Southern Clinics of Istanbul Eurasia by KAREPUBLISHING

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Southern Clinics of Istanbul Eurasia Volume 29 • Issue 3 • September 2018

Southern Clinics

•

ır m a H a

Formerly Kartal Eğitim ve Araştırma Hastanesi Tıp Dergisi

Volume 29 • Issue 3 • September 2018 Editor-in-Chief

ORIGINAL ARTICLES

Recep DEMİRHAN

Surgical Treatment of Pulmonary Metastasectomy: Analysis of 92 Cases E. E. Cesur et al.

Associate Editors

The Relationship Between Health Literacy, Diabetic Control, and Disease-Specific Complications in Patients with Type 1 Diabetes Mellitus İ. Esen et al.

Özcan KESKİN Sevda ŞENER CÖMERT Gaye FİLİNTE Fatih TARHAN Ayşe BATIREL Publishing Manager Hüseyin ÇETİN

The Alvarado Score and Computed Tomography for Predicting Acute Appendicitis in Elderly Patients S. Kaya et al. Comparison of Early Postoperative Recovery after Desflurane or Sevoflurane Anesthesia Ö. Sezen et al. Which Biomarkers Help to Distinguish Between Candida and Aspergillus in Patients with Pulmonary Infections? A. F. Hazar et al. Predictors of Vesicoureteral Reflux in the Pretransplant Evaluation of Patients with End-Stage Renal Disease E. Parmaksız et al. How Urgent are Blood Transfusions Provided in Emergency Service? Y. Özgür et al. Evaluation of the Factors Affecting Percutaneous Success and Complications of Nephrolithotomy O. M. İpek et al. Parathyroidectomy After Kidney Transplantation: A Single-Center Experience E. Parmaksız et al.

KARE

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Southern Clinics

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ır m a H a

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EDITOR-IN-CHIEF

Recep DEMİRHAN Department of Chest Surgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

ASSOCIATE EDITORS

Özcan KESKİN Department of Internal Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

Sevda ŞENER CÖMERT Department of Pulmonary Diseases, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

Gaye FİLİNTE Department of Plastic and Reconstructive Surgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

Fatih TARHAN Department of Urology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

Ayşe BATIREL Department of Infectious Diseases and Clinical Microbiology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

PUBLISHING MANAGER

Hüseyin ÇETİN Department of Family Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

Publication Secretary Canan KIRÇIÇEK KARATAŞ

English Editing

Publisher KARE

Statistical Services

Suzan ATWOOD Gürkan KAZANCI Contact: Sevda ŞENER CÖMERT Kartal Dr. Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi, Denizer Cad., No: 1, 34865 Cevizli, İstanbul Phone: +90-216-441 39 00 Phone 2: +90-216-399 85 69 Fax: +90-216-399 85 69 e-mail: info@scie.online, editor@scie.online Owned by on behalf of the Director of University of Medical Sciences Kartal Dr. Lütfi Kırdar Health Practice and Research Center, İstanbul: Recep DEMİRHAN | Executive Editor: Recep DEMİRHAN | Publication Type: Periodical | Printed: Yıldırım Matbaacılık +90 212 629 80 37 | Printing Date: September 2018 | Circulation: 600

ISSN 2587-0998

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Southern Clinics

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EDITORIAL BOARD Adnan DAĞÇINAR

Çağatay OYSU

Gökhan YAPRAK

Department of Neurosurgery, Marmara University Faculty of Medicine, İstanbul

Department of Ear Nose and Throat, Marmara University Faculty of Medicine, İstanbul

Department of Radiation Oncology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Ali MERT

Celalettin KOCATÜRK

Gülen HATEMİ

Department of Infectious Diseases And Clinical Microbiology, Medipol University Faculty of Medicine, İstanbul

Department of Chest Diseases, Yedikule Chest Diseases Training and Reseacrh Hospital, İstanbul

Department of Internal Medicine, IU Cerrahpaşa Faculty of Medicine, İstanbul

Ali ÖZDEMİR

Cem Cahit BARIŞIK

Gültekin Sıtkı ÇEÇEN

Department of Internal Medicine, Fatih Sultan Mehmet Training and Research Hospital, İstanbul

Department of Radiology, Medipol University Faculty of Medicine, İstanbul

Department of Orthopedics and Traumatology, VM Medical Park Pendik Hospital, İstanbul

Alpaslan MAYADAĞLI

Cem FIÇICIOĞLU

Güntülü AK

Department of Radiation Oncology, Bezm-i Alem Faculty of Medicine, İstanbul

Department of Obstetrics and Gynecology, Yeditepe University Faculty of Medicine, İstanbul

Department of Pulmonary Medicine, Eskişehir Chest Diseases and Thoracic Surgery, Eskişehir

Altuğ KOŞAR

Cengiz GEMİCİ

Güven BULUT

Department of Pulmonary Diseases, Maltepe University Medical Faculty Hospital, İstanbul

Department of Radiation Oncology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Orthopedics and Traumatology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Asuman ORÇUN

Cumhur YEĞEN

Halim Ömer KAŞIKÇI

Department of Biochemistry, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of General Surgery, Marmara University Faculty of Medicine, İstanbul

Department of Family Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Ateş KARATEKE

Deniz GÜLABİ

Hanefi Yekta GÜRLER

Department of Obstetrics and Gynecology, Medeniyet University Faculty of Medicine, İstanbul

Department of Orthopedics and Traumatology, VM Medical Park Pendik Hospital, İstanbul

Department of Cardiology, Trakya University Faculty of Medicine, Edirne

Ayça VİTRİNEL

Dilşat TÜRKDOĞAN

Hasan Fehmi KÜÇÜK

Department of Pediatrics, Mehmet Toprak Hospital, İstanbul

Department of Pediatrics, Marmara University Faculty of Medicine, Institute of Neurological Sciences, İstanbul

Department of General Surgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Ayşe Yeşim AYDIN ORAL

Doğan VATANSEVER

Hasan SUNAR

Department of Ophthalmology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Obstetrics and Gynecology, Koç University Hospital, İstanbul

Department of Cardiology, Kartal Koşuyolu Cardiovascular Diseases Training and Research Hospital, İstanbul

Aysu KARATAY ARSAN

Ekrem ORBAY

Department of Ophthalmology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Haydar SUR

Department of Family Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Üsküdar Faculty of Health Sciences (Dean), İstanbul

Banu ELER ÇEVİK

Elif ARI BAKIR

Department of Anesthesiology and Reanimation, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Nephrology, BAU Medical Park Göztepe Hospital, İstanbul

Banu ÖZEN BARUT

Elif BOMBACI

Hülya ILIKSU GÖZÜ Department of Internal Medicine, Marmara University Hospital, İstanbul İhsan KARAMAN Department of Urology, Haydarpaşa Numune Training and Research Hospital, İstanbul

Department of Neurology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Anesthesiology and Reanimation, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Başar CANDER

Emrah ŞENEL

İlknur AKTAŞ

Department of Emergency Medicine, Selçuk University Faculty of Medicine, Konya

Department of Pediatric Surgery, Yıldırım Beyazıt University, Ankara

Department of Physical Theraphy and Rehabilitation, Fatih Sultan Mehmet Training and Research Hospital, İstanbul

Benan ÇAĞLAYAN

Engin Ersin ŞİMŞEK

İsmail CİNEL

Department of Family Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Anesthesiology and Reanimation, Marmara University Faculty of Medicine, İstanbul

Department of Pulmonary Medicine, Koç University Hospital, İstanbul Berrin TELATAR

Esin KORKUT

İsmet TAMER

Department of Public Health, İstanbul Bilim University European Florence Nightingale Hospital Research, İstanbul

Department of Internal Medicine, Medipol University Faculty of Medicine, İstanbul

Department of Family Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Bilal ERYILDIRIM

Fatih GÜLŞEN

Kaan GİDEROĞLU

Department of Radiology, İU Cerrahpaşa Faculty of Medicine, İstanbul

Department of Plastic and Reconstructive Surgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Urology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul Bülent SATAR

Fatma KAYA NARTER

Kemal MEMİŞOĞLU

Department of Ear Nose and Throat, Ankara Gülhane Training and Research Hospital, Ankara

Department of Pediatrics, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of General Surgery, Fatih Sultan Mehmet Training and Research Hospital, İstanbul

Bülent YAŞAR

Gaye TAYLAN FİLİNTE

Kemal SARICA

Department of Internal Medicine, Başkent University Faculty of Medicine, Ankara

Department of Plastic and Reconstructive, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Urology, Kafkas University Health Research and Practice Hospital, İstanbul

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Southern Clinics

of Istanbul Eurasia Formerly Kartal Eğitim ve Araştırma Hastanesi Tıp Dergisi

EDITORIAL BOARD Levent CANSEVER

Orhan ÜNAL

Süleyman GÖRPELİOĞLU

Department of Chest Diseases, Yedikule Chest Diseases Training and Reseacrh Hospital, İstanbul

Department of Obstetrics and Gynecology, Sakarya University Faculty of Medicine, İstanbul

Department of Family Medicine, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara

Mahmut GÜMÜŞ

Özcan KESKİN

Department of Internal Medicine Sciences, İstanbul Medeniyet University, İstanbul

Department of Internal Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Şirin YAŞAR Department of Dermatology, Haydarpaşa Numune Training and Research Hospital, İstanbul

Mehmet ALİUSTAOĞLU

Özlem GÜNEYSEL

Department of Medical Oncology, Yeditepe University Faculty of Medicine, İstanbul

Department of Emergency Medicine, Maltepe University Faculty of Medicine, Training and Research Hospital, İstanbul

Mehmet BAYRAMİÇLİ

Recep DEMİRHAN

Tamer BAYSAL

Department of Plastic and Rec. Surgery, Marmara University Faculty of Medicine, İstanbul

Department of Chest Surgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Radiology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Şuayip BİRİNCİ Deputy Undersecretary, Turkish Ministry of Health, Ankara

Mehmet Emin KALKAN

Recep ÖZTÜRK

Tamer KUZUCUOĞLU

Department of Cardiology, Kartal Koşuyolu Cardiovascular Diseases Training and Research Hospital, İstanbul

Department of Infectious Diseases and Clinical Microbiology, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul

Department of Anesthesiology and Reanimation, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Mehmet SARGIN

Reşat DABAK

Department of Family Medicine, Medeniyet University Faculty of Medicine, İstanbul

Department of Family Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Mehmet VELİDEDEOĞLU

Salih PEKMEZCİ

Department of General Surgery, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul

Mehmet YANARTAŞ

Sedat AYDIN

Department of Cardiovascular Surgery, Kartal Koşuyolu Cardiovascular Diseases Training and Research Hospital, İstanbul

Department of Ear Nose and Throat, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Mesut ŞEKER Department of Medical Oncology, Bezmi Alem University, Medical Faculty Hospital, İstanbul Murat DEMİRTAŞ Department of Cardiology, Siyami Ersek Chest Diseases and Cardiovascular Surgery, Training and Research Hospital, İstanbul Mustafa TAŞDEMİR Department of Public Health, Marmara University Faculty of Medicine, İstanbul

Selami ALBAYRAK Department of Urology, Medipol Faculty of Medicine, İstanbul Selin Gamze SÜMEN Department of Underwater and Hyperbaric Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul Semih KORKUT General Secretary of Bakırköy Region Public Hospitals Association, İstanbul

Nagehan ÖZDEMİR BARIŞIK

Semra BİÇEROĞLU

Department of Pathology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

İzmir Suat Seren, Chest Diseases and Thoracic Surgery Training and Research Hospital, İzmir

Nejdet BİLDİK

Şenol TURAN

Department of General Surgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Psychiatry, İU Cerrahpaşa Faculty of Medicine, İstanbul

Nejdet SAĞLAM

Serap GENCER

Department of Orthopedics and Traumatology, Ümraniye Training and Research Hospital, İstanbul

Department of Infectious Diseases and Microbiology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Nesrin KIRAL Department of Pulmonary Medicine, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Serdar CÖMERT Department of Newborn, Süleymaniye Hospital, İstanbul

Oğuz TAN

Sergülen ONAN DERVİŞOĞLU

Department of Psychiatry, Üsküdar University Faculty of Medicine, İstanbul

Department of Pathology, Medipol University Faculty of Medicine, İstanbul

Tayfun AKÖZ Department of Plastic and Rec. Surgery, Maltepe University Faculty of Medicine, İstanbul Tufan HİÇDÖNMEZ Department of Neurosurgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul Tunçay PALTEKİ Department of Public Health, Biruni University Faculty of Medicine, İstanbul Ülkü TÜRK BÖRÜ Department of Neurology, Afyonkarahisar Medical Faculty of Health Sciences University, Afyonkarahisar Volkan BAYSUNGUR Department of Chest Diseases, Süreyyapaşa Training and Research Hospital, İstanbul Yasemin AKIN Department of Pediatrics, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul Zehra Meltem PİRİMOĞLU Department of Obstetrics and Gynecology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul Zekayi KUTLUBAY Department of Dermatology, İU Cerrahpaşa Faculty of Medicine, İstanbul Zerrin BİCİK BAHÇEBAŞI Department of Nephrology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul Ziya ŞİMŞEK Department of Cardiology, Atatürk University Faculty of Medicine, Ankara

Oktay AKÇA

Sevda ŞENER CÖMERT

Zuhal KARAKURT

Department of Urology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Pulmonary Diseases, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul

Department of Pulmonary Medicine, Süreyyapaşa Chest Diseases and Thoracic Surgery, İstanbul

ISSN 4162-3684

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AIMS AND SCOPE Southern Clinics of Istanbul Eurasia - SCIE (formerly Kartal Eğitim ve Araştırma Hastanesi Tıp Dergisi / Medical Journal of Kartal Training and Research Hospital) is the scientific open access publication of University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital (the content may be accessed free of charge through the web site www. scie.online). Four issues are released every year in March, June, September, and December. The language of publication is English. The aim of the journal is to publish high level clinical and experimental studies conducted in all medical branches, reviews comprising the latest research findings, reports on rare and educational cases, and letters to the editor. The journal observes a double-blinded, peer-review process with external and independent reviewers in the evaluation and approval of manuscripts for publication. The target population of the journal includes specialists in all medical branches, academicians, and relevant health care professionals. Publication policy and editorial processes follow the guidelines of the International Committee of Medical Journal Editors, the World Association of Medical Editors, the Council of Science Editors, the European Association of Science Editors, and the Committee on Publication Ethics. SCIE is indexed in the TUBITAK ULAKBIM TR Index, EBSCO, and GALE. The journal is financially supported by University of Health Sciences Kartal Dr. Lütfi Kırdar Training and Research Hospital. Kartal Dr. Lütfi Kırdar Training and Research Hospital is the sole copyright holder of the name and brand of the journal and all content. Any part of the content may be quoted only by providing a reference to the journal. For all other utilizations, permission should be obtained from the editorial office. Editor: Recep DEMİRHAN Address: Kartal Dr. Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi, Denizer Cad., No: 1, 34865 Cevizli, İstanbul Phone: +90-216-441 39 00 (2845) Fax: +90-216-399 85 69 E-mail: editor@scie.online

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INSTRUCTIONS FOR AUTHORS About the Journal

Submission and peer reviewing

Southern Clinics of Istanbul Eurasia - SCIE (formerly Kartal Eğitim ve Araştırma Hastanesi Tıp Dergisi - The Medical Journal of Kartal Training and Research Hospital) is published four issue in English by the Kartal Dr. Lütfi Kırdar Training and Research Hospital, and is a peer reviewed general medical journal for all physicians, doctors, medical researchers, and health workers. The journal reports the advances and progress in current medical sciences and technology. The journal covers basic and clinical studies in medicine. Articles of clinical interest and implications will be given preference.

The official language of the Journal is English. Following an initial evaluation and elimination for sufficient priority, manuscripts are subject to blind peer review by at least two reviewers. The Editor, who judges and analyzes the entire review process, reaches a final decision to accept or reject a manuscript, or to recommend a revision. The Editor has the right to reject a revised manuscript.

with the manuscript. Authors of case reports must submit the written informed consent of the subject(s) of the report or of the patient’s legal representatives for the publication of the manuscript.

Important notice

All studies should be carried out in accordance with the World Medical Association Declaration of Helsinki, covering the latest revision date. Patient confidentiality must be protected according to the universally accepted guidelines and rules. Manuscripts reporting the results of experimental studies on animals must include a statement that the study protocol was approved by the animal ethics committee of the institution and that the study was conducted in accordance with the internationally accepted guidelines, including the Universal Declaration of Animal Rights, European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, Principles of Laboratory Animal Science, and the Handbook for the Care and Utilization of Laboratory Animals. The authors are strongly requested to send the approval of the ethics committee together with the manuscript. In addition, manuscripts on human and animal studies should describe procedures indicating the steps taken to eliminate pain and suffering.

Manuscript preparation

The authors should disclose all issues concerning financial relationship, conflict of interest, and competing interest Contributions may be in the form of clinical and basic research that may potentially influence the results of the research or articles, case reports, personal clinical and technical notes, and scientific judgement. All financial contributions or sponsorship, letters to the Editor. The Journal also publishes brief reports on financial relations, and areas of conflict of interest should be original studies or evaluations, book reviews, and proceedings clearly explained in a separate letter to the editor at the time of of scientific meetings. The Editor-in-Chief may request from the submission, with full assurance that any related document will be authors additional data, information, or complementary material submitted to the Journal when requested. concerning the manuscripts, and the authors must comply with Manuscripts should be sent with the Copyright-Authors’ Approvalsuch requests. Conflict of Interest Letter signed by the author(s). A copy of this Manuscripts should be prepared in accordance with the Uniform letter can be found at web site. Manuscripts will not be accepted Requirements for Manuscripts Submitted to Biomedical Journals for evaluation until the receipt of this document by the Journal. regularly updated by the International Committee of Medical The Editorial Office inspects all submitted manuscripts concerning Journal Editors, available at http:// www.icmje.org. plagiarism and duplication. If an ethical problem is detected, the Ethics editorial office will act according to the COPE guidelines. SCIE follows the ethics flowcharts developed by the Committee Submitting a manuscript on Publication Ethics for dealing with cases of possible scientific misconduct and breach of publication ethics. For detailed SCIE accepts only on-line submission via the official web site (please click, http://www.scie.online/en/?s=online_submission) and information please visit www.publicationethics.org. All manuscripts presenting data obtained from research involving refuses printed manuscript submissions by mail. All submissions human subjects must include a statement that the written are made by the on-line submission system called Journal Agent, informed consent of the participants was obtained and that by clicking the icon “Online manuscript submission” at the above the study was approved by an institutional review board or an mentioned web site homepage. The system includes directions at equivalent body. This institutional approval should be submitted each step but for further information you may visit the web site.

ISSN 4162-3684

Before the corresponding author submits the manuscript, all authors must obtain ORCİD ID number and provide it to the corresponding author. The author(s) must declare that they were involved in at least 3 of the 5 stages of the study stated in the “acknowledgement of authorship and transfer of copyright agreement” as “designing the study”, “collecting the data”, “analyzing the data”, “writing the manuscript” and “confirming the accuracy of the data and the analyses”. Those who do not fulfill this prerequisite should not be stated as an author. The number of authors should not exceed 6 for clinical, basic and experimental studies, 4 for case reports and technical notes, and 3 for letters to the editor and reviews. In multi-center or multidiscipline studies, each author’s contribution regarding the 5 stages mentioned above should be stated clearly. For this kind of multi-center or multi-discipline studies with excessive number of authors, the editor has the right to request that the number of authors be reduced.

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From the beginning of introduction to the end of discussion, clinical, basic and experimental studies should not exceed 2,500 words, case reports and surgical techniques 1,500 words, letters to the editor 350 words. Manuscripts exceeding these limits will be returned to the author(s) to be shortened.

All authors if six or fewer should be listed; otherwise, the first six and “et al.” should be written.

Abstract: It should not exceed 300 words. Abstracts should be structured in four paragraphs using the following subtitles: Objectives, Methods, Results, and Conclusion. Abstracts of case reports should be unstructured.

Günal İ, Barton NJ, Çallı İ, editors. Current management of scaphoid fractures. Twenty questions answered. London: The Royal Society of Medicine Press; 2002.

Epub ahead of print Articles:

Rupprecht H, Heppner HJ, Wohlfart K, Türkoglu A. The geriatric polytrauma: Risk profile and prognostic factors. Ulus Travma Acil Manuscripts should be designed in the following order: title page, Cerrahi Derg 2017 Jan 05. doi: 10.5505/tjtes.2016.77177. [Epub abstract, main text, references, and tables, with each typeset on a ahead of print]. separate page. Personal author(s): Title page: This page should only include the title of the manuscript, which should be carefully chosen to better reflect the Enzingerz FM, Weiss SW. Soft tissue tumors. St. Louis: Mosby; 1995. contents of the study. Author names should not appear in the title p. 27-50. Editor(s), compiler(s) as author: and subsequent pages.

Chapter in a book: Main text: The body consists of Introduction, Patients/Materials Henick DK, Kennedy DW. Fungal sinusitis. In: Stankiewicz JA, and methods, Results, and Discussion. Use “Patients and methods” editor. Advanced endoscopic sinus surgery. St Louis: Mosby; 1995. for clinical studies, and “Materials and methods” for animal and p. 69-80. laboratory studies. Conference paper: The Introduction section clearly states the purpose of the Kouzelis A, Matzaroglou C, Kravvas A, Mylonas S, Megas P, Gliatis manuscript and includes a brief summary of the most relevant J. Anterior cruciate ligament reconstruction: patellar tendon literature. autogaft versus four strand hamstring tendon. In: Proceedings The Patients/Materials and Methods section describes the study of the 9th Turkish Sports Traumatology, Arthroscopy and Knee population and the study design, with adequate information on Surgery Congress; 2008 Oct 14-18; İstanbul, Turkey. p. 223. the techniques, materials, and methods used. A clear description Unpublished conference papers should not be used in the of the statistical methods should also be given. reference list. The Results section should provide a detailed report on the Direct use of references is strongly recommended and the findings of the study. Data should be concisely presented, authors may be asked to provide the first and last pages of certain preferably in tables or illustrations, which should not exceed the references. Publication of the manuscript will be suspended until page layout of the Journal. this request is fulfilled by the author(s). The Discussion section should mainly rely on the conclusions Figures and tables derived from the results of the study, with relevant citations from All illustrations (photographs, graphics, and drawings) the most recent research. accompanying the manuscript should be referred to as “figure”. Letter to the Editor: Letters to the editor should not exceed 350 All figures should be numbered consecutively and mentioned in words. the text. Figure legends should be added at the end of the text as References: References should be numbered in the order in a separate section. Each figure should be prepared as a separate which they are mentioned in the text. Only published articles or digital file in “jpeg” format, with a minimum of 9×13 cm and at 300 articles in press can be used in references. Unpublished data or dpi or better resolution. personal communications should not be used. The style should All illustrations should be original. Illustrations published conform to the standards described in detail in “Citing Medicine- elsewhere should be submitted with the written permission of the The NLM Style Guide for Authors, Editors, and Publishers” (http:// original copyright holder. www.nlm.nih.gov/citingmedicine), which is recommended in the For recognizable photographs of human subjects, written most recent update of “Uniform Requirements for Manuscripts permission signed by the patient or his/her legal representative Submitted to Biomedical Journals”. A brief presentation of these should be submitted; otherwise, patient names or eyes must be standards can also be found at http://www.nlm.nih.gov/bsd/ blocked out to prevent identification. Microscopic photographs uniform_requirements.html. Journal titles should be abbreviated should include information on staining and magnification. according to the Index Medicus. The Journal’s title is abbreviated Upon the author’s request, color prints will be considered for as “South Clin Ist Euras”. publication; however, the authors are responsible for the extra The style and punctuation should follow the formats outlined cost of printing color illustrations. Each table should be prepared below: on a separate page, either at the end of the text file or as a separate Standard journal article: supplementary file, with table heading on top of the table. Table Napolitano LM, Corwin HL. Efficacy of red blood cell transfusion in heading should be added to the main text file on a separate page when a table is submitted as a supplementary file. the critically ill. Crit Care Clin 2004;20:255-68.

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Checklist

of the article and summarize the rationale for the study or observation. Give only strictly pertinent references

Covering letter

The references cited in the text should be after punctuation marks

Signed by all contributors Previous publication / presentations mentioned

References according to the journal’s instructions, punctuation marks checked

Source of funding mentioned Conflicts of interest disclosed

Language and grammar

ORCİD ID number of all contributors

Uniformly American English

Authors Last name and given name provided along with Middle name initials (where applicable)

Write the full term for each abbreviation at its first use in the title, abstract, keywords and text separately unless it is a standard unit of measure. Numerals from 1 to 10 spelt out

Author for correspondence, with e-mail address provided

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Number of contributors restricted as per the instructions

Check the manuscript for spelling, grammar and punctuation errors

Identity not revealed in paper except title page (e.g. name of the institute in Methods, citing previous study as ‘our study’, names on figure labels, name of institute in photographs, etc.)

If a brand name is cited, supply the manufacturer’s name and address (city and state/country).

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Recep DEMİRHAN

Address: Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Denizer Cad., No: 1, 34865 Cevizli, İstanbul Phone:

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w w w .s c i e .o n l i n e

Volume 29 Issue 3 Year 2018 ORIGINAL ARTICLES 147 Surgical Treatment of Pulmonary Metastasectomy: Analysis of 92 Cases

E. E. Cesur, K. B. Özer, A. Özdemir, F. T. Özlü, R. Demirhan

151 The Relationship Between Health Literacy, Diabetic Control, and Disease-Specific Complications

in Patients with Type 1 Diabetes Mellitus İ. Esen, H. Demirci, M. Güçlü, S. Aktürk Esen, E. E. Şimşek

157 The Alvarado Score and Computed Tomography for Predicting Acute Appendicitis in Elderly Patients

S. Kaya, Ö. Altın, Y. E. Altuntaş, A. Şeker, L. Kaptanoğlu, N. Bildik, H. F. Küçük

161 Comparison of Early Postoperative Recovery after Desflurane or Sevoflurane Anesthesia

Ö. Sezen, E. Bombacı

168 Which Biomarkers Help to Distinguish Between Candida and Aspergillus in Patients with Pulmonary Infections?

A. F. Hazar, H. Türker

176 Predictors of Vesicoureteral Reflux in the Pretransplant Evaluation of Patients with End-Stage Renal Disease

E. Parmaksız, M. Meşe, Z. Doğu, Z. Bicik Bahçebaşı

180 How Urgent are Blood Transfusions Provided in Emergency Service?

Y. Özgür, S. Akın, G. Gecmez, N. Aladağ, Ö. Keskin

187 Evaluation of the Factors Affecting Percutaneous Success and Complications of Nephrolithotomy

O. M. İpek, K. Horasanlı

194 Parathyroidectomy After Kidney Transplantation: A Single-Center Experience

E. Parmaksız, M. Meşe, S. F. Yalın, A. B. Haras, O. Akyüz, Z. Bicik Bahçebaşı CASE SERIE

198 Efficient Treatment of Resistant Orbital Pseudotumor with CyberKnife: Case Series and Short Review of Literature

G. Yaprak, A. K. Kılıç, N. Işık, D. Çelik Yaprak, Ö. O. Şeşeogulları

CASE REPORTS 203 A Rare Cause of Lung Metastasis - Glioblastoma Multiforme

G. Türkeş, E. T. Parmaksız, N. Kıral, C. Doğan, S. B. Sağmen, A. Fidan, S. Cömert

206 From Basic Chronic Wounds To Mortal Endings: Squamous Cell Carcinoma Arising from

Hidradenitis Suppurativa and Pilonidal Sinus S. Öz, G. Filinte, K. Gideroğlu, C. Alioğlu, A. Akgün, S. Yalçın, K. Kalafatlar, T. Tunçbilek, C. Sınacı, Z. Arpacık, B. Cüce, B. Kanık

209 Methemoglobinemia After Prilocaine Application During Neonatal Circumcision and Treatment with Ascorbic Acid

N. Haykır, F. Narter, M. Güllü, M. B. Aslan

213 Plasmablastic Lymphoma of the Maxillary Sinus Causing Orbital Complication

S. Aydın, N. Ünlü, E. Gültürk, H. Avcı, N. Özdemir Barışık, B. Başlı

217 Treatment of Subdeltoid Calcific Bursitis with Ultrasound-Guided Percutaneous Lavage

E. Dilşat Bayrak, İ. Aktaş, F. Ünlü Özkan

DOI: 10.14744/scie.2018.55706 South. Clin. Ist. Euras. 2018;29(3):147-150

Original Article

Surgical Treatment of Pulmonary Metastasectomy: Analysis of 92 Cases Ekin Ezgi Cesur, Kadir Burak Özer, Attila Özdemir, Fatma Tuğba Özlü, Recep Demirhan

ABSTRACT Department of Thoracic Surgery, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey Submitted: 23.07.2018 Accepted: 25.07.2018 Correspondence: Ekin Ezgi Cesur, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi Göğüs Cerrahisi Kliniği, İstanbul, Turkey E-mail: ezgicesur@gmail.com

Keywords: Complete resection; disease-free survival; pulmonary metastasectomy.

Objective: The lungs are the second most common site of metastasis, and for selected patients, pulmonary metastasectomy can be a curative option. The surgical goal is complete resection with minimal parenchymal loss in order to prolong life. In well-selected cases, minimally invasive approaches can increase quality of life and offer equivalent oncological outcomes. Methods: Patients diagnosed with pulmonary metastasis who underwent a metastasectomy in a single hospital between January 2012 and December 2017 were evaluated retrospectively. A total of 92 patients (55 male and 37 female) underwent thoracotomy or thoracoscopy procedures with the goal of complete resection. Results: Among the patients included in the study, 8 were symptomatic: cough was reported in 3, chest pain (pneumothorax) was experienced in 3, and hemoptysis occurred in 2 cases. The longest disease-free survival (DFS) period was seen in cases of epithelial tumor (40.1 months) and sarcoma (28.2 months); the shortest survival was seen in those with germ cell tumor (8.3 months) and melanoma (8.1 months). Conclusion: Patients with pulmonary metastasis require a multidisciplinary approach for treatment. When the primary disease is under control and there is no other distant metastasis, metastasectomy with complete surgical resection can provide an extended period of DFS, particularly for patients with epithelial or sarcomatous tumors.

INTRODUCTION The metastatic potential of malignant diseases is one of the most important challenges in cancer treatment.[1] The lungs are a frequent site of metastasis; however, complete resection of pulmonary metastases can significantly affect survival.[2] There is a survival advantage associated with isolated lung metastasis compared with other organ metastases, and pulmonary tumors respond very well to local and systemic treatment methods.[3] Although there are different opinions among oncologists and surgeons concerning the decision if and when to perform a metastasectomy, the 5 years survival rate after complete resection has been reported to be between 20% and 40% in selected patients.[4] Control of the primary tumor, and a lack of extrapulmonary metastasis, or when present,

extrapulmonary metastasis that can be controlled, have been reported as important factors.[5,6] Pulmonary metastasectomy is a well-known procedure that has been performed for many years. The prognostic factors affecting DFS include the extent of pulmonary metastasis, duration of disease-free survival, successful radical surgery, and the carcinoembryonic antigen level in colorectal cancers.[7] Most often, patients with pulmonary metastasis are asymptomatic, but occasionally cough or hemoptysis may be seen in centrally located metastases. Most are diagnosed during primary tumor staging or follow-up. Computed tomography (CT) is the preferred means of diagnosis. Positron-emission tomography/CT or bone scintigraphy may also be used. A small number of metastases, DFS for more than 36 weeks, the ability to perform a complete resection, a lack of mediastinal lymph node involvement,

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and negative tumor markers are good prognostic factors. Mediastinal involvement, extrathoracic metastasis, incomplete surgery, a shorter DFS expectancy, and a shorter tumor doubling time reflect a poorer prognosis. The most important goal of surgical procedures in these cases is to achieve complete resection with minimal loss of parenchyma. Enucleation with monopolar cautery, excision using energy devices, Nd-YAG laser, wedge resection, or anatomical resection may be applied. Minimally invasive methods that have been used in recent years include classic thoracotomy and bimanual palpation with metastasectomy, and less frequently, sternotomy and bilateral intervention. The present study was an evaluation of the methods used to treat patients with pulmonary metastasis in the clinic of one hospital and an analysis of the survival results.

MATERIAL AND METHODS In all, 92 patients with distant organ metastasis in the lung who underwent a metastasectomy between January 2012 and December 2017 at a single hospital were identified. The median age of the 55 men and 37 women was 41 years (range: 33–67 years). Clinical follow-up data, surgical details, and pathology reports were reviewed after receiving the approval of the ethics committee. Characteristics of age, sex, tumor histology, number of metastases, operative technique, and survival time were used to group the patients.

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Table 1. The distribution of the primary tumors Histological type of the tumors

Colorectal tumor

Sarcoma

14 15

Breast carcinoma

Renal cell carcinoma

Malignant mesenchymal tumor

Bladder tumor

Testicular tumor

Choriocarcinoma

2 2

Malignant melanoma

Adenoid cystic carcinoma

lobectomy was performed because the tumor was large and centralized, and attacks of hemoptysis had been observed in the patient’s clinical evaluation. In the pulmonary metastasectomies performed, the distribution of the primary tumors was: colorectal cancer (n=42; 46%), sarcomatous metastasis (n=14; 15%), breast cancer metastasis (n=7; 7%), renal cell carcinoma metastasis (n=6; 6%), malignant mesenchymal tumor metastasis (n=5; 5%), bladder tumor (n=4; 4%), testicular tumor metastasis (n=4; 4%), choriocarcinoma metastasis (n=2; 2%), malignant melanoma metastasis (n=1; 1%), and adenoid cystic carcinoma metastasis (n=1; 1%) (Table 1).

All of the patients were referred to us by oncology clinics after systemic screenings. PET/CT was initially used by the oncology clinic to evaluate pulmonary metastases, and thorax CT was used in the following months. The quantity, distribution, anatomical localization, and operability of pulmonary metastases were evaluated. After clinical and anesthesia evaluations, patients who had no medical contraindication for surgery and were suitable for complete resection based on a surgical evaluation were operated on.

An average of 4 (range: 4–8) metastatic foci were removed. When pulmonary metastases were radiologically observed, the mediastinal lymph nodes were removed, and mediastinal lymph node dissection was performed in cases with colorectal cancer metastases even if no pathological lymph nodes were observed radiologically. The analysis of the data was performed using the SPSS program and survival of the patients was assessed using Kaplan-Meier survival analysis.

A thoracotomy was performed in 84 (91%) cases and a videothoracoscopy in 8 (9%). Thin-section helical CT determined that the patients selected for videothoracoscopy had a single peripheral metastasis. Of the thoracotomy patients, 11% (n=8) were a repeat thoracotomy procedure. Nine (10%) patients underwent a bilateral, staged metastasectomy. In patients who underwent videothoracoscopy-aided metastasectomy, wedge resection was performed using an endostapler.

RESULTS

In cases of metastasectomy performed with a classic thoracotomy and bimanual palpation, monopolar cautery, energy device, enucleation, and wedge resection with a stapler were used at the site of metastasis to achieve complete resection with minimal parenchymal loss. In 1 case,

Of the 92 patients who were enrolled in the study, 8 were symptomatic and the remaining 84 patients were asymptomatic. Chest pain was seen in 3 patients (pneumothorax), a cough in 3, and hemoptysis in 2. The length of DFS varied according to the histopathological type of tumor: the mean for epithelial tumors was 40.1 months (range: 9–75.2 months), while it decreased to 28.2 months (range: 3–44.3 months) in cases of sarcomatous tumors, 8.3 months in germ cell tumors and 8.1 months in melanoma patients. In almost all (90%) of those with an epithelial tumor histology, and 58% of the patients with sarcoma metastasis, the DFS was less than 12 months.

Cesur. Surgical Treatment of Pulmonary Metastasectomy

In all, 22 of the cases had a single metastasis, while the remainder had multiple metastatic lesions. Patients with sarcoma and germ cell tumor metastasis were more likely to have a single metastasis, whereas multiple metastatic foci were detected in 82% of epithelial tumors. Cases of a solitary metastasis, no distant metastasis, and a controlled primary cancer were found to have a significantly higher 1-year (83%) and 2-year DFS (69%) after complete resection when compared with those with multiple metastases (p<0.05). Eighty (86.9%) patients underwent a single operation, while 10 underwent 2 surgeries, and 2 underwent 3 operations. The length of DFS did not differ significantly according to the number of operations, while mean survival time was significantly longer in patients who underwent multiple operations. A significant difference in life span was observed in a comparison of the patients who underwent chemoradiotherapy before or after the operation and those who underwent just a metastasectomy operation. The 2-year and 5-year survival rate of the chemoradiotherapy patients was 63.9% and 21.7%, respectively, while the corresponding survival rate was 57.7% and 11.5% in the untreated cases (p<0.012). No instance of mortality was observed during the 92 operations included in the study. Morbidity was observed in 6 patients. There were 2 cases of cardiac arrhythmia (atrial fibrillation), a prolonged air leak was detected in 2, pneumonia in 1, and pleurisy in 1. There was no significant difference in the morbidity and mortality rates between cases of videothoracoscopic or thoracotomy procedure.

