Ehud Melzer

Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease : Echocardiographic and tissue doppler imaging assessment

Nonalcoholic fatty liver disease (NAFLD) is linked to the metabolic syndrome. The aim of the present study is to determine the effect of the metabolic syndrome on left ventricular (LV) geometry and function using as a model patients with NAFLD. Thirty-eight patients with NAFLD, less than 55 years of age and with a normal exercise test, were compared with an age and sex-matched control group. Patients with diabetes mellitus, hypertension, and body mass index>40 were excluded. A complete echocardiographic study including tissue Doppler imaging (TDI) was performed. The following parameters were assessed by echo Doppler: peak velocities of early (E) and late (A) diastolic filling, E/A ratio, flow propagation velocity (Vp). Using TDI early diastolic velocity (E′), and systolic velocity (S′) of mitral annulus were obtained. The patients with NAFLD had a significantly higher body mass index (31.4±5 vs. 26.4±4 kg/m2, P=0.01), higher glucose (100.6±13 vs. 83.0±10 mg/dL, P=0.01), and triglyceride levels (126.5±44 vs. 206.5±67 mg/dL, P<0.001). Increased thickness of the intraventricular septum, posterior wall (11.03±2.2 vs. 8.9±2.9 mm, P=0.001; 8.5±1.7 vs. 9.7±2.3 mm, P=0.04), and larger LV mass and LV mass/height (160.7±58.7 vs.115.3±35.4 g, P=0.001 and 92.6±29.5 vs. 69.2±19.8 g/m, P=0.001, respectively) were found in NAFLD group. LV systolic function was similar in both groups. Patients with NAFLD had a lower E (73.6±11.0 vs. 86.4±20.0 cm/s, P<0.006) and E/A ratio (1.0±0.3 vs. 1.76±0.8 P<0.0001). Moreover, the Vp and the E′ on TDI were significantly lower compared with the control group (49.0±9.7 vs. 74.7±18.4 cm/s, P<0.0001 and 10.3±2.0 vs. 13.8±1.7 cm/s, P<0.0001, respectively). On multivariate analysis the E′ on TDI was the only independent parameter associated with NAFLD. In conclusion, patients with NAFLD in the absence of morbid obesity, hypertension, and diabetes have mildly altered LV geometry and early features of left ventricular diastolic dysfunction. Early diastolic velocity on TDI was found to be the only index that could identify the patients with NAFLD and metabolic syndrome.

Mesalamine Did Not Prevent Recurrent Diverticulitis in Phase 3 Controlled Trials

BACKGROUND & AIMS No therapy has been proven to prevent the recurrence of diverticulitis. Mesalamine has shown efficacy in preventing relapse in inflammatory bowel disease, and there is preliminary evidence that it might be effective for diverticular disease. We investigated the efficacy of mesalamine in preventing recurrence of diverticulitis in 2 identical but separate phase 3, randomized, double-blind, placebo-controlled, multicenter trials (identical confirmatory trials were conducted for regulatory reasons). METHODS We evaluated the efficacy and safety of multimatrix mesalamine vs placebo in the prevention of recurrent diverticulitis in 590 (PREVENT1) and 592 (PREVENT2) adult patients with ≥1 episodes of acute diverticulitis in the previous 24 months that resolved without surgery. Patients received mesalamine (1.2 g, 2.4 g, or 4.8 g) or placebo once daily for 104 weeks. The primary end point was the proportion of recurrence-free patients at week 104. Diverticulitis recurrence was defined as surgical intervention at any time for diverticular disease or presence of computed tomography scan results demonstrating bowel wall thickening (>5 mm) and/or fat stranding consistent with diverticulitis. For a portion of the study, recurrence also required the presence of abdominal pain and an increase in white blood cells. RESULTS Mesalamine did not reduce the rate of diverticulitis recurrence at week 104. Among patients in PREVENT1, 53%-63% did not have disease recurrence, compared with 65% of those given placebo. Among patients in PREVENT2, 59%-69% of patients did not have disease recurrence, compared with 68% of those given placebo. Mesalamine did not reduce time to recurrence, and the proportions of patients requiring surgery were comparable among treatment groups. No new adverse events were identified with mesalamine administration. CONCLUSIONS Mesalamine was not superior to placebo in preventing recurrent diverticulitis. Mesalamine is not recommended for this indication. ClinicalTrials.gov ID: NCT00545740 and NCT00545103.

Autoimmune hepatitis in southern Israel: A 15-year multicenter study

In this study we aimed to assess the incidence, prevalence and clinical outcomes of patients with autoimmune hepatitis (AIH) in southern Israel.

Detection of Pancreatic Carcinoma (Diagnostic Value of K-ras Mutations in Circulating DNA from Serum)

Somatic activating mutations at codon 12 of theK-ras gene are present in the majority of exocrinepancreatic cancers and occur early in tumorgenesis. Theaim of this study was to test the feasibility of using a mutated K-ras gene from the serum as apotential tumor marker for detection of exocrinepancreatic carcinoma. Codon 12 K-ras mutations wereexamined in DNA extracted from the sera of 20 patients with pancreatic carcinomas, six patients withchronic pancreatitis, and five healthy individuals.K-ras gene mutations at codon 12 were detected in thesera of 14 of 20 patients with pancreatic carcinoma and in none of the six patients with chronicpancreatitis, or in the five healthy controls. Elevationof either CA19-9 or K-ras mutation was detected in 19/20patients. These results suggest that K-ras abnormalities in serum could be used as apotential tumor marker in patients with a pancreaticlesion. The absence of K-ras mutations in serum andpresence of CA19-9 in the normal range make thediagnosis of pancreatic cancer unlikely.

