclusion Intussusception is very rarely seen in adult patients. Compared to the idiopathic variant in observed in
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childhood, in almost all adult patients an underlying cause is found. GIST is a rare etiology in adult intussusception, and since the growth pattern does not usually suggest this possibility, this atypical presentation should be kept in mind in adult cases of intussusception. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – M.M.F.; Design – M.M.F.; Supervision – M.M.F.; Materials – M.M.F., N.E.B; Data collection &/or processing – M.M.F., A.T.F., N.E.B, B.S.A.N.; Literature search – M.M.F.; Writing – M.M.F., S.T.; Critical review – A.T.F.
REFERENCES 1. Azar T, Berger DL. Adult intussusception. Ann Surg 1997;226:134–8. 2. Begos DG, Sandor A, Modlin IM. The diagnosis and management of adult intussusception. Am J Surg 1997;173:88–94. 3. Sornmayura P. Gastrointestinal stromal tumors (GISTs): a pathology view point. J Med Assoc Thai 2009;92:124–35. 4. Wang LT, Wu CC, Yu JC, Hsiao CW, Hsu CC, Jao SW. Clinical entity and treatment strategies for adult intussusceptions: 20 years’ experience. Dis Colon Rectum 2007;50:1941–9. 5. Ghaderi H, Jafarian A, Aminian A, Mirjafari Daryasari SA. Clinical presentations, diagnosis and treatment of adult intussusception, a 20 years survey. Int J Surg 2010;8:318–20. 6. Jai SR, Bensardi F, Chehab F, Khaiz D, Bouzidi A. Jejunal lipoma with intermittent intussusception revealed by partial obstructive syndrome. Saudi J Gastroenterol 2008;14:206–7. 7. Vasiliadis K, Kogopoulos E, Katsamakas M, Karamitsos E, Tsalikidis C, Pringos B, et al. Ileoileal intussusception induced by a gastrointestinal stromal tumor. World J Surg Oncol 2008;6:133. 9. Gupta A, Gupta S, Tandon A, Kotru M, Kumar S. Gastrointestinal stromal tumor causing ileo-ileal intussusception in an adult patient a rare presentation with review of literature. Pan Afr Med J 2011;8:29. 9. Hoshino N, Murata T, Oka K, Kawakami K, Hoshino K, Sekoguchi S, et al. Gastrointestinal stromal tumors of the small intestine that expressed c-kit protein. Intern Med 2000;39:914–9. 10. Nilsson B, Sjölund K, Kindblom LG, Meis-Kindblom JM, Bümming P, Nilsson O, et al. Adjuvant imatinib treatment improves recurrence-free survival in patients with high-risk gastrointestinal stromal tumours (GIST). Br J Cancer 2007;96:1656–8. 11. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, et al; American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009;373:1097–104. 12. Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA 2012;307:1265–72.
Case Report
DERMATOLOGY
North Clin Istanb 2017;4(2):195–198 doi: 10.14744/nci.2016.51523
Coexistence of eruptive syringoma and bilateral nipple vitiligo: Could there be a common immunopathogenesis? Sirin Yasar,1 Nurhan Doner,2 Pembegul Gunes3 Department of Dermatology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
1
Department of Dermatology, Erzurum Numune Training and Research Hospital, Erzurum, Turkey
2
Department of Pathology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
3
ABSTRACT The rarely seen eruptive syringoma (ES) is characterized by small, skin-colored, papules. Lesions are benign; however, treatment is often unsuccessful. Recent studies have a suggested role of the autoimmune response, rather than reactive proliferation of acrosyringium in the pathogenesis of ES. There are reports in the literature of an association between syringoma and diabetes mellitus as well as alopecia areata, which support a theory of an autoimmune role; however, there has been no report of coexistence of ES and vitiligo thus far. Presently described is a case of bilateral nipple vitiligo and eruptive syringoma in a 29-year old female. Keywords: Autoimmunity; syringoma; vitiligo.
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yringomas are benign adnexal tumors originating from the eccrine sweat glands. They usually appear as several small, round, smooth-surfaced, yellowish, papules. They are often located on the face and around the eyelids [1]. Eruptive syringoma (ES), occurring more often in puberty and adolescence, presents as multiple papules, often located on the trunk [1, 2]. Although ES may appear to be simple, lesions may be confused with acne vulgaris, sebaceous hyperplasia, eruptive xanthoma, Darier’s disease, Fox-Fordyce disease, verruca plana, lichen planus, mastocytosis, granuloma annulare, lichen nitidus, pseudoxanthoma elasticum, trichoepithelioma or sarcoidosis [1–3].
