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Aim: To determine the prevalence of occult hepatitis B (HBV) infection (OBI) in patients with nonviral liver disease. Materials & methods: This study included 83 HBsAg-negative patients followed up at a gastroenterohepatology clinic. The presence of HBV DNA was investigated by using an in-house nested-PCR method applied to liver parenchymal biopsy samples obtained from patients who underwent due nonviral chronic liver disease. Results: OBI was detected in 19 (22.9%) of the 83 cases, in 11 (44%) of 25 anti-HBc-positive patients, and 15 (31.9%) of 47 anti-HBc and/or anti-HBs antibodies-positive patients. Conclusion: There is a considerable prevalence of OBI among patients with nonviral chronic liver disease. Therefore, it is suggested that closely monitoring HBV can be useful to prevent or more effectively manage possible OBI-related complications among patients with nonviral chronic liver disease, especially those who are HBsAg seronegative or anti-HBV antibody seropositive.

Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (P 0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (P 0.05). Positive anti-HBc results may predict OBI and may also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression.

Amac: Okult Hepatit B Virus (HBV) enfeksiyonu (Occult HBV infection; OBI) mevcut serolojik testler ile HBV yuzey antijeni (Surface antigen; HBsAg) negatif tespit edilen bireylerin karacigerinde HBV genomunun uzun sureli persistan varligi ile karakterizedir. Bu calismada OBI tanili hastalardan elde edilen HBV’lerin genotip, subgenotip ve subtip profillerinin karakteristiginin irdelenmesi amaclanmistir. Gerec ve Yontem: Calismaya HBsAg negatif farkli klinik endikasyonlar nedeniyle karaciger parankim biyopsisi gerceklestirilen hastalarin karaciger biyopsi orneklerinde Nested PCR yontemiyle HBV DNA varligi tanimlanan 32 OBI tanili hasta ile 17 kronik hepatit B hastasi dahil edildi. HBV S gen MHR bolgesini hedefleyen DNA fragmanlari nested PCR kullanilarak amplifiye edildi. HBV’nin genotip, subgenotip ve subtip/serotiplerinin belirlemek icin Sanger sekans metodu kullanildi. Bulgular: Bu calismada OBI ve kronik hepatit B hastalarindan izo le edilen HBV’lerin tumununun genotipi D, subgenotipler sirasiyla HBV/D1 (%75,5), HBV/D2 (%6,1) ve HBV/D3 (%18,4) serotipler sirasiyla ayw2 (%73,5) ve ayw3 (%26,5) olarak belirlenmistir. OBI’li hastalarin %28,1’nin subgenotipi HBV/D3 olarak belirlenmesine karsin kronik hepatit B hastalarinin hic birinde HBV/D3 subgenotipi saptanmamistir. Sonuc: Subgenotip HBV/D3’un viral biyogenezin dinamigi uze rindeki potansiyel etkileri HBsAg negatifligi ve dusuk replikasyon yetkinligi ile karakterize OBI ile iliskili olabilir.

The purpose of this study was to evaluate the relationship of IL28B rs12979860 and rs8099917 polymorphisms with the clinical, histological, and virological outcomes of patients with chronic hepatitis B (CHB) also the treatment responses of patients who received Nucleos(t)ide analogs (NAs) therapy.This study included 152 CHB patients who were underwent liver parenchymal biopsy. The IL28B rs12979860 and rs8099917 polymorphism were genotyped using the TaqMan assay.The IL28B rs12979860 CC and IL28B rs8099917 TT were identified as the genotypes with the highest frequency in all patients. On the other hand, IL28B rs12979860 TT and IL28B rs8099917 GG were the genotypes with the lowest frequency. The frequency of IL28B rs8099917 TG genotype was significantly different between patients with hepatitis B, who has histologically defined liver cirrhosis and no-fibrosis (p=0.02). In addition, a statistically significant correlation was found between the presence of IL28B rs8099917 G allele and virological unresponsiveness to NAs treatments in CHB patients (p=0.028).The presence of the IL28B rs8099917 G allele in CHB patients might be associated with the risk of developing cirrhosis and virological unresponsiveness to NAs treatments.

Living donor liver transplantation may complement cadaveric transplantation in acute liver failure (ALF) patients. Between 2008 and 2017, 89 patients were treated for ALF; 15 patients (17%) recovered with intensive care treatment; 31 (35%) died without transplant. The records of the remaining 43 patients (median (range) age: 14 (1–62)) who underwent transplantation were evaluated. The etiologic factors were toxic agents (10; mushrooms: 8; herbs: 2), hepatitis viruses (7; A: 1; B: 6), Wilson’s disease (7), autoimmune hepatitis (4), and Budd-Chiari syndrome (2); 13 cases were idiopathic. Cadaveric organs (whole, split, reduced) were transplanted to 32 patients; 11 patients underwent living donor transplantation. One patient (2%) died of septic shock on the second postoperative day. Bacterial infection was the most common early (< 3 months) complication in the remaining patients (31/42; 74%), followed by delirium (5/42; 12%) and acute rejection requiring steroid pulse (5/42; 12%). Seven other patients died during median (range) follow-up of 94 (14–142) months: various infections (5), leukemia (1), and acute myocardial infarction (1). The 1-, 5-, and 10-year survival rates were 100%, 96%, and 92% in children and 94%, 82%, and 65% in adults respectively. Cadaveric organ sharing and transplantation from living donors when appropriate yield a high survival rate, despite high early morbidity, in ALF patients whose conditions deteriorate despite intensive care treatment. Efforts to eliminate preventable causes of acute liver failure will lead to more efficient use of health care resources.

