Acta Medica Anatolia 2016 Volume 4 Issue 3

Acta Medica Anatolia

Volume 4 Issue 3 Year 2016

JOURNAL INFO

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EDITORS Assoc. Prof. Dr. Aytekin Alcelik

ASSISTANT EDITORS

Assoc. Prof. Dr. Nadir Goksugur Assoc. Prof. Dr. Alim Erdem,

Publication Committee Prof. Dr. Aiji Ohtsuka,

Department of Anatomy, Okayama University School of Medicine, Japan.

Prof. Dr. PhD. Selma Uzunovic, Cantonal Public Health Institute Zenica Chief,

Department for Laboratory Diagnostics Fra Ivana Jukica, Zenica, Bosnia and Herzegovina.

Prof. Dr. Noboru Yamanaka, Wakayama Medical University, Japan.

Assoc. Prof. Dr. Serkan Ozturk,

Abant Izzet Baysal University, School of Medicine, Cardiology Department, Turkey.

Assist. Prof. Satoshi Hirohata, Department of Molecular Biology and Biochemistry, Okayama, Japan.

Prof. Dr. PhD. Manabu Nemoto,

Director of Shock & Trauma Center Saitama International Medical Center, Japan.

Dr. PhD. Suleyman Gulsuner, University of Washington, United States.

Dr. Yoko Bekku,

Departments of Neuroscience Institute and Neuroscience, New York University, United States.

Scientific Advisory Board Assoc. Prof. Dr. Toshitaka Oohashi,

Department of Molecular Biology and Biochemistry, Okayama, Japan.

Prof. Dr. Hakan Ozhan, Duzce University, School of Medicine, Department of Cardiology, Turkey.

Assoc. Prof. Dr. Mehmet Akkaya,

Minnesota University, Medical School, United States.

Prof. Dr. Mustafa Aydin, Bulent Ecevit University, Cardiology Department, Turkey.



Prof. Dr. Hayrettin Akdeniz, Abant Izzet Baysal University, Infectious Disease Department, Turkey.

Assoc. Prof. Dr. Davut Baltaci, Duzce University, Department of Family Medicine, Turkey.

Assoc. Prof. Dr. Gulali Aktas,

Abant Izzet Baysal University, Internal Medicine Department, Turkey.

Assist. Prof. Dr. Tomoko Yonezawa, Molecular Biology and Biochemistry Okayama University School of Medicine, Japan.



Table of Contents

ORIGINAL ARTICLE

1. The Effects of Initial cortisol levels and Vitamin D on Mortality and Hospital Infection Development in Geriatric Patients at Intensive Care Unit Leyla Kutlucan, Ali Kutlucan doi: 10.5505/actamedica.2016.98159 Pages 93 - 97

Abstract | Full Text PDF

2. Acinetobacter Infection and Resistance Profile of Intensive Care Units In a City of Northwestern Anatolia İsa Yıldız, Hakan Bayır, Abdulkadir Küçükbayrak, Hamit Yoldaş, Mehmet Balcı, Mansur Kürşat Erkuran, Kadir Korkmaz Akkaya, Aliye Yaşayacak doi: 10.5505/actamedica.2016.52714 Pages 98 - 100


3. Screening Cytomegalovirus Infections in First Trimester of Gestation Among High Prevalence Population Akın Usta, Mine Islimye Taskin, Ceyda Sancakli Usta, Eylem Sen Dalkiran, Osman Kilinc, Elif Dus doi: 10.5505/actamedica.2016.53215 Pages 101 - 106


4. Relationship between Prostate Size and Positive Surgical Margin in the Open Radical Prostatectomy Surgery Mehmet Emin Özyalvaçlı, Ramazan Kocaaslan, Ugur Yücetaş, Erkan Erkan, Ali Feyzullah Şahin, Mustafa Kadıhasanoğlu, Yusuf Şahin, Erdinç Ünlüer doi: 10.5505/actamedica.2016.30502 Pages 107 - 111


5. Thyroid Masses: An Analysis of 135 Cases Engin Şengül, Beyhan Yılmaz, Musa Özbay, İsmail Topçu doi: 10.5505/actamedica.2016.25349 Pages 112 - 117


6. Quantitative Comparison of 2D and 3D MRI Techniques for the Evaluation of Chondromalacia Patellae in 3.0T MR Imaging of the Knee Ali Özgen, Zeynep Fırat doi: 10.5505/actamedica.2016.81905 Pages 118 - 123


http://www.anatoliamedica.com/jvi.aspx?pdir=actamedica&plng=eng&un=ACTAMED-98159


http://dx.doi.org/10.5505/actamedica.2016.98159

http://www.anatoliamedica.com/jvi.aspx?pdir=actamedica&plng=eng&un=ACTAMED-98159&look4=

http://www.journalagent.com/z4/download_fulltext.asp?pdir=actamedica&plng=eng&un=ACTAMED-98159




























ANATOLIAN HISTORY OF MEDICINE

7. The Importance of Informatics for Health Care Industry Abdullah Talha Kabakuş, Resul Kara doi: 10.5505/actamedica.2016.81300 Pages 124 - 125


CASE REPORTS

8. Brucellar Arthritis Involving Left Sternoclavicular Joint Senem Şaş, Hatice Rana Erdem, Burcu Uysal doi: 10.5505/actamedica.2016.72691 Pages 126 - 128


9. Pilomatrixoma Localized in the Right Preauricular Region Murat Şereflican, Betül Şereflican, Sinan Seyhan, Nadir Göksügür, Fahri Yılmaz doi: 10.15824/actamedica.2016.78309 Pages 129 - 131


LETTER

10. Bilateral Temporomandibular Joint Dislocation Secondary to Epileptic Seizure Fatma Aktaş, Zafer Özmen, Turan Aktaş, Ayşegül Altunkaş, Fitnet Sönmezgöz, Eda Albayrak doi: 10.15824/actamedica.2016.83803 Pages 132 - 134


11. Acute Inferior Wall Myocardial Infarction with Anaphylactic Shock Due to Bee Sting: What Should We Do? Hüseyin Katlandur, Hüseyin Özdil, Şeref Ulucan, Ahmet Keser, Kerem Özbek doi: 10.5505/actamedica.2016.96168 Pages 135 - 136

























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Original Article Acta Medica Anatolia

Correspondence: Leyla Kutlucan, Department of Anesthesiology, Konya Training and Research Hospital, Konya, Turkey Conflict of Interest: NoneE-mail: [email protected]

Volume 4 Issue 3 2016

Leyla Kutlucan1, Ali Kutlucan2

1 Department of Anesthesiology, Konya Training and Research Hospital, Konya, Turkey2 Department of Internal Medicine, Selcuk University, School of Medicine, Konya, Turkey

Introduction: Vitamin D deficiency is a common problem throughout the world. Also vitamin D deficiency has been reported in up to 82% of patients in intensive care unit (ICU). In addition, corticosteroid insufficiency is a common problem in ICU patients. In this study, we investigated the effects of initial cortisol and vitamin D levels on mortality, hospital infection development and intubation status in geriatric ICU patients.

Methods: This study was conducted in a tertiary ICU. In a one-year period, 117 consecutive ICU patients older than 65 years of age were evaluated retrospectively. Looking at the first with Vitamin D and cortisol levels of the patients were collected in the first 24 hours of hospitalization. At follow up period, relationship between these data’s and mortality, hospital infection, and intubation conditions were evaluated.

Results: Initial Vitamin D, the morning cortisol, and albumin levels were found to be significantly lower (respectively; p <0.001, p <0.001 and p <0.001), and lactate levels were found to be significantly higher (p <0.001) in patients who died in ICU than alive patients. Development rate of hospital-acquired infection was found to be significantly higher (p = 0.025) in patients with low vitamin D levels than alive patients. Vitamin D and cortisol levels were found to be lower and lactate levels were found to be higher (respectively: p <0.001, p = 0.004, p = 0.035) in intubated patients than alive patients.

Conclusion: In geriatric patients, relationship between initial vitamin D and cortisol levels and mortality, hospital infection and intubation conditions were evaluated in our study for the first time. The low level of vitamin D is seen as an important risk factor for the mortality, development of hospital-acquired infections and intubation. Also it is determined that the low cortisol creates a negative situation in terms of mortality and intubation.

Keywords: Intensive Care Unit, Geriatric Patients, Vitamin D, Cortisol, Mortality, Hospital Infection.

Received: 06.03.2016 Accepted: 13.04.2016

doi: 10.5505/actamedica.2016.98159

Abstract

The Effects of Initial Cortisol Levels and Vitamin D on Mortality and Hospital Infection Development in Geriatric Patients at Intensive Care Unit

Introduction

Vitamin D is a fat-soluble vitamin, is synthesized in the skin by the sunlight effect, and is taken via diet in small amounts. Vitamin D which is in a steroidal structure plays important role in bone metabolism. Vitamin D regulates inflammation, immunity, cell division, apoptosis, and angiogenesis with its pleiotropic activity (1-3).

Vitamin D deficiency is a common problem all over the world, and it can be frequently observed in hospitalized patients. It has been shown that vitamin D deficiency is associated with increase in morbidity and mortality in various systemic diseases (4,5). Vitamin D deficiency has been reported to be prevalent between 26-82% in the intensive care unit (ICU) patients (6,7). As a result of that high rate of deficiency, positive pleiotropic activity of vitamin D cannot be occurred and problems about natural immunity, mucosal barrier, and endothelial

dysfunction appear. It has been shown that low level of vitamin D has emerging association with severity of the disease, mortality, and short life span in the ICU patients. In some studies, it was shown to be associated with extension of mechanic ventilator dependency, increase in infection rate, and long stay in ICU (8-11).

During acute stress, increase in cortisol level is a protective response against stress in order to meet the physiological requirements. This homeostasis is balanced by hypothalamic-pituitary-adrenal axis. Deficiency of corticosteroid that has positive activities is a common problem in the ICUs, particularly in the patients with sepsis and septic shock. Risk of development of adrenal insufficiency increases in the patients who stay in the ICUs for a long time. Though evaluation of adrenal insufficiency is recommended in case of clinical suspicion, it hasn’t

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Original Article Kutlucan et al.

Acta Med Anatol 2016;4(3):93-97

still been known that how often it should be done (12-17). In many studies, it has been shown that low level of albumin and high level of lactic acid have significant association with increase in mortality in the ICU patients (18-20).

There are no studies available in the literature conducted on evaluation of vitamin D and cortisol parameters in a geriatric patient group that constitutes a significant number of ICU patients, and that requires a more careful monitoring and treatment. In the present study, we aimed to evaluate the association of the parameters of lactate and albumin with mortality, nosocomial infection and intubation status as well as the effects of vitamin D and cortisol that have been evaluated within 24 hours of admission in a geriatric ICU patient group.

Material and Methods

The present study was conducted in a third-step ICU of a university hospital. A total of 117 patients over 65 years old followed up for a year were included in the study retrospectively. The patients who had end-stage malignancies, who had chemotherapy and/or radiotherapy, who stayed in ICU less than two days, who were younger than 65 years, who had taken vitamin D treatment, who had kidney insufficiency, and who had parathyroid or granulomatous disease in their history were excluded.

At the first admission of the patients to ICU, their demographical characteristics and detailed medical and family histories were taken from them or their relatives. Detailed physical examination was performed for all systems. At the first admission, Acute Physiology and Chronic Health Evaluation II (APACHE) and Glasgow Coma Scale (GCS) were calculated, and hemogram, blood gas analyses and biochemical tests were conducted. Within the first 24 hours, vitamin D and cortisol tests were requested. During the intensive care follow-up, the patients that had nosocomial infection that were intubated in case of need for mechanical ventilation, and that died were recorded.

Amongst the tests, 25-OH test was performed with gamma counter using Radioactive Immune Assay method, and PCT test was performed with Epoch plate reader using Enzyme Linked Immunosorbent Assay method. In the vitamin D level evaluation, the levels over 30 ng/mL were accepted as sufficient, the levels between 21-30 ng/mL were accepted as insufficiency, the levels below 20 ng/mL as deficiency, and the levels below 10 ng/mL as severe deficiency. Cortisol test was performed using chemiluminescent

enzyme immunoassay (Immulite 2000, Roche, USA). According to the previous studies, cortisol level below 15 μg/dl is accepted as low, and replacement is recommended (21-23).

Statistical analysis was performed using the software package SPSS (Version 20.0) (SPSS Inc, Chicago, IL, USA). Examination of the dispersion was performed using Kolmogorov-Smirnov test. Values in parametric distribution were expressed as mean ± standard deviation, while the non-parametric ones were as “median (minimum-maximum)”. In the continuous variables, statistical significance was analyzed using Student’s t test for parametric variables, and using Mann-Whitney U test for non-parametrics. p <0.05 was considered statistically significant.

Results

A total of 63 of the patients were males, and 54 were females. The mean age of the patients was 77.07 in males, 77.81 in females, and 77.44 overall. The mean GCS was calculated as 7.97±4.1, the mean APACHE II Score was 28.06±9.1, and expected mortality rate was 60.37% ±23.93%. After the follow-up in ICU, 51 patients were discharged, and 66 patients (56.4%) were died. Nosocomial infection occurred in 31 out of 117 (26.5%) patients followed up in ICU, and 93 patients (79.5%) had to be intubated.

The mean vitamin D level was 7.1±3.71 ng/mL (3- 21.5) in the patients died, and was 13.10±6.68 ng/mL (3-37) in the discharge group, and the mean vitamin D level was found to be significantly lower in the died group (p<0.001). Cortisol levels were detected as low in a total of 23 patients consisting 21 died and 2 discharged ones. The mean morning serum cortisol level was 21.15±11.31µg/dL (4.7-84) in the died patients group, was 34.00±16.17 µg/dL (14.2-94.8) in the discharged patients, and was found to be significantly lower in the died group (p<0.001). The mean lactate level was 2.2±4.05 mmol/L (0.9-18) in the died group, was 1.5±1.05 mmol/L (0.1-5.1) in the discharge group, and wa found to be significantly higher in the died group (p<0.001). The mean albumin level was 2.59±0.51 g/dL (1.3-3.6), was 3.00±0.54 g/dL (1.35-4.40) in the discharge group, and was found to be lower in the died group (p<0.001). No significant differences were found between the groups in terms of calcium and phosphorus levels (Table 1).

The mean vitamin D level was found to be lower in the patients that nosocomial infection occurred during the ICU follow-up [8.00±6.40 ng/mL (3-32)] than the ones that nosocomial infection did not

95



occur [10.90±6.26 ng/mL (3-37)] (p=0.025). No significant associations were detected between nosocomial infection and serum levels of cortisol, lactate, albumin, calcium, and phosphorus (Table 2).

Table 1. Effects of serum levels of vitamin D, cortisol, albu-min, lactate, calcium, and phosphorus on discharge status.

Parameters

Discharge status (n=117)p

valuePatients died (n=66)

Patients discharged(n=51)

Vitamin D 7.15±3.71 13.10±6.68 p<0.001

Cortisol 21.15±11.31 34.00±16.17 p<0.001

Lactate 2.2±4.05 1.5±1.05 p<0.001

Albumin 2.59±0.51 3.00±0.54 p<0.001

Calcium 7.93±0.68 8.00±0.65 p=0.276

Phosphorus 2.90±1.02 2.90±1.00 p=0.511

Table 2. Effects of serum levels of vitamin D, cortisol, albu-min, lactate, calcium, and phosphorus on development of nosocomial infections.

ParametersNosocomial infection (n=117)

p valuePresent (n=31) Absent (n=86)

Vitamin D 8.00±6.40 10.90±6.26 p<0.025

Cortisol 27.50±15.57 24.00±16.09 p<0.636

Lactate 1.90±2.14 1.80±3.66 p<0.965

Albumin 2.90±0.10 2.75±0.06 p<0.365

Calcium 8.10±0.63 7.93±0.68 p=0.453

Phosphorus 3.20±1.00 2.80±1.00 p=0.073

The mean vitamin D level was found to be lower in the patients who were intubated [9.00±6.36 ng/mL (3-37)] than the ones were not [13.00±5.18 ng/mL (9.7-34)] (p<0.001). The mean cortisol level was found to be lower in the intubated group [23.30±14.83 mcg/dL (4.7-84)] than the non-intubated group [30.50±17.83 mcg/dL (15-94)] (p<0.004). The mean lactate level was found to be higher in the intubated group [1.90±3.53 mmol/L (0.1-18)] than the non-intubated group [1.55±2.17 mmol/L (0.7-11.2)] (p<0.035) (Table 3).

Discussion

In the present study, we detected a significant association between vitamin D deficiency and increase in mortality in geriatric ICU patients. We also found a significant association between

vitamin D deficiency and either nosocomial infection development or increase in intubation rate in the same age group. Depending to our results, the cortisol levels within the first 24 hours of admission was to be significantly lower in the geriatric patients who died in ICU than the ones discharged. Cortisol levels were found to be significantly lower in the intubated patients, and they seem to be protective against intubation. No association was detected between cortisol levels and nosocomial infection development. Amongst the parameters evaluated additionally in our study, lactate levels were found to be higher in the patients died and in the ones intubated, as expected. In addition, albumin levels were detected as low in the patients died.

Table 3. Effects of serum levels of vitamin D, cortisol, albu-min, lactate, calcium, and phosphorus on intubation.

ParametersIntubation (n=117)

p valuePresent (n=93) Absent (n=24)

Vitamin D 9.00±6.36 13.00±5.18 p<0.001

Cortisol 23.30±14.83 30.50±17.83 p<0.004

Lactate 1.90±3.53 1.55±2.17 p<0.035

Albumin 2.76±0.58 2.90±0.41 p<0.192

Calcium 8.00±0.67 8.05±0.64 p=0.661

Phosphorus 2.90±0.98 2.60±1.12 p=0.251

The mean age of our patients was so high, and number of the patients who needed intubation was also extremely high. Expected mortality rate was found to be high in our patient population that co-morbidity rate was also high. Depending on these negative factors, died patient rate overall was detected as high.

The retrospective study conducted on 42 patients about vitamin D level and ICU mortality by Lee et al. was amongst the first researches done at this topic. They reported that mortality rate was high in the patients with vitamin D deficiency. As the cause of this, they considered that vitamin D deficiency and insufficiency could affect the immune system negatively, and could cause metabolic dysfunction (9). In the study conducted on 135 ICU patients by Moraes et al., vitamin D levels were tested at the first admission, and mortality rate within 28 days was compared between the patients with vitamin D levels below and over 12 ng/mL, and they detected that mortality rate was significantly higher in the patients with low vitamin D levels. They also reported no

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significant differences between the groups in terms of mechanic ventilation requirement and nosocomial infection rates. They did not evaluate cortisol levels (11). In our study, the patients were not divided into groups according to vitamin D levels, and the mean vitamin D level was quite low. In addition, there were significant association between low vitamin D levels and nosocomial infection development and high intubation rate in our study. Since our patients were in geriatric age, vitamin D levels might have been detected as low. However, susceptibility to infections and respiratorial problems might be more severe because of the same reason. Quraishi et al. measured vitamin D levels in blood samples of 100 surgery patients taken preoperatively. They reported that an association could be between 25-hydroxy vitamin D levels measured within 24 hours and re-hospitalization in 90 days, 90-day-mortality rate, and the length of hospital stay. In their study, the patient group consisted of the surgery patients, and neither nosocomial infections nor cortisol levels were evaluated (24). In the study conducted with retrospective evaluation of 201 patients in ICU by Aygencel et al., association between vitamin D and mortality was researched. They found that mortality rate was significantly higher in the group with low vitamin D levels. They also reported that mechanic ventilation requirement rate was significantly higher in the patients with low vitamin D levels, however they found no significant association between vitamin D levels and nosocomial infection development rates (25). Much lower mean vitamin D level and higher mean patient age in our study in comparison to that study might have caused significantly high nosocomial infection rate. In a

meta-analysis conducted on 14 researches by Haan et al., association between vitamin D levels and rates of mortality and infection was evaluated in 9715 ICU patients. Depending to that analysis, it was reported that severe infection and mortality rates were high in vitamin D deficiency. In that analysis, risk for nosocomial infection development and intubation status were not evaluated (26).

In critically ill patients, increase in corticosteroid levels has been considered to be a protective mechanism against stress. However, corticosteroid levels don’t increase enough in ICU patients due to insufficient immune response. There are few studies available in the literature evaluating the association between cortisol levels and either mortality or nosocomial infection (27-29). In the study conducted on 57 patients by Wu et al., cortisol levels were detected to be low in most of ICU patients. They reported that cortisol levels decreased again after replacement treatment. It was also reported that cortisol levels could cause negative results. Therefore, they recommended to re-evaluation of adrenal functions in the patients who stayed for a long time in ICU (30).

In conclusion, the present study has been the first research that evaluated the serum levels of vitamin D, cortisol, albumin, lactate, calcium, and phosphorus measured within the first 24 hours of admission to ICU, and mortality, nosocomial infection, and intubation status in geriatric patients. According to these information, closely monitoring of levels of cortisol and vitamin D and replacement seem to be quite useful in the geriatric ICU patients who require close follow-up and treatment.

1. Pramyothin P, Holick MF. Vitamin D supplementation:guidelines and evidence for subclinical deficiency. Curr Opin Gastroenterol 2012;28:139-50

2. Holick MF, Binkley NC, Bischoff-Ferrari HA, GordonCM, Hanley DA, et al. Evaluation, treatment, andprevention of vitamin D deficiency: an EndocrineSociety clinical practice guideline. J Clin EndocrinolMetab 2011;96:1911-30

3. Biesalski HK. Vitamin D recommendations: beyonddeficiency. Ann Nutr Metab. 2011;59:10-16.

4. Holick MF. Vitamin D: importance in the preventionof cancers, type 1 diabetes, heart disease, andosteoporosis. Am J Clin Nutr. 2004;79:362-371.

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11. Moraes RB, Friedman G, Wawrzeniak IC, MarquesLS, Nagel FM, Lisboa TC, et al. Vitamin D deficiencyis independently associated with mortality amongcritically ill patients. Clinics (Sao Paulo) 2015;70:326-32

12. Annane D, Sébille V, Charpentier C, Bollaert PE, François B, Korach JM, et al. Effect of treatment with low dosesof hydrocortisone and fludrocortisone on mortality inpatients with septic shock. JAMA 2002;288:862-71

13. Lebel MH, Freij BJ, Syrogiannopoulos GA, Chrane DF,Hoyt MJ, Stewart SM, et al. Dexamethasone therapyfor bacterial meningitis. Results of two double-blind,placebo-controlled trials. N Engl J Med 1988;319:964-71

14. Meduri GU, Headley AS, Golden E, Carson SJ,Umberger RA, Kelso T, et al. Effect of prolongedmethylprednisolone therapy in unresolving acuterespiratory distress syndrome: a randomizedcontrolled trial. JAMA 1998;280:159-65

15. Bollaert PE, Charpentier C, Levy B, Debouverie M,Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit CareMed 1998;26:645-50

16. Briegel J, Forst H, Haller M, Schelling G, Kilger E,Kuprat G, et al. Stress doses of hydrocortisonereverse hyperdynamic septic shock: a prospective,randomized, double-blind, single-center study. CritCare Med 1999;27:723-32

17. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549-56

18. Freire AX, Bridges L, Umpierrez GE, Kuhl D, KitabchiAE. Admission hyperglycemia and other risk factorsas predictors of hospital mortality in a medical ICUpopulation. Chest 2005;128:3109-16

19. Klouche K, Amigues L, Massanet P, Garrigue V,Delmas S, Szwarc I, et al. Outcome of renal transplantrecipients admitted to an intensive care unit: a 10-year cohort study. Transplantation 2009;87:889-95

20. Matsumura Y, Nakada TA, Abe R, Oshima T, Oda S.Serum procalcitonin level and SOFA score at dischargefrom the intensive care unit predict post-intensivecare unit mortality: a prospective study. PLoS One2014;9:e114007

21. Jacobs HS, Nabarro JD. Plasma 11-hydroxycorticosteroid and growth hormone levels in acute medical illnesses.Br Med J 1969;2:595-8

22. Kidess AI, Caplan RH, Reynertson RH, Wickus GG,Goodnough DE. Transient corticotropin deficiency incritical illness. Mayo Clin Proc 1993;68:435-41

23. Cooper MS, Stewart PM. Corticosteroid insufficiencyin acutely ill patients. N Engl J Med 2003;348:727-34

24. Quraishi SA, Bittner EA, Blum L, McCarthy CM, BhanI, Camargo CA. Prospective study of vitamin D statusat initiation of care in critically ill surgical patients andrisk of 90-day mortality. Crit Care Med 2014;42:1365-71

25. Aygencel G, Turkoglu M, Tuncel AF, Candır BA, BildacıYD, et al. Is vitamin d insufficiency associated withmortality of critically ill patients? Crit Care Res Pract2013;2013:856747

26. de Haan K, Groeneveld AB, de Geus HR, Egal M, StruijsA. Vitamin D deficiency as a risk factor for infection,sepsis and mortality in the critically ill: systematicreview and meta-analysis. Crit Care 2014;18:660

27. Prigent H, Maxime V, Annane D. Clinical review:corticotherapy in sepsis. Crit Care 2004;8:122-9

28. Lamberts SW, Bruining HA, de Jong FH. Corticosteroidtherapy in severe illness. N Engl J Med 1997;337:1285-92

29. Loisa P, Rinne T, Kaukinen S. Adrenocortical functionand multiple organ failure in severe sepsis. ActaAnaesthesiol Scand 2002;46:145-51

30. Wu JY, Hsu SC, Ku SC, Ho CC, Yu CJ, Yang PC. Adrenalinsufficiency in prolonged critical illness. Crit Care2008;12:R65

98


Correspondence: Dr. İsa Yıldız, Department Of Anesthesiology and Reanimation, Abant Izzet Baysal University, TurkeyConflict of Interest: NoneE-mail: [email protected]


İsa Yıldız1, Hakan Bayır1, Abdulkadir Küçükbayrak2, Hamit Yoldaş1, Mehmet Balcı3, Mansur Kürşat Erkuran4, Kadir Korkmaz Akkaya1, Aliye Yaşayacak5

1 Department of Anesthesiology and Reanimation, Abant Izzet Baysal University, Turkey2 Department of Infectious Diseases and Clinical Microbiology, Abant Izzet Baysal University, Turkey3 Union of Public Hospitals, Abant Izzet Baysal State Hospital, Clinic of Infectious Diseases, Turkey4 Department of Emergency Medicine, Abant Izzet Baysal University, Turkey5 Infection Control Unit, Abant Izzet Baysal University Training and Research Hospital, Turkey

Introduction: Determination of suitable antibiotics in treatment of Acinetobacter infections is through the hospital ascertain-ing the resistance state to bacteria causing the problem. In this study, the evaluation of antibiotics sensitivity of Acinetobacter strains isolated as infection factor in patients hospitalized in intensive care units is aimed.

Methods: Acinetobacter strains isolated from the samples of patients hospitalized in the 2nd and 3rd Stage adult intensive care units of a province in in northwestern Anatolia have been studied.

Results: A total of 165 patients were included in the study. The most isolated samples were respiratory tract samples, blood and urine. The antibiotics which the factors were most sensitive were cholistin (66,1%) gentamicin (22,4%) and trimethoprim sulfamethoxazole (18,2%).

Conclusion: We face increasing resistance ratios in Acinetobacter strains. Necessary precautions should be taken for this.

Keywords: Acinetobacter, Colistin, Intensive care unit.


Abstract

doi: 10.5505/actamedica.2016.52714

Acinetobacter Infection and Resistance Profile of Intensive Care Units in a City of Northwestern Anatolia

Introduction

Acinetobacter is a gram-negative, coccobacillus, immobile, non-fermentative, opportunistic pathogen microorganism (1). This pathogen can be commonly seen in intensive care units due to capability of staying alive in dry surfaces and colonizing in respiratory devices and human skin (2,3). It may cause meningitis, pneumonia, bacteremia and urinary system infection (3). Due to easily developing resistance to antimicrobial agents by various mechanisms, difficulties are experienced in its control and treatment (4,5). Antibiotic resistance may vary from hospital to hospital and determination of suitable antibiotic is vey important in treatment of Acinetobacter infections (1,6).

In this study, we aimed to evaluate the antibiotic sensitivity of Acinetobacter strains isolated as infection factor in intensive care units.


In this study, the Acinetobacter strains isolated from the blood, urine, tracheal aspirate, wound site,

catheter and other samples as infection factors from the patients hospitalized in Adult Intensive Care Units of 2nd and 3rd stage hospitals in a province of Northwestern Anatolia between 2014 and 2015 were studied. The samples were planted in 5% defibrinated sheep blood agar and Eosin Methylene-Blue mediums and incubated at 37°C. Sterile body samples were incubated for a maximum of 10 days at 37°C in bottles belonging to Bactec 9120 (Becton Dickinson, USA) blood culture system. After the bacteria is isolated, it is first evaluated by conventional methods. It is taken to panels belonging to BD Phoenix 100 (Becton Dickinson, USA) automated identification device for certain identification and determination of antimicrobial sensitivities. Amikacin, ampiciline-sulbactam, gentamicin, imipenem, meropenem, ertapenem, cholistin, piperacillin-tazobactam, ceftriaxone, ciprofloxacin, tigecycline, trimethoprim-sulfamethoxazole and aztreonam sensitivities were studied. A strain from each patient were studied, moderately sensitive strains were considered resistant. The results were interpreted according to CLSI standards.

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Results

A total of 165 patients were included in the study and recurrent reproductions in each patient were not included in the study. Of the patients, 76 were female, 89 were male and age average was 73+17. Most commonly isolated samples were respiratory tract samples, blood and urine (Table 1). Most sensitive antibiotics were cholistin (66,1%) gentamicin (22,4%) and trimethoprim sulfamethoxazole (18,2%) (Table 2).

Table 2. Antibiotic sensitivity of isolated strains

Antibiotic Sensitive Resistance

Colistin 109 (66,1) 56 (33,9)

Amicasin 15 (9,1) 150 (90,9)

Gentamicin 37 (22,4) 128 (77,6)

Trimethoprim /Sulfamethoxazole 30 (18,2) 135 (81,8)

Tigecycline 11 (6,7) 154 (93,3)

Ertapenem 1 (0,6) 164 (99,4)

Imipenem 11 (6,7) 154 (93,3)

Meropenem 3 (1,8) 162 (98,2)

Seftriakson 1 (0,6) 164 (99,4)

Aztreonam 1 (0,6) 164 (99,4)

Ampicillin-Sulbactam 9 (5,5) 156 (94,5)

Ciprofloxacin 2 (1,2) 163 (98,8)

Levofloxacin 3 (1,8) 162 (98,2)

Tetracycline 15(9,1) 150 (90,9)

Piperacillin-Tazobactam 2 (1,2) 163(98,8)

Discussion

The importance of Acinetobacter infections is increasing. Multiple antibiotic use with the increase in the number of intensive care units and patients

is thought to be one of the considerable underlying causes of antibiotic resistance of microorganisms. This study showed that resistance for Acinetobacter infections is increasing in intensive care units. Difficulties in treatments related to multiple resistance are encountered.

Acinetobacter infections cause multiple drug resistance infections in parallel to increase risk factors such as duration of length of stay in intensive care unit, frequent use of antimicrobial agents, immunosuppressing, invasive procedures (7,8).

Acinetobacter infections are isolated from various samples. Acinetobacter infections are most commonly isolated from tracheal aspirates, wound site, blood and urine samples (9). Aral et al. (1) reported tracheal aspirate 30%, wound site 29% and blood 25%. Kurtoğlu et al. (10) have determined tracheal aspirate 42%, wound site 28%, urine 12% and blood 10%. Similarly, in our study, the bacteria was most commonly isolated in respiratory tract samples, blood and urine samples.

The resistance rates to carbapenems, quinolones and aminoglycosides in Acinetobacter strains increased to very high rates. At the same time, an increasing resistance against cholistin, which is used effectively in resistant strains, can be developed. Different Carbapenem resistance results for Acinetobacter have been reported in our country. A multi-centered HITI-1 study conducted in 2008, imipenem resistance in hospital-origin Acinetobacter strains was reported as 52,2% (11). This rate was reported as 61% by Mansur et al. (12). In the intensive care units, Kuşçu et al. (13) have reported this ratio as 80%. In a multi-center study conducted in Korea, it was reported that imipenem resistance in A. baumannii increased from 52.9% to 89.8% (14). The imipenem resistance ratio in the intensive care unit of our hospital was 93,3%. Ciprofloxacin, meanwhile, was found 84% in the study of Mansur et al. (12), 82% in Balcı et al. (15) and 89% in Özer et al. (16). This ratio was found as 98,8% in our own intensive care units. This finding is one of the highest ratios in our country. Additionally, there are different results of the studies in which the aminoglycoside resistance was investigated. The resistance rates for amikacin may vary between 71,6% and 94%, and for gentamicin 66-97% (12,16,17). Gentamicin resistance (77,6%) was found lower than amikacin (90,9%) in our sudy. We believe this may be related to frequent preferrence of amikacin instead of gentamicin in treatment of nosocomial infections in our center.

Table 1. Acinetobacter isolated spaces

n %

Respiratory tract 102 35,2

Urine 12 7,3

Catheter 8 4,8

Blood 30 18,2

Wound 9 5,5

Pleural effusion 3 1,8

Cerebrospinal Fluid 1 0,6

Total 165 100,0

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For Acinetobacter strains with multiple drug resistances, cholistin is considered as a suitable antibiotic. Cholistin resistance was reported to be less than 10% in our country (1). In studies conducted in different countries it was reported as 5.3%, 3.6% and 0.7% (18,19). According to UHESA data, this resistance ratio is generally 2,95% in our country. This still makes us think cholistin a suitable treatment in Acinetobacter infection with multiple drup resistance treatment. However, we found a

relatively high cholistin resistance in our intensive care units (33,9%).

In conclusion; we have demonstrated that a relatively high rate of resistance of antibiotics to clinically important Acinetobacter strains. Additionally, we also recommend that the intensive care unit personnel must be informed about bacteria infection control practices because of the tendency of these pathogens to persist and spread in the hospital environment easily.

1. Aral M, Doğan S, Paköz NIE. Investigations of Antibiotic Resistance of Acinetobacter baumannii Strains Isolated from Various Clinical Samples. Ankem Derg. 2010; 24: 215-219.

2. Villegas MV, Hartstein AI. Acinetobacter outbreaks, 1977-2000. Infect Control Hosp Epidemiol. 2003; 24: 284-295.

3. Iraz M, Ceylan A, Akkoyunlu Y. Investigation of Antibiotic Resistance Rates of Acinetobacter Species Isolated from Various Clinical Samples. Ankem Derg. 2012; 26: 80-85.

4. Jain R, Danziger LH. Multidrug-resistant Acinetobacter infections: an emerging challenge to clinicians. Ann Pharmacother. 2004; 38: 1449-1459.

5. Richet H, Fournier PE. Nosocomial infections caused by Acinetobacter baumannii: a major threat worldwide. Infect Control Hosp Epidemiol. 2006; 27: 645-646.

6. Yoon J, Urban C, Terzian C, Mariano N, Rahal JJ. In vitro double and triple synergistic activities of Polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2004; 48: 753-757.

7. Bergogne-Berezin E, Towner KJ. Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clin Microbiol Rev. 1996; 9: 148-165.

8. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: Emergence of a successful pathogen. Clin Microbiol Rev 2008; 21: 538-582.

9. Colpan A, Güngör S, Baykam N, Dokuzoğuz B. Yoğun bakım ünitelerinden izole edilen Acinetobacter suşlarının antibiyotik direnç durumlarının araştırılması. Turkish Journal of Infection. 2002; 16: 55-58.

10. Kurtoglu MG, Ayşegül O, Meral K, Kesli R, Güzelant A, Yüksekkaya S. Antimicrobial Resistance of Acinetobacter baumannii Strains Isolated from Clinical Samples in an Education and Research Hospital (2008-2010). Ankem Derg. 2011; 25: 35-41.

11. Gür D, Gülay Z, Akan OA, Aktas Z, Kayacan CB, Cakici O, et al. Resistance To Newer Beta-Lactams And Related Esbl

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Types In Gram-Negative Nosocomial Isolates In Turkish Hospitals: Results Of The Multicentre Hitit Study. Bulletin of Microbiology. 2008; 42: 537-544.

12. Mansur A, Kuzucu C, Ersoy Y, Yetkin F. Acinetobacter Strains Isolated from Hospitalized Patients and their Antibiotic Susceptibility in Turgut Ozal Medical Center of Inonu University in 2008. Ankem Derg. 2009; 23: 177-181.

13. Kuşçu F, Oztürk DB, Tütüncü EE, Uslu M, Gürbüz Y, Gülen G, et al. Evaluation of Tigecycline Susceptibility by E-Test® in Multidrug-Resistant Acinetobacter baumannii Isolates. Klimik Journal. 2009; 22: 48-51.

14. Hoi JY, Kwak YG, Yoo H, Lee SO, Kim HB, Han SH, et al. Trends in the distribution and antimicrobial susceptibility of causative pathogens of device-associated infection in Korean intensive care units from 2006 to 2013: results from the Korean Nosocomial Infections Surveillance System (KONIS). J Hosp Infect. 2016; 92: 363-371.

15. Balcı M, Bitirgen M, Kandemir B, Türk Arıbas E, Erayman I. Antibiotic Susceptibility of Nosocomial Acinetobacter baumannii Strains. Ankem Derg. 2010; 24: 28-33.

16. Ozer B, Tatman-Otkun M, Memis D, Otkun M. The Nosocomial Infections, Microorganisms And Their Antimicrobial Susceptibilities And Antibiotic Consumption In Intensive Care Unit. Turkish Journal of Infection. 2006; 20: 165-170.

17. Ozdem B, Gürelik FC, Celikbilek N, Balıkcı H, Acıkgöz Z. Antibiotic Resistance Profiles of Acinetobacter Species Isolated from Several Clinical Samples Between 2007-2010. Bulletin of Microbiology. 2011; 45: 526-534.

18. Zilberberg MD, Kollef MH, Shorr AF. Secular trends in Acinetobacter baumannii resistance in respiratory and blood stream specimens in the United States, 2003 to 2012: A survey study. J Hosp Med. 2016; 11: 21-26.

19. Sader HS, Farrell DJ, Flamm RK, Jones RN. Antimicrobial susceptibility of Gram-negative organisms isolated from patients hospitalized in intensive care units in United States and European hospitals (2009-2011). Diagn Microbiol Infect Dis. 2014; 78: 443-48.

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Original Article Acta Medica AnatoliaVolume 4 Issue 3 2016

Akın Usta1, Mine Islimye Taskin1, Ceyda Sancakli Usta2, Eylem Sen Dalkiran3, Osman Kilinc4, Elif Dus2

1 Balikesir University, School of Medicine, Department Of Obstetrics And Gynecology, Turkey2 Balikesir Ataturk State Hospital, Department of Obstetrics And Gynecology, Turkey3 Balikesir Ataturk State Hospital, Department of Pediatrics, Turkey4 Balikesir Ataturk State Hospital, Department of Microbiology, Turkey

Introduction: Cytomegalovirus (CMV) is known as a major cause of congenital viral infection in humans. The aim of this study was to evaluate the rate of CMV infection and identify risk factors for infection by screening pregnant women in high prevalence population.