The case of a 29-year-old female with bilateral vitiligo localized to bilateral breast areolae and coexisting eruptive syringoma is presently described. CASE REPORT A 29-year-old female patient presented at the outpatient clinic with complaints of depigmentation on bilateral nipples that appeared during childhood and yellow-brown papules proliferating over time on the trunk and face. She had no complaints other than for cosmetic reasons. The patient reported that approximately 2 years after nipple depigmentation, yellow-brown lesions began to spread from front
Received: February 26, 2015 Accepted: June 13, 2016 Online: August 26, 2017 Correspondence: Dr. Sirin YASAR. Haydarpasa Numune Egitim ve Arastirma Hastanesi, Dermatoloji Klinigi, Istanbul, Turkey. Tel: +90 216 - 414 45 02 e-mail: drsirin@gmail.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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B
C
Figure 1. (A, B, C) Multiple syringomas located near the eyes, on the neck, and on the thorax. A
B
C
Figure 2. (A, B, C) Coexistence of bilateral nipple areolae vitiligo and eruptive syringoma. part of the chest to the lower part of the abdomen and to the face, including the eyelids. There was nothing noteworthy in the past medical history of the patient. Family history revealed that her sister was being followed-up with diagnosis of morphea. Systemic inquiry and physical examination were normal. Dermatological examination revealed some skin-colored lesions around the eyes, and multiple, yellow-brown pigmented papular lesions under the chin, on the neck, the trunk, on both breasts (Figure 1 A–C), and the abdomen measuring 1 to 5 mm in diameter (Figure 2 A–C). Some hypo-pigmented patches were observed on the bilateral areolae and
Wood’s lamp examination was consistent with vitiligo. The patient refused biopsy from areola region. No abnormality was detected in the laboratory test results (complete blood count, biochemical parameters, blood glucose, glycated hemoglobin, and extractable nuclear antigen antibody profiles). A 4-mm punch biopsy was taken from papular lesions on front of the chest with prediagnosis of eruptive histiocytosis, eruptive xanthoma, eruptive lichen, urticaria pigmentosa and syringoma. Histopathological examination established diagnosis of syringoma by determining dilated cystic cavities lined with epi-
Yasar et al., Coexistence of eruptive syringoma and bilateral nipple vitiligo
A
B
Figure 3. (A, B) Diagnosis of syringoma was established in the histopathological examination by determining dilated cystic cavities lined with epithelial and cuboidal cells (H&E x100, x200).
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A
B
thelial and cuboidal cells (Figure 3 A, B). Based on assessment of clinical and histopathological findings, the patient was diagnosed with ES. Cryotherapy was performed twice for 5 seconds to all lesions separately to create double freeze-thaw cycle, but there was no satisfactory response. Topical tretinoin and systemic isotretinoin 20 mg for 6 months also resulted in only slight flattening of lesions (Figure 4 A, B). DISCUSSION Syringomas are benign eccrine sweat gland tumors with a frequency in the population of 0.6%. Females are affected by syringomas more often than males. The clinical appearance of syringomas is typically several, asymptomatic, small, round, smooth-surfaced, yellowish papules. They are more commonly located on the face and around the eyelids, less often in the genital area, on the scalp, the neck, the trunk, or the armpits [1â&#x20AC;&#x201C;3]. Tumors mostly occur in adolescence and may increase in number with age. Friedman and Butler distinguished 4 clinical variants of syringoma: a localized form, a form associated with Downâ&#x20AC;&#x2122;s syndrome, a familial form, and a form that encompasses ES [3]. ES, first described by Darier and Jaquet, is rare variant of syringoma and is characterized by multiple papules occurring in puberty and in adolescence, usually located on the trunk [3]. Histopathology of syringoma reveals ductal structures that are usually
Figure 4. (A) Edema and erythema after cryosurgery. (B) Partial remission after therapy.
lined by 2 rows of cuboidal-to-flattened epithelial cells in the upper and middle dermis embedded in sclerotic stroma, and some ducts have elongated tails of epithelial cells that produce the characteristic comma-shaped or tadpole appearance [1, 2]. Histopathology examination of papular lesions on the trunk of our patient was consistent with syringoma.