DISCUSSION Distant organ metastasis is frequently seen in advanced stage malignant disease, followed by lung metastasis. Control of systemic metastasis is still controversial, and differences can be observed, especially in oncological and surgical approaches. Patients with metastases limited to the lungs have a better prognosis than those with multi-organ metastases. Patients with pulmonary metastases are usually asymptomatic. The metastasis is usually detected in follow-up imaging studies, and the cases are directed by oncology clinics. Follow-up usually includes a thorax CT. PET/CT is another method used for diagnosis. Lucas et al.[8] found a diagnostic sensitivity and specificity of PET in patients with pulmonary metastatic sarcoma of 86.9% and 100%, respectively. In our study, we detected that diagnosis was made using PET/CT in 45% of the cases referred by oncology clinics, while thoracic CT was used in 55%. It has been reported that that a smaller number of metastatic nodules indicated a better prognosis.[3] Our

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research revealed the largest quantity of nodules was detected in cases of sarcoma, with as many as 8 nodules resected at one time. Pastorino et al.[6] found a 5-year survival rate of 43% in cases with single metastasis, while it was 27% in patients with â&#x2030;Ľ4 metastases. However, Monteiro et al.[9] and Robert et al.[5] determined no significant correlation between survival rate and the number of nodules. The histopathological type is an important prognostic factor in the survival of patients with pulmonary metastasis. In a study of some 5200 patients, Pastorino et al.[6] indicated that germ cell tumors had the best survival rate, while melanoma cases had the worst survival rate. The mean length of survival for patients with epithelial tumors was 40 months, while it was 30 months for sarcoma, and 20 months for melanoma.[10] In our study, the length of survival was greatest in cases of epithelial tumors and lowest in cases of melanoma, which was consistent with the literature. In this country, Evman et al.[12] researched 126 metastasectomy operations and detected the greatest survival in cases with epithelial tumors. The most common tumors in our study were epithelial tumors and they were also the group for which metastasectomy had the greatest effect in terms of DFS. As we could not obtain information about the 10-year survival rate of the patients in this study, the 2-year and 5-year survival rates were calculated. The results indicated a 2-year rate of 63.9% and a 5-year rate of 21.7% in cases of epithelial tumor, while it was 54.9% and 10.1%, respectively, in sarcoma patients. The mean DFS was 40.1 months in patients with epithelial tumors and 28.2 months in sarcoma cases. Metastasectomy contributes directly to survival, particularly in cases of epithelial and sarcomatous tumors. Pastorino et al.[6] reported that survival was longer in patients who underwent multiple operations due to pulmonary metastasis compared with a single metastasectomy operation. In our study, the 2-year and 5-year survival rates of metastatic cases with multiple operations were found to be greater than those of cases who underwent a single operation in accordance with the literature findings. The use of systemic chemoradiotherapy to control the disease in pulmonary metastasis patients is the basis of treatment. While the postoperative role of chemoradiotherapy is still controversial, Marina et al.[11] reported that chemotherapy administered after a complete surgical resection had demonstrated positive contributions to survival. In our study, the survival rates of the patients who received concurrent or postoperative chemoradiotherapy were significantly greater than those of the untreated patient group.

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CONCLUSION Patients with pulmonary metastasis require a multidisciplinary treatment approach. In cases without distant metastasis and in which the primary disease is under control, we believe that metastasectomy can contribute significantly to DFS if complete surgical resection is possible, and particularly in cases of epithelial and sarcomatous tumors. Ethics Committee Approval Approved by the local ethics committee. Informed Consent Retrospective study. Peer-review Internally peer-reviewed. Authorship Contributions Concept: R.D..; Design: E.E.C.; Data collection &/or processing: K.B.O.; Analysis and/or interpretation: F.T.O.; Literature search: A.O.; Writing: E.E.C.; Critical review: R.D. Conflict of Interest None declared.

REFERENCES 1. Hornbeck K, Ravn J, Steinbruchel DA. Current status of pulmonary metastasectomy. European Journal of Cardio-Thoracic Surgery 2011;39:955–62. 2. Abecasis N, Cortez F, Bettencourt A, Costa CS, Orvalho F, de Almeida JM. Surgical treatment of lung metastases: prognostic factors for long-term survival. J Surg Oncol 1999;72:193–8.

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3. Putnam JB. Secondary tumors of the lung. In: Shields TW, Locicero J, Ponn RB, editors. General thoracic surgery. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 1555–76. 4. Şengül AT, Başoğlu A, Büyükkarabacak AB, Yetim TD, Kutlu T. Assessment of metastasectomy and prognostic factors in the treatment of metastatic lung tumors [Article in Turkish]. Türk Göğüs Kalp Damar Cer Derg 2009;17:87–91. 5. Robert JH, Ambrogi V, Mermillod B, Dahabreh D, Goldstraw P. Factors influencing long-term survival after lung metastasectomy. Ann Thorac Surg 1997;63:777–84. 6. Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, et al; International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997;113:37–49. 7. Petrella F, Diotti C, Rimessi A, Spaggiari L. Pulmonary Metastasectomy: an overview. J Thorac Dis 2017;9:S1291–8. 8. Lucas JD, O’Doherty MJ, Wong JC, Bingham JB, McKee PH, Fletcher CD, et al. Evaluation of fluorodeoxyglucose positron emission tomography in the management of soft-tissue sarcomas. J Bone Joint Surg Br 1998;80:441–7. 9. Monteiro A, Arce N, Bernardo J, Eugénio L, Antunes MJ. Surgical resection of lung metastases from epithelial tumors. Ann Thorac Surg 2004;77:431–7. 10. Turna A, İşcan M. Lymphdenectomy in Patients Undergoing Pulmonary Metastasectomy [Article in Turkish]. Turkiye Klinikleri J Thor Surg-Special Topics 2017;8:411–4. 11. Marina NM, Pratt CB, Rao BN, Shema SJ, Meyer WH. Improved prognosis of children with osteosarcoma metastatic to the lung(s) at the time of diagnosis. Cancer 1992;70:2722–7. 12. Evman S, Demirhan R, Çardak E, Özer KB. Who Actually Profits From Pulmonary Metastasectomy Operation? Retrospective Analysis of 12 Years. Eurasian J Pulmonol 2014;16:164–8.

Pulmoner Metastazektomilerde Cerrahi Tedavi: 92 Olgu Analizi Amaç: Akciğer, tüm vücut kanserleri için ikinci en sık metastaz organı olup seçilmiş hastalarda pulmoner metastazektomi küratif seçenektir. Operatif yaklaşımda temel amaç en az parankim kaybı ile komplet rezeksiyon yapmak ve doğru hasta seçimi ile sağ kalım süresini uzatmaktır. İyi seçilmiş hastalarda minimal invaziv girişimler hastanın ameliyat sonrası yaşam kalitesini, eşit onkolojik sonuçlarla artırabilmektedir. Gereç ve Yöntem: Ocak 2012–Aralık 2017 tarihleri arasında pulmoner metastaz tanısı ile kliniğimizde metastazektomi yapılan hastalar incelendi. Klinik değerlendirme sonrasında pulmoner rezeksiyona uygun olan 92 hasta (55 erkek ve 37 kadın) operasyona hazırlandı. Torakotomi ve torakoskopi prosedürleri ile cerrahi uygulanan hastalarda komplet rezeksiyon amaçlandı. Bulgular: Çalışmamıza alınan hastalar başvuru anında semptomlar açısından değerlendirildiğinde, 8 olgu semptomlu olarak saptandı ve bunlardan 3’ünde öksürük, 3’ünde göğüs ağrısı (pnömotoraks nedeni ile) mevcuttu. Histopatolojik tip ile hastalıksız yaşam süresi değerlendirmesinde ise en yüksek yaşam süresi epiteltal tümörlerde (40.1 ay) ve sarkomlarda (28.2 ay) saptanırken, germ hücreli tümörlerde (8.3 ay) ve melanomlarda (8.1) ise en düşük olarak izlendi. Sonuç: Multidisipliner bir tedavi yaklaşımı gerektiren pulmoner metastazlı hastaların; primer hastalığı kontrol altında, uzak metastazı olmayıp ve komplet cerrahi rezeksiyon uygulanabiliyor ise özellikle epitelyal tip ve sarkom tipi tümörlerde metastazektominin hastalıksız yaşam süresine ve ortalama sağkalıma ciddi katkısı olduğu kanaatindeyiz. Anahtar Sözcükler: Hastalıksız yaşam süresi; komplet rezeksiyon; pulmoner metastazektomi; sağkalım.

DOI: 10.14744/scie.2018.77200 South. Clin. Ist. Euras. 2018;29(3):151-156

Original Article

The Relationship Between Health Literacy, Diabetic Control, and Disease-Specific Complications in Patients with Type 1 Diabetes Mellitus İrfan Esen,1 Hakan Demirci,2 Metin Güçlü,1 Selin Aktürk Esen,3 Engin Ersin Şimşek4 Department of Internal Medicine, University of Health Sciences Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey 2 Department of Family Medicine, University of Health Sciences Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey 3 Department of Internal Medicine, Gürsu Cüneyt Yıldız State Hospital, Bursa, Turkey 4 Department of Family Medicine, University of Health Sciences Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey 1

Submitted: 17.08.2018 Accepted: 04.09.2018 Correspondence: Hakan Demirci, SBÜ Bursa Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Aile Hekimliği Kliniği, Bursa, Turkey E-mail: drhakandemirci@hotmail.com

Keywords: Cardiovascular disease; hemoglobin A1c; health literacy; nephropathy; neuropathy; retinopathy.

ABSTRACT Objective: The aim of this study was to investigate the relationship between health literacy, diabetic control, and diabetic complications in patients with type1 diabetes mellitus (DM). Methods: This was a descriptive study. A total of 106 patients with type 1 DM who were between 18 and 65 years of age and who could speak and understand Turkish and had no cognitive disease were included in the study. The Turkish version of the European Health Literacy Survey Questionnaire (HLS-EU-Q47) was used to assess health literacy. The retinopathy status and levels of hemoglobin A1c, fasting blood sugar, and urine albumin of the patients were obtained from the hospital files. Results: Overall health literacy was inadequate in 10.4%, problematic in 54.7%, adequate in 20.8%, and excellent in 14.2% of the participants. Retinopathy was found to be statistically significantly higher in the problematic+inadequate group than in the adequate+excellent group in the overall health literacy evaluation (24.6% and 5.4%, respectively). There was no significant difference in the frequency of neuropathy, nephropathy, or cardiovascular disease in the health literacy groups. Conclusion: The present study demonstrated that low health literacy in patients with type 1 DM was associated with increased retinopathy. Physicians should keep the positive effects of education in mind in order to better control the disease and prevent complications.

INTRODUCTION Type 1 diabetes mellitus (DM) is a chronic, autoimmune disorder and constitutes approximately 10% of the patients with DM. It occurs due to pancreatic beta cell damage and requires lifelong insulin therapy.[1] In the case of poor disease control, various micro- and macro-vascular complications can develop in diabetic patients.[2] These complications are determinants of morbidity and mortality.[3–5]

Communication between health care providers and diabetic patients, disease awareness among patients, and selfcare of patients are very important in the management of diabetes.[6] Patients should receive accurate information to achieve desired hemoglobin A1c (HbA1c) levels, to reduce the risk of hypoglycemia, and to improve the quality of life. Educational programs developed for self-management of patients should be presented to all diabetic patients.[7] Educational programs to provide better glycemic control

152

and to improve the quality of life should include self-monitoring of blood glucose, carbohydrate count, and pre-meal insulin dose adjustment.[8,9] However, studies on this topic are limited. Implementation of formal educational programs based on evidence and follow-up of the results are key points for successful diabetes treatment. The concept of health literacy emerged in the literature in the early 1990s.[10] The World Health Organization defines health literacy as personal characteristics and social resources that enable individuals and communities to access, understand, evaluate, and use information to make healthrelated decisions.[11] Health literacy can be summarized as an individual’s ability to understand and interpret the provided medical information and to behave appropriately based on this information.[12] The positive impact of health literacy in chronic diseases has been revealed in many studies.[13–16] There are various studies on the relationship between health literacy and DM, and conflicting results were obtained in some studies.[17–19] HbA1c is an important determinant in glycemic control. In some studies, no relationship was found between HbA1c and health literacy,[20–22] whereas in other studies, there was a relationship between high HbA1c level and low health literacy.[23,24] Low health literacy can further lead to poor outcomes caused by DM.[25,26] The aim of the present study was to investigate the relationship between health literacy, diabetic control, and diabetic complications in patients with type 1 DM.

MATERIAL AND METHODS The study was conducted in the internal medicine outpatient clinics and endocrinology and metabolic disease outpatient clinics of the hospital. A total of 106 patients with type 1 DM, between 18 and 65 years old, who could speak and understand Turkish, and who had no cognitive disease were included in the study. The study was approved by the ethics committee of the hospital (decision 2011-KAEK25 2018/01-09). Written informed consent was obtained from all participants in accordance with the Declaration of Helsinki. The Turkish version of the European Health Literacy Survey Questionnaire (HLS-EU-Q47) was used to assess health literacy.[27] Participants were asked questions in the context of a 47-item health literacy questionnaire, and their responses were recorded. The answers for the 47 questions were ranked as 1 = very difficult, 2 = quite hard, 3 = quite easy, and 4 = very easy. Survey questions were divided into subgroups and assessed as follows: health care: questions 1–16, disease prevention: questions 17–31, and health improvement: questions 32–47. At the end of the scoring, 0–25 points were insufficient, 25–33 points were problematic, 33–42 points were sufficient, and 42–50 points were excellent.

South. Clin. Ist. Euras.

Participant’s marital, educational, occupational, and economic status and monthly monetary income levels and duration of diabetes were noted. Their retinopathy status, HbA1C, fasting blood sugar, and urine albumin levels were obtained from the patient’s files. Patients who did not have a retinopathy examination within the last 1 year and who had no HbA1c, fasting blood sugar, and albuminuria values within the last 3 months were excluded from the study. To identify the presence of distal symmetric polyneuropathy, symptoms of neuropathy (paresthesia, dulled sensation, and pain) were asked to the patients. Vibration perception on the distal plantar faces of the toes and metatarsal joints and 10 g of microfibrillated pressures were applied. The presence of microvascular complications was determined according to the guidelines of the American Diabetes Association.[28]

Statistical analysis The normal distribution suitability of variables was examined by Shapiro–Wilk test. Continuous variables are expressed as median (minimum–maximum) values. Categorical variables are expressed as n (%). Pearson’s chi-square or Fisher’s exact test was used in the analyses to compare disease incidence among sufficient and insufficient health literacy groups. Mann–Whitney U test was used to compare health literacy with diabetes age and HbA1c. The internal consistency of the health literacy scale was examined by the Cronbach’s α coefficient. The reliability coefficients of the health literacy scale and subscales were found to be α=0.92 for health care, α=0.91 for disease prevention, α=0.93 for health improvement, and α=0.97 for general health. The SPSS program was used for statistical analysis (released 2012, IBM SPSS statistics for Windows, version 21.0; IBM Corp., Armonk, NY, USA). A p-value of <0.05 was considered statistically significant.

RESULTS A total of 106 (63 female and 43 male) patients with type 1 DM with a mean age of 32 years were studied. The mean disease duration was 11 years, mean HbA1c level was 8.75%, and mean fasting blood glucose level was 219 mg/dl. Tables 1 and 2 summarize the socio-demographic characteristics of the volunteers. Diabetic retinopathy was found in 17.9%, diabetic neuropathy in 6.6%, and diabetic nephropathy in 32.1% of the volunteers. Of the patients, 4.7% had cardiovascular disease, and 31% had additional diseases (e.g., bronchial asthma and psoriasis) other than diabetes and diabetic complications (Table 2). Table 3 shows the results of HLS-EU-Q47. Overall health literacy was insufficient in 10.4% of the patients, problematic in 54.7%, sufficient in 20.8%, and excellent in 14.2%.

Esen. Health Literacy and Type 1 Diabetes Mellitus

Table 1. Socio-demographic characteristics of participants

n=106

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Table 2. Participant’s fasting blood glucose and HbA1c values and presence of diabetic complications

Age (years), median (min–max)

Duration of diabetes (years),

Gender, n (%)

Female Male

n=106

32 (18–55) 63 (59.40)

median (min–max)

11 (1–32)

43 (40.60)

Retinopathy, n (%)

19 (17.90)

Marital status, n (%)

Neuropathy, n (%)

7 (6.60)

Single

41 (38.70)

Nephropathy, n (%)

34 (32.10)

Married

60 (56.60)

Cardiovascular disease, n (%)

Divorced

5 (4.70)

Additional disease, n (%)

Education status, n (%)

HbA1c, median (min–max)

Illiterate

Proteinuria, n (%)

Primary school

1 (0.90) 28 (26.40)

No microalbuminuria, n (%)

Secondary school

10 (9.40)

Microalbuminuria, n (%)

High school

41 (38.70)

Overt proteinuria, n (%)

26 (24.50)

Fasting blood glucose median (min–max)

University

Job, n (%) Housewife

25 (23.60)

Worker

23 (21.70)

Professional occupation

13 (12.30)

Artisan

8 (7.50)

Student

8 (7.50)

Unemployed

8 (7.50)

Craftsman

7 (6.60)

Officer

4 (3.80)

Retired

3 (2.80)

Farmer

2 (1.90)

Other

5 (4.70)

Health insurance, n (%) Social security institution

Special insurance

None

8.75 (5.70–15) 76 (71.70) 17 (16) 13 (12.30) 219 (55–583)

Min: Minimum; Max: Maximum.

5 (4.70) 33 (31.10)

93 (87.70) 1 (0.90) 12 (11.30)

Monthly monetary income, n (%)

None

18 (17)

500–1000 TL

9 (8.50)

1000–2000 TL

49 (46.20)

2000–4000 TL

25 (23.60)

>4000 TL

5 (4.70)

TL: Turkish Lira.; Min: Minimum; Max: Maximum.

When the subgroups were examined, health care health literacy was insufficient in 7.5% of the patients, problematic in 32.1%, sufficient in 37.7%, and excellent in 22.6%. Disease prevention health literacy was insufficient in 19.8% of the patients, problematic in 44.3%, sufficient in 21.7%, and excellent in 14.2%. Finally, health improvement health

literacy was insufficient in 27.4% of the patients, problematic in 36.8%, sufficient in 19.8%, and excellent in 16%. The relationship between retinopathy and health literacy is shown in Table 4 and Fig. 1. Retinopathy was found to be statistically significantly higher in the “problematic+insufficient” group than in the “sufficient+excellent” group in the overall health literacy evaluation (24.6% and 5.4%, respectively) (p=0.014). In the health literacy subgroup analysis, the frequency of retinopathy was found to be significantly higher in the “problematic+insufficient” group according to the assessment based on health improvement (p=0.044). Calculation of sample size was based on the presence of retinopathy for the health literacy subgroups. The percentage of retinopathy was found to be 26% for the insufficient health literacy group and 5.40% for the sufficient health literacy group; insufficient health literacy group of n=50 and sufficient health literacy group of n=28 formed a total of 78 patients in a pilot study. Calculated by G*Power 3.1 (http://www.gpower.hhu.de/), the achieved power was found to be 73%. We also calculated the target sample size that was needed to achieve at least 80% power with retinopathy proportions obtained from a pilot study. As a result, priori power analysis was conducted using a medium effect size (Cramer’s V=0.28) based upon findings of a pilot study. Using this effect size, V=0.28, a total sample size of 78 (n=56 for the limited health literacy group and n=21 for the adequate health literacy group) participants was estimated for a power of 0.80 and α of 0.05. Finally, 106 people were included in the study when the limitations of the study were taken into consideration.

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South. Clin. Ist. Euras.

Table 3. Health literacy scores and distribution of subgroups

Insufficient

Problematic

Sufficient

Excellent

n % n % n % n %

Overall health literacy (Q 1–47)

10.40

54.70

20.80

14.20

Health care health literacy (Q 1–16)

7.50

32.10

37.70

22.60

Disease prevention health literacy (Q 17–31)

19.80

44.30

21.70

14.20

Health improvement health literacy (Q 32–47)

27.40

36.80

19.80

Table 4. Relationship with health literacy and retinopathy

Retinopathy

No Yes (n=87) (n=19)

Table 5. Comparison of age, duration of diabetes, and HbA1c levels among health literacy groups

Overall HL, n (%)

Insufficient+problematic

52 (75.40) 17 (24.60) 0.014a

Sufficient+excellent

35 (94.60) 2 (5.40)

Health care HL, n (%)

Insufficient+problematic

32 (76.20) 10 (23.80) 0.201a

Sufficient+excellent

55 (85.90) 9 (14.10)

Health literacy

Insufficient+ Sufficient+ problematic excellent (n=69) (n=37)

Age

31 (18–55)

32 (18–48)

0.635a

Duration of diabetes

11 (1–32)

11 (1–25)

0.902a

HbA1c

8.90 (5.70–15) 7.80 (6–14.80) 0.009a

Data are expressed as median (minimum–maximum). a: Mann–Whitney U test.

Disease prevention HL, n (%)

Insufficient+problematic

53 (77.90) 15 (22.10) 0.138a

Sufficient+excellent

34 (89.50) 4 (10.50)

Health improvement HL, n (%)

Insufficient+problematic

52 (76.50) 16 (23.50) 0.044a

Sufficient+excellent

35 (92.10) 3 (7.90)

ditional disease between the “problematic + insufficient” and “sufficient + excellent” groups in the general health literacy (p=0.417, p=0.705, p=0.656, and p=0.504, respectively).

DISCUSSION

: Chi-square test. HL: Health literacy.

In the overall health literacy assessment, the HbA1c ratio was significantly higher in the “problematic + insufficient” group than in the “sufficient + excellent” group (8.9% and 7.8%, respectively) (p=0.009). However, there was no relationship between health literacy and age or duration of diabetes (Table 5). There was no significant difference in the frequency of neuropathy, nephropathy, cardiovascular disease, and adWith retinopathy Without retinopathy

Sufficient+excellent

Problematic+insufficient

100

Figure 1. The frequency of retinopathy in general health literacy.

Overall health literacy was insufficient in 10.4% of the patients, problematic in 54.7%, sufficient in 20.8%, and excellent in 14.2%. Retinopathy was found to be statistically significantly higher in the “problematic + insufficient” group than in the “sufficient + excellent” group in the overall health literacy evaluation (24.6% and 5.4%, respectively). There was no significant difference in the frequency of neuropathy, nephropathy, and cardiovascular disease in the health literacy groups. In the present study, we found health literacy to be 54.7% problematic and 10.4% insufficient in patients with type 1 DM. Souza et al.[29] found that functional health literacy below adequate was 56.6% in patients with DM. Protheroe et al.[30] noted that 60.5% have low health literacy among patients with DM in the United Kingdom. Mohammadi et al.[31] reported that inadequate health literacy was 70.0% in Iranian diabetic patients. Hussein et al.[32] showed that 44.5% of patients with type 2 DM had inadequate health literacy. It is difficult to make a complete comparison if the scales used are different. However, it is observed that health literacy among patients with DM is low. Since low

Esen. Health Literacy and Type 1 Diabetes Mellitus

155

health literacy is associated with poor prognosis, it can be said that these patients need training in addition to drug treatment for the management of the disease.

Peer-review

Diabetic retinopathy was found to be statistically significantly higher in the “problematic + insufficient” health literacy group than in the “sufficient + excellent” health literacy group, which is one of the most striking results of the present study. In the health improvement health literacy subgroup analysis, a significant retinopathy rate was found in the group with “problematic + insufficient” health literacy. It is thought that this is caused by poor health literacy leading to poor disease control. In a study, it was found that 50.8% of diabetic patients knew that routine eye examinations are required and only 19% of the patients had information about diabetic retinopathy.[33] Rani et al.[34] found that 25% of the population in the urban area and 67% of the population in the rural area did not have diabetic retinopathy screening. The present study and other studies show that patients with diabetes do not have adequate knowledge about their current illnesses due to low health literacy. Low health literacy in the community makes it difficult to make progress against diseases and complications. Increasing levels of health literacy should be one of the leading targets in the struggle against diabetes.

Concept: İ.E., H.D.; Design: İ.E., H.D.; Data collection &/ or processing: İ.E., M.G., S.A.E.; Analysis and/or interpretation: M.G., S.A.E., E.E.Ş.; Literature search: İ.E., H.D., E.E.Ş.; Writing: İ.E., H.D., M.G., S.A.E., E.E.Ş.; Critical review: İ.E., H.D.

In the present study, patients with “problematic + insufficient” general health illiteracy were found to have higher HbA1c levels, and this was statistically significant. However, no relationship between health literacy and age or duration of diabetes was established. Mounce et al.[35] found no difference between low and high health literacy patients in terms of HbA1c and proteinuria levels. These conflicting results may be due to different populations in different cultures and geographies. In addition, health care providers in different geographical regions may be an essential factor for the levels of health literacy of the patients. Furthermore, health literacy questionnaire forms used in studies may be different. In the present study, we used HLS-EU-Q47, which is more comprehensive than other health literacy surveys and applicable to various populations. The reliability of the survey also strengthens the relationship between elevated HbA1c and low health literacy. In conclusion, the present study showed that low health literacy in patients with type 1 DM was associated with increased retinopathy. Physicians should keep in mind the positive effects of education in controlling a disease and the prevention of its complications. Ethics Committee Approval The study was approved by the ethics committee of the hospital (decision 2011-KAEK-25 2018/01-09). Informed Consent Written informed consent was obtained from all participants.

Internally peer-reviewed. Authorship Contributions

Conflict of Interest None declared.

REFERENCES 1. van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 2011;91:79–118. 2. Harada M, Fujihara K, Osawa T, Yamamoto M, Kaneko M, Matsubayashi Y, et al. Effects of treatment-achieved HbA1c on incidence of micro-/macrovascular complications in patients with diabetes mellitus. Diabetes 2018;67:444. 3. Garcia MJ, McNamara PM, Gordon T, Kannel WB. Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study. Diabetes 1974;23:105–11. 4. Huang ES, Laiteerapong N, Liu JY, John PM, Moffet HH, Karter AJ. Rates of complications and mortality in older patients with diabetes mellitus: the diabetes and aging study. JAMA Intern Med 2014;174:251–8. 5. Packer M. Heart Failure: The Most Important, Preventable, and Treatable Cardiovascular Complication of Type 2 Diabetes. Diabetes Care 2018;41:11–13. 6. Speight J, Amiel S, Bradley C, Heller S, James P, Oliver L, et al. The dose adjustment for Normal Eating (DAFNE) Trial. Improvements in HBA1c still apparent and quality of life benefits well-maintained at 4-year follow-up. Diabet Med 2007;24:95, Abstract P224. 7. DAFNE Study Group. Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes: dose adjustment for normal eating (DAFNE) randomised controlled trial. BMJ 2002;325:746. 8. Powers MA, Bardsley J, Cypress M, Duker P, Funnell MM, Fischl AH, et al. Diabetes self-management education and support in type 2 diabetes: a joint position statement of the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics. Clin Diabetes 2016;34:70–80 9. Saffari M, Ghanizadeh G, Koenig HG. Health education via mobile text messaging for glycemic control in adults with type 2 diabetes: a systematic review and meta-analysis. Prim Care Diabetes 2014;8:275–85. 10. Dodson S, Good S, Osborne R. Regional Office for South-East Asia. Health literacy toolkit for low- and middle-income countries: a series of information sheets to empower communities and strengthen health systems. WHO; 2015. Available at: http://apps.searo.who. int/PDS_DOCS/B5148.pdf?ua=1. Accessed Sep 6, 2018. 11. Çopurlar KC, Kartal M. What is Health Literacy? How to Measure It? Why is It Important? TJFM&PC 2016;10:42–7. 12. Sørensen K, Pleasant A. Understanding the conceptual importance of the differences among health literacy definitions. Stud Health

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Technol Inform 2017;240:3–14. 13. Mackey LM, Doody C, Werner EL, Fullen B. Self-management skills in chronic disease management: what role does health literacy have? Med Decis Making 2016;36:741–59. 14. Chiauzzi E, Rodarte C, DasMahapatra P. Patient-centered activity monitoring in the self-management of chronic health conditions. BMC Med 2015;13:77. 15. Miller TA. Health literacy and adherence to medical treatment in chronic and acute illness: a meta-analysis. Patient Educ Couns 2016;99:1079–86. 16. Poureslami I, Nimmon L, Rootman I, Fitzgerald MJ. Health literacy and chronic disease management: drawing from expert knowledge to set an agenda. Health Promot Int 2017;32:743–54. 17. Kim SH, Lee A. Health-literacy-sensitive diabetes self-management Interventions: A Systematic Review and Meta-Analysis. Worldviews Evid Based Nurs 2016;13:324–33. 18. Bailey SC, Brega AG, Crutchfield TM, Elasy T, Herr H, Kaphingst K, et al. Update on health literacy and diabetes. Diabetes Educ 2014;40:581–604. 19. Fransen MP, von Wagner C, Essink-Bot ML. Diabetes self-management in patients with low health literacy: ordering findings from literature in a health literacy framework. Patient Educ Couns 2012;88:44–53. 20. Gerber BS, Pagcatipunan M, Smith EV Jr, Basu SS, Lawless KA, Smolin LI, et al. The assessment of diabetes knowledge and self-efficacy in a diverse population using Rasch measurement. J Appl Meas 2006;7:55–73. 21. Morris NS, MacLean CD, Littenberg B. Literacy and health outcomes: a cross-sectional study in 1002 adults with diabetes. BMC Fam Pract 2006;7:49. 22. Kim S, Love F, Quistberg DA, Shea JA. Association of health literacy with self-management behavior in patients with diabetes. Diabetes Care 2004;27:2980–2. 23. van der Heide I, Wang J, Droomers M, Spreeuwenberg P, Rademakers J, Uiters E. The relationship between health, education, and health literacy: results from the Dutch Adult Literacy and Life Skills Survey. J Health Commun 2013;18:172–84. 24. Brega AG, Ang A, Vega W, Jiang L, Beals J, Mitchell CM, et al; Special Diabetes Program for Indians Healthy Heart Demonstration Project. Mechanisms underlying the relationship between health literacy and glycemic control in American Indians and Alaska Natives.

Patient Educ Couns 2012;88:61–8. 25. Schillinger D, Grumbach K, Piette J, Wang F, Osmond D, Daher C, et al. Association of health literacy with diabetes outcomes. JAMA 2002;288:475–82. 26. Levin-Zamir D, Baron-Epel OB, Cohen V, Elhayany A. The Association of Health Literacy with Health Behavior, socioeconomic indicators, and self-assessed health from a national adult survey in Israel. J Health Commun 2016;21:61–8. 27. HLS-EU Consortium. Comparative report of health literacy in eight EU member states. The European Health Literacy Survey HLS-EU; 2012. Available at: http://ec.europa.eu/chafea/documents/news/ Comparative_report_on_health_literacy_in_eight_EU_member_ states.pdf, Accessed Sep 6, 2018. 28. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care 2013;36:S11–66. 29. Souza JG, Apolinario D, Magaldi RM, Busse AL, Campora F, Jacob-Filho W. Functional health literacy and glycaemic control in older adults with type 2 diabetes: a cross-sectional study. BMJ Open 2014;4:e004180. 30. Protheroe J, Whittle R, Bartlam B, Estacio EV, Clark L, Kurth J. Health literacy, associated lifestyle and demographic factors in adult population of an English city: a cross-sectional survey. Health Expect 2017;20:112–9. 31. Mohammadi Z, Tehrani Banihashemi A, Asgharifard H, Bahramian M, Baradaran HR, Khamseh ME. Health literacy and its influencing factors in Iranian diabetic patients. Med J Islam Repub Iran 2015;29:230. 32. Hussein SH, Almajran A, Albatineh AN. Prevalence of health literacy and its correlates among patients with type II diabetes in Kuwait: A population based study. Diabetes Res Clin Pract 2018;141:118–25. 33. Tajunisah I, Wong P, Tan L, Rokiah P, Reddy S. Awareness of eye complications and prevalence of retinopathy in the first visit to eye clinic among type 2 diabetic patients. Int J Ophthalmol 2011;4:519– 24. 34. Rani PK, Raman R, Sharma V, Mahuli SV, Tarigopala A, Sudhir RR, et al. Analysis of a comprehensive diabetic retinopathy screening model for rural and urban diabetics in developing countries. Br J Ophthalmol 2007;91:1425–9. 35. Mounce LT, Steel N, Hardcastle AC, Henley WE, Bachmann MO, Campbell JL, et al. Patient characteristics predicting failure to receive indicated care for type 2 diabetes. Diabetes Res Clin Pract 2015;107:247–58.

Tip 1 Diyabetes Mellitus Hastalarında Sağlık Okuryazarlığı ve Diyabet Kontrolü ve Hastalığa Özgü Komplikasyonlar Arasındaki İlişki Amaç: Tip 1 diyabetes mellitus hastalarında sağlık okuryazarlığının diyabet kontrolü ve hastalığa özgü komplikasyonlarla ilişkisini araştırmak amaçlandı. Gereç ve Yöntem: Bu araştırma tanımlayıcı bir çalışmadır. On sekiz–altmış beş yaş aralığında olan Türkçe konuşan ve herhangi bir bilişsel rahatsızlığı olmayan 106 tip 1diyabetes mellitus hastası araştırmaya dahil edildi. Avrupa Sağlık Okuryazarlığı Araştırması Anket soruları kişilerin sağlık okuryazarlığı düzeylerini ölçmede kullanıldı. Katılımcıların retinopati muayeneleri, HbA1c sonuçları, açlık kan şekeri sonuçları ve albuminüri seviyeleri hasta dosyalarından elde edildi. Bulgular: Toplamda sağlık okuryazarlığı %10.4 katılımcıda yetersiz, %54.7 katılımcıda problemli, %20.8 katılımcıda yeterli ve %14.2 katılımcıda mükemmeldi. Retinopati sıklığı, sağlık okuryazarlığı problemli ve yetersiz olan grupta yeterli ve mükemmel olan gruba oranla daha sıktı (%24.6 ve %5.4). Sağlık okuryazarlığı gruplarında nöropati ve nefropati ve kardiyovasküler hastalıklar arasında fark yoktu. Sonuç: Çalışma sonucunda tip 1 diyabetes mellitus hastalarında sağlık okuryazarlığının artmış retinopati riski ile ilişkili olduğu görüldü. Hekimler hastalık kontrolü ve korunmasında eğitimin önemini akılda tutmalıdırlar. Anahtar Sözcükler: HbA1c; kardiyovasküler hastalıklar; nefropati; nöropati; retinopati; sağlık okuryazarlığı.

DOI: 10.14744/scie.2018.70894 South. Clin. Ist. Euras. 2018;29(3):157-160

Original Article

The Alvarado Score and Computed Tomography for Predicting Acute Appendicitis in Elderly Patients Selçuk Kaya, Önder Altın, Yunus Emre Altuntaş, Ahmet Şeker, Levent Kaptanoğlu, Nejdet Bildik, Hasan Fehmi Küçük

ABSTRACT Objective: The aim of this study was to modify the Alvarado scoring system to increase its sensitivity and specificity in predicting acute appendicitis in elderly patients. Department of General Surgery, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey Submitted: 24.05.2018 Accepted: 31.07.2018 Correspondence: Selçuk Kaya, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey E-mail: selcukkaya_36@hotmail.com

Keywords: Alvarado score; appendicitis in the elderly; computerized tomography.

Methods: The data of 81 patients older than 70 years of age who were admitted for acute abdominal pain between January 2015 and December 2017 were randomized into 2 groups and evaluated retrospectively. In Group 1 patients, acute appendicitis was not histopathologically established postoperatively, while Group 2 patients had pathological results consistent with acute appendicitis. The sensitivity and specificity of computed tomography (CT) scans and Alvarado scores were evaluated in the 2 groups. Results: The specificity and sensitivity of the modified Alvarado score was 86% and 81%, respectively, whereas the specificity and sensitivity of a CT scan was 93% and 92.1%, respectively, in diagnosing acute appendicitis. Conclusion: There are a limited number of studies related to acute appendicitis in elderly patients and the current strategy for treatment is not clear. Due to the decreased sensitivity of the Alvarado score in the diagnosis of acute appendicitis in elderly patients, the goal of this research was to adjust the scoring system. Scores >7 are more reliable in predicting appendicitis. We believe that patients can be more accurately diagnosed in a short period of time using this modified Alvarado scoring system. In combination with a CT scan evaluation, the success rate of diagnosis may be improved and delayed diagnosis prevented.

INTRODUCTION Acute appendicitis is the most common cause of acute abdominal surgery and its lifetime risk is 7%.[1] Appendicitis is a disease of the young age group, which accounts only for 5%–10% of the acute causes of the elderly population. However, the incidence of disease in the elderly is increasing, possibly due to the increase in life expectancy. [2,3] Perforated appendicitis constitutes approximately 20% of all appendicitis cases and significantly increases the rate of postoperative complications.[4] Diagnosis of elderly patients with acute appendicitis is usually delayed, due to its atypical presentation and delay in admission to the hospital. Delay in diagnosis and treat-

ment in the elderly causes an increase in perforation rates, thus worsening the clinical condition and an increase in morbidity and mortality.[5] It has been reported that the perforation and morbidity rates are 70% and 48%, respectively.[6] Advance age is an independent high risk factor for surgery and anesthesia.[7,8] For this reason, researchers are trying to develop management strategies tailored to the elderly population. The management strategy of acute appendicitis in the elderly is still uncertain and there are few studies in this regard. Clinically, evaluation of acute appendicitis requires systematic examination of symptoms, signs and diagnostic tests which reduces diagnostic errors.

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In 1986, Alfredo Alvarado developed a total 10-point scoring system, also known as the abbreviation of MANTRELS, based on symptoms, findings, and diagnostic tests for the diagnosis of acute appendicitis in patients who present with suspect acute appendicitis.[9] According to this scoring system, it is recommended that the patients who have ≥7 points should undergo surgery and those who have <7 points should be followed up.[9,10] It has been reported that the use of the current interpretation of the Alvarado score in elderly patients will increase complications, mortality and morbidity in patients with acute appendicitis due to erroneous, and delayed diagnosis.[11] When the probability of appendicitis is within the suspected range, then advanced examinations such as ultrasonography and computed tomography (CT) scan are recommended.[12] In recent studies, the sensitivity and specificity of CT scans for acute apendicitis were found to be 87%–100% and 83%–98%, respectively.[13] By modifying Alvarado scoring system, we aimed to improve its sensitivity and specificity in the prediction of acute appendicitis in elderly patients.

MATERIAL AND METHODS We performed a retrospective study between January 2015 and December 2017 with 81 patients over 70 years of age who were admitted to our clinic with acute abdominal pain. Forty-eight of 81 patients underwent appendectomy due to acute appendicitis, while the remaining 33 patients were discharged with medical treatment after observation or hospitalization. The patients were divided into Group 1 that consisted of 38 patients who were discharged with medical treatment and whose pathologic diagnosis was incompatible with acute appendicitis. Group 2 comprised of 43 patients whose definite diagnosis was compatible with appendicitis based on histopathological examination. Patient’s examination findings, laboratory values and CT scan results were evaluated by compiling, and scanning the hospital database and file system. Pathology slides were re-examined. Some patients with acute appendicitis who achieved cure, and followed up with antibiotherapy were not operated and thus excluded from the study.[14] In this study Alvarado scoring system was used as clinical scoring system (Table 1). The patients were divided into subgroups with 1–6 points and 7–10 points based on Alvarado scoring. At CT: Grade 0 indicated normal appendix, and Grade 1 suspect cases of acute appendicitis. These patients had not any remarkable CT findings suggesting inflammation. There was a slight increase in appendiceal diameter or findings of inflammation at its loge. The appendiceal diameter of these patients was normal or the

South. Clin. Ist. Euras.