Methods: A retrospective study was conducted between January 2014 and December 2014 in women presenting for their first antenatal visit (between 6-12 weeks of gestation). All women were tested for IgG and IgM antibodies. Subsequently, avidity test was used to discriminate between primary or non-primary CMV infection. They were followed until delivery and newborns were examined by a pediatrician.

Results: A total of 3212 pregnant women were screened during the study period. The rate of seropositivity and seronegativity were found as 97.9% and 2.1% respectively. The prevalence of maternal CMV infection was found as 1.1% (34 women). Among these women, the rate of primary and recurrent CMV infection were found to be 0.3% (8 women) and 0.8% (26 women) respectively. Pregnants with primary CMV infection were referred to perinatal care unit. Pregnants with recurrent infection were followed by ultrasonography for the presence of fetal abnormalities. None of the women who completed follow-up until delivery showed gross evidence of in utero CMV transmission. Isolated IgM antibody positivity was not detected in any women.

Conclusion: Seroprevalence of CMV infection is very high in our region during the pregnancy. Although, there was no difference in terms of birth weight and gestational age at delivery, detection of primary CMV infection is associated with higher rate of spontaneous abortion.

Keywords: Cytomegalovirus, Congenital infection, IgG antibody.


doi: 10.5505/actamedica.2016.53215

Abstract

Screening Cytomegalovirus Infections in First Trimester of Gestation among High Prevalence Population

Introduction

The IgG antibodies, the only type of antibody that can cross the placenta, provide passive immunization in the fetus throughout the pregnancy. However, the IgG2 subclass antibodies cannot pass through the placenta and merge capsular/polysaccharide antigen which create IgG2 response; therefore, some infections related to these antigens may persist and can lead to serious intrauterine infection (1–3).

Cytomegalovirus (CMV), which is a member of human herpesvirus, is the most common causative viral agent of intrauterine infection worldwide (4). Previous studies reported that approximately 0.7% of live-born neonates are infected with CMV (5) and that 15%–20% of these infected children developed symptoms ranging from sensorineural hearing lost to multiple organ failure even fetal and neonatal death (6).

Congenital CMV infection manifest as a primary infection, non-primary infection with a new strain of CMV, or reactivation of a latent infection (7). The most severe cases of congenital CMV infection are those with consequences of primary infection during pregnancy (8,9) . The objective of the prenatal care is accurate diagnosis of primary infection and assessment of the risk of fetal transmission (10,11).

Diagnosis of primary maternal CMV infection depends on detection of virus-specific Immunoglobulin G (IgG) antibody in the blood of a pregnant woman who was previously seronegative, or on detection of specific Immunoglobulin M (IgM) antibody associated with low IgG avidity (12). IgM antibody is present 4 to 8 weeks following the primary infection and can persist for years. Nevertheless, false-positive results can occur due to cross-reactivity with other diseases, such as autoimmune disorders

Correspondence: Akın Usta, Balikesir University, Department of Obstetrics and Gynecology, Balikesir, Turkey. Conflict of Interest: NoneE-mail: [email protected]

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or other viral infections. The value and the over implementation of screening in all pregnant women for CMV infection are still under debate in many countries of the world (13). However, data regarding the prevalence of maternal CMV infection is quite insufficient in Turkey.

The aim of this study was to evaluate the rate of CMV infection and identify risk factors for infection by screening pregnant women in high prevalence population.

Materials and Method

This study was approved by the Institutional Review Board of Balikesir University. Participants were recruited from Balikesir Ataturk State Hospital between January 2014 and December 2014. Pretest counseling was given to all participants by the physician and 5 ml blood was collected from antecubital vein. A total of 3212 pregnant women have been tested for CMV IgG and IgM in the first trimester of pregnancy. All women were followed until delivery. To assess the neonatal CMV infection, newborns were examined by experienced pediatricians. This study demonstrates a rural population from the Aegean Territory of Turkey. The clinical characteristic’s including, age and pregnancy outcomes were entered into a database.

A standardized protocol was used for screening of CMV infection. Serum samples of all women were tested for the presence of IgG and IgM antibodies against CMV. Enzyme linked fluorescent assay (VIDAS, Biomerieux, France) was used to measure antibody titers. Those with high IgG and IgM levels were tested by IgG avidity test to confirm or exclude acute infection. According to manufacturer’s instructions, IgG levels greater than 6 IU/ml for CMV were noted as positive. A value of IgM greater than 0.9 IU/ml for CMV was considered as positive. Determination of the avidity of IgG was also performed by using VIDAS (Biomerieux, France) for CMV. Avidity index greater than 0.8 for CMV was considered as high avidity and whereas an index less than 0.2 for CMV was considered as low avidity.

MedCalc Statistical Software Program version 15.8 (MedCalc Software bvba, Ostend, Belgium) was carried out. One-way analysis of variance (ANOVA), the log-transform method with Scheffe multiple comparison tests, the Kruskal-Wallis test, the Mann-Whitney test, and the x2 test were used as appropriate. A p-value <0.05 was accepted as statistically significant.

Results

A total of 3212 pregnant women were screened for CMV infection. The mean ± SD age was 26.9 ± 5.8 and that of parity was 0.8 ± 0.8. Demographic characteristics of women were presented in Table 1.

Table 1. Characteristics of study participants (N = 3212).

Characteristics ValueMaternal age (years) 26.97 ± 5.59Parity (no.) 0.86 ± 0.82Miscarriage Rate (%) 7,25Infant birth weight (g) 3,235 ± 556İnfant birth height (cm) 49,98 ± 2,53Gestational age at delivery (weeks) 39,6 ± 0,97Apgar score, 1 min 8.51 ± 1.25Apgar score, 5 min 9.36 ± 1.74

According to serological status of the CMV infection, 3111 women had CMV IgM (-) with IgG (+), 34 women had CMV IgM (+) with IgG (+), 67 women had CMV IgM (-) with IgG (-) and there were no pregnant women screened for CMV infections with isolated IgM antibody positivity (Table 2).

Table 2. Maternal CMV seroprevalence.

CMV serology Number of patients (%)

CMV IgM (-) IgG (+) 3111 (96,9)

CMV IgM (-) IgG (-) 67 (2,1)

CMV IgM (+) IgG (+) 34 (1,1)

CMV IgM (+) IgG (-) -

As shown in table 3, the majority of the participants were between 20-24 or 25-29 years of age (29.23% and 31.16%, respectively). Parity was 0 in 1,065 (33.16%) and 1 in 1,725 (53.70%) patients. Overall 3145 (97.9 %) women were positive for anti-CMV IgG in the first trimester of the gestation and seropositivity of CMV IgG appeared to be increased with age and parity. However, analysis of x2 test revealed that differences for age and parity did not reach statistical significance (p=0,05 and p=0,07 respectively). (Table 4,5).

Thirty-four (1.1%) women were positive or equivocal for CMV IgM with IgG in the study. High avidity was detected in 26 women, which excluded primary infection and avidity index was low or borderline in 8 women (5 with low and 3 with borderline), with IgG and IgM antibodies positive against CMV (Table 6).

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Table 3. Maternal age group and parity.

Parity

Age group(Y) Total(n) 0 1 2 3 ≥4

<20 260 116 135 6 3 0

20-24 939 356 488 76 16 3

25-29 1001 319 540 96 44 2

30-34 650 181 365 55 37 12

35-39 311 80 172 24 30 5

≥40 51 13 25 2 5 6

Total 3212 1065 1725 259 135 28

Table 4. Maternal age group and cytomegalovirus IgG seropositivity.

Age group (Y) Maternal cytomegalovirus IgG seropositivity (%)

<20 96,5

20-24 97,8

25-29 97,9

30-34 98,2

35-39 98,7

≥40 100

Table 5. Maternal parity and cytomegalovirus IgG seropositivity.

ParityMaternal cytomegalovirus

IgG seropositivity (%)

0 97,3

1 98,1

2 98,5

3 98,5

≥4 100

Table 6. Outcome of pregnancies by types of CMV infection.

Primary infection (%)

n=8

Non-primary infection (%)

n=26

P value

Miscarriage rate (%) 62,50 7,69 0,004

Live Birth (%) 37,50 92,31 0,004

Gestational age at delivery(week)

38,4 ± 1,2 39,1 ± 1,5 0,657

Infant weight (week) 3573 ± 651 3215 ± 339 0,142

Comparing the non-primary infection, women with primary CMV infection had significantly higher miscarriage rate than those with non-primary infection (Table 6). In 5 of 8 women with primary infection the pregnancies resulted in spontaneous

abortion at first trimester or early second trimester before the detailed ultrasonographic examination. Primary infections were resulted in a 62.5% miscarriage rates before the first 20 weeks of gestation, while after 20 weeks of gestation all pregnancies were full term. However, infant birth weight and gestational age at the delivery were similar between primary and non-primary infection groups. The median gestational age was 9 weeks (6–12 weeks), and the median number of pregnancies was 1 (range 1–10). All pregnant women, underwent a detailed sonographic examination at 18-22th

week of gestation by obstetricians. No abnormal sonographic finding implicating any of the congenital infections screened was detected. Data regarding the first examinations of all neonates were obtained and no clinical symptoms or laboratory results of the infections were reported. Sixty-seven women (2.1%) were negative for CMV IgG antibody in the first trimester and susceptible to acute infection during pregnancy.

Discussion

Seroprevalence of CMV infection is very high in Aegean region of Turkey during the pregnancy and detection of primary CMV infection is associated with higher rate of spontaneous abortion.

The IgG antibodies, the only type of antibody that can cross the placenta, provides passive immunization in the fetus throughout pregnancy. However, the IgG2 subclass pass through the placenta and some infection agents related to IgG2 response can cause intrauterine infections in the fetus (1–3).

CMV is one of the most common causative viral agent that can cause intrauterine infection (4). Congenital CMV infection can be due to a primary infection, non-primary infection with a new strain of CMV, or with reactivation of a latent CMV infection (7). The most severe cases of congenital CMV infection are the consequence of primary infection during pregnancy (8,9). The objective of the prenatal care is the accurate identification of primary infection and accurate evaluation of the risk of fetal transmission (10,11).

In the present study, a total of 3212 pregnant women were screened for CMV infection and the results revealed a CMV IgG seropositivity rate of 97.9% among pregnant women in Turkey. This result is in accordance with reports from Turkey (14,15), in which the CMV seropositivity rate was ranging from 84.5% to 97.3%. However, In a study performed among Turkish women living in an urban area, The

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prevalence of seropositivity was found 84.1%, which is lower than those reported in other parts of Turkey (16). A major factor contributing to this decline may be the decreased risk of CMV infection because of improved life standards in urban Turkish population.

Our findings showed that the seropositivity of CMV IgG was not associated with increased age or parity. On the contrary, reports from developed countries revealed that the prevalence of CMV IgG seropositivity appeared to increase with both age and parity. Furthermore, parity was found to be an independent determinant of CMV IgG seropositivity for each previous delivery (17). This difference may be caused by CMV IgG seroprevalance rate and that almost every person contaminated with CMV in early childhood in our country.

Also, 67 women (2.1%) were negative for CMV IgG antibody in the first trimester and deemed to be susceptible to acute infection during pregnancy. However, there was no seroconversion for CMV antibody in these patients during pregnancy. In previous reports, the seroconversion rate for CMV IgG antibody during pregnancy was found as 0.37%. Our results are not compatible with this finding due to both high IgG seropositivity and restricted individual enrollment to the study.

34 (1.1%) women had positive or equivocal test results for CMV IgM with IgG in the current study. High avidity was detected in 26 women, which excluded the presence of primary infection. The 8 women whose avidity index was low or borderline (5 with low and 3 with borderline test results), had positive anti-CMV IgG and IgM antibodies were considered to have primary infection. Pregnancies with primary infection had significantly higher miscarriage rate than for those with non-primary infection. Primary infections in the first 20 gestational weeks was associated with a high (62.5%) miscarriage rate. However, all pregnants with CMV infections after 20 weeks of gestation had live births. There was no significant differences between primary and non-primary CMV infection groups in terms of infant birth weight and gestational age at the delivery.

Currently, there are conflicting results regarding the association between maternal CMV infection and spontaneous abortion. In several case reports were suggested that CMV infection may cause of fetal death (18,19). Few studies have been conducted to evaluate the association between maternal CMV infection and spontaneous abortion. Their results indicated that maternal CMV infection can cause

miscarriage and fetal death (20–23). However, in some reports suggest that viral replication in genital tract is associated with fetal transmission and early fetal death (23). Regarding the association between CMV IgG antibody positivity and recurrent abortions, there are few studies have been conducted to evaluate the association between early fetal loss with or without CMV IgG antibody positivity. One of them compared the results of 309 women with or without CMV IgG antibody positivity and found that CMV IgG antibody was not association with spontaneous recurrent abortions (24).

In our study we found that there was no difference between the groups in terms of birth weight. Contrary to our results, previous studies, showed that maternal CMV infection has been associated with low birth weight (25).

The value and the over implementation of screening in all pregnant women for CMV infection are still under debate in many countries of the world (13). However, data lacks regarding the maternal CMV infection in our country. The objective of the prenatal care is the accurate diagnosis of primary infection and evaluation of the risk of fetal transmission. (10,11). We assessed IgG and IgM antibodies in pregnant women applying to the hospital in the first trimester. Thus, only women with elevated IgM antibody titers together with high IgG titers were further evaluated with avidity test to diagnose or exclude primary infection. This study may help clinicians to evaluate pregnant women who live in a population with high prevalence of CMV IgG.

Serological assessment for CMV may be considered for all women during pregnancy or in the presence of sonographic findings such as intrauterine growth retardation, microcephaly, ventriculomegaly, periventricular calcifications and echogenic bowel (26). However, sonographic findings often imply poor prognosis, but their absence does not rule out health problems following birth. In our study, we did not observe any abnormality suggestive of acute CMV infection on ultrasound in pregnant women with seropositive test for CMV.

In conclusion, seroprevalence of CMV infection is very high in Aegean region of Turkey during the pregnancy. Although, there was no association between CMV infection and birth weight and gestational age at delivery, detection of primary CMV infection is associated with higher rate of spontaneous abortion.

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1. Molina DM, Pal S, Kayala MA, Teng A, Kim PJ, Baldi P,et al. Identification of immunodominant antigens ofChlamydia trachomatis using proteome microarrays.Vaccine. 2010;28(17):3014–24.

2. Rodriguez GE, Adler SP. Immunoglobulin G subclassresponses to cytomegalovirus in seropositive patientsafter transfusion. Transfusion (Paris). 1990;30(6):528–31.

3. Sanders LA, Feldman RG, Voorhorst-Ogink MM, de Haas M, Rijkers GT, Capel PJ, et al. Human immunoglobulinG (IgG) Fc receptor IIA (CD32) polymorphism and IgG2-mediated bacterial phagocytosis by neutrophils. Infect Immun. 1995;63(1):73–81.

4. Mcgavran MH, Smith MG. Ultrastructural,cytochemical, and microchemical observations oncytomegalovirus (salivary gland virus) infectionof human cells in tissue culture. Exp Mol Pathol.1965;76:1–10.

5. Dollard SC, Grosse SD, Ross DS. New estimates of theprevalence of neurological and sensory sequelae andmortality associated with congenital cytomegalovirusinfection. Rev Med Virol. 2007;17(5):355–63.

6. Kenneson A, Cannon MJ. Review and meta-analysisof the epidemiology of congenital cytomegalovirus(CMV) infection. Rev Med Virol. 2007;17(4):253–76.

7. Nyholm JL, Schleiss MR. Prevention of maternalcytomegalovirus infection: current status and futureprospects. Int J Womens Health. 2010;2:23–35.

8. Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA. The outcome of congenital cytomegalovirus infectionin relation to maternal antibody status. N Engl J Med.1992;326(10):663–7.

9. Stagno S, Dworsky ME, Torres J, Mesa T, HirshT. Prevalence and importance of congenitalcytomegalovirus infection in three differentpopulations. J Pediatr. 1982;101(6):897–900.

10. Jacquemard F, Yamamoto M, Costa J-M, Romand S,Jaqz-Aigrain E, Dejean A, et al. Maternal administration of valaciclovir in symptomatic intrauterinecytomegalovirus infection. BJOG Int J Obstet Gynaecol. 2007;114(9):1113–21.

11. Nigro G, Adler SP, La Torre R, Best AM, CongenitalCytomegalovirus Collaborating Group. Passiveimmunization during pregnancy for congenitalcytomegalovirus infection. N Engl J Med.2005;353(13):1350–62.

12. Sonoyama A, Ebina Y, Morioka I, Tanimura K, Morizane M, Tairaku S, et al. Low IgG avidity and ultrasound

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fetal abnormality predict congenital cytomegalovirus infection. J Med Virol. 2012;84(12):1928–33.

13. Johnson JM, Anderson BL. Cytomegalovirus: shouldwe screen pregnant women for primary infection? AmJ Perinatol. 2013;30(2):121–4.

14. Uyar Y, Balci A, Akcali A, Cabar C. Prevalence ofrubella and cytomegalovirus antibodies amongpregnant women in northern Turkey. New Microbiol.2008;31(4):451–5.

15. Uysal A, Taner CE, Cüce M, Atalay S, Göl B, Köse S,et al. Cytomegalovirus and rubella seroprevalencein pregnant women in Izmir/Turkey: follow-up andresults of pregnancy outcome. Arch Gynecol Obstet.2012;286(3):605–8.

16. Karacan M, Batukan M, Cebi Z, Berberoglugil M,Levent S, Kır M, et al. Screening cytomegalovirus,rubella and toxoplasma infections in pregnant womenwith unknown pre-pregnancy serological status. ArchGynecol Obstet. 2014;290(6):1115–20.

17. Shigemi D, Yamaguchi S, Otsuka T, Kamoi S, TakeshitaT. Seroprevalence of cytomegalovirus IgG antibodiesamong pregnant women in Japan from 2009-2014. Am J Infect Control. 2015;43(11):1218–21.

18. Inoue T, Matsumura N, Fukuoka M, Sagawa N, FujiiS. Severe congenital cytomegalovirus infection withfetal hydrops in a cytomegalovirus-seropositivehealthy woman. Eur J Obstet Gynecol Reprod Biol.2001;95(2):184–6.

19. Ko HM, Kim KS, Park JW, Lee YJ, Lee MY, Lee MC, et al.Congenital cytomegalovirus infection: three autopsycase reports. J Korean Med Sci. 2000;15(3):337–42.

20. Dollard SC, Grosse SD, Ross DS. New estimates of theprevalence of neurological and sensory sequelae andmortality associated with congenital cytomegalovirusinfection. Rev Med Virol. 2007;17(5):355–63.

21. Kenneson A, Cannon MJ. Review and meta-analysisof the epidemiology of congenital cytomegalovirus(CMV) infection. Rev Med Virol. 2007;17(4):253–76.

22. Grosse SD, Ross DS, Dollard SC. Review: Congenitalcytomegalovirus (CMV) infection as a cause ofpermanent bilateral hearing loss: A quantitativeassessment. J Clin Virol. 2008;41:57–62.

23. Yan XC, Wang JH, Wang B, Huang LL, Zhou LQ, ZhuB, et al. Study of human cytomegalovirus replicationin body fluids, placental infection, and miscarriageduring the first trimester of pregnancy. J Med Virol.2015;87(6):1046–53.

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24. Odland JØ, Sergejeva IV, Ivaneev MD, Jensen IP,Stray-Pedersen B. Seropositivity of cytomegalovirus,parvovirus and rubella in pregnant women andrecurrent aborters in Leningrad County, Russia. ActaObstet Gynecol Scand. 2001;80(11):1025–9.

25. Kharrazi M, Hyde T, Young S, Amin MM, Cannon MJ,Dollard SC. Original Article: Use of Screening Dried

Blood Spots for Estimation of Prevalence, Risk Factors, and Birth Outcomes of Congenital Cytomegalovirus Infection. J Pediatr. 2010;157:191–7.

