Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

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, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-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 ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-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 HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-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.

Evaluation of colon mucosa using screening colonoscopy and flexible spectral imaging color enhancement in patients with long lasting ulcerative colitis.

AIM: To determine which flexible spectral imaging color enhancement (FICE) channel best visualizes colon mucosa in ulcerative colitis (UC) and to compare FICE imaging with standard imaging. METHODS: The study enrolled patients with ulcerative colitis in remission who had inflammatory bowel disease for at least 8 years. All patients underwent screening colonoscopy. The entire colon, especially the suspicious areas in terms of dysplasia, were imaged with standard endoscopy and FICE. Random and target biopsies were obtained. Histopathological diagnosis was made and image patterns were evaluated. Seven endoscopists evaluated normal, colitis, and polyp images obtained with FICE. RESULTS: One hundred and twenty-three colon segments were evaluated and 1831 images were obtained from 18 patients. A total of 1652 images were FICE and 179 were standard images. Separate FICE images were obtained for normal colon mucosa, polypoid lesions, and colitis areas. Normal colon mucosa was best visualized using the second, sixth, and ninth FICE channel; polyps using the third, seventh, and ninth channel; and colitis using the second, third, and ninth channel. When all images were analyzed, the second and ninth channel were significantly better than the other channels. A total of 584 biopsies were obtained, including 492 (84.2%) random biopsies and 92 (15.7%) target biopsies. Random biopsies detected no dysplasia, but target biopsies detected low-grade dysplasia in three diminutive polyps. CONCLUSION: FICE was not significantly better at dysplasia screening than the standard procedure, but it effectively detected diminutive polyps and evaluated surface patterns without using magnification. FICE might contribute to the assessment of inflammation severity in patients with UC in clinical remission. However, more extensive studies are necessary to confirm these findings.

Magnetic resonance-based pelvimetry and tumor volumetry can predict surgical difficulty and oncologic outcome in locally advanced mid-low rectal cancer.

PURPOSE: To investigate the impact of the pelvic dimensions and tumor volume on surgery in locally advanced rectal cancer. METHODS: Patients who underwent open surgery after neoadjuvant long-course chemoradiation for primary rectal cancer were included. The predictive value of magnetic resonance-based pelvic measurements and tumor volume on the surgical difficulty and oncologic outcome were analyzed. RESULTS: 125 patients were included. The independent risk factors related to the circumferential resection margin status were the pT stage [odds ratio (OR) 3.64, confidence interval (CI) 1.409-7.327] and tumor volume after neoadjuvant chemoradiotherapy (OR 1.59, CI 1.018-2.767). The operative time (p = 0.014, OR 1.453) and pelvic depth (p = 0.023, OR 1.116) were independent predictive factors for anastomotic leak. The median follow-up was 72 (2-113) months. Local recurrence was seen in 17 (14.1%) patients. Anastomotic leak (OR 1.799, CI 0.978-3.277), the circumferential resection margin status (OR 3.217, CI 1.262-7.870) and the relative tumor volume rate (OR 1.260, CI 1.004-1.912) were independent prognosticators of local recurrence. The 5-year overall survival was 66.7%. The circumferential resection margin status (hazard ratio: 4.739, CI 2.276-9.317), pN stage (OR 3.267, CI 1.195-8.930) and relative tumor volume rate (OR 2.628, CI 1.042-6.631) were independent prognostic factors for the overall survival. CONCLUSIONS: Relative dimensions of the tumor in the pelvis influence the local recurrence and overall survival rates. Magnetic resonance-based measurements can predict the difficulty of surgery and allow surgeons to consider the appropriate surgical approach.

Neutrophil-to-lymphocyte ratio: could it be used in the clinic as prognostic marker for gastrointestinal stromal tumor?