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ES is disease of unknown pathogenesis that may have a sporadic or hereditary etiology. Diseases reported to be associated with ES include trisomy 21, Marfan syndrome, Ehler-Danlos syndrome, sarcoidosis, diabetes mellitus, cicatricial alopecia, and alopecia areata [2–6]. Some authors have reported that in the etiology of the disease, the inflammatory process leads to syringoma by evoking a hyperplasic response in the eccrine glands [2, 7, 8]. Vitiligo is known as pigmentary disorder of the skin and mucous membranes. Autoimmune mechanisms, neural interaction, and cytotoxicity are focuses of etiology. Diseases associated with vitiligo include autoimmune diseases, such as Hashimoto’s thyroiditis, pernicious anemia, alopecia areata, morphea, and diabetes mellitus [9]. It has been suggested that the disease occurs as result of melanocytes targeted by autoantibodies produced by these diseases. Damage to melanocytes may also be induced by autocytotoxic effect occurring in response to viral or other triggering factors [9]. Reports on an association of other autoimmune diseases with ES and vitiligo suggest that, as in our case, coexistence of vitiligo and ES may be result of common immunopathogenesis. In our patient, lesions of vitiligo on the nipples developed first, subsequently followed by syringomas. We believe that the inflammatory response leading to vitiligo also gave rise to syringoma by evoking a hyperplasic response to acrosyringium. In our patient, because evident inflammatory cell infiltration was not observed around the eccrine glands on histological examination, noncell-dependent immune response mechanisms may have played a role in incidence of these 2 conditions. To our knowledge, no association of ES and vitiligo has been reported in the literature. Although patients with vitiligo and syringoma were encountered in studies dermatologically assessing patients with Down’s syndrome, an association of the 2 diseases was not mentioned [10].
For the first time, we report case of coexisting vitiligo and ES. It is thought that the inflammatory process caused by a factor or factors that triggered vitiligo may have given rise to ES. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – S.Y., N.D., P.G.; Design – S.Y., N.D., P.G.; Supervision – S.Y., N.D., P.G.; Materials – S.Y., N.D., P.G.; Data collection &/or processing – S.Y., N.D., P.G.; Literature search – S.Y., N.D., P.G.; Writing – S.Y., N.D., P.G.; Critical review – S.Y., N.D., P.G.
REFERENCES 1. Thomas VD, Swanson NA, Lee KK.Benign epithelial tumors, hamartomas and hyperplasias.In:Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Pallers AS, Lefell DJ, et al., editors.Fitzpatrick’s. Dermatology in general medicine. 7th ed. New York: Mc Graw Hill; 2008. pp. 1054–67. 2. Soler-Carrillo J, Estrach T, Mascaró JM. Eruptive syringoma: 27 new cases and review of the literature. J Eur Acad Dermatol Venereol 2001;15:242–6. 3. Jamalipour M, Heidarpour M, Rajabi P. Generalized eruptive syringomas. Indian J Dermatol 2009;54:65–7. 4. Janniger CK, Brodkin RH. Eruptive syringomas. Cutis 1990;46:247–9. 5. Urban CD, Cannon JR, Cole RD. Eruptive syringomas in Down’s syndrome. Arch Dermatol 1981;117:374–5. 6. Barnhill RL, Goldberg B, Stenn KS. Proliferation of eccrine sweat ducts associated with alopecia areata. J Cutan Pathol 1988;15:36–9. 7. Guitart J, Rosenbaum MM, Requena L. ‘Eruptive syringoma’: a misnomer for a reactive eccrine gland ductal proliferation? J Cutan Pathol 2003;30:202–5. 8. Dyall-Smith DJ, Connors TJ, Scurry J. Generalised eruptive syringoma--a papular dermatosis. Australas J Dermatol 1990;31:95–8. 9. Sehgal VN, Srivastava G. Vitiligo: auto-immunity and immune responses. Int J Dermatol 2006;45:583–90. 10. Daneshpazhooh M, Nazemi TM, Bigdeloo L, Yoosefi M. Mucocutaneous findings in 100 children with Down syndrome. Pediatr Dermatol 2007;24:317–20.