Non-sebaceous lymphadenoma is a sporadic benign tumor of salivary glands. Histopathologic and immunohistochemical properties, diagnostic criteria, and theories for the histologic origin of the disease have been defined and well-discussed in the literature. However, none of the cases showed malignant transformation to date. We reported a case of 54 years old female patient with a right preauricular mass. Magnetic resonance imaging demonstrated a 2 cm, well-defined contrast-enhanced mass in the right parotid gland. Fine needle aspiration cytology was undiagnostic but suspicious for malignancy. Total parotidectomy with facial nerve preservation was done. In the histopathological examination, non-sebaceous lymphadenoma regions and malignant cells with abundant cytoplasm, large vesicular nuclei, and prominent nucleoli, which occupied approximately 70% of the mass, were seen. The diagnosis was undifferentiated carcinoma arisen from non-sebaceous lymphadenoma. Adjuvant radiotherapy was given. No recurrence was detected during ten months of follow-up. This case is the first case of a malignancy developed from non-sebaceous lymphadenoma.

Primary anorectal melanomas (AMs) are uncommon neoplasms with aggressive behavior. Molecular profile and clinicopathologic features of AMs are still not well established. In this study, we aimed to investigate BRAF, NRAS, KIT, TERT, and GNAQ/GNA11 mutation status and clinicopathologic features of AMs.All diagnostic slides of 15 AMs were reviewed. Histopathological and follow-up information were documented. Mutations in exon 15 of the BRAF gene; exons 2 and 3 of the NRAS gene; exons 9, 11, 13, 17, and 18 of the KIT gene; and exons 4 and 5 of the GNAQ/GNA11 genes and mutations in the promoter region of the TERT gene (chr.5, 1,295,228CT and 1,295,250CT) were analyzed.BRAF(V600E) and KIT(V555I and K642E) mutations were observed in one (7%) and two cases (14%), respectively. NRAS, TERT and GNAQ/GNA11 mutations were not detected. The mean age was 65. Patients presented with rectal mass, rectal bleeding, pain, and weight loss. 73% of the lesions were macroscopically polypoid. The most common tumor cell type was epithelioid. Mean tumor thickness was 10.4 mm. One third of the cases lacked pigmentation. In situ melanoma was present in one third of the cases. Among 14 patients with follow-up data, 12 succumbed to disease. The mean overall survival was 36 months.AMs are uncommon tumors with dismal survival, usually occurring in the elderly in various gross and microscopic appearances. In terms of molecular profile, BRAF and KIT mutations are rarely detected. Profiling of larger cohorts is required to elucidate the pathogenesis and to identify potential molecular indicators that may contribute to the development of individualized targeted therapies.

OBJECTIVES Isoniazid (INH) prophylaxis is recommended for the prevention of tuberculosis (TB) reactivation before or/and during initiation of treatment with tumour necrosis factor antagonists (anti-TNF agents). Nonetheless, the long-term effectiveness of chemoprophylaxis is not clear. In this study, we aimed to evaluate the characteristics of patients who developed TB reactivation in spite of INH prophylaxis associated with anti-TNF treatment. PATIENTS AND METHODS In this retrospective study, medical records of 1263 patients with inflammatory bowel disease were reviewed. Baseline TB screening tests (purified protein derivative test and/or QuantiFERON-TB Gold test) were performed on all patients before initiation of anti-TNF therapy. Patients with purified protein derivative of more than 5 mm and/or a positive result of the QuantiFERON-TB Gold test received INH prophylaxis for 9 months. We analysed the data of patients diagnosed with TB reactivation during the anti-TNF treatment despite INH chemoprophylaxis. RESULTS Overall, 175 patients underwent anti-TNF treatment. Sixty of these 175 patients had pretreatment testing showing latent TB infection and therefore were treated concomitantly with INH for 9 months in addition to their anti-TNF treatment. TB reactivation occurred in four of these 60 co-INH/anti-TNF treated patients. Active TB was diagnosed after 37.5±27 (range: 18-84) months of anti-TNF treatment. In two of the four patients that active TB was diagnosed, was also detected other Mycobacterium spp.: M. bovis in one patient and M. genavense in the other one. CONCLUSION INH chemoprophylaxis may not prevent the reactivation of TB during anti-TNF therapy in the long-term. Patients should be carefully and periodically screened for TB reactivation during anti-TNF therapy.

Objective: genomic DNA obtained from paraffin blocks of the intended colorectal cancer cases was evaluated for promoting colorectal cancer by investigating the promoter methylation of 6 different gene promoter regions and microsatellite instability. Methods: DNA was isolated from the paraffin tissue of 76 sporadic colorectal cancer patients by cross sections from the areas determined to be tumorous. The methylation specific PCR (MS-PCR) method was used for these DNA samples fo rmethlylation studies in promoter region of six different APC, hMLH1, p16INK4A, p15, p73 and DAPK1 genes. In the same samples, the presence of microsatellite instability (MSI). Results: the fequencey of methylation was 24% for hMLH1, 31.5% for APC, 19.6% for DAPK1, 42.8% for p16, 30% for p15, 17% for p73. We calculated a methylation index (MI=ratio between the number of genes methylated and the number of genes analyzed). MI was ranged from 0-0.83, with an average of 0.271 corresponding to 1.6 genes/sample and median was 0.225 and there were 15 samples which doesn't methylated in any loci. We analysed MSI in C-kit (21%), hMSH2 (18%) and APC (15%), microsatellite region. Conclusion: we observed APC methylation was common then the other population for Turkish patient. P16 was the most commenest methylated loci among the 6 of gene and it seems storongly related with female patients. P73 was releated with left colorectal cancer and additionally it was related with the MSI., Istanbul University Research Fund

Aims Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. Methods and results The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, beta-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1 alpha (HNF1 alpha)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) beta-catenin-activated HCAs, three (6%) beta-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the beta-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the beta-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. Conclusion In our series, the major HCA subtype was HNF1 alpha-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that beta-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

Objective: Metastatic involvement of the stomach is a rare event. Our aim in this study was to document the clinicopathological findings in patients with gastric metastases and find out if there are any potentially significant features to be used in the differential diagnosis. Material and Method: Our cohort consisted of 17 histologically verified gastric metastasis cases. Clinical, endoscopic and microscopic features were retrospectively analyzed. Results: The primary sites were the breast, skin, lungs, ovaries, colon, and gluteal soft tissue. Three patients were symptomatic because of the metastatic involvement of the stomach and 9 patients had concomitant metastasis in other sites. Invasive lobular breast carcinoma and malignant melanoma were the most common metastatic malignancies. The most common macroscopic appearance was the diffuse infiltrative type (Borrmann Type 4). Most of the metastatic lesions endoscopically mimicked primary gastric cancer. Furthermore, some of the metastatic lesions, particularly invasive lobular carcinoma of the breast and malignant melanoma, displayed histopathologic features similar to the primary gastric malignancies to a certain extent. Conclusion: The possibility of metastatic involvement of stomach must be kept in mind while dealing with a gastric mass lesion in a cancer patient, even though the clinical and endoscopic features suggest primary gastric cancer. Our study points out the importance of conveying the information about medical history and clinical findings of the patients for correct pathologic differential diagnosis.

This study was designed to predict the fibrosis stage with a clinical scoring system that may reduce the need for liver biopsy.The study cohort included the treatment of 430 chronic hepatitis B (CHB) and 170 chronic hepatitis C (CHC) of naive patients. The patients were divided into two groups as mild to moderate and severe fibrosis. After an index obtained in the study cohort, the index was tested in a validation cohort and compared with the FIB-4 Index.The AUC of CHC index was found of 0.89 the sensitivity of 0.91 the specificity of 0.74, the positive predictive value (PPV) of 0.54 and the negative predictive value (NPV) of 0.96. The FIB-4 Index was applied to the CHC study cohort and the ATA Index Hepatitis C was found to be superior in terms of AUC (0.89-0.82), sensitivity (0.91-0.76) and NPV (0.96-0.86). The AUC of CHB Index was determined of 0.92, the sensitivity of 0.90, the specificity of 0.84, the PPV of 0.53 and the NPV of 0.98. Compared to the FIB-4 Index in CHB study cohort, the ATA Index Hepatitis B was predominant in terms of AUC (0.92-0.88), sensitivity (0.90-0.75), NPV (0.98-0.94) and PPV (0.53-0.49).ATA Indexes can predict the non-existence of severe fibrosis with an accuracy similar to FIB-4 Index and may reduce the need for liver biopsy.

Background Regarding the incidence of colorectal malignancy and polyps in patients with acromegaly, studies reported different results in different populations. For this reason, the aim of this study was to determine the frequency of possible colonic pathologies, such as diverticula, polyps, and malignancies in Turkish patients with active acromegaly and factors affecting them. Methods A total of 134 patients with acromegaly and 134 patients with irritable bowel syndrome/dyspeptic symptoms as a control group were included in the study. None of these patients had a previous or family history of colonic neoplasms. Colonoscopies of patients with acromegaly were performed before definitive surgery in a single center by experienced endoscopists. Results The acromegaly and control groups were similar in terms of age and sex. The incidence of all colonic polyps was significantly higher in the acromegaly group (p= 0.012). The frequency of hyperplastic polyps was also increased in the acromegaly group (p= 0.004); however, the frequencies of adenoR. Iliaz, M.D. () Biruni Faculty of Medicine, Department of Gastroenterology, Biruni University, 34295 Istanbul, Turkey raimiliaz@gmail.com S. C. Dogansen · S. Tanrikulu · G. Y. Yalin · S. Yarman Istanbul Faculty of Medicine, Department of Endocrinology and Metabolism, Istanbul University, Istanbul, Turkey B. Cavus · F. Akyuz Istanbul Faculty of Medicine, Department of Gastroenterology, Istanbul University, Istanbul, Turkey M. Gulluoglu Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey matous polyps and colonic diverticula were similar in both groups. In the comparison of patients with acromegaly for the presence of polyps, those with polyps were older, had higher levels of insulin-like growth factor (IGF-1), were of male sex, and skin tags were more common (p= 0.016, p= 0.034, p= 0.006 and p= 0.001, respectively). There were no colorectal malignancies in the patients with active acromegaly. Conclusion The frequency of hyperplastic polyps was increased, whereas colonic malignancy was not observed in Turkish patients with active acromegaly.

Ki67 scoring is required for the grading of pancreatic neuroendocrine tumors. Ongoing debate exists about the best scoring method in terms of accuracy and practicality. Manual counting of cells in camera-captured/printed images is a widely used and accepted method and considered the most reliable one among the manual methods. It requires counting 500 to 2000 cells to determine the Ki67 score accurately and it is time and energy consuming. We investigated the possibility of achieving the same results by counting only a particular fraction of tumor cells in a printed image in a series of 45 (24 grade 1 and 21 grade 2) pancreatic neuroendocrine tumors. After counting Ki67-positive tumor cells in the whole image, the tumor cells were counted within one-tenth of the same image with the aid of a previously prepared grid on an acetate sheet. The cell number obtained was multiplied by 10 to estimate the total cell count and the Ki67 score was calculated. The agreement between the results of the acetate grid and conventional whole-image counting method was assessed. Near-perfect agreement was achieved regarding the total cell count and Ki67 score. The agreement on tumor grade between the two methods was perfect. The time spent on the process was significantly less than that spent on the conventional method. Although it needs to be validated in a larger series, the acetate grid method might be considered an alternative method for Ki67 scoring in neuroendocrine tumors.

Background Oral white sponge nevus (WSN) is a rare autosomal dominant benign condition, characterized by asymptomatic spongy white plaques. Mutations in Keratin 4 (KRT4) and 13 (KRT13) have been shown to cause WSN. Familial cases are uncommon due to irregular penetrance. Thus, the aim of the study was: a) to demonstrate the clinical and histopathological features of a three-generation Turkish family with oral WSN b) to determine whether KRT4 or KRT13 gene mutation was the molecular basis of WSN. Material and Methods Out of twenty members of the family ten were available for assessment. Venous blood samples from six affected and five unaffected members and 48 healthy controls were obtained for genetic mutational analysis. Polymerase chain reaction was used to amplify all exons within KRT4 and KRT13 genes. These products were sequenced and the data was examined for mutations and polymorphisms. Results Varying presentation and severity of clinical features were observed. Analysis of the KRT13 gene revealed the sequence variant Y118D as the disease-causing mutation. One patient revealed several previously unreported polymorphisms including a novel mutation in exon 1 of the KRT13 gene and a heterozygous deletion in exon 1 of KRT4. This deletion in the KRT4 gene was found to be a common polymorphism reflecting a high allele frequency of 31.25% in the Turkish population. Conclusions Oral WSN may manifest variable clinical features. The novel mutation found in the KRT13 gene is believed to add evidence for a mutational hotspot in the mucosal keratins. Molecular genetic analysis is required to establish correct diagnosis and appropriate genetic consultation. Key words:White sponge nevus, leukokeratosis, oral mucosa, keratins, mutation.

Introduction and aim Over the years, there has been a change in the profile of patients with chronic hepatitis C (CHC). In recent years, more patients with CHC have presented to the clinics at the cirrhotic stage, with decompensated liver disease, and with hepatocellular carcinoma. The aim of this study was to investigate the changing epidemiological, clinical, and virological characteristics of CHC patients. Patients and methods A total of 313 CHC patients were included in this study. The patients were classified into group 1 (1996–2001) and group 2 (2011–2016). Epidemiological, clinical, and virological differences were investigated between two periods. Results Overall, 44.7% (n=140) of the patients were in group 1. The sex distribution between the two groups was similar. The patients in group 2 was older than those in group 1 (54±15 vs. 45±12 years, retrospectively, P

Background: Microvillous inclusion disease (MVID) is one of the most severe congenital diarrhea disorders, caused by a genetic defect in enterocyte differentiation and polarization. Case report: We describe a neonate who presented with severe weight loss, hypernatremic dehydration and metabolic acidosis due to intractable diarrhea due to MVID, confirmed by electron microscopy Conclusion: MVID can present with severe weight loss, hypernatremic dehydration and metabolic acidosis that is life threatening. The diagnosis is made by typical findings on light microscopy and electron microscope of small bowel biopsies. The only therapeutic options at this time are total parenteral nutrition and bowel rest and intestinal transplantation.

Preoperative short-course radiotherapy (SCRT) followed by surgery has shown advantage over surgery alone in patients with resectable rectal carcinoma (RC); however, the importance of the timing of surgery after SCRT has not been well defined. This study aimed to investigate the effect of this duration on treatment outcomes.Patients who underwent surgery after SCRT (25 Gy/500 cGy/daily/5fr, monday-friday) for resectable and infraperitoneal rectal adenocarcinoma (T3N0/(+)) were included into the study. Patients were divided into two groups in terms of the timing of surgery: delayed surgery (4 weeks) or immediate surgery (4 weeks).A hundred and thirty-six patients were included in the study. Median time between RT and surgery was 4 ± 5.7 (1-58) weeks, where 68% (n = 93) patients underwent delayed surgery (≥4 weeks). The two groups did not differ in terms of surgical margin positivity, pathological tumor regression, N downstaging, or T downstaging (p 0.05 for all). However, the number of positive lymph nodes was higher in the immediate surgery group [median 3 (0-18) vs. 1 (0-17), p = 0.009]. Median follow-up time was 36 ± 9 (6-93) months. Delayed surgery group had significantly longer mean overall survival (p = 0.038); however, the two groups did not differ in terms of local recurrence, mean time to local recurrence, or mean disease-free survival.Our findings seem to support the benefit of a longer time interval between radiotherapy and surgery after short-course neoadjuvant radiotherapy in resectable rectal cancer in terms of overall survival. However, there is a need to better define patient characteristics that might benefit from delayed surgery.

Background/aims Recently, mucosal inflammation has been proposed to be one of the mechanisms underlying the pathophysiology of irritable bowel syndrome (IBS); however, there are controversial results regarding this hypotheses. Our aim was to evaluate immune cell infiltration in rectal and ileal biopsy specimens of patients with IBS and to compare it with those of healthy controls. Materials and methods In total, 36 patients with IBS (15 with diarrhea and 21 with constipation) and 16 healthy volunteers were enrolled. Ileocolonoscopy and ileal/rectal biopsies were performed. Rectal and terminal ileal biopsy specimens were evaluated for mucosal immune cell infiltration using immunohistochemical analysis. Serotonin positivity as well as counts of intraepithelial lymphocytes (IEL) and CD4+, CD8+, CD20+, and CD3+ cells were determined by a single pathologist who is an expert in the gastrointestinal system. Results CD3+ and CD4+ cell counts in rectal and terminal ileal biopsy specimens were lower in the IBS group than in the controls. Conversely, there was no statistically significant difference between the IBS and control groups in terms of serotonin positivity as well as counts of IEL and CD20+ and CD8+ cells. Comparison between the IBS subgroups revealed a higher number of IEL in rectal biopsy specimens of the diarrhea dominant group. In the IBS subgroups, immune cell counts in terminal ileal and rectal biopsy specimens showed a positive correlation. Conclusion IBS and its subgroups showed lower immune cell counts than the controls in our study. These results indicate that there is no significant mucosal inflammation in homogeneous groups of patients with IBS. Rectal biopsies may be sufficient for the evaluation of inflammation in IBS.

Purpose: In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers. Methods: The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed. Results: No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72). Conclusions: Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.

Aim: To investigate clinical, etiological, and prognostic features in patients with hepatocellular carcinoma. Methods: Patients with hepatocellular carcinoma who were followed-up from 2001 to 2011 were included in the study. The diagnosis was established by histopathological and/or radiological criteria. We retrospectively reviewed clinical and laboratory data, etiology of primary liver disease, imaging characteristics and treatments. Child-Pugh and Barcelona Clinic Liver Cancer stage was determined at initial diagnosis. Kaplan-Meier survival analysis was done to find out treatment effect on survival. Risk factors for vascular invasion and overall survival were investigated by multivariate Cox regression analyses. Results: Five hundred and forty-five patients with hepatocellular carcinoma were included in the study. Viral hepatitis was prevalent and 68 patients either had normal liver or were non-cirrhotic. Overall median survival was 16 (13-19) mo. Presence of extrahepatic metastasis was associated with larger tumor size (OR = 3.19, 95% CI: 1.14-10.6). Independent predictor variables of vascular invasion were AFP (OR = 2.95, 95% CI: 1.38-6.31), total tumor diameter (OR = 3.14, 95% CI: 1.01-9.77), and hepatitis B infection (OR = 5.37, 95% CI: 1.23-23.39). Liver functional reserve, tumor size/extension, AFP level and primary treatment modality were independent predictors of overall survival. Transarterial chemoembolization (HR = 0.38, 95% CI: 0.28-0.51) and radioembolization (HR = 0.36, 95% CI: 0.18-0.74) provided a comparable survival benefit in the real life setting. Surgical treatments as resection and transplantation were found to be associated with the best survival compared with loco-regional treatments (log-rank, P < 0.001). Conclusion: Baseline liver function, oncologic features including AFP level and primary treatment modality determines overall survival in patients with hepatocellular carcinoma., NA

Familial Mediterranean fever (FMF) is the most common form of autoinflammatory diseases. We aimed to evaluate the small bowel mucosa by capsule endoscopy (CE) in FMF patients for investigation of other possible causes of abdominal pain.The study group consisted of 41 patients with FMF. A standard questionnaire was used to record the gastrointestinal symptoms, other clinical findings, Mediterranean fever gene (MEFV) mutations, and history of medications including non-steroidal anti-inflammatory drugs (NSAIDs). Gastroscopy, colonoscopy and small bowel CE were performed in all patients, and biopsies were taken from terminal ileum and duodenum.The mean age of the patients was 34 ± 11 years, 63% of them were female, and 76.5% of them were carrying MEFV exon 10 mutations. Only one patient used NSAIDs in addition to colchicine. In endoscopic investigations, gastric erosion was detected in only one patient, and no significant findings were detected in colonoscopy. CE showed small bowel mucosal defects in 44% (erosions in 26.8%, ulcer in 17.1%) and edema in 29.3% of the patients. Most (64%) of the ulcer and erosions were localized to jejunum, and only 24% were in ileum. Mitotic changes as an indirect finding of colchicine toxicity were not different from the changes observed in samples of independent group of patients with irritable bowel syndrome.Mucosal defect was observed in half of the FMF patients, which may be associated with underlying inflammation or chronic colchicine exposure. Detection of nonspecific chronic inflammation without mitotic changes supports that mucosal defects may be associated with the autoinflammatory process.

Previous studies demonstrated survival benefits in association with the addition of chemoradiotherapy after surgery in gastric cancer. This study aimed to examine the efficacy in terms of loco-regional control and survival and safety of 5-FU-based adjuvant chemoradiotherapy after D2 curative surgery. This study included 228 patients (81 female, 147 male) treated for gastric cancer with curative surgery plus adjuvant chemoradiotherapy. Majority of the patients underwent at least D2 lymph node resection. Median three cycles of fluorouracil chemotherapy were administered, and 45-Gy radiotherapy was delivered at 1.8 Gy/fraction concomitantly during the second cycle of chemotherapy. Local control, regional control, distant metastasis and overall survival rates were estimated. The median age of the patients was 54 years (range 25–74 years). The most common grade III toxicities were nausea (10 %) and neutropenia (9 %). During radiotherapy, grade IV local skin reaction occurred in one patient. Median duration of follow-up was 47 months. Local, regional and distant recurrence developed in 9 (4 %), 41 (18 %) and 45 (20 %) patients, respectively. Overall 5-year survival rate was 57.2 %, and disease-free 5-year survival rate was 53.8 %. Multivariate analysis identified less than 15 lymph node involvement as an independent predictor of better survival (p