BACKGROUND/AIMS: The association between systemic inflammatory response and tumor biology has been well documented over the last decade. The aim of this study is to investigate the prognostic role of neutrophilto- lymphocyte ratio (NLR) in gastrointestinal stromal tumors (GISTs). METHODOLOGY: A prospectively recorded database of 67 patients who underwent surgical resection for GIST was reviewed. High and low NLR were defined with respect to the sample median, which was 1.92. Demographical, clinicopathological, and surgical characteristics were analyzed as well as disease free survival (DFS) rates according to NLR classification. RESULTS: We observed better disease free survival rates in patients with low NLR compared to patients with high NLR (85.7% and 69%, respectively; p=0.037). Estimated five-year overall and disease free survival rates were 95.1% and 78.7%, respectively. In univariate analysis synchronous sarcomatosis, tumor size, mitotic rate, presence of necrosis, lymph node metastasis, surgical margin status, risk category and NLR were associated with DFS. On multivariate analysis sarcomatosis (HR: 30.455), surgical margin status (HR: 4.228) and necrosis (HR: 4.415) were found as independent prognostic factors for DFS. CONCLUSIONS: NLR can give information about inflammatory status, tumor aggressivity and prognosis in GIST patients. It could be a new prognostic factor for GIST patients.

lncRNA XIST Interacts with Regulatory T Cells within the Tumor Microenvironment in Chronic Hepatitis B-Associated Hepatocellular Carcinoma.

OBJECTIVE: Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment. MATERIAL AND METHODS: Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed. RESULTS: Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19). CONCLUSION: lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.

CD40 expression in pancreatic cancer.

BACKGROUND: CD40, a tumor necrosis factor receptor family member, is expressed in a variety of cell types. This widespread expression suggests that CD40 may play an important role in normal physiology and disease pathogenesis. The objective of the current study was to investigate the expression of CD40, and its association with clinicopathological features and survival in patients with pancreatic ductal adenocarcinoma. METHODOLOGY: CD40 expression was assessed in 53 pancreatic ductal adenocarcinoma surgical specimens by immunohistochemistry, and expression was correlated with patient clinicopathological parameters and outcome. RESULTS: Among 53 pancreatic cancer specimens, CD40 expression was detected in 13 specimens (24.5%), and peritumoral lymphocytes were present in 45 specimens (84.9%). Patients with CD40-positive tumors exhibited prolonged median disease-free survival (DFS) compared with patients with CD40-negative tumors (15.60 +/- 3.87 versus 10.03 +/- 1.92); however, this was not significant (p = 0.845). Patients with peritumoral lymphocytic reaction exhibited prolonged median DFS compared with patients without peritumoral lymphocytes (10.96 +/- 1.40 vs. 7.60 +/- 0.47); however, this was not significant (p = 0.624). Patients with peritumoral lymphocytic reaction exhibited higher median overall survival compared with patients without peritumoral lymphocytes (15.20 +/- 1.78 vs. 10.13 +/- 1.39); however, again this was not significant (p = 0.100). CONCLUSIONS: These results suggest that CD40 expression on pancreatic cancer cells and peritumoral lymphocytic reaction may serve as prognostic markers.

Endoscopic and histological characteristics of small bowel tumors diagnosed by double-balloon enteroscopy.

BACKGROUND/AIMS: Double-balloon enteroscopy (DBE) allows for the diagnoses and treatment of small bowel tumors (SBTs). This study aimed to evaluate the utility of DBE for the diagnosis and treatment of SBTs. METHODS: Patients diagnosed with SBTs who underwent DBE were included in this study. According to their endoscopic appearances, they were categorized as polyps or masses, and according to their histological characteristics, they were categorized as benign or malignant SBTs. RESULTS: A total of 704 patients were retrospectively analyzed, and 90 (12.8%) were diagnosed with SBTs. According to their endoscopic appearance, 48 (53.3%) had polyps and 42 (46.7%) had masses. Additionally, 53 (58.9%) and 37 (41.1%) patients had malignant and benign SBTs, respectively, depending on their histological characteristics. Patients diagnosed with polyps were younger than those diagnosed with masses (p<0.001). Patients diagnosed with benign SBTs were younger than those diagnosed with malignant SBT (p<0.001). Overall, histological diagnosis was determined using DBE in 73 (81.1%) patients. CONCLUSION: DBE is a useful method for diagnosing SBTs. Additionally, the histological type of the lesion can be determined using DBE.