The Involvement of the Liver in Systemic Diseases

The liver has a double blood supply and plays a central role in the metabolism of proteins, carbohydrates, and many medications. In addition, it has a role in the induction of immune tolerance and may also be a target for immune-mediated damage. For these reasons, the liver may be involved in many systemic diseases. In this review, we discuss the involvement of the liver in granulomatous, rheumatologic, malignant, and circulatory diseases. An understanding of the wide spectrum of liver involvement in systemic diseases will aid in both diagnosis and treatment of patients with a wide range of medical conditions.

Perforations following endoscopic retrograde cholangiopancreatography: a single institution experience and surgical recommendations.

BACKGROUND Perforation after endoscopic retrograde cholangiopancreatography (ERCP) is uncommon, and its management is dependent on the mechanism and the graded classification of injury. METHODS Records of patients undergoing ERCP were analyzed over a 16-year period, patterning the types of injuries, diagnosis, management, and patient outcome. Type I injuries damage the medial or lateral duodenal wall before sphincter cannulation. Type II injuries are periampullary and occur as a result of a precut or a papillotomy. Type III injuries occur secondary to guidewire insertion or stone extraction from the common bile duct. Type IV injuries are probably microperforations that are noted on excessive insufflation during and after ERCP withdrawal. RESULTS Between 1995 and 2011, 27 perforations were identified from 1,638 ERCP procedures (1.6%). Nearly half of the procedures were regarded as difficult by the endoscopist, with 70% of the ERCPs (19 of 27) being for therapeutic indications. There were 5 type I, 12 type II, 5 type III, and 5 type IV perforations, of which 18 cases were diagnosed at the time of ERCP. Delayed diagnosis of type I perforations that were associated with free intraperitoneal air and contrast leakage proved fatal. Most type II perforations required immediate surgery with pyloric exclusion; delayed surgery with simple drainage had a high mortality rate. Most type III and type IV injuries can successfully be managed conservatively without delayed sepsis. CONCLUSIONS In perforation, the mechanism of injury during ERCP predicts the need for surgical management. Type I and type II injuries require early diagnosis and aggressive surgery, whereas type III and type IV injuries may be managed conservatively.

The endoscopic ultrasonographic appearance of Brunner's gland hamartoma

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Alcoholic liver disease: Clinical and translational research

The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical research, translational research, pathogenesis and therapies. A special accent is placed on alcohol misuse, as alcohol is a legally commercialized and taxable product. Drinking alcohol, particularly from a young age, is a major health problem. Alcoholism is known to contribute to morbidity and mortality. A systematic literature search was performed in order to obtain updated data (2008-2015). The review is focused on genetic polymorphisms of alcohol metabolizing enzymes and the role of cytochrome p450 2E1 and iron in ALD. Alcohol-mediated hepatocarcinogenesis is also discussed in the presence or absence of co-morbidities such as viral hepatitis C as well as therapeutic the role of innate immunity in ALD-HCV. Moreover, emphasis was placed on alcohol and drug interactions, as well as liver transplantation for end-stage ALD. Finally, the time came to eradicate alcohol-induced liver and intestinal damage by using betaine.

Helicobacter pylori infection is associated with advanced colorectal neoplasia.

Abstract Objective. The aim of this article was to evaluate the prevalence of Helicobacter pylori infection in patients diagnosed with advanced colorectal neoplasia undergoing a colonoscopy compared to patients without neoplasia. Material and methods. This cross-sectional study investigated the association of neoplastic lesions diagnosed on colonoscopy with H. pylori infection in a consecutive series of subjects who had undergone a pancolonoscopy in a single academic medical center. All patients were tested by ELISA and the immunoblot technique for serum anti-H. pylori and CagA protein IgG antibodies. Multivariate analyses were adjusted for potential-relevant confounders, including age, sex, smoking, childhood socioeconomic status, and family history of colorectal cancer. Results. Two hundred and seventy-three patients were included in the study: 75% (84/112), diagnosed with neoplastic colorectal lesions and 48% (77/161) without neoplastic lesions, were found to be seropositive for H. pylori infection (p < 0.001). H. pylori infection was found in 66/77 (86 %) patients with advanced neoplasia, 18/35 (51%) patients with nonadvanced neoplasia, and 48% (77/161) patients without neoplasia (p < 0.001). In the adjusted analysis, H. pylori infection was found to be associated with advanced colorectal neoplasia (odds ratio, OR 9.57; 95% CI 4.31–21.2; p < 0.001) and CRC (OR 7.98;95% CI 3.16–20.16; p < 0.001). There was no association in patients who were CagA positive. Conclusion. H. pylori infection is associated with the development of advanced colorectal neoplasia. More studies are needed to confirm our findings.

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial

Therapy for Crohns disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed‐dose, delayed‐release 6‐mercaptopurine (DR‐6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR‐6MP in patients with moderately severe CD compared to systemically delivered 6‐mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12‐week, double‐blind controlled trial. The primary end‐point was the percentage of subjects with clinical remission [Crohns Disease Activity Index (CDAI) < 150] or clinical response (100‐point CDAI reduction). Twenty‐six (56·5%) and 13 (54·2%) subjects from the DR‐6MP and Purinethol cohorts, respectively, completed the study. DR‐6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR‐6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR‐6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR‐6MP group. DR‐6MP led to a decrease of CD62+ expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR‐6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug‐induced leucopenia in the DR‐6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR‐6MP. Non‐absorbable DR‐6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects.