Gut Microbiome and Gastrointestinal Cancer: Les liaisons Dangereuses.

Gastrointestinal (GI) cancers are the leading cause of mortality worldwide. These cancers are the end result of a complex interplay between gene and environment. Bacteria, parasites, and viruses have been implicated in some cancers. Recent data have put at focus the gut microbiome as the key player firing tumorigenesis. Experimental and human studies have provided evidence on the role of microbiota in cancer development. Although subject to changes in different settings such as antibiotic treatment, diet or lifestyle, our microbiome is quite stable and is capable of increasing susceptibility to cancer or decrease and halt its progression. The crucial event in carcinogenesis triggered by microbiome seems to be chronic inflammation influencing the genomic stability of host cells and activating immune mechanisms. Infection-related cancers represent 5.5% of the global cancer burden. Chronic inflammation predisposes to cancer in various GI organs, including hepatocellular carcinoma caused by hepatitis B or hepatitis C virus-related chronic hepatitis, gastric cancer (GC) caused by Helicobacter pylori-associated chronic gastritis, colorectal cancer caused by inflammatory bowel disease, bile duct cancer by primary sclerosing cholangitis, and esophageal cancer caused by Barrett esophagus. Apart from its impact in GI cancer development microbiota can also play an important role in the progression of cancer, response to chemotherapy or cancer prevention. In this review we will discuss the role of microbiome in GI cancers in the light of the current literature and the possible therapeutic options targeting microbiota in the near future.

Regular coffee intake improves liver enzyme levels and liver histology in patients with chronic alcohol consumption, non-alcoholic fatty liver and non-alcoholic steatohepatitis: Report of 259 cases.

Background and Aim: This study aims to investigate the effects of chronic coffee consumption (>5 years) and type of coffee in non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFLD) and patients who have regular alcohol consumption. Materials and Methods: In this study, 158 healthy individuals and 101 patients with histologically proven NASH were enrolled. The daily amount of coffee intake, amount of alcohol use and type of coffee were calculated for all patients. The degree of steatosis and fibrosis was analyzed by transient elastography and liver ultrasound in non-NASH and by liver biopsy in NASH patients. Results: Patients with a history of coffee consumption (n=132) had lower liver enzyme levels compared to the non-coffee group (n=127) (p=0.001). Serum ALT level was significantly lower [ALT: 21.2±11.7 U/L vs. 56.4±15.6 U/L (p=0.004)], and the liver histopathology was significantly better for patients with a coffee consumption of daily for >5years (p=0.045 for fibrosis score for NASH, p=0.036 for LSM and p=0.015 for CAP measurements for the non-NASH patient). Conclusion: Coffee seems to have a positive protective effect on liver histology and liver enzyme levels in healthy individuals, in patients with chronic alcohol consumption, NAFLD and NASH. These results are more prominent in patients who drink coffee on a regular daily base for more than five years.

Soluble P selectin levels in chronic liver disease: relationship to disease severity.

BACKGROUND/AIMS: Thrombocytopenia and platelet function abnormalities are problems commonly found in patients with chronic liver disease (CLD). Despite lack of widespread recognition as to the clinical significance of Soluble P-selectin (sP-selectin), in that increased levels of sP-selectin have been described in patients with CLD, it has been proposed as a marker of in-vivo platelet activation. The study's aim was to determine whether levels of sP-selectin in patients with CLD increase in accordance with the degree of liver failure, the likelihood of CLD patients with high sP-selectin levels being more prone to thrombosis, as well as investigating the coagulation and fibrinolytic parameters related to the sP-selectin. METHODOLOGY: This study was comprised of two groups: 40 patients with cirrhosis and portal hypertension (28 males and 12 females); and a control group of 10 healthy volunteers (6 males and 4 females). In both groups, biochemical parameters, sP-selectin, coagulation and fibrinolytic activity levels were measured and a Doppler ultrasound was performed. RESULTS: Plasma sP-selectin levels were found to be higher in the patients compared to those of the control group (p < 0.01), while at the same time significant differences were observed with respect to the stage of disease. Patients with low platelet counts were found to have higher sP-selectin levels than those with normal platelet counts (p < 0.01). Seven patients (17.5%) were seen to have portal vein thrombosis upon doppler ultrasound examination, while sP-selectin levels were significantly lower in those patients with thrombosis than those without (p < 0.05). It was our finding that sP-selectin levels inversely correlated with anti thrombin III. CONCLUSIONS: In conclusion, sP-selectin levels related to the degree of liver disease and thrombosis are seen together with low platelet and sP-selectin levels in patients with cirrhosis.