Complications and Long-Term Outcomes in Adult Patients Undergoing Living Donor Liver Transplantation Because of Fulminant Hepatitis.

BACKGROUND: The present study investigates the complications that may occur during long-term follow-up in patients aged 18 years and older undergoing living donor liver transplantation (LDLT) in our clinic because of fulminant hepatitis. METHODS: The study included patients aged 18 years and older with a minimum survival of 6 months who underwent an LDLT between June 2000 and June 2017. The demographic data of the patients were evaluated in terms of late-term complications. RESULTS: Of the 240 patients who met the study criteria, 8 (3.3%) underwent LDLT for fulminant hepatitis. The indication for transplantation in patients with fulminant hepatitis was cryptogenic liver hepatitis in 4 patients, acute hepatitis B infection in 2 patients, hemochromatosis in 1 patient, and toxic hepatitis in 1 patient. Of the 240 patients, 65 (27%) undergoing LDLT underwent a liver biopsy for suspected rejection because of an elevation in liver function test results during follow-up. Histopathologic scoring was carried out according to the Banff scoring system. A diagnosis of late acute rejection was made in only 1 of the 8 patients (12.5%) who underwent LDLT for fulminant hepatitis. CONCLUSION: Patients with fulminant hepatitis must be prepared for an LDLT, if available, while waiting for a cadaveric donor. The results of the present study suggest that LDLTs in patients with fulminant hepatitis are safe, and the outcomes are acceptable in terms of survival and complications.

Diagnostic performance of magnetic resonance imaging in preoperative local staging of rectal cancer after neoadjuvant chemoradiotherapy

PURPOSE: This paper aims to investigate the diagnostic performance of magnetic resonance imaging (MRI) in predicting the pathologic stage of locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) and the role of MRI in selecting patients with a pathologic complete response (ypCR). METHODS: Restaging MRI (yMRI) examinations of 136 patients with LARC treated with neoadjuvant CRT followed by surgery were retrospectively analyzed by two radiologists. All examinations were performed on a 1.5 Tesla MRI machine with a pelvic phased-array coil. T2-weighted turbo spin-echo images and diffusion-weighted imaging were obtained. Histopathologic reports of the surgical specimens were the reference standard. The accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) of yMRI in predicting the pathologic T-stage (ypT), N-stage, and ypCR were calculated. The inter-observer agreement was evaluated using kappa statistics. RESULTS: The yMRI results showed 67% accuracy, 59% sensitivity, 80% specificity, 81% PPV, and 56% NPV in identifying ypT (ypT0-2 versus ypT3-4). In predicting the nodal status, the yMRI results revealed 63% accuracy, 60% sensitivity, 65% specificity, 47% PPV, and 75% NPV. In predicting ypCR, the yMRI results showed 84% accuracy, 20% sensitivity, 92% specificity, 23% PPV, and 90% NPV. The kappa statistics revealed substantial agreement between the two radiologists. CONCLUSION: Utilization of yMRI showed high specificity and PPV in predicting the tumor stage and high NPV in predicting the nodal stage; in addition, yMRI revealed moderate accuracy in the T and N classifications, mainly due to underestimating the tumor stage and overestimating the nodal status. Finally, yMRI revealed high specificity and NPV but low sensitivity in predicting the complete response.

Diagnosis and Treatment of Autoimmune Hepatitis: Questions, Answers, and Illustrative Cases: Endorsed by Autoimmune Liver Diseases Special Interest Group, Turkish Association for the Study of Liver.

Autoimmune hepatitis (AIH) is a rare, immune-mediated liver disease. It has a heterogeneous nature with varied clinical presentations. The management of patients with AIH is challenging in many ways. The main difficulties are inexperience due to the rarity of the disease, diagnostic confusion in controversial areas such as variant/overlap cases, acute presentations, the presence of non-alcoholic fatty liver disease or drug-induced liver injury features, and the long and complex course of treatment. Here, we provide a clear, concise, and visualized review regarding the diagnosis and treatment of AIH, including illustrative cases.