Case Report
GENERAL SURGERY
North Clin Istanb 2017;4(2):199–202 doi: 10.14744/nci.2016.72677
Acute gastric dilatation due to binge eating may be fatal Oguzhan Dincel, Mustafa Goksu Department of General Surgery, Adiyaman University, Faculty of Medicine, Adiyaman, Turkey
ABSTRACT Acute gastric dilatation was first described by Duplay in 1833. Since the stomach has rich blood circulation, necrosis and perforation due to dilatation are rarely seen. Clinically, more than 90% of cases have complaints of vomiting. The most useful method to determine diagnosis and etiology is computerized tomography (CT). Medical treatment is suitable for cases that have no necrosis or peritonitis findings. Delay in surgical treatment increases the risk of mortality. The present case is that of a diagnosis of gastric perforation due to acute gastric dilatation in a 24-year-old female patient. Keywords: Binge eating; gastric dilatation; intravascular disseminated coagulation; mortality.
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astric necrosis and perforation after gastric dilatation are rare because the stomach has a rich blood supply, but occurrence can be life threatening. Pathogenesis is still controversial. The most frequent complaints are abdominal pain and vomiting, and there is usually also abdominal bloating. Emergency surgery is required for patients with gastric necrosis and perforation [1-3]. The present case reports on gastric decompression and closure of perforation in a patient with acute gastric dilatation due to overeating. CASE REPORT A 24-year-old female was admitted to the emergency room (ER) with sudden onset of abdominal
pain, nausea and vomiting after eating a heavy meal 6 hours previously. Patient reported eating an excessive amount of grapes and pomegranates hours prior. Her pain was sharp, severe, and worst in the epigastrium. Physical examination revealed a thin, uncomfortable-appearing young woman. Patient exhibited abdominal swelling, rigidity, and diffuse tenderness with peritonitis on palpation. All other examination findings were non-contributory. When the patient presented to the ER, vital signs were as follows: blood pressure (BP) 125/80 mmHg, pulse 75 beats/minute, respiratory rate 16 breaths/minute, and a body temperature of 36.5°C. Amount of urine from urinary catheter placed in bladder was approximately zero. Nasogastric tube inserted into
Received: November 26, 2015 Accepted: February 07, 2016 Online: April 04, 2016 Correspondence: Dr. Oguzhan DINCEL. Adiyaman Universitesi Tip Fakultesi, Genel Cerrahi Anabilim Dali, Adiyaman, Turkey. Tel: +90 416 781 61 31 e-mail: droguzhandincel@yahoo.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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the stomach was not effective because it was full of undigested stomach contents. Chemistries and hemogram were normal. Abdominal computed tomography (CT) showed a grossly distended stomach occupying the entire abdominal cavity. Coronal image of abdominal CT scan revealed distended stomach containing air and radiodense material, later determined to be grapes and pomegranates (Figure 1). Sagittal image of abdominal CT showed that stomach over-distended with food content led to displacement of intra-abdominal structures (Figure 2). During systemic examination, patient was checked for cyanotic condition and no pulse could be detected in either of lower extremities. Moreover, pulse rose to tachycardic rate of 125-135 beats/minute, respiratory rate was 30-35 breaths/minute and BP was 70/45 mmHg 2 hours after first checked. The patient was intensively resuscitated preoperatively with crystalloid intravenous (IV) fluids and
plasma expander. Shock occurred and patientâ&#x20AC;&#x2122;s breathing worsened (oxygen saturation of 65% on air). An emergency operation was performed. The patient underwent laparotomy (epigastric midline incision) that revealed massively distended stomach with perforation of gastric antrum. Stomach was filled with nearly 5 liters of partially and minimally digested food, including whole grapes and pomegranate matter. Following adequate decompression, stomach was moved from wound site, remaining contents were emptied, and perforation was closed (Figure 3). No discrete bezoar or mechanical gastric outlet obstruction was identified.
Figure 1. Distended stomach containing air and radiodense material.
Figure 2. Distended stomach containing food material.
DISCUSSION Duplay first defined acute gastric dilatation in 1833 [4]. Although there is no mechanical obstruction in acute gastric dilatation, stomach becomes increasingly hypotonic and over-stretched [5]. A heavy
Dincel et al., Acute gastric dilatation due to a binge eating may be fatal
Figure 3. Perforation of gastric antrum.