Table 1. Components of the Alvarado score Alvarado score

Score

Leukocytosis >10.000/mm3 2 Tenderness in right lower quadrant

Migration of pain

Rebound pain

Elevated temperature (>37.3ºC)

Nausea 1 Anorexia 1 Neutrophilia >65%

Total 10 Scores: 1–4: Discharge 30% appendicitis; 5–7: Monitoring/admission 66% appendicitis; 8–10: Surgery 93% appendicitis.

presence of their appendices could not be revealed. Grade 2 indicates typical acute appendicitis; the findings of CT include dilation of appendiceal lumen, edematous thickening of the appendiceal wall, and contamination in lymph nodes in the surrounding fatty tissues and/or fatty tissue. Grade 3 had CT findings of acute appendicitis associated with irregularity of the appendiceal wall and / or presence of intense nonreactive free fluid around it. When the results of CT were assessed, normal appendixes and suspect cases with acute appendicitis (Grade 0 + Grade 1) were included in Group 1. The cases with CT findings evaluated as acute appendicitis (Grade 2 + Grade 3) were included in Group 2. Sensitivity and specificity of CT and Alvarado scoring were assessed in patients older than 70 years. The ethics committee of our hospital approved the realization of this study.

Statistical analysis Statistical analyses were performed in the SPSS 20 statistical program. Normally distributed data were analyzed by ttests. Data with non-normal distribution were defined by median and range and analyzed by Mann-Whitney U test. Relationships between the variables in the cross- tables were analyzed, if necessary, using square test or Fisher’s test. Normality of data was analyzed using Kolmogorov– Smirnov test.

RESULTS Forty-six (56.7%) female and 35 (43.3%) male patients (total n=81) aged 70 years or older presented to our clinic with acute abdominal pain. The mean age of the patients in Group 1 who were not reported as appendicitis based on histopathological evaluation of the appendectomy specimen and discharged with medical treatment without reoperation was 79.16 (±7.13) years, whereas the mean age

Kaya. Alvarado Score in Elderly Appendicitis Patients

mated to increase in proportion to the number of patients treated.

Table 2. Demographic characteristics of patients, Alvarado scores and CT findings

Negative Pozitive n % n %

Alvarado score 1–6

31 81.6

7–10

14.0

18.4 37 86.0

Computed tomography 0–1

35 92.1

2–3

40 93.0

Age

7.9

79.16 (±7.13)

7.0

76.56 (±5.56)

Gender Female

21 55.3 25 58.1

Male

17 44.7 18 41.9

Table 3. Proposed changes in the interpretation of the Alvarado scores for elderly Alvarado scoring system 1–4 low risk 5–6 intermediate risk

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Our modified interpretation 1–6 low risk 7–10 high risk

7–10 high risk

of the patients in Group 2 who were evaluated as acute appendicitis by pathological evaluation was 76.56 (±5.56) years. There were 38 patients in Group 1 and 43 patients in Group 2. Five patients in Group 1 were treated with acute appendicitis but their pathologic diagnosis was incompatible with appendicitis. Our negative appendectomy rate was 10.4% According to the Alvarado scoring system, 37 patients received scores ranging from 1 to 6 points, while 44 patients had scores ranging from 7 to 10 points. According to these CT findings, 38 Grade 0–1 and 43 Grade 2–3 patients were included in the study (Table 2). In our study, the specificity, and sensitivity of Alvarado scores in establishing the diagnosis of acute appendicitis were 81%, and 86%, respectively. In our study, the specificity and sensitivity of CT findings in establishing the diagnosis of acute appendicitis were 93% and 92.1%, respectively.

DISCUSSION It is known that as the elderly population in the society increases, the number of patients who will present with acute abdominal pain will increase. The proportion of elderly patients diagnosed with acute appendicitis is esti-

In many studies mortality and morbidity rates increased in the elderly population due to delays in diagnosis.[3,15] Therefore, elderly patients require accurate and prompt diagnosis of acute appendicitis. In many studies, acute appendicitis has been reported to have a higher incidence in women than in men.[16,17] In our study, female / male ratio was 56.7% / 43.3%. Lucas and colleagues found 83.3% false negatives and 45.5% false positives in scores of ≤5 according to the Alvarado scoring system in the diagnosis of acute appendicitis in patients aged 60–80 years.[18] Some authors have suggested that acute appendicitis should be completely excluded in scores of ≤5 in the Alvarado scoring system.[19] In their interpretation of the general population using the classical Alvarado scoring system, rates of suspect cases with acute appendicitis in patients with scores 1–4, 5–7, and 8–10 points were reported as 30%, 66%, and 93%, respectively.[9] The use of the current interpretation of the Alvarado scores in elderly patients has been reported to increase complications, mortality and morbidity rates in patients with acute appendicitis due to false and delayed diagnosis.[11] In our study, we also modified the Alvarado scoring system in two groups of 1–6 and 7–10 scores to minimize delay in diagnosis, complications, mortality and morbidity rates (Table 3). In our study, we determined the diagnostic value of the Alvarado scoring system with a higher accuracy, in patients who had a score of 1–6 points, which established diagnosis, and those with a score of 7–10 points that excluded acute appendicitis. Alvarado score as 81.6% and 86%, respectively. In the diagnosis of acute appendicitis sensitivity of CT has been reported to be 95%–100% for the general population, while in some studies it has been demonstrated as 81.6% for the elderly population.[11,20,21] In our study, the specificity, and sensitivity of CT in the diagnosis of acute appendicitis were 93% and 92.1%, respectively.

CONCLUSION Since Alvarado scoring system has a lower diagnostic accuracy in elderly patients, we think that by modifying the Alvarado scoring system the diagnosis of acute appendicitis in elderly patients who score ≥7 can be made in a timely manner with a higher diagnostic accuracy rate When the Alvarado scoring system is combined with CT in the diagnosis of acute appendicitis, we believe that the diagnostic success will increase and the diagnostic delays will decrease. Ethics Committee Approval Approved by the local ethics committee.

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Informed Consent Retrospective study. Peer-review Internally peer-reviewed. Authorship Contributions Concept: S.K., Ö.A.; Design: S.K., Ö.A., Y.E.A.; Data collection &/or processing: S.K., Ö.A.; Analysis and/or interpretation: S.K., Y.E.A., A.Ş.; Literature search: S.K., Y.E.A., A.Ş.; Writing: S.K., Ö.A., Y.E.A.; Critical review: H.F.K, N.B. Conflict of Interest None declared.

REFERENCES 1. Ergul E. Importance of family history and genetics for the prediction of acute appendicitis. The Internet Journal of Surgery 2006;10:1–4. 2. Horattas MC, Guyton DP, Wu D. A reappraisal of appendicitis in the elderly. Am J Surg 1990;160:291–3. 3. Storm-Dickerson TL, Horattas MC. What have we learned over the past 20 years about appendicitis in the elderly? Am J Surg 2003;185:198–201. 4. Butler C. Surgical pathology of acute appendicitis. Human pathology 1981;12:870–8. 5. Franz MG, Norman J, Fabri PJ. Increased morbidity of appendicitis with advancing age. Am Surg 1995;61:40–4. 6. Wilcox RT, Traverso LW. Have the evaluation and treatment of acute appendicitis changed with new technology? Surg Clin North Am 1997;77:1355–70. 7. Hamel MB, Henderson WG, Khuri SF, Daley J. Surgical outcomes for patients aged 80 and older: morbidity and mortality from major noncardiac surgery. J Am Geriatr Soc 2005;53:424–9. 8. Bentrem DJ, Cohen ME, Hynes DM, Ko CY, Bilimoria KY. Identification of specific quality improvement opportunities for the elderly undergoing gastrointestinal surgery. Arch Surg 2009;144:1013–20.

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9. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64. 10. Nirajlal B, Gabriel R, Anand R, Sohil AK. Evaluation of Alvarado score in acute appendicitis: A prospective study. The Internet Journal of Surgery 2007;9. 11. Shchatsko A, Brown R, Reid T, Adams S, Alger A, Charles A. The utility of the Alvarado score in the diagnosis of acute appendicitis in the elderly. Am Surg 2017;83:793–8. 12. Terasawa T, Blackmore CC, Bent S, Kohlwes RJ. Systematic review: computed tomography and ultrasonography to detect acute appendicitis in adults and adolescents. Ann Intern Med 2004;141:537–46. 13. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidimiol 1990;132:910–25. 14. Turhan AN, Kapan S, Kütükçü E, Yiğitbaş H, Hatipoğlu S, Aygün E. Comparison of operative and non operative management of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2009;15:459–62. 15. Gurleyik G, Gurleyik E. Age-related clinical features in older patients with acute appendicitis. Eur J Emerg Med 2003;10:200–3. 16. Blomqvist PG, Andersson RE, Granath F, Lambe MP, Ekbom AR. Mortality after appendectomy in Sweden, 1987-1996. Ann Surg 2001;233:455–60. 17. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidimiol 1990;132:910–25. 18. Gwynn LK. The diagnosis of acute appendicitis: clinical assessment versus computed tomography evaluation. J Emerg Med 2001;21:11923. 19. Ohle R, O’Reilly F, O’Brien KK, Fahey T, Dimitrov BD. The Alvarado score for predicting acute appendicitis: a systematic review. BMC Med 2011;9:139. 20. Gwynn LK. The diagnosis of acute appendicitis: clinical assessment versus computed tomography evaluation. J Emerg Med 2001;21:119–23. 21. Dahabreh IJ, Adam GP, Halladay CW, Steele DW, Daiello LA, Wieland LS, et al. Diagnosis of right lower quadrant pain and suspected acute appendicitis. Rockville: Agency for Healthcare Research and Quality; 2015.

Yaşlı Hastalarda Akut Apandisit Tahmini İçin Alvarado Skoru ve Bilgisayarlı Tomografi Amaç: Yaşlı hastalarda akut apandisitin tahmininde Alvarado skorlama sistemini modifiye ederek, skorlamanın sensivite ve spesifitesini arttırmayı amaçladık. Gereç ve Yöntem: Ocak 2015–Aralık 2017 tarihleri arasında kliniğimizde akut karın ağrısı ile başvuran yetmiş yaş üstü 81 hastanın dahil edildiği geriye dönük bir çalışma yürüttük. Tıbbi takiple taburcu edilen ve ameliyat sonrası patolojik tanısı apandisit ile uyumlu olmayan hastalar Grup 1, ameliyat sonrası histopatolojik olarak apandisit olduğu gösterilmiş hastalar Grup 2 olarak tanımlandı. Bilgisayarlı tomografi (BT) ve Alvarado skorunun yetmiş yaş üstü hastalarda sensivitesi ve spesifitesi değerlendirildi. Bulgular: Çalışmamızda, modifiye Alvarado skorunun akut apandisit tanısını koymada spesifitesi %81, sensitivitesi %86 iken BT’nin spesifitesi %93, sensitivitesi %92.1 olarak bulunmuştur. Sonuç: Yaşlılarda akut apandisite yönelik stratejisi hala belirsizdir ve bu konuda az sayıda çalışma vardır. Alvarado skorlama sisteminin yaşlı hastalarda tanıda duyarlılığının düşük olduğundan dolayı, Alvarado skorlama sistemini modifiye ederek 7 ve üzerinde skor alan yaşlı hastalarda akut apandisit tanısının daha yüksek doğrululuk oranıyla, zamanında teşhis edilebileceğini düşünmekteyiz. Akut apandisit tanısında Alvarado skorlama sistemi ile BT kombine edildiğinde tanıdaki başarının artıp teşhisteki gecikmenin azalacağı kanaatindeyiz. Anahtar Sözcükler: Alvarado skoru; bilgisayarlı tomografi; yaşlılarda apandisit.

DOI: 10.14744/scie.2018.44265 South. Clin. Ist. Euras. 2018;29(3):161-167

Original Article

Comparison of Early Postoperative Recovery after Desflurane or Sevoflurane Anesthesia Özlem Sezen,

Elif Bombacı

ABSTRACT Objective: The aim of this study was to compare the early postoperative recovery effects between patients who were given sevoflurane or desflurane before having lower abdominal surgery under general anesthesia.

Department of Anesthesiology and Reanimation, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey Submitted: 20.07.2018 Accepted: 25.07.2018 Correspondence: Özlem Sezen, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, İstanbul, Turkey E-mail: drozlemsezen@hotmail.com

Keywords: Desflurane; postoperative; recovery; sevoflurane.

Methods: Eighty patients aged between 18 and 75 years with an American Society of Anesthesiologists physical status classification of I or II who were scheduled for elective lower abdominal surgery were divided into 2 groups. Before the induction of anesthesia, heart rate (HR), blood pressure, and peripheral oxygen saturation (SpO2) were measured, and neuromuscular monitoring was performed. Following the intravenous (IV) administration of 5 to 7 mg/kg thiopental and 1 mcg/kg fentanyl, 0.6 mg/kg rocuronium was used to facilitate endotracheal intubation. Maintenance of anesthesia was provided using 4% desflurane in Group I and 1.3% sevoflurane in Group II in a 50% oxygen-air mixture. During surgery, additional doses of 1 mcg/kg fentanyl were administered and the concentration of volatile anesthetics was adapted according to hemodynamic conditions. At the end of the operation, volatile agents were discontinued and 100% oxygen was administered to all patients. When the train-of-four stimulation value exceeded 85%, the patients were extubated and oxygen was provided via facemask. Perioperative axillary temperature, SpO2, hemoglobin (Hb), arterial pressure, HR, and total opioid consumption were recorded. SpO2 level, airway control value and modified Aldrete score were recorded at the 1st, 5th, 10th, 15th, 20th, 30th, 45th, and 60th minutes during the postoperative period. Pain evaluation was performed using a visual analog scale (VAS) of 1 to 10 at the same intervals. Results: There were no significant differences between the 2 groups in terms of the duration of anesthesia and surgery, extubation time, change in axillary temperature, perioperative hemodynamic changes, airway control, or VAS scores. In Group I, the total opioid dose was significantly higher and the preoperative and postoperative Hb values were significantly lower (p<0.01). The modified Aldrete scores of Group I were significantly higher than those of Group II at 10 minutes and at later intervals (p<0.002). In Group I, the postoperative SpO2 values were significantly higher than those seen in Group II (p<0.05 and above) at the 5th, 10th, 20th, 30th, and 45th minutes. Conclusion: It was concluded that desflurane may be a better choice of anesthesia during lower abdominal surgery than sevoflurane for patients with the potential for respiratory complications.

INTRODUCTION Postoperative complications, mainly hypoxia, are common in noncardiac surgeries, and may be long-lasting, leading to

extended periods of hospitalization, increased costs, and greater rates of morbidity and mortality.[1,2]

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Postoperative hypoxia may develop due to the deterioration of gas exchange in the lungs (atelectasis) or worsening of the respiratory mechanism (obstructive apnea). The patient’s position on the operating table, or the anesthetic drugs or muscle relaxant used may be responsible for atelectasis, while obstructive apnea may be a result of the method of anesthesia used (general or regional) or the opioid used.[3,4] All inhalation agents used during general anesthesia cause respiratory depression by decreasing tidal volume and minute ventilation, depending on the dose used. This negative effect on the respiratory system may also persist during the postoperative period.[5] The purpose of this study was to compare the early postoperative effects of sevoflurane and desflurane in patients who underwent lower abdominal surgery under general anesthesia.

MATERIAL AND METHODS After receiving the approval of the local ethics committee, 80 patients with an American Society of Anesthesiologists physical status classification of I or II who were aged between 18 and 75 years and were to undergo elective lower abdominal surgery were included in the study. Patients with anemia; cardiac, pulmonary, or neuromuscular disease; those who were obese (body mass index [BMI] >25 kg/m2); smokers; and those who were to have thoracic or upper abdominal surgery were excluded from the study. The patients were allocated into 2 groups using a simple randomization method and premedication was not applied. Heart rate (HR) and noninvasive arterial blood pressure (BP) were measured, and peripheral oxygen saturation (SpO2) was monitored in the DII derivation in the operating room. In addition, the neuromuscular junction of the adductor pollicis brevis muscle was monitored using the TOF-Watch SX (Organon International, Oss, Netherlands) in order to see that the effect of the pre-extubation muscle relaxant had completely receded and to avoid any development of postoperative hypoxia. Endotracheal intubation was performed 2 minutes after induction of anesthesia with thiopental (5–7 mg/kg IV), rocuronium (0.6 mg/kg IV), and fentanyl (1 mcg/kg IV). To maintain anesthesia, a 50% oxygen-air mixture and 4% desflurane were used in Group I, and a 50% oxygen-air mixture and 1.3% sevoflurane were administered in Group II. When HR and BP values increased by 20% compared to baseline values, fentanyl (1 mcg/kg IV) was administered. When hemodynamic parameters decreased by 20%, the concentration of volatile gases was reduced by 0.5%. The administration of inhalation gases was discontinued 5 minutes before surgery. Delivery of the air-oxygen mixture was maintained until the final skin suturing at the

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conclusion of the procedure, at which time inhalation of 100% oxygen was initiated. The muscle relaxant effect was reversed with atropine (0.05 mg/kg IV) and neostigmine (0.07 mg/kg IV). When the train-of-four measurement was ≥85%, the patients were extubated. The recovery time was calculated and recorded from the moment of switching to 100% oxygen inhalation until eye opening with verbal stimulation, time until extubation, and response to verbal commands. Preoperative and postoperative axillary temperature, SpO2, Hb, arterial pressure, HR, and total opioid dose were recorded. Oxygen delivery was initiated with a mask at a rate of 2 L/minute in the postoperative recovery room. From this point on, the SpO2 level, airway control value, and modified Aldrete postanesthesia recovery score were recorded at the postoperative 1st, 5th, 10th, 15th, 20th, 30th, 45th, and 60th minutes. Pain was assessed at the same time intervals using a 10-cm visual analogue scale (VAS). Airway control was scored as 1: calm breathing, 2: mild (snoring), 3: moderate (deep snoring, obstruction may be relieved via airway or change in position), or 4: severe (obstruction requiring intubation). The GraphPad Prism 7 program (GraphPad Software Inc., La Jolla, CA, USA) was used to perform the statistical analysis. Student’s t-test was used for comparisons of descriptive variables between the 2 groups, as well as one-way analysis of variance with a Tukey post-test (mean, SD, minimum and maximum values). Statistical significance was evaluated as *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001.

RESULTS No significant difference between the groups was observed in the comparison of descriptive statistical data (Table 1; p>0.05). In Group I, the youngest participant was 20 years old, while the oldest was 60 years old. The body weight of the patients ranged between 55 and 89 kg. In Group II, the age range of the participants was 19 to 69 years and the body weight varied between 45 and 95 kg. Furthermore, no statistically significant differences were seen between the groups in terms of the duration of anesTable 1. Comparison of descriptive data (mean±SD)

Group I Group II (n=40) (n=40)

Age (years)

42.7±8.9

45.3±12.7

Body weight (kg)

70.2±7.8

71±11.3

35/65

25/75

1.5±0.5

1.6±0.5

Gender (% male/female) ASA physical status

ASA: American Society of Anesthesiologists.

>0.05

Sezen. Desflurane or Sevoflurane Anesthesia

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thesia or surgery, time until extubation, change in axillary temperature, preoperative SpO2 value, or preoperative and postoperative BP and HR values. Use of a significantly

larger total opioid dose was detected in the desfluranetreated group, while the preoperative and postoperative Hb values were significantly lower in that group (Table 2).

Table 2. Intergroup comparison of preoperative and postoperative values

Group I

Group II

Mean difference

Mean±SD Mean±SD

Mean±SD

Duration of anesthesia (min)

89.28±4.63

92.4±6.18

3.125±7.73

Duration of surgery (min)

76.35±4.58

81.58±6.18

5.225±7.69

>0.05

Opioid dose (mcg)

111.3±3.09

94±4.39

17.25±5.38

<0.01

>0.05

Time to eye opening upon verbal stimuli

5.80± 3.64

6.3± 5.19

0.76±0.57

>0.05

Compliance with verbal commands

7.23± 3.61

8.79±5.56

0.80± 0.61

>0.05

Length of time until extubation (min)

6.05±0.43

6.9±0.45

0.85±0.62

>0.05

Preoperative axillary temperature (°C)

36.57±0.05

36.43±0.04

0.12±0.04

>0.05

Postoperative axillary temperature (°C)

36.07±0.03

36.17±0.05

0.11±0.06

>0.05

Preoperative SpO2 (%)

98.4±0.12

97.99±0.18

0.52±0.20

>0.05

Preoperative hemoglobin (% gr)

11.77±0.24

12.90±0.24

1.13±0.34

<0.01

Postoperative hemoglobin (% gr)

10.85±0.21

12.06±0.24

1.208±0.32

<0.001

Preoperative arterial blood pressure (mmHg)

107.2±2.76

104.5±2.21

2.65±3.53

>0.05

Postoperative arterial blood pressure (mmHg)

112.4±2.84

105.8±2.56

6.6±3.82

>0.05

Preoperative heart rate (bpm)

83.58±1.99

86.1±2.13

2.52±2.92

>0.05

Postoperative heart rate (bpm)

88.55±2.34

87.25±2.72

1.3±3.58

>0.05

SpO2: Peripheral oxygen saturation; SD: Standard deviation.

Table 3. Intergroup comparison of Aldrete score (mean±SD) Measurement intervals

Groups

Mean±SD Aldrete score

Mean±SD difference

Is it significant?

0.15±0.24

0.5336

1st minute

Group I

7.42±0.13

Group II

7.27±0.19

5th minute

Group I

8.47±0.16

Group II

8.3±0.21

0.17±0.26

0.5047

10th minute

Group I

9.42±0.10

Group II

8.87±0.14

** Yes

0.55±0.17

0.002

Yes

15 minute

Group I

9.8±0.07

Group II

9.3±0.11

***

20 minute

Group I

9.95±0.03

Yes

Group II

9.6±0.08

*** Yes

0.5±0.13 0.35±0.09

0.0003 0.0001

30 minute

Group I

9.97±0.02

Group II

9.67±0.07

45 minute

Group I

Group II

60 minute

Group I

Group II

SD: Standard deviation.

10±0

0.3±0.08 0.27±0.07

0.0003 0.0002

9.72±0.07 10±0

0.22±0.07

0.0012

9.77±0.07

*** Yes *** Yes **

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No statistically significant intergroup difference was found between the 1st and 5th minute Aldrete scores. However, the score was higher in the desflurane group compared with the sevoflurane group at 10 minutes and afterwards.

The difference between the 2 groups was statistically significant (Table 3). The postoperative SpO2 values of Group I and Group II were similar at the 1st, 15th, and 60th minutes, and no signif-

Table 4. Intergroup comparison of postoperative peripheral oxygen saturation measurement (mean±SD) Measurement intervals

Groups

Mean±SD SpO2

Mean±SD difference

Is it significant?

1st minute

Group I

98.5±0.11

0.37±0.23

0.1067

Group II

98.13±0.2

5th minute

Group I

98.48±0.11

0.7±0.24

0.0049

Yes

Group II

97.38±0.21

10th minute

Group I

98.7±0.11

Yes

0.55±0.22

0.0145

Group II

98.15±0.19

15th minute

Group I

98.65±0.11

0.27±0.21

0.1995

Group II

98.38±0.18

20th minute

Group I

98.75±0.11

0.55±0.20

0.0091

* No Yes

Group II

98.2±0.18

30th minute

Group I

98.83±0.10

Yes

0.77±0.21

0.0004

Group II

98.05±0.18

***

45th minute

Group I

98.8±0.102

Yes

0.67±0.19

0.0008

Group II

98.13±0.16

***

60th minute

Group I

98.85±0.10

Group II

98.85±0.10

0±0.14

>0.9999

SpO2: Peripheral oxygen saturation; SD: Standard deviation.

Table 5. Intergroup comparison of airway control (mean±SD) Measurement intervals

Groups

Mean±SD obstruction

Mean±SD difference

Is it significant?

0.1±0.12

0.4201

1st minute

Group I

1.17±0.08

Group II

1.27±0.09

5th minute

Group I

1.02±0.02

Group II

1.1±0.06

10th minute

Group I

Group II

15th minute

Group I

Group II

20th minute

Group I

Group II

30th minute

Group I

Group II

45th minute

Group I

Group II

1±0

0±0.04

0.2515 >0.9999

No No

1±0.03 1±0

0.02±0.02

0.3204

0.97±0.02 1±0

0.02±0.02

0.3204

0.97±0.02 1±0

0.02±0.02

0.3204

0.97±0.02 1±0

0.02±0.02

0.3204

0.97±0.02

60th minute

Group I

1±0

Group II

0.97±0.02

SD: Standard deviation.

0.07±0.06

0.02±0.02

0.3204

Sezen. Desflurane or Sevoflurane Anesthesia

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Table 6. Intergroup comparison of visual analogue scale score (mean±SD) Measurement intervals

Groups

Mean±SD VAS

Mean±SD difference

Is it significant?

1st minute

Group I

1.97±0.24

0.2±0.34

0.5532

Group II

1.77±0.23

5th minute

Group I

2.52±0.29

Group II

2.15±0.23

10th minute

Group I

2.87±0.31

Group II

2.35±0.19

15th minute

Group I

2.62±0.19

Group II

2.97±0.25

20th minute

Group I

2.7±0.18

Group II

3.17±0.20

30th minute

Group I

2.7±0.17

Group II

3.22±0.23

45th minute

Group I

2.85±0.33

Group II

2.33±0.21

60th minute

Group I

2.7±0.17

Group II

3.16±0.21

0.37±0.37 0.52±0.36 0.35±0.31 0.47±0.26 0.52±0.28 0.52±0.34 0.46±0.25

0.3156 0.154 0.2662 0.0751 0.0678 0.152 0.0748

No No No No No No No

VAS: Visual analogue scale; SD: Standard deviation.

icant difference was found. However, at the postoperative 5th, 10th, 20th, 30th, and 45th minutes, the SpO2 value was statistically significantly higher in the desflurane-treated group (Table 4). No statistically significant difference was found between the groups in airway control or VAS values (Tables 5, 6).

DISCUSSION Abdominal and thoracic surgery include the risk of early postoperative complications. These patients may also have respiratory insufficiency requiring endotracheal intubation and respiratory support.[6] The presence of comorbid conditions and diseases, such as smoking, advanced age, obesity, and chronic obstructive pulmonary disease, increases the risk of postoperative respiratory insufficiency. [7] Non-elderly patients with a BMI <25 kg/m2, who had no pulmonary disease or smoking history, and had normal biochemical values who underwent only lower abdominal surgery were included in this study of the early-term postoperative effects of desflurane and sevoflurane. Hypoxia most often develops during the postoperative period due to atelectasis. Both general anesthesia and the administration of a muscle relaxant reduce muscle tonus and functional residual capacity, which may lead to atelectasis as a complication of endotracheal intubation, especially in the left lung.[8] The anesthetic medication used may be responsible for postoperative respiratory failure during surgery.[9]

In our study, no significant difference was observed in the duration of surgery or anesthesia between the 2 groups. In the desflurane-treated group, the total opioid dose was significantly larger than that of the other group; however, the oxygen saturation values were significantly higher in the early recovery period in that group. According to a study by Duggan et al.,[10] 0.9% of their patients experienced respiratory distress during the postoperative period that required intervention. The effects of volatile anesthetics may affect respiratory function during the postoperative period. It has been established that, among these anesthetics, desflurane and sevoflurane have a low blood-gas partition coefficient that allows for early recovery from anesthesia.[11] This study also examined the effects of the blood-gas partition coefficient of these anesthetic drugs on early postoperative recovery. The postoperative SpO2 values of our patients were similar at the 1st, 15th, and 60th minutes, and there was no significant difference between the 2 groups. However, at the postoperative 5th, 10th, 20th, 30th, and 45th minutes, the SpO2 values were greater in the desflurane- treated group and a statistically significant difference was observed between the groups. Desflurane induces transient hypertension and tachycardia by stimulating the sympathetic nervous system, especially at concentrations above 5% to 6%.[12] In this study, additional opioid doses were administered based on an increase in BP and HR, and the total opioid dose was determined to be greater in the desflurane group.

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Postoperative airway obstruction can lead to a deterioration of the ventilation-perfusion ratio, and eventually, to hypoxia.[13] We found no difference in the postoperative airway control values between the 2 groups in this study. Many studies have shown that recovery is faster after desflurane anesthesia when compared with sevoflurane.[14,–17] For example, Chen et al.[15] found that the postanesthesia recovery of patients who had been given desflurane was faster. It has also been stated that desflurane has other advantages compared to sevoflurane in terms of early recovery. Recovery time from the termination of anesthesia to the opening of eyes, tracheal extubation, response to verbal commands, and orientation was shorter in the desflurane group. In our study, there was no difference between the desflurane and sevoflurane groups in terms of extubation time, time until eye opening with verbal stimuli, or compliance with verbal commands. In another study, Song et al.[18] compared sevoflurane, desflurane, and propofol anesthesia, and found no difference between the desflurane and sevoflurane groups in terms of the time until extubation, recovery, and orientation, consistent with our study. However, delayed extubation and recovery were detected in the propofol group.

minutes were higher in the desflurane group than in the sevoflurane group, and the difference was statistically significant. Desflurane appears to provide a faster recovery than sevoflurane.

CONCLUSION The administration of desflurane or sevoflurane with opioid support has a similar effect in terms of perioperative hemodynamic control. We observed no significant differences in extubation time, time until eye opening, response to verbal commands, axillary temperature change, preoperative SpO2 value, airway control, or VAS value. Desflurane did, however, provide a somewhat faster recovery. Lower levels of SpO2 in the postoperative period in patients who received sevoflurane anesthesia suggest that the respiratory depressant effect is greater. Therefore, particularly for patients with a high risk of postoperative hypoxia, desflurane may be preferable to sevoflurane in lower abdominal surgery. Ethics Committee Approval Approved by the local ethics committee. Informed Consent Retrospective study.

McKay et al. compared the effects of desflurane and sevoflurane on the return of airway reflexes during the early postoperative period, and a quicker return was detected in the desflurane group. This has been attributed to the lower resolution of desflurane in blood and tissues. It was noted that the early return of postoperative airway reflexes is especially important in patients with a high risk of pulmonary aspiration.

Peer-review

White et al. compared desflurane and sevoflurane in laparoscopic gynecological day-case interventions, and demonstrated that the intraoperative hemodynamic parameters were similar in both groups. Desflurane patients had a faster recovery after anesthesia, though there was no significant difference between the 2 groups in terms of discharge.

None declared.

[19]

[20]

Dupont et al.[21] compared desflurane, sevoflurane, and isoflurane anesthesia in 1000 patients undergoing pulmonary surgery. Comparable arterial pressure, HR, and oxygenation values were observed with all 3 agents over the course of the period of anesthesia. Eger et al.[22] also found no significant difference in vital findings either during or after anesthesia when comparing sevoflurane and desflurane groups. Similarly, in our study, the hemodynamic parameters were comparable between groups and did not exceed 20% above baseline levels. When we compared recovery parameters, we did not find any significant difference in the 1st and 5th minute modified Aldrete scores of the 2 groups. However, the scores at 10

Internally peer-reviewed. Authorship Contributions Concept: Ö.S.; Design: Ö.S.; Data collection &/or processing: Ö.S.; Analysis and/or interpretation: Ö.S.; Literature search: Ö.S., E.B.; Writing: Ö.S.; Critical review: E.B. Conflict of Interest

REFERENCES 1. Köksal N. Ozlu T, Metintaş M, Karadağ M, Kaya A. Preoperative evoluation. In: Respiratory system and Diseases. 1st ed. Istanbul; Medical Publishing; 2010. p. 2543–55. 2. Sun Z, Sessler DI, Dalton JE, Devereaux PJ, Shahinyan A, Naylor AJ, et al. Postoperative Hypoxemia Is Common and Persistent: A Prospective Blinded Observational Study. Anesth Analg 2015;121:709–15. 3. Xue FS, Huang YG, Tong SY, Liu QH, Liao X, An G, et al. A comparative study of early postoperative hypoxemia in infants, children, and adults undergoing elective plastic surgery. Anesth Analg 1996;83:709–15. 4. Kurth DC. Postoperative arterial oxygen saturation: what to expect. Anesth Analg 1995;80:1–3. 5. Saraswat V. Effects of anaesthesia techniques and drugs on pulmonary function. Indian J Anaesth 2015; 59: 557–64. 6. Squadrone V, Coha M, Cerutti E, Schellino MM, Biolino P, Occella P, et al; Piedmont Intensive Care Units Network (PICUN). Continuous positive airway pressure for treatment of postoperative hypox-

Sezen. Desflurane or Sevoflurane Anesthesia

emia: a randomized controlled trial. JAMA 2005;293:589–95. 7. Arozullah AM, Daley J, Henderson WG, Khuri SF. Multifactorial risk index for predicting postoperative respiratory failure in men after major noncardiac surgery. The National Veterans Administration Surgical Quality Improvement Program. Ann Surg 2000;232:242–53. 8. Hedenstierna G, Edmark L. Mechanisms of atelectasis in the perioperative period. Best Pract Res Clin Anesthesiol 2010;24:157–69. 9. Warner DO. Preventing postoperative pulmonary complications: the role of the anesthesiologist. Anesthesiology 2000;92:1467–72. 10. Duggan M, Kavanagh BP. Pulmonary atelectasis: a pathogenic perioperative entity. Anesthesiology 2005;102:838–54. 11. Mashour GA, Forman SA, Campagna JA. Mechanisms of general anesthesia: from molecules to mind. Best Pract Res Clin Anaesthesiol 2005;19: 349–64. 12. Ebert TJ, Muzi M. Sympathetic hyperactivity during desflurane anesthesia in healthy volunteers. A comparison with isoflurane. Anesthesiology 1993;79:444–53. 13. Rock P, Rich PB. Postoperative pulmonary complications. Curr Opin Anesthesiol 2003;16:123–31. 14. Eshima RW, Maurer A, King T, Lin BK, Heavner JE, Bogetz MS, et al. A comparison of airway responses during desflurane and sevoflurane administration via a laryngeal mask airway for maintenance of anesthesia. Anesth Analg 2003;96:701–5. 15. Chen X, Zhao M, White PF, Li S, Tang J, Wender RH, et al. The recovery of cognitive function after general anesthesia in elderly patients: a comparison of desflurane and sevoflurane. Anesth Analg

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2001;93:1489–94. 16. Mahmoud NA, Rose DJ, Laurence AS. Desflurane or sevoflurane for gynaecological day-case anaesthesia with spontaneous respiration? Anaesthesia 2001;56:171–4. 17. De Baerdemaeker LE, Struys MM, Jacobs S, Den Blauwen NM, Bossuyt GR, Pattyn P, et al. Optimization of desflurane administration in morbidly obese patients: a comparison with sevoflurane using an ‘inhalation bolus’ technique. Br J Anaesth 2003;91:638–50. 18. Song D, Joshi GP, White PF. Fast-track eligibility after ambulatory anesthesia: a comparison of desflurane, sevoflurane, and propofol. Anesth Analg 1998;86:267–73. 19. McKay RE, Large MJ, Balea MC, McKay WR. Airway Reflexes Return More Rapidly After Desflurane Anesthesia than after sevoflurane anesthesia. Anesth Analg 2005;100:697–700. 20. White PF, Tang J, Wender RH, Yumul R, Stokes OJ, Sloninsky A, et al. Desflurane versus sevoflurane for maintenance of outpatient anesthesia: the effect on early versus late recovery and perioperative coughing. Anesth Analg 2009;109:387–93. 21. Dupont J, Tavernier B, Ghosez Y, Durinck L, Thevenot A, MoktadirChalons N, et al. Recovery after anaesthesia for pulmonary surgery: desflurane, sevoflurane and isoflurane. Br J Anaesth 1999;82:355–9. 22. Eger EI 2nd, Bowland T, Ionescu P, Laster MJ, Fang Z, Gong D, et al. Recovery and kinetic characteristics of desflurane and sevoflurane in volunteers after 8-h exposure, including kinetics of degradation products. Anesthesiology 1997;87:517–26.

Desfluran ya da Sevofluran Anestezisinden Sonra Erken Ameliyat Sonrası Derlenmenin Karşılaştırılması Amaç: Bu çalışmanın amacı, genel anestezi altında alt karın cerrahisi geçirecek olan hastalarda sevofluran ve desfluran kullanımının ameliyat sonrası erken dönem etkilerinin karşılaştırılmasıdır. Gereç ve Yöntem: Elektif alt batın cerrahisi geçirecek 18-75 yaş arası ASA fizik durumu I ya da II olan 80 hasta seçilerek iki gruba ayrıldı. Anestezi indüksiyonundan önce kalp hızı, kan basıncı, periferik oksijen satürasyonu ölçüldü ve nöromusküler monitörizasyon uygulandı.Tiyopental 5-7 mgr/kg ve fentanil 1 µgr/kg iv uygulanmasının ardından rokuronyum 0.6 mg/kg iv uygulanarak endotrakeal entübasyon gerçekleştirildi. Anestezi idamesi Grup I’de %4 desfluran Grup II’de %3 sevofluran %50 oksijen-hava karışımı ile sağlandı. Cerrahi sırasında hemodinamik değişikliklere göre fentanil 1 µgr ve volatil anesteziklerin konsantrasyonları değiştirilerek uygulandı. Cerrahinin sonunda volatil anestezikler kesilerek bütün hastalara %100 oksijen solutuldu. TOF %85 değerine ulaşınca hastalar ekstübe edildi ve yüz maskesi ile oksijen verildi. Peroperatif aksiller ısı, SpO2 ,hemoglobin (Hb), arteriyel basınç, kalp hızı ve total opioid tüketimi kaydedildi. Postoperatif dönemde 1., 5., 10., 15., 20., 30., 45., 60. dakikalarda SpO2 değerleri, havayolu kontrol ve modifiye Aldrete derlenme skorları kaydedildi. Ağrı değerlendirilmesi vizüel analog skala (VAS) ile 1-10 arası olacak şekilde aynı zaman aralıklarında değerlendirildi. Bulgular: Gruplar arasında tanımlayıcı değerler, anestezi süreleri, cerrahi süreleri, ekstübasyon süreleri, aksiller ısı, ameliyat öncesi SpO2, ameliyat öncesi ve sonrası hemodinamik değerler havayolu kontrol skoru ve VAS değerleri arasında anlamlı fark tespit edilmedi. Grup I’de toplam opioid dozunun anlamlı olarak daha yüksek, ameliyat öncesi Hb ve ameliyat sonrası Hb değerlerinin ise anlamlı olarak daha düşük olduğu gözlendi (p<0.01). Sonuç: Genel anestezi uygulamalarında desfluranın özellikle ameliyat sonrası komplikasyon riski yüksek olan hastalarda sevoflurana tercih edilebilir. Anahtar Sözcükler: Ameliyat sonrası; derlenme; desfluran, sevofluran.

DOI: 10.14744/scie.2018.92486 South. Clin. Ist. Euras. 2018;29(3):168-175

Original Article

Which Biomarkers Help to Distinguish Between Candida and Aspergillus in Patients with Pulmonary Infections? Armağan Fatma Hazar,

Department of Chest Diseases, University of Health Sciences İstanbul Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital, İstanbul, Turkey Submitted: 19.06.2018 Accepted: 13.08.2018 Correspondence: Armağan Fatma Hazar, SBÜ İstanbul Süreyyapaşa Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, İstanbul, Turkey E-mail: armaganhazar@yahoo.com

Keywords: Aspergillosis, candidiasis; mean platelet volume; neutrophil-tolymphocyte ratio; platelet count/mean platelet volume; pulmonary fungal infection.

Hatice Türker

ABSTRACT Objective: This study was an evaluation of differences in the inflammatory markers of Creactive protein (CRP) level, the neutrophil-to-lymphocyte ratio (NLR), the platelet countto-mean platelet volume ratio (PLT/MPV), and the platelet-to-lymphocyte ratio (PLR) in patients with pulmonary candidiasis and pulmonary aspergillosis. Methods: A retrospective, cross-sectional study was performed with the data of patients who were diagnosed with pulmonary candidiasis and pulmonary aspergillosis between 2016 and 2017 according to the records of the hospital information system. The results and date of hemograms, the biochemistry values, and C-reactive protein (CRP) levels were recorded. The NLR, PLT/MPV, and PLR were calculated. The documented parameters of the study groups were compared and analyzed. Results: There were 44 patients (29 men) (candidiasis, n=19; aspergillosis, n=25), with a median age of 65 years. In both groups, the incidence of chronic obstructive pulmonary disease, level of CRP, and the NLR, PLR, MPV, and PLT/MPV were statistically similar. At discharge, the CRP, PLR, NLR, and PLT values were still similar in the 2 groups; however, the MPV was significantly lower in the pulmonary aspergillosis group when compared with the pulmonary candidiasis group (7.3 vs 8.4; p=0029). Conclusion: Most biomarkers were similar in the pulmonary aspergillosis and the candidiasis groups; however, a PLT elevation and an MPV decrease were significant in the diagnosis of aspergillus. Similar findings in prospective, multicenter studies performed with patients who are suspected of having a fungal lung infection will add to the ultimate determination of the value to be given to PLT and MPV biomarkers in the initiation of empirical treatment.

INTRODUCTION Fungal infections of the respiratory system are diseases with a high rate of mortality and morbidity. They often present in immunosuppressed patients.[1] Early diagnosis and early initiation of treatment in fungal infections markedly reduces morbidity and mortality.[2] Candida spp. and Aspergillus spp. are primary agents of fungal infection in patients with parenchymal disease and sequelae, such as chronic obstructive pulmonary disease (COPD), interstitial lung disease, tuberculosis, and bronchiectasis, and

in patients with the chronic use of steroids or immunosuppressive drugs.[2] Candida spp. are endogenous in the mucosa and may become pathogenic with antibiotics used to fight infectious disease.[3] In respiratory system infections, the most important way to reduce mortality is to initiate treatment as soon as possible. Treatment differs between Candida and Aspergillus infections: As first-line antifungals, fluconazole has been used in cases of candidiasis, and the varicosanol group of drugs in Aspergillus infections. As treatment options, the echinocandin group of drugs has been used for candidiasis

Hazar. Biomarkers in Candidiasis, Aspergillosis

and amphotericin B for both Candida and Aspergillus infections.[2] Among the known biomarkers, C- reactive protein (CRP) and leukocyte counts do not aid the physician in the discrimination between Candida and Aspergillus infections, so new hemogram parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-mean platelet volume ratio (PLT/MPV), platelet-to-lymphocyte ratio (PLR), and procalcitonin level are being investigated for use in the discrimination between fungal and bacterial infections.[4â&#x20AC;&#x201C;7] At present, studies in the literature about the role of inflammatory markers in the fungal infections of Candida albicans and Aspergillus fumigatus are still insufficient. This study was an investigation of whether platelets, which are fragments of megakaryocytes, and NLR, PLR, MPV, and other hemogram subparameters could be used as an inflammatory biomarkers in Aspergillus and Candida infections.

MATERIAL AND METHODS This study was constructed as a retrospective, crosssectional observational trial and conducted in the chest diseases and thoracic surgery department of the education and research hospital of a university. The study was approved by the Scientific Committee of the Hospital (14.05.2018 / 035) and ethical approval was granted based on compliance with the Helsinki Declaration. All of the study data were collected retrospectively from the hospital electronic information management system. The need to obtain informed consent from the patients for the use of medical data for publication was waived by the scientific committee due to the retrospective nature of the study in accordance with local legislation. The identity information of all patients was strictly protected.

The patients Among patients receiving inpatient treatment between January 1and December 31, 2016, those whose diseases were coded as pulmonary candidiasis (IDC B 37) or pulmonary aspergillosis (ICD B 44) according to the International Classification of Diseases 10th Revision, and who underwent a hematological examination at admission and prior to discharge were enrolled in the study. Patients who were classified as cases of colonization of fungal infection as described below were excluded from the study. Patients with etiological factors for non-fungal infections that could cause changes in inflammatory biomarkers were also excluded. Adult patients with a pulmonary infection that was considered to be a pathogenic agent of Candida or Aspergillus were included in the study. The definition of Candida and Aspergillus infections is provided below.

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Definitions Fungal colonization: Samples were harvested from different regions of the body and if the ratio of areas with intense growth of Candida spp. to areas with only general growth of Candida spp. were detected was greater than 0.4 in semiquantitive culture media, these areas were considered to be colonized and these patients were excluded from the study.[8] Patients hospitalized in the intensive care unit, immunosuppressed patients, surgical patients, those receiving total parenteral nutrition, with a central venous catheter, a history of diabetes mellitus, severe sepsis, or prolonged mechanical ventilation were considered to be at risk for fungal infection. Fungal growth was accepted as a pathogenic condition.[9] Candidiasis: The presence of candidiasis was defined with Candida spp. detected in patients with clinical and radiological (plain pulmonary radiography and computed tomography) evidence of pulmonary infiltration and increased CRP and hemogram values, a microbiological examination that did not demonstrate growth of any pathogen other than Candida spp., immunosuppressed cases, patients who were using systemic steroids for more than 6 months, those who were hospitalized in the intensive care unit and using two or more antibiotics.[10,11] Aspergillosis: The presence of clinical and radiological (pulmonary plain radiograph and computerized) evidence, infection parameters, and cases where no pathogenic organism other than Aspergillus spp. was detected in the sputum/bronchoscopy lavage/blood samples which could explain the infection was considered aspergillosis.[11â&#x20AC;&#x201C;13]

Diagnostic methods Flexible bronchoscopy In our center, the presence of a whitish, sticky secretion and edematous hyperemic mucosa and/or mucosal plaque formation observed on bronchoscopy in patients with COPD, diabetes mellitus, or those using steroids is defined as a suspect tracheobronchial fungal infection (TBFI).[14] The results of bronchial lavage and bronchial mucosal biopsy were recorded in cases of a suspected TBFI.

Evaluation of microbiological material Bronchoscopic lavage: Bronchial and tracheal lavage material was inoculated on Sabouraud dextrose agar and a microbiological culture analyzer (mini API; Biomerieux, Marcy lâ&#x20AC;&#x2122;Etoile, France) was used to identify molds and yeasts. The distinction between Candida albicans and Candida non-albicans was not recorded. Aspergillus was also identified by inoculating bronchial and tracheal lavage

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material in Sabouraud’s dextrose agar. Fast growing white, yellow, yellow-brown, brown-black, or green colonies were considered positive for aspergillosis. Bronchoscopic suspicion in patients based on clinical findings or the observance of growth of Candida spp. in deep tracheal aspirate or bronchoscopic lavage material was recorded as a diagnosis of pulmonary candidiasis, and galactomannan positivity seen in lavage material was used as a rapid method of diagnosis of pulmonary aspergillosis.

Calculations Neutrophil-to-lymphocyte ratio (NLR): NLR as a marker of systemic inflammation was defined as the absolute number of neutrophils divided by the absolute lymphocyte count.[15,16] Platelet-to-lymphocyte ratio (PLR): PLR was defined as the absolute platelet count divided by the absolute lymphocyte count.[16,17] PLT-to-mean platelet volume ratio (PLT/MPV):

The PLT/MPV was the calculated value of the ratio of the platelet volume to the mean platelet volume.[18] C-reactive protein-to-serum albumin ratio (CAR): The CRP was divided by the serum albumin value to determine the CAR.[19]

Recorded data Patient admission and discharge hemogram and subparameter data, as well as demographic characteristics, additional diseases, length of hospitalization, and hospital mortality details were recorded based on hospital records. CRP, NLR, PLT/MPV, and PLR values were calculated and recorded.

Statistical analysis Statistical analyses were performed using the portable SPSS Statistics for Windows, Version 20.0 program (IBM Corp., Armonk, NY, USA). Patient demographics and clinical data were summarized using descriptive analysis. The Student’s t-test was used for continuous variables, such

Table 1. Demographic characteristics of pulmonary candidiasis and pulmonary aspergillosis groups

Pulmonary candidiasis (n=19) %

Pulmonary aspergillosis (n=25)

Age median, years (IQR)

Male

11 58

18 72

0.020

COPD

0.89

Asthma

0.84

Immune deficiency

0.44

Hypertension

0.040

Heart failure

0.25

0.72

Pneumonia

80.0

78.9

0.93

66 (54–79)

% 61 (55–73)

0.39

Additional diseases

Malignancy Indications for hospitalization

12.0

15.8

0.72

Bronchiectasis

COPD/Asthmatic episodes

4.0

0.0

0.38

Hospital stay, median, days (IQR)

8 (7–12)

5 (2–6)

0.009

Diagnostic methods

Bronchoscopic appearance, lavage/culture

89.5

68.0

Surgical biopsy

0.0

20.0

Medical history and physical examination* 2 10.5

0.11

3 12.0

Hospitalization

In the service

68.0

42.1

In the intensive care unit

32.0

57.9

Mortality

0.09 0.77

COPD: Chronic obstructive pulmonary disease, chi-square test; IQR: Interquartile range, Mann-Whitney U test; *: Findings of oral candida mucositis, thrush on the epiglottis and surrounding area, history of respiratory fungal infection, ambulatory treatment follow-up in polyclinics with galactomannan positivity.

Hazar. Biomarkers in Candidiasis, Aspergillosis

171

statistically significantly longer in the pulmonary candidiasis group.

as age, hemogram values, biochemistry values, NLR, PLR, PLT/MPV, and CRP when the distribution was normal. Values obtained using the Student’s t-test were presented as mean±SD. The non-parametric Mann-Whitney U test was used for non-normally distributed numerical values and the results were expressed as median value and interquartile range (IQR: 25% and 75%). Dichotomic values, such as sex and the presence of additional disease, were tested with a chi-square test. A p value <0.05 was considered statistically significant.

Table 2 provides a comparison of hemogram values at hospital admission and discharge between patients with pulmonary candidiasis and those with pulmonary aspergillosis. Comparisons of leukocyte, erythrocyte, and other hemogram values between the 2 groups yielded similar results. Biochemical values of glucose, creatinine, blood urea nitrogen, protein, albumin, electrolytes, lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase were also compared (Table 3). The LDH value measured at admission was significantly higher in patients with pulmonary candidiasis; however, the overall biochemical values measured at admission and discharge were similar between groups.

RESULTS A total of 44 (men: n=29, 66%) patients with a median age of 65 years (IQR: 55–74 years) who were diagnosed with pulmonary aspergillosis (n=25) or pulmonary candidiasis (n=19), who had the appropriate hemogram values accessible in the hospital records, and who met the eligiblility criteria were included in the study.

Inflammatory biomarkers were also analyzed at hospital admission and discharge (Table 4). The admission values were similar in both groups, while the discharge MPV value was significantly higher in the pulmonary aspergillosis group.

The demographic characteristics of the participants, additional diseases present, and causes of hospitalization and mortality are summarized in Table 1. A statistically significantly greater number of male patients were found in the pulmonary aspergillosis group, and the hospital stay was

Figure 1 illustrates the MPV values of the patient groups compared with the normal range (MPV <7.4 fL), and the platelet counts (PLT >440.000/mm3) recorded at admission and discharge.

Table 2. Comparison of admission and discharge hemogram values of patients with pulmonary candidiasis and pulmonary aspergillosis

On admission

At discharge

Pulmonary Pulmonary p Pulmonary Pulmonary p candidiasis aspergillosis candidiasis aspergillosis (n=19) (n=25) (n=19) (n=25) Md. 25% 75% Md. 25% 75%

White blood cell count (x109/mL) 9.7 7.4 15.8 10

Md. 25% 75% Md. 25% 75%

8.5 13.4 13.8 11.1 8.7 13.6 10.8 8.4 13.8 0.89

Neutrophil count (x109/mL)

8.8 5.7 12.1 7.8 5.9 10.5 1.0 8.2 6.2 11.8 8.8 5.5 11.5 0.92

Monocyte count (x109/mL)

0.5 0.3 0.7 0.5 0.42 0.8 0.21 0.5 0.3 0.8 0.7 0.5 0.8 0.12

Lymphocyte count (x109/mL)

1.0 0.7 1.9 1.5 0.8 1.8 0.43 1.2 0.8 2 1.1 0.94 2 0.82

Neutrophil (%)

79 71.7 86.9 75.55 66.15 87.9 0.34 80 73.02 88.4 81.8 66 87.8 0.90

Monocyte (%)

5.23 2.3 7.6 5.4 3.7 7.7 0.51 5.2 2.8 7.3 6 4.8 6.8 0.30

Lymphocyte (%)

10.9 5.7 17.2 13.1 5.7 21.5 0.69 13.2 7.2 19.8 9.36 7.7 22.3 0.91

Eosinophil (%)

0.57 0.1 1.9 0.9 0.2 1.4 0.38 0.7 0.1 1.42 0.4 0.1 1.2 0.97

Basophil (%)

0.3 0.1 1.1 0.3 0.2 0.7 0.89 0.2 0 0.4 0.2 0.1 0.5 0.81

Erythrocyte count (x109/mL)

4.22 3.56 4.73 4.04 3.54 4.54 1.0 4.21 3.37 4.8 4 3.53 4.59 0.73

Hemoglobin cell count (x109/mL) 11.1 10 13.4 12.4 9.6 13.6 0.78 11.4 9.4 13 11.6 9.3 13 0.93 Hematocrit cell count (x109/mL) 34.7 29.7 39.4 38 29.1 40.5 0.62 34.3 28.9 38.9 34.5 30.2 38.9 0.90 Mean corpuscular volume

83.7 78.7 89.2 86.2 84 88.8 0.33 83.7 79 88.9 86.7 83.9 89.3 0.18

Platelet distribution width

17 16.7 17.8 17.2 16.98 17.5 0.85 17 16.5 17.5 17 16.8 17.5 0.72

RDW-CV

17.67 15.4 19.4 15.8 14.7 17.5 0.16 17.77 15.3 19.5 15.5 15.1 17.9 0.14

Md.: Median; RDW: Red cell distribution width; RDW-CV: Stands for coefficient variation of RDW.

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Table 3. Comparison of admission and discharge biochemical values of patients with pulmonary candidiasis and pulmonary aspergillosis

On admission

At discharge

Pulmonary Pulmonary P* Pulmonary Pulmonary candidiasis aspergillosis candidiasis aspergillosis

n Md. 25% 75% n Md. 25% 75%

Fasting blood glucose (mg/dL)

11 112 92 192 12 107 83 142 0.28 19 131 91 162 23 103 86 148 0.62

BUN (mg/dL)

17 44 25 81 16 33 22 47 0.28 19 36 23 71 23 33 25 64 0.82

Creatinine (mg/dL)

17 0.58 0.44 0.99 17 0.63 0.55 0.76 0.84 19 0.66 0.55 0.9 23 0.62 0.51 1 0.92

Protein (mg/dL)

5 6.2 6 6.2 5 7.5 6.8 7.6 0.08 13 5.8 5 6.4 14 6.6 5.5 7.2 0.29

Albumin (mg/dL)

9 3.5 3.1 3.6 14 3.1 2.5 3.7 0.73 18 3.3 2.3 3.6 22 3 2.6 3.5 0.49

Sodium (mg/dL)

17 138 134 140 16 136 131 139 0.33 19 137 134 142 23 137 133 140 0.65

Potassium (mg/dL)

17 4.5 3.9 4.8 15 4.6 4 4.9 0.42 19 4.2 3.9 4.9 22 4.3 4.1 4.6 0.65

Calcium (mg/dL)

12 9.1 8.6 9.3 13 8.9 8.2 9.3 0.46 18 8.8 8.2 9.4 21 8.6 8.4 9.1 0.70

LDH (mg/dL)

4 266 258 401 3 141 122 200 0.034 12 318 214 394 12 231 170 304 0.11

SGOT (mg/dL)

10 29 15 78 11 34 17 50 0.78 19 22 15 56 22 25 17 41 0.92

SGPT (mg/dL)

10 31 14 46 11 22 11 29 0.10 19 28 14 61 23 23 13 31 0.29

*Mann-Whitney U Test. Md.: Median; BUN: Blood urea nitrogen; LDH: Lactate dehydrogenase; SGOT: Serum glutamic oxaloacetic transaminase; SGPT: Serum glutamic pyruvic transaminase.

Table 4. Comparison of admission and discharge inflammatory biomarkers of patients with pulmonary candidiasis and pulmonary aspergillosis

On admission Pulmonary candidiasis (n=19)

At discharge

Pulmonary p* aspergillosis (n=25)

Pulmonary candidiasis (n=19)

Pulmonary aspergillosis (n=25)

n Md. 25% 75% n Md. 25% 75% n Md. 25% 75% n Md. 25% 75%

CRP (mg/dL) 11 70.8 1.8 140 7 30.3 7.8 74.1 0.56 19 15.3 8.5 113 20 19.6 3.1 48.7 0.51 PLR

19 198.57 114.35 410 21 257.5 216 330 0.49 19 220.45 104.33 413.75 25 362.73 153.7 528 0.40

IQR

7 20.17 6.55 40.67 6 18.38 4.43 29.64 0.89 18 6.03 2.18 47.92 19 5.21 1.03 17 0.40

NLR

19 7.11 4.38 1.13 21 5.83 3.17 15.56 0.62 19 5.9 3.75 11.45 25 9 2.93 11 0.90

PLT/MPV

19 28.73 16.17 4.78 21 48.59 22.58 60.72 0.11 19 39.13 16.5 54.26 25 52.38 31.34 64.26 0.12

PLT

19 259 152.6 394 21 324 210 424 0.19 19 279 170 355 25 399 257 47.2 0.19

MPV

19 8.7 7.8 9.5 21 7.4 6.93 9.1 0.07 19 8.3 7.5 9.8 25 7.3 6.9 8.2 0.029

*Mann-Whitney U Test. Md.: Median; CRP: C-reactive protein; IQR :CRP/albumin ratio; MPV: Mean platelet volume; NLR: Neutrophil-lymphocyte ratio; PLR: Platelet-lymphocyte ratio; PLT/MPV: Platelet-mean platelet volume ratio.

DISCUSSION

Inflammatory biomarkers in fungal infections

The NLR, PLR, and CRP values of patients with pulmonary candidiasis and pulmonary aspergillosis were similar; however, the MPV of the patients with pulmonary aspergillosis was significantly lower than the normal value (<7.4 fL), and platelet counts were higher relative to pulmonary candidiasis patients.

MPV, PLT/MPV Ates et al.[20] reported that there was a significant difference in the MPV and MPV/PLT values between healthy subjects and patients with systemic inflammatory response syndrome (SIRS). In their study, they reported that there

Hazar. Biomarkers in Candidiasis, Aspergillosis

173

100% 90% 80% 70% 60%

28.0% 40.0%

36.0%

56.0%

50% p=0.60

40% 30% 20% 10% 0%

p=0.08

15.8%

Admission MPV <7.4 fL

p=0.053

p=0.007

10.5%

15.8%

Admission PLT >440x109 L

Discharge MPV <7.4 fL

Pulmonary candidiasis (n=19)

21.1%

Discharge PLT >440x109 L

Pulmonary aspergillosis (n=25)

Figure 1. A comparison of the mean platelet volume (MPV) and platelet count (PLT) at admission and discharge in pulmonary candidiasis and pulmonary aspergillosis groups.

was no significant difference between the MPV values of SIRS and sepsis patients and that MPV values increased in sepsis patients. Zampieri et al.[21] have demonstrated that the increase in MPV was proportional to the mortality rate in sepsis patients. Eser et al.[22] found that platelet counts in sepsis patients were similar to the control group, suggesting that a reduction in the MPV value might be a diagnostic marker for pneumonia. In their study, infection among intensive care patients was markedly more severe. Though not statistically significant, a larger number of patients were hospitalized in the intensive care unit in the pulmonary aspergillosis group. The MPV values at admission and discharge were lower, but platelet counts were higher in the pulmonary aspergillosis group compared with the pulmonary candidiasis group, which was interpreted as the possible result of a bone marrow response due to an exogenous etiological infection agent. There are studies showing that platelets are sensitive to stress, ischemia, obesity, hypoxia, and that smoking increases the activation of platelets.[23] It has been also reported that chemokines and cytokines are secreted from the membranes of platelets and that they have a role in the immune response like that of acute phase reactants and thus exert antimicrobial activities.[22,24] In their studies, Redlant[25] and Speth[26] demonstrated that Aspergillus spp. activate platelets, and that platelets act as antimicrobial and antifungal agents. An increased platelet count and a decreasing MPV may be considered an important finding in the differential diagnosis of fungal infections that suggests the diagnosis of aspergillosis rather than candidiasis.

CRP, NLR, PLR The role of the inflammatory markers of CRP, NLR, leukocytes, and platelets have been investigated in the differential diagnosis between bacterial infections, Gram-pos-

itive and Gram-negative infections, and fungal infections. [27â&#x20AC;&#x201C;29] LjungstrĂśm et al.[27] analyzed the levels of procalcitonin, CRP, NLR, and LDH in 1572 patients evaluated in the emergency service with the suspicion of sepsis, and reported that though these parameters were not significant markers, especially in the early diagnosis of sepsis, the NLR-procalcitonin and LDH-CRP combination could identify bacterial sepsis. In a recent, similar study, Miglietta et al.[28] did not investigate fungi other than Candida, but studied the biomarkers of CRP, procalcitonin, platelet count, and LDH to differentiate between sepsis patients, patients with SIRS and systemic Candida infections among intensive care patients. Seventy patients with sepsis, 42 patients with SIRS, and 33 patients with systemic candidiasis were retrospectively enrolled in the study. The biomarkers were measured at intensive care admission and 2 days later. They found slightly lower CRP values (60.5 mg/L) in candidiasis patients when compared with those with Gram-negative (112 mg/L), and Gram-positive (184 mg/L) bacterial infections, while platelet counts were higher in patients with candidiasis. Pan et al.[29] retrospectively investigated the use of the inflammatory markers of procalcitonin; leukocyte, neutrophil, and lymphocyte counts; NLR; CRP level; and platelet count in 1807 patients with chronic bacterial and fungal blood-borne infections. They reported that among 230 patients with bacterial growth in their blood cultures, higher procalcitonin, NLR, and neutrophil values were detected only in patients with Gram-negative infections when compared with those with Gram-positive, and that fungal infections were reliable biomarkers. In our study, in addition to other studies, higher platelet counts were seen in patients with aspergillosis relative to those with candidiasis. Unlike other studies, we also studied the PLR and CAR in the differential diagnosis between Candida and Aspergillus diagnoses, and no significant difference was found.

Limitations There are some limitations to the study. Firstly, it was a single-center, retrospective study. However, patients data were retrieved from the hospital electronic system and data entry errors were minimized. The second limitation was the absence of fungal growth in tissue biopsy specimen in every case in order to identify the fungi. Although the diagnosis of fungal infection and fungal pneumonia is primarily made by demonstrating growth of fungi in the tissue culture material,[30] due to difficulties encountered in diagnosing fungal infections, beta-D glucan was used for rapid diagnosis and the identification of Candida, and galactomannan was used for Aspergillus,[31] in addition to clinical and microbiological results. In this study, we also indicated that the appearance of bronchoscopic material can be used in conjunction with microbiological results as a diagnostic tool in the identification of possible tracheo-

174

bronchial fungal infections.[14] As a third limitation, the results of the study cannot be generalized for any infection other than pulmonary candidiasis or aspergillosis.

CONCLUSION Pulmonary candidiasis and pulmonary aspergillosis are common opportunistic fungal infections in COPD patients. The platelet count, MPV, and PLT/MPV estimated in pulmonary aspergillosis patients differ from those found in patients with pulmonary candidiasis. In patients with pulmonary aspergillosis, the platelet count and PLT/ MPV were higher, but the MPV value was lower relative to patients with pulmonary candidiasis. These findings may aid chest disease specialists in the discrimination between pulmonary candidiasis and pulmonary aspergillosis. Platelet count, MPV, and PLT/MPV values can be assessed with advanced diagnostic tests in patients at risk for pulmonary aspergillosis and their diagnostic values may be investigated in further studies. Ethics Committee Approval The study was approved by the Scientific Committee of the Hospital (14.05.2018 / 035) and ethical approval was granted based on compliance with the Helsinki Declaration. Informed Consent Retrospective study. Peer-review Internally peer-reviewed. Authorship Contributions Concept: F.A.H, H.T.; Design: F.A.H, H.T.; Data collection &/or processing: F.A.H., H.T.; Analysis and/or interpretation: F.A.H., H.T.; Literature search: F.A.H., H.T.; Writing: F.A.H., H.T.; Critical review: F.A.H., H.T. Conflict of Interest None declared.

REFERENCES 1. Limper AH. Clinical approach and management for selected fungal infections in pulmonary and critical care patients. Chest 2014;146:1658–66. 2. De Pascale G, Tumbarello M. Fungal infections in the ICU: advances in treatment and diagnosis. Curr Opin Crit Care 2015;21:421–9. 3. Ener S, Ener B, Akalın H. Deep candida infections that developed in intensive çare units after long operations [Article in Turkish]. Ege Tıp Dergisi 2001;40:185–9. 4. Rødland EK, Ueland T, Pedersen TM, Halvorsen B, Muller F, Aukrust P, et al. Activation of platelets by Aspergillus fumigatus and potential role of platelets in the immunopathogenesis of Aspergillosis. Infect Immun 2010;78:1269–75. 5. Heinekamp T, Schmidt H, Lapp K, Pähtz V, Shopova I, Köster-Eiserfunke N, et al. Interference of Aspergillus fumigatus with the immune response. Semin Immunopathol 2015;37:141–52.

South. Clin. Ist. Euras.

6. Bruns S, Kniemeyer O, Hasenberg M, Aimanianda V, Nietzsche S, Thywissen A, et al. Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA. PLoS Pathog 2010;6:e1000873. 7. Roques M, Chretien ML, Favennec C, Lafon I, Ferrant E, Legouge C, Plocque A, et al. Evolution of procalcitonin, C-reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis. Mycoses 2016;59:383–90. 8. Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 1994;220:751–8. 9. Muskett H, Shahin J, Eyres G, Harvey S, Rowan K, Harrison D. Risk factors for invasive fungal disease in critically ill adult patients: a systematic review. Crit Care 2011;15:R287. 10. Lindau S, Nadermann M, Ackermann H, Bingold TM, Stephan C, Kempf VA, et al. Antifungal therapy in patients with pulmonary Candida spp. colonization may have no beneficial effects. J Intensive Care 2015;3:31. 11. Tessier JM. Infections in the Non-Transplanted Immunocompromised Host. Surg Infect (Larchmt) 2016;17:323–8. 12. Atalay MA, Koç an, Sav H, Demir G. Antifungal Susceptibility of Aspergillus Species Isolated from Patients Diagnosed with Invasive Aspergillosis [Article in Turkish]. ANKEM Derg 2014;28:129–33. 13. Akan H. EORTC Definitions in Fungal Infections [Article in Turkish]. ANKEM Derg 2009;23:130–4. 14. Yazıcıoğlu Moçin O, Karakurt Z, Aksoy F, Güngör G, Partal M, Adıgüzel N, et al. Bronchoscopy as an indicator of tracheobronchial fungal infection in non-neutropenic intensive-care unit patients. Clin Microbiol Infect 2013;19:E136–41. 15. Farah R, Ibrahim R, Nassar M, Najib D, Zivony Y, Eshel E. The neutrophil/lymphocyte ratio is a better addition to C-reactive protein than CD64 index as a marker for infection in COPD. Panminerva Med 2017;59:203–9. 16. Unal D, Eroglu C, Kurtul N, Oguz A, Tasdemir A. Are neutrophil/ lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis? Asian Pac J Cancer Prev 2013;14:5237–42. 17. Yoon NB, Son C, Um SJ. Role of the neutrophil-lymphocyte count ratio in the differential diagnosis between pulmonary tuberculosis and bacterial community-acquired pneumonia. Ann Lab Med 2013;33:105–10. 18. Nacaroglu HT, Erdem SB, Karaman S, Yazici S, Can D. Can mean platelet volume and neutrophil-to-lymphocyte ratio be biomarkers of acute exacerbation of bronchiectasis in children? Cent Eur J Immunol 2017;42:358–62. 19. Ranzani OT, Zampieri FG, Forte DN, Azevedo LC, Park M. C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLoS One 2013;8:e59321. 20. Ates S, Oksuz H, Dogu B, Bozkus F, Ucmak H, Yanıt F. Can mean platelet volume and mean platelet volume/platelet count ratio be used as a diagnostic marker for sepsis and systemic inflammatory response syndrome? Saudi Med J 2015;36:1186–90. 21. Zampieri FG, Ranzani OT, Sabatoski V, de Souza HP, Barbeiro H, da Neto LM, et al. An increase in mean platelet volume after admission is associated with higher mortality in critically ill patients. Ann Intensive Care 2014;4:20. 22. Eser İ, Günay Ş, Sak ZHA, Yalçın F, Kürkçüoğlu İC. Mean Platelet

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cyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis. PLoS One 2017;12:e0181704.

23. Guzmán-Grenfell A, Nieto-Velázquez N, Torres-Ramos Y, Montoya-Estrada A, Ramírez-Venegas A, Ochoa-Cautiño L, et al. Increased platelet and erythrocyte arginase activity in chronic obstructive pulmonary disease associated with tobacco or wood smoke exposure. J Investig Med 2011;59:587–92.

28. Miglietta F, Faneschi ML, Lobreglio G, Palumbo C, Rizzo A, Cucurachi M, et al. Procalcitonin, C-reactive protein and serum lactate dehydrogenase in the diagnosis of bacterial sepsis, SIRS and systemic candidiasis. Infez Med 2015;23:230–7.

24. Yalçın KS, Tahtacı G, Balçık ŞÖ. Role of platelets in inflammation. Dicle Medical Journal 2012;39:455–7. 25. Rødland EK, Ueland T, Pedersen TM, Halvorsen B, Muller F, Aukrust P, et al. Activation of platelets by Aspergillus fumigatus and potential role of platelets in the immunopathogenesis of Aspergillosis. Infect Immun 2010;78:1269–75. 26. Speth C, Rambach G, Lass-Flörl C. Platelet immunology in fungal infections. Thromb Haemost 2014;112:632–9. 27. Ljungström L, Pernestig AK, Jacobsson G, Andersson R, Usener B, Tilevik D. Diagnostic accuracy of procalcitonin, neutrophil-lympho-

29. Pan YP, Fang YP, Xu YH, Wang ZX, Shen JL. The Diagnostic Value of Procalcitonin Versus Other Biomarkers in Prediction of Bloodstream Infection. Clin Lab 2017;63:277–85. 30. Kontoyiannis DP, Reddy BT, Torres HA, Luna M, Lewis RE, Tarrand J, et al. Pulmonary candidiasis in patients with cancer: an autopsy study. Clin Infect Dis 2002;34:400–3. 31. Su KC, Chou KT, Hsiao YH, Tseng CM, Su VY Lee YC, Perng DW, et al. Measuring (1,3)-β-D-glucan in tracheal aspirate, bronchoalveolar lavage fluid, and serum for detection of suspected Candida pneumonia in immunocompromised and critically ill patients: a prospective observational study. BMC Infect Dis 2017;17:252.

Pulmoner Enfeksiyonu Olan Hastalarda Kandida ve Aspergillus Etken Ayrımında Hangi Biyobelirteçler Yardımcı Olur? Amaç: Çalışmada pulmoner kandidiaziz ve aspergilloziz enfeksiyonunda enflamatuvar belirteçlerden C-reaktif protein (CRP), nötrofil lenfosit oranı (NLO), platelet ve ortalama platelet hacmi (PLT/MPV), platelet lenfosit oranı (PLO) farklı olup olmadığı araştırıldı. Gereç ve Yöntem: Çalışma 2016–2017 yıllarında geriye dönük kesitsel olarak yapıldı. Hastalar hastane bilgi yönetim sisteminden (HBYS) pulmoner kandidiaziz (ICD tanı kodu B 37), pulmoner aspergilloziz (ICD tanı kodu B44) kodu ile tarandı. Yatış, çıkış hemogramları, ek hastalıkları, yatış günü, hastane mortaliteleri kaydedildi. CRP, NLO, PLT/MPV, PLO hesaplandı. Grupların kayıt edilen değerleri, enflamatuvar biyobelirteçleri karşılaştırıldı. Bulgular: Çalışmaya 44 (kandida n=19, aspergillus n=25) hasta alındı. Ortanca yaşları 65 ve 29 erkekdi (%66). Pulmoner kandidiazis ve aspergilloziz hastalarında KOAH, hastaların yatış CRP, NLO, PLO, MPV, PLT/MPV değerleri benzer idi; taburculuk sırasında CRP, PLO, NLO, PLT benzer iken taburculukta MPV pulmoner aspergillozizde, pulmoner kandidiaziz hastalarından anlamlı düşük (7.3 ve 8.4, p=0.029) idi. Sonuç: Pulmoner aspergilloziz ve kandidiaziz enfeksiyonlarında çoğu biyobelirteç benzerdi. Aspergillus tanısında PLT yüksekliği ve MPV düşüklüğü anlamlıdır. Fungal akciğer enfeksiyonu düşünülen hastalarda yapılacak olan ileriye yönelik, çok merkezli çalışmalarda benzer bulgular olması amprik tedavi başlanmasında platelet ve MPV biyobelirteçlerinin önemini artıracaktır. Anahtar Sözcükler: Aspergillus; kandidiaziz; nötrofil lenfosit oranı; ortalama platelet hacmi; platelet; platelet ortalama platelet hacmi; pulmoner fungal enfeksiyonlar.

DOI: 10.14744/scie.2018.63935 South. Clin. Ist. Euras. 2018;29(3):176-179

Original Article

Predictors of Vesicoureteral Reflux in the Pretransplant Evaluation of Patients with End-Stage Renal Disease Ergün Parmaksız,

Meral Meşe,

Zuhal Doğu,

Zerrin Bicik Bahçebaşı

ABSTRACT Department of Nephrology, University of Health Sciences Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey Submitted: 10.05.2018 Accepted: 27.08.2018 Correspondence: Ergün Parmaksız, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Nefroloji Kliniği, İstanbul, Turkey E-mail: drergnprmksz@hotmail.com

Keywords: Renal transplantation; vesicoureteral reflux; voiding cystourethrography.

Objective: Voiding cystourethrography (VCUG) is widely performed in the pretransplant evaluation of patients with a history of urological disorders to detect vesicoureteral reflux (VUR). The aim of this study was to evaluate the relationship between the primary etiology of end-stage renal disease (ESRD) and the prevalence of VUR, thereby determining the necessity for VCUG in pretransplant patients. Methods: A total of 319 pretransplant cases that underwent VCUG were retrospectively reviewed. Results: VCUG revealed VUR in 53 (16.6%) cases. VUR was left-sided in 21 (41.2%), rightsided in 18 (35.3%), and bilateral in 12 (3.8%), and grade 1 in 10 (19.6%), grade 2 in 19 (37.3%), grade 3 in 20 (39.2%), and grade 4 in 2 (3.9%). The etiology of ESRD was hypertension in 125 (39.2%), diabetes mellitus (DM) in 46 (14.4%), polycystic kidney disease (PKD) in 21 (6.6%), amyloidosis in 16 (5%), VUR in 11 (3.4%), and glomerulonephritis (GN) in 11 (3.4%). The incidence of VUR was significantly higher in female patients. Hypertension, DM, PKD, amyloidosis, and GN were not found to predict VUR. The rate of abnormal VCUG findings was similar in cases with secondary and idiopathic ESRD. Conclusion: The findings demonstrate that only sex was a predictor of VUR in pretransplant cases. The presence of VUR was not related to any cause of ESRD; therefore, VCUG is not needed in all cases as a part of pretransplant evaluation.

INTRODUCTION Vesicoureteral reflux (VUR) is a congenital or acquired abnormality of the urinary tract. It is diagnosed in 30%–40% of children presenting with urinary tract infections (UTIs), predominantly girls.[1] VUR is classified by radiological evaluation on voiding cystourethrography (VCUG) into five grades as defined by the International Reflux Study in Children.[2] Renal injury is the combination of VUR and repeated UTI, which is also called acquired reflux nephropathy (RN). RN is diagnosed using technetium 99 m dimercaptosuccinic acid renal scanning as defects in the renal outline.[3] The presence of VUR increases the risk of upper UTI, and in case of bilaterally, it can cause renal injury, leading to scarring of the kidney

termed RN. RN may present as hypertension or chronic kidney disease (CKD). Some patients have proteinuria as a result of secondary focal segmental glomerulosclerosis (FSGS). Renal scarring is responsible for 5%–10% of endstage renal disease (ESRD) in adult patients.[4,5] The loss of nephron is associated with hyperfiltration and hypertension that result in proteinuria and progressive loss of renal function that leads to the development of FSGS. The clinical manifestations of RN are varied and may include complicated UTI, hypertension,[6] proteinuria,[7] an increased risk of renal calculi, and various manifestations of CKD.[8] VUR is most commonly found after repeated UTI. The prevalence of VUR is higher in younger patients and decreases with age; 5% of sexually active women with UTI have VUR.