The Prognostic Significance of Circulating Tumor Cells in Patients with Pancreatobiliary Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are cancer cells which separate from the primary tumor and enter systemic circulation. In this study, it was aimed to examine the relationship between CTCs isolated and identified from the peripheral blood of patients with pancreatobiliary cancer, with the clinicopathological characteristics of the patients and their overall survival. METHODS: A total of 21 patients were included the study. Density gradient centrifugation with the OncoQuick® assay was performed for isolation of CTCs from peripheral blood. In order to identify CTCs, enriched samples underwent flow cytometric analysis. RESULTS: The rate of patients with positive surgical margin in the high CTC group (CTC <15) was identified to be statistically significantly high compared to the group with low CTC (CTC ≤15) (83.3% vs. 16.7%; P = .041). Median neutrophil/lymphocyte ratio (NLR) was found to be higher in the high CTC group compared to the low CTC group, which was close to statistical significance (2.37 vs. 1.41; P = .055). CONCLUSIONS: Circulating tumor cells were identified to have a significant relationship with surgical margin positivity in our study for the first time, suggesting that the CTCs count in peripheral blood in preoperative patients may be a biomarker predicting positive surgical margin. Due to the very low number of studies assessing the relationship between CTCs and NLR, our study which identified relationship close to statistical significance between CTCs and NLR, significantly contributes to the literature on the topic of the possible role of lymphocytes in CTC clearance.

Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

BACKGROUND: Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. RESULTS: MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of ß-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. CONCLUSIONS: These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the ß-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

Tumoral and Parenchymal Morphological Assessment in Liver Metastases of Colorectal Carcinoma: Micrometastasis, Peritumoral Lymphocytes, Tumor Budding and Differentiation are Potential Prognostic Factors.

Introduction: Various potential prognostic histopathologic factors for colorectal carcinoma liver metastasis have been proposed. However, there is still no consensus on pathological reporting of colorectal carcinoma liver metastasis resection materials. The aim of this study was to investigate the relation between selected tumoral and parenchymal histopathologic features and prognostic factors for better characterization and prognostic prediction of the patients with colorectal carcinoma liver metastasis. Methods: Hematoxylin-eosin stained slides from 100 patients who underwent hepatic resection were evaluated. Pathologic characteristics; including number of tumor nodules, largest tumor size, status of surgical margin, tumor distance to closest margin, tumor necrosis, the presence of tumor capsule, tumor differentiation, perineural and lymphovascular invasion, micrometastasis, tumor budding, peritumoral lymphocytic infiltrate and parenchymal features including steatosis, steatohepatitis, lobular inflammation, confluent necrosis, hepatocyte ballooning, portal inflammation were assessed. For 49 patients who were treated with preoperative chemotherapy, tumor regression grade and chemotherapy-related parenchymal changes such as sinusoidal damage, venous obstruction, nodular regenerative hyperplasia, steatosis and steatohepatitis were also evaluated. Results: The presence of lymphovascular invasion (p < 0.001), micrometastasis (p=0.004), absent or mild peritumoral lymphocytic infiltration (p =0.013), high tumor budding score (p=0.033) and moderate/poor differentiation (p=0.022) were significantly associated with shorter overall survival. Lymphovascular invasion (p < 0.001) was an independent predictor of mortality in multivariate analysis. Conclusions: We conclude that tumor differentiation, lymphovascular invasion, micrometastasis, peritumoral lymphocytic reaction and tumor budding score are potential prognostic histopathological features and candidates for inclusion in pathology reports of colorectal carcinoma liver metastasis resections.