meal, adhesive ileus, infection, parturition, central nervous system damage, and trauma are some causes of gastric dilatation [6]. Acute gastric dilatation due to overeating is more common in females with underlying eating disorders, such as anorexia nervosa [7]. In the present case, the patient was female and had eaten an excessive quantity of grapes and pomegranates. Because of its extensive vascular network, the stomach is usually protected from ischemia, so necrosis and perforation of the stomach are rare. Due to the fact that excessive gastric dilatation increases intragastric pressure, intramural blood circulation can be reduced, possibly leading to gastric necrosis or perforation [8]. In the present case, perforation was observed in the gastric antrum. Rapid gastric decompression and appropriate fluid resuscitation reduce the pressure inside the stomach, thus preventing necrosis and perforation
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of the stomach. For that reason, these methods should be employed as early as possible [9]. In the present case, there was not effective gastric drainage and due to an increase in intragastric pressure, a perforation occurred. Clinically, more than 90% of cases present with vomiting. Epigastric fullness, abdominal distention and pain may also be present [10, 11]. The present patient experienced abdominal pain, nausea, and vomiting. Abdominal distension, epigastric sensitivity, defence and rebound tenderness can be detected on physical examination. Abdominal x-ray may reveal a large air-fluid level that belongs to the fundus of the stomach, and subdiaphragmatic free air in cases with perforation. The most useful imaging modality is abdominal CT, which is not only useful in diagnosis but also in revealing the etiology [12]. The excessive increase in stomach contents through acute gastric dilatation compresses the gastric wall and leads to necrosis and perforation of the stomach. It also leads to compression on the inferior vena cava, and causes hypotension due to the decrease in venous return. Acute gastric dilatation can be controlled by nasogastric decompression and appropriate fluid-electrolyte therapy. Upper gastrointestinal endoscopy can help decompression. Medical treatment is suitable in cases without signs of peritonitis on examination [1, 4]. Advanced cases with necrosis and perforation require surgical intervention [1]. Mortality rates after delayed surgery in patients with necrosis and perforation are reported to be as high as 80% [13]. Surgical treatment options include surgical decompression, partial gastrectomy, total gastrectomy and esophago-jejunostomy, total gastrectomy with cervical esophagostomy, and feeding jejunostomy [1, 3, 4, 11]. In the present case, perforation at the antrum of the stomach was detected during operation. Therefore, decompression and simple closure were performed. However, the patient died on the first postoperative day due to sepsis and disseminated intravascular coagulopathy. Acute gastric dilatation is a condition to be considered in patients with eating disorders. The sus-
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pected diagnosis and early management can avoid complications and decrease mortality substantially. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support. Authorship contributions: Concept – O.D., M.G.; Design – O.D., M.G.; Data Collection – O.D., M.G.; Analysis – O.D., M.G.; Literature search – O.D., M.G.; Writing – O.D.
REFERENCES 1. Turan M, Sen M, Canbay E, Karadayi K, Yildiz E. Gastric necrosis and perforation caused by acute gastric dilatation: report of a case. Surg Today 2003;33:302–4. 2. Bortul M, Scaramucci M, Tonello C, Spivach A, Liguori G. Gastric wall necrosis from organo-axial volvulus as a late complication of laparoscopic gastric banding. Obes Surg 2004;14:285–7. 3. Lim JE, Duke GL, Eachempati SR. Superior mesenteric artery syndrome presenting with acute massive gastric dilatation, gastric wall pneumatosis, and portal venous gas. Surgery 2003;134:840–3. 4. Todd SR, Marshall GT, Tyroch AH. Acute gastric dilatation revisited. Am Surg 2000;66:709–10. 5. Hiraga M, Ono F, Omura N, Sato M, Yamamura A. A case of gastric necrosis and perforation due to overeating-induced gastric
North Clin Istanb dilatation: A case report. J Jpn Surg Assoc 2012;73:1933–37. 6. Kaneda T, Miyazawa H, Kobayashi T, Shimizu N, Katayama M, Sato T. A case of acute gastric dilatation occurring after bulimia while on a diet. J Tokyo Med Univ 1996;54:66–8. 7. Natsume S, Terasaki M, Goto Y, Kurumiya Y, Shingu Y. A case of gastric necrosis. J Abdom Emerg Med 2003;23:1075–8. 8. Usuda M, Koizumi M, Kouda H, Nakahara C, Ueki H, Shibazaki S. Gastric necrosis caused by acute gastric dilatation after an episode of bulimia-A case report. Jpn J Gastroenterol Surg 1998;31:2346–9. 9. Nakao A, Isozaki H, Iwagaki H, Kanagawa T, Takakura N, Tanaka N. Gastric perforation caused by a bulimic attack in an anorexia nervosa patient: report of a case. Surg Today 2000;30:435–7. 10. Chaun H. Massive gastric dilatation of uncertain etiology. Can Med Assoc J 1969;100:346–8. 11. Holtkamp K, Mogharrebi R, Hanisch C, Schumpelick V, Herpertz-Dahlmann B. Gastric dilatation in a girl with former obesity and atypical anorexia nervosa. Int J Eat Disord 2002;32:372– 6. 12. Adson DE, Mitchell JE, Trenkner SW. The superior mesenteric artery syndrome and acute gastric dilatation in eating disorders: a report of two cases and a review of the literature. Int J Eat Disord 1997;21:103–14. 13. Koyazounda A, Le Baron JC, Abed N, Daussy D, Lafarie M, Pinsard M. Gastric necrosis caused by acute gastric dilatation. Total gastrectomy. Recovery. J Chir (Paris) 1985;122:403–7.
