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.

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.

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.

Effects of polymorphisms in interferon λ 3 (interleukin 28B) on sustained virologic response to therapy in patients with chronic hepatitis D virus infection.

BACKGROUND & AIMS: We investigated the association between interferon λ 3 (IFNL3) genotype (also known as interleukin 28B) and response to IFNα therapy in patients with chronic hepatitis D virus (HDV) infection. METHODS: We studied IFNL3 genotypes of 32 patients (19 men; median age, 42.5 y) with chronic HDV infection. Nineteen patients (59%) were treated with pegylated IFNα and 13 patients (41%) were treated with standard IFNα, for at least 12 months. Levels of HDV RNA were measured before the initiation of treatment and every 6 months thereafter; patients were followed up for a median time of 16 months (range, 6-164 mo) after treatment ended. We used real-time polymerase chain reaction to classify the IFNL3 polymorphism rs12979860 as CC, CT, or TT, and rs8099917 as TT, GT, or GG. A virologic response was defined as undetectable HDV RNA in serum, and a sustained virologic response (SVR) was defined as undetectable HDV RNA after cessation of treatment until the end of the follow-up period. We evaluated the association between IFNL3 polymorphism and treatment response using univariate and multivariate analyses. RESULTS: After treatment, a response was achieved in 16 patients (50%) and an SVR was achieved in 9 (28%). The percentages of patients with CC, CT, and TT at rs12979860 were 47%, 47%, and 6%, respectively; the percentages of patients with TT, GT, and GG at rs8099917 were 69%, 28%, and 3%, respectively. Rates of SVR were 27%, 27%, and 50% in patients with CC, CT, TT at rs12979860 (P = .78 for CC vs CT vs TT) and 36%, 11%, and 0% in patients with TT, GT, and GG at rs8099917 (P = .30 for TT vs GT vs GG). CONCLUSIONS: The IFNL3 polymorphisms rs12979860 and rs8099917 do not significantly affect responses of patients with chronic HDV infection to treatment with IFNα.

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.

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.

Lamivudine treatment failure risks in chronic hepatitis B patients with low viral load.

AIM: To analyze the risk factors of lamivudine treatment failure (LTF) for the long-term use in patients with low viral load (LVL). MATERIAL AND METHODS: In this multicenter study, 548 antiviral naïve noncirrhotic adult patients with LVL (for HBeAg+ patients HBV DNA <10 9 copies/ml and for HBeAg­patients HBV DNA <10 7 copies/ml) were enrolled. As a control group, 46 lamivudine-initiated patients with high viral load (HVL) were included. Primary outcome was switching to or adding on another antiviral drug as a consequence of primary nonresponse, partial response, viral breakthrough or adverse events. Secondary outcomes included LTF rates at 1, 2, 3, 4 and 5 years and LTF-related viral and host factors. RESULTS: Among 594 patients, 294 had to change lamivudine at the follow-up. Primary nonresponse, partial response, viral breakthrough or adverse events frequencies were 6.8, 1.6, 64.5 and 0.1%, respectively. Five-year LTF rates were 61.3 and 84.2% in patients with LVL and HVL, respectively. Among patients with LVL, patients with <100,000 copies/ml and ≥ 100,000 copies/ ml had 54.8 and 67.3% LTF rates at the end of the 5th year, respectively. Logistic regression analysis of risk factors showed HBeAg+, hepatic activity index, HBV DNA, virological response at 6 months and duration of follow-up were independent predictors for LTF (p values were 0.001, 0.008, 0.003, 0.020 and 0.003, respectively). CONCLUSION: Similar to patients with HVL, first-line lamivudine therapy is not efficient for long-term use in patients with LVL. LTF risk is so high even in the absence of worse predictive factors.

Effects of Crataegus microphylla on vascular dysfunction in streptozotocin-induced diabetic rats.

Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5) M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-α and IL-6 and by preventing lipid peroxidation.

Is the Y90-radioembolization treatment effective on the intermediate-advanced stage of hepatocellular carcinoma and what is the albumin-bilirubin score's prediction factor for survival?

