The Consequences of HLA Screening in the Prevention of Graft-Versus-Host Disease in Living Donor Liver Transplantation.

AIMS: To study the effects of routine HLA screening and the policy of avoiding donor-dominant one-way HLA match to prevent graft-versus-host disease (GVHD) after living donor liver transplantation (LDLT). PATIENTS AND METHODS: The records of potential living liver donors and recipients who attended our center between 2007 and 2018 were reviewed retrospectively. RESULTS: Of the 149 patients who underwent LDLT and survived longer than 3 months, two developed GVHD despite our strict policy. The first patient presented with grade II GVHD limited to the skin. She was treated successfully by briefly discontinuing immunosuppression and switching to everolimus. In the second case, the policy had been relaxed due to the availability of a single donor for ABO-incompatible transplantation without any intervention to decrease anti-A antibody levels (special case: A2 to O). Nevertheless, the patient presented with grade I GVHD limited to skin and was treated successfully by adding oral methylprednisolone to tacrolimus and mycophenolate mofetil. To the best of our information, this is the second reported case who recovered from GVHD after LDLT from a donor, homozygous at HLA A, B and DR and a recipient, heterozygous for all. Sixteen potential donors (1.2% of all candidates) of 14 recipients were disqualified solely on the basis of the HLA results; five of these patients died due to unavailability of another donor. CONCLUSION: The results support the policy of avoiding HLA combinations that preclude immune recognition of graft lymphocytes as foreign to decrease the risk of GVHD after LDLT.

Can Interferon Therapy Change the Natural Course of Hepatitis Delta Infection?: a Clinical and Pathological Study.

Chronic delta hepatitis (CDH) has a worse outcome than other types of viral hepatitis. High-dose, long-term alpha interferon (IFN-α) is the approved treatment and may ameliorate the course of infection. We evaluated long-term histological outcomes of CDH patients treated with IFN-α. Patients with histologically proved noncirrhotic CDH who were treated with high-dose IFN-α for at least 1 year were classified as cirrhotic or noncirrhotic at the end of treatment. Noncirrhotic patients also had posttreatment liver biopsies. Patients were designated histologically responsive or nonresponsive on the basis of fibrosis status. Histological, virological, and biochemical courses were analyzed. Forty-eight patients were treated with IFN-α (conventional and/or pegylated) for a median of 24 months with a posttreatment follow-up of 5 years. During the follow-up, cirrhosis developed in 24 patients, 5 of whom were decompensated. There was no difference between pre- and posttreatment fibrosis scores for 24 noncirrhotic patients at the end of follow-up. Among patients, 13% (n = 6) had decreased, 21% (n = 10) had steady, and 16% (n = 8) had increased fibrosis scores. Persistent viral response (PVR) was achieved in 16 patients (33%). Twenty percent of the entire group was histologically responsive (decreasing or steady fibrosis scores with improved necroinflammatory scores), while nearly 80% had histological progression/cirrhosis. PVR was significantly associated with histological response. The long-term natural course of patients who were treated with high dose IFN-α for at least 1 year was evaluated clinically and histologically. Despite the association of PVR with histological response, IFN-α treatment did not change the natural course of CDH; clinical and histological progression continued in two-thirds of the cases despite treatment.

What is the clinical impact of occult HBV infections and anti-HBc positivity in patients with chronic hepatitis C?

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.

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.

A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3.

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.

Endoscopic submucosal resection of gastric subepithelial lesions smaller than 20 mm: a comparison of saline solution-assisted snare and cap band mucosectomy techniques.

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.

A Case Study of Intractable Diarrhea Due to Neonatal Microvillous Inclusion Disease.

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.

The effect of neoadjuvant therapy on the size, number, and distribution of mesorectal lymph nodes.

The current therapeutic approach to patients with locally advanced rectal cancer is neoadjuvant radiotherapy or chemoradiotherapy followed by total mesorectal excision. We aimed to investigate the number, size, and distribution of metastatic and nonmetastatic lymph nodes within the mesorectum; whether neoadjuvant therapy has any impact on the number and size of the lymph nodes; and the impact of metastatic lymph node localization on overall and disease-free survival. Specimens from 50 consecutive patients with stage II/III rectal cancer receiving either neoadjuvant radiotherapy or chemoradiotherapy were investigated. Lymph node dissection was carried out by careful visual inspection and palpation. The localization of the each lymph node within the mesorectum and the relation with the tumor site were noted. The size and the number of lymph nodes retrieved decreased significantly with neoadjuvant therapy. Majority of the metastatic and nonmetastatic lymph nodes were located at or proximally to the tumor level and posterior side of the mesorectum. No relation was observed between the overall and disease-free survival, and the localization of the metastatic lymph nodes. Presence of lymph node metastases proximal to the tumor level has no impact on survival compared with the presence of lymph node metastasis only in the peritumoral region of the mesorectum. Although neoadjuvant therapy decreases the size and the number of lymph nodes, reaching an ideal number of lymph nodes for accurate staging is still possible with careful naked eye examination and dissection of perirectal fat. As the majority of metastatic and nonmetastatic lymph nodes are located in peritumoral and proximal compartment, and posterior side of the mesorectum, these regions should be the major interest of dissection.