ABCD3 is one of three ATP-binding cassette (ABC) transporters present in the peroxisomal membrane catalyzing ATP-dependent transport of substrates for metabolic pathways localized in peroxisomes. So far, the precise function of ABCD3 is not known. Here, we report the identification of the first patient with a defect of ABCD3. The patient presented with hepatosplenomegaly and severe liver disease and showed a striking accumulation of peroxisomal C27-bile acid intermediates in plasma. Investigation of peroxisomal parameters in skin fibroblasts revealed a reduced number of enlarged import-competent peroxisomes. Peroxisomal beta-oxidation of C26:0 was normal, but beta-oxidation of pristanic acid was reduced. Genetic analysis revealed a homozygous deletion at the DNA level of 1758bp, predicted to result in a truncated ABCD3 protein lacking the C-terminal 24 amino acids (p.Y635NfsX1). Liver disease progressed and the patient required liver transplantation at 4 years of age but expired shortly after transplantation. To corroborate our findings in the patient, we studied a previously generated Abcd3 knockout mouse model. Abcd3-/- mice accumulated the branched chain fatty acid phytanic acid after phytol loading. In addition, analysis of bile acids revealed a reduction of C24 bile acids, whereas C27-bile acid intermediates were significantly increased in liver, bile and intestine of Abcd3-/- mice. Thus, both in the patient and in Abcd3-/- mice, there was evidence of a bile acid biosynthesis defect. In conclusion, our studies show that ABCD3 is involved in transport of branched-chain fatty acids and C27 bile acids into the peroxisome and that this is a crucial step in bile acid biosynthesis.

Clear cell sarcoma is a rare tumor classically associated with tendons and aponeuroses of lower extremities of young adults and has a distinctive histopathologic and molecular profile. It has been rarely described in other locations other than soft tissues, including the gastrointestinal tract. Herein we report a case of clear cell sarcoma of gastrointestinal tract arising in the ileum, which is rich in osteoclast-like giant cells with a review of the literature.

Purpose This study was designed to evaluate the impact of a standardized laparoscopic total mesorectal excision (TME) on the long-term oncologic outcome of unselected patients with rectal cancer (RC). Methods Unselected consecutive patients with histologically proven RC underwent a standardized laparoscopic TME with medial to lateral approach encompassing 9 sequential steps: (1) ligation of inferior mesenteric vessels, (2) mobilization of the left colon and sigmoid colon (medial to lateral), (3) posterior dissection of the rectum, (4) lateral mobilization of the sigmoid, left colon, and splenic flexure, (5) left and right side dissection of the rectum, (6) anterior dissection of the rectum, (7) transection of the rectum, (8) delivery of the specimen, and (9) colorectal anastomosis. Results From 2005 to June 2012, laparoscopic sphincter-preserving TME was attempted in 217 patients with a 6.5% conversion rate. There were 91 women and 126 men, aged 58.3 years (range, 22 to 84 y), with body mass index of 26.10 (range, 20 to 45), operative time was 150.4 minutes (range, 60 to 330 min), and 24.7 (range, 4 to 98) lymph nodes were harvested. Length of stay was 7.56 days (range, 3 to 32 d). Complication rate was 17.05%. The mean follow-up time of all patients was 36.12 months (range, 1 to 89 mo). Local recurrence rate was 3.6% and distant recurrence rate was 8.7%. The 5-year disease-free survival rates were 81.5%. Conclusions A standardized laparoscopic sphincter-preserving TME resulted in a favorable short-term outcome in unselected patients with RC.

Summary Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon-based therapy. We aimed to investigate long-term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty-three patients had TF, and 62 patients were treatment-naive (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥2 stage increase in fibrosis during follow-up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma-glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P

Background/aims: Endothelial dysfunction is an early and reversible feature in the pathogenesis of atherosclerosis. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. This study was designed to evaluate the carotid intima-media thickness and myocardial microvascular circulation in patients with non-alcoholic fatty liver disease. Materials and Methods: Twenty-four patients with non-alcoholic fatty liver disease and 28 healthy subjects were studied. Ac- cording to the pathology of liver biopsies, patients with non-alcoholic fatty liver disease were divided into non-alcoholic fatty liver and non- alcoholic steatohepatitis groups. Coronary diastolic peak flow velocities were measured at baseline, and then dipyridamole infusion was me- asured by transthoracic Doppler echocardiography. The ratio of hyperemic to baseline diastolic peak velocities was calculated and the inti- ma-media thicknesss of the carotid arteries were measured. Results: Baseline average diastolic peak and diastolic mean flow velocities we- re similar between non-alcoholic fatty liver disease patients and healthy subjects. However, hyperemic average diastolic peak and diastolic mean flow velocities were significantly lower in the patient groups compared to those in the controls (p=0.005 and p=0.002). Coronary flow velocity reserve was 1.65±0.36 and 2.67±0.81 in patients and healthy subjects, respectively (p

Interferon (IFN) therapy is associated with low rates of treatment success and high rates of recurrence in hepatitis D virus (HDV) infection. Several strategies to increase efficacy, including extending the treatment duration, have been tested. This study aimed to compare treatment outcomes between patients receiving 12 months vs. longer courses of interferon therapy for chronic delta hepatitis (CDH).Data from CDH patients receiving standard or pegylated IFN therapy were retrospectively evaluated. Patients were divided into two groups: group I received ≤12 months of therapy and group II received12 months (maximum: 24 months) of therapy. Viral response at the end of treatment (EOT-VR), post-treatment week 24 viral response (PTW24- VR) and viral response after long-term follow-up (LTFU-VR) were compared. Parameters affecting virologic response were investigated.Sixty-five patients, 14 in group I and 51 in group II, were included. The EOT-VRs were 21% and 45% (p 0.05), and the PTW24-VRs were 7% and 41% (p = 0.02), respectively. Recurrence rates were 66% and 17% in Groups I and II, respectively. The LTFU-VRs were 7% and 37%, respectively (p = 0.04). The HDV RNA at week 24 of treatment was the only parameter significantly affecting the PTW24-VR (odds ratio: 71.2; 95% CI: 3.7-1353, p = 0.005). PTW24-VR was achieved in 68% and 5% of patients with negative and positive HDV RNA, respectively, at week 24 of treatment (p 0.01).IFN treatment for up to 24 months may increase the virologic response rate for CDH. HDV RNA negativity at week 24 of treatment was a significant predictor of virologic response.