26. Guerra B, Simonazzi G, Puccetti C, Lanari M, FarinaA, Lazzarotto T, et al. Ultrasound prediction ofsymptomatic congenital cytomegalovirus infection.Am J Obstet Gynecol. 2008;198(4):380.e1–7.

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Correspondence: Mehmet Emin Ozyalvacli, Department of Urology, Abant Izzet Baysal University, Turkey.Conflict of Interest: NoneE-mail: [email protected]


Relationship between Prostate Size and Positive Surgical Margin in the Open Radical Prostatectomy Surgery

Mehmet Emin Özyalvaçlı1, Ramazan Kocaaslan2, Uğur Yücetaş3, Erkan Erkan3, Ali Feyzullah Şahin4, Mustafa Kadıhasanoğlu3, Yusuf Şahin3, Erdinç Ünlüer2

1 Department of Urology, Abant Izzet Baysal University, Bolu, Turkey2 Department of Urology, Kafkas University, Kars, Turkey3 Department of Urology, Ministry of Health Istanbul Education and Research Hospital, Istanbul, Turkey4 Department of Urology, Sifa University, İzmir, Turkey

Introduction: Our study aims to reveal the correlation between positive surgical margins and prostate volume, thus determin-ing a cutoff value for the prostate volume to predict PCM in patients with open radical prostatectomy.

Methodology: In our study, a number of 450 patients who had undergone radical prostatectomy surgery at 2 centers within the last 5 years was evaluated. Age, total PSA, number of positive cores for prostate cancer, Gleason score, transfusion amount and prostate volume were all evaluated in the study. Evaluated all these parameters, 170 consecutive patients of whom data were available were included in the study

Results: Stage T3 and PSA>10 ng/dL were statistically significant for positive surgical margins (p=0,002 and p<0,001, respec-tively). The number of positive cores and Gleason score from these biopsies was also statistically higher in those with positive surgical margins (p=0,002 and p<0,001, respectively). In the multivariate logistic regression analysis, the risk for PCM was found to be 2.67 times higher in patients with PSA>10 ng/dL (95% CI: 1.18 to 6.04; p = 0.018) and stage T3 increased the risk for PCM by 8.51 times (95% CI: 3.54 to 20.51, p = <0.001). When we performed AUROC analysis to determine the positivity of surgical margin in terms of prostate volume, we achieved a cutoff value of 34.5 with 55% sensitivity and 71% specificity (AUC: 0.646, 95% CI: 0.555 to 0.737, p = 0.002). Again, any value above 34.5 cc was found to statistically significantly increase the risk for PCM by 2.86 times (95% CI: 1.31 to 6.28; p = 0.009).

Conclusion: We found that the prostate volume had an important role in positivity of surgical margins. It is likely that addi-tion of prostate volume as well to nomograms used before surgery may be useful in improving of risk assessment in prostate cancer. Furthermore, evaluation of the prostate volume can be used as a prognostic factor for prostate cancer.

Key Words: Radical Prostatectomy, Prostate Size, Surgical Margin


doi: 10.5505/actamedica.2016.30502

Abstract

Introduction

Radical prostatectomy (RP) in patients with localized prostate cancer is considered the gold standard compared to the other treatment alternatives. Considering the fact that the most useful method in diagnostic and clinical aspects is the one providing us with the best information on stage, grade and surgical margin, this treatment method gives us more precise information. RP is achieved by using any one of three methods including open, laparoscopic and robotic approaches. Although many studies have suggested both the benefits and the disadvantages of each method, there is need for further studies with large series, particularly in robotic surgery. All of these three methods revealed particularly the importance of prostate volume on RP outcomes (1-9). Positive surgical margin (PCM)

is a common problem confronted after surgery. The term positive surgical margin refers to a correlation of cancer cells with margins of radical prostatectomy specimens. It is probably a result of an intra-prostatic incision. This usually results from the efforts to leave a longer urethra during apical dissection to preserve its continence or at spacing the neurovascular bundle for the protection of erectile function (10). The importance of PCM includes higher recurrence rate in these patients during postoperative period and shorterlife expectation (11, 12). One of the factors affecting PCM is the prostate volume (PV). A few recent studies have pointed out a negative correlation between the PV and the PCM (1, 3, 13). However, a wide range of prostate volumes was assessed in these studies.

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Özyalvaçlı et al.

Our study aims to reveal the correlation between positive surgical margins and prostate volume, thus determining a cutoff value for the prostate volume to predict PCM in patients with open radical prostatectomy.


In our study, a number of 450 patients who had undergone radical prostatectomy surgery at 2 centers within the last 5 years was evaluated. Upon the approval from the ethics committee of our hospital; demographic, radiological and operational data were obtained from the hospital data bank for these patients. On the other hand, pathological data were extracted from the pathology database and archive. Age, total PSA, number of positive cores for prostate cancer, Gleason score, transfusion amount and prostate volume were all evaluated in the study. The Gleason score was assessed according to 2009 International Society of Urology Pathology (ISUP) application. The prostate volume was determined using the formula of ᴨ / 6 x height x width x length for elliptical volume accompanied by transrectal ultrasonography. Any use of nerve-sparing technique or approach was left to the discretion of surgeon and/or institution. All patients underwent open RP by physicians with at least 10 years of experience using the technique described by Walsh. Evaluated all these parameters, 170 consecutive patients of whom data were available were included in the study. Pathological specimens were evaluated in a similar manner at both institutions. Surgical specimens were fixed in 10% formalin. The outer surface of prostate was stained with Indian ink. Samples were collected from seminal vesicles for bladder neck as well as from apex for surgical margins. Sectioning at intervals of 4-5 mm was performed from bladder neck to apex, and these sections were pathologically staged according to the 2002 TNM calcifications.

Statistical Analysis

Statistical analyses were performed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY). Continuous variables were tested for normality by the Kolmogorov–Smirnov test. Normally distributed data are presented as means ± standard deviation. The rates and proportions of discrete variables were determined using the chi-squared test. The median with data range (minimum to maximum) was used for non-normally distributed data. The independent-samples t-test and Mann–Whitney U test were used for parametric and nonparametric groups, respectively. For the multivariate analysis, parameters which are significant in the univariate

analysis in terms of positive surgical margins were analyzed using logistic regression analysis to determine the independent predictive terms. Results were expressed as odds ratio (OR) and 95% confidence interval (CI). The two-sided p value of <0.05 was considered to indicate statistical significance.

Results

When evaluated 170 patients included in the study, the mean age was 63.3 ± 6.2 for patients with negative surgical margin, whereas it was 63.6 ± 5 for those with positive surgical margins. Compared to those with PSA ≤ 10 ng/dl, the patients with PSA >10 ng/dl demonstrated statistically significant PCM in univariate analysis (p=0,002). The number of positive cores was statistically significantly higher in those with positive surgical margin in transrectal biopsies obtained before radical prostatectomy (p = 0.002). The Gleason score from these biopsies was also statistically higher in those with positive surgical margins (p <0.001). Evaluated the stages again, a statistically significantly higher T3 stage was found in the patient group with positive surgical margin (p <0.001) (Table 1). When we performed AUROC

analysis to determine the positivity of surgical margin in terms of prostate volume, we achieved a cutoff value of 34.5 with 55% sensitivity and 71% specificity (AUC: 0.646, 95% CI: 0.555 to 0.737, p = 0.002) (Figure 1). When we examine the prostate volume at this level, we found the positivity of surgical margin to be statistically significantly higher in patients with prostate volume being equal to or less than 34.5 cc

Table 1. Comparison of patients according to the presence of surgical margin.

Negative Surgical Margin

Positive Surgical Margin

p

N 108 (63,5%) 62 (36,5%)

Age 63,3±6,2 63,6±5,0 0,764

Total PSA≤10 80 (74,1%) 31 (50%)

0,002>10 28 (25,9%) 31 (50%)

Number of Core 3 (1-10) 4 (1-12) 0,002

Gleason Score 6 (4-9) 6 (5-9) < 0,001

Transfusion 0 (0-7) 1 (0-8) 0,183

Prostate Volume

≤ 34,5

31 (28,7%) 34 (54,8%)

0,001>

34,577 (71,3%) 28 (45,2%)

StageT2 97 (89,8%) 27 (43,5%)

< 0,001T3 11 (10,2%) 35 (56,5%)

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compared to those with above 34.5 cc (p = 0.001). In the multivariate logistic regression analysis, the risk for PCM was found to be 2.67 times higher in patients with PSA> 10 ng / dL when compared to those with ≤10 ng / dl (95% CI: 1.18 to 6.04; p = 0.018). We also found that stage T3 increased the risk for PCM by 8.51 times than the stage T2 (95% CI: 3.54 to 20.51, p = <0.001). Again, considering the value of prostate volume as 34.5 cc, any value above 34.5 cc was found to statistically significantly increase the risk for PCM by 2.86 times (95% CI: 1.31 to 6.28; p = 0.009) (Table 2).

Table 2. Multivariate logistic regression analysis of independ-ent predictive factors for positive surgical margin of the pros-tate cancer.

Reference OR95%

Confidence Interval

Age 0,99 0,93-1,07 0,92

Total PSA≤10

>10 2,67 1,18-6,04 0,018>10

Number of Core 1,11 0,94-1,32 0,20

Gleason Score 1,44 0,85-2,43 0,17

Prostate Volume

≤34,5

≤34,5 2,86 1,31-6,28 0,009

>34,5

StageT2

T3 8,51 3,54-20,51 < 0,001T3

Discussion

In our study, there was a significant correlation between the patients with PSA > 10 ng / dL and those in stage T3 to the extent that the positivity of surgical margin increased by 2.67 and 8.51 times, respectively. Likewise, concordant to the current studies, a significant correlation was found between decreased prostate volume and the positivity of surgical margin to increase the risk by 2.86 times.

Positive surgical margins after radical prostatectomy have been reported as 11% to 46% in several studies (14-16). Our study suggested this rate as 36.5%. One of the most important factors in the development of local recurrence after RP is the positivity of surgical margins (17, 18).In a study, the recurrence rate was found 19% in patients with positive surgical margin, whereas it was 7% in those with negative (19). The nonrecurring rate over 5 years in patients with positive surgical margin was 64%, whereas it was found 83% in those with negative surgical margin. As a consequence, positive surgical margin has shown to be an independent risk factor of PSA recurrence, with an emphasis on the importance of its prevalence and number (20). One study showed a 10-year-survival rate of 88% in recurrent patients, while it was found 93% in those without recurrence, emphasizing that recurrence could be a sign for additional treatment (21). However, publications pointing out the effect of PCM on metastatic progression and cancer-specific mortality are fairly not very consistent. Wright et al. reported in a study that the mortality risk due to prostate cancer was 1.7 times higher in patients with PCM than those without it (22). Chalfie et al. suggested the adverse effect of PCM on survival in their study (23), but they also noted that this effect was relatively low when compared to Gleason score and pathological stage.

In current studies, the relationship between prostate volume and PCM was evaluated for all surgical treatment methods of prostate cancer (2, 13, 24, 25). In a study of Freedland et al., a number of 1602 patients who received open RP surgery were evaluated. In this study, the rate of high-grade disease was found to be significantly higher in those with lower prostate weight (with the risk being elevated by 7.61 times in patients with PV of 20 g compared to those with ≥100 g). Again, in this study, PCM was significantly higher in patients with lower PV (with the risk being elevated by 3.09 times in patients with PV of 20 g compared to those with ≥100 g). Furthermore, in this study, biochemical progression was found higher in patients with lower PV (with the

Figure 1. Assessment of cut off value of prostate volume for positive surgical margin.

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risk being elevated by 3.94 times in patients with PV of 20 g compared to those with ≥100 g). When the study was evaluated; high-grade cancer, advanced disease and biochemical progression were all found significantly higher after RP in patients with lower PV, suggesting a possibly prognostic importance of PV on prostate cancer (2). Unlike our study, this study did not indicate a cut-off value for PV; various prostate volumes were rather compared. In a multicenter study of Patel VR et al., 6169 robotic RP patients due to prostate cancer were included in the study. This study investigated any relevant factors associated with PCM as well as its incidence in robotic RP. The rates for PCM in patients with T2 and T3 were found to be 9.5% and 37.2%, respectively. In multivariate analysis, pathological stage (4.588 times higher in patients with T3 than those of T2) and preoperative PSA (2.918 times higher in patients with PSA >10 ng/dl than those with ≤4) were found to be independent predictive factors for PCM in robotic RP. Again, this study demonstrated a correlation of increased PV with decreased PCM (24). Similarly, elevated PSA levels and stage were found to be an independent predictive factor for PCM in our study. We also found that any value of PV under 34.5 cc was an independent predictive factor for PCM. In their study, Link BA et al. investigated whether the prostate weight had any effect on pathological and operative outcomes in 1847 patients who underwent robotic RP by 4 distinct surgeons. Prostate weights were classified as <30 g, 30 - 49.9 g, 50 - 69.9 g and 70 g ≤. In this study, the PCM rate was significantly higher in patients with lower PV (13). Again, this study did not provide with a cutoff value for PV in determining PCM. Foley et al., in their study, evaluated the effects of prostate size on controlling

cancer, continence and potency rates. A number of 440 patients who underwent open RP surgery were included in the study. The patients were divided into two groups, namely ≤ 75 g and > 75 g. The grade, tumor size and stage were found to be significantly lower in patients with > 75 g. Likewise; biochemical non-recurrence was significantly higher in patients with larger prostates (3). The presence of PCM does not only affect patients based on their oncologic outcomes, but also raises generalized anxiety and often increases the need for additional treatment (26). Therefore, surgeons should make more of an effort to decrease the rates of positive surgical margins, while trying to maintain the quality of life of patients in terms of postoperative urinary and erectile function.

In general; the grade of disease, stage, biochemical progression and positivity for surgical margin tend to increase in patients with lower prostate volume. This is related to a deteriorated course of illness. The reason for increased positivity of surgical margin in those with lower prostate volume may be the challenge of distinguishing between prostatovesical and prostatourethral junctions.

In conclusion, we found that the prostate volume had an important role in positivity of surgical margins. It is likely that addition of prostate volume as well to nomograms used before surgery may be useful in improving of risk assessment in prostate cancer. Furthermore, evaluation of the prostate volume can be used as a prognostic factor for prostate cancer. Our study is a breakthrough in that it provides with a cutoff value in determining the positivity of surgical margins. Yet, further studies are needed with greater numbers of patients.

1. Hsu EI, Hong EK, Lepor H. Influence of body weightand prostate volume on intraoperative, perioperative,and postoperative outcomes after radical retropubicprostatectomy. Urology. 2003 Mar;61(3):601-606.

2. Freedland SJ, Isaacs WB, Platz EA, Terris MK, AronsonWJ, Amling CL, et al. Prostate size and risk of high-grade, advanced prostate cancer and biochemicalprogression after radical prostatectomy: a searchdatabase study. J Clin Oncol. 2005 Oct 20;23(30):7546-7554.

3. Foley CL, Bott SR, Thomas K, Parkinson MC, Kirby RS.A large prostate at radical retropubic prostatectomydoes not adversely affect cancer control, continenceor potency rates. BJU Int. 2003 Sep;92(4):370-374.

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5. Chang CM, Moon D, Gianduzzo TR, Eden CG. The impact of prostate size in laparoscopic radical prostatectomy.Eur Urol. 2005 Aug;48(2):285-290.

6. Singh A, Fagin R, Shah G, Shekarriz B. Impact ofprostate size and body mass index on perioperativemorbidity after laparoscopic radical prostatectomy. JUrol. 2005 Feb;173(2):552-554.

7. El-Feel A, Davis JW, Deger S, Roigas J, Wille AH, Schnorr

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D, et al. Laparoscopic radical prostatectomy--an analysis of factors affecting operating time. Urology. 2003 Aug;62(2):314-318.

8. Zorn KC, Orvieto MA, Mikhail AA, Gofrit ON, LinS, Schaeffer AJ, et al. Effect of prostate weight onoperative and postoperative outcomes of robotic-assisted laparoscopic prostatectomy. Urology. 2007Feb;69(2):300-305.

9. Boczko J, Erturk E, Golijanin D, Madeb R, Patel H, Joseph JV. Impact of prostate size in robot-assisted radicalprostatectomy. J Endourol. 2007 Feb;21(2):184-188.

10. Saranchuk JW, Kattan MW, Elkin E, Touijer AK,Scardino PT, Eastham JA. Achieving optimal outcomesafter radical prostatectomy. J Clin Oncol. 2005 Jun20;23(18):4146-4151.

11. Billis A, Watanabe IC, Costa MV, Telles GH, MagnaLA. Iatrogenic and non-iatrogenic positive margins:incidence, site, factors involved, and time to PSAprogression following radical prostatectomy. Int UrolNephrol. 2008;40(1):105-111.

12. Brimo F, Partin AW, Epstein JI. Tumor grade at marginsof resection in radical prostatectomy specimens is anindependent predictor of prognosis. Urology. 2010Nov;76(5):1206-1209.

13. Link BA, Nelson R, Josephson DY, Yoshida JS, CrocittoLE, Kawachi MH, et al. The impact of prostategland weight in robot assisted laparoscopic radicalprostatectomy. J Urol. 2008 Sep;180(3):928-932.

14. Hull GW, Rabbani F, Abbas F, Wheeler TM, Kattan MW,Scardino PT. Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol. 2002Feb;167(2 Pt 1):528-534.

15. Cheng L, Slezak J, Bergstralh EJ, Myers RP, ZinckeH, Bostwick DG. Preoperative prediction of surgicalmargin status in patients with prostate cancertreated by radical prostatectomy. J Clin Oncol. 2000Aug;18(15):2862-2868.

16. Obek C, Sadek S, Lai S, Civantos F, Rubinowicz D,Soloway MS. Positive surgical margins with radicalretropubic prostatectomy: anatomic site-specificpathologic analysis and impact on prognosis. Urology.1999 Oct;54(4):682-688.

17. Wieder JA, Soloway MS. Incidence, etiology, location,prevention and treatment of positive surgical marginsafter radical prostatectomy for prostate cancer. J Urol.1998 Aug;160(2):299-315.

18. Budaus L, Isbarn H, Eichelberg C, Lughezzani G, Sun M, Perrotte P, et al. Biochemical recurrence after radicalprostatectomy: multiplicative interaction betweensurgical margin status and pathological stage. J Urol.2010 Oct;184(4):1341-1346.

19. Simon MA, Kim S, Soloway MS. Prostate specificantigen recurrence rates are low after radicalretropubic prostatectomy and positive margins. J Urol. 2006 Jan;175(1):140-144; discussion 144-145.

20. Pound CR, Partin AW, Epstein JI, Walsh PC. Prostate-specific antigen after anatomic radical retropubicprostatectomy. Patterns of recurrence and cancercontrol. Urol Clin North Am. 1997 May;24(2):395-406.

21. Frazier HA, Robertson JE, Humphrey PA, Paulson DF.Is prostate specific antigen of clinical importance inevaluating outcome after radical prostatectomy. JUrol. 1993 Mar;149(3):516-518.

22. Wright JL, Dalkin BL, True LD, Ellis WJ, Stanford JL,Lange PH, et al. Positive surgical margins at radicalprostatectomy predict prostate cancer specificmortality. J Urol. 2010 Jun;183(6):2213-2218.

23. Chalfin HJ, Dinizo M, Trock BJ, Feng Z, Partin AW,Walsh PC, et al. Impact of surgical margin status onprostate-cancer-specific mortality. BJU Int. 2012Dec;110(11):1684-1689.

24. Patel VR, Coelho RF, Rocco B, Orvieto M, Sivaraman A,Palmer KJ, et al. Positive surgical margins after roboticassisted radical prostatectomy: a multi-institutionalstudy. J Urol. 2011 Aug;186(2):511-516.

25. Rassweiler J, Seemann O, Schulze M, Teber D,Hatzinger M, Frede T. Laparoscopic versus openradical prostatectomy: a comparative study at a singleinstitution. J Urol. 2003 May;169(5):1689-1693.