Background and Aim: Radioembolization (RE) is a one of the palliative treatments that have been used to down stage and/or increase the survival time in intermediate-advanced stages of HCC. We aimed to evaluate the clinical impact of RE and the clinical use of the albumin-bilirubin (ALBI) score as a predictor for survival in HCC patients. Materials and Methods: Fifty-nine unresectable hepatocellular carcinoma (HCC) patients were enrolled. RE was performed in 28 of them (group 1) and 31 patients were followed up in the natural course (NC) (group 2). Patients were classified according to the Child-Pugh score (only cirrhotic patients), Barcelona clinic liver cancer (BCLC) staging, and ALBI scores were also calculated. Results: All patients in Group 1 were cirrhotic and their BCLC stages were as follows: 60.7% stage B and 39.3% stage C. In Group 2, 83.9% of patients were cirrhotic and their BCLC stages were as follows: 9.7% stage B, 51.6% stage C, and 38.7% stage D. Mortality rates were 82% and 100% in Groups 1 and 2, respectively. The median overall survival (OS) was 13.5 months (95% CI: 10.4-16.6 months) and 4.5 months (95% CI: 3.5-5.5 months) in Groups 1 and 2, respectively (p=0.000). When RE was applied to patients with ALBI Grade 1 and 2, the median OS was statistically higher than in the NC group, respectively (p<0.001, p<0.001). Conclusion: RE is an effective treatment method at the advanced stages of HCC. The ALBI score is a more useful and practical than the other prognostic tools.

Evaluation of safety and efficacy of tenofovir disoproxil in hemodialysis and renal transplant patients monoinfected with hepatitis B virus based on real life data.

Introduction: There are limited data about the safety of tenofovir disoproxil fumarate (TDF) in chronic renal failure (CRF). In this study, we aimed to evaluate the safety and efficacy of TDF in renal transplant recipients and hemodialysis patients with chronic hepatitis B (CHB) during long-term follow-up. Material and methods: CHB patients undergoing hemodialysis (group 1), renal transplant recipients (group 2) and patients with normal renal function were included in the study. All patients were treated with TDF for at least 6 months. The groups were compared with regards to safety and efficacy. HBV-DNA levels were studied using a Cobas-TaqMan 96 system. Results: A total of 217 patients with CHB (group 1: 8 patients, group 2: 9 patients, group 3: 200 patients) were enrolled in this study. The frequency of clinical adverse effects was significantly higher in groups 1 and 2compared with group 3 (37.5% vs. 11.1% vs. 0.5%, respectively, p < 0.001). However, no patients discontinued the drug due to the adverse effects. Serum creatinine levels were similar at baseline and at the end of follow-up in groups 1 and 2 (6.5 ±1.8 mg/dl and 6.9 ±1.5 mg/dl; 1.3 ±0.2 and 1.4 ±0.4 mg/dl, respectively, p < 0.05). HBV-DNA negativity rates were comparable at the 12th month and at the end of follow-up (50-83% for group 1, 60-67% for group 2 and 70-75% for group 3, respectively, p > 0.05). Conclusions: Clinical adverse effects of TDF were more common in patients with CRF in comparison with patients without CRF. However, the occurrence of adverse effects did not necessitate discontinuation of the drug. TDF was safe and effective for this group of patients.

Cyclosporine Therapy as a Rescue Treatment in Steroid Refractory Acute Severe Ulcerative Colitis: A Real Life Data From a Tertiary Center.

BACKGROUND: Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients. METHODS: Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylpredniso- lone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index. RESULTS: In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy. CONCLUSION: Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive.

Feasibility of EUS-guided injection of irinotecan-loaded microspheres into the swine pancreas.