ParmaksÄąz. Vesicoureteral Reflux in Renal Transplant

Screening for genitourinary disorders before renal transplantation is indicated in those with a history or renal ultrasonography suggestive of urinary obstruction, especially in whom urological problems are a major cause of ESRD. Traditional management includes prompt treatment of UTI or surgical correction of the VUR in those who are unfit for medical management. VCUG is widely performed to detect VUR in the pretransplant evaluation of patients with a history of urological disorders. We aimed to evaluate the relationship between primary etiology of ESRD and prevalence of VUR, thereby finding the necessity of VCUG in pretransplant patients.

MATERIAL AND METHODS We retrospectively examined the files of renal transplant candidates applying to our transplantation clinic between January 2008 and January 2014. All patients who underwent VCUG as a part of pretransplant evaluation were included in the study. Demographic data and known etiologies of ESRD were recorded. None of the subjects had a history of surgery for VUR. We examined the VCUGs of 319 patients who underwent assessment for renal transplantation in our center. VCUG had been performed after the bladder was emptied. A 150 cc of contrast media was infused through a urethral catheter under fluoroscopy until the bladder became full. During the procedure, any vesicoureteral reflux was noted. We tried to find an abnormal VCUG finding including any grade of VUR (1 through 4). Statistical analyses were performed using SPSS for Windows, version 17.0. Continuous data are expressed as means; discrete data are presented as counts and percentages (%). Chi-square tests were used for comparison of categorical data. Logistic regression analysis was used to determine the effect of different etiological factors on VUR. A p-value <0.05 was considered statistically significant.

RESULTS The study population consisted of a total of 319 renal transplant recipient candidates, with 173 (54.2%) male and 146 (45.8%) female cases. The mean age of the whole group was 51 (16â&#x20AC;&#x201C;70) years. The etiology of ESRD could be detected in only 197 (61.8%) cases; 122 cases had ESRD of unknown etiology. The etiological pathologies included hypertension, diabetes mellitus (DM), polycystic kidney disease (PKD), amyloidosis, VUR, and glomerulonephritis (GN). Hypertension was accompanied by DM in 25 cases, amyloidosis in 3 cases, GN in 1 case, PKD in 3 cases, and VUR in 1 case. Table 1 shows the frequencies of these pathologies.

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Table 1. Frequencies of end-stage renal disease* Etiology of end-stage renal disease

Hypertension

125 39.2

Diabetes mellitus

14.4

Polycystic kidney disease

6.6

Amyloidosis

16 5

Vesicoureteral reflux

3.4

Glomerulonephritis

11 3.4

Unknown

122 38.2

*25 cases had hypertension+diabetes mellitus, 3 cases had hypertension+amyloidosis, 3 cases had hypertension+polycystic kidney disease, 1 case had hypertension+glomerulonephritis, and 1 case had hypertension+vesicoureteral reflux.

Table 2. Frequency of vesicoureteral reflux in each group* Etiology of ESRD

VUR (+) (n)

P value

Hypertension

125 17 0.24

Diabetes mellitus

0.48

Polycystic kidney disease

0.13

Amyloidosis

16 0 0.06

Glomerulonephritis 11 3 0.33 Unknown

122 20 0.93

VCUG revealed VUR in 53 (16.6%) cases. VUR was leftsided in 22 (41.5%), right-sided in 19 (35.8%), and bilateral in 12 (22.6%). When classified according to severity, 10 (18.9%) cases had grade 1, 21 (39.6%) cases had grade 2, 20 (37.7%) cases had grade 3, and 2 (3.8%) cases had grade 4 VUR. Of 146 women, 32 had VUR, whereas of 173 men, 21 had abnormal VCUG results. The incidence of VUR was significantly higher in female cases (p=0.019; odds ratio=0.49). Table 2 shows the frequency of various comorbidities accompanying VUR. Hypertension, DM, PKD, amyloidosis, and GN could not be found to predict VUR. The rate of abnormal VCUG findings was similar in cases with ESRD of unknown and known etiologies. When VCUG was consistent with findings of grade 2, 3, and 4 VURs, these patients underwent surgical repair of the condition.

DISCUSSION In the current study, we classified pretransplant ESRD based

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on etiologies and evaluated VUR prevalence detected by VCUG. The frequency of VUR was not significantly different in groups with known and unknown etiologies. This result is critically important to denote that VCUG is required only for cases with urological abnormalities, but not for the whole group. Detection of VUR as a part of pretransplant evaluation is essential for predicting the outcome and prognosis during the post-transplant period.

Concept: E.P.; Design: E.P.; Data collection &/or processing: E.P., Z.D.; Analysis and/or interpretation: E.P.; Literature search: M.M.; Writing: E.P.; Critical review: Z.B.B.

The role of pretransplant VCUG in adults has been questioned owing to the low prevalence of abnormal findings. Our study reveals that 53 out of 319 cases with ESRD had VUR; in 11 cases, VUR was the etiology for ESRD. Song et al.[9] found VUR in 110 out of 622 (17.5%) cases with ESRD, whereas Agarwal et al.[10] demonstrated that 21 out of 150 (14%) cases showed VUR on pretransplant work-up. According to Shandera et al.,[11] 51 out of 333 cases had VUR, and 19 had urological abnormalities as the cause of ESRD. Several studies indicate the necessity of VCUG in cases with known urological abnormalities.[11,12] We point out the fact that VUR can be detected with similar prevalence in ESRD due to various known causes. In this regard, it may be thought that VCUG should be indicated for only a selected group of patients in pretransplant work-up. Simsir et al.[13] reported that lower urinary tract evaluation is not recommended in patients with ESRD due to parenchymal disorders.

1. Jonhson R, Feehally J. Comprehensive clinical nephrology. 5th ed. Philadelphia: Elsevier; 2015.

A previous study showed that VUR was more frequent in males.[14] This finding is contrary to our results, as the female group had higher incidence of VUR than male cases. There was no statistically significant difference in VUR frequency due to known or unknown etiologies of ESRD, as well as in different groups with various etiologies. Therefore, VCUG should be restricted to a special group of patients. Treatment of VUR contributes to better prognosis in renal transplant patients, and detection carries major importance. Our findings demonstrate that only sex was found as a predictor of VUR in pretransplant cases. In conclusion, the presence of VUR could not be related to any cause of ESRD; therefore, VCUG is not needed for all cases as a part of pretransplant evaluation. Ethics Committee Approval This was a retrospective study, therefore no ethics committee approval was taken. Informed Consent Retrospective study. Peer-review Internally peer-reviewed. Authorship Contributions

Conflict of Interest None declared.

REFERENCES

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Renal Transplantasyon Öncesi Değerlendirmede Vezikoüreteral Reflünün Belirteçleri Amaç: Voiding sistoüretrografi (VSUG) ürolojik hastalık öyküsü olan olguların transplantasyon öncesi vezikoüretral reflü (VUR) açısından değerlendirilmesinde sıklıkla kullanılır. Gereç ve Yöntem: Son dönem böbrek hastalığının (SDBH) etiyolojisi ile VUR prevalansı ilişkisini ve VSUG gerekliliğini değerlendirmeyi amaçladık. Transplantasyon öncesi VSUG uygulanan 319 hasta geriye dönük olarak değerlendirildi. Bulgular: Voiding sistoüretrografi ile 53 (%16.6) olguda VUR saptandı; 21 (%41.2) sol taraflı, 18 (%35.3) sağ taraflı, 12 (%3.8)iki taraflı; 10 (%19.6) grade 1, 19 (%37.3) grade 2, 20 (%39.2) grade 3 ve 2 (%3.9) grade 4 idi. SDBH sebebi 125 (%39.2) olguda hipertansiyon, 46 (%14.4) olguda, polya DM, 21 (%6.6) kistik böbrek hastalığı, 16 (%5) olguda amiloidoz, 11 (%3.4) olguda VUR ve 11 (%3.4) olguda glomerulonefrit idi. VUR sıklığı kadınlarda anlamlı olarak daha fazla bulundu. Hipertansiyon, DM, polikistik böbrek hastalığı, amiloidoz ve glomerulonefrit VUR belirteci olarak bulunmadı. Anormal VSUG bulgusu sıklığı sekonder ve idyopatik SDBH olgularında benzer bulundu. Sonuç: Çalışmamız, cinsiyetin VUR için anlamlı bir belirteç olduğu sonucunu ortaya koymuştur. VUR varlığı ile SDBH etiyolojisi arasında ilişki bulunmadı. Bu nedenle transplantasyon öncesi değerlendirmede VSUG yapılmasının gerekli olmadığı kanaatindeyiz. Anahtar Sözcükler: Böbrek nakli; vezikoüreteral reflü; voiding sistoüreterografi.

DOI: 10.14744/scie.2018.08370 South. Clin. Ist. Euras. 2018;29(3):180-186

Original Article

How Urgent are Blood Transfusions Provided in Emergency Service? Yasemin Özgür, Seydahmet Akın, Nazire Aladağ, Özcan Keskin

Gizem Gecmez,

ABSTRACT Department of Internal Medicine, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey Submitted: 18.05.2018 Accepted: 25.07.2018 Correspondence: Yasemin Özgür, SBÜ, Kartal Dr. Lütfü Kırdar Eğitim ve Araştırma Hastanesi, İç Hastalıkları Kliniği, İstanbul, Turkey E-mail: dryaseminozgur@gmail.com

Keywords: Emergency blood transfusion indications; internal medicine: red blood cell; thrombocyte.

Objective: A blood transfusion, defined as a procedure to replace lost blood, is actually a tissue transplantation, performed with consideration given to the impact profile, the potential development of complications, and the risk of anaphylaxis and rejection, which may lead to death. This study is an analysis of emergency blood transfusions in terms of symptoms and indications. Methods: Hospital records of blood transfusions administered in the emergency service were retrospectively reviewed. The patients were categorized into 2 groups: emergency patients and non-emergency patients, based on the presentation. Results: Over the course of 3 months, 1156 transfusions (2.18 per person) were performed in 528 patients (61.4% male). It was determined that the most commonly seen patient complaints were weakness (19%) and melena (14%), followed by cases in which the patient was asymptomatic, but there was laboratory pathology (12.9%). In all, 47% of all cases of blood transfusion were considered urgent. Conclusion: No correlation was determined between urgency requirement and hemoglobin level. Aside from those administered for active bleeding, most blood transfusions were not performed due to an urgent indication. The establishment of separate, ambulatory parenteral treatment units in could reduce the burden on emergency services to some extent and protect the priority status real emergency patients need.

INTRODUCTION The aim of a blood transfusion is to reduce the risks caused by anemia and to provide oxygen to tissues. Though the goal of a blood transfusion is to provide life-saving treatment, there are many studies indicating that the use of a blood transfusion has increased mortality and morbidity.[1] Transfusion-transmitted infections and transfusion-related immunomodulation have led to more discussion of the safety of blood transfusions.[2,3] For many decades, the decision to transfuse red blood cells was based upon the “10/30 rule”: a transfusion was used to maintain a blood hemoglobin (Hb) concentration above 10 g/dL (100 g/L) and a hematocrit above 30%.[4] In recent years, a large body of clinical evidence resulted in the publication of many guidelines for blood transfusion in

different settings according to the patient’s clinical status and oxygen delivery needs.[5–7] The objective of this study was to examine the blood transfusions performed in the internal medicine emergency service unit of a hospital in terms of symptoms and indications, and to investigate whether the factors affecting the decision for an urgent transfusion were the patient’s clinical status or the Hb level.

MATERIAL AND METHODS Study population The records of blood transfusions done in the emergency service unit of the Internal Medicine Clinic at the at University of Health Sciences,Kartal Dr. Lütfi Kırdar

Özgür. Emergency Blood Transfusion Experience

Training and Research Hospital between September 23 and December 23, 2015 were examined retrospectively. A total of 528 patients were included in the study. Sociodemographic data, diagnosis at the time of arrival, knowledge of known diseases, quantity of blood components requested and transfused from the blood bank, blood group, type of transfusion, and Hb and platelet (Plt) levels were examined. The hemograms were measured using a Coulter LH780 analyzer (Beckman Coulter, Inc. Inc., Brea, CA, USA). The study protocol was approved by the ethics committee of Kartal Dr. Lutfi Kırdar Training and Research Hospital, in accordance with the Declaration of Helsinki (2018/514/128/13).

Definitions The blood components transfused were analyzed in 3 sections: erythrocyte products, Plt products, and plasma. Erythrocyte products, that is, erythrocyte suspension (ES) and irradiated erythrocytes (IE); Plt products, namely, pooled Plt (PP), apheresis Plt (AP), and irradiated Plt (IP); and fresh frozen plasma (FFP) were examined separately.

Separation of patients into groups The patients were categorized into 2 groups: emergency patients and non-emergency patients, based on condition at presentation. The patients who presented at the hospital due to complaints of intraabdominal acid, diabetic foot complications, nausea, diarrhea, constipation, vomiting, inappetency, weakness, faintness, itching, edema, coughing, falling, dysmenorrhea, dysuria, abdominal pain, widespread pain, icterus, hyperglycemia, hypoglycemia, epigastric pain, scrotal edema, decubitus ulcer, sore throat, petechia, oliguria, fever, and patients who were examined before a biopsy or tooth extraction, surgery, or in the case of a catheter dysfunction, were classified in the non-emergency group. Patients with active bleeding, such as cases of hematochezia, melena, hematuria, hemoptysis, hematemesis, gingival bleeding, petechia, ecchymosis, tracheostomy bleeding, mucosal bleeding, conjunctival hemorrhage and epistaxis, and patients who presented with complaints of chest pain, dizziness, dyspnea, exertional dyspnea, syncope, tachycardia, impaired consciousness, anuria, hypotension, and seizures were included in the emergency group.

Statistical analyses IBM SPSS Statistics for Windows, Version 24.0 (IBM Corp., Armonk, NY, USA) was used to perform the statistical analysis. One-way analysis of variance was applied for multiple intergroup comparisons. After distribution of the variables was controlled using the Kolmogorov-Smirnov test, the independent samples t-test was used in paired comparisons of normally distributed quantitative variables. The

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Mann-Whitney U test was used for abnormally distributed groups, and a chi-square test was used to compare qualitative variables. A paired samples t-test was used for the intergroup comparison of continuous parameters, and a post-hoc least significant difference test was used to determine whether there was a statistically significant relationship between the groups. Pearson correlation analysis was performed for normally distributed parameters and Spearman correlation analysis was conducted for abnormally distributed parameters. Receiver-operating characteristic curves were used to determine the optimal urgency cut-off values of Hb. The results were calculated with a 95% confidence interval with a significance level of p<0.05.

RESULTS The records of 528 patients (61% men), received blood transfusion in the emergency service of an internal medicine clinic over the course of 3 months were examined. The average age of the patients, whose ages ranged from 16 to 94 years, was 61±16 years; 44% were geriatric patients. The average Hb level of the patients was 7.12±1.17g/dL, and the average Plt level was 19±12109/L at the time of arrival. The mean age of the patients was 61.27±15 years among the men and 60.89±18 years in the women. The average Hb level was 7.25±1.71 g/dL in men and 6.93±1.68g/dL in women, and the average Plt level was 19±11x109/L in men and 17±14x109/L in women. There was no statistically significant difference between the groups in these parameters. A total of 1505 different blood components were requested for these patients, and 1156 transfusions were performed. That is, 76% of the requests from the blood bank for blood components were ultimately determined to be necessary and subsequently administered: an average of 2.18 blood components per person. The blood components transfused were erythrocyte products (70%), Plt products (10.7%), and plasma (19.3%). It was observed that 307 patients received ES, 62 patients received IE, 42 patients received PP, 8 patients received AP, 7 patients received IP, and 102 patients received FFP. The average Hb level in the patients who received ES was 6.69 g/dL. The average Plt level in the patients who received TS was 36x109/L. The blood group distribution of the patients is shown in Figure 1. The 3 most common complaints/conditions at the time of arrival were weakness (19%), melena (14%), and being asymptomatic (only laboratory pathology) (13%). Other complaints and symptoms observed are provided in Table 1. At the time of emergency service presentation, the prediagnosis was most often related to the specialties of gas-

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South. Clin. Ist. Euras.

Endocrinology Other 2% 2%

B(-) 0(-) AB(+) 3% 3% 5%

Hematology 7%

A(-) 6%

Cardiology B(+)

A(+)

10%

43%

Gastroenterology 35%

Nephrology 12% 0(+)

Hematological

30%

Oncology

13%

20%

Figure 1. Blood group distribution.

Figure 2. Prediagnosis.

troenterology (34%), oncology (19%), and hematological oncology (13%), as shown in Figure 2. The only statistically significant difference in terms of urgency was in the gastroenterology patients (Fig. 5).

most frequent accompanying diseases were nephrological (21%), hematological (16%), oncological (15%), and cardiological (15%) disorders (Fig. 3). Examination in more detail revealed that chronic renal disease (21%) was most common, followed by hypertension (17%) and diabetes mellitus (13%) (Table 2).

As in both the clinic and polyclinic setting, it was determined in this emergency service of internal medicine that patients often have a number of chronic diseases, rather than a single isolated disease. When the additional diseases of the patients in our study were examined by branch, excluding acute hemorrhage, it was determined that the

Excluding 23 patients (4.4%) referred from another hospital, only 50% of the patients who received a transfusion of blood components had urgent complaints. The average Hb level of the 200 patients who received ES replacement and

Table 1. Patient condition at hospital admission Symptom/Condition Frequency Percent

Symptom/Condition

Frequency Percent

Weakness

101

19.1

Anorexia

1.1

Melena

14.0

Paleness

1.1

Asymptomatic

12.9

Diarrhea

Dyspnea

10.6

Preparation for tooth extraction

Hematemesis

8.7

Angina

Another hospital

3.4

Hemoptysis

Abdominal pain

3.4

Vomiting

Syncope

2.7

Gingival bleeding

Epistaxis

2.5

Bleeding

Hematochezia

1.9

Preoperation

Widespread pain

1.9

Tachycardia

Dizziness

1.7

Epigastric pain

Ununconsciousness

1.5

Catheter dysfunction

Hematuria

8 1.5

Ecchymosis

7 1.3

Edema

Nausea

6 1.1

1.3

Petechiae Fever Sore throat Dysmenorrhea

2 .4 1 .2 1

1 .2

Özgür. Emergency Blood Transfusion Experience

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relation was observed between Hb level and the degree of urgency (Fig. 4). The area under the curve (AUC) was calculated for different threshold levels of Hb based on the level of urgency. Using Hb cut-off levels of 5 g/dL, 6 g/dL, 7 g/dL, 8 g/dL, 9 g/dL, and 10 g/dL, the AUC was 0.523, 0.534, 0.486, 0.497, 0.504, and 0.503, respectively. No statistical significance was found.

Other 14%

Nephrology 21%

Endocrinology 9% Gastroenterology

Hematology 16%

10%

DISCUSSION This study examined the complaints, prediagnoses, tests, and examinations performed, as well as any additional diseases diagnosed in patients who received a transfusion of blood components in the emergency service of internal medicine at a hospital with significant experience performing blood transfusions. The factors affecting the decision to provide a blood transfusion were analyzed.

Cardiology Oncology

15%

Figure 3. Additional diagnosis.

Number of patients

Non-emergency Emergency

50 40 30 20 10 0

4–5

5–6

6–7 7–8 8–8 Hemoglobin level (g/dL)

9–10

10<

150

Non-emergency Emergency

100 50

er ol og O nc y H o lo em gy at ol og N ep ical hr ol o C ar gy di ol og H em y at En ol og do y cr in ol og Pu N y lm eu on ro lo ar gy y di s R he eas es um at ol og y

tro

en t

Number of patients

Figure 4. Emergency classification and hemoglobin level.

Figure 5. Emergency classification and prediagnosis.

presented at the hospital with non-urgent complaints was 7.03±1.65 g/dL; the average of Hb level of the 185 patients in the emergency group was 7.13±1.65 g/dL. Similarly, the average Plt level of the 53 patients in the non-emergency group who received Plt replacement was 18x109/L, and the average of the 4 patients in the emergency group was 25x109/L. Analysis of the Hb level at the time of arrival indicated that a transfusion of blood components of between 6 and 8 g/ dL was administered to many patients. However, no cor-

The transfusion of blood components is a deceptively complex form of tissue transplantation in which the ABO rH compatibility between donor and recipient must be considered and cross-matching is performed to avoid a hemolytic transfusion reaction. All possible risks to the patient should be evaluated before performing a transfusion, as well as the advantages/disadvantages for the patient, the contribution to the present condition of disease that can be expected, the potential to address existing symptoms, and alternative treatment methods. In our study, the patient’s Hb level at the time of arrival did not have a significant correlation with the urgency of their symptoms. AUC analysis calculated for different Hb cut-off levels was not statistically significant, and the ideal threshold level for transfusion was determined to be 6 g/ dL (AUC: 0.534 [0.477-0.591]; p=0.211). Therefore, the Hb level of the patient at the time of arrival should not be a sole determinant for the administration of a blood transfusion. However, a decreased Hb level in the follow-up period, or more importantly, the development of symptoms of anemia and the impairment of vital findings, are indications for a blood transfusion. We found that the patients 76% of the blood components requested for the patients were necessary, while 24% of the blood products were not ultimately necessary. A review of the literature confirms that while a blood transfusion is done in the expectation that it will benefit the patient, paradoxically, it may add to the complication rate or ultimately provide no particular advantage. A study examined the Hb threshold level for ES replacement in 921 patients with acute gastrointestinal bleeding in terms of efficacy and safety and it was determined that a restrictive strategy (Hb<7 g/dL) resulted in less need for a transfusion (therefore, it is cost-effective), a lower rate of complica-

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Table 2. Additional diseases of patients receiving emergency blood transfusion Diagnosis

Frequency Diagnosis Idiopathic thrombotic purpura

Frequency

Gastrointestinal bleeding

122

Chronic renal failure

109

Breast cancer

Hypertension

Pancreas cancer

Diabetes mellitus

Rheumatoid arthritis

Coronary artery disease

Hodgkin’s lymphoma

Congestive heart failure

Chronic lymphocytic leukemia

Gastric carcinoma

Larynx cancer

Liver cirrhosis

Myelofibrosis

Coumadin overdose

Pulmonary hypertension

Lung cancer

Cervix cancer

Cerebrovascular disease

Non-Hodgkin’s lymphoma

Esophageal varices

Fistula

Myelodysplastic syndrome

Familial Mediterranean fever

Chronic obstructive respiratory disease

Cholelithiasis

Peptic ulcer

Iron deficiency anemia

Psychosis

Acute myeloid leukemia

Gall bladder cancer

Urinary bladder cancer

Ulcerative colitis

Multiple myeloma

Pulmonary embolism

Valve op.

Hyperthyroidism

Colon cancer

Mental retardation

Prostate cancer

Mesothelioma

Asthma

Overian cancer

Brain tumor

Pnomototaks

Hemorrhoid

Renal cell cancer

Menometrorrhagia

Pre-operation

Atrial fibrillation

Acute kidney disease

Gastritis

9 Brucellosis

Chronic myeloid leukemia

Cerebral palsy

Goiter

Crohn’s disease

Amyloidosis

Febrile neutropenic fever

Benign prostatic hyperplasia

Kaposi’s sarcoma

Deep vein thrombosis

Osler-Weber-Rendu

Epilepsy

6 Osteosarcoma

Hepatitis B (+)

Paraplegia

B12 deficiency

Parkinson’s disease

Dementia

5 Psychosis

1 1

Etilizm

Primary indeterminate cancer

Factor V Leiden mutation

Thyroid cancer

Hepatitis C (+)

Thalassemia

tions and recurrence of bleeding, and a lower rate of death with uncontrolled bleeding and other reasons when compared with a more liberal strategy (Hb<9 g/dL).[8] On the

other hand, Carson et al.[9] reported that a liberal transfusion strategy has been associated with a trend of fewer major cardiac events and deaths than a more restrictive

Özgür. Emergency Blood Transfusion Experience

strategy. Another study showed that a liberal transfusion strategy did not reduce the rate of death or the inability to walk independently at a 60-day follow-up, or reduce in-hospital morbidity in elderly high-risk patients who underwent hip surgery.[10] An analysis of 12 observational studies that included 653 anemic patients with advanced cancer who were given a transfusion found a subjective response rate of 31% to 70%.[11] Thus, we believe the use of a transfusion in oncology patients should be made on a case-by-case basis. In fact, other studies have come to the same conclusion, which indicates that rather than the present use of Hb level, the symptoms of the patient should be a primary consideration in indication for a blood transfusion. In the presence of anemic symptoms, a blood transfusion may be considered regardless of the Hb value. The symptoms of anemia are usually defined based on a decrease in oxygen delivery to the tissues and an increase in hypovolemia as a result of active bleeding. The symptoms of anemia are indicated as follows: 1. Myocardial ischemia findings or 2. Orthostatic hypotension or 3. Tachycardia unresponsive to fluid replacement or 4. Dyspnea at rest.[12] These symptoms may be significant if they cannot be explained by another condition, such as a massive pulmonary embolism, and furthermore, it should be noted that some patients may not display the typical symptoms of anemia, such as those with diabetic neuropathy. The impact of a red blood cell transfusion on outcomes in patients with acute coronary syndrome is controversial. A red blood cell transfusion has been associated with an increased risk of short- and long-term mortality, as well as myocardial reinfarction. However, a transfusion appeared to have beneficial or neutral effects on mortality at Hb levels below 8.0 g/dL, and harmful effects above 10 g/dL.[13,14] The symptoms of chronic anemia are tiredness, weakness, headache, vertigo, angina, exercise intolerance, and dyspnea. The underlying cause is most likely iron deficiency anemia or anemia based on other nutritional deficiencies. Chronic anemia develops slowly as the body adapts via various mechanisms over the long term. Rather than breaking this chain rapidly with the transfusion of blood components, it has been suggested that the deficiency should be corrected in a controlled manner while treating the underlying disease.[15] In our study, unfortunately, the first 3 conditions that led to the administration of a transfusion of blood components were weakness (19%), melena (14%), and asymptomatic with laboratory pathology. Unnecessary transfusions may be one reason for density experienced in emergency ser-

185

vices. It should not be forgotten that impatience of both patients and physicians in the treatment of anemia and efforts made to increase the Hb level immediately may provide disadvantages as well as advantages to the patients. If the bone marrow is healthy, it may be sufficient to wait and provide only any necessary components. In a study conducted in New York between 2008 and 2010 to reduce the growing use of blood components and the rates of mortality and morbidity, a more limited blood transfusion threshold was implemented based on continuous monitorization of the patient’s clinical condition. As a result, the ES transfusion decreased by 30.1%, the Plt transfusion rate decreased by 24.3%, the use of FFP decreased by 41.8%, and the use of cryoprecipitate decreased by 38.7% in the first year.[16] These results provide us with insight on potential benefits to be obtained by decreasing the rate of unnecessary transfusions and instituting a more controlled approach to both increase patient safety and decrease hospital costs. Gastroenterology patients, including a relatively large number with gastrointestinal bleeding, were the most frequent emergency service patients to receive a transfusion, followed by oncology patients and hematological oncology patients. Our hospital is a kind of oncology center for the region. Excluding the patients with active gastrointestinal bleeding, it was determined that fewer than 50% of the patients in these groups required an emergency transfusion of blood components. Ambulatory parenteral treatment units could provide treatment for such patients and decrease the density experienced in emergency services and thereby ensure that patients with a genuine emergency receive priority (Fig. 5). A limitation of this study is that analysis of vital findings and follow-up could not be performed.

CONCLUSION In conclusion, the transfusion of blood components is a very serious intervention and has serious potential complications, though it seems simple and routine. Therefore, the foreseeable risks should be considered when the level of Hb falls below a certain threshold value, rather than performing a transfusion immediately. The advantages and disadvantages to the patient, the expected contribution to the present condition of disease, the possibility to resolve symptoms, and alternative treatment methods should be carefully analyzed before making a decision to provide a blood transfusion. The decision to administer a transfusion should be made evaluating not just the Hb level, but the patient’s clinical condition, the underlying reasons for anemia, and important morbidity and mortality considerations.

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Ethics Committee Approval Approved by the local ethics committee. Informed Consent Retrospective study. Peer-review Internally peer-reviewed. Authorship Contributions Concept: Y.Ö.; Design: Y.Ö., S.A.; Data collection &/or processing: S.A., G.G.; Analysis and/or interpretation: Y.Ö.; Literature search: N.A.; Writing: Y.Ö., G. G.; Critical review: Ö.K. Conflict of Interest None declared.

REFERENCES 1. Cortés Buelvas A. Anemia and transfusion of red blood cells. Colomb Med (Cali) 2013;44:236–42. 2. Vasudev R, Sawhney V, Dogra M, Raina TR. Transfusion-related adverse reactions: From institutional hemovigilance effort to National Hemovigilance program. Asian J Transfus Sci 2016;10:31–6. 3. Ürkmez S. Blood Transfusions in the Intensive Care Unit [Article in Turkish]. Turkiye Klinikleri J Anest Reanim-Special Topics 2012;5:53–63. 4. Wang JK, Klein HG. Red blood cell transfusion in the treatment and management of anaemia: the search for the elusive transfusion trigger. Vox Sang 2010;98:2–11. 5. Napolitano LM, Kurek S, Luchette FA, Corwin HL, Barie PS, Tisherman SA, et al; American College of Critical Care Medicine of the Society of Critical Care Medicine; Eastern Association for the Surgery of Trauma Practice Management Workgroup. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med 2009;37:3124–57.

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6. Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA 2016;316:2025– 35. 7. Qaseem A, Humphrey LL, Fitterman N, Starkey M, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2013;159:770–9. 8. Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368:11–21. 9. Carson JL, Brooks MM, Abbott JD, Chaitman B, Kelsey SF, Triulzi DJ, et al. Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J 2013;165:964–71.e1. 10. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, et al; FOCUS Investigators. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011;365:2453–62. 11. Preston NJ, Hurlow A, Brine J, Bennett MI. Blood transfusions for anaemia in patients with advanced cancer. Cochrane Database Syst Rev 2012:CD009007. 12. Weiskopf RB, Viele MK, Feiner J, Kelley S, Lieberman J, Noorani M, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998;279:217–21. 13. Garfinkle M, Lawler PR, Filion KB, Eisenberg MJ. Red blood cell transfusion and mortality among patients hospitalized for acute coronary syndromes: a systematic review. Int J Cardiol 2013;164:151–7. 14. Allonen J, Nieminen MS, Hiippala S, Sinisalo J. Relation of Use of Red Blood Cell Transfusion After Acute Coronary Syndrome to Long-Term Mortality. Am J Cardiol 2018;121:1496–504. 15. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron deficiency anaemia. Lancet 2016;387:907–16. 16. Politsmakher A, Doddapaneni V, Seeratan R, Dosik H. Effective reduction of blood product use in a community teaching hospital: when less is more. Am J Med 2013;126:894–902.

Acil Servisteki Kan Transfüzyonları Ne Kadar Acil? Amaç: Kan transfüzyonu eksik olanın yerine konulmasıdır; etki profili, komplikasyon gelişimi, anaflaksi riski, ölüme kadar gidebilen rejeksiyon epizotları ile beraber düşünüldüğünde aslında bir doku transplantasyonudur. Klinik pratiğimizi dahiliye gözüyle semptom ve endikasyon açısından gözden geçirmek amacıyla acil dahiliye servisinde yapılan kan transfüzyonlarını derlemeyi amaçladık. Gereç ve Yöntem: Hastanemiz acil dahiliye servisinde yapılan kan transfüzyonları geriye dönük olarak hastane bilgi sistemi üzerinden tarandı. Hastalar başvuru şikayetlerine göre aciliyet gerektirenler ve aciliyet gerektirmeyenler diye iki gruba kategorize edildi. Bulgular: Üç ayda dahiliye acil servisinde %61.4’ü erkek toplamda 528 hastaya 1156 adet transfüzyon gerçekleştirildi (kişibaşı ortalama 2.18 adet). Başvuru şikayetlerinde ilk üç sırada halsizlik (%19), melena (%14), yakınmasız (sadece laboratuvar patolojisi) (%12.9) yer alıyordu. Aktif kanamayla gelen gastrointestinal sistem kanamaları hariç tutulduğunda ne onkoloji ne hematolojik onkoloji ne de diğer hasta gruplarının temel başvuru şikayetlerine bakıldığında aciliyet gerektiren şikayet oranları %50 dahi değildi. Tüm hastaların %47’sini ancak acil hastalar oluşturmaktaydı. Sonuç: İstanbul Anadolu yakasının en kalabalık hastanelerinden biri olan hastanemiz yoğun bir transfüzyon deneyimine sahiptir. Sonuç olarak aciliyet gereksinimi ile hastaların geliş hemoglobin düzeyleri arasında bir korelasyon olmadığı gibi; aktif kanama haricinde acilde yapılan kan ürünleri transfüzyonlarının çoğunun acil endikasyonla yapılmadığı görüldü. Acil servislerin yükünü bir nebze azaltılması ve gerçek acil hastaların önceliğinin korunması adına hastanelerde ayaktan parenteral tedavi ünitelerinin kurulması düşünülebilir. Anahtar Sözcükler: Acil kan transfüzyonu endikasyonları; eritrosit, iç hastalıkları; trombosit.

DOI: 10.14744/scie.2018.18480 South. Clin. Ist. Euras. 2018;29(3):187-193

Original Article

Evaluation of the Factors Affecting Percutaneous Success and Complications of Nephrolithotomy Osman Murat İpek,1

Kaya Horasanlı2

ABSTRACT Objective: Nowadays, surgical procedures become more reliable as urinary system stone disease begins to be treated with minimally invasive methods. Percutaneous nephrolithotomy (PNL) is the first treatment option for kidney stones >2 cm. An increase in postoperative stone-free (SF) rates due to improvements in technology and experience, operation, and hospital stay is reduced. Over time, complications of PNL have been reduced and more standardized with classifications similar to the developed Clavien grading system. The aim of the present study was to comparatively investigate the factors that are considered to affect success and complications in PNL operation.

Department of Urology, University of Health Sciences Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey 2 Department Of Urology, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul, Turkey

Submitted: 06.07.2018 Accepted: 01.09.2018 Correspondence: Osman Murat İpek, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, İstanbul, Turkey E-mail: omipek@hotmail.com

Keywords: Clavien ratings; complication; percutaneous nephrolithotomy; stone.

Methods: The present study included 928 patients (1011 renal units) who underwent PNL operation between November 2004 and January 2013 in our clinic. These patients had preoperative (sex, age, body mass index (BMI), operation side, previous stone operations, hydronephrosis and grade, stone localization, stone area, and volume), operative (operation time, fluoroscopy time, number of access, and calyces of access), and postoperative (hemoglobin, hematocrit, complication, transfusion, stone removal, nephrostomy withdrawal time, length of hospital stay, and need for additional intervention). The complications that occurred during and after the operation were classified according to the modified Clavien system. Subsequently, patients were divided into two groups: patients with complications (Group 1) and those with no complications (Group 2). The groups were analyzed comparatively. Results: Overall, 628 male and 383 female (M/F: 8/5) patients were included in the study. The mean age of the patients was 41.9 years. Of the evaluated operations, 185 had minor or major complications, and 826 had no complications. Complications in PNL operation are classified according to the modified Clavien grading: 23 (2.27%) complications in grade 1, 143 (14.14%) complications in grade 2, 11 (1.08%) complications in grade 3A, 6 (0.59%) complications in grade 3B, 4 (0.39%) complications in grade 4A, and 15 (4.48%) complications in grade 4B. No complication according to grade 5 was observed. Statistically, stone size, preoperative hydronephrosis grade, time of operation and fluoroscopy, length of stay in the hospital, and SF rates were found to be effective parameters on complication development in both groups (p<0.05). Age, gender, BMI, number of access to the kidney, and postoperative complications were not found to be effective parameters in terms of complication development (p>0.05). Conclusion: PNL is an effective and reliable method for the treatment of urinary stone disease. Most of the complications are minor. Stone size, presence of preoperative hydronephrosis, long operation times, and excessive access to the kidney collecting system increase the complication rates. Another important result obtained in the present study is that the complication rates are higher in patients with high SF rates than in other patients.