26. Hong YM, Hu JC, Paciorek AT, Knight SJ, Carroll PR.Impact of radical prostatectomy positive surgicalmargins on fear of cancer recurrence: results fromCaPSURE. Urol Oncol. 2010 May-Jun;28(3):268-273.

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Correspondence: Dr. Engin Şengül, Dicle University, Faculty of Medicine, Diyarbakir, Turkey.Conflict of Interest: NoneE-mail: [email protected]



doi: 10.5505/actamedica.2016.25349

Abstract

Department of Otolaryngology, Dicle University, Faculty of Medicine, Diyarbakir, Turkey.

Engin Şengül, Beyhan Yılmaz, Musa Özbay, İsmail Topçu

Thyroid Masses: An Analysis of 135 Cases

Introduction

The incidence of thyroid nodules is different between societies; however, it may be observed frequently in regions with iodine deficiency, in women and in people exposed to radiation. Although thyroid nodules are diagnosed on admission of the patients with the complaint of palpation of a mass on the neck, it has recently been diagnosed randomly during high-resolution thyroid ultrasonography (USG) at a significant rate. On the high-resolution ultrasonography performed randomly on individuals, thyroid nodules have been detected at a rate of 19-68%, being higher among women and the elderly (1). Presence of or suspected malignancy, pressure symptoms, cosmetic concerns, substernal goiter and hyperthyroidism resistant to medical treatment are the surgical indications of nodular goiter, which is commonly treated surgically (2). The decision of surgery with a proper indication is important in preventing unnecessary interventions in this disease with a high rate of surgical treatment. The usage of diagnostic thyroid and neck USG is suggested as an obligation in the evaluation of suspected or already

known thyroid nodules and cervical lymph nodes according to 2016 American Thyroid Association (ATA) guidelines (3). The characteristic of thyroid nodule like size, echogenicity, border regularity, vascularity, calcification and solid-cystic content arouse suspicion of malignancy and guide us to fine needle aspiration (3). Complications following thyroidectomy are rare; however, they have the potential of negatively affecting the life-quality of the patient. These include vocal cord paralysis, hypocalcaemia, hemorrhage, scarring and seroma (4).

The aim of this study was to retrospectively investigate the data of the patients undergoing thyroid surgery and to discuss these data in the light of the literature.


A total of 135 patients operated due to thyroid nodule in the Ear-Nose-Throat Clinic of Dicle University Medical Faculty between January 2008 and January 2016 were included in the study.

Introduction: The aim of this study was to retrospectively evaluate the pre- and post-operative findings, the procedures per-formed and the complications in patients undergoing thyroid surgery.

Methods: The files of 135 patients, who had undergone thyroid surgery in the Ear-Nose-Throat Clinic of Dicle University Medical Faculty between January 2008 and January 2016 were retrospectively investigated, and the age, gender and the complaints of the patients, examinations and surgical procedures performed, pathological diagnoses, complications and the duration of follow-up of the patients were recorded.

Results: Among the 135 patients, 101 were female (74.8%) and 34 were male (25.2%). The mean age was 43.3±12.3 (range: 7-84) years. Nodules detected on the ultrasonography were single in 39 patients (28.9%) and multiple in 96 patients (71.1%). The most frequently detected nodules on the USG examination were nodules with mixed echogenicity (42.2%) and hypo echoic solid nodules (40.0%), whereas micro-calcification was detected in 20.7% of the patients. The procedures performed were to-tal thyroidectomy in 79 patients, lobectomy+isthmusectomy in 34, completion thyroidectomy in 5, total thyroidectomy+neck dissection in 14, and completion thyroidectomy+neck dissection in 3. The histopathological examination results for the speci-mens were benign in 95 (70.4%) and malignant in 40 (29.6%). The most common post-operative complication was temporary hypocalcaemia (18 patients; 13.3%). Statistical analysis showed that the presence of micro-calcification and hypo echoic nod-ule significantly increased the risk of malignancy.

Conclusion: In recent years, thyroid surgery, which has been performed frequently by the ear-nose-throat specialists, is a surgery in which the pre-operative evaluation is of great concern, and may lead to significant problems by means of complications.

Keywords: Complication, thyroid carcinoma, thyroid gland, thyroid surgery.

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The patient files were retrospectively evaluated. The age, gender and complaints of the patients, examinations and surgical procedures performed, pathological diagnoses, complications and the duration of follow-up of the patients were recorded. The mean duration of follow-up was 20.4 months (3-48 months). In particular, patients with a minimum duration of follow-up of 12 months were included in the presence of a malignant thyroid disease. Thyroid function tests (free T3, free T4 and TSH), thyroid USG and FNAB were performed on all patients prior to the operation. Furthermore, the pre- and post-operative vocal cord functions of all patients were evaluated. During thyroidectomy, the recurrent laryngeal nerve was found and protected in all cases in the surgical approach. During the dissection, the parathyroid glands were attempted to be protected without impairment in its blood circulation. The serum calcium levels of the patients were evaluated during the operation and post-operative thyroid hormone replacement was administered to each patient undergoing total thyroidectomy. The normal range for calcium level was accepted as 8.4 – 10.2 mg/dl in our laboratory. The hypocalcaemia and vocal cord paralysis that did not improve within 6 months after the operation were considered permanent. The pre-operative demographic characteristics and the USG findings (number of nodules, presence of micro-calcification, echogenicity of the nodule) of the patients, and the main specimen pathology reports were investigated and statistical comparison was made. The distribution of the complications was investigated in benign and malignant pathologies, and statistical comparison was made. Finally, comparisons of the results of FNAB and the main specimen pathologies were carried out.

The SPSS program package (ver. 18.0; SPSS, Chicago, IL, USA) was used for the statistical evaluation of the data. The Yates correction Chi-Square (Continuity Correction) test was used as the statistical method. P < 0.05 was considered to indicate statistical significance.

Results

Among the 135 patients, 101 were female (74.8%) and 34 were male (25.2%). The mean age was 43.3±12.3 (range: 7-84) years. The most common reason for admission was swelling in the neck (85.9%). The other complaints on admission included difficulty in swallowing (22.2%), pain in the neck (14.8%) and respiratory distress (14.1%). The most common causes of surgery were nodules with increasing sizes on the control visits (60.6%) and presence of pressure symptoms (24.7%).

Thyroid functions tests, USG and FNAB were performed for all patients prior to the operation. All patients were underwent operation when they were euthyroid. Nodules detected on the USG examination were single in 39 patients (28.9%) and multiple in 96 patients (71.1%). USG revealed hypoechoic solid nodules in 54 patients (40.0%), isoechoic nodules in 13 (9.6%), hyper-echoic nodules in 11 (8.1%) and nodules with mixed echogenicity including both solid and cystic components in 57 (42.2%). Additionally, micro-calcification was observed in 28 (20.7%) patients on USG (Table 1). The results of FNAB, which was accompanied by USG in the vast majority of the patients, were reported as benign cytology in 90, malignancy-positive cytology in 16, suspicious malignancy in 6, suspicious follicular

Table 1. Comparison of preoperative demographic characteristics and USG findings, and the main specimen pathology results.

Factors Benign Malign P value

Mean Age; (years) 42.1±11.2 46.0±14.3 0.096

Sex; n (%)FemaleMale

74 (73.3)21 (61.8)

27 (26.7)13 (38.2)

0.204

Nodularity; n (%)Solitary Multinodular

27 (69.2)68 (70.8)

12 (30,8)28 (29.2)

0.853

Echogenicity; n (%)HypoechogenicityIso echogenicity+ HyperechogenicityMixed echogenicity

31 (57.4)21 (87.5)43 (75.4)

23 (42.6)3 (12.5)

14 (24.6)

0.015

Microcalcification; n (%) 10 (33.3) 20 (66.7) <0.001

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neoplasia in 14 and non-diagnostic cytology in 9 patients (Table 2). Histopathological examination revealed benign specimens in 95 cases (70.4%) and malignant specimens in 40 (29.6%). The most frequent benign pathology was nodular colloidal goiter, whereas papillary carcinoma (classic variant+ follicular variant) was the most frequent malignant pathology (Table 3). Table 2 presents the comparison of FNAB results and the main specimen pathology results.

Table 3. Distribution of the patients according to the his-topathological diagnosis.

Diagnosis Number of patients (n)

%

Benign 95 70.4

Nodular colloidal goiter 85 63.0

Follicular adenoma 4 3.0

Hashimoto’s disease 4 3.0

Diffuse colloidal goiter 2 1.5

Malign 40 29.6

Papillary carcinoma; classic variant 20 14.8

Papillary carcinoma; follicular variant 15 11.1

Follicular carcinoma 3 2.2

Medullary carcinoma 1 0.7

Hurthle cell carcinoma 1 0.7

The procedures performed were total thyroidectomy in 79 patients, lobectomy and

isthmusectomy in 34, completion thyroidectomy in 5, total thyroidectomy+ neck dissection in 14, and completion thyroidectomy+ neck dissection in 3. Lobectomy and isthmusectomy was performed on 34 patients with nodular goiter and without suspicious or observed malignant cytology in FNAB, and papillary carcinoma was detected in only 2 of these patients via histopathological examination. Total thyroidectomy was performed on 71 patients with mostly multinodular goiter and without suspicious or observed malignant cytology in FNAB, and papillary carcinoma was determined in 7 of these patients and follicular carcinoma in 1, via histopathological examination. Completion total thyroidectomy (n=5) and completion thyroidectomy+ neck dissection (n=3) were performed as revision surgeries in 8 patients undergoing partial thyroidectomy, who were reported as papillary carcinoma in the histopathological examination despite no suspicious or observed malignant cytology in FNAB performed prior to the first operation. Only total thyroidectomy was performed on 8 of the 22 patients with suspicious or observed malignant cytology in FNAB, whereas total thyroidectomy+ neck dissection was performed on the remaining 14. The histopathological examination of these patients revealed papillary carcinoma in 18, follicular carcinoma in 2, medullary carcinoma in 1, and benign pathology in 1. Among the 17 patients undergoing neck dissection (4 underwent only central, and 13 underwent central+ lateral neck dissection), 7 were pre-operatively clinically N-positive cases, and malignancy was reported in the dissection material of the neck in all. Seven cases were pre-operatively clinical lymph node negative (No), and only 2 of these cases revealed malignancy in the neck dissection material.

Table 2. Comparison of fine needle aspiration biopsy (FNAB) results and main specimen pathology results.

The results of FNABHistopathological diagnosis

TotalBenign Malign

Benign; n (%) 76 (84.4) 14 (15.6) 90 (100)

Malignancy-positive; n (%) 0 (0) 16 (100) 16 (100)

Suspicious malignancy; n (%) 1 (16.7) 5 (83.3) 6 (100)

Suspicious follicular neoplasia; n (%) 11 (78.6) 3 (21.4) 14 (100)

Non-diagnostic; n (%) 7 (77.8) 2 (22.2) 9 (100)

Total; n (%) 95 (70.4) 40 (29.6) 135(100)

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The tumor size in 1 of these 2 cases was 1cm, and in the other, it was 2.5 cm.

The comparison of pre-operative demographic characteristics, USG findings and the specimen pathology results of the patients have been presented in Table 1. Accordingly, the presence of micro-calcification and hypo echoic nodule detected on USG significantly increased the risk of malignancy (p<0.001 and p=0.015, respectively).

No serious complication was observed post-operatively. During thyroidectomy, the recurrent laryngeal nerve was found and protected in all cases. The parathyroid glands were attempted to be protected without impairment in its blood circulation during dissection. The most frequent post-operative complication was transient hypocalcaemia (18 patients; 13.3%). The other complications included permanent hypocalcaemia (2 patients; 1.5%), transient vocal cord paralysis (2 patients; 1.5%), hematoma and scar infection (2 patients; 1.5%). No permanent vocal cord paralysis was observed. Most of the complications were observed in patients undergoing completion thyroidectomy and those with malignant thyroid pathologies (transient hypocalcaemia: 3, transient vocal cord paralysis: 1) (Table 4). The statistical analysis revealed a significantly increased rate of hypocalcaemia in malignant thyroid diseases compared to benign diseases (p<0.001).

Discussion

Findings of FNAB and USG are very important in evaluation and selection of surgical technique in patients with thyroid mass. Nodular goiter is an important clinical situation, since its incidence is high, its surgery is frequent, and it may cause post-operative complications that impair the life quality

of the patients. Nodular goiter is more frequent among women than men (5,6). In our study series, women were also higher in number than men. Histopathological examination reports for the specimens were benign in 95 (70.4%) and malignant in 40 (29.6%) patients. Papillary carcinoma was the most common result in patients with a malignant pathology (classic variant + follicular variant). These rates are similar to that in the study of Hu et al. (5) including 4632 patients.

Many nodules that cannot be detected by palpation in previous years can be identified with the use of high resolution USG and Doppler USG. Furthermore, with the help of high-resolution USG that is performed randomly on patients, thyroid nodules can be detected at a rate of 19-68%, being higher among women and the elderly (1). Advances in imaging modalities have contributed a major benefit in early diagnosis of thyroid malignancies (6,7). However this situation has increased the number of surgeries intended to thyroid gland as well. This has significantly contributed to the early-diagnosis of thyroid malignancies, and increased the number of surgeries of the thyroid gland as well. Benign and malignant differentiation of a nodule is very important in approach to thyroid nodules. Therefore, it is very important to perform USG, Doppler USG and FNAB accompanied by USG. Various characteristics such as the solid hypo echoic nature of the nodule, irregular contours, micro-calcification content, extra-thyroidal dispersion, and having a length longer than the width are important findings suggesting malignancy on USG (8). Micro-calcification, not containing a cystic component and heterogeneous internal structure have been reported as important USG findings in the diagnosis of thyroid carcinoma in many studies (9,10). In our study, the comparison of pre-operative USG findings and main specimen pathology results

Table 4. Distribution of the complications in benign and malignant thyroid pathologies.

Complications Benign(n=95) Malign (n=40) Total (n=135) P value

Primary surgery(n=32)

Revision surgery(n=8)

Hypocalcemia; n (%)TransientPermanent

5 (5.26)1 (1.05)

10 (31.25)1 (3.13)

3 (37.50)0

18 (13.33)2 (1.48)

<0.001

Recurrent laryngeal nerve palsy; n (%)TransientPermanent 0 (0)

0 (0)1 (3.13)

0 (0)1 (12.50)

0 (0)2 (1.48)

0 (0)

Wound hematoma and infection; n (%) 0 (0) 2 (6.25) 0 (0) 2 (1.48)

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revealed a significantly higher risk of malignancy in solid hypo echoic nodules compared to others (11-14). Furthermore, it was observed that as the solid component of the nodule increases (mixed echogenicity), the risk of malignancy increases. The presence of micro-calcification was observed to significantly increase the risk of malignancy in the nodule, similar to the literature (9,10,12-16).

FNAB should be precisely performed for the evaluation of suspicious nodules. FNAB, particularly when accompanied by USG, has been shown in many studies to reduce the risk of misdiagnoses and false negative results (11). Recently, in our clinics, all thyroid FNAB are performed with the guidance of USG. In different studies performing cytological evaluations with FNAB, the false negativity rate of malignancy was reported as 0-4%, and the false negative rate as 4-20% (6,12,17). In our study, the false positivity and negativity rates were 0% and 15.6%, respectively. We believe that FNAB and USG findings with malignancy potential should be evaluated together for the decision of the operation due to the high false negativity rate with FNAB, and that subtotal surgeries may be avoided, based on the results of FNAB.

In thyroid carcinomas, therapeutic lateral lymph node dissection has been recommended in lateral cervical lymphadenopathy confirmed by biopsy (3). Prophylactic central neck dissection has been recommended at a weak rate at a low evidence level in the presence of stage T3/T4 papillary carcinomas or lateral cervical lymph node metastasis (3). In our series, 7 of 17 patients undergoing neck dissection were pre-operatively clinically N-positive cases and malignancy was reported in the neck dissection materials of all. However, 7 cases were pre-operatively clinically N-negative, and only 2 of these cases revealed malignancy in the neck dissection material. The presence of central neck metastasis despite the 1 cm tumor size in 1 of these

2 cases indicates that it should not be disregarded that papillary carcinomas may show metastasis independent from the size of the tumor.

Complications such as transient and permanent hypoparathyroidism, recurrent laryngeal nerve paralysis, superior laryngeal nerve paralysis, as well as bleeding and scar infection may be observed after thyroid surgeries (4). In the series of Hu et al. (5) including 4632 patients, the rates of complications were reported as hypoparathyroidism (3,53%), transient recurrent laryngeal nerve paralysis (0,84%), permanent recurrent laryngeal nerve paralysis (0.34%) and permanent hypoparathyroidism (0,02%), respectively, in patients whose primary surgeries were performed by the same group as well. In the same series, transient hypoparathyroidism (13.76%), transient recurrent laryngeal nerve paralysis (11.11%), permanent recurrent laryngeal nerve paralysis (5.82%) and permanent hypoparathyroidism (1.59%) were observed in patients undergoing revision surgery. Similarly, in our study, most of the complications were observed in malignant thyroid pathologies and following revision surgeries. When it is considered that the complications may mostly be observed following completion surgeries needed after malignant thyroid mass surgeries and subtotal surgeries. We believe that subtotal surgeries must be avoided and that the minimal surgery be performed should be lobectomy- isthmusectomy.

Thyroid surgery, which has is currently performed frequently by ear-nose-throat specialists as well, is a surgery in which pre-operative evaluation is of great concern, and may lead to important problems due to complications. We believe that the FNAB results and USG findings that have the potential of malignancy should be evaluated together under the light of the recommendations of the recent guidelines for the decision of the operation.

References

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2. Süslü N, Hoşal Ş. Management of thyroid nodules and surgical indications. J Surg Med Sci 2007; 3(49):5-12.

3. Haugen BR, Alexander EK, Bible KC, Doherty G, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Associa-

tion Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016; 26:1-133

4. Christou N, Mathonnet M. Complications after total thyroidectomy. J Visc Surg 2013; 150(4):249-256

5. Hu J, Zhao N, Kong R, Wang D, Sun B, Wu L. Total thy-

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roidectomy as primary surgical management for thy-roid disease: surgical therapy experience from 5559 thyroidectomies in a less-developed region. World J Surg Oncol. 2016; 22;14(1):20.

6. Lew JI, Snyder RA, Sanchez YM, Solorzano CC. Fine needle aspiration of the thyroid: correlation with final histopathology in a surgical series of 797 patients. J Am Coll Surg 2011; 213(1):188-194.

7. Arslan MS, Sahin M, Delibasi T. Vitamin D and thyroid cancer. Acta Med Anatol 2014; 2(4): 152156.

8. Remonti LR, Kramer CK, Leitao CB, Pinto LC, Gross JL. Thyroid ultrasound features and risk of carcinoma: a systematic review and meta-analysis of observational studies. Thyroid 2015; 25(5):538-550.

9. Moon WJ, Jung SL, Lee JH, Na DG, Baek JH, Lee YH et al. Benign and malignant thyroid nodules: US differ-entiation-multicenter retrospective study. Radiology 2008; 247(3):762-770.

10. Bonavita JA, Mayo J, Babb J, Bennett G, Oweity T, Ma-cari M et al. Pattern Recognition of Benign Nodules at Ultrasound of the Thyroid: Which Nodules Can be Left Alone? AJR 2009; 193(1):207-213.

11. Alexander EK, Heering JP, Benson CB, Frates MC, Dou-bilet PM, Cibas ES et al. Assessment of nondiagnostic ultrasound-guided fine needle aspirations of thyroid nodules. J Clin Endocrinol Metab. 2002; 87(11):4924-4927

12. Maia FFR, Matos PS, Silva BP, Pallone AT, Pavin EJ, Vas-

sallo J et al. Role of ultrasound, clinical and scintigra-phyc parameters to predict malignancy in thyroid nod-ule. Head Neck Oncol 2011; 22(3):17.

