Correlation of Endoscopic Ultrasonography Features with the Mitotic Index in 2- to 5-cm Gastric Gastrointestinal Stromal Tumors.

BACKGROUND: Predicting the malignancy potential of gastrointestinal stromal tumor (GIST) before resection could improve patient management strategies as gastric GISTs with a low malignancy potential can be safely treated endoscopically, but surgical resection is required for those tumors with a high malignancy potential. This study aimed to evaluate endoscopic ultrasound (EUS) features of 2- to 5-cm gastric GISTs that might be used to predict their mitotic index using surgical specimens as the gold standard. PATIENTS AND METHODS: Forty-nine patients (30 females and 19 males; mean age 55.1 ± 12.7 years) who underwent EUS examinations, followed by surgical resections of 2- to 5-cm gastric GISTs, were retrospectively reviewed. RESULTS: The mean tumor size was 3.44 ± 0.97 (range 2.1-5.0) cm. A univariate analysis revealed no significant differences in age, sex, and tumor location in the low mitotic index and high mitotic index groups (all p > 0.05). In terms of EUS features, there were no significant differences in the mitotic indexes with respect to the shape, surface lobulation, border regularity, echogenicity, homogeneity, growth patterns, presence of mucosal ulceration, hyperechogenic foci, anechoic spaces, and hypoechoic halos (all p > 0.05). However, the tumor size was larger in the high mitotic index group than that in the low mitotic index group (3.97 ± 1.05 vs. 3.27 ± 0.9 cm, p = 0.03). CONCLUSION: Conventional EUS features are not reliable for predicting the mitotic index of 2- to 5-cm gastric GISTs. Further modalities for predicting the mitotic index are needed to prevent unnecessary surgical resections in patients with a low risk of malignancy.

Use of Artificial Intelligence in the Prediction of Malignant Potential of Gastric Gastrointestinal Stromal Tumors.

BACKGROUND AND AIMS: This study aimed to investigate whether AI via a deep learning algorithm using endoscopic ultrasonography (EUS) images could predict the malignant potential of gastric gastrointestinal stromal tumors (GISTs). METHODS: A series of patients who underwent EUS before surgical resection for gastric GISTs were included. A total of 685 images of GISTs from 55 retrospectively included patients were used as the training data set for the AI system. Convolutional neural networks were constructed to build a deep learning model. After applying the synthetic minority oversampling technique, 70% of the generated images were used for AI training and 30% were used to test AI diagnoses. Next, validation was performed using 153 EUS images of 15 patients with GISTs. In addition, conventional EUS features of 55 patients in the training cohort were evaluated to predict the malignant potential of GISTs and mitotic index. RESULTS: The overall sensitivity, specificity, and accuracy of the AI system for predicting malignancy risk were 83%, 94%, and 82% in the training dataset, and 75%, 73%, and 66% in the validation cohort, respectively. When patients were divided into low-risk and high-risk groups, sensitivity, specificity, and accuracy increased to 99% in the training dataset and 99.7%, 99.7%, and 99.6%, respectively, in the validation cohort. No conventional EUS features were found to be associated with either malignant potential or mitotic index (P > 0.05). CONCLUSIONS: AI via a deep learning algorithm using EUS images could predict the malignant potential of gastric GISTs with high accuracy.

Diagnostic performance of immediate colposcopy among women with high-risk human papillomavirus (HPV) other than HPV 16/18 and normal cytology.

AIM: Persistent infection with 1 of 14 high-risk genotypes human papillomavirus (HPV) genotypes is the crucial for the development of high-grade cervical cancer precursors. The reassuring management of women with cytology negative, high-risk HPV (HrHPV) positive is important especially after the widespread use of HPV testing either as a cotest. The aim of our study was to compare the colposcopic biopsy results of women with HPV 16/18 with other Hr-HPV genotypes and determine positive predictive values (PPV) for CIN2+ of other HR HPV genotypes. METHODS: We prospectively had included the women with negative cytology and positive Hr-HPV test other than HPV 16/18. Control group was composed of women with negative cytology positive test results for either HPV 16 or HPV 18. Women with HrHPV positive, cytology negative referred to immediate colposcopy. RESULTS: The prevalence of CIN1 and CIN2 is significantly higher in HPV 16/18 group than pooled other HrHPV group (34.1% vs 17.5%, P = 0.01 for CIN 1+; 14.8% vs 5.2%, P = 0.03 for CIN 2+). The prevalence of CIN3 was almost three fold in women with HPV 16/18 (9.1% vs 3.1%). PPV for CIN 2+ was 16.4 (9.1-27.3) for HPV 16, 11.7 (2-37.7) for HPV 18, 20 (3.5-55.7) for HPV 31, 11.1 (0.6-49.3) for HPV 51, 12.5 (0.6-53.3) for HPV 58 and 59. CONCLUSION: We showed the relative high PPV for CIN2+ in OHrHPV other than HPV 16/18 positive group among cytology negative population. HPV 33, 51, 58, 59 and 18 had similar PPV for CIN2+ in basal cytology negative population.