Original Images
CARDIAC SURGERY
North Clin Istanb 2017;4(2):203–204 doi: 10.14744/nci.2017.97658
A rare involvement in Behcet’s Disease: Carotid artery aneurysm Hamit Serdar Basbug, Yalcin Gunerhan, Hakan Gocer, Kanat Ozisik Department of Cardiovascular Surgery, Kafkas University Faculty of Medicine, Kars, Turkey
A 20-year-old male was admitted to the outpatient clinic with the complaint of a mass on the left side of his neck. According to the anamnesis, the mass had initially appeared 1 year earlier and slowly grew larger. He had a 4-year history of relapsing oral and genital ulcers that was diagnosed as Behcet’s disease 2 years prior. He had impaired vision in his left eye and a minimal sense of light in his right eye. Physical examination revealed a pulsatile mass on the left side of his neck (Figure 1). Color Doppler ultrasound examination revealed a true aneurysm of the left carotid artery with dimensions of 27.5 mm x 20.3 mm (Figure 2). Transverse slice of computerized tomography (CT) angiography demonstrated an aneurysm at the level of the left carotid bifurcation (Figure 3). A 3-dimensional reconstruction of the CT angiography views illustrated a saccular aneurysm and its relationship to the skeletal system (Figure 4A) and to vascular structures only (Figure 4B), indicating that the aneurysm was discrete and did not involve the aortic arch or other great vessels. The patient was prescribed prednisone (80 mg/day), azathioprine (150 mg/day), colchicine (1 mg/day), and acetylsalicylic acid (150 mg/ day), and discharged upon his rejection of surgical or endovascular treatment. Behcet’s disease is a systemic immune vasculitis that often presents with recurrent oral and genital mucous membrane ulcers (aphthae) accompanied
Figure 1.
Morphological view.
by skin lesions, gastrointestinal involvement, ocular disease, neurological manifestations, vascular pathologies, or arthritis. Although some compo-
Received: January 23, 2017 Accepted: March 23, 2017 Online: August 26, 2017 Correspondence: Dr. Hamit Serdar BASBUG. Kafkas Universitesi Tip Fakultesi Kalp ve Damar Cerrahisi Pasacayiri, 36100 Kars, Turkey. Tel: +90 474 - 225 11 90 e-mail: s_basbug@hotmail.com © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com
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Figure 2. Color Doppler ultrasound view showing the true carotid aneurysm (top) and the diameter (bottom). nents of Behcet’s may have been referenced by Hippocrates, the disease was first fully described and brought to the attention of medical society by Hulusi Behcet in 1937. Clinical manifestations of Behcet’s disease are mostly due to systemic vasculitis. Compared to all other systemic vasculitides, Behcet’s disease is notable for its potential to affect blood vessels of all sizes (large, medium, and small) on both the venous and arterial side of the vasculature. Deep venous thrombosis and thrombophlebitis are the most frequent vascular manifestations, followed by an arterial aneurysm and obstruction. Arterial aneurysms mostly occur in the abdominal aorta and pulmonary arteries. According to the recent literature, less than 50 cases of extracranial carotid artery aneurysm have been reported. In conclusion, vascular complications are the most important predictors of mortality and morbidity in Behcet’s disease. Appropriate medical treatment should be constituted as far as possible and surgical and endovascular treatment options should be evaluated without delay before a possibly irreversible complication occurs.
Figure 3.
Computed tomography angiography transverse slice revealing the carotid aneurysm.
A
Figure 4.
B
(A) Computed tomography (CT) angiography (3-dimensional reconstruction with vascular and bony structures) illustrating the relationship of the carotid aneurysm to the skeletal system. (B) CT angiography (3-dimensional reconstruction with only vascular structures) indicating that the carotid aneurysm was discrete and that there was no accompanying aneurysm(s) of the great vessels.