13. Cakir B, Aydin C, Korukluoglu B, Ozdemir D, Sisman IC, Tuzun D et al. Diagnostic value of elastosonographical-ly determined strain index in the differential diagnosis of benign and malignant thyroid nodules. Endocrine 2011; 39(1):89–98.

14. Cantisani V, D’Andrea V, Biancari F, Medvedyeva O, Di Segni M, Olive M et al. Prospective evaluation of mul-tiparametric ultrasound and quantitative elastosonog-raphy in the differential diagnosis of benign and ma-lignant thyroid nodules: preliminary experience. Eur J Radiol. 2012; 81(10):2678–2683.

15. Lippolis PV, Tognini S, Materazzi G, Polini A, Mancini R, Ambrosini CE et al. Is elastography actually useful in the presurgical selection of thyroid nodules with in-determinate cytology? J Clin Endocrinol Metab 2011; 96(11):1826– 1830.

16. Frates MC, Benson CB, Charboneu WJ, Cibas ES, Clark OH, Coleman BG et al. Management of Thyroid Nod-ules Detected at US: Society of Radiologist in Ultra-sound Consensus Conference Statement. Radiology 2005; 237(3):794-800.

17. Sclabas GM, Staerkel GA, Shapiro SE, Fornage BD, Sherman SI, Vassillopoulou-Sellin R et al. Fine needle aspiration of the thyroid and correlation with histopa-thology in a contemporary series of 240 patients. Am J Surg 2003;186(6):702-709.

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Correspondence: Dr. Ali Özgen, Department of Radiology, Yeditepe University Hospital, Istanbul, TurkeyConflict of Interest: NoneE-mail: [email protected]

Original ArticleVolume 4 Issue 3 2016

Quantitative Comparison of 2D and 3D MRI Techniques for the Evaluation of Chondromalacia Patellae in 3.0T MR Imaging of the Knee

Ali Özgen, Zeynep Fırat

Department of Radiology, Yeditepe University Hospital, Istanbul, Turkey


doi: 10.5505/actamedica.2016.81905

Abstract

Introduction

Chondromalacia patellae is a very common disorder of patellar cartilage. Diagnosis of chondromalacia cannot be made solely on the basis of symptoms or with physical examination (1,2). Magnetic resonance imaging (MRI) has become a powerful non-invasive tool to investigate patellar cartilage lesions. Although many MRI sequences have been used in MR imaging of the patellar cartilage and the optimal pulse sequence is controversial, fat-saturated proton density images have been considered very valuable to evaluate patellar cartilage with high spatial resolution and good contrast-to-noise (CNR) ratio in a reasonable scan time (3,4). However, there still have been ongoing studies evaluating various two-dimensional (2D) and three-dimensional (3D) imaging techniques in detecting patellar cartilage lesions (5-8). T2 mapping also has been considered very valuable in detecting patellar cartilage lesions

(9-11). However very long imaging time and relatively low spatial resolution of this technique limits its use.

The purpose of this study is to quantitatively compare the diagnostic performance of various widely used 2D and 3D MRI techniques for the evaluation of chondromalacia patellae in 3.0T MR imaging of the knee using T2 mapping images as the reference standard.

Materials and Method

This prospective study was approved by the institutional ethics committee. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was

Introduction: Chondromalacia patellae is a very common disorder of patellar cartilage. Magnetic resonance imaging (MRI) is a powerful non-invasive tool to investigate patellar cartilage lesions. Although many MRI sequences have been used in MR imaging of the patellar cartilage and the optimal pulse sequence is controversial, fat-saturated proton density images have been considered very valuable to evaluate patellar cartilage. The purpose of this study is to quantitatively compare the diag-nostic performance of various widely used 2D and 3D MRI techniques for the evaluation of chondromalacia patellae in 3.0T MR imaging of the knee using T2 mapping images as the reference standard.

Methods: Seventy-five knee MRI exams of 69 adult consecutive patients were included in the study. Fat-saturated T2-weighted (FST2), fat-saturated proton density (FSPD), water-only T2-weighted DIXON (T2mD), T2-weighted 3 dimensional steady state (3DT2FFE), merged multi-echo steady state (3DmFFE), and water selective T1-weighted fat-suppressed (WATSc) images were acquired. Quantitative comparison of grade 1 and grade 5 lesions were made using contrast-to-noise (CNR) ratios. Grade 2-4 lesions were scored qualitatively and scorings of the lesions were compared statistically. Analysis of variance and Tukey’s tests were used to compare CNR data. Two sample z-test was used to compare the ratio of MR exams positive for grade 1 lesions noted on T2-mapping and other conventional sequences. Paired samples t-test was used to compare two different pulse sequences.

Results: In detecting grade 1 lesions, FSPD, FST2 and T2mD images were superior in comparison to other sequences. FSPD and FST2 images were statistically superior in detecting grade 2-4 lesions. Although all grade 5 lesions were noted in every single sequence, FST2 images have the highest mean CNR followed by 3DT2FFE images.

Conclusion: FST2 sequence is equal or superior in detecting every grade of patellar chondromalacia in 3.0T MR imaging of the knee in comparison to FSPD, T2mD, WATSc, 3DT2FFE, and 3DmFFE images.

Keywords: Patella, patellar chondromalacia, cartilage, magnetic resonance imaging.

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obtained from all individual participants included in the study.

Patients

Between June 2014- March 2015, 100 consecutive adult patients who underwent MR examination of knee were enrolled in the study. Fifteen patients with suspected tumors, previous surgery or implants that would cause artefacts were excluded. Sixteen patients were excluded because of motion of the patients that prevented optimum comparison of MR images. Finally 75 knee MRI exams of 69 adult consecutive patients (31 women and 38 men, mean age, 38 years; range, 21–76 years) were included in the study. Leading clinical diagnosis was patellar chondromalacia in 28 (41%), nonspesific pain in 16 (23%), meniscopathy in 13 (19%), anterior cruciate ligament tear in 5 (6%), and miscellaneous in 7 (10) patients.

MRI Protocol

All images were obtained with a 3T machine (Ingenia; Philips Medical Systems, Best, Netherlands) using a 16 channel transmit/receive dedicated knee coil. Technical data of used MR sequences were given in Table 1. Field of view was 80 mm. Slice thickness was 2 mm with no intersection gap. Resolution was 0.4x0.5 mm. Acquisition times of all 2D and 3D sequencesin the study were set between 2 minutes 3 secondsand 2 minutes 15 seconds by adjusting number of

excitations and acceleration factor except for T2 mapping sequence. Corresponding T2 mapping sequence (TR 2000/TE 13, 26, 39, 52, 65, 78) were obtained with the same slice thickness, 0.6x0.6 mm resolution with single excitation. Acquisition time of the T2 mapping sequence was 5 minutes and 40 seconds. In these images, orange areas represent normal cartilage whereas yellow, green and blue areas represent cartilage lesions with higher water content in that order.

Qualitative image analyses

All examinations were routinely reviewed by a radiologist with 17 years’ experience excluding the T2 mapping images. Patellar chondromalacia in each knee was graded according to Table 2. Patellar cartilage lesions graded between 2 and 4 were scored between 1 and 5 qualitatively according to ease of separation of the lesion from nearby normal appearing cartilage. Qualitative scorings of the lesions were compared statistically. Then T2 mapping images were reviewed for the detection of such cartilage lesions as the reference standard.

Quantitative image analyses

All grade 1 lesions noted on T2-mapping images were reviewed with standard sequences. CNR of all grade 1 lesions in all sequences were calculated using the formula:

Table 1. Grading systems for articular cartilage lesions

Grade Outer bridge ICRS Modified Noyes Current study

0 Normal Normal Normal Normal

1Softening and swelling, intact surface

Nearly normal (soft indentation and/or superficial fissures and cracks)

Increased T2 signal inten-sity of morphologically normal cartilage

Increased signal intensity of morphologically normal car-tilage

2

Fragmentation and fissuring of articular cartilage affecting anarea of less than 0.5 inches

Abnormal (Lesions extending to <50% of cartilage depth)

Superficial partial-thickness cartilage defect <50% of total articular surface thicknessDeep partial-thickness cartilage defect >50% of total articular surface thickness

Lesions extending to <50% of cartilage depth

3

Fragmentation and fissuring of articular cartilage affect-ing an area greater than 0.5 inches

Severely abnormal(Lesions extending >50% of cartilage depth, but not through subchondral bone)

Full-thickness cartilage defectLesions extending to ≥50% of cartilage depth

4 Cartilage erosion to boneLesions involving sub-chondral bone

Full-thickness cartilage lesions

5Lesions involving subchondral bone

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CNR = [Mean lesion – Mean cartilage] / SD air

Mean lesion is mean signal intensity of the grade 1 cartilage lesion, Mean cartilage is mean signal intensity of normal appearing cartilage nearby the lesion, and SD air is standard deviation of signal intensity of the air. Then all grade 5 lesions noted on each image sequence were evaluated with the same formula to reveal CNR data for those lesions.

Statistical analysis

Analysis of variance (ANOVA) and Tukey’s tests were used to compare CNR data. A P value less than 0.05 was considered to indicate a significant difference. Two sample z-test was used to compare the ratio of MR exams positive for grade 1 lesions noted on T2-mapping and other conventional sequences. Paired samples t-test was used to compare two different pulse sequences. All statistical analyses were performed with SPSS 20 software (Chicago, Illinois, USA).

Results

Fifty-seven grade 1 lesions were noted on T2-mapping images in 49 patients. Fifty-two of these lesions were also noted on both fat-saturated T2-weighted (FST2) and fat-saturated proton-density (FSPD) images. T2-mapping were statistically significantly

superior to both FST2 and FSPD images in detecting grade 1 lesions (p=0,022). Detection ratio of grade 1 lesions by other sequences remained lower; 48 for T2mD, 36 for 3DT2FFE, 42 for 3DmFFE, and 38 for WATSc images, respectively. Statistical comparison of quantitative CNR data in evaluating grade 1 lesions were given in Table 3. There was statistically significant difference in between groups (ANOVA test, p<0.0001). FSPD, FST2 and T2MD images were superior in comparison to other sequences (Tukey’s tests, p≤0.03) whereas these sequences were not statistically significantly different from each other (Tukey’s tests, p>0.05).

Twenty-seven lesions between grade 2 and 4 were noted on 24 patients on FST2, FSPD, and, while 17 were missed on WATSc images, 3 were missed on 3DT2FFE images, and 2 were missed on 3DmFFE images. Statistical comparison of CNR data in qualitative evaluation of lesions between grade 2 and 4 were given in Table 4. There was statistically significant difference in between groups (ANOVA test, p<0.0001). FSPD and FST2 images were statistically superior in detecting such lesions (Tukey’s tests, p≤0.024) whereas these two sequences were not statistically significantly different from each other (Tukey’s tests, p>0.05).

Fifteen grade 5 lesions in 13 patients were noted in every single MR sequence. All lesions were noted

Table 2. Technical specifications of MR pulse sequences.

Pulse sequence FST2 FSPD T2MD 3DT2FFE 3DmFFE WATSc

TR 3700 2000 2500 10 15 20

TE 65 30 70 5.8 9.2 4.1

Technique 2D TSE 2D TSE 2D TSE 3D FFE 3D FFE 3D FFE

Flip Angle 90 90 90 45 15 15

Fat suppression SPAIR SPAIR - - - SPIR

FST2; Fat-saturated T2-weighted, FSPD; Fat-saturated proton density, T2mD; Water-only T2-weighted DIXON, 3DT2FFE; T2-weighted 3D Steady state, 3DmFFE; Merged multi-echo steady state, WATSc; Water selective T1-weighted fat-suppressedTSE; Turbo spin echo, FFE; Fast field echo, SPAIR; Spectral attenuated inversion recovery, SPIR; Spectral presaturation inversion recovery.

Table 3. Quantitative comparison of CNR data for grade 1 lesions

Sequence FST2 FSPD T2MD 3DT2FFE 3DmFFE WATSc

Mean CNR 30.9 28.3 22.3 8.4 12.9 8.7

Standard deviation 24.4 19.0 16.2 6.0 12.8 9.3

FST2; Fat-saturated T2-weighted, FSPD; Fat-saturated proton density, T2MD; Water-only T2-weighted DIXON, 3DT2FFE; T2-weighted 3D Steady state, 3DmFFE; Merged multi-echo steady state, WATSc; Water selective T1-weighted fat-suppressed, CNR; Contrast-to-noise ratioThere was statistically significant difference in between groups (ANOVA test, p<0.0001).

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in every single sequence therefore there was no statistically significant difference in detecting grade 5 lesions (p=1). However CNR data showed statistically significantly difference as shown in Table 5 (ANOVA test, p<0.0001). FST2 images have the highest mean CNR followed by 3DT2FFE images. However mean CNR data for these two sequences were not statistically significantly different (Tukey’s tests, p>0.05). Totally 67 of 69 patients were diagnosed having chondromalacia patellae on MR imaging.

Discussion

Chondromalacia patellae is a very common disorder that cannot be diagnosed on the basis of symptoms or with physical examination (1,2). Although arthroscopy is generally considered reference standard for diagnosis, with current strength of magnets and development in coil production, MRI has become a very promising non-invasive tool in the diagnosis of patellar cartilage lesions. There have been many studies evaluating the capabilities of various 2D and 3D imaging techniques in detecting patellar cartilage lesions however optimal pulse sequence is still controversial (3-8).

In the literature, Outerbridge first described a basic grading system for patellar chondromalacia based on his surgical findings (1). This system has been widely used clinically in its original or revised forms. Noyes introduced another system for grading articular cartilage lesions based on arthroscopic findings (12). His system has also been used and has been modified for using MR classification of chondral lesions.

Recently, International Cartilage Research Society (ICRS) developed an arthroscopic cartilage injury grading system (13). Although there have also been some solitary or revised systems from Noyes or ICRS classifications for MR grading of cartilage damage used in clinical practice, there is no widely accepted MR grading system for patellar chondromalacia in the literature (2,5,9,10,14,15). Therefore, in this study, we preferred using a somewhat basic grading system which is given in Table 2 in comparison to other commonly used systems.

Our results suggest that for grade 5 subchondral lesions, diagnostic ability of all 2D and 3D MR pulse sequences in this study were not statistically significantly different. Therefore, these pulse sequences seem equal in detecting grade 5 patellar chondromalacia although mean CNR of these lesions were statistically significantly different and FST2 images had the highest mean CNR. Considering grade 2-4 lesions, FST2 and FSPD sequences are not statistically significantly different whereas these images are superior in comparison to all other pulse sequences. In detecting grade 1 lesions, although mean CNR data is the highest for FST2 images closely followed by FSPD images, FST2, FSPD, and T2mD sequences are not statistically significantly different whereas these pulse sequences seem statistically significantly superior in comparison to 3D pulse sequences. According to our results, FST2 pulse sequence is equal or superior in detecting every grade of patellar chondromalacia in MR imaging of the knee closely followed by FSPD sequence.

Table 4. Qualitative comparison of grade 2-4 lesions.


Mean CNR 4.25 4.33 3.55 1.1 1.33 0.89


FST2; Fat-saturated T2-weighted, FSPD; Fat-saturated proton density, T2mD; Water-only T2-weighted DIXON, 3DT2FFE; T2-weighted 3D Steady state, 3DmFFE; Merged multi-echo steady state, WATSc; Water selective T1-weighted fat-suppressedThere was statistically significant difference in between groups (ANOVA test, p<0.0001).

Table 5. Quantitative comparison of CNR data for grade 5 lesions.


Mean CNR 67.4 40.8 40.7 47.6 13.8 54.2


FST2; Fat-saturated T2-weighted, FSPD; Fat-saturated proton density, T2mD; Water-only T2-weighted DIXON, 3DT2FFE; T2-weighted 3D Steady state, 3DmFFE; Merged multi-echo steady state, WATSc; Water selective T1-weighted fat-suppressed, CNR; Contrast-to-noise ratioThere was statistically significant difference in between groups (ANOVA test, p<0.0001).

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There were many studies in the literature searching for the optimal image sequence in detecting cartilage lesions. Although fat-saturated proton density or intermediate weighted images have been generally considered very valuable to evaluate patellar cartilage with high spatial resolution and good CNR in a reasonable scan time the search for a better sequence has been continued (3,4,8). In the last decade, many 3D sequences were extensively investigated in detecting cartilage lesions in comparison to conventional 2D images however their diagnostic ability were not considered superior (6-8). More recently, isotropic 3D sequences with fat-suppression have been targeted in the search for optimal image sequences. Although there were some promising results, their exact value has not been well documented yet (16,17).

Although most of the studies in the literature have arthroscopic or surgical reference standards, their primary goal was to compare these sequences qualitatively with multiple observers and inter- and intraobserver reliability tests while comparing them

to arthroscopic findings (5,6,8). To the best of our knowledge, such quantitave comparison of CNR data regarding patellar chondromalacia have never been documented. Therefore, our study seems unique since we performed quantitative comparison of abovementioned sequences in grade 1 and grade 5 lesions which arthroscopy might not be considered as the reference standard for making the diagnosis. Besides, T2mD sequence has never been studied before in detecting patellar cartilage lesions. We also set almost equal acquisition times by adjusting number of excitations and acceleration factor for all 2D and 3D sequences to provide a fair comparison which many of the studies in the literature did not.

This study has some limitations. First, we do not have arthroscopic examinations as reference standard. However, this study largely depend on quantitative comparison of images and we used T2 mapping sequence as the reference standard for lesion detection. Besides, arthroscopic evaluation might not detect grade 1 lesions with intact articular surface as well as grade 5 subchondral lesions. Second, we

Figure 1. Axial MR images of a 27-year-old female showing grade 1 patellar chondromalacia in lateral facet of the patella (arrow). a) FST2 image, b) FSPD image, c) T2mD image, d) 3DWATSc image, e) 3DmFFE image, and f) 3DT2FFE image. Note chondral hyperintensity is best seen in two dimensional images.

Figure 1. a

Figure 1. d

Figure 1. b

Figure 1. e

Figure 1. c

Figure 1. f

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lack a fat-suppressed isotropic 3D sequences in comparison. However, these isotropic 3D sequences provides different temporal resolution than other conventional 2D and 3D images and therefore similar comparison with standard sequences is challenging. Besides, comparatively long acquisition times makes a fair comparison unlikely. Finally, although this study mainly depends on quantitave comparison, we lack interobserver reliability testing for detecting grade 2-4 lesions.

In conclusion, FST2 sequence is equal or superior in detecting every grade of patellar chondromalacia in 3.0T MR imaging of the knee in comparison to FSPD, T2mD, WATSc, 3DT2FFE, and 3DmFFE images. Newer isotropic 3D fat-suppressed proton density or intermediate weighted sequences might be considered as possible alternatives and be further studied.

References

1. Outerbridge RE. The etiology of chondromalacia patel-lae. J Bone Joint Surg Br. 1961;43(4):752-757.

2. Pihlajamäki HK, Kuikka PI, Leppänen VV, Kiuru MJ,Mattila VM. Reliability of clinical findings and magnet-ic resonance imaging for the diagnosis of chondroma-lacia patellae. J Bone Joint Surg Am. 2010;92(4):927-934.

3. Gold GE, Chen CA, Koo S, Hargreaves BA, BangerterNK. Recent advances in MRI of articular cartilage. Am J Roentgenol. 2009;193(3):628-638.

4. Crema MD, Roemer FW, Marra MD, Burstein D, GoldGE, Eckstein F, et al. Articular cartilage in the knee: cur-rent MR imaging techniques and applications in clinical practice and research. Radiographics 2011;31(1):37-62.

5. Recht MP, Piraino DW, Paletta GA, Schils JP, BelhobekGH. Accuracy of fat-suppressed three-dimensionalspoiled gradient-echo FLASH MR imaging in the detec-tion of patellofemoral articular cartilage abnormali-ties. Radiology 1996;198(1): 209-212.