Clinicopathological Features of Gastroenteropancreatic Neuroendocrine Neoplasms.

ABSTRACT  Objective: To describe the clinical, pathological and survival characteristics of Turkish patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Bezmialem Vakif University School of Medicine Hospital from April 2012 to September 2018. METHODOLOGY: Sixty-one patients with GEP-NENs were analysed in retrospect for the clinical, pathological and survival characteristics. The Kaplan-Meier method was used for survival analysis and the Log-rank test was performed to analyse the comparisons between the groups. RESULTS:  Forty-five of the 61 GEP-NENs patients (73.8%) were neuroendocrine tumor (NET) and 26.2% of patients were neuroendocrine carcinoma (NEC). The mean age of patients was 55.5 ± 11.3 years. The most frequent localisation of tumors was stomach (34.4%), and the most common symptom was abdominal pain (27.9%). The rate of distant metastases was 31.1% at diagnosis and 63.9% of the patients were operated. The median follow-up period was 27 months. The rate of three-years overall survival (OS) was 88.5% and the five-years OS rate was 86.9%. The variables that can significantly influence the OS rate were high grade (grade 3; p= 0.005), Ki-67 proliferation index (Ki-67 >20%; p= 0.002) and distant metastases (p= 0.018). CONCLUSION: GEP-NENs may develop anywhere in the digestive tract. Approximately one-third of the patients may be metastatic due to delay in diagnosis. Key Words: Gastroenteropancreatic neuroendocrine tumor, Neuroendocrine cancers, Neuroendocrine neoplasms.

Transforming a U.S. scholarly concentrations program internationally: lessons learned.

BACKGROUND: Scholarly Concentrations programs in U.S. medical schools aim to instill passion for critical thinking and promote careers in academic medicine. The rise of these programs has seen variable goals, structure, and outcomes. Transformation of these programs internationally is in its infancy. METHODS: We describe implementation of the Johns Hopkins School of Medicine Scholarly Concentrations program, offering Basic Science, Clinical Science, Medical Ethics/Healing Arts, History of Medicine, and Public Health/Community Service, at Bezmiâlem Vakif University in Istanbul, Turkey. Over six modules in the preclinical years, students develop a faculty-mentored experience which encourages the acquisition of attitudes and skills for self-directed, lifelong learning and scholarship. This culminates in abstract and project presentation. We report program characteristics (context and logistics) and outcomes (student engagement and experiences). RESULTS: The Scholarly Concentrations program at Bezmiâlem began in 2014, with nearly two completed cohorts of students. In comparison to Johns Hopkins, students at Bezmiâlem begin at an earlier age (thus do not have as much prior research experience) and are subsequently evaluated for residency in terms of test scores rather than scholarship and publications, but have a similar level of intellectual curiosity and desire to take ownership of their project. Eighty-two percent of Bezmiâlem students stated the project they pursued was either their own idea or was an idea they formed after meeting with their mentor. Students at Bezmialem were more likely to choose Clinical Science projects (p = 0.009). Only 5% of Bezmiâlem students in end-of-course survey felt dissatisfied with the level of ownership they experienced with their project, a frequency similar to that seen by Johns Hopkins students (2%). CONCLUSIONS: Scholarly Concentrations programs play an important role in U.S. medical schools, and these programs can be successfully implemented internationally. The Scholarly Concentrations program at Johns Hopkins has been transformed to a program at Bezmiâlem in Istanbul, the first program outside North America or the European Union. When designing these programs, one must consider the context, logistics, student engagement, and outcomes. While long-term outcomes are needed, this can serve as a model for implementation elsewhere.

Unusual Histopathological Findings in Appendectomy Specimens: A Retrospective Analysis of 2047 Cases.

BACKGROUND: In this study, we retrospectively evaluated cases of patients who had undergone appendectomy in our hospital and aimed to present the efficiency of diagnostic tests and demographic data of cases. Pathological reports were analyzed for the following parameters: age, gender, and pathological diagnosis. In addition, the demographic and clinicopathologic characteristics of patients with unusual histopathologic findings were evaluated in detail, and reanalysis of archived resected appendix specimens was carried out. METHODS: Files of 2047 patients (1329 males, 718 females, sex ratio: 1.85, age range: 1-87 years, mean age: 26, 50 years), who had been operated with a diagnosis of acute appendicitis in the emergency department of Bezmialem Vakif University Medical Faculty from November 2011 to June 2014, were retrospectively evaluated. RESULTS: Cases were separated into 2 groups. Cases with histopathologic examination reported as acute appendicitis constituted group 1 (n = 2013, 98.34%), and cases with pathologic findings other than acute appendicitis constituted group 2 (n = 34, 1.66%). The second group consisted of 8 low-grade mucinous neoplasms, 7 mucoceles, 6 carcinoid, 5 granulomatous inflammation, 4 intraluminal Enterobius vermicularis, 1 endometriosis externa, 1 adenocarcinoma infiltrated to serosa, 1 mesenteric cyst, and 1 low-grade adenocarcinoma formed in mucinous cystic neoplasm background. CONCLUSION: Acute appendicitis is the most common emergency surgical condition. Although most of the resected appendectomy specimens showed typical histopathologic findings, some (1.66%) showed unusual histopathologic findings. Even if the macroscopic appearance of the specimen is normal or acute appendicitis, we suggest routine histopathological examination.

Glomus tumor of the stomach.

Glomus tumor is a rare benign mesenchymal neoplasm derived from the glomus body, an arteriovenous shunt mainly located in dermis and subcutis. The most common localization of this tumor is extremities, especially nailbed. Glomus tumor in the gastrointestinal system is a rare condition. Here we report a gastric glomus tumor to raise awareness of this tumor and show the difficulties in the diagnosis.

Cotyledonoid Dissecting Leiomyoma with Symplastic Features: Case Report.

Purpose Cotyledonoid dissecting leiomyoma is a leiomyoma variant exhibiting unusual growth patterns. We aimed to demonstrate this, as well as to point out another feature that has not been previously reported. Case Report A congested, multinodular myomectomy specimen was resected. Histologically, smooth muscle fascicles with marked vascularity and extensive hydropic degeneration were detected. A total of 2 mitoses per 10 high power fields were counted, and the Ki-67 index was of 2-3%. We encountered atypical bizarre cells that have not been previously reported. Coagulative necrosis was not present. The patient was alive and well 36 months after surgery, with no evidence of recurrence. Conclusions Albeit the gross aggressive appearance, cotyledonoid dissecting leiomyomas are benign in nature. To this day, atypical cells have not been reported in this type of tumor. Despite the presence of symplastic features, cotyledonoid dissecting leiomyomas are clinically benign entities. Surgeons and pathologists should be acquainted with this variant.

Introdução O leiomioma dissecante na forma cotiledonoide é uma variante de leiomioma com padrões raros de crescimento. Além de demonstrá-los, vamos apontar outro aspecto anteriormente não relatado. Relato de Caso Uma amostra congestionada, multinodular de miomectomia foi excisada. Histologicamente, detectaram-se fascículos de músculos lisos com marcada vascularidade e extensa degeneração hidrópica. Contaram-se 2 mitoses por 10 campos de alta potência, e o índice Ki-67 foi de 2­3%. Encontramos células atípicas, bizarras, que não haviam sido relatadas anteriormente. Não foi observada necrose coagulativa. A paciente encontrava-se saudável e sem evidências de recorrência 36 meses após a cirurgia. Conclusão De aparência bruta e grosseira, os leiomiomas dissecantes na forma cotiledonoide têm natureza benigna. Até hoje, células atípicas não haviam sido relatadas nesse tipo de tumor. Apesar dos aspectos simplásticos, os leiomiomas dissecantes na forma cotiledonoide são entidades clínicas benignas. Cirurgiões e patologistas devem estar familiarizados com essa variante.

A Six Sigma Trial For Reduction of Error Rates in Pathology Laboratory.

OBJECTIVE: A major target of quality assurance is the minimization of error rates in order to enhance patient safety. Six Sigma is a method targeting zero error (3.4 errors per million events) used in industry. The five main principles of Six Sigma are defining, measuring, analysis, improvement and control. Using this methodology, the causes of errors can be examined and process improvement strategies can be identified. The aim of our study was to evaluate the utility of Six Sigma methodology in error reduction in our pathology laboratory. MATERIAL AND METHOD: The errors encountered between April 2014 and April 2015 were recorded by the pathology personnel. Error follow-up forms were examined by the quality control supervisor, administrative supervisor and the head of the department. Using Six Sigma methodology, the rate of errors was measured monthly and the distribution of errors at the preanalytic, analytic and postanalytical phases was analysed. Improvement strategies were reclaimed in the monthly intradepartmental meetings and the control of the units with high error rates was provided. RESULTS: Fifty-six (52.4%) of 107 recorded errors in total were at the pre-analytic phase. Forty-five errors (42%) were recorded as analytical and 6 errors (5.6%) as post-analytical. Two of the 45 errors were major irrevocable errors. The error rate was 6.8 per million in the first half of the year and 1.3 per million in the second half, decreasing by 79.77%. CONCLUSION: The Six Sigma trial in our pathology laboratory provided the reduction of the error rates mainly in the pre-analytic and analytic phases.

Vulvar granular cell tumor.

Granular cell tumors (GCTs) are rare and approximately half of the all lesions arise from head and neck, especially from the tongue. However, they are rarely seen in the vulva. They can occur in patients of any age, but peak age incidence is in the fourth to sixth decades. They generally occur as small, slow growing, and skin-colored nodule. GCTs are usually benign, but malignant cases were reported. Recurrence can be seen in benign tumors with clear margins, but rates increase with positive margins. The treatment is complete surgical excision. We report a case of benign GCT of the vulva. A 41-year-old patient presented with vulvar mass, and biopsy was consisted with GCT.

Should Core Needle Biopsy be Used in the Evaluation of Thyroid Nodules?

Fine needle aspiration (FNA) is the first choice in thyroid nodules suspected of harboring malignancy on sonography in routine practice. However, sampling with core needle biopsy (CNB) is also being used, especially in cases with repeated nondiagnostic/indeterminate diagnoses. The aim of this study was the retrospective evaluation of CNB samples. A total of 604 thyroid CNB samples registered in the Department of Pathology at Bezmialem Foundation University Medical Faculty within the 1-year period between June 2014 and June 2015 were re-evaluated by correlation with previous FNA and later resection results. CNB was divided into diagnostic groups of insufficient, malignant, suspicious for malignancy, no evidence of malignancy/benign, atypia of uncertain significance (AUS)/follicular lesions of uncertain significance (FLUS), and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN). Among the 604 cases, 15 cases (2.48 %) were classified as malignant and 9 cases (1.49 %) as suspicious for malignancy. No evidence of malignancy was seen in 512 cases (84.76 %). There were 26 (4.3 %) cases in the AUS/FLUS-FN/SFN group, and the sample was inadequate in 42 cases (6.95 %). Resection was performed for 17 of the cases classified as malignant or suspicious for malignancy, and all were found to be malignant. There were also 10 resected cases with a diagnosis of no evidence of malignancy, and all were found to be benign. We think that sampling with CNB may be useful especially in repeating inadequate biopsies or cases diagnosed with AUS/FLUS that have hesitations regarding clinical management. Larger series including comparisons with FNA and resection results are required.

Carcinoid tumor arising in a mature cystic teratoma: A case report.