BACKGROUND: LC beads (Biocompatibles International plc) are designed for the time-released delivery of the chemotherapeutic agent irinotecan into focal, hypervascularized, hepatic tumors. OBJECTIVE: To determine the feasibility of EUS-guided injection of LC beads (with/without irinotecan) into the swine pancreas. DESIGN: Survival animal study. SETTING: Academic center. SUBJECTS: This study involved 12 Yorkshire swine. INTERVENTION: LC beads without irinotecan and loaded with up to 300 mg of irinotecan were injected under EUS guidance with a 19-gauge needle into the tail of the pancreas. CT scanning and necropsy with histology were performed at day 7. MAIN OUTCOME MEASUREMENTS: Feasibility of the injections, gross and microscopic evidence of pancreatic inflammation, and clinical tolerance by the animals. RESULTS: After injection of LC beads with/without irinotecan, in 10 of 12 animals an intrapancreatic, hyperechoic focus with an average diameter of 2.2 cm was visible by EUS, and a hypodense area in the tail of the pancreas was visible by contrast CT. In 2 animals (1 with irinotecan and 1 without) no beads were seen on CT. In 10 of 12 animals, a depot of beads was located in the tail of the pancreas on gross inspection and histology. Drug depot with only localized pancreatic tissue reactions was seen on histopathologic review. LIMITATIONS: Animal study. CONCLUSION: The EUS-guided injection of LC beads (with/without irinotecan) into the pancreas of the pig is feasible and safe. This technique is a potential minimally invasive local treatment option for locally advanced pancreatic cancer.

Could complement C4 be an alternative to biopsy for chronic hepatitis B histopathologic findings?

BACKGROUND: Hepatitis B leads to chronic liver disease, cirrhosis, and hepatocellular cancer. Viral markers and other laboratory tests used in diagnosis and follow-up of chronic hepatitis B (CHB) do not correlate well with disease activity and liver histopathology. For this reason, alternative tests that indicate disease activity are needed. We aimed to investigate the utility of serum complement levels for follow-up in patients with CHB with normal and high transaminase levels. METHODS: One hundred forty-three patients that were evaluated between 2009 and 2010 were included in the study. Hepatitis B early antigen negative CHB cases with high transaminase levels were evaluated as the first group, and cases with normal transaminase level (inactive hepatitis B surface antigen carrier) as the second group, patients with cirrhosis were included as a third group. Age, sex, hepatitis B surface antigen, anti-HBcAg IgM, hepatitis B early antigen, anti-δ, anti-HCV, anti-HIV, serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), complement C3, and C4 levels of both groups were compared. The relationship between Knodell histologic activity index (HAI) score and fibrosis in liver biopsy specimens and serum complement levels of cases with high transaminase levels were investigated. FINDINGS: There were 49 patients with CHB with high transaminase levels; (Female/Male: 22/27). Mean age was 42.3±15.7 y, ALT=104.41±101.74, AST=69.7±65.2, GGT=35.37±20.4, C3 level=104.2±28.8, C4=16.11±4.17, and HBV DNA >2000 IU/mL (>105 copies/mL) in all cases. Remaining 27 patients had cirrhosis. There were 67 patients with CHB with normal transaminase levels (Female/Male: 32/35). Mean age was 39.56±12.9 y, ALT=22.7±5.5, AST=22±5.18, GGT=48.8±60.4, C3=117.85±22.15, and C4=21.44±5.46. Serum complement C4 level in 4 of the CHB cases with normal transaminase levels was low. Serum C3 (P=0.024) and C4 (P=0.001) levels in patients with CHB with high transaminase level were significantly lower. Low serum complement levels were negatively correlated with Knodell-HAI scores in patients with high transaminase levels (r=-0.84; P<0.001). There was no correlation between HAI and HBV DNA, AST, ALT, and GGT. There was no significant correlation between complement C3 and C4 levels and ALT, AST, HBV DNA, and GGT in any of the groups. Child score in patients with cirrhosis negatively correlated with both C3 (P=0.001) and C4 levels (P=0.001). Complement levels in patients with cirrhosis and CHB with high transaminase levels did not significantly differ. RESULTS: Serum complement C4 levels (in contrast to virologic markers and transaminases) significantly correlate with liver biopsy findings and may be a useful indicator of disease activity and/or damage in patients with CHB with high transaminase levels.

Body weight reducing effect of oral boric acid intake.

BACKGROUND: Boric acid is widely used in biology, but its body weight reducing effect is not researched. METHODS: Twenty mice were divided into two equal groups. Control group mice drank standard tap water, but study group mice drank 0.28mg/250ml boric acid added tap water over five days. Total body weight changes, major organ histopathology, blood biochemistry, urine and feces analyses were compared. RESULTS: Study group mice lost body weight mean 28.1% but in control group no weight loss and also weight gained mean 0.09% (p<0.001). Total drinking water and urine outputs were not statistically different. Cholesterol, LDL, AST, ALT, LDH, amylase and urobilinogen levels were statistically significantly high in the study group. Other variables were not statistically different. No histopathologic differences were detected in evaluations of all resected major organs. CONCLUSION: Low dose oral boric acid intake cause serious body weight reduction. Blood and urine analyses support high glucose, lipid and middle protein catabolisms, but the mechanism is unclear.