Background and Aims Application of endoscopic submucosal resection (ESMR) in the management of gastric subepithelial lesions (GSLs) less than 20 mm is gradually increasing because it allows diagnosis and treatment at the same operative session. In this study, we compare and evaluate the benefits of ESMR with an endoscopic cap band mucosectomy technique or saline solution–assisted snare technique in GSLs smaller than 20 mm. Methods This was a retrospective analysis of a prospectively maintained database used at 2 academic tertiary care centers. A total of 63 patients (34 females, mean age 52 years) with endoscopically resected GSLs were included in this study. Results The mean tumor size determined by EUS was 12.3 mm (range, 5-20 mm). Sixty-seven percent of the GSLs were localized in the antrum in all groups. The endoscopic cap band mucosectomy technique was used to resect 32 (50.8%) GSLs, whereas 31 (49.2%) were resected with the saline solution–assisted snare technique. The en bloc resection rates were 97% for the saline solution–assisted snare technique and 100% for the endoscopic cap band mucosectomy. Intraoperative bleeding occurred in 1 of 31 patients (3.2%) when ESMR was performed with the saline solution–assisted snare technique. Postoperative bleeding was seen in 1 of 32 patients (3.1%) who underwent the endoscopic cap band mucosectomy technique. Conclusions In GSLs smaller than 20 mm, ESMR with saline solution–assisted snare or endoscopic cap band mucosectomy techniques is safe, the adverse event rate is low, accurate diagnosis is achieved, and treatment with en bloc resection is provided in a single session. Given similar success and adverse event rates, saline solution–assisted ESMR may be the preferred technique because of its lower cost advantages.

WOS: 000389516600014 PubMed ID: 27619844 Objectives: Serum alanine aminotransferase (ALT) is a controversial marker for disease monitoring in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. The aim of this study was to determine the fibrosis stage and histological activity index (HAI) in HBeAg-negative CHB patients with persistently normal ALT (PNALT) and high serum HBV DNA (>= 2000 IU/ml) and to investigate clinical risk factors for the requirement of treatment through the examination of liver biopsy specimens. Methods: HBeAg-negative CHB patients with PNALT (= 2000 IU/ml) were included. HBV fibrosis stage and HAI were scored according to the Ishak system. Multivariate logistic regression analysis was used to estimate the independent risk factors for fibrosis stage >= 2 and/or HAI >= 6. Receiver operating characteristic curve analysis was used to determine an optimal age cut-off for liver biopsy. Results: A total 120 patients were enrolled. These patients had a mean HBV DNA level of 123 680 +/- 494 500 IU/ml; the HBV DNA load was 2000-20 000 IU/ml in 68 patients (56.6%) and >= 20 000 IU/ml in 52 (43.4%). Eighteen patients (15%) had moderate-to-severe histological activity (HAI >= 6). Forty-three patients (35.9%) had a fibrosis stage >= 2. Forty-eight patients (40%) had a fibrosis stage >= 2 and/or HAI >= 6. On multivariate logistic regression analysis, independent variables associated with fibrosis stage >= 2 and/or HAI >= 6 included age and HBV DNA viral load. Patients with HBV DNA 2000-20 000 IU/ml were more likely to require treatment compared to those with a viral load >= 20 000 IU/ml. The optimal age cut-off to predict fibrosis stage >= 2 and/or HAI >= 6 was 46 years. Conclusions: Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years.

This study investigated the impact of phosphohistone-H3 (PHH3)-assisted mitotic count by comparing its performance with conventional mitotic count and Ki67 score as well as the status of distant metastasis. A total of 43 surgically resected pancreatic neuroendocrine tumors (panNET) with complete follow-up information has been subjected to a standardized assessment with respect to mitotic count (both conventional and PHH3-assisted) and Ki67 score. Five participants assessed mitotic count and the time spent was recorded in both methods. All tumors were assigned to a G1 category of mitotic rate on conventional mitotic count that failed to identify three tumors with a G2 category of mitotic rate on PHH3. Near-perfect and fair agreements were achieved among observers when using PHH3 and conventional method, respectively. The mean time spent to determine mitotic count on PHH3-stained slides was significantly shorter (p

Background: This study retrospectively analyzed the clinical data, laboratory results, imaging findings, and histopathological features of 28 patients who underwent ultrasound-guided core-needle biopsy from a hepatic lesion and were diagnosed with alveolar echinococcosis. Results: Among 28 patients included in the study, 16 were females and 12 were males. The mean age of the studied population was 53 ± 16 years, and the age range was 18–79 years. The most common presenting symptom was abdominal pain, which was observed in 14 patients. A total of 36 lesions were detected in the patients’ livers, out of which 7 had a cystic appearance. Hepatic vascular involvement, bile duct involvement, and other organ involvement were depicted in 14, 5, and 7 patients, respectively. The average number of cores taken from the lesions was 2.7, ranging between 2 and 5. In histopathological evaluation, PAS+ parasitic membrane structures were visualized on a necrotic background in all cases. Regarding seven patients, who were operated, the pathological findings of preoperative percutaneous biopsies were in perfect agreement with the pathological examinations after surgical resections. None of the patients developed major complications after biopsy. Conclusion: Ultrasound-guided core-needle biopsy is a minimally invasive, reliable, and effective diagnostic tool for the definitive diagnosis of hepatic alveolar echinococcosis.