6. Duc SR, Koch P, Schmid MR, Horger W, Hodler J,Pfirrmann CWA. Diagnosis of articular cartilage le-sions of the knee: prospective clinical evaluation ofa 3D water-excitation true FISP sequence. Radiology2007;243(2):475-482.

7. Milewski MD, Smitaman E, Moukaddam H, Katz LD, Es-sig DA, Medvecky MJ, et al. Comparison of 3D vs. 2Dfast spin echo imaging for evaluation of articular carti-lage in the knee on a 3 T system scientific research. Eur J Radiol. 2012;81(7):1637-1643.

8. Kim HJ, Lee SH, Kang CH, Ryu JA, Shin MJ, Cho KJ, et al.Evaluation of the chondromalacia patella using a micros-copy coil: comparison of the two-dimensional fast spinecho techniques and the three-dimensional fast fieldecho techniques. Korean J Radiol. 2011;12(1):78-88.

9. Kijowski R, Blankenbaker DG, Munoz Del Rio A, Baer

GS, Graf BK. Evaluation of the articular cartilage of the knee joint: value of adding a T2 mapping se-quence to a routine MR imaging protocol. Radiology 2013;267(2):503-513.

10. Dautry R, Bousson V, Manelfe J, Perozziello A, BoyerP, Loriaut P, Koch P, et al. Correlation of MRI T2 mapping sequence with knee pain location in young patientswith normal standard MRI. JBR-BTR 2014;97(1):11-16.

11. Xu J, Xie G, Di Y, Bai M, Zhao X. Value of T2-mappingand DWI in the diagnosis of early knee cartilage injury. J Radiol Case Rep. 2011;5(2):13-18.

12. Noyes FR, Stabler CL. A system for grading articularcartilage lesions at arthroscopy. Am J Sports Med.1989;17(4):505-513.

13. Brittberg M, Winalski CS. Evaluation of cartilage inju-ries and repair. J Bone Joint Surg Am. 2003; 85-A Suppl 2:58-69.

14. Gagliardi JA, Chung EM, Chandnani VP, KeslingKL, Christensen KP, Null RN, et al. Detection and stag-ing of chondromalacia patellae: relative efficacies ofconventional MR imaging, MR arthrography, and CTarthrography. Am J Roentgenol. 1994;163(3):629-636.

15. Pauli C, Whiteside R, Heras FL, Nesic D, Koziol J, Grogan SP, et al. Comparison of cartilage histopathology as-sessment systems on human knee joints at all stagesof osteoarthritis development. Osteoarthritis Carti-lage 2012;20(6):476-485.

16. Ristow O, Steinbach L, Sabo G, Krug R, HuberM, Rauscher I, et al. Isotropic 3D fast spin-echo imag-ing versus standard 2D imaging at 3.0 T of the knee -image quality and diagnostic performance. Eur Radiol.2009;19(5):1263-1272.

17. Friedrich KM, Reiter G, Kaiser B, Mayerhöfer M, Deim-ling M, Jellus V, et al. High-resolution cartilage imaging of the knee at 3T: basic evaluation of modern isotropic 3D MR-sequences. Eur J Radiol. 2011;78(3):398-405.

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Correspondence: Abdullah Talha Kabakuş, IT Center, Abant Izzet Baysal University, TurkeyConflict of Interest: NoneE-mail: [email protected]

Volume 4 Issue 3 2016doi: 10.15824/actamedica.2016.81300

Anatolian Medicine History

1 IT Center, Abant Izzet Baysal University, Turkey2 Department of Computer Engineering, Duzce University, Faculty of Engineering, Turkey

Abdullah Talha Kabakus1, Resul Kara2

The importance of informatics for health care industry

There is no industry that does not benefit from the advantages of information technology (IT). Health care industry is no different from them. IT solutions are used to (1) minimize the human resource required for labor-intensive or time consuming tasks by automating them, (2) benefit from the intelligent software solutions that not just store the data in electronic format but also ease the decision making process, (3) accelerate the business processes by providing services simultaneously, and (4) provide maintainable and consistent services. Despite all of these advantages, health care industry spends only 2% of its revenues on technology, which is very limited when it is compared to other industries that spend around 10% (1). According to the report published by University of Illinois at Chicago’s Online Health Informatics Program, 50,000 health care informatics professionals will be needed in the next 5-7 years which means 21% projected increase in health care informatics jobs between 2010 and 2020 (2). The advantages of IT solutions for health care industry can be listed as:

• Clinical decision support systems (CDSSs) are equipped with various software technologies such as artificial intelligent, fuzzy logic, artificial neural networks, and data mining to evaluate existing patients’ data to make a deduction about the patient’s diagnosis and make recommendations for the treatment.

• Electronic health record (EHR) refers to systematized collection of patient in a digital format (3). This record contains detailed information about the patient such as medical history, medication and allergies, immunization status, laboratory test results, radiology images, vital signs, personal stats like age and weight (4). Since this data is stored in digital format, it is accessible from anywhere and anytime when the access is granted. EHR lets patients to be informed about their laboratory test results and treatment processes. Also, storing the data in

digital format makes it possible to backup the whole data easily thanks to the state-of-the-art digital backup solutions. Storing the patient data in a central server is necessary in order to construct a knowledge base for the diseases and regarding treatments.

• Telemedicine is the use of communication technology based on the internet to provide health and social care directly to the patient located in a remote area (5). Telemedicine lets patients who may not be able to drive to meet physicians face-to-face such as patients with advanced level of muscle diseases, respiratory system diseases, and diabetes (6–8), to have a chance to communicate with their physicians through the internet. Another necessity for the use of Telemedicine is that underdeveloped countries are in need of large number of physicians as it is reported that in sub-Saharan Africa, on average, there are fewer than ten physicians per 100,000 people and 14 countries do not have radiologists (9). Telemedicine currently is widely used in different medical specialties such as psychiatry, neurology, cardiology, surgery, ophthalmology, genetics, pathology, microbiology, oncology, dermatology, dentistry, geriatrics (10). Telesurgery is one of telemedicine applications that lets physicians to operate patients with using manageable robots. The communication channel is in need of high bandwidth in order to provide a lag free synchronous communication between the surgeon and the robot.

It is evident that health care industry is in need of IT solutions more than any other industries due to three major reasons: (1) It is necessary to store and process large amount of patient data, (2) physicians need to use intelligent systems to make better diagnosis and arrange patient’s treatment with taking the advantage of being able to review arranged


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treatments for similar patients and their courses of disease, (3) physicians need to communicate with patients located in remote places. Informatics will not only ease the things for patients by letting them to drive the whole health care processes by online, but also will help physicians to make better decision for the patients’ treatments with using intelligent software systems and will let physicians

to monitor their patients closely. We experiment that telemedicine is not commonly used by the health care industry in Turkey especially when it is compared to overdeveloped countries. Despite that we think that the technological requirements for telemedicine are ready to popularize it in Turkey thanks to the latest developments in the information technology.

1. Clark C. Healthcare information systems. In: e-Health-care. Aspen; 1995. p. 300–1.

2. The Intersection of Healthcare and IT [Internet]. Uni-versity of Illinois at Chicago Program Online Health In-formatics. 2013 [cited 2016 May 10]. Available from: http://healthinformatics.uic.edu/resources/info-graphics/the-intersection-of-healthcare-and-it/

3. Gunter TD, Terry NP. The emergence of national elec-tronic health record architectures in the United States and Australia: Models, costs, and questions. Journal of Medical Internet Research. 2005.

4. Dinya E. Health Informatics: eHEALTH and TELEMEDI-CINE. 2013.

5. Barlow J, Singh D, Bayer S, Curry R. A systematic review of the benefits of home telecare for frail elderly peo-ple and those with long-term conditions. J Telemed Telecare. 2007;13(4):172–9.

6. Cherry JC, Moffatt TP, Rodriguez C, Dryden K. Diabetes

disease management program for an indigent popula-tion empowered by telemedicine technology. Diabe-tes Technol Ther. 2002;4(6):783–91.

7. Samii A, Ryan-Dykes P, Tsukuda RA, Zink C, Franks R, Nichol WP. Telemedicine for delivery of health care in Parkinson’s disease. J Telemed Telecare [Internet]. 2006;12(1):16–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16438773

8. Vitacca M, Bianchi L, Guerra A, Fracchia C, Spanevello A, Balbi B, et al. Tele-assistance in chronic respiratory failure patients: A randomised clinical trial. Eur Respir J. 2009;33(2):411–8.

9. Fraser HSF, McGrath SJD. Information technology and telemedicine in sub-Saharan Africa. BMJ Br Med J. 2000;321(7259):465–6.

10. Di Cerbo A, Morales-Medina JC, Palmieri B, Iannitti T. Narrative review of telemedicine consultation in medi-cal practice. Patient Prefer Adherence. 2015;9:65–75.

References

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Correspondence: Senem Şaş, Ahi Evran University Training and Research Hospital, Kirsehir, Turkey.Conflict of Interest: NoneE-mail: [email protected]


Senem Sas1, Hatice Rana Erdem2, Burcu Uysal3

1 Department of Physical Medicine and Rehabilitation, Ahi Evran University Training and Research Hospital, Kirsehir, Turkey2 Department of Physical Medicine and Rehabilitation, School of Medicine, Ahi Evran University, Kirsehir, Turkey3 Department of Infectiosus Disease and Clinical Microbiology, Ahi Evran University Training and Research Hospital, Kirsehir, Turkey

Brucellosis is a widely spread zoonosis and an important global public health problem, especially in the Mediterranean region. Brucellosis is a systemic infectious disease, and it is transmitted to humans by consumption of raw milk or its by-products as well as by contact with products of infected animals. Clinical findings differ depending on the Brucella species, the host, and the duration of illness. The diagnosis of brucellosis is made by positive culture. Since the organism is cultured on blood, the examination is made primarily on the basis of suspicion as well as the high levels of humoral antibody titer. The disease may cause various complications. The most common complications of brucellosis are osteoarticular complications, including arthritis, bursitis, and tendinitis. In this report, brucellar arthritis involving the sternoclavicular joint (STCJ) is presented. In this report we present a rare example of an osteoarticular complication caused by brucellosis.

Keywords: Brucellosis, sternoclavicular joint, osteoarticular complications.


doi: 10.15824/actamedica.72691

Abstract

Brucellar Arthritis Involving Left Sternoclavicular Joint: A Case Report

Case Report

Introduction

Brucellosis is a widely spread zoonosis and an important global public health problem, especially in the Mediterranean region. Brucellosis is a systemic infectious disease, and it is transmitted to humans by consumption of raw milk or its by-products as well as by contact with products of infected animals (1,2).

Brucellosis in humans is characterized mainly by fever. Clinical findings differ depending on the Brucella species, the host, and the duration of illness. The disease may cause various complications (1-4). The diagnosis of brucellosis is made by positive culture. Since the organism is cultured on blood, the examination is made primarily on the basis of suspicion as well as the high levels of humoral antibody titer (1,5).

The most common complications of brucellosis are osteoarticular complications, including arthritis, bursitis, and tendinitis. The most severe type of brucellosis is caused by B. Melitensis (1). The prevalence of this complication varies from 10% to 80% depending on the Brucella species. It was reported that genetic predisposition is linked with HLA-B39 (6).

In this report, brucellar arthritis involving the sternoclavicular joint (STCJ) is presented. It presents a rare example of an osteoarticular complication caused by brucellosis.

Case Report

A-39-year-old woman was admitted to ouroutpatient clinic of chest diseases with one weeklong chest pain, swelling, and redness in the leftsternoclavicular joint. Cardiac enzymes, troponin,and electrocardiogram (ECG) tests were performedand assessed as a routine procedure. The patientwas questioned to determine etiology of chest pain.During the palpation part of the clinical examination,the STCJ was tender over erythema and edemaregions. There was no other joint symptoms or clinical findings. The patient reported fever and fatigue.She was asked whether she consumed raw milk orits by-products since brucellar is endemic in Turkey.She reported no consumption of raw milk or its by-products. Hence, STCJ tomography was performedto find the etiology of arthritis. Radiology reporteda 2.5 mm hypodense area on the STCJ as seen inFigure 1-2. To determine the soft tissue pathologies,STCJ magnetic resonance (MR) was also performed.The results of the STCJ MR were reported as softtissue edema and inflammation around the left STCJ.Laboratory values were found as follows: (ESR) 75mm/h and C-reactive protein 0.6 mg/dl (0-0.5 mg/dl). The patient reported that she suffered fromfever and night sweats when the clinical examinationrepeated one week later. She also mentioned thehistory of miscarriage of a cow and her contact withits meat. To diagnose brucellosis, the patient wasadministered the brucellar agglutination test and the result of the test was positive with a value of 1/320.

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She consulted with the department of infectious diseases. The five weeks treatment involved 900 mg rifampin and 200 mg doxycycline. She was also prescribed ibuprofen 1600 mg daily for two weeks. As a result, rapid recovery of arthritis was observed.

Discussion

Brucellosis is a zoonosis caused by the species of the genus Brucella. Arthritis is commonly presented in the disease. Brucellar arthritis develops by seeding the microorganism or as a reactive arthritis (1,7).

The prevalence of sternoclavicular brucellosis is around 1 case out of every 250 cases of brucellosis or 1 case per 77 cases of osteoarticular brucellosis according to the data reported Mousa et al. (7,8).

Sternoclavicular arthritis is commonly considered to be infectious rather than reactive, and it was reported by Mousa et al. that sternoclavicular arthritis occurs in chronic brucellosis. However, our patient did not have chronic brucellosis.

Sternoclavicular arthritis occurs in 9% of patients of infectious arthritis. The most common microorganisms involved are gram-positive cocci (Staphylococcus aureus, hemolytic streptococci, Streptococcus pneumonia) or gram-negative rods, primarily Pseudomonas, Escherichia coli, Haemophilus influenza, and less commonly Salmonella or Brucella (9-11).

Adak et al. reported a-28-year old woman with a 4-month history of pain and stiffness in the lefttemporomandibular and left sternoclavicular joints,and left ankle with brucellosis. They reportedoligo arthritis involving the STCJ (12). However, wepresent a patient with acute monoarthritis on theSTCJ. Our patient’s disease history was two weekswhile the aforementioned patient’s disease historywas four months. The case presented in this reportwas diagnosed early because the patient lives in anendemic region for brucellosis.

In a study from Lima covering over a 21-year period, 1729 patients were reported to have been diagnosed with brucellosis. Only seven patients

Figure 1. (A,C) Axial T2W image and axial fat saturation T1W image show soft tissue edema and inflammation around left sternoclaviculer joint. (B) Soft tissue edema and inflammation around left sternoclavicular joint are seen also axial CT image.

Figure 2. Redness and swelling in sternoclavicular joint.

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had sternoclavicular arthritis. Moreover, only five of these seven patients had an acute course with current or past evidence of systemic infection (13).

The Pain in the STCJ may be confused with other articular pathologies, such as cervical spine, shoulder, acromioclavicular articulation, or costochondral arthritis. Furthermore, chest pain from sternoclavicular arthritis imitates cardiac pain, or pulmonary pathologies in addition to tumors (14).

The diagnosis of brucellosis is fairly difficult. The culture of the organism from the joint or bursae helps making a definite diagnosis. Increase in the serum agglutination titer, as well as clinical and

a radiological finding also supports a confident diagnosis (4,5).

Brucella involves the STCJ rarely (8). We considered Tietze`s syndrome (costochondritis) for differential diagnosis firstly. However, there was no trauma or occupational predisposition. Moreover, the elevation of acute phase reactants pointed to inflammatory arthritis.

In Summary, most of the patients report the consumption of unpasteurized cheese. On the other hand, there was a history of contact with infected meat in our case. In conclusion, Brucellosis should be considered in patients with sternoclavicular arthritis.

References

1. Young EJ. Brucella species. In: Mandell GL,Bennet JEDolin R, eds. Principles and Practice of Infectious Dis-ease. Philadelphia, PA: Churchill Livingstone; 2005:2669-74.

2. Taleski V, Zerva L, Kantardjiev T, Cvetnic Z, Erski-BiljicM, Nikolovski B, et al. An overview of the epidemiol-ogy and epizootology of brucellosis in selected coun-tries of Central and Southeast Europe. Vet Microbiol2002;90:147-55.

3. Wernaers P, Handelberg F. Brucellar arthritis of theknee: a case report with delayed diagnosis. Acta Or-thop Belg 2007;73:795-8.

4. Eales KM, Norton RE, Ketheesan N. Brucellosis innorthern Australia. Am J Trop Med Hyg 2010;83:876-8

5. Hashemi SH, Keramat F, Ranjbar M, Mamani M, Far-zam A, Jamal-Omidi S. Osteoarticular complications ofbrucellosis in Hamedan, an endemic area in the westof Iran. Int J Infect Dis 2007;11:496-500.

6. Bravo MJ, Colmenero JD, Alonso A, Caballero A. HLA-B*39 allele confers susceptibility to osteoarticularcomplications in human brucellosis. J Rheumatol2003;30: 1051-3.

7. Mousa AR, Muhtaseb SA, Almudallal DS, Khodeir SM,Marafie AA. Osteoarticular complications of brucello-sis: a study of 169 cases. Rev Infect Dis.1987;9:531-43.

8. Mousa AM, Muhtaseb SA, Al-Mudallal DS, MarafieAA, Habib FM. Brucellar sternoclavicular arthritis,the forgotten complication. Ann Trop Med Parasitol1988;82:275-81.

9. Womack J. Septic arthritis of the sternoclavicular joint. J Am Board Fam Med. 2012;25: 908-91.

10. Belkhir L, Rodriguez-Villalobos H, Vandercam B, MarotJC, Cornu O, Lambert M, et al. Pneumococcal septicarthritis in adults: clinical analysis and review. Acta ClinBelg 2014;69:40-6.

11. Ross JJ, Shamsuddin H. Sternoclavicular septic ar-thritis: review of 180 cases. Medicine (Baltimore)2004;83:139-48

12. Adak B, Tekeoglu I, Kutluhan A, Akdeniz H, Sakarya ME, Ugras S. Brucellar oligoarthritis involving the left tem-poromandibular, left sternoclavicular and left anklejoints. Clin Exp Rheumatol 1997;15:122-3.

13. Berrocal A, Gotuzzo E, Calvo A, Carrillo C, CastañedaO, Alarcón GS. Sternoclavicular brucellar arthritis: areport of 7 cases and a review of the literature. J Rheu-matol 1993;20:1184-6.

14. Van Tongel A, Karelse A, Berghs B, Van Isacker T, DeWilde L. Diagnostic value of active protraction and re-traction for sternoclavicular joint pain. BMC Musculo-skelet Disord 2014;15:421

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Acta Medica AnatoliaCase Report

Murat Şereflican1, Betül Şereflican2, Sinan Seyhan1, Nadir Göksügür2, Fahri Yılmaz3

1 Department of Otorhinolaryngology, Abant Izzet Baysal University School of Medicine, Bolu, Turkey 2 Department of Dermatology, Abant Izzet Baysal University School of Medicine, Bolu, Turkey 3 Department of Pathology, Abant Izzet Baysal University School of Medicine, Bolu, Turkey

Pilomatrixoma is a benign appendageal tumor derived from hair matrix cells which is also known as calcifying epithelioma of Malharbe. It usually appears as a solitary, asymptomatic, firm nodule. It is most common on the face and neck, but is occasionally found somewhere else on the body. A 18-year-old female was referred to dermatology clinic with a two year history of painless subcutaneous nodule in front of her right ear. The computed tomography imaging study demonstrated 8.5x12 mm subcutaneous mass lesion with calcification. Histopathological examination of the excised material showed the presence of basaloid cells associated with phantom cells, with areas of multinucleated giant cells, pigmented macrophages and widespread dystrophic calcification compatible with pilomatrixoma. In this case, we wished to present a patient who un-derwent excisional biopsy as a result of computed tomography imaging and whose pathological result was reported to be pi-lomatrixoma. Pilomatrixoma has long been supposed to be an infrequent tumor, but it may be more common than previously realized, so the clinicians must keep in mind the diagnosis of pilomatrixoma for subcutaneous nodules on the head and neck.