Accuracy of EUS in the evaluation of small gastric subepithelial lesions.

BACKGROUND: EUS combined with endoluminal resection techniques is increasingly used to provide a definitive diagnosis of small gastric subepithelial lesions seen on standard upper endoscopy. OBJECTIVE: To evaluate the accuracy of EUS in diagnosing small gastric subepithelial lesions by using histology as the criterion standard. DESIGN: A retrospective study. SETTING: Academic tertiary care center. PATIENTS: A total of 22 patients (15 women, mean age 62.2 years) with an endoscopically resected gastric subepithelial lesion were included in this 3-year retrospective study. MAIN OUTCOME MEASUREMENTS: The size, echogenicity, the layer of origin, and presumptive diagnosis were determined by EUS. The diagnostic accuracy of EUS was determined by using histology as the criterion standard. RESULTS: The mean size of the 22 lesions was 13.6 mm (range 8-20 mm). An endoscopic cap band mucosectomy device was used to resect 16 (72.7%) lesions, whereas 6 (27.3%) were resected with a saline solution-assisted and snare technique. Using histology as a criterion standard, we found that the accuracy of the EUS diagnosis was 10 of 22 (45.5%). EUS alone had an accuracy rate of 30.8% and 66.7%, respectively, in the diagnosis of neoplastic and non-neoplastic lesions. LIMITATIONS: A single-center, retrospective analysis. CONCLUSION: EUS imaging had a low accuracy rate in the diagnosis of gastric subepithelial lesions, and endoscopic submucosal resection should be performed to provide a histologic diagnosis. Resection of small subepithelial lesions of 20 mm or less can be accomplished en bloc with an endoscopic cap band mucosectomy device.

Feasibility of endoscopic transesophageal thoracic sympathectomy (with video).

BACKGROUND: Thoracoscopic sympathectomy is the preferred surgical treatment for patients with disabling palmar hyperhidrosis. Current methods require a transthoracic approach to permit ablation of the thoracic sympathetic chain. OBJECTIVE: To develop a minimally invasive, transesophageal endoscopic technique for a sympathectomy in a swine model. DESIGN: Nonsurvival animal study. SETTING: Animal trial at a tertiary care academic center. SUBJECTS: This study involved 8 healthy Yorkshire swine. INTERVENTIONS: After insertion of a double-channel gastroscope, a Duette Band mucosectomy device was used to create a small esophageal mucosal defect. A short, 5-cm submucosal tunnel was created by using the tip of the endoscope and biopsy forceps. Within the submucosal space, a needle-knife was used to incise the muscular esophageal wall and permit entry into the mediastinum and chest. The sympathetic chain was identified at the desired thoracic level and was ablated or transected. The animals were killed at the completion of the procedure. MAIN OUTCOME MEASUREMENTS: Feasibility of endoscopic transesophageal thoracic sympathectomy. RESULTS: The sympathetic chain was successfully ablated in 7 of 8 swine, as confirmed by gross surgical pathology and histology. In 1 swine, muscle fibers were inadvertently transected. On average, the procedure took 61.4+/-24.5 minutes to gain access to the chest, whereas the sympathectomy was performed in less than 3 minutes in all cases. One animal was killed immediately after sympathectomy, before the completion of the observation period, because of hemodynamic instability. LIMITATIONS: Nonsurvival series, animal study. CONCLUSIONS: Endoscopic transesophageal thoracic sympathectomy is technically feasible, simple, and can be performed in a porcine model.