The Site of Lymph Node Metastasis: A Significant Prognostic Factor in Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: While the presence and number of metastatic lymph nodes (LNs) are important prognostic factors for pancreatic ductal adenocarcinoma (PDAC), there is no recommendation to specify metastatic regional LN localization in the current staging system. The aim of this study was to evaluate the prognostic effect of regional metastatic LN localizations in PDAC. MATERIAL AND METHOD: Metastatic sites of 101 consecutive PDAC patients who underwent pancreaticoduodenectomy were classified as peripancreatic, perigastric, hepatica communis, hepatoduodenal, and superior mesenteric artery. The frequency of metastasis in each region and the association between the presence of metastasis in each site and overall and disease-free survival were statistically analyzed. RESULTS: Eighty cases (79.2%) had peripancreatic, 7 (6.9%) had perigastric, 6 (5.9%) had hepatica communis, 7 (6.9%) had hepatoduodenal, and 4 (4%) had superior mesenteric artery LN metastasis. The overall and disease-free survival values were significantly shorter in patients with hepatoduodenal LN metastasis (log rank; p= 0.001, p=0.017, respectively). The presence of metastatic superior mesenteric artery LN was significantly associated with shorter disease-free survival in univariate analysis (p=0.017). Hepatoduodenal LN metastasis was an independent predictor of mortality (p=0.005) in multivariate analysis. CONCLUSION: The presence of hepatoduodenal LN metastasis is an independent poor prognostic factor for mortality. The presence of metastatic LN in the superior mesenteric artery region was significantly associated with shorter disease-free survival time, although not an independent predictor. We conclude that the metastatic regional LN sites, especially the hepatoduodenal region, have an impact on the prognosis, and should be included in synoptic pathology reports.

Peritumoral histopathologic findings in patients with chronic viral hepatitis-associated hepatocellular carcinoma.

Data on peritumoral histopathologic findings in patients with hepatocellular carcinoma (HCC) is limited. In this retrospective study, we evaluated the peritumoral histopathologic changes in patients with chronic viral hepatitis (CVH)-associated HCC (CVH-HCC) and their prognostic value. 61 consecutive cirrhotic patients who underwent liver transplantation due to CVH-HCC were included. Histopathologic features within 1 cm distance of the tumor, and their association with clinicopathological characteristics and prognosis were evaluated. A random representative slide of cirrhotic parenchyma unrelated to invasive and/or dysplastic foci was also evaluated for the same histopathologic criteria. The majority (85%, n = 52) were male with a median age of 55 ± 6.38 (range, 39-67). The etiologic agent was only HBV in 90% (n = 55). The most common peritumoral findings were portal inflammation (100%; n = 61), ductular reaction (100%; n = 61) and sinusoidal dilatation (95%; n = 58). Macrovascular invasion was observed only in four cases (7%) with mild peritumoral portal inflammation. Neutrophilic infiltration of the peritumoral portal tracts (n = 18; 30%) was significantly associated with pT4 tumor stage, tumor grade, macrovascular invasion, and pretransplant therapy. Patients with moderate or severe peritumoral sinusoidal dilatation tended to have worse prognosis, albeit not significantly. Peritumoral ballooning degeneration was associated with multifocality, recurrence and recurrence-free survival in both uni- and multivariate analysis. Peritumoral histopathologic changes in CVH-HCC can be classified as: changes related to pathogenesis, changes indirectly affecting prognosis, and changes directly affecting prognosis. Peritumoral prominent ballooning degeneration may be a predictor of recurrence while portal neutrophilic infiltration and sinusoidal dilatation seem to indicate poor prognosis.

Reconsideration of Clinicopathologic Prognostic Factors in Pancreatic Neuroendocrine Tumors for Better Determination of Adverse Prognosis.

The question of how successful we are in predicting pancreatic neuroendocrine tumors (panNET) with poor prognosis has not been fully answered yet. The aim of this study was to investigate the effects of clinicopathological features on prognosis and to determine their validity in prediction of prognosis and whether a better prognostic classification can be made. Fifty-six patients who underwent pancreatic resection for pancreatic neuroendocrine tumor were included. The associations between clinicopathological parameters and prognosis were evaluated statistically. Efficiencies of different thresholds for tumor size, mitotic count, and Ki67 proliferation index for prognosis prediction were compared. Vascular invasion was statistically associated with high tumor grade, advanced pT stage, and mortality rate. The presence of non-functional tumor, lymphatic invasion, and > 10 cm tumor size were significantly related to shorter overall survival. Advanced pT stage (pT3-4), > 5 cm tumor size, and high tumor grade (grades 2-3) were significantly associated with shorter disease-free survival. The mortality rate showed the strongest statistical significance with mitotic count when grouped as 1: < 2, 2: 2-10, and 3: > 10 mitosis/ 2 mm2. The 10% threshold value for Ki67 index was more successful in predicting adverse prognosis. Among the morphologic variants, the ductulo-insular variant was the most promising to have positive prognostic value in our series, although no statistical significance was detected. In conclusion, threshold values of 5 cm and 10 cm for tumor size, 10% for Ki67 proliferation index, and 10/2 mm2 for mitotic count and vascular and lymphatic invasion assessed separately are potential prognostic candidates for better stratification of panNETs.

Investigation of Cytomegalovirus in Intestinal Tissue in a Country With High CMV Seroprevalence.

BACKGROUND: In Turkey, cytomegalovirus (CMV) seropositivity has been reported to be high, between 85 and 100%. CMV has been responsible for disease exacerbation in inflammatory bowel disease (IBD). We aimed to evaluate the presence of CMV in intestinal tissue by immunohistochemical staining in IBD and non-IBD patient groups, in a country with high CMV seroprevalence. METHODS: In this prospective cross-sectional study, the presence of intestinal CMV was investigated with tissue immunohistochemistry (IHC) staining, which is accepted as the gold standard method, and with polymerase chain reaction (PCR) in tissue and blood. Patients (≥18 years old, n = 189) who had a colonoscopic biopsy between January and May 2017 were included in the study at our hospital. Clinical, laboratory, endoscopic, and histopathological data of patients were assessed by dividing them into IBD (n = 34) and non-IBD (n = 155) groups. RESULTS: In this study, 567 colonic biopsy samples from 189 patients were evaluated. Tissue IHC staining was positive for 3 (1.58%) non-IBD patients. One of them was diagnosed as CMV ileitis. CMV DNA was also detected in 14 plasma (7.40%, <80-469 copies/mL) and 20 tissue samples (10.69%, 7-15 289 copies/mL). Tissue IHC staining is accepted as the gold standard for CMV ileitis, and the sensitivity and specificity of tissue PCR was 33% and 89.67%, while the sensitivity and specificity of plasma PCR was 66.66% and 93.54%, respectively. CONCLUSION: Although CMV seroprevalence is high in Turkey, CMV ileitis was diagnosed in only one non-IBD patient (0.53%). Compared to tissue IHC staining, the sensitivity of tissue and blood CMV PCR was low while their specificity was higher.

Molecular characteristics of colorectal hyperplastic polyp subgroups.

BACKGROUND/AIMS: The importance of hyperplastic polyps during colorectal carcinogenesis is appreciated related to the understanding of serrated pathway. The morphologic subtypes of hyperplastic polyps in carcinogenesis and the nomenculature of lesions with both hyperplastic and adenomatous areas are controversial. We aimed to reveal the molecular properties of hyperplastic polyp subtypes and the molecular changes in polyps containing both hyperplastic and adenomatous areas. Matherial and Methods: 49 hyperplastic polyps [19 microvesicular (MVHP), 19 goblet-rich (GRHP), 11 mucin-poor (MPHP)] and 10 mixed hyperplastic and adenomatous polyps were analysed for KRAS, BRAF mutations and MSI with real-time PCR. RESULTS: 68,4% of MVHPs and 81% of MPHPs which were localized in right colon had BRAF mutations. While none of the GRHPs showing a KRAS mutation with a rate of 73% was localized in the ascending colon, 63% of them were localized in the rectosigmoid area. In five (50%) of the mixed polyps, KRAS mutation was detected both in the hyperplastic and adenoma components. There was no BRAF mutation in any of the mixed polyps. However, in two cases, the hyperplastic component was MSI-H and the adenoma area was MSS. CONCLUSION: Hyperplastic polyps, even if smaller than 5 mm, are precancerous lesions bearing different mutations. GRHPs with predominant KRAS mutations and MVHPs and MPHSs with predominant BRAF mutations are precancerous. Although the molecular investigations for HPP/SP are not necessary the morphological subtyping should be included if the case is diagnosed with HPP/SP as it will be useful for attracting the gastroenterologist's attention.