This study was designed to investigate the role of HO-1 induction in prevention of thioacetamide (TAA)-induced oxidative stress, inflammation and liver damage. The changes in hepatic dimethylarginine dimethylaminohydrolase (DDAH) activity as well as plasma arginine and asymmetric dimethylarginine (ADMA) levels were also measured to evaluate nitric oxide (NO) bioavailability. Rats were divided into four groups as control, hemin, TAA and hemin + TAA groups. Hemin (50 mg kg−1, i.p.) was injected to rats 18 h before TAA treatment to induce HO-1 enzyme expression. Rats were given TAA (300 mg kg−1, i.p.) and killed 24 h after treatment. Although TAA treatment produced severe hepatic injury, upregulation of HO-1 ameliorated TAA-induced liver damage up to some extent as evidence by decreased serum alanine transaminase, aspartate transaminase and arginase activities and histopathological findings. Induction of HO-1 stimulated antioxidant system and decreased lipid peroxidation in TAA-treated rats. Myeloperoxidase activity and inducible NO synthase protein expression were decreased, whereas DDAH activity was increased by hemin injection in TAA-treated rats. Induction of HO-1 was associated with increased arginine levels and decreased ADMA levels, being the main determinants of NO production, in plasma of TAA-treated rats. In conclusion, our results indicate that HO-1 induction alleviated increased oxidative stress and inflammatory reactions together with deterioration in NO production in TAA-induced liver damage in rats. Copyright © 2012 John Wiley & Sons, Ltd.

BACKGROUND/AIMS We aimed to determine the etiology of patients with duodenal and gastric ulcers. METHODS 140 patients diagnosed with peptic ulcer between April 2002-2009 were enrolled in this prospective study. Two biopsy specimens were collected from the antrum and corpus for histology and one for rapid urease testing, and stool samples were analyzed for Helicobacter pylori antigen. Serum calcium and gastrin levels were also analyzed. RESULTS 82 (58%) patients were male, with a median age of 47.70±15.03 years (range: 16-92). The ulcer was located in the duodenum in 96 patients, stomach in 40, and both duodenum and stomach in 4. The rates of patients positive for Helicobacter pylori antigen in stool, positive in urease testing and positive for Helicobacter pylori presence in antral and corpus samples were 48%, 52%, 67%, and 60%, respectively. 107 (76%) patients were positive for Helicobacter pylori in one of the test methods. 64 (46%) patients had a history of nonsteroidal antiinflammatory drug use within the last month. Mean levels of calcium and gastrin were 9.29±0.40 (7.90-10.20) and 73.96±89.88 (12.86-562.50), respectively. Gastrin level was correlated to inflammatory activity (p

The association of Takayasu’s arteritis (TAK) and inflammatory bowel disease (IBD) has previously been reported in case series. Microscopic colitis (MC) has IBD-like symptoms with regard to clinical and histopathological feature. We aim to assess the presence of MC in TAK patients in this study. We cross-sectionally assessed TAK patients, between the ages of 18–65 years, who were diagnosed according to the American College of Rheumatology (ACR) criteria. Disease activity was evaluated by Kerr’s criteria. Age- and sex-matched irritable bowel syndrome (IBS) patients were selected as control group. All patients and controls have been interviewed for IBD and IBS symptoms using the questionnaires of WHO guideline and Rome III criteria, respectively. Lower endoscopic procedure was performed with at least five random biopsies taken from different colonic segments and the terminal ileum. A blinded expert pathologist evaluated the specimens for the features of MC. Thirty TAK patients (29 females and 1 male) with the mean age of 35 ± 11 years (range, 20–59 years) and 15 IBS controls with the mean age of 38 ± 13 years were included in the study. TAK patients all fulfilled the MC criteria (three “complete” and six “incomplete” cases). MC was found to be significantly higher in active TAK patients in comparison to inactive group (67 vs 14 %, p = 0.03, OR = 7.9). Our results show that there is an increased frequency of MC in TAK patients, and this is the first report on the association of TAK and MC.

Benefits of somatostatin analogues have been mostly studied in mixed samples of patients including both functional and non-functional neuroendocrine tumors. This study aimed to examine the response of patients with non-functional metastatic or inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that received first-line treatment with the somatostatin analogue octreotide LAR.The medical records of 23 patients with locally inoperable or metastatic non-functional neuroendocrine tumors who received octreotide LAR (long acting release) treatment were retrospectively reviewed for clinical data and disease course. All patients had received first-line octreotide LAR 30 mg for 4 weeks. Progression free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively.All patients were followed for a median of 47 months. Mean PFS and OS were 25.0 ± 3.4 months (95% CI: 18.4-31.5) and 71.3 ± 9.5 months (95% CI: 52.7-89.9), respectively, with an estimated 5-year OS of 58%. Patients with ≤ 25% of hepatic tumor load had better PFS when compared to patients with25% hepatic tumor load (32.2 ± 6.2 vs 19.4 ± 2.7 months, p=0.043). During treatment, the following adverse events developed: skin reaction (N=1, 4.3%), cholestasis (N=1, 4.3%), grade 1 diarrhea (N=1, 4.3%), and newly onset diabetes (N=3; 13.0%).Octreotide LAR seems to be an effective treatment option with acceptable tolerability for patients with well-differentiated non-functional GEP-NETs. Survival benefits warrant further testing in future large-scale prospective trials.