Tenofovir disoproxil fumarate has a substantial efficacy against multidrug-resistant strains of hepatitis B virus.

BACKGROUND & AIMS: To evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF-R) and suboptimal response to adefovir (ADF-S). METHODS: Nucleos(t)ide analogue (NA)-naïve patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6 months thereafter. The primary outcome measure was complete virological response (CVR) (HBVDNA < 20 IU/ml). CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional hazard model was generated to find out factors independently associated with CVR. RESULTS: A total of 165 patients (118 men, mean age 42 ± 12, 64 HBeAg(+) ) were included in the study. There were 105 patients in NA-naïve, 32 patients in ADF-S and 28 patients in ADF-R groups. All patients in the ADF-R group had multidrug resistance patterns. Mean duration of tenofovir treatment was 29 ± 14 months. CVR rates in NA-naïve, ADF-S and ADF-R groups were 65% vs. 75% vs. 58% at 12th month, 77% vs. 87% vs. 79% at 24th month and 83% vs. 94% vs. 79% at 36th month respectively. According to multivariate Cox regression model, HBeAg positivity (HR = 0.56, 95%CI 0.36-0.86, P = 0.008), high baseline HBVDNA level (HR = 0.64, 95%CI 0.55-0.74, P < 0.001) and ADF-R (HR = 0.47, 95%CI 0.28-0.81, P = 0.006) were independent predictors for CVR. Seven patients encountered mild renal dysfunction and were managed by dose adjustments. CONCLUSION: CVR rates during the follow-up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug-resistant strains of HBV.

Prenatal ultrasonographic diagnosis of generalized arterial calcification of infancy.

A healthy 19-year-old nulliparous pregnant woman was referred to our clinic because of fetal pericardial effusion and ascites. The sonographic examination performed at 28 weeks' gestation revealed scalp edema, severe skin edema, bilateral hydrocele, ascites, and pleural and pericardial effusion. Fetal echocardiographic examination showed that both ventricles were dilated with severely depressed contractility. The aortic annulus, ascending aorta, aortic arch, descending aorta, common iliac arteries, main pulmonary artery, tricuspid valve, and mitral chordae tendinae were hyperechogenic. Right ventricular outflow tract was narrow with decreased blood flow. There was tricuspid and mitral valve regurgitation and tricuspid valve stenosis. On the basis of these findings, we made the diagnosis of generalized arterial calcification, which is characterized by extensive calcification of internal elastic lamina and intimal proliferation of medium-sized and large arteries. This diagnosis was confirmed histologically after the termination of pregnancy.

Outcomes of first-line long-acting octreotide treatment in non-functional, advanced gastroenteropancreatic neuroendocrine tumors.

PURPOSE: 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. METHODS: 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. RESULTS: 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 with >25% 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%). CONCLUSION: 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.

Small bowel mucosal damage in familial Mediterranean fever: results of capsule endoscopy screening.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH).

AIM: Idiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH. MATERIALS AND METHODS: Hematoxylin-eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls. RESULTS: In INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001). CONCLUSION: In the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.

Efficacy of tenofovir in patients with Lamivudine failure is not different from that in nucleoside/nucleotide analogue-naive patients with chronic hepatitis B.

We evaluated the efficacy of tenofovir disoproxil fumarate (TDF) in patients with lamivudine failure (LAM-F) in comparison with that in nucleoside/nucleotide analogue (NA)-naïve patients with chronic hepatitis B (CHB). The criteria for inclusion were being NA naïve or having previous LAM-F and receiving TDF therapy for at least 6 months. Biochemical and virological tests were performed at the baseline, at 3-month intervals in the first year, and every 6 months thereafter. The primary outcome measure for efficacy was a complete virological response (CVR), defined as an HBV DNA level of <20 IU/ml. CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional-hazard model was generated in order to find predictive factors independently associated with the time to a CVR. We included 197 patients in the study (136 males; mean age, 43 ± 12 years; 105 patients were NA naïve). Sixty-five patients had hepatitis B e antigen (HBeAg)-positive CHB. The median duration of TDF treatment was 29 (range, 6 to 52) months. Seventy-one patients (77%) in the LAM-F group were treated with TDF add-on therapy. The CVR rates of the NA-naïve and LAM-F groups were comparable in HBeAg-negative (94% versus 96% at month 36, P = 0.10) and HBeAg-positive patients (67% versus 83% at month 36, P = 0.48). According to the multivariate Cox regression model, only HBeAg positivity (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.26 to 0.59; P < 0.001) and a high baseline HBV DNA level (HR, 0.44; 95% CI, 0.29 to 0.67; P < 0.001) had a significant influence on the time to a CVR. The similar cumulative CVR rates during the follow-up show that TDF has comparable efficacy in lamivudine-experienced and NA-naïve patients, and the presence of resistance mutations did not alter the response rates.