The Role of Log Odds of Positive Lymph Nodes in Predicting the Survival after Resection for Ampullary Adenocarcinoma.

Lymph node metastasis is a important factor on survival in ampullary adenocarcinoma. Log odds of positive lymph nodes (LODDS) is a novel prognostic indicator on lymph node status. We aimed to evaluate the prognostic impact of LODDS for the patients with ampullary adenocarcinoma who underwent R0 pancreaticoduodenectomy. The study includes 42 patients.. LODDS was calculated as "log (number of metastatic lymph nodes+0.5)/(number of total harvested nodes - metastatic lymph nodes+0.5)". LODDS subgroups were created based on their LODDS value: LODDS1(LODDS≤ - 1.5), LODDS2(-1.5 < LODDS≤ - 1.0), LODDS3(-1.0 < LODDS≤ - 0.5), LODDS4(LODDS> - 0.5). The mean survival time was 72.7 ± 7.82 months. Survival rates for 1, 3 and 5 years were 93%, 65% and 45%, respectively. The mean LODDS value was -1.0466 ± 0.51. LODDS subgroups show strong correlation with Overall Survival(OS). The mean survival were 114.8, 81.8, 56.6 and 25.6 months in LODDS subgroups 1, 2, 3 and 4, respectively (Log-rank; p = 0.002), in addition LOODS values shows correlation with perineural invasion and micro vascular invasion (p = 0.015 and p = 0.001 respectively). Findings in our patient group support the hypothesis that LODDS subgroups correlate with OS, and that value of LODDS has considerable role in prediction of OS as well.

Comparison of Resection and Liver Transplant in Treatment of Hepatocellular Carcinoma.

OBJECTIVES: Hepatic resection and liver transplant are regarded as 2 potentially curative treatments for hepatocellular carcinoma. Here, we compared both options in patients with hepatocellular carcinoma secondary to cirrhosis seen at a single center over 12 years. MATERIALS AND METHODS: We evaluated early complications and survival of patients with hepatocellular carcinoma treated with liver transplant (57 patients) or hepatic resection (36 patients) at our center between 1998 and 2010. RESULTS: The 34-month mean follow-up period was similar for both treatment groups. The liver transplant group had a longer hospital stay than the hepatic resection group (P ⟨ .001). Patients with Child-Turcotte-Pugh A stage were treated by hepatic resection more than by liver transplant (P ⟨ .001),with Child-Turcotte-Pugh B stage patients treated by liver transplant more than by hepatic resection (P = .03). All patients with Child-Turcotte-Pugh C stage had liver transplant. Both treatment groups had similar postoperative complications and early postoperative mortality rates, but liver transplant resulted in longer overall (P = .001) and higher event-free (P = .001) survival than hepatic resection. Among the liver transplant group, 57.8% of patients met the Milan criteria. Patients who met Milan criteria were treated by liver transplant statistically more than hepatic resection, and these patients had longer overall survival (P = .01) and higher event-free survival (P ⟨ .001) than patients who had hepatic resection. Hepatocellular carcinoma recurrence rates were higher after hepatic resection (P = .232). CONCLUSIONS: In patients with hepatocellular carcinoma, hospital stay was longer after liver transplant, but morbidity and mortality rates for liver transplant versus hepatic resection were similar. However, overall and event-free survival rates were better after liver transplant than after hepatic resection. These results suggest that liver transplant should be considered as the primary treatment option for patients with hepatocellular carcinoma secondary to cirrhosis.