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INTRODUCTION Urinary system stone disease plays a significant role in daily urology practice. It has been affecting humans since the first ages. Until the 1980s, surgical procedures were applied to a considerable number of patients owing to urinary tract stones with ensuing renal loss. Endoscopic and minimally invasive methods are the gold standard of treatment of stone disease considering that urinary system stones recur on an average of 50% of the cases within 10 years.[1] The prevalence of urinary system stone disease varies between 2% and 15% and may show regional and ethnic differences.[2,3] The prevalence rates are 2%–3% in the United States, 3%–11% in Europe, 7% in Japan, and 14.8% in Turkey and have risen to approximately 20% in Arab countries dominated by warm climate.[3–7] In 1989, in the questionnaire survey conducted with 1500 individuals from 14 regions in Turkey, it was found that 2.2% of the survey responders were contracting stone disease at least once in their lifetime.[3] The incidence of urinary system stone disease is high in North India, Pakistani, North Australia, Central Europe, China, Central America, and Scandinavian and Mediterranean countries. All of these findings emphasize that the urinary system stone disease is endemic in Turkey. Today, the treatment approaches to kidney stones depend on the stone size and consist of extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PNL), retrograde intrarenal surgery (RIRS), laparoscopic surgery, open surgery, and combination treatment according to the condition of the patient. Owing to technological developments, RIRS and percutaneous surgery reduced the incidence of open surgery to 0.7%–4%, and PNL has become the first alternative in the treatment of large renal stones.[8]

MATERIAL AND METHODS Between November 2004 and January 2013, we included 1011 renal units that were subjected to PNL in our clinic. For each unit, preoperative (gender, age, body mass index (BMI), operation side, previous stone operations, renal ectasia and grade, stone localization, stone area, and volume), operative (operative time, fluoroscopy time, number of renal accesses, and calyx to be accessed), and postoperative (hemoglobin, hematocrit, complications, transfusion procedures, stone-free (SF) rates, nephrostomy withdrawal time, and need for additional interventions) parameters were evaluated retrospectively. Cases were categorized as those who developed and did not develop complications. Complications were graded according to the modified Clavien system. Life-threatening complications were taken into consideration. Patients with bleeding diathesis, solitary kidneys, urinary tract infections, retrorenal colon, and renal tumor were

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excluded from the study. Informed consent was obtained from all patients before the operation. Preoperative, operative, and postoperative data of the cases were compared. On computed tomography (CT), the stone area was calculated by multiplying the longest diameter with the longest diameter intersecting it perpendicularly and expressed in mm2. On the other hand, the stone volume was estimated using coronal and axial sections. If there were more than one stone, stone load was calculated for each stone separately, and their sum was the total stone burden. Postoperatively, opaque stones were evaluated using direct urinary system X-rays (kidney, ureter, and bladder (KUB)), and non-opaque stones using urinary tract ultrasonography (USG) or CT. During preoperative preparation, laboratory analyses including urine cultures and radiological imaging studies of all patients were performed. According to the results of the antibiograms, patients with urine cultures were treated with appropriate antibiotics to ensure that their urine was sterile. After induction of general anesthesia, a 6F open-ended ureter catheter was inserted ipsilaterally and fixed to the Foley catheter, which would provide delivery of contrast material for opacification and dilatation of the cavities of the collecting system with the patient in the lithotomy position. Patients were then turned into a prone position on a table compatible with the C-arm, and under fluoroscopic control, a percutaneous access needle (18G Percutaneous Access Needle; Boston Scientific Corporation, Natick, MA, USA) was inserted into the appropriate calyx visualized at various planes with the aid of the C-arm. A guidewire (Sensor Guide Wire; Boston Scientific Corporation) was placed in the collecting system, and the access path was dilated up to 14F over the guidewire. A second guidewire was advanced for safety purposes over dual-lumen catheter (Dual Lumen Ureteral Access Catheter; Cook Medical, IN, USA), and then dilations up to 30F were performed using a balloon dilator (NephroMax Microvasive High Pressure Balloon Catheter; Boston Scientific Corporation) or Amplatz dilators (Amplatz Renal Dilator Set, Cook Medical). A 26F nephroscope (Karl Storz GmbH, Tuttlingen, Germany) was advanced into the collecting system through a 30F Amplatz sheath. Then, the stones were fragmented with the aid of pneumatic, ultrasonic lithotriptors or both (Swiss LithoClast; EMS, Nyon, Switzerland), and the fragments were extracted using endoscopic graspers. After the operation, a 14F nephrostomy tube (Malecot Nephrostomy Catheter; Cook Medical) was placed and fixed to the skin, and the procedure was terminated. On postoperative day 1, patients with opaque stones were evaluated using KUB, and those with non-opaque stones using urinary USG or CT. Asymptomatic stone fragments <4 mm that did not cause obstruction and/or infection were accepted as clinically insignificant residual fragments (CIRFs), and particles >4 mm were accepted as residual

İpek. The Factors Affectıng Percutaneous Nephrolithotomy’s Success

fragments. Nephrostomy tubes of patients with complete SF, CIRF, or without complication; fever; and hemorrhage were clamped. Nephrostomy tubes of patients without pain were removed. A double J ureter catheter was inserted in case of urine leakage lasting >48 h. Where necessary, ureterorenoscopy and ESWL were evaluated as additional treatment options. In cases where SF or CIRF was achieved, the PNL surgery was considered “successful.” Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) for Windows 15.0 program. Findings were classified into two groups: those with and without complications. Statistical methods (mean and standard deviation) as well as descriptive statistical methods (Student’s t-test) and Mann–Whitney U test were used for comparison of two parameters with normal distribution. Paired sample t-test was used for intragroup, preoperative, and postoperative comparisons of the parameters. Chisquare test was used for comparison of qualitative data. A p value <0.05 was accepted as statistically significant.

RESULTS The study included 1011 PNL operations performed on 980 renal units of 928 patients. A total of 1011 PNL inter-

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ventions were performed, including 952 unilateral single session and 28 bilateral single session PNL operations. PNL operations in 31 patients were performed at a second session. All operations were divided into two groups: those associated with (Group 1) and without (Group 2) complications (Table 1). Any statistically significant difference was not detected between the groups in terms of age, gender, BMI, operation side, and patients who had previous intervention. The mean stone area of complicated cases was found to be statistically significantly higher than that of cases without complications (p=0.014; p<0.05). The mean stone area and volume of the complicated cases were found to be statistically higher than those of cases without complication. Complications demonstrated a negative correlation with operative success rates, and success rate decreased as the stone load increased (p=0.01; p<0.05). Therefore, PNLs associated with the development of complications were terminated prematurely, especially due to perioperative bleeding. In both groups, mostly access into the lower calyx was attempted, and manipulations were made through a single working channel (Table 2). A significant difference was not found between both groups as for the number of working channels, whereas operative and fluoroscopy times were

Table 1. Demographic characteristics of the cases

Patients who developed complications (n=185)

Patients who did not develop complications (n=826)

Mean±SD (Median)

Age (years)+

41.87±15.68

Body mass index (kg/m ) 2 +

Stone area (mm2)++

26.86±6.21

41.97±15.25 0.936 26.52±7.45 0.567

950.75±712.62 (707)

888.71±874.98 (589)

0.014*

3 ++

3899.03±3351.91 (2703)

3751.14±3176.67 (1977)

0.001**

Grade of preoperative hydronephrosis++

1.59±1.25 (2)

1.20±1.15 (1)

0.001**

n (%)

Stone volume (mm )

Gender+++

Male

110 (59.5)

518 (62.7)

Female

75 (40.5)

308 (37.3)

0.410

Percutaneous nephrolithotomy+++

Right

102 (55.1)

396 (47.9)

Left

83 (44.9)

430 (52.1)

136 (73.5)

534 (64.6)

Preoperative presence of hydronephrosis+++ Previous treatment interventions

0.077 0.021*

+++

Open surgery

27 (14.6)

145 (17.6)

0.333

Extracorporal shock wave lithotripsy

40 (21.6)

182 (22.0)

0.903

Percutaneous nephrolithotomy

24 (13.0)

75 (9.1)

0.107

Student’s t-test. ++Mann–Whitney U test. +++Chi-square test. *p<0.05. **p<0.01.

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Table 2. Evaluation of calyceal locations accessed and the number of access sites according to groups*

Group-1 Group-2

n (%)

14 (7.6)

68 (8.2%)

Calyces accessed

Upper

Middle

32 (17.3)

166 (20.1)

Lower

85 (45.9)

357 (43.2)

Upper-Middle

11 (5.9)

51 (6.2)

Upper-Lower

9 (4.9)

40 (4.8)

Middle-Lower

22 (11.9)

98 (11.9)

Upper-Middle-Lower

11 (5.9)

44 (5.3)

Upper-Lower-Lower

1 (0.5)

2 (0.2)

0.982

Number of entries

149 (80.5)

650 (78.7)

25 (13.5)

127 (15.4)

11 (5.9)

47 (5.7)

0 (0.0)

2 (0.2)

0.830

Table 3. Evaluation of operative and fluoroscopy times and mean number of entries

Group-1 Group-2 p

Mean±SD Mean±SD (Median) (Median)

Operative time (min)+

135.02±48.08 122.58±49.36 0.002**

Fluoroscopy time (min)++

6.30±4.80 (5) 5.72±5.32 (4) 0.003**

Number of entries++ 1.25±0.55 (1) 1.27±0.57 (1)

0.599

Chi-square test. **p<0.01. +Student’s t-test. ++Mann–Whitney U test.

significantly higher in Group 1 (Table 3). The groups were evaluated for bleeding complications, and a statistically significant difference was found between preoperative and postoperative hemoglobin and hematocrit values (Table 4). In addition, the rates of blood transfusions performed (73%) and complications (0.2%) were found to be statistically significantly higher in complicated cases (p=0.001; p<0.01). Patients who developed complications had statistically significantly longer hospital stays (p=0.043; p<0.05). The dwell time of nephrostomy tubes was found to be statistically significantly longer in patients who developed complications (p=0.001; p<0.01) (Table 4). The SF rate in Group 2 (71.2%) was significantly higher than that in Group 2 (48.1%) (p=0.001, p<0.01) (Table 5). The average overall complication rate was 18.29% in all cases. The number of complications classified according to the modified Clavien grading system was as follows: grade 1 (n=23, 2.27%), grade 2 (n=143, 14.14%), grade 3A (n=11, 1.08%), grade 3B (n=6, 0.59%), grade 4A (n=4, 0.39%), and grade 4B (n=15, 1.48%), whereas any grade 5 complication was not seen. In Group 1, 196 complications developed in 185 patients due mostly to bleeding. Disseminated intravascular coagulation developed in 2 (0.19%) and acute renal failure in 1 (0.09%) patients, and nephrectomy was performed in 1 (0.09%) patient. Renal angiography was performed in 3 (0.29%) patients due to serious decrease in hemoglobin and hematocrit values caused by bleeding despite the fact that the nephrostomy catheter was clamped for 24 h. During renal angiography, lacerated renal vessel was detected in 2, and pseudoaneurysm in one patient, and selective angioembolization was performed using metallic coils. Two (0.19%) patients who underwent PNL developed colon perforation, and one patient jejunum perforation. Hemothorax developed in 1 (0.09%) patient during supracostal access into the upper calyx. Postoperative urinary tract infection was seen in 24 (2.37%) patients after PNL. Antibiotherapy was started in accordance with the results

Table 4. Comparison of postoperative data of the groups

Group-1

Mean±SD (Median)

Group-2 p

Mean±SD (Median)

Postoperative hemoglobin decrease (g/dL)+

-3.07±1.52

-1.92±1.00 0.001**

Postoperative hematocrit decrease (%)

-8.69±4.27

-5.12±2.75 0.001**

Postoperative hematocrit decrease (%)+

-21.35±9.53

-12.17±6.07 0.001**

Length of hospital stay (days)

5.88±4.34 (6)

5.17±2.46 (5)

0.043*

Dwell time of the nephrostomy tube (days)++

4.11±2.93 (4)

3.18±1.45 (3)

0.001**

Blood transfusion rate (n,%)

135 (73.0%)

2 (0.2%)

0.001**

+++

+Student t test,++ Mann Whitney U test; +++ chi-square test.

İpek. The Factors Affectıng Percutaneous Nephrolithotomy’s Success

Table 5. Intergroup comparison of stone-free rates

Group-1 Group-2 p n (%)

n (%)

Stone clearance+ 0.001** No

96 (51.9)

238 (28.8)

Yes

89 (48.1)

588 (71.2)

Student’s t-test. **p<0.01. *p<0.05. +Chi-square test.

of blood/urine culture and antibiogram. Subsequently, 12 (1.18%) of these patients had sepsis, and disseminated intravascular coagulation developed in 1 (0.09%) patient. Postoperatively, 1 (0.1%) patient had coughing and fever, and antibiotherapy was started after the consolidation area was observed in the chest X-ray. Four (0.39%) patients developed perforation in the collecting system during PNL. No additional procedure was performed except a nephrostomy catheter was left in situ for 1 week. Urine leak from the catheter site 24 h after withdrawal of the nephrostomy catheter seen in 5 (0.49%) patients necessitated insertion of a double J stent. Newly developed ureteropelvic junction stenosis was detected in 3 (0.29%) patients 1 year after PNL operation.

DISCUSSION In the treatment of kidney stones, complications of open kidney stone surgery decreased since the introduction of PNL in 1976. In addition, many technological developments realized up to now in PNL have made PNL a safe and effective procedure. However, operation-specific complications have not been completely prevented. In the preoperative evaluation of patients, it was seen that in the elderly, patients with increased BMI, and previously treated patients in whom the urologists attributed higher risk of complication development, PNL did not increase the risk compared with other patients. In elderly patients, PNL may be considered as an invasive treatment modality owing to reduced body reserve due to the prone position of the patient during PNL and the presence of a greater number of comorbidities in elderly patients.[9] In patients aged ≥65 years who had undergone, higher (85%) SF rates were found, and well-controlled comorbidities had not increased the risk of operation.[10] In our study, the effect of age on the risk of development of complications was not seen. The prevalence of obesity is increasing worldwide, and obesity in urinary system stones is considered as an important risk factor. Recurrent open surgeries patients experienced and bulky stone size of these patients cause frequent use of PNL operation, whereas obesity complicates

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the operation. In a study where 1121 patients were divided into two groups according to their BMIs, differences in complication rate, additional treatment requirement, and hospital stay were not observed in the study group. [11] The main problem is longer distance between the skin and the collecting system of obese patients, and with the instruments used, it is hard to reach the targeted stone. While alternative instruments can be provided, the operation can be continued by incising the muscle layer and fixing the Amplatz sheath with sutures. When our patients were assessed for BMI, any effect of BMI on the success of the operation and the occurrence of complications was not observed. In patients who underwent open kidney surgery, deterioration in the anatomy of the pelvical and retroperitoneal structures is expected.[12] If kidney stones are considered to have a 50% risk of recurrence within 5–7 years, a recurring need for surgery will arise.[13] PNL reoperation is again considered as the first treatment alternative for stone disease even though fear from excessive bleeding, peripheral organ damage, and failure still exists. In comparative studies in the literature, there was no increase in complication rates in patients with PNL.[14,15] In the present study, according to the literature, there was no increase in complications due to PNL operation in patients who had previously undergone renal surgery. Predominantly, the presence of hydronephrosis, increased stone area, and volume are effective factors in the development of complications. An increase in complication rates in parallel with the grade of hydronephrosis may be attributed to the high stone load in these patients. Development of complications decreases hemoglobin and hematocrit values, thereby increasing blood transfusion rates. As the complication develops, fluoroscopy and operative times, hospital stay, and dwell time of the nephrostomy tube also increase. The SF rates decrease as the complication rates increase. Staghorn renal stones are assessed based on their surface area and volume, whereas excess stone load will increase the number of complications, the need for secondary surgical treatment, and the number of accesses.[16] In Group 1, it was detected that surface area and volume of the stone affect the development of complication (p<0.005). Negative correlations were observed between the mean stone area and volume and the success rate of surgery (p=0.001). In addition, surgery was terminated prematurely due to complications, especially peroperative bleeding. Instead, of using surface area and volume of the stone in relevant studies, more frequently, the groups of partial staghorn, complex staghorn, and non-staghorn are considered. Desai et al.[17] studied 5335 patients with PNL from 96 centers worldwide and categorized them into two groups: staghorn (27.5%) and non-staghorn (72.5%) groups. Preoperative

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urine culture positivity, multiple working channels, postoperative fever, bleeding, amount of blood transfusion, operative time, and length of hospital stay were significantly higher in patients who had undergone PNL for staghorn kidney stones, whereas the average SF rates were 82.5% in non-staghorn kidney stones and 56.9% in staghorn kidney stones. In addition, Soucy et al.[18] reported a 91% SF rate after PNL in the treatment of staghorn renal calculi. In patients with excess stone burden, multiple working channels may reduce the development of complications due to the difficulty of reaching all calyces through a single working channel. However, higher PNL complication rates are also seen while increasing the SF rate is targeted. When most of the evaluation criteria were compared, it was reported that complications were related to the number of working channels rather than the stone size.[19] When the results of PNLs performed through single and multiple working channels were compared, increases in fluoroscopy, operative times, amount of bleeding, and SF rates but unchanged creatinine levels were observed.[20] In cases where two or more than two working channels were used, bleeding was seen in 18.5%, and when a single working channel was used, it was seen in 7.6% of the cases.[21] Complications developed in 149 (149/185: 80.5%), 25 (13.5%), and 11 (5.9%) patients when single, two, or three working channels were used, respectively. Compared with the non-complicated group, although intergroup difference in the number of working channels was not found to be statistically significant, the need for transfusion was found to be increased in these patients (p=0.830).

first-line treatment method for kidney stones >2 cm. In the present study, the factors that might affect the success and complications in patients with renal stone during PNL were investigated. None of the demographic characteristics of the patients had an impact on surgical outcomes. As was seen in the group who developed complications, stone surface area and volume were higher, and bleeding and amount of blood transfusion increased with lower SF rates. Most complications that occur were minor complications. Stone size, presence of preoperative hydronephrosis, long operation times, and greater number of accesses into the renal collecting system increase the complication rates. Complication rates are expected to gradually decrease owing to experience in PNL and new developments.

PNL has the highest SF rate among all kidney stone treatment options. Greater number of working channels or combination therapies has been developed to increase this SF rates.

None declared.

In the literature, SF rates ranging between 51% and 100% have been cited in patients with PNL.[22] The first large series was reported to have achieved a 98% success rate in a series of 1000 patients who had undergone PNL in 1985.[23] Stone clearance was reported to be 68% in the UK as a result of the assessment of 1028 PNLs performed throughout the UK, whereas the SF rate of 75.7% was reported in the Clinical Research Office of the Endourological Society study, where 5803 participants were studied. [24,25] After 1011 PNLs were performed in our study, 67% (677 renal units) of all patients were completely cleared of their stones; whereas the SF rates were 48.6% (90 renal units) and 71.1% (588 renal units) among patients in the group with and without complications, respectively. Our results showed similarities with those of the objective studies cited in the literature.

CONCLUSION Nowadays, PNL is accepted as an effective and reliable

Ethics Committee Approval Approved by from the Şişli Etfal Training and Research Hospital. Informed Consent Retrospective study. Peer-review Internally peer-reviewed. Authorship Contributions Concept: O.M.İ., K.H.; Design: O.M.İ., K.H.; Supervision: K.H., O.M.İ.; Data collection &/or processing: O.M.İ.; Analysis and/or interpretation: O.M.İ.; Literature search: O.M.İ.; Writing: O.M.İ., O.M.İ.; Critical review: O.M.İ. Conflict of Interest

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stones. J Endourol 2011;25:1263–8. 18. Soucy F, Ko R, Duvdevani M, Nott L, Denstedt JD, Razvi H. Percutaneous nephrolithotomy for staghorn calculi: a single center’s experience over 15 years. J Endourol 2009;23:1669–73. 19. Maghsoudi R, Etemadian M, Shadpour P, Radfar MH, Ghasemi H, Shati M. Number of tracts or stone size: which influences outcome of percutaneous nephrolithotomy for staghorn renal stones? Urol Int 2012;89:103–6. 20. Akman T, Sari E, Binbay M, Yuruk E, Tepeler A, Kaba M, et al. Comparison of outcomes after percutaneous nephrolithotomy of staghorn calculi in those with single and multiple accesses. J Endourol 2010;24:955–60. 21. Muslumanoglu AY, Tefekli A, Karadag MA, Tok A, Sari E, Berberoglu Y. Impact of percutaneous access point number and location on complication and success rates in percutaneous nephrolithotomy. Urol Int 2006;77:340–6. 22. Skolarikos A, Alivizatos G, de la Rosette JJ. Percutaneous nephrolithotomy and its legacy. Eur Urol 2005;47:22–8. 23. Segura JW, Patterson DE, LeRoy AJ, Williams HJ Jr, Barrett DM, Benson RC Jr, et al. Percutaneous removal of kidney stones: review of 1,000 cases. J Urol 1985;134:1077–81. 24. Seitz C, Desai M, Häcker A, Hakenberg OW, Liatsikos E, Nagele U, et al. Incidence, prevention, and management of complications following percutaneous nephrolitholapaxy. Eur Urol 2012;61:146–58. 25. Armitage JN, Irving SO, Burgess NA; British Association of Urological Surgeons Section of Endourology. Percutaneous nephrolithotomy in the United kingdom: results of a prospective data registry. Eur Urol 2012;61:1188–93.

Perkütan Nefrolitotomi Başarı ve Komplikasyonlarını Etkileyen Faktörlerin Değerlendirilmesi Amaç: Günümüzde üriner sistem taş hastalığının minimal invaziv yöntemlerle tedavi edilmeye başlamasıyla cerrahi prosedürler güvenilir hale gelmeye başlamıştır. Perkütan nefrolitotomi (PNL) operasyonu, 2 cm’den büyük böbrek taşlarında ilk tedavi seçeneği haline gelmiştir. Teknolojideki gelişmeler ve tecrübenin artmasıyla operasyon sonrası taşsızlık oranlarında artış; operasyon ve hastanede yatış sürelerinde azalma olmuştur. Zaman içinde PNL komplikasyonları azalmış ve geliştirilen Clavien derecelendirme sistem benzeri sınıflandırılmalarla daha standart hale getirilmiştir. Bu çalışmada, PNL operasyonunda başarıyı ve komplikasyonları etkilediği düşünülen faktörlerin karşılaştırmalı olarak araştırılması amaçlandı. Gereç ve Yöntem: Çalışmamızda Kasım 2004 ile Ocak 2013 arasında kliniğimizde PNL operasyonu uygulanmış 928 hasta (1011 renal ünite) dahil edildi. Bu hastaların ameliyat öncesi [cinsiyet, yaş, vücut kitle indeksi (VKİ), operasyon tarafı, daha önce taş nedeniyle yapılan işlemler, hidronefroz ve derecesi, taş lokalizasyonu, taş alanı ve hacmi], operatif (operasyon süresi, skopi süresi, giriş yeri sayısı, giriş yapılan kaliks) ve ameliyat sonrası (hemoglobin, hemotokrit, komplikasyon, transfüzyon yapılması, taşsızlık, nefrostomi çekilme süresi, hastanede kalış süresi, ek girişim ihtiyacı) verileri geriye dönük olarak dosya kayıtlarından incelendi. Operasyon esnasında ve operasyon sonrasında meydana gelen komplikasyonlar modifiye Clavien sistemine göre sınıflandırıldı. Daha sonra olgular, komplikasyon gelişen hastalar (Grup 1) ve gelişmeyenler (Grup 2) olarak ikiye ayrıldı. Gruplar karşılaştırmalı olarak analiz edildi. Bulgular: Çalışmaya alınan hastaların 628 erkek, 383 kadın (E/K: 8/5), yaş ortalaması ise 41.9 idi. Değerlendirilen operasyonların 185’inde minör veya majör bir adet komplikasyon gelişirken, 826’sında komplikasyon gelişmediği görüldü. PNL operasyonunda görülen komplikasyonlar modifiye Clavien derecelendirilmesine göre sınıflandırıldığında derece 1’de 23 (%2.27) komplikasyon, derece 2’de 143 (%14.14) komplikasyon, derece 3A’da 11 (%1.08) komplikasyon, derece 3B’de 6 (%0.59) komplikasyon, derece 4A’da 4 (%0.39) komplikasyon, derece 4B’de 15 (%1.48) komplikasyon görülürken, derece 5’e uygun komplikasyon görülmedi. Her iki grup arasında yapılan karşılaştırmada taşın büyüklüğü, preoperatif hidronefroz derecesi, operasyon ve floroskopi süreleri, hastanede kalış süreleri ve taşsızlık oranlarının komplikasyon gelişimi üzerine etkili parametreler olduğu istatistiksel olarak gösterildi (p<0.05). Hastanın yaşı, cinsiyeti, VKİ, böbreğe giriş sayısı, operasyon sonrası ek girişimlerin ise komplikasyon gelişimi açısından etkili parametreler olmadığı saptandı (p>0.05). Sonuç: Perkütan nefrolitotomi, üriner sistem taş hastalığı tedavisinde etkin ve güvenilir bir yöntemdir. Meydana gelen komplikasyonların çoğu minör komplikasyonlardır. Taş büyüklüğü, ameliyat öncesi hidronefroz varlığı, uzun operasyon süreleri, böbrek toplayıcı sistemine fazla giriş yapılması komplikasyon oranlarını artırmaktadır. Bu çalışmada elde ettiğimiz başka önemli bir sonuç ise taşsızlık oranlarının yüksek olduğu hastalarda komplikasyon oranlarının da diğer hastalara göre yüksek olmasıdır. Anahtar Sözcükler: Clavien derecelendirme; komplikasyon; perkütan nefrolitotomi; taş.

DOI: 10.14744/scie.2018.02996 South. Clin. Ist. Euras. 2018;29(3):194-197

Original Article

Parathyroidectomy After Kidney Transplantation: A Single-Center Experience Ergün Parmaksız, Meral Meşe, Serkan Feyyaz Yalın, Ali Burak Haras, Okan Akyüz, Zerrin Bicik Bahçebaşı

ABSTRACT Department of Nephrology, University of Health Sciences Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey Submitted: 12.08.2018 Accepted: 27.08.2018 Correspondence: Ergün Parmaksız, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Nefroloji Kliniği, İstanbul, Turkey E-mail: drergnprmksz@hotmail.com

Keywords: Calcium; parathyroidectomy; renal transplantation.

Objective: Even after successful kidney transplantation, 10% to 50% of kidney transplant recipients have persistent hyperparathyroidism. Parathyroidectomy (PTX) has been reported to be associated with deterioration of renal function and reduced graft survival. The aim of this single-center, retrospective study was to analyze the long-term effect of PTX on calcium, phosphorus, and parathyroid hormone (PTH) levels, as well as the estimated glomerular filtration rate (eGFR), in renal transplantation patients who underwent PTX. Methods: The study population consisted of 154 patients followed between January 2014 and December 2017, 9 of whom underwent PTX. The median PTH, calcium, phosphorus, and eGFR values were recorded before and after PTX. Results: The median preparathyroidectomy PTH, calcium, phosphorus, and eGFR values were 311.57 pg/mL, 11.02 mg/dL, 2.35 mg/dL, and 90.88 mL/minute, respectively. When compared with the baseline figures, there was a decrease in PTH (311.5 vs. 147.5 pg/mL; p=0.015), calcium (11.02 vs. 9.01 mg/dL; p=0.017), and eGFR (90.88 vs. 75.44 mL/minute; p=0.008), and an increase in the phosphorus level (2.35 vs. 3.4 mg/dL; p=0.06) 1 month after surgery. The eGFR returned to the baseline rate 1 year after surgery (90.88 vs. 79.39 mL/ minute; p=0.11). Conclusion: PTX in renal transplant recipients appears to be a safe procedure. Although renal function deteriorates in the acute period following PTX, long-term stabilization occurs.

INTRODUCTION It is supposed that hyperparathyroidism (HPT) improves in the first year after renal transplantation.[1] Nevertheless, 10%–50% of the cases still show persistent HPT even after a successful renal transplantation,[2] and its occurrence is thought to be related to the period elapsed under dialysis prior to transplantation.[3] Although HPT has been recognized after a long time from renal transplantation, management of the disease is still controversial.[4] Vitamin D is the suggested treatment method for cases with persistent HPT; however, hypercalcemia limits its usage.[5] Following transplantation, parathyroidectomy (PTX) is the preferred choice of treatment because nodular hyperplasia of the

parathyroid glands shows monoclonality and aggressive proliferation that is resistant to medical therapy.[6] If hypercalcemia is refractory to medical treatment for more than a year following transplantation, PTX is the best choice of treatment.[7] On the other hand, there are controversial opinions for consequences of PTX. After PTX, a decrease in kidney function may be observed after transplantation.[8] However, Tseng et al.[9] did not confirm this deterioration following surgery. The aim of the present study was to analyze the effects of PTX on parathyroid hormone (PTH), phosphorus, and calcium concentrations as well as its impact on kidney function.

Parmaksız. Parathyroidectomy After Kidney Transplantation

MATERIAL AND METHODS We retrospectively evaluated renal transplant recipients who had undergone PTX due to HPT after transplantation between January 2014 and January 2017. Demographic data, such as age, gender, type of dialysis, time on dialysis, time of PTX after transplantation, immunosuppressive treatment applied, and usage of vitamin D or cinacalcet, were obtained from medical records. We checked the blood concentrations of PTH, calcium, phosphorus, and estimated glomerular filtration rate (eGFR) before PTX and at postoperative first month, first year, and the last record of follow-up. The Chronic Kidney Disease Epidemiology Collaboration formula is used to determine eGFR. PTH is measured as intact PTH (reference range: 10–65 pg/mL). The SPSS 17.0 package program was used for statistical analysis. Continuous variables were expressed as median. Table 1. Demographic and clinical characteristics of kidney transplantation patients who underwent PTX n=9 Age, years (median)

51.78 (44–64)

Dialysis vintage, years (median)

9.56 (5–13)

Immunosuppressive regimen (n, %)

Containing TAC

5 (55.6)

Containing CsA

1 (11.1)

Containing everolimus

3 (33.3)

Time from transplantation to surgery, month

33.67 (5–64)

Use of cinacalcet, n (%)

2 (22.2)

PTH level at the time of transplantation, pg/mL (median) Calcium level before surgery (mg/dL)

887.33 (475–1378) 11.02 (9.8–12.6)

Phosphorus level before surgery (mg/dL)

2.35 (1.7–3)

PTH level before surgery (pg/mL)

311.57 (102.8–685.3)

TAC: Tacrolimus; CsA: Cyclosporin A; PTH: Parathyroid hormone.

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Wilcoxon rank test was used for comparison of calcium, phosphorus, PTH, and eGFR before and after PTX. A pvalue <0.05 was considered statistically significant.

RESULTS The mean age of two female and seven male patients was 51.78 (44–64) years. Between January 2014 and December 2017, 9 out of 154 renal transplant patients underwent PTX due to persistent HPT. The rate of PTX in our transplant clinic was found to be 5.8% during the study. Renal replacement therapy before transplantation was hemodialysis for all patients. The median period of dialysis prior to renal transplantation was 9.56 (5–13) years. The median time for parathyroid surgery after renal transplantation was 34 (5–64) months (Table 1). The method of surgery was subtotal PTX. The median pre-operative values were 311.57 (102.8– 685.3) pg/mL for intact PTH, 11.02 (9.8–12.6) mg/dL for calcium, 2.35 mg/dL for phosphorus, and 90.88 (50–141) ml/min for eGFR. One month after surgery, PTH (311.57 vs. 147.5 pg/mL, p=0.015), calcium (11.02 vs. 9.01 mg/ dL, p=0.017), and eGFR levels (90.88 vs. 75.44 ml/min, p=0.008) decreased, and phosphorus (2.35 vs. 3.4 mg/ dL, p=0.06) increased compared with pre-PTX levels. There were a decrease in PTH (311.57 vs. 134.54 pg/mL, p=0.008), calcium (11.02 vs. 9.56 mg/dL, p=0.038), and eGFR levels (90.88 vs. 81.55 mL/min, p=0.11) and an increase in phosphorus (2.35 vs. 3.06 mg/dL, p=0.038) 1 year after surgery. There were a decrease in PTH (311.57 vs. 112.2 pg/mL, p=0.008), calcium (11.02 vs. 9.51 mg/dL, p=0.021), and eGFR (90.88 vs. 79.39 mL/min, p=0.06) levels and an increase in phosphorus (2.35 vs. 2.82 mg/dL, p=0.08) at the end of follow-up. eGFR was found to decrease significantly 1 month following PTX. It was observed that this decrease was reversed after 1 year of follow-up (Table 2). A decrease in eGFR (p=0.066) and an increase in serum phosphorus (p=0.08) were not found to be statistically sig-

Table 2. Calcium, phosphorus, PTH, and eGFR levels before and after PTX Calcium (mg/dL) Phosphorus (mg/dL)

Pre-PTX

1 month level/p value

1 year level/p value

End of follow-up level/p value

11.02

9.01/0.017

9.56/0.038

9.51/0.021

2.35

3.4/0.066

3.06/0.038

2.82/0.08

PTH (pg/mL)

311.75

147.5/0.015

134.54/0.008

112.2/0.008

eGFR (mL/min)

90.88

90.88/0.008

81.55/0.11

79.39/0.066

PTH: Parathyroid hormone; eGFR: Estimated glomerular filtration rate; PTX: Parathyroidectomy.

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nificant at the end of the follow-up period. Calcium and PTH levels were found to be significantly decreased at the end of follow-up (p=0.021 and p=0.008, respectively. During follow-up time, three patients relapsed and were administered cinacalcet.

DISCUSSION In case of HPT following renal transplantation, successful PTX prevents various consequences of prolonged hypercalcemia and improves symptoms of established complications, as well.[10,11] In the current analysis, PTH and calcium levels decreased significantly, and phosphorus levels were normalized in the long term following PTX. Stabilizing normal serum calcium levels positively affects allograft survival.[12] Therewithal, cessation of loss of phosphorous in urine due to PTH results in increase in bone mineral density.[13] Although PTX is thought to play a role in graft protection,[14] Garcia et al.[8] suggested that PTX itself has a deteriorating effect on allograft function, resulting in allograft dysfunction in the long term. The reason of renal allograft function deterioration following PTH is unclear. However, acute decrease in serum PTH following PTX may cause a decrease in kidney perfusion. PTH plays a role on kidney blood flow and glomerular filtration rate. It has an important role in both preglomerular vasodilatation and efferent vasoconstriction.[15] Finding out how acute deterioration of renal function occurs shortly after PTX may enable better selection of the right cases.[16] Consistently, we observed a significant decrease in eGFR at the first month following PTX in transplant recipients; however, eGFR approaches to presurgery levels 1 year after PTX. Deterioration of renal function at the last follow-up visit was statistically insignificant compared with baseline. This suggests that deterioration persists only for a short term. Schwarz et al.[17] showed that higher PTH levels prior to PTX and total PTX with autotransplantation are significant predictors of kidney allograft deterioration in 76 cases. Schlosser et al.[18] also reported that factors including decreased renal function during PTX and total PTX rather than subtotal PTX increase the incidence of allograft function deterioration. In our study, PTX type was subtotal PTX. Longer dialysis treatment is thought to increase the possibility of tertiary HPT.[19] In our analysis, the duration of dialysis prior to transplantation was 9.56 years. PTX has a negative hemodynamic effect on renal perfusion. This may be more important in the first year because calcineurin inhibitor-induced renal vasoconstriction is prominent,[20] and acute rejection may occur.

South. Clin. Ist. Euras.

HPT following renal transplantation improves gradually in the first year of transplantation,[1] and early post-transplant PTX increases the risk of renal allograft dysfunction. For this reason, PTX may be delayed for 1 year after transplantation. During this period, cinacalcet is administered. Late post-transplant PTX is not expected to have a detrimental effect on kidney function.[21] Cruzado et al.[22] reported that PTX is better than cinacalcet in normalizing blood calcium concentrations and PTH levels. Three patients were found to have recurrent HPT in the long-term follow-up and were treated with cinacalcet. Since our study was performed with a small number of retrospective patients, future prospective studies should be conducted to further elucidate the relationship between PTX and eGFR.

CONCLUSION In HPT after renal transplantation, PTX decreases GFR level at 1 month but does not cause deterioration of GFR level in the long term. For this reason, PTX is a safe procedure for HPT after renal transplantation. Ethics Committee Approval This was a retrospective study, therefore no ethics committee approval was taken. Informed Consent Retrospective study. Peer-review Internally peer-reviewed. Authorship Contributions Concept: E.P.; Design: E.P.; Data collection &/or processing: E.P., M.M.; Analysis and/or interpretation: E.P., S.F.Y.; Literature search: O.A., A.B.H.; Writing: E.P.; Critical review: Z.B.B. Conflict of Interest None declared.

REFERENCES 1. Evenepoel P, Claes K, Kuypers D, Maes B, Bammens B, Vanrenterghem Y. Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study. Nephrol Dial Transplant 2004;19:1281–7. 2. Messa P, Sindici C, Cannella G, Miotti V, Risaliti A, Gropuzzo M, et al. Persistent secondary hyperparathyroidism after renal transplantation. Kidney Int 1998;54:1704–13. 3. D’Alessandro AM, Melzer JS, Pirsch JD, Sollinger HW, Kalayoglu M, Vernon WB, et al. Tertiary hyperparathyroidism after renal transplantation: operative indications. Surgery 1989;106:1049–56. 4. Kandil E, Florman S, Alabbas H, Abdullah O, McGee J, Noureldine S, et al. Exploring the effect of parathyroidectomy for tertiary hyperparathyroidism after kidney transplantation. Am J Med Sci

Parmaksız. Parathyroidectomy After Kidney Transplantation

2010;339:420–4. 5. Kasiske BL, Zeier MG, Chapman JR, Craig JC, Ekberg H, Garvey CA, et al: Improving Global Outcomes. KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. Kidney Int 2010;77:299–311. 6. Tominaga Y, Kohara S, Namii Y, Nagasaka T, Haba T, Uchida K, et al. Clonal analysis of nodular parathyroid hyperplasia in renal hyperparathyroidism. World J Surg 1996;20:744–52. 7. Kinnaert P, Nagy N, Decoster-Gervy C, De Pauw L, Salmon I, Vereerstraeten P. Persistent hyperparathyroidism requiring surgical treatment after kidney transplantation. World J Surg 2000;24:1391– 5. 8. Garcia A, Mazuecos A, Garcia T, Gonzalez P, Ceballos M, Rivero M. Effect of parathyroidectomy on renal graft function. Transplant Proc 2005;37:1459–61. 9. Tseng PY, Yang WC, Yang CY, Tarng DC. Long-term Outcomes of Parathyroidectomy in Kidney Transplant Recipients with Persistent Hyperparathyroidism. Kidney Blood Press Res 2015;40:386–94. 10. Schlosser K, Zielke A, Rothmund M. Medical and surgical treatment for secondary and tertiary hyperparathyroidism. Scand J Surg 2004;93:288–97. 11. Milas M, Weber CJ. Near-total parathyroidectomy is beneficial for patients with secondary and tertiary hyperparathyroidism. Surgery 2004;136:1252–60. 12. Gwinner W, Suppa S, Mengel M, Hoy L, Kreipe HH, Haller H, et al. Early calcification of renal allografts detected by protocol biopsies: causes and clinical implications. Am J Transplant 2005;5:1934–41. 13. Weisinger JR, Carlini RG, Rojas E, Bellorin-Font E. Bone disease after renal transplantation. Clin J Am Soc Nephrol 2006;1:1300–13.

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14. Ozdemir FN, Afsar B, Akgul A, Usluoğullari C, Akçay A, Haberal M. Persistent hypercalcemia is a significant risk factor for graft dysfunction in renal transplantation recipients. Transplant Proc 2006;38:480–2. 15. Massfelder T, Parekh N, Endlich K, Saussine C, Steinhausen M, Helwig JJ. Effect of intrarenally infused parathyroid hormone-related protein on renal blood flow and glomerular filtration rate in the anaesthetized rat. Br J Pharmacol 1996;118:1995–2000. 16. Montenegro F, Ferreira G, Ianhez L. Surgical treatment of tertiary hyperparathyroidism: the choice of procedure matters! World J Surg 2008;32:1892–3. 17. Schwarz A, Rustien G, Merkel S, Radermacher J, Haller H. Decreased renal transplant function after parathyroidectomy. Nephrol Dial Transplant 2007;22:584–91. 18. Schlosser K, Endres N, Celik I, Fendrich V, Rothmund M, Fernández ED. Surgical treatment of tertiary hyperparathyroidism: the choice of procedure matters! World J Surg 2007;31:1947–53. 19. Apaydin S, Sariyar M, Erek E, Ataman R, Yiğitbaş R, Hamzaoğlu I, et al. Hypercalcemia and hyperparathyroidism after renal transplantation. Nephron 1999;81:364–5. 20. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4:481–508. 21. Jeon HJ, Kim YJ, Kwon HY, Koo TY, Baek SH, Kim HJ, et al. Impact of parathyroidectomy on allograft outcomes in kidney transplantation. Transpl Int 2012;25:1248–56. 22. Cruzado JM, Moreno P, Torregrosa JV, Taco O, Mast R, GómezVaquero C, et al. A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism. J Am Soc Nephrol 2016;27:2487–94.

Böbrek Nakli Sonrası Paratiroidektomi: Tek Merkez Deneyimi Amaç: Başarılı böbrek transplantasyonundan sonra bile, alıcıların %10–50’sinde kalıcı hiperparatiroidi görülebilir. Paratiroidektominin (PTX) böbrek fonksiyonlarında ve graft sağkalımında bozulma ile ilişkili olduğu bildirilmiştir. Çalışmamızda, merkemizde takip edilen ve PTX uygulanan böbrek nakli hastalarında PTX’in kalsiyum, fosfor, parathormon (PTH), tahmini glomerüler filtrasyon hızına (eGFR) uzun dönem etkilerini geriye dönük olarak değerlendirmeyi amaçladık. Gereç ve Yöntem: Ocak 2014–Aralık 2017 tarihleri arasında takip edilen 154 olgudan dokuzuna PTX uygulanmıştı. PTX öncesi ve sonrası medyan PTH, kalsiyum, fosfor ve eGFR değerleri kaydedildi. Bulgular: Paratiroidektomi öncesi medyan PTH, kalsiyum, fosfor ve eGFR değerleri sırasıyla 311.57 pg/mL, 11.02 mg/dL, 2.35 mg/dL ve 90.88 mL/dk idi. Bazal değerler ile bir aylık kontrol değerleri karşılaştırıldığında PTH (311.5 pg/mL vs. 147.5 pg/mL, p=0.015), kalsiyum (11.02 mg/dL vs. 9.01 mg/dL, p=0.017) ve eGFR (90.88 mL/dk vs.75.44 mL/dk, p=0.008) değerlerinde azalma, fosfor seviyerinde artma (2.35 vs 3.4 mg/dL, p=0.06) görüldü. Bir yıllık konrolde eGFR bazal seviyelerine döndü (90.88 mL/dk vs. 79.39 mL/dk, p=0.11). Sonuç: Böbrek nakli sonrası PTX uygulanması güvenilir bir metoddur. Her ne kadar PTX sonrası böbrek fonksiyonlarında erken dönemde bozulma görülse de, uzun dönemde stabilizasyon sağlanır. Anahtar Sözcükler: Böbrek nakli; kalsiyum; paratiroidektomi.

DOI: 10.14744/scie.2018.92400 South. Clin. Ist. Euras. 2018;29(3):198-202

Case Series

Efficient Treatment of Resistant Orbital Pseudotumor with CyberKnife: Case Series and Short Review of Literature Gökhan Yaprak,1 Ahmet Kasım Kılıç,2 Naciye Işık,1 Dilber Çelik Yaprak,3 Özgür Ozan Şeşeogulları4

Department of Radiation Oncology, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey 2 Department of Neurology, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey 3 Department of Ophthalmology, Ümraniye Training and Research Hospital, İstanbul, Turkey 4 Department of Radiation Oncology, Medicana International Hospital, Biruni University, İstanbul, Turkey Submitted: 31.07.2018 Accepted: 29.08.2018 Correspondence: Gökhan Yaprak, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Radyasyon Onkolojisi Kliniği, İstanbul, Turkey E-mail: gokhanyaprak@gmail.com

ABSTRACT Orbital inflammatory syndrome (OIS) or orbital pseudotumor is the most frequent cause of an orbital mass. Most cases are steroid responsive, but treatment of patients with refractory OIS may also include radiotherapy. Presently described are 3 cases of orbital pseudotumor that had a partial steroid response or recurrence and were treated successfully with CyberKnife (Accuray Inc., Sunnyvale, CA, USA).

Keywords: CyberKnife; orbital pseudotumor; radiotherapy.

INTRODUCTION

disorders, sarcoidosis, and granulomatosis with polyangiitis.[5–8]

Orbital inflammatory syndrome (OIS)—previously known as idiopathic orbital inflammation, inflammatory orbital pseudotumor, or non-specific orbital inflammation— is the most frequent cause of painful orbital masses in adults.[1,2] The OIS incidence is between 4.7% and 6.3%,[3,4] and it constitutes about 10% of orbital mass lesions.[1,2] The etiological factors include thyroid disorders, systemic lupus erythematous, rheumatoid arthritis, IgG4-related

Pseudotumors are rarely infiltrative. Radiological findings were summarized as infiltration of the retrobulbar fat, enlargement of the extraocular muscles, thickening of the optic nerve/sheath complex, contrast enhancement, and proptosis.[9] Intracranial extension is rare, but it has been documented in up to 8.8% of patients.[10] Soft-tissue edema, decreased ocular motility, proptosis, decreased visual acuity, or pain can be seen clinically.

Yaprak. Efficient Treatment of Resistant Orbital Pseudotumor with CyberKnife

The OIS treatment mainly consists of steroids, and about 80% of patients are steroid responsive.[11] Also, 33%–58% of patients may have recurrent OIS.[12,13] Patients with refractory OIS can be effectively treated with radiation therapy.[14,15] Here, we present three cases of patients with refractory OIS who were treated with hypofractionated stereotactic radiotherapy (HSRT) with CyberKnife (Accuray Inc., Sunnyvale, CA, USA). We also present a short review of literature.

CASE SERIES Case 1– A 39-year-old female patient was admitted to a hospital with diplopia occurring by down gaze and swelling on left eyelid for three months. Her biochemical and serological tests were normal. She had no systemic or rheumatologic condition. Her magnetic resonance imaging (MRI) revealed mass lesion located in left superior rectus muscle in left orbital that was compatible with pseudotumor or inflammation. She was given a two-month steroid treatment course with adequate dosing. Despite the steroid regimen, she had partial response, and she was referred to our center for radiotherapy option. After 1500 cGy (three fractions) HSRT with CyberKnife, the patient had complete clinical recovery. However, after 12 months of follow-up, repeat MRI showed partial regression. Case 2– A 17-year-old male patient complained of swelling of left eyelid, and MRI showed a mass that invades superior oblique and superior rectus muscles in the left orbit. Lesion has shown very dense enhancing that was compatible with orbital pseudotumor. There was no rheumatological or neoplastic finding in his diagnostic tests. He was also given the steroid treatment. After two months

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of steroid treatment, there was no evident regression of lesion. Therefore, he was evaluated for radiotherapy. 2000 cGy radiotherapy 10 fraction protocol was applied to left orbit. After three months of follow-up, left-sided mass lesion showed complete resolution. Four months from the last visit, onset of new symptom was observed in the right eye. MRI showed 45×29 mm sized lesion compatible with pseudotumor. After the complete failure of two-month steroid regimen, 800 cGy radiotherapy with CyberKnife was applied to the right orbit as a single fraction. Recurrence was obtained at the seven-month control visit. Reirradiation was given as 10 fraction with a total dose of 2000 cGy. Regression was achieved after second radiotherapeutic approach. Case 3– A 62-year-old female patient was admitted with right orbital swelling. Her MRI showed mass lesion of pseudotumor (Fig. 1). She had no past medical history. Oral steroid treatment was started, but due to treatment resistance, radiotherapy was planned. After 1500 cGy HSRT (three fractions) with CyberKnife (Fig. 2), lesion showed full recovery (Fig. 3). After about a 12 month of follow-up, no recurrence was obtained.

DISCUSSION OIS or orbital pseudotumor represents the most frequent cause of orbital masses.[1,2] Most of the patients have monophasic disease course, but some of the patients can show recurrence.[16] In a study performed in 153 non-specific orbital inflammation with a single or multiple recurrences showed that younger age, bilateral disease, partial initial steroid response increased risk of recurrence.[16] Additionally, there may be some risk factors precipitating

Figure 1. T1-weighted sagittal magnetic resonance images before CyberKnife treatment that shows lesion surrounding right orbit.

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Figure 2. CyberKnife treatment plan of lesion for radiosurgery was shown.

the disease recurrence in the presence of infection[17,18] and autoimmune disease.[19,20] Also, obesity, pregnancy, and bisphosphonate use may also cause disease recurrence.[20] In our case series, a patient showed disease recurrence despite the lack of presented risk factors except onset of young age. Corticosteroids are usually preferred as the first-line treatment option. Dose of 80 mg/day for 1 week followed by tapering oral dose of prednisone is generally considered as the first-line treatment.[21] Most of the lesions were resolved under steroid treatment.[11] In a small number of

patient group, low dose of cyclosporine alone or with the combination of prednisone has achieved to stabilize disease course in 1 or 2 years of treatment.[22] Methotrexate was successfully used in a group of non-infectious orbital inflammatory disease as a long-term therapy.[23] Adalimumab as a TNF-Îą blocker was able to control disease activity in two steroid dependent and treatment refractory patients.[24] Local therapy at doses between 20Gy and 30Gy is generally reserved for patients who fail to respond to medical treatments. These consisted of radiation therapy at

Figure 3. Axial T1-weighted Gd scans after radiation therapy. Lesion regressed after treatment.

Yaprak. Efficient Treatment of Resistant Orbital Pseudotumor with CyberKnife

conventional fractionation.[25] In refractory course or in the situation of pharmacologic treatment side effects or contraindications, radiotherapy may be considered as a treatment option. In a study consisting of 16 patients, 15 started with corticosteroids.[15] Eight patients had disease recurrence, and one had progression.[15] External-beam radiotherapy was applied to 14 patients.[15] Thirteen patients showed prominent improvement, but the rest of three patients could not have long-term control.[15] Another study with 20 patients revealed that 17 of the treatment group responded to radiotherapy.[14] Among responders, seven cases had partial recovery without an increase of steroid dose, one had complete response with a steroid dose reduction, and nine had complete response without steroid use.[14] HSRT with frameless stereotactic radiosurgery system provides a better optic apparatus protection and a short treatment time (3–5 fractions). In our cases, HSRT was effective, and it was safely used for treatment of orbital pseudotumor.

CONCLUSION As a result, besides the steroids, chemotherapeutic agents or monoclonal antibodies radiotherapy seems to be an efficient treatment option. Informed Consent Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review Internally peer-re viewed. Authorship Contributions Concept: G.Y, A.K.K; Design: N.I, G.Y; Data collection &/ or processing: G.Y, D.Ç.Y; Analysis and/or interpretation: A.K.K, N.I ; Literature search: Ö.O.Ş, N.I.; Writing: A.K.K., G.Y; Critical review: D.Ç.Y, Ö.Ö.Ş. Conflict of Interest None declared.

REFERENCES 1. Shikishima K, Kawai K, Kitahara K. Pathological evaluation of orbital tumours in Japan: analysis of a large case series and 1379 cases reported in the Japanese literature. Clin Exp Ophthalmol 2006;34:239–44. 2. Shields JA, Bakewell B, Augsburger JJ, Flanagan JC. Classification and incidence of space-occupying lesions of the orbit. A survey of 645 biopsies. Arch Ophthalmol 1984;102:1606–11. 3. Szabo B, Szabo I, Crişan D, Stefănuţ C. Idiopathic orbital inflammatory pseudotumor: case report and review of the literature. Rom J Morphol Embryol 2011;52:927–30. 4. Ding ZX, Lip G, Chong V. Idiopathic orbital pseudotumour. Clin

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Radiol 2011;66:886–92. 5. Espinoza GM. Orbital inflammatory pseudotumors: etiology, differential diagnosis, and management. Curr Rheumatol Rep 2010;12:443–47. 6. Min HK, Lee YS, Yang SW, Lee J, Kwok SK, Ju JH, Kim WU, Park SH. Clinical outcomes and pathological characteristics of immunoglobulin G4-related ophthalmic disease versus orbital inflammatory pseudotumor. Korean J Intern Med 2017 Oct 19 [Epub ahead of print], doi: 10.3904/kjim.2016.304. 7. Leo M, Maggi F, Dottore GR, Casini G, Mazzetti P, Pistello M, et al. Graves’ orbitopathy, idiopathic orbital inflammatory pseudotumor and Epstein-Barr virus infection: a serological and molecular study. J Endocrinol Invest 2017;40:499–503. 8. Fernández-Codina A, Pinilla B, Pinal-Fernández I, López C, FraileRodríguez G, Fonseca-Aizpuru E, et al; Spanish Registry of IgG4 Related Disease (REERIGG4) investigators; Autoimmune Diseases Group (GEAS); Spanish Internal Medicine Society (SEMI). Treatment and outcomes in patients with IgG4-related disease using the IgG4 responder index. Joint Bone Spine 2018. pii: S1297319X(18)30017–4. 9. Flanders AE, Mafee MF, Rao VM, Choi KH. CT characteristics of orbital pseudotumors and other orbital inflammatory processes. J Comput Assist Tomogr 1989;13:40–7. 10. Clifton AG, Borgstein RL, Moseley IF, Kendall BE, Shaw PJ. Intracranial extension of orbital pseudotumour. Clin Radiol 1992;45:23–6. 11. Mendenhall WM, Lessner AM. Orbital pseudotumor. Am J Clin Oncol 2010;33:304–6. 12. Swamy BN, McCluskey P, Nemet A, Crouch R, Martin P, Benger R, et al.Idiopathic orbital inflammatory syndrome: clinical features and treatment outcomes. Br J Ophthalmol 2007;91:1667–70. 13. Yuen SJ, Rubin PA. Idiopathic orbital inflammation: distribution, clinical features, and treatment outcome. Arch Ophthalmol 2003;121:491–9. 14. Prabhu RS, Kandula S, Liebman L, Wojno TH, Hayek B, Hall WA, et al. Association of clinical response and long-term outcome among patients with biopsied orbital pseudotumor receiving modern radiation therapy. Int J Radiat Oncol Biol Phys 2013;85:643–9. 15. Matthiesen C, Bogardus C Jr, Thompson JS, Farris B, Hildebrand L, Wilkes B, Syzek E, Algan O, Ahmad S, Herman T. The efficacy of radiotherapy in the treatment of orbital pseudotumor. Int J Radiat Oncol Biol Phys 2017;79:1496–502. 16. Braich PS, Kuriakose RK, Khokhar NS, Donaldson JC, McCulley TJ. Factors associated with multiple recurrences of nonspecificorbital inflammation aka orbital pseudotumor Int Ophthalmol 2018;38:1485–95. 17. Casteels I, De Bleecker C, Demaerel P, Van Wilderode W, Missotten L, Wilms G, et al. Orbital myositis following an upper respiratory tract infection: contribution of high resolution CT and MRI. J Belge Radiol 74:45–7. 18. Nieto JC, Kim N, Lucarelli MJ. Dacryoadenitis and orbital myositis associated with lyme disease. Arch Ophthalmol 2008;126:1165–6. 19. McCarthy JM, White VA, Harris G, Simons KB, Kennerdell J, Rootman J. Idiopathic sclerosing inflammation of the orbit: immunohistologic analysis and comparison with retroperitoneal fibrosis. Mod Pathol 1993:6:581–7. 20. Bijlsma WR, van Gils CH, Paridaens D, Mourits MP, Kalmann R. Risk factors for idiopathic orbital inflammation: a case-control study.

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Br J Ophthalmol 2011;95:360–4. 21. Mombaerts I, Schlingemann RO, Goldschmeding R, Koornneef L. Are systemic corticosteroids useful in the management of orbital pseudotumors? Ophthalmology 1996;103:521–8. 22. Bielory L, Frohman LP. Low-dose cyclosporine therapy of granulomatous optic neuropathy and orbitopathy. Ophthalmology 1991;98:1732–6.

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23. Smith JR, Rosenbaum JT. A role for methotrexate in the management of non-infectious orbital inflammatory disease. Br J Ophthalmol 2001;85:1220–4. 24. Adams AB, Kazim M, Lehman TJ. Treatment of orbital myositis with adalimumab (Humira). J Rheumatol 2005;32:1374–5. 25. Notter M, Kern T, Forrer A, Meister F, Schwegler N. Radiotherapy of pseudotumor orbitae. Front Radiat Ther Oncol 1997;30:180–91.

Dirençli Orbital Psödo Tümörün CyberKnife Etkin Tedavisi: Olgu Serisi ve Literatürün Kısa Gözden Geçirilmesi Orbital enflamatuvar sendrom veya orbital psödotümör orbital kitlelerin en sık nedenidir. Olguların çoğu steroid yanıtlıdır ancak tedaviye dirençli hastalar radyoterapi seçeneğine sahip olabilirler. Burada başarılı bir CyberKnife tedavisi yaklaşımı ile kısmi steroid cevabı veya nüks gösteren üç orbital psödotümör olgusu sunduk. Anahtar Sözcükler: CyberKnife; orbital psödo tümör; radyoterapi.

DOI: 10.14744/scie.2018.36035 South. Clin. Ist. Euras. 2018;29(3):203-205

Case Report

A Rare Cause of Lung Metastasis Glioblastoma Multiforme Gizem Türkeş, Elif Torun Parmaksız, Nesrin Kıral, Seda Beyhan Sağmen, Ali Fidan, Sevda Cömert

Coşkun Doğan,

Department of Chest Diseases, University of Health Sciences Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey Submitted: 30.05.2018 Accepted: 06.08.2018 Correspondence: Gizem Türkeş, Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Göğüs Hastalıkları Kliniği, İstanbul, Turkey E-mail: gizemturkes@gmail.com

ABSTRACT Glioblastoma multiforme (GBM), comprised of astrocytes, is the most common brain tumor of the central nervous system. Although extracranial metastasis of GBM is very rare (<2%), when it occurs, the lungs are the most common site. Presently described are the cases of 2 male patients, aged 55 and 69 years, who were ultimately diagnosed with pulmonary metastasis of GBM. A lesion that appears to be a primary malignancy on lung imaging may, in fact, be a metastasis. Treatment of the primary malignancy can lead to regression. A detailed anamnesis, evaluation of accompanying diseases, and a pathological diagnosis are of vital importance.

Keywords: Glioblastoma multiforme; lung cancer; lung metastasis.

INTRODUCTION

CASE REPORT

Glioblastoma multiforme (GBM), which is comprised of astrocytes, is the most frequently seen brain tumor of the central nervous system. It constitutes 15.4% of all brain tumors, and 60% to 75% of all astrocytic tumors.[1] The potential for malignancy is high because astrocytes multiply very rapidly and are supported by large vascular networks. These tumors are known to be fast-growing and fatal.[2] Such glial tumors are prone to local recurrence; however, distant intracranial metastasis has been reported in the literature (<2%).[3]

Case 1– In December 2016, a left frontal mass was observed on a computed tomography (CT) image of the brain of a 55-year-old male patient who admitted to the hospital with complaints of forgetfulness and speech impairment (Fig. 1). The patient underwent surgery and total excision of the cranial mass was achieved. The histopathological diagnosis was a high-grade glial tumor.

Extracranial metastases are seen most frequently in the lungs, the posterior cervical soft tissue, and the lumbar intradural space.[4] Metastases are usually seen after resection of the primary tumor.[5] In the presently described cases, a mass lesion suggestive of primary pulmonary carcinoma was detected, but the pathological diagnosis was pulmonary metastasis of GBM.

A thoracic CT performed as part of the preoperative evaluation had revealed a cavitary mass lesion measuring about 6x5 cm with an irregular, thickened wall located in the apical right upper lobe segment of the lung. The radiological appearance was consistent with a primary lung malignancy (Fig. 2). A CT-guided transthoracic needle biopsy was performed. The pathological diagnosis was metastasis of a high-grade glial tumor. Adjuvant radiotherapy (RT) of 30 grays (Gy) administered in 10 fractions was delivered as cranial RT and for the

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patient who complained of headaches and occasional forgetfulness with gradually increasing severity for 6 months. Complete resection of the tumor was performed in July 2017. The histopathological examination revealed that the tumor was consistent with GBM. The patient was then treated with 6 cycles of CT and 28 sessions of RT.

Figure 1. Case 1 – Left frontal mass observed on a computed tomography image of the brain.

A mass lesion was detected in the left main bronchus on a thorax CT image performed following the development of hemoptysis in November 2017. A CT-guided transthoracic needle aspiration biopsy was performed. The histopathological examination of the inguinal biopsy sample was reported as consistent with metastasis of GBM. RT and chemotherapy of 25 Gy in 16 fractions was administered to the site of metastasis (Fig. 3).

DISCUSSION Extracranial metastases of GBM are very rare (<2%). It may, however, occur in the lungs, the soft tissue of the posterior cervical region, or the lumbar intradural space. The lungs are the most common site.[3,4] Pulmonary metastasis of GBM was observed in both of the cases currently presented. GBM is molecularly divided into 2 subtypes: primary GBM and secondary GBM. Secondary glioblastoma, which indicates malignant progression of the astrocytoma, constitutes 5% of GMBs and is seen mostly in young patients.[6] The patients in our case were at 55 and 68 years of age and the tumors were classified as the primary GBM subtype.

Figure 2. Case 1 – A mass lesion measuring approximately 6x5 cm was seen in the apical segment of the upper lobe of the right lung.

Figure 3. Case 1 – Complete regression seen after after 30 grays of radiotherapy delivered in 10 fractions directed at site of metastasis localized in the apical segment of the right lung.

metastatic focus at the apex of the right lung. Follow-up radiological imaging indicated that there was complete regression of the metastatic lesion in the lung. Case 2– A right frontal mass was observed on a cranial magnetic resonance image (MRI) of a 68-year-old male

Extracranial and intracranial metastases of GBM are generally known to occur after resection of the primary tumor, usually about 8.5 months after the diagnosis of the primary tumor.[7] Craniotomy procedures and intraventricular shunting during the operation are thought to enable tumor cells to reach other regions of the body via lymphatic and hematogenous pathways.[5] In Case 1, lung metastasis was detected preoperatively before resection of the cranial tumor. In Case 2, lung metastasis developed after an initial cure was achieved with adjuvant CT and RT after the operation. The treatment modalities for primary tumors and metastases involve surgical procedures and adjuvant chemoradiotherapy directed at the primary tissue.[4] It is thought that the use of chemotherapy after the development of metastasis is particularly helpful to improving survival. Chemotherapy was applied with RT for lung metastasis of GBM in both case 1 and case 2.

CONCLUSION Some theories associated with the developmental pathways of extracranial metastases of GBM have been pro-

Türkeş. Lung Metastasis of Glioblastoma Multiforme

posed, but the mechanism of metastasis has not yet been fully explained. The incidence of extracranial metastasis of GBM has increased in recent years, and this is thought to be due to improved diagnostic devices and methods, as well as extended survival after effective treatment of the primary tumor. Informed Consent Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review Internally peer-reviewed. Authorship Contributions Concept: E.T.P.; Design: G.T.; Data collection &/or processing: C.D.; Analysis and/or interpretation: S.B.S.; Literature search: N.K., A.F.; Writing: G.T.; Critical review: S.S.C. Conflict of Interest None declared.

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REFERENCES 1. Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer 2004:2293–9. 2. Fonkem E, Lun M, Wong ET. Rare phenomenon of extracranial metastasis of glioblastoma. J Clin Oncol 2011;29:4594–5. 3. Yasuhara T, Tamiya T, Meguro T, Ichikawa T, Sato Y, Date I, Nakashima H, et al. Glioblastoma with metastasis to the spleen-case report. Neurol Med Chir (Tokyo) 2003;43:452–6. 4. Taskapilioglu MO, Aktas U, Eser P, Tolunay S, Bekar A. Multiple extracranial metastases from secondary glioblastoma: a case report and review of the literature. Turk Neurosurg 2013;23:824–7. 5. Ray A, Manjila S, Hdeib AM, Radhakrishnan A, Nock CJ, Cohen ML, et al. Extracranial metastasis of gliobastoma: Three illustrative cases and current review of the molecular pathology and management strategies. Mol Clin Oncol 2015;3:479–86. 6. Zhen L, Yufeng C, Zhenyu S, Lei X. Multiple extracranial metastases from secondary glioblastoma multiforme: a case report and review of the literature. J Neurooncol 2010;97:451–7. 7. Lun M, Lok E, Gautam S, Wu E, Wong ET. The natural history of extracranial metastasis from glioblastoma multiforme. J Neurooncol 2011:261–73.

Nadir Görülen Bir Akciğer Metastazı - Glioblastoma Multiforme Glioblastoma multiforme (GBM) astrositlerden köken alan ve merkezi sinir sisteminin en sık görülen beyin tümörüdür. GBM’nin ekstrakraniyal metastazları oldukça nadir görülmekle birlikte (<%2) metastaz yaptığı yerlerin başında akciğer gelir. Bu olgularda akciğerde primer akciğer karsinomu düşündürür. Bu yazıda kitle saptanan ve GBM’nin akciğer metastazı olarak tanı alan 55 ve 69 yaşında iki erkek hasta sunuldu. Akciğer görüntülemesinde primer maligniteyi düşündüren lezyonlar metastaz tanısı alabilmekte ve primer malignitenin tedavisi ile regrese olabilmektedir. Bu nedenle ayrıntılı anamnez, eşlik eden hastalıkların değerlendirilmesi ve patolojik tanı hayati önem arz etmektedir. Anahtar Sözcükler: Akciğer tanseri; akciğer metastazı; glioblastoma multiforme.

DOI: 10.14744/scie.2018.93063 South. Clin. Ist. Euras. 2018;29(3):206-208

Case Report

From Basic Chronic Wounds To Mortal Endings: Squamous Cell Carcinoma Arising from Hidradenitis Suppurativa and Pilonidal Sinus Sedat Öz,1 Gaye Filinte,1 Kaan Gideroğlu,2 Celal Alioğlu,1 Arda Akgün,1 Sultan Yalçın,1 Kübra Kalafatlar,1 Tunç Tunçbilek,1 Cem Sınacı,1 Zeynep Arpacık,1 Bükem Cüce,1 Barış Kanık1

Department of Plastic and Reconstructive Surgery, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey 2 Department of Plastic and Reconstructive Surgery, University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital, İstanbul, Turkey 1

Submitted: 15.02.2018 Accepted: 07.09.2018 Correspondence: Sedat Öz, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Plastik ve Rekonstrüktif Cerrahi Kliniği, İstanbul, Turkey E-mail: oz.sedat@hotmail.com

ABSTRACT Marjolin’s ulcer is an aggressive ulcerating malignancy that arises in a chronic wound and most often takes the form of squamous cell carcinoma (SCC). It often occurs in old burn scars, but it may also develop in post-traumatic lesions or chronic wounds. The prognosis is often poor as a result of delayed diagnosis. Presently described are cases in which chronic hidradenitis suppurativa and pilonidal sinus developed into SCC.

Keywords: Hidradenitis suppurativa; Marjolin’s ulcer; pilonidal sinus; squamous cell carcinoma.

INTRODUCTION Cutaneous squamous cell carcinoma (SCC) is a malignant, invasive, and metastatic skin tumor originating from epidermal keratinocyte cells, and constitutes approximately 20% to 30% of malignant skin tumors.[1] A number of factors may play a role in the etiology of SCC. The most frequently seen are environmental carcinogens such as arsenic, ultraviolet light exposure, fair skin, DNA repair

defects, human papilloma virus infection, immunosuppression, ionizing radiation exposure, and chronic ulcers.[2] Tumors may develop in healthy skin, or they may originate from precursor lesions in cases of Bowen’s disease, actinic cheilitis, Marjolin’s ulcer, leukoplakia, and diseases.[3] Ulcerative lesions in chronic scar tissue were first described by Jean Nicholas Marjolin in 1828, and malignant degeneration was demonstrated by Daccosta in 1903.[4] Marjolin’s ulcer is a rare lesion frequently originating from aggressive,

Öz. SCC from Chronic Basic Wounds

chronic wounds and old scars that then become cancerous growths.[5] Cases of Marjolin’s ulcer have been reported most often in chronic burns (76%), and less frequently (2%), venous ulcers (6.3%), and traumatic injuries (8.1%). [6] The formation typically occurs slowly, but the pathogenesis is not fully understood.[7] Therefore, it is important to monitor chronic wounds carefully and diagnostic biopsies should be performed if there is any suspicion.

CASE REPORT Case 1– A 54-year-old male patient presented at an outpatient clinic to inquire about an area of scarring with an occasional malodorous discharge located in the sacral region that had been present for approximately 30 years. The patient did not have any additional illnesses; however, his history did include 35 pack-years of smoking. The clinical findings were determined to be compatible with hidradenitis suppurativa and medical treatment was planned. A malignant transformation was suspected and a biopsy was performed. The reported result was hyperkeratosis. The patient was reassessed a year later upon worsening of his complaints of discharge and wound dehiscence, and the result of an incisional biopsy was a preliminary diagnosis of SCC and verrucous carcinoma. Magnetic resonance imaging and ultrasound results of the sacrum and regional lymph nodes did not suggest metastasis. A broad area was excised and the material was evaluated by pathologists using frozen section analysis. The result confirmed the diagnosis of SCC. The wound site was repaired with a partial thickness skin graft. No evidence of a recurrent lesion was detected during a year of follow-up. Case 2– A 52-year-old male patient presented at the general surgery clinic with painful and swollen lesions in the gluteal region. The clinical findings were consistent with pilonidal sinus and medical treatment was initiated; however, an optimal response was not obtained. Surgery was performed, and the pathology report for the excised material indicated the presence of pilonidal sinus. Followup for the wound and tissue defect was performed at the polyclinic, and following periodic episodes of exacerbation over the course of a year, a diagnostic biopsy was planned. Debridement was performed and the pathology report of the material indicated a preliminary diagnosis of well-differentiated SCC in the fistula tract. Advanced imaging techniques were used during the follow-up period, and subsequently, extensive excision and reconstruction were planned. The pathology report of the specimen obtained during surgery indicated a finding of well-differentiated SCC that had developed in a pilonidal cyst. Reconstruction was performed using a local flap. No evidence of a recurrent lesion was detected during 2 years of follow-up.

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DISCUSSION Marjolin’s ulcer frequently develops in burn wounds, but it can also originate in chronic lesions such as pressure sores, venous ulcers, or perianal sites of chronic inflammation or hydronephrosis suppurativa that heal with a scar. The most important clinical signs that may suggest the development of Marjolin’s ulcer are rolled wound edges, irregular borders, skin infiltration, and increased pain at the site. Most commonly, it will become well differentiated SCC, but it can also develop into other malignant lesions, such as BCC and sarcomas.[8] The average length of time for malignant transformation is 28.7 years.[9] Clinical suspicion of Marjolin’s ulcer in the presence of risk factors is very important for early diagnosis. In cases of small, noninvasive, well-differentiated tumors, surgical excision and grafting are sufficient. In moderately or poorly differentiated lesions or well- differentiated large and invasive ulcers, broad surgical excision is recommended, and if it is localized on an extremity, amputation may be required.[10] Since SCC is the most common lesion to develop after Marjolin’s ulcer, the lymph nodes and distant organs should be assessed for metastasis. The metastasis rate is approximately 15% and most commonly occurs in the regional lymph nodes. Distant organ metastasis may also occur in the lungs, brain, or spleen. In cases of lymph node or visceral metastasis, the survival rate drops to 35% to 50%.[11] Postoperative oncological treatment may be necessary. The prognosis of Marjolin’s ulcers varies depending on local spread, location, histological type of the ulcer, immune status of the patient, and most importantly, lymph node metastasis.[12] When SCC develops from Marjolin’s ulcer, the prognosis is poorer and the rate of metastasis increases.[13] The average 5-year survival rate is 30%.[14] For early prevention of this condition, diagnostic biopsies are recommended as part of wound care and repeated at frequent intervals and from multiple sites as necessary.[15]

CONCLUSION As demonstrated in this study, awareness of the potential for malignant transformation in a wound over time is important, even though the wound may appear to be no more than a simple lesion. Marjolin’s ulcer is likely to develop into SCC, and the prognosis can be poor. Surgeons and practitioners in other branches frequently encounter chronic wounds and must manage wound care and follow-up. Clinicians should maintain suspicion of a malignant formation in chronic wounds and work with plastic and reconstructive surgery specialists in order to achieve healthy outcomes. Informed Consent Written informed consent was obtained from the patients

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for the publication of the case reports and the accompanying images. Peer-review Internally peer-re viewed. Authorship Contributions Concept: S.Ö., G.F.; Design: S.Ö., A.A.; Data collection &/or processing: S.Ö., K.G., C.A., K.K., T.T., Z.Y., B.C., B.K.; Analysis and/or interpretation: S.Y., C.B.S.; Literature search: S.Ö.; Writing: S.Ö.; Critical review: G.F. Conflict of Interest None declared.

REFERENCES 1. Fishman JR, Parker MG. Malignancy and chronic wounds: Marjolin’s ulcer. J Burn Care Rehabil 1991;12:218–23. 2. Kundakçı N, Erdem C. Lepra ve diğer mikobakteriyel deri infeksiyonları. Dermatoloji’de. In: Tüzün Y, Gürer MA, Serdaroğlu S, Oğuz O, Aksungur, editors. 3rd. İstanbul: Nobel Tıp Kitabevi; 2008. p. 433–58. 3. Hensel KS, Ono CM, Doukas WC. Squamous cell carcinoma in chronic ulcerative lesions: a case report and literature review. Am J Orthop 1999;28:253–6. 4. Da Costa JC. III. Carcinomatous Changes in an Area of Chronic Ulceration, or Marjolin’s Ulcer. Ann Surg 1903;37:496–502. 5. Daya M, Balakrishan T. Advanced Marjolin’s ulcer of the scalp in a

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13-year-old boy treated by excision and free tissue transfer: Case report and review of literature. Indian J Plast Surg 2009;42:106–11. 6. Agale SV, Kulkarni DR, Valand AG, Zode RR, Grover S. Marjolin’s ulcer-a diagnostic dilemma. J Assoc Physicians India 2009;57:593–4. 7. Dupree MT, Boyer JD, Cobb MW. Marjolin’s ulcer arising in a burn scar. Cutis 1998;62:49–51. 8. Calikapan GT, Akan M, Karaca M, Aköz T. Marjolin ulcer of the scalp: intruder of a burn scar. J Craniofac Surg 2008;19:1020–5. 9. Kerr-Valentic MA, Samimi K, Rohlen BH, Agarwal JP, Rockwell WB. Marjolin’s ulcer: modern analysis of an ancient problem. Plast Reconstr Surg 2009;123:184–91. 10. Samira Y, Sérgio H, Michalany NS, de Almeida FA, Jane T. Squamous cell carcinoma in chronic ulcer in lepromatous leprosy. Dermatol Surg 2009;35:2025–30. 11. Karadağ AS, Akdeniz N, Çalka Ö, Çeçen İ, Bayram İ, Ceylan F. Plantar Ülser Zemininde Skuamöz Hücreli Karsinom Gelişen Bir Lepra Olgusu. Dermatoz 2010;1:185–7. 12. Rook’s textbook of dermatology. D. A. Burns, S. M. Breathnach, Neil Cox, Christopher E. Griffiths, editors. 7th. Oxford: Blackwell Publishers; 2004. p. 4568. 13. Huang CY, Feng CH, Hsiao YC, Chuang SS, Yang JY. Burn scar carcinoma. J Dermatolog Treat 2010;21:350–6. 14. Esther RJ, Lamps L, Schwartz HS. Marjolin ulcers: secondary carcinomas in chronic wounds. J South Orthop Assoc 1999;8:181–7. 15. Sabin SR, Goldstein G, Rosenthal HG, Haynes KK. Aggressive squamous cell carcinoma originating as a Marjolin’s ulcer. Dermatol Surg 2004;30:229–30.

Basit Kronik Yaralardan Mortal Sonuçlara; Hidradenitis Suppurativa ve Pilonidal Sinüs Zemininde Gelişen Skuamöz Hücreli Karsinom Marjolin ülseri (MU) yanık ve kronik yara zemininde gelişen, agresif seyreden ve skuamöz hücreli karsinom (SHK) dönüşümü gösteren malign cilt tümörüdür. Daha sıklıkla uzun dönem yanık zemininde görülmekle birlikte travma sonrası ya da kronik diğer yaralarda da karşımıza çıkmaktadır. Genellikle ön tanılarda düşünülmeyip tanısı geç konmakta ve bu yüzden prognozu kötü seyretmektedir. Bu çalışmada, iki olguda uzun dönem takip edilen hidradenitis suppurativa ve pilonidal sinüs lezyonlarının MU zemininde SHK’ya dönüşümü sunuldu. Anahtar Sözcükler: Hidradenitis suppurativa; Marjolin ülseri; pilonidal sinüs; skuamöz hücreli karsinom.

DOI: 10.14744/scie.2018.40412 South. Clin. Ist. Euras. 2018;29(3):209-212

Case Report

Methemoglobinemia After Prilocaine Application During Neonatal Circumcision and Treatment with Ascorbic Acid Nahide Haykır,1

Fatma Narter,1

1 Department of Pediatrics, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey 2 Department of Pediatrics, Osmaniye State Hospital, Osmaniye, Turkey

Submitted: 23.07.2018 Accepted: 31.07.2018 Correspondence: Nahide Haykır, SBÜ, Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Pediatri Kliniği, İstanbul, Turkey E-mail: drnahide@gmail.com

Merve Güllü,2

Mehmet Berk Aslan1

ABSTRACT Methemoglobinemia occurs when the hemoglobin molecule is oxidized from the normal ferrous state to the ferric state. Rarely, it may be a congenital condition (methemoglobin-reductase deficiency), but more frequently it is a result of oxidant exposure. Among the large number of agents that can cause acquired methemoglobinemia is prilocaine, commonly used for local anesthesia during circumcision. Methylene blue is known to be the best treatment option; however it is not always available, and there is no universally accepted alternative. Vitamin C has been reported as an alternative treatment in recent years, but there is no definitive information about efficacy, dose, and renal side effects at high doses. Presently described is the case of an infant who developed cyanosis after a local application of prilocaine during circumcision who was successfully treated with the intravenous administration of vitamin C.