Gastroesophageal Reflux in Asymptomatic Patients with Diabetes: An Impedance Study Diabetes, Obesity and Gastroesophageal Reflux.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is more frequent in patients with diabetes mellitus (DM).The aim of the present study was to evaluate gastroesophageal reflux (GER) in asymptomatic patients with DM using 24-h pH impedance. MATERIALS AND METHODS: 19 healthy controls and 35 patients with DM without typical GERD symptoms were enrolled in the study. A 24-h pH-impedance study, esophageal manometry and gastroscopy were performed on all patients with DM. In the control group, an impedance study was performed on all subjects, and gastroscopy and esophageal manometry were performed on those who consented to the procedures. Patients with diabetes were categorized as obese [body mass index (BMI)>30 kg/m2] or non-obese (BMI<30 kg/m2) and both groups were compared with healthy controls. RESULTS: The mean BMI was similar in the control group (27.3±2.6 kg/m2) and the diabetic group (28.7±5 kg/m2) (p>0.05).Erosive esophagitis was found in 7.5% of the DM group. Esophageal dysmotility was higher in diabetics compared to the control group (45.5 vs. 11%, p=0.04). Neuropathy was found to be an independent risk factor for dysmotility. The mean DeMeester score (DMS) (25.6±32.5 vs. 11.2±17, p=0.01) and bolus exposure time (2.1±1.3 vs.1.3±1.3 min, p=0.009) were higher in the DM group compared with the control group.The difference was mainly observed between obese diabetics and the control group (p<0.05). The mean DMS, pathologic acid reflux, and esophageal dysmotility rate were higher in patients without complications of DM (p<0.05). BMI was higher in these patients than in patients with complications. CONCLUSION: Acid reflux is common in patients with diabetes.GER is associated with the existence of obesity rather than hyperglycemia.

Is HCV genotyping cost-effective even when the prevalences of genotypes 2 and 3 are low?

BACKGROUND/AIMS: The management of chronic hepatitis C virus (HCV) infection is costly. Genotyping determines the indication, probability of response, and duration of treatment and the dose of ribavirin. Although genotyping is accepted cost-effective, the cost of genotyping in all of the patients to find out a minority may offset the gain. The present study aimed; (1) to determine the frequency rate of HCV genotypes and (2) to compare the cost of HCV treatment tailored according to the genotype versus that planned supposing it to be genotype 1. METHODOLOGY: Six centers were included into the study. Name, age, genotype, and serotype of each patient were entered. For genotyping, HCV-RNA was extracted by acid-guanidium-phenol-chloroform method. Cost of genotyping, HCV-RNA studies and the treatment with pegylated interferon and ribavirin was estimated. The cost was determined according to two scenarios: (A) To manage patients as if all had genotypes other than 2-3. (B) To manage them after determining the geno type. The management was assumed to be made by current guidelines. RESULTS: The data of 834 patients were analyzed: Genotypel was predominant: 730 (87.5%). The rest was composed of G2:26 (3.1%), G3:26 (3.1%), G4:14 (1.7%), mixed: 13 (1.6%), undetermined: 25(3%). The cost of approach A (for 100 patients) was 1,718,200 USD; that of approach B (for 100 patients) was 1,671,900 USD. With genotype targeted therapy, every 100 patient would save 46,300 USD. CONCLUSIONS: The prevalent genotype in our country is genotypel. The sum of genotypes 2 and 3 corresponds to 6%. Genotyping HCV and tailoring the treatment thereafter are cost-effective even in the countries where prevalence of these genotypes is low.

Inflammatory bowel disease and mycobacteria: how much can we trust isoniazid prophylaxis during antitumor necrosis factor therapy?

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.

Changing epidemiology of chronic hepatitis C: patients are older and at a more advanced stage at the time of diagnosis.

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 < 0.001). Whereas 19.8% of the patients in group 1 were treatment-experienced, this rate was found to be 35.5% in group 2 (P = 0.01). Patients who presented in the first period had fewer comorbidities compared with group 2 (P < 0.001). More patients in group 2 had liver cirrhosis than group 1 (45.1 vs. 18.6%, respectively, P < 0.001). Among the patients with cirrhosis, the rate of decompensation was higher in group 2 (46.7 vs. 23.3%, P = 0.03). The presence of hepatocellular carcinoma was significantly higher in group 2 than group 1 (12.8 vs. 3.6%, respectively, P = 0.004). CONCLUSION: In recent years, CHC patients have presented to hospitals with advanced stage of liver disease; these patients are older and have more comorbidities.