Keywords: Pilomatrixoma, Malharbe epithelioma, subcutaneous nodule.Received: 08.02.2016 Accepted: 01.03.2016

Pilomatrixoma Localized in the Right Preauricular Region

Figure 1. CT image of pilomatrixoma.

Introduction

Pilomatrixoma, also known as Malherbe’s calcifying epithelioma, is a slow-growing benign soft tissue tumor occurring in cutaneous or subcutaneous tissues. This tumor was first described as a calcified tumor arising from the sebaceous gland by Malherbe and Chenantais in 1880 (1,2). Forbis and Helwig suggested that the tumor arises from primitive germ cells of the hair matrix and proposed the name pilomatricoma or pilomatrixoma (3). Pilomatrixoma is often asymptomatic and usually presents as a slow-growing, solitary, firm, deeply seated, benign tumor and rarely as a superficial lesion with discoloration on the surface skin. Pilomatrixoma typically presents as a solitary nodule and rarely as a multiple lesion (4).

In this report, we present a case of pilomatrixoma localized in the right postauricular region with the review of the literature.

Case Report

An 18-year-old female patient presented with the complaint of swelling in the preauricular region. The swelling was firstly noticed two years ago and became gradually larger. No pain, redness, or temperature rise was reported. Physical examination revealed a


Abstract

Correspondence: Murat Şereflican, Department of Otorhinolaryngology, TurkeyConflict of Interest: NoneE-mail: [email protected]

firm, well-circumscribed, mobile, painless solitary nodule with an approximate size of 2 cm in the postero-inferior portion of the right auricular lobule. A neck computed tomography (CT) showed that the nodule was localized in the subcutaneous tissue and calcified (Figure 1). The patient was operated on under local anesthesia. A 3-cm skin incision was performed on the lesion site and the lesion was

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dissected from the surrounding tissue and totally excised. Pathological examination indicated ossified pilomatrixoma (Figure 2). No additional treatment was required since the lesion was total excised. No recurrence was observed in the follow-up period.

Discussion

Pilomatrixoma is a hamartomatous lesion prone to calcification, originating from the hair follicle matrix. It may be seen in any age group, with the highest incidence in pediatric and adolescent age groups. About 40% of pilomatrixomas occur in the first decade of life, whereas about 60% of them occur in the first two decades of life, and the peak incidence is seen in patients between 8-13 years of age (5). The most common localization of pilomatrixoma is the head and neck region, followed by upper extremities, torso, and lower extremities (6). In the head and neck region, pilomatrixoma is mostly seen in the cervical, frontal and temporal regions, eyelids, and preauricular regions (7). However, pilomatrixomas have never been reported on the palms or soles, presumably because these sites lack hair-bearing skin. The female to male ratio is 3/2, with a predominance of the white race. Pilomatrixoma typically presents as a solitary

nodule but may occur as a multiple lesion in 2-3% of the cases. The multiple or recurrent tumors may be associated with a number of disorders including the Gardner syndrome, myotonic dystrophy, and the Turner syndrome (6).

Pilomatrixoma clinically presents as a slow-growing, solitary, firm, well-circumscribed, painless dermal or subcutaneous tumor. The overlying skin varies in color from red to blue in 24% of the cases (8).

Histopathological examination is highly useful in the diagnosis of pilomatrixoma since the clinical diagnosis of pilomatrixoma is difficult. Histopathological examination reveals round islets of epithelial cells surrounded by a connective tissue capsule. In these islets, the eosinophilic ghost cells that have lost their nuclei are the specific indicators of pilomatrixoma. In addition to these islets, there are foreign-body giant cells and basaloid cells that have prominent nucleoli. Calcification is seen in 70-85% of the cases (2). The differential diagnosis of pilomatrixoma should include epidermoid cyst, foreign body granuloma, dermatofibroma, keratoacanthoma, nodular subepidermal fibrosis, basal cell carcinoma, osteoma, and skin metastasis (6).

Surgical excision is the method of choice in the treatment of pilomatrixoma since pilomatrixoma is a benign lesion and does not regress spontaneously. Postoperative recurrence of pilomatrixoma is extremely rare and occurs in 0-3% of the cases (6). Though rare, locally-aggressive malignant pilomatrixomas characterized by large lesions with a metastatic potential have also been reported. In malignant pilomatrixomas, metastasis is often local and occurs only in the surrounding tissues (9,10).

In conclusion, pilomatrixoma can easily be confused with other skin tumors since it is a rare entity and has no specific symptoms, and little is known about its clinical features. Pilomatrixoma should be kept in mind in the differential diagnosis of head and neck tumors. It should also be noted that pilomatrixoma may lead to recurrence or malignancy, though very rarely.

1. Brandner MD, Bunkis J. Pilomatrixoma presenting as aparotid mass. Plast Reconstr Surg. 1986 Oct;78(4):518-21.

2. Yencha MW. Head and neck pilomatricoma in thepediatric age group: a retrospective study and lit-

erature review. Int J Pediatr Otorhinolaryngol. 2001 Feb;57(2):123-8

3. Street ML, Rogers RS 3rd. Multiple pilomatricomasand myotonic dystrophy. J Dermatol Surg Oncol. 1991Sep;17(9):728-30.

Figure 2. Histopathologic image of pilomatrixoma.

References

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4. Kulahci Y, Sever C, Uygur F, Kucukodaci Z, Duman H.Pilomatrixoma: Malherbe tumor. Turk Plas Surg. 2006;17(1): 19-24.

5. Moehlenbeck FW. Pilomatrixoma (calcifying epi-thelioma). A statistical study. Arch Dermatol. 1973Oct;108(4):532-4.

6. Agarwal RP, Handler SD, Matthews MR, Carpentieri D.Pilomatrixoma of the head and neck in children. Oto-laryngol Head Neck Surg. 2001 Nov;125(5):510-5.

7. Duflo S, Nicollas R, Roman S, Magalon G, Triglia JM. Pi-lomatrixoma of the head and neck in children: a studyof 38 cases and a review of the literature. Arch Oto-

laryngol Head Neck Surg. 1998 Nov;124(11):1239-42.

8. Wells NJ, Blair GK, Magee JF, Whiteman DM. Piloma-trixoma: a common, benign childhood skin tumour.Can J Surg. 1994 Dec;37(6):483-6

9. Gould E, Kurzon R, Kowalczyk AP, Saldana M. Piloma-trix carcinoma with pulmonary metastasis. Report of a case. Cancer. 1984 Jul 15;54(2):370-2

10. Durmus SE, Çalik İ, Kurt A, Balta H, Ozmen SA. PatientCharacteristics, Locations and Histopathological Fea-tures of Pilomatrixomas in Erzurum/Turkey. Acta MedAnatol 2015; 3(4): 129-131.

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Dear Editor,

Temporomandibular joint (TMJ) is a complicated joint consisting of temporal bone’s glenoid fossa, mandibula’s condylar process, disc and joint capsule. It functions while chewing, breathing, swallowing and speaking. TMJ dislocation develops as a result of mandibular condyle getting out from glenoid fossa due to a traumatic or non-traumatic reason. It is seen in 3% of all joint dislocations (1). Most of the dislocations are based on non-traumatic reasons like yawning, eating, dental treatment, convulsion, endoscopic procedure, transoesophageal echocardiography examination or oral intubation (2). It can be diagnosed through the radiography directly, computed tomography (CT) or magnetic resonance imaging (MRI). Its treatment is closed or open reduction. In this study, radiological and clinical findings of the patients with dislocation which is secondary to epileptic seizure which is one of the rare causes of TME dislocation were emphasized.

27 years old male patient diagnosed with epilepsy ten years ago visited emergency department with epileptic seizure complaint. Vital findings such as fever and blood pressure were stable in the patient whose history doesn’t include any finding apart from epilepsy. There was suspicious consolidation at lower zone of the left lung according to the P-A chest radiography of the patient having also coughing complaint. Nonspecific treatment was given to the patient. The patient was taken into intensive care unit with the diagnosis of status epilepticus by consulting to neurology department as generalized tonic-clonic seizures started again one hour after the patient was given diazepam and phenytoin. After the patient’s seizures were kept under control, complaint of not being able to close mouth and sharp pain at localization of jaw joint evolved. Depression in preauricular region was seen in the physical examination.

It was seen in the examinations of direct graphy

(Image 1) and maxillofacial CT carried on with eight-channel multidedector CT system (MDCT) (GE, Medical Systems Milwaukee, WI, USA) that bilateral mandibular condyles were in front of articular eminence (Image 2a,2b,3). There weren’t any fracture and erosion in bone structures. Under local anesthesia and sedation, closed reduction was performed by plastic and reconstructive surgery. He was advised to eat soft food.

TMJ dislocation is the extreme movement of mandibular condyle’s to the anterosuperior aspect of the articular eminence and total parting of glenoid fossa and mandibular condyle from each other and getting fixed in this way (3). It has four types as anterior, posterior, superior and lateral based on the condyle’s relationship with articular eminence. Clinically it can be classified as acute, chronic and recurrent (1). The most frequent type is bilateral anterior dislocation (4). There was bilateral acute anterior dislocation in our case, too.

Acta Medica AnatoliaLetter to the Editor

Fatma Aktaş1, Zafer Özmen1, Turan Aktaş2, Ayşegül Altunkaş1, Fitnet Sönmezgöz1, Eda Albayrak1

1 Gaziosmanpaşa University School of Medicine, Department of Radiology, Tokat, Turkey 2 Gaziosmanpaşa University School of Medicine, Department of Chest Diseases, Tokat, Turkey


Bilateral Temporomandibular Joint Dislocation Secondary to Epileptic Seizure


Correspondence: Fatma Aktaş, Gaziosmanpaşa University School of Medicine, Tokat, Turkey.Conflict of Interest: NoneE-mail: [email protected]

Figure 1. It is seen in lateral direct radiography that condyle (blue arrow) is dislocated towards anterior of articular emi-nence (black arrow).

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Most common cause of the TMJ dislocation is excessive opening of the mouth during yawning. Other non-traumatic mechanisms which spreads mouth excessively include taking a big bite while eating and laughing. Masseter, temporalis, and internal pterygoid muscles spasms result in trismus which prevents return of the condyle to the temporal fossa (5). It can also develop secondary to some systemic diseases such as chronic cough, eclampsia. Drug use and alcoholism can be other underlying causes (1). In our case, cause was epileptic seizure. In a study conducted by Ugboko et al. with 96 TMJ dislocation patient, epileptic seizure was detected as the cause in only 4 patients (4). In literature, cases having unilateral or bilateral TMJ dislocation secondary to epileptic seizure have been reported rarely. The reason of TMJ

dislocation in epilepsy is due to the muscle contraction during the seizure (7). Moreover, factors like joint capsule weakness, muscle tone lowness, flattening of eminence can have predisposing roles. (6) TMJ dislocation can be diagnosed easily when there is pain in preauricular region and when the patient cannot close his mouth. Radiological examination is performed for the exclusion of fracture accompanying TME dislocation in general.

However, diagnosis can be easily overlooked in subacute clinics (8). TMJ dislocation was diagnosed on time by clear physical examination, direct radiography and CT in our patient

Acute TMJ dislocation treatment is manual reduction with or without anesthesia-analgesia (5). Closed reduction techniques were discussed in detail in study conducted by Chan et al. (9). Surgery techniques like condylectomy are used for the treatment in long lasting chronic cases. If the treatment is delayed, masseter and pterygoid muscles’ spasticity increases, fibrosis develops and thus reduction becomes difficult. Also, possibility of fractures increases (10). Closed reduction was done without any problem by applying local anesthesia and sedation to the patient in our case

There are many causes of temperomandibular joint dislocation. TMJ dislocation following epileptic seizure develops rarely. Its treatment is easy in general unless the diagnosis is done late. When the diagnosis is done late, spasm develops in masseter and pterygoid muscles, and fibrosis and fractures can be seen in cases lasting more than 14 days. Therefore, quick diagnosis and early treatment are important in prognosis of the dislocation.

Figure 3. The findings can be seen as three-dimensional in three-dimensional reformat CT image.

Figure 2a. Mandibular condyle is not seen in both TMJ locali-zations in axial CT image. 2b. It is seen in sagittal reformat CT that mandibular condyle (black arrow) is dislocated towards anterior of normal joint (white arrow).

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1. Vasconcelos BC, Rocha NS, Cypriano RV. Posteriordislocation in intact mandibular condyle: an unusualcase. Int J Oral Maxillofac Surg 2010;39:89-91

2. Anantharam B, Chahal N, Stephens N, Senior R. Tem-poro-mandibular joint dislocation: an unusual compli-cation of transoesophageal echocardiography. Eur JEchocardiogr 2010;11:190-1

3. Vasconcelos BC, Porto GG, Lima FT. Treatment ofchronic mandibular dislocations using miniplates:follow-up of 8 cases and literature review. Int J OralMaxillofac Surg 2009;38:933-6

4. Ugboko VI, Oginni FO, Ajike SO, Olasoji HO, AdebayoET. A survey of temporomandibular joint dislocation:aetiology, demographics, risk factors and manage-ment in 96 Nigerian cases. Int J Oral Maxillofac Surg2005;34:499-502

5. Chan TC, Harrigan RA, Ufberg J, Vilke GM. Mandibularreduction. J Emerg Med 2008;34:435-40

6. Sia SL, Chang YL, Lee TM, Lai YY. Temporomandibularjoint dislocation after laryngeal mask airway insertion.Acta Anaesthesiol Taiwan 2008;46:82-5

7. Behere PB, Marmarde A, Singam A Dislocation of theUnilateral Temporomandibular Joint a Very Rare Pres-entation of Epilepsy. Dislocation of the unilateral tem-poromandibular joint a very rare presentation of epi-lepsy. Indian J Psychol Med. 2010;32(1):59-60.

8. Rastogi NK, Vakharia N, Hung OR. Perioperative anteri-or dislocation of the temporomandibular joint. Anesth Analg 1997;84:924-6

9. Chan TC, Harrigan RA, Ufberg J, Vilke GM. Mandibularreduction. J Emerg Med 2008;34:435-40

10. Thangarajah T, McCulloch N, Thangarajah S, StockerJ. Bilateral temporomandibular joint dislocation ina 29-year-old man: a case report. J Med Case Rep2010;4:263

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References

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Acta Medica AnatoliaLetter to the EditorVolume 4 Issue 3 2016doi: 10.15824/actamedica.96168

Correspondence: Hüseyin Katlandur, Mevlana University School of Medicine, Konya, TURKEY Conflict of Interest: NoneE-mail: [email protected]

Department of Cardiology, Mevlana University, Konya, Turkey


Hüseyin Katlandur, Hüseyin Özdil, Şeref Ulucan, Ahmet Keser, Kerem Özbek

Acute Inferior Wall Myocardial Infarction with Anaphylactic Shock Due to Bee Sting: What Should We Do?

Dear Editor;

A 70 years old man came to emergency department with the history of bumblebee stung. His blood pressure 100/60 mmHg and pulse 60/min and rhythm were normal sinus rhythm. Patient biochemical analyses were normal. Complaint of chest discomfort started after given intravenous hydrocortisone 1 mg/kg, diphenhydramine 1 mg/kg and ranitidine 1 mg/kg.

The electrocardiogram showed 1 mm ST segment elevation in leads DII, DIII, aVF derivations and also complete AV block. His general condition and hemodynamic parameters were suddenly deteriorated. His blood pressure and heart rate dropped to 60/40 mmHg and 40/min respectively. Isotonic solution infusion started 1000 cc/hour and Atropin 1 mg initiated intravenously. After that his cardiac rhythm changed to the ventricular fibrillation. Following cardiac defibrillation, immediately coronary angiography performed.

Coronary angiography revealed that total thrombotic occlusion of the right coronary artery. Following premedication with aspirin, clopidogrel and heparin, the thrombotic occlusion successfully opened with the balloon and stenting. After successful reperfusion, ventricular fibrillation developed and treated with defibrillation. In spite of successful reperfusion, isotonic solution infusion and additional 2 mg atropin initiation, the patient hemodynamic parameters and general condition not improved.

We gave 1 mg adrenalin intracoronary and the patient hemodynamic parameters improved very quickly. The patient transferred to the intensive care unit. 5 μg/kg/min dobutamine, 6 μg/kg/min dopamine infusion started. Patient hemodynamic supports stopped 6 hours latter and discharged 3 days later without any complaint.

Kounis syndrome defined as one type of acute coronary syndrome related to allergic sources. There are three types of Kounis syndrome were defined in the literature (1).

Type 1: This type includes normal or minimal coronary artery disease with acute release of inflammatory mediators due to allergic substance (ie. bee venom) that may induce coronary vasospasm or progressing to acute myocardial infarction

Type 2: This variant includes culprit but silent lesions, which is activated by inflammatory mediators leads to coronary vasospasm progressing to myocardial infarction.

Type 3: Different from type 2 it includes aspirated thrombus specimens which have eosinophils and mast cells stained with Hematoxylin - eosin and Giemsa respectively.

Heart is not only source of allergic signs and symptoms but also target of chemical mediators of anaphylactic reaction. The mast cells have available most critical regions of the coronary artery tree which is destination of the allergen substance (2). Mast cells release very biologically active cytokines and neurohormones (3). As a result of releasing histamine, leukotrienes, prostaglandins, platelet activating factor, renin and chymase causes both development of fatal myocardial infarction and severe hemodynamic disturbances.

In the literature many cases of heart attack due to a bee sting were defined (4). Clinical presentation spectrum and the treatment of this syndrome are very versatile. The main goal of treatment to fight against the deadly complication of myocardial infarction and treat to allergic reaction which is may turn to the complete anaphylaxis. In spite of there are some fears about positive inotrope use in the Kounis syndrome cases there is no absolute contraindication in the literature (5).

The combination of anaphylactic shock and myocardial infarction is rare and leads to clinical problems which can be solved very difficult (6). In these cases, some drugs such as adrenalin which

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used for the treatment of anaphylaxis make some troubles on the process of revascularization. In our case we have observed a rapid improvement regarding to hemodynamic status after intracoronary administration of adrenaline. Similar methods regarding to anaphylaxis described in the literature previously (5).

As a result, we believe that the administration of intracoronary adrenaline with adequate anticoagulation makes more hemodynamic stability in case of myocardial infarction and anaphylactic shock combination.

1. Kounis NG. Coronary hypersensitivity disorder:the Kounis syndrome. Clinical therapeutics. 2013May;35(5):563-71.

2. Alevizos M, Karagkouni A, Panagiotidou S, Vasiadi M,Theoharides TC. Stress triggers coronary mast cellsleading to cardiac events. Ann Allergy Asthma Immu-nol 2014;112:309-16.

3. Hakim-Rad K, Metz M, Maurer M. Mast cells: makersand breakers of allergic inflammation. Curr Opin Al-lergy Clin Immunol 2009;9:427-30.

References

4. Aribas A, Akilli H, Aribas FZ, Kayrak M, Turan Y. Acutemyocardial infarction triggered by bee sting. EmergMed Australas 2013;25:282-3.

5. Ihdayhid AR, Rankin J. Kounis syndrome with Samter-Beer triad treated with intracoronary adrenaline.Catheter Cardiovasc Interv 2015;86:E263-7.

6. Triggiani M, Montagni M, Parente R, Ridolo E. Anaphy-laxis and cardiovascular diseases: a dangerous liaison.Curr Opin Allergy Clin Immunol 2014;14:309-15.

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Acta Medica Anatolia 2016 Volume 4 Issue 3