Keywords: Ascorbic acid; methemoglobinemia; newborn; prilocaine.

INTRODUCTION

CASE REPORT

Methemoglobinemia occurs when the normal ferrous state of the hemoglobin molecule is oxidized to a ferric state. Rarely, it may be a congenital condition (methemoglobinreductase deficiency), but more frequently, it occurs as a result of oxidant exposure. Numerous agents have been reported to cause acquired methemoglobinemia, including the application of prilocaine, which is commonly used for local anesthesia in circumcision procedures. It has been established that methylene blue is the optimal treatment; however, alternative treatments include the administration of vitamin C, though there is no clear information about efficacy, dose, or renal side effects at high doses. This report describes a neonatal patient who developed cyanosis after a local prilocaine application during circumcision who was successfully treated with intravenous vitamin C in the absence of methylene blue.

A newborn male patient weighing 3430 g, who was born at term via spontaneous vaginal delivery to a healthy mother and without postpartum problems, was hospitalized in the neonatal unit after pallor and cyanosis were detected at a polyclinic control visit on the 22nd day after birth. The patient had been circumcised that day, including the use of local anesthesia, and there were no problems immediately after the circumcision; however, cyanosis developed approximately 2 hours after the procedure. There was no family history available for the patient. He weighed 3940 g, and exhibited signs of cyanosis with a blood pressure reading of 70/45 mmHg, pulse rate of 144 beats/minute, and a respiratory rate of 60 breaths/minute. Further physical examination findings were normal, and other system examinations were normal. The results of

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the complete blood count were: leukocyte count of 8990/ mm3, hemoglobin count of 12.5 g/dL, hematocrit value of 35%, and a platelet count of 406000/mm3. Routine biochemistry was normal. Additional results were: blood gas Ph of 7.46, pO2 of 52.4 mmHg, HCO3 of 29.5 mmol/L, and lactate level of 3.3 mmol/L. Pulse oximeter readings included a saturation rate of 70% and a methemoglobin (metHb) level of 28.5. Dextrose solution 10% and 10 L/ minute oxygen via hood was administered with a diagnosis of methemoglobinemia. As no methylene blue was available, intravenous 100 mg vitamin C was provided in 20 cc of 10% dextrose for 2 hours. The cyanosis decreased significantly and the metHb level in the blood gas decreased to 12.1% in the first hour and 2.4% in 9 hours. The metHb level was 1.6% on the second day, and the patient was discharged after 48 hours.

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1.3 diphosphoglycerate

NAD+

NADH Cytochrome b5 reductase

Fe+++-hemoglobin (methemoglobin)

Fe++-hemoglobin

NADPH methemoglobin reductase plus exogenous methylene blue

The NADPH diaphorase II system is pharmacologically active and constitutes the basis of methylene blue treatment. [3,4] Exposure to oxidizing agents causes 100 to 1000 times more metHb formation than normal. Infants less than 3 months of age are particularly prone to acquired methemoglobinemia. Hemoglobin F, which is more prevalent in infants, is more susceptible to oxidation than hemoglobin A, and the NADH diaforase I system is immature in infants. Furthermore, the cytochrome b5 metHb reductase activity and concentration are low before 6 months of age. [4,5] Other factors include the higher gastric pH in infants

NADP+

NADPH

Glucose-6-phosphate dehydrogenase

DISCUSSION MetHb is an oxidized and non-oxygen-binding form of hemoglobin. Severe methemoglobinemia is rare, but it is an important potential cause of cyanosis in the very young. The hemoglobin molecule contains 4 ferrous (Fe2+) ions, binds with oxygen and transports it to tissues. When iron is oxidized to a ferric state (metHb or hemoglobin M) it cannot carry oxygen and the oxygen dissociation curve slips to the left, causing tissue hypoxia and lactic acidosis.[1] Erythrocytes contain approximately 1% (0-3%) metHb. It is provided through 2 mechanisms: nicotinamide adenine dinucleotide (NADH) diaphorase I (cytochrome b5 reductase) and glucose-6-phosphate dehydrogenase (G6PD), and via the hexose monophosphate pathway and the nicotinamide adenine dinucleotide phosphate hydrate (NADPH) diaphorase II system (NADPH-reductase metHb). This second pathway for reduction of metHb is mediated by NADPH-(flavin) methemoglobin reductase. It uses NADPH generated by G6PD in the hexose monophosphate (pentose phosphate) shunt as a source of electrons. However, there is normally no electron carrier present in red blood cells to interact with NADPH. As a result, electron acceptors or redox dyes, such as methylene blue, (Fig. 1) can activate this pathway.[2]

glyceraldehyde-3-phosphate Glyceraldehyde phosphate dehydrogenase

6-phospho-gluconate

Glucose-6-phosphate

Figure 1. The major pathway for methemoglobin reduction is via cytochrome b5 reductase (bold arrows). An alternative pathway, which requires an exogenous electron acceptor, such as methylene blue, is via nicotinamide adenine dinucleotide phosphate methemoglobin reductase. Fe: Ferrous; NAD: Nicotinamide adenine dinucleotide; NADH: Nicotinamide adenine dinucleotide + hydrogen; NADP: Nicotinamide adenine dinucleotide phosphate; NADPH: Nicotinamide adenine dinucleotide phosphate hydrate.

and the higher proliferation of nitrate to nitrite-converting bacteria in the gut. The presence of nitrite facilitates the conversion of hemoglobin to metHb.[6] One of the drugs that can cause methemoglobinemia is prilocaine, a sodium channel blocker used as a local anesthetic. Ortho-toluidine, which is a metabolite of prilocaine, can induce methemoglobinemia. The half-life of prilocaine is about 55 minutes, and methemoglobinemia can occur 20 to 60 minutes after drug administration.[7] Prilocaineassociated methemoglobinemia is age- and dose-dependent; doses of 2â&#x20AC;&#x201C;2.5 mg/kg or more are considered a predisposing risk factor. It has been reported in the literature that prilocaine may also cause methemoglobinemia in therapeutic doses, as well as the use of prilocaine-containing creams (EMLA 5%).[3,7] The dose administered in our case was above these doses. An increased metHb level induces clinical symptoms by causing functional anemia and tissue hypoxia. In healthy subjects without anemia, only minor symptoms will appear with a metHb level of less than 15%; however, cyanosis may appear at a level greater than 15%, and at 20% to 45%, mental changes, headache, lethargy, tachycardia, malaise, dizziness, or syncope may be seen. Dysrhythmia, convulsion, coma, and fatalities have been reported at levels exceeding 50%.[3] In our case, the metHb level was 28.5% and

Haykır. Methemoglobinemia After Prilocaine and Treatment with Ascorbic Acid

perioral and peripheral cyanosis, tachypnea, and uneasiness were apparent in the patient. Patient history is important in the diagnosis process. Drug applications that may cause methemoglobinemia should be considered and investigated in cases of oxygen-resistant cyanosis and an absence of cardiopulmonary disease. It is also a clue if the difference between the arterial blood gas oxygen saturation value and that measured with pulse oximetry is more than 5%. Pulse oximeters cannot distinguish between different abnormal hemoglobin types. The blood count should be checked, as anemia aggravates the symptoms, and the lactate level and acid base balance will reveal tissue ischemia. In our case, the lactate level was 3.3 mmol/L, which was slightly high. In patients with methemoglobinemia, blood is chocolate brown or very dark red in color, and this color does not change even when the blood has contact with oxygen. It is also important that fresh samples are used when measuring metHb levels because the count will increase with waiting time. Prevention of further exposure to the oxidizing agent is the first step in treatment. Infants can tolerate a metHb level of 10% to 20% asymptomatically if there is no anemia. [6] Treatment with 1–2 mg/kg methylene blue for 5 minutes is usually recommended in patients with a metHb blood level of >20% if symptomatic, and >30% in asymptomatic patients.[3,4] However, methylene blue is always available in our country for emergency treatment. In addition, methylene blue does not have an effect on the clinic in G6PDdeficient patients and it can trigger hemolysis as a source of oxidant stress. It has also been reported to induce hemolysis in patients without G6PD deficiency.[8] It may be impractical to measure a patient’s G6PD level, particularly in an emergency situation. The use of ascorbic acid is recommended in patients with a known G6PD deficiency. Other potential side effects of methylene blue are chest pain, dyspnea, hypertension, diaphoresis, and a paradoxical increase in the metHb level. Urine may be blue in color because it is excreted via the kidneys, and the dose of methylene blue should be adjusted with consideration for renal function.[3] Although there is an accepted need for an alternative to methylene blue, there is currently no universally accepted alternative for treatment of methemoglobinemia. In recent years, the administration of high-dose vitamin C has been reported to be a fast, safe, and effective option;[1–4] however, concerns about a slow response and renal complications as a result of high doses of vitamin C have deterred use.[8,9] The mechanism of high-dose vitamin C treatment for methemoglobinemia is the reduction of metHb through its antioxidant effect using a non-enzymatic pathway. Intravenous high dose administration of vitamin C is the best way to rapidly increase the plasma concentration of vitamin C. Peak plasma concentration has been achieved

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in less than 1 hour with 10 g or more administered intravenously. Vitamin C administration can increase urinary oxalate excretion and has been reported lead to oxalate nephropathy in patients with renal disease or insufficiency. There is little information available on short-term highdose vitamin C administration in patients with no history of kidney failure.[10] A dose of 100-300 mg/day,[6] or 200500 mg/kg/day has been recommended.[7] In our case, 100 mg was administered intravenously. Vitamin C may also be used orally for long periods to treat congenital methemoglobinemia; however, up to now the dose recommendations remain uncertain.

CONCLUSION Prilocaine, a local anesthetic, may cause methemoglobinemia. That disorder can cause cyanosis and other serious symptoms even at treatment doses in infants 3 months of age and younger. Methemoglobinemia should be considered in the differential diagnosis of oxygen-resistant cyanosis in infants. Vitamin C may be used as a safe alternative to methylene blue treatment for patients without renal insufficiency if methylene blue is unavailable or ineffective/the patient is unresponsive. Informed Consent Written informed consent was obtained from the parents of the patient for the publication of the case report and the accompanying images. Peer-review Internally peer-re viewed. Authorship Contributions Concept: F.N., N.H.; Design: F.N.; Data collection &/or processing: F.N., N.H., M.G.; Analysis and/or interpretation: F.N., N.H., M.A.; Literature search: F.N., N.H.; Writing: F.N., N.H., M.A.; Critical review: F.N., N.H., M.A. Conflict of Interest None declared.

REFERENCES 1. Titheradge H, Nolan K, Sivakumar S, Bandi S. Methaemoglobinaemia with G6PD deficiency: rare cause of persistently low saturations in neonates. Acta Paediatr 2011;100:e47–8. 2. Agarwal N, Nagel RL, Prchal JT. Dyshemoglobinemias. In: Steinberg MH, Forget BG, Higgs DR, editors. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. 2nd. Cambridge University Press; 2009. p. 607–22. 3. Shamriz O, Cohen-Glickman I, Reif S, Shteyer E. Methemoglobinemia induced by lidocaine-prilocaine cream. Isr Med Assoc J 2014;16:250–4. 4. van de Vijver M, Parish E, Aladangady N. Thinking outside of the blue box: a case presentation of neonatal methemoglobinemia. J Perinatol 2013;33:903–4.

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5. Sayın P, Türk Ş, Ünsal O, Dobrucalı UH, Açık E, Hancı A. Sünnet sırasında lokal prilokain kullanımına bağlı methemoglobinemi: Bir olgu sunumu. Şişli Etfal Hastanesi Tıp Bülteni 2012; 46:33–35. 6. DeBaun MR, Frei-Jones M, Vichinsky E. Hemoglobinopathies. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, Behrman RE, editors. Nelson textbook of pediatrics. 19th. Philadelpiha: Saunders; 2016;1662–77. 7. Karavelioğlu A, Şen TA. Lokal prilokaine bağlı methemoglobinemi: olgu sunumu. GÜSBD 2012;1:304–8. 8. Sutter M. Goldfrank’s Manual of Toxicologic Emergencies. Acad

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Emerg Med 2009;16:e7–e8. 9. Ohno S, Ohno Y, Suzuki N, Soma G, Inoue M. High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Anticancer Res 2009;29:809–15. 10. Yurttutan S, Öncel MY, Özdemir R, Canpolat FE, Erdeve Ö, Dilmen U. Methemoglobinemi tedavisinde metilen mavisi kullanılan bir yenidoğanda ciddi hemolize bağlı sarılık: olgu sunumu. JinekolojiObstetrik ve Neonatoloji Tıp Dergisi 2012;8:1391–92. 11. Lee KW, Park SY. High-dose vitamin C as treatment of methemoglobinemia. Am J Emerg Med 2014;32:936.

Sünnette Prilocain İle Lokal Anesteziye Bağlı Askorbik Asit İle Tedavi Edilen Methemoglobinemi: Bir Yenidoğan Olgusu Methemoglobinemi hemoglobin molekülünün normal ferroz durumdan ferik duruma okside olması ile oluşur. Nadiren doğumsal (methemoglobin redüktaz eksikliği) veya daha sıklıkla oksidanlarla karşılaşma sonucu edinsel olarak görülebilmektedir. Edinsel methemoglobinemi yapan çok sayıda ajan bildirilmekte olup, nedenlerinden biri de sünnet pratiğinde lokal anestezi için sık kullanılan prilocain uygulamasıdır. Tedavide kullanılan metilen mavisine ihtiyaç olduğu bilinmekle birlikte genel olarak kabül edilmiş alternatif tedavi yoktur. Bu tedaviler içinde son yıllarda bildirilen C vitaminin; etkinliği, dozu ve yüksek dozda renal yan etkileri konusunda net bilgi bulunmamaktadır. Sünnet sırasında lokal prilocain uygulaması sonrası siyanoz gelişen yenidoğan olgusu metilen mavisi bulunamadığı için intravenöz vitamin C ile başarı tedavi edilmesi nedeniyle sunulmuştur. Anahtar Sözcükler: Askorbik asit; methemoglobinemi; prilocain; sünnet; yenidoğan.

DOI: 10.14744/scie.2018.57966 South. Clin. Ist. Euras. 2018;29(3):213-216

Case Report

Plasmablastic Lymphoma of the Maxillary Sinus Causing Orbital Complication Sedat Aydın,1 Nazmiye Ünlü,1 Emine Gültürk,2 Nagehan Özdemir Barışık,3 Begüm Başlı3

Department of Otolaryngology, Heath Sciences University Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey 2 Department of Hematology, Heath Sciences University Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey 3 Department of Pathology, Heath Sciences University Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

Hakan Avcı,1

Submitted: 10.12.2017 Accepted: 28.12.2016 Correspondence: Sedat Aydın, SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi KBB Kliniği, İstanbul, Turkey E-mail: sedataydin63@yahoo.com

ABSTRACT Plasmablastic lymphoma (PBL) is a rarely seen diffuse large B cell lymphoma variant associated with acquired immunodeficiency syndrome, oral mucosa localization, and a poor prognosis. There is not yet a standard protocol for the treatment of PBL; the treatment of a small number of human immunodeficiency virus (HIV)-negative cases has been reported in case reports and series and shared on a case-by-case basis. Presently described is the case of a 60-year-old man with PBL that originated in the sinus and spread to the orbit. The patient was HIV-negative and immunocompetent. The treatment and follow-up are presented in the context of the available literature.

Keywords: Complication; HICV-negative; maxillary sinus; nasal obstruction; orbita; plasmablastic lymphoma.

INTRODUCTION Plasmablastic lymphoma (PBL) is characterized by excessive proliferation of cells that morphologically resemble immunoblasts and antigenically demonstrate a plasma cell phenotype. It is also a rare subtype of large B cell lymphomas with poor prognosis. The male-to-female ratio in PBL is 1.9:1, which may be seen in HIV-negative cases, although it is usually extranodal in HIV-positive cases.[1,2] Symptoms of B cell lymphomas are seen in 33% of HIVpositive and 50% in HIV-negative cases. In addition, the Ki-67 index is usually >90%. Epstein–Barr virus-encoded RNA (EBER) positivity supports PBL. Chemotherapy is

administered as the initial treatment. The most important factor affecting the prognosis is the amount of response given to chemotherapy, and the average life span for untreated patients is 3 months.[3,4]

CASE REPORT A 60-year-old male patient presented to our clinic with nasal obstruction on the right side, frontal growth in the right eye, blurred vision, and impaired balance. The patient’s father and uncle had lung cancer, and two brothers had passed away due to colon cancer. Proptosis in the right eye, limitation in inward gaze, and decrease in visual acuity were observed.

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The pupils were isochoric. Direct light reflex was negative in the right eye and positive in the left eye, whereas indirect light reflex was positive in the right eye and negative in the left eye. On nasal endoscopic examination, septum deviation in the right nasal cavity and posterior to the nasal septum a pale-colored mass with lobular contours, which completely filled the nasal cavity and whose source could not be clearly defined, were observed. There was lymphadenopathy of approximately 1 cm in size in the right submandibular region that was painless on palpation. The patient’s hematological values were remarkable. They were as follows: white blood cell 9300/mm3, hemoglobin 13.6 g/dL, platelets 257,000/mm3, sedimentation rate 30 mm/h, and C-reactive protein 11,5 md/L. Other biochemical test results were within normal limits, and serology tests for HbsAg, anti-HBs, anti-HCV, and anti-HIV were negative. A nasal mass with a diameter of 75×28 mm disrupted the integrity of the medial wall of the right orbita was observed on paranasal sinus computed tomography (CT) and this lesion completely filled the maxillary, ethmoid sinuses and nasal cavity and also partially the right half of the frontal sinus extending into the sphenoid sinuses on facial magnetic resonance imaging (MRI) (Fig. 1a and b). Informed consent was obtained from the patient. On endoscopic examination, under general anesthesia, we en(a)

(d)

(b)

countered a pale, lobular, fragile, and hemorrhagic mass affecting the middle concha in the right nasal cavity that invaded the lamina papyracea, orbit, and paranasal sinuses. The mass was excised so as to ensure nasal respiration of the patient. Histopathological sections showed diffuse proliferation, pleomorphic large hyperchromatic nuclei with prominent nucleoli, and large cells with eosinophilic cytoplasm. Infiltrating cells were CD38 and CD138-positive, whereas CD20, CD56, and CD3 were negative, and EBER was positive. Ki-67 proliferative indexes were >90%. Owing to the findings, the present case was interpreted as PBL (Fig. 1c-f). Patient underwent positron emission tomography (PET)– CT after consultation with the hematology clinic. PET-CT revealed intensely hypermetabolic (SUDmax: 21.0) spaceoccupying lesion measuring approximately 30×40×50 mm of primary malignant involvement that completely obliterated the frontal sinus and right ethmoid sinus and partially the right maxillary sinus and a moderately hypermetabolic lymph node (SUDmax: 5.5) measuring approximately 8 mm in diameter in the right submandibular lymphatic loge, suggesting the involvement of primary disease. At 28-day intervals, 6 cycles of chemotherapy regimen using the EPOCH protocol (dose-increasing etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisolone) were administered by the hematology clinic to (c)

(e)

(f)

Figure 1. (a) Coronal section of paranasal sinus CT shows invasion of the mass stemming from the maxillary sinus into orbit and other sinuses. (b) On the facial MRI T1 coronal section, diffuse invasion of the mass into the right nasal passages, maxillary sinuses, orbits, and other sinuses is observed. (c) Histopathological appearance of plasmablastic lymphoma is stained with hematoxylin and eosin (×40). (d) Histopathologically, CD138 positivity of the plasmablastic lymphoma is observed (×40). (e) Immunohistochemical staining with Ki-67, high proliferative index (×40). (f) Histopathologically, EBER has been shown to have an in situ hybridization positivity.

Aydın. Plasmablastic Lymphoma of the Maxillary Sinuse

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the patient who did not demonstrate any evidence for involvement of lymphoma in the bone marrow biopsy specimen. In addition, intrathecal methotrexate therapy was applied for central nervous system prophylaxis. When the patient was evaluated 1 month after chemotherapy, proptosis of the right eye and limitation of inward gaze proceeded. At the control visit after 3 months, face MRI demonstrated considerable regression of the lesion, and face MRI and PET–CT showed complete response after 6 months. The patient under our surveillance is currently in remission for 2 years without recurrence.

gastrointestinal tract, skin, and lymph nodes in HIV-negative individuals has been reported.[6-9] The majority of the cases were stage 4, followed by stage 1 disease. As in our case, bone marrow involvement is rare.[10–13] EB virus infection is present in 74% of the cases, and there is no standard chemotherapy regimen currently accepted for PBL. [5,9,14] Although in patients with extranodal involvement the median survival is <1 year, our patient is in remission and is followed up by the hematology clinic for 2 years without disease recurrence.

DISCUSSION PBL is a rare, rapidly progressive form of diffuse large B cell lymphomas and is often observed with jaw and oral mucosal involvement in HIV-positive cases. A small part of cases consist of HIV-negative cases, patients under immunosuppressive treatment after tissue–organ transplantation, patients with congenital immunosuppression, and patients with advanced age. It is especially important that PBL is shared on a case-by-case basis, as it is seen even more rarely in immunocompetent patients.[2] PBL should be considered in the differential diagnosis of benign (nasal polyposis, mucus retention cysts, sinonasal papillomas, and juvenile nasopharyngeal angiofibromas) and malignant (epidermoid carcinoma, adenoid cystic carcinoma and adenocarcinoma, lymphoma, melanoma, esthesioneuroblastoma, undifferentiated carcinoma, sarcoma, and plasmacytoma) pathologies originating from the paranasal sinuses. We should often think of malignant pathologies in the presence of symptoms and signs of nasal obstruction, pain, history of epistaxis, malodorous bloody nasal discharge, cheek swelling, diplopia, proptosis, malformations, and loss of maxillary teeth. On the other hand, in these cases, we encounter radiological evidence of invasion in the sinuses as opacification, softening of the surrounding structures, and erosion in the bone tissues.[5] It was determined that the majority of the above symptoms and signs were present in our patient, and also the integrity of the medial wall of the right orbita was disrupted as revealed in radiological imaging. Histopathologically, diffuse large B cell lymphoma, PBL, and plasmablastic myeloma were considered in the differential diagnosis. The absence of CD20 positivity excluded the possible diagnosis of diffuse large B cell lymphoma. Detection of EBERpositive tumor cells, high Ki-67 proliferation index, CD56 negativity, and absence of bone marrow involvement also ruled out the diagnosis of anaplastic plasmacytoma. In the meta-analysis of many case reports and studies, an increased incidence of PBL in the nasal cavity and sinus,

In conclusion, PBL is a rare, rapidly progressive variant of diffuse large B cell lymphomas. Until treatment becomes standardized, the selection and outcome of the chemotherapy protocol will vary based on individual cases. Orbital involvement secondary to primary sinus lymphoma is rare, but it is possible that the clinician will discern these rarely seen cases after the evaluation of the clinical signs and symptoms specific to non-Hodgkin lymphoma together with the nasal cavity mass. Informed Consent Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review Internally peer-re viewed. Authorship Contributions Concept: S.A., N.Ü.; Design: S.A., H.A., E.G.; Data collection &/or processing: N.Ü., B.B., H.A.; Analysis and/or interpretation: S.A., N.Ö.B., N.Ü., E.G.; Literature search: S.A.; Writing: S.A., E.G.; Critical review: S.A., E.G. Conflict of Interest None declared.

REFERENCES 1. Delecluse HJ, Anagnostopoulos I, Dallenbach F, Hummel M, Marafioti T, Schneider U, et al. Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. Blood 1997;89:1413–20. 2. Liu JJ, Zhang L, Ayala E, Field T, Ochoa-Bayona JL, Perez L, et al. Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma: a single institutional experience and literature review. Leuk Res 2011;35:1571–7. 3. Folk GS, Abbondanzo SL, Childers EL, Foss RD. Plasmablastic lymphoma: a clinicopathologic correlation. Ann Diagn Pathol 2006;10:8–12. 4. Akı H, Difüz Büyük B Hücreli Lenfoma Patolojisi. Klinisyen-Patolog Ortak Lenfoma Kursu 2004;63–75. 5. Citardi MJ, Batra PS. The nose and paranasal sinuses. In: Lee KJ. Essential otolaryngology: head & neck surgery. 9th ed. New York: McGraw-Hill; 2008. p. 365–412. 6. Scheper MA, Nikitakis NG, Fernandes R, Gocke CD, Ord RA, Sauk JJ. Oral plasmablastic lymphoma in an HIV-negative patient: a case

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report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:198–206. 7. Saraceni C, Agostino N, Cornfield DB, Gupta R. Plasmablastic lymphoma of the maxillary sinus in an HIV-negative patient: a case report and literature review. Springerplus 2013;2:142. 8. Basavaraj A, Kadam M, Kadam DB. Primary Maxillary Sinus Plasmablastic Lymphoma in HIV/AIDS. J Assoc Physicians India 2016;64:71–2. 9. Kim JE, Kim YA, Kim WY, Kim CW, Ko YH, Lee GK, et al. Human immunodeficiency virus-negative plasmablastic lymphoma in Korea. Leuk Lymphoma 2009;50:582–7. 10. Choi SY, Cho YA, Hong SD, Lee JI, Hong SP, Yoon HJ. Plasmablastic lymphoma of the oral cavity in a human immunodeficiency virusnegative patient: a case report with literature review. Oral Surg Oral

Med Oral Pathol Oral Radiol 2014;117:e115–20. 11. Hatanaka K, Nakamura N, Kishimoto K, Sugino K, Uekusa T. Plasmablastic lymphoma of the cecum: report of a case with cytologic findings. Diagn Cytopathol 2011;39:297–300. 12. Cao C, Liu T, Zhu H, Wang L, Kai S, Xiang B. Bortezomib-contained chemotherapy and thalidomide combined with CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) play promising roles in plasmablastic lymphoma: a case report and literature review. Clin Lymphoma Myeloma Leuk 2014;14:e145–50. 13. Lin L, Zhang X, Dong M, Li L, Wang X, Zhang L, et al. Human immunodeficiency virus-negative plasmablastic lymphoma: A case report and literature review. Medicine (Baltimore) 2017;96:e6171. 14. Reagan L, Castillo JJ, Reagan JL. Plasmablastic lymphoma: a systematic review. ScientificWorldJournal 2011;11:687–96.

Orbital Komplikasyona Yol Açan Maksiller Sinüs Plazmablastik Lenfoması Nadir görülen plazmablastik lenfoma (PBL) AIDS ile ilişkili, oral mukoza yerleşimli, kötü prognozlu, diffüz büyük B hücreli lenfoma varyantı olarak kabul edilmektedir. Plazmablastik lenfomanın henüz tedavisinde standart bir protokol olmaması, olgu bildirimi ve çalışmalar halinde yapılan az sayıda HIV negatif olguların tedavisi olgu bazlı olarak yapılmakta ve paylaşılmaktadır. Bu yazıda maksiller sinüs kaynaklı ve orbitaya yayılmış olan PBL’li 60 yaşında erkek, HIV negatif ve immün kompetan hastamıza uyguladığımız tedavi ve takip süreci literatür bilgileri eşliğinde sunulmuştur. Anahtar Sözcükler: Burun tıkanıklığı; HIV negatif; komplikasyon; maksiler sinüs; orbita; plazmablastik lenfoma.

DOI: 10.14744/scie.2018.04127 South. Clin. Ist. Euras. 2018;29(3):217-219

Case Report

Treatment of Subdeltoid Calcific Bursitis with Ultrasound-Guided Percutaneous Lavage Esra Dilşat Bayrak,1

Department of Rheumatology, İstanbul Fatih Sultan Mehmet Training and Research Hospital, İstanbul, Turkey 2 Department of Physical Medicine and Rehabilitation, İstanbul Fatih Sultan Mehmet Training and Research Hospital, İstanbul, Turkey

İlknur Aktaş,2

Feyza Ünlü Özkan2

Submitted: 31.07.2018 Accepted: 11.09.2018 Correspondence: Esra Dilşat Bayrak, İstanbul Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi Romatoloji Kliniği, İstanbul, Turkey E-mail: drdilsat@hotmail.com

Keywords: Calcific bursitis; shoulder pain; percutaneous lavage; steroid injection; ultrasound.

ABSTRACT Calcific bursitis most commonly affects the subacromial and trochanteric bursae. Patients most often present at the hospital because of increased pain at night and when performing overhead activities. A physical examination of the shoulder typically reveals restriction in abduction and internal rotation. Pain is usually observed during the resorption phase of the deposit. Chronic pain is also related to the inflammatory process caused by calcification. Calcified lesions in a bursa or tendon are not always visible on an X-ray, and may not be apparent among physical examination findings. Small and scattered deposits can often be detected on an X-ray; however, a calcific slurry mass in the subacromial-subdeltoid bursa can be found more reliably with ultrasonography (US) than with plain film. Pain is often resistant to steroid injections. In symptomatic patients, US-guided fragmentation of the lesion with a needle, using a local anesthetic, saline lavage, and a steroid injection, can often achieve complete healing in a very short period of time. Presently described is successful treatment of a calcified lesion located in the subdeltoid bursa achieved by performing lavage, splitting the calcified lesion, and administering a steroid injection.

INTRODUCTION Shoulder pain affects about 1% of people over 45 years of age.[1] Most often, the pain is caused by rotator cuff or bursa pathologies in the subdeltoid region. Subdeltoid bursa inflammation in this region may be a result of trauma, long-term pressure, overuse, crystal arthropathy, inflammatory arthritis, or infection. Pain caused by subdeltoid bursitis typically occurs during rest, becomes more apparent with use, and then may be so severe as to disrupt sleep. It may result in adhesive capsulitis in the long term. Superficially localized lesions (olecranon, prepatellar, retrocalcaneal) may produce symptoms that are evident during a physical examination, while deep lesions (subdeltoid, anserine bursitis, trochanteric) may not yield physical findings suggesting the presence of bursitis. In such cases, diagnostic tests, such as direct radiography, ultrasonography (US), computed tomography, and magnetic resonance

imaging (MRI), may prove useful. US can be valuable in making the diagnosis and in providing treatment at the site. The goal is to relieve the pain and to provide full range of shoulder movement. This report describes the successful treatment of a patient with bursitis that was the result of a calcified lesion in the subdeltoid bursa. Splitting the calcific lesion, performing percutaneous lavage, and administering a steroid injection led to complete recovery.

CASE REPORT A 63-year-old woman had admitted to another clinic with pain and restriction of movement in the right shoulder during overhead activities nearly 3 months earlier. The patient’s shoulder MRI demonstrated impingement findings, so she was included to a physical therapy program. She

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admitted to our clinic because of a lack of improvement in her complaints. A physical examination revealed swelling of the shoulder without redness and an increase in local temperature with restricted shoulder flexion and internal rotation. Neer and Hawkins tests were positive. Muscle strength and neurological examination values were within normal limits. Acute phase reactant levels (sedimentation, C-reactive protein, uric acid, calcium, phosphate, whole blood, renal function tests, thyroid-stimulating hormone, and parathormone) were within normal limits for patients without any known systemic disease and drug use. Tests performed for autoantibodies (rheumatoid factor, anticyclic citrulline protein antibody) yielded negative results. No pathology of the shoulder was observed on direct radiogram; however, the increased power Doppler signal intensity observed on US revealed a subdeltoid bursal effusion with a large calcific lesion in the bursa (Fig. 1). The effusion in the subdeltoid bursa was drained with US guidance, the calcific lesion was fragmented using a 21-G needle, 2 cc 2% lidocaine and 2 cc saline were injected into the bursa, and the cavity was irrigated once again. Betamethosone 6 mg was then injected into the bursa. At a follow-up visit 1 week later, the pain and restriction of movement had been completely resolved. Repeated US demonstrated complete regression of the calcified lesion and the bursitis.

DISCUSSION Calcific bursitis is frequently seen in the subdeltoid bursa and the trochanteric bursa. Patients typically present with pain aggravated by overhead movements, and a physical examination usually reveals restricted abduction and internal rotation of the shoulder. Calcification of the rotator cuff and bursa can take many forms. Large calcific foci may be hard or soft. Calcification is thought to have various phases. The first accumulation occurs in a harder form. Subsequently, the calcification is disintegrated or softened in the inflammatory resorptive phase. There may be severe pain during this phase. This is followed by the postcalcific phase.[2] Often, chronic pain is also the result of inflammation as a result of calcification. (a)

(b)

In many cases, the pain is resistant to steroid injections. Large, muddy calcifications and bursal calcifications can be detected better with US than direct graphy, while small, scattered deposits have a high direct radiogram detection rate.[3] US is very useful in the evaluation of pathologies of the rotator cuff, biceps tendon, and bursa of the shoulder. In cases of shoulder impingement, dynamic assessment and therapeutic interventions are also possible. It has been reported that 25% to 30% of blind injections do not reach the bursa, and this can lead to false negative results.[4] The available data suggest that injections performed with US guidance are much more effective than blind injection.[5] Surgical interventions have also been performed in addition to conservative approaches (steroid and anesthetic injections). Two supraspinatus calcific lesions were reported to have completely regressed with steroid injections after lavage.[6] In another case report, successful treatment of calcific bursitis in the medial collateral bursa was achieved with percutaneous lavage using US guidance. [7] Furthermore, a study of 431 patients with calcific tendinitis of the rotator cuff indicated that needle aspiration of calcific deposits was successful.[8] In the present case, the patient arrived with right shoulder pain and physical examination revealed restricted abduction and internal rotation. A large calcific lesion and bursitis were observed on the US image in the subdeltoid bursa; however, the direct radiogram had not revealed any pathology. The subdeltoid bursa was located and penetrated with a needle using US guidance, and the calcific lesion was disintegrated. Subsequently, a local anesthetic and saline were injected into the bursa, and the area was irrigated. An intrabursal steroid injection was administered, and at follow-up 1 week later, the patient reported that she had no pain, and the physical examination and ultrasound findings confirmed complete resolution. As demonstrated in this case, calcified lesions in structures such as bursa and the tendons do not always appear on direct radiograms, and physical examination findings are not discriminative. US imaging is very valuable in these (c)

Figure 1. (a, b) The initial ultrasound image, which demonstrates a calcific lesion, effusion, and increased signal intensity in the subdeltoid bursa. (c) Ultrasonographic images obtained 1 week after treatment.

Bayrak. Calcific Bursitis and Ultrasound-Guided Percutaneous Lavage

cases. In symptomatic patients, US-guided disintegration of the lesion with a needle, using local anesthetic, saline lavage, and steroid injection can achieve complete healing in a very short time. Informed Consent Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review Internally peer-reviewed. Authorship Contributions Concept: E.D.B., İ.A.; Design: E.D.B., İ.A.; Data collection &/or processing: E.D.B., İ.A.; Analysis and/or interpretation: E.D.B., F.Ü.Ö.; Literature search: E.D.B., F.Ü.Ö.; Writing: E.D.B., İ.A.; Critical review: İ.A., F.Ü.Ö. Conflict of Interest None declared.

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2. Henkus HE, Cobben LP, Coerkamp EG, Nelissen RG, van Arkel ER. The accuracy of subacromial injections: a prospective randomized magnetic resonance imaging study. Arthroscopy 2006;22:277–82. 3. Farin PU, Jaroma H. Sonographic findings of rotator cuff calcifications. J Ultrasound Med 1995;14:7–14. 4. Uhthoff HK, Loehr JW. Calcific Tendinopathy of the Rotator Cuff: Pathogenesis, Diagnosis, and Management. J Am Acad Orthop Surg 1997;5:183–191. 5. Hsieh LF, Hsu WC, Lin YJ, Wu SH, Chang KC, Chang HL. Is ultrasound-guided injection more effective in chronic subacromial bursitis? Med Sci Sports Exerc 2013;45:2205–13. 6. Farin PU, Jaroma H, Soimakallio S. Rotator cuff calcifications: treatment with US-guided technique. Radiology 1995;195:841–3. 7. Del Castillo-González F, Ramos-Álvarez JJ, González-Pérez J, Jiménez-Herranz E, Rodríguez-Fabián G. Ultrasound-guided percutaneous lavage of calcific bursitis of the medial collateral ligament of the knee: a case report and review of the literature. Skeletal Radiol 2016;45:1419–23. 8. Oudelaar BW, Schepers-Bok R, Ooms EM, Huis In ‘t Veld R,

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Subdeltoid Kalsifik Bursitin Ultrason Eşliğinde Perkütan Lavaj İle Tedavisi Kalsifik bursit, sıklıkla subakromial ve trokanterik bursada izlenmektedir. Omuzda gözlendiğinde hastalar genellikle istirahat, hareketlerle ve gece artan ağrı nedeniyle başvurmakta, fizik muayenede omuz hareketleri kısıtlanmaktadır. Ağrı genellikle depozitin rezolüsyon fazında izlenmektedir. Kronik ağrı aynı zamanda kalsifikasyon nedeniyle oluşan enflamasyon sonucu oluşmaktadır. Bursa, tendon gibi yapılarda kalsifik lezyonlar her zaman MRG ve direkt grafilerde bulgu vermez, fizik muayene bulguları da ayırt edici olmamaktadır. Büyük çamursu kalsifikasyonlar ve bursal kalsifikasyonlar ultrasonografi ile çok daha iyi saptanır, küçük ve dağınık depozitlerin ise direkt grafide görülme oranı daha yüksektir. Birçok olguda ağrı birçok durumda steroid enjeksiyonlarına dirençli olmaktadır. Semptomlu hastalarda lezyonun iğne ile parçalanması, lavajı ve steroid enjeksiyonu ile çok kısa sürede komplet iyileşme sağlanabilmektedir. Bu yazıda, subdeltoid bursa içinde kalsifik lezyonu ve bursiti olan hastanın ultrason eşliğinde yapılan girişimle kalsifik lezyonun parçalanarak bursa içine lavaj yapılması ve sonrasında steroid enjeksiyonu yapılarak başarılı bir şekilde tedavisi sunuldu. Anahtar Sözcükler: Kalsifik bursit; omuz ağrısı; perkütan lavaj; steroid enjeksiyonu; ultrasonografi.