Mature cystic teratomas are common benign tumors of the ovary. The most common form of malignant transformation is squamous cell carcinoma, however, malignant transformation is rarely observed and cases are usually asymptomatic. Carcinoid tumors are rare tumors of the neuroendocrine system. A number of the carcinoids result in clinical syndromes due to the secretion of vasoactive substances produced by the tumor. A 75-year-old woman suffering from groin pain was admitted to the Faculty of Medicine at Bezmialem Vakif University (Istanbul, Turkey). An adnexal mass was detected during the physical examination. Magnetic resonance imaging scans exhibited an 8×7-cm mass in the right ovary. Surgical excision of the mass was performed and histopathological examination revealed a mature cystic teratoma with three germ layers. An area consisting of nests and trabeculae was evident in the cyst wall. The pathological diagnosis was of an insular and trabecular variant of carcinoid tumor arising in a mature cystic teratoma. The patient did not present with carcinoid syndrome, and no recurrence was observed after 11 months of follow-up examinations.

Diffusion MRI on lymph node staging of gastric adenocarcinoma.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of diffusion weighted magnetic resonance imaging (MRI) in preoperative assessment of metastatic lymph nodes of gastric cancer. METHODS: A total of 23 gastric cancer patients with a mean age of 59.4±10.9 years were analyzed. Lymph nodes were grouped as perigastric lesser curvature (Group Ia), perigastric greater curvature (Group Ib), D1+/D2 lymph nodes (Group II). Identification of histologically metastatic lymph nodes by diffusion weighted MRI was regarded as the main outcome. RESULTS: A total of 1,056 lymph nodes including 180 histologically proven metastatic lymph nodes were dissected. Although diffusion weighted MRI could identify the metastatic lymph nodes in 18 out of 23 patients (77.8%), only 69 of total 1,056 nodes (6.53%), either metastatic or non-metastatic, could be detected. There was no correlation between histopathology and diffusion weighted MRI with regard to lymph node groups (P>0.05 for all). Overall accuracy was calculated as 69.56, 65.21 and 52.17 for Groups II, Ib and Ia lymph nodes, respectively. Apparent diffusion coefficient (ADC) values could not be helpful to differentiate metastatic lymph nodes (P=0.673). CONCLUSIONS: Diffusion weighted MRI has low accuracy to detect or to differentiate metastatic and non-metastatic lymph nodes based on their ADC values in gastric cancer.

Metachronous metastatic paraganglioma in jejunum as a rare entity: A case report.

Pheochromocytomas and paragangliomas are neuroendocrine tumors that arise from chromaffin cells of adrenal medulla and extra-adrenal paraganglia, respectively. The recurrence of these neuroendocrine tumors as a jejunal mass causing obstruction in the small intestine is an exceptional entity. The present study reports the case of a 70-year-old male who presented to the Emergency Department of Bezmialem Vakif University Hospital with abdominal pain and vomiting. The patient possessed a history of left nephrectomy due to malignant pheochromocytoma that had invaded into the left kidney eight months prior to presentation. Bowel obstruction was diagnosed and the patient underwent a laparoscopic procedure. Partial resection of the jejunum was performed and immunohistochemical studies revealed the lesion to be malignant paraganglioma. The majority of paragangliomas are chemo- and radioresistant. Surgical excision remains the primary treatment. Metachronous paraganglioma arising from the small intestine is an extremely rare entity and may be a relevant consideration in patients presenting with bowel obstruction.

Apoptotic effects of topical antiglaucoma medications on conjunctival epithelium in glaucoma patients.

PURPOSE: In this study, we aimed to investigate the apoptotic effects of topical antiglaucoma medications on the conjunctival epithelium. METHODS: A total of 65 patients were included in the study. Thirty patients were included in the first group who had received antiglaucomatous therapy before trabeculectomy. In the second group, 20 patients who had received no drugs before trabeculectomy were included, while the third group underwent only cataract surgery as control. During the surgery, 2 x 4 mm conjunctival samples were harvested from the upper bulbar conjunctiva. The mean apoptosis rate was calculated by determining apoptosis at conjunctival epithelium using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. RESULTS: The mean apoptosis rate was 0.537 ± 0.369 (0.026 ± 0.962) in group 1, 0.139 ± 0.162 (0.005 ± 0.676) in group 2, and 0.078 ± 0.035 (0.035 ± 0.142) in the control group (group 3). The mean apoptosis rate was significantly higher in the first group than the other 2 groups (p = 0.0001). CONCLUSION: Apoptotic effects of topical antiglaucoma drugs on the conjunctival epithelial cells were found. However, our results revealed that the number of medications, duration of medication, and type of glaucoma had no effect on the apoptotic effect.