Laparoscopic surgery for rectal cancer: outcomes in 513 patients.

BACKGROUND: Few reports have demonstrated the feasibility and efficacy of laparoscopic resection in patients with rectal cancer (RC). The objective of the present study was to assess the effectiveness of laparoscopic resection for RC, with an emphasis on perioperative variables and long-term oncological outcomes. METHODS: This prospective study was carried out between January 2005 and September 2010 and included 513 patients diagnosed with RC who underwent laparoscopic surgery. Patients with locally advanced RC (cT3/cT4 or N+) received neoadjuvant treatment. Adjuvant treatment was applied to patients with stage II/III disease or according to the neoadjuvant protocol. All patients were followed-up prospectively for the evaluation of complications and oncological outcome. Survival rate analysis was performed using the Kaplan-Meier method. RESULTS: Sphincter-preserving surgery was performed on 389 patients, and the remaining 124 patients underwent abdominoperineal resection. Perioperative mortality occurred in only one patient (0.2 %), and 27 (5.3 %) intraoperative complications were recorded. The most common postoperative complication was anastomotic leakage (5.5 %). The conversion rate was 6.4 %. The mean number of harvested lymph nodes was 23.6 ± 13. The mean distance to the distal margin was 2.6 ± 1.9 (0-7) cm. Distal margin positivity was detected in 9 (1.7 %) patients. The circumferential margin was positive in 39 (7.6 %) cases. After a median follow-up period of 30 (1-78) months, recurrence occurred in a total of 59 patients (11.5 %). Local recurrence was detected in 16 patients (3.1 %), and both local and distant recurrence was found in 7 patients (1.4 %). Distant recurrence only was detected in 43 patients (8.4 %). The overall 5-year survival rate was 84 %, and the 5-year disease-free survival rate was 77.4 %. The local recurrence-free survival rate was 98.4 % at 2 years, 95.7 % at 3 years, and 94.3 % at 5 years. CONCLUSIONS: Our results, together with the review of the literature, clearly demonstrate that laparoscopic resection for RC is a feasible method at specialized high-volume centers. The long-term outcomes are at least as good as those from open surgery as long as the principles of oncologic surgery are respected and faithfully performed.

The protection by heme oxygenase-1 induction against thioacetamide-induced liver toxicity is associated with changes in arginine and asymmetric dimethylarginine.

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.

Hepatoportal sclerosis in childhood: descriptive analysis of 12 patients.

Hepatoportal sclerosis (HPS) is defined as sclerosis of portal areas in the absence of cirrhosis. There is little information about HPS in children in the literature. The aim of this study was to describe the clinical presentation, associated disorders, laboratory characteristics and outcome of children who were diagnosed as HPS. This study included 12 children diagnosed as HPS by the Pathology Department between 2005 and 2011. Data were collected from the gastroenterology clinic charts retrospectively, including demographics, presentation characteristics, laboratory data and recent status of patients. Twelve patients were enrolled (6 girls, 6 boys). The median age of patients was 13.5 yr. Median age at the time of biopsy was 11 yr. Four patients had splenomegaly, 3 had esophageal varices, one had hepatopulmonary syndrome and had been transplanted. Smooth muscle antibody was found positive in 4 patients, without autoimmune hepatitis findings in liver biopsy. One patient had celiac disease and another patient had positive celiac disease serology but pathology findings. Another patient had Turner's syndrome. Mean follow-up time was 39 months (3.3 yr) after biopsy. Hepatoportal sclerosis does not necessarily present with portal hypertension in children.

An atypically localized gastrointestinal stromal tumor: a case report of pancreas gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They can arise from any part of the tract as well as the omentum, mesentery or retroperitoneum. In this study, we present a case of a GIST originating from an extraordinary site, the pancreas. Evaluation of 30-year-old man with complaints of abdominal distension revealed a cystic, distal pancreatic lesion 13 cm in diameter. There were no intra-abdominal or distant organ metastases. The patient was operated with a diagnosis of cystic pancreas tumor, distal pancreatectomy and splenectomy was performed. The lesion was diagnosed as gastrointestinal stromal tumor upon histopathological examination. He was discharged on the sixth postoperative day without any complications and is being followed up for 21 months without systemic or local recurrence. Extragastrointestinal GISTs are reported rarely. To our knowledge, only one pancreatic GIST has been reported previously in the English literature.

BRAF, NRAS, KIT, TERT, GNAQ/GNA11 Mutation Profile and Histomorphological Analysis of Anorectal Melanomas: A Clinicopathologic Study.

OBJECTIVE: 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. MATERIAL AND METHOD: 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, 1,295,228C > T and 1,295,250C > T) were analyzed. RESULTS: 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. CONCLUSION: 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.