Ki67 as a prognostic factor for long-term outcome following surgery in gastrointestinal stromal tumors.

OBJECTIVE: This study aimed to examine the value of Ki67 expression along with other potential prognostic factors for predicting overall survival and disease-free survival in patients with gastrointestinal stromal tumors who underwent curative resection. PATIENTS AND METHODS: Sixty-eight histologically confirmed and operated patients with gastrointestinal stromal tumors were included. Clinical and follow-up data were retrieved from medical records and patients were contacted at the end of the study. The effects of certain clinical and histopathological parameters on survival outcomes were examined. RESULTS: Sixty-eight patients were followed for a mean duration of follow-up of 2923.3 patient-months. Twelve deaths (17.6%), seven metastasis (10.3%), and two local recurrences (2.9%) occurred. Overall survival was 102.5 months [95% confidence interval (CI), 88.3-116.8] and disease-free survival was 91.8 months (95% CI, 76.5-107.2). Multivariate analyses identified a high Ki67 index (≥ 10%) as an independent predictor of both poor overall survival (hazard ratio, 4.8; 95% CI 1.2-19.2; P=0.027) and poor disease-free survival (hazard ratio, 15.3; 95% CI, 4.7-50.2). CONCLUSION: A high Ki67 expression seems to be a useful prognostic factor that would aid in predicting disease course in gastrointestinal stromal tumors. These findings deserve further investigation in larger studies.

Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1), IL-17 (Th17), and FOXP3 (Treg) expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

Dual infection in chronic hepatitis C patients.

UNLABELLED: Hepatitis C and B virus(HCV, HBV) dual infection may occur and even persist in the same patient. Different results have been found in clinical and laboratory studies of dually infected patients. AIM: In our study, we aimed to investigate the effect of previous or present hepatitis B virus infection to clinical course and antiviral therapy in patients with chronic hepatitis C. METHOD: Hundredthirty consecutive patients with hepatitis C, who were referred to our gastroenterology unit, were studied retrospectively. Patients who were exposed to HBV infection were named as group 1, and patients who had pure hepatitis C infection were named as group 2. Fifty patients in group 1 were compared with 80 patients in group 2. HBs Ag was positive in 12, and HBV antibodies were positive in the other 38 patients of group 1. RESULTS: Age, sex, follow-up duration, transaminase levels, liver synthesis functions, histopathological findings, Child-Pugh stages and presence of complications were not statistically different in groups 1 and 2. HBV-DNA by PCR assay was negative in all 12 HBs Ag positive patients. Hepatocelluler carcinoma(HCC) was found totally in 8 cases, 2 in group 1 and 6 in group 2, while none in HBs Ag positive patients. Antiviral therapy was administired to 39 patients, 15 in group 1 and 24 in group 2. There was no difference in regard to treatment duration and response to treatment between both groups. CONCLUSION: In our study, we have found previous or present HBV infections were observed frequently in chronic hepatitis C patients, although it's effect to clinical course and antiviral therapy is not significant.

Effects of intrarectal and intraperitoneal N(G)-nitro-L-arginine methyl ester treatment in 2,4,6-trinitrobenzenesulfonic acid induced colitis in rats.

Inflammatory bowel disease (IBD) has been associated with an increased generation of nitric oxide (NO). Different authors have shown that NO in IBD can be either harmful or protective. The aim of this study was to investigate the efficiency of intrarectal (i.r.) and intraperitoneal (i.p.) application of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor, in experimental acute colitis in the rats. Acute colitis was induced in rats by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. Twenty-eight rats were divided into four groups. L-NAME (50 mg/kg/day) was administered i.p. (Group 1) and i.r. (Group 2) for 7 days following the day when colitis was induced. Group 3 rats were not given any treatment after induction of colitis. Control group rats were given saline solution i.r. instead of TNBS. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic damage. The severity of colitis was assessed by microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, inflammatory cell infiltration, and vascular dilatation. Rectal tissue myeloperoxidase (MPO) activity and serum-rectal tissue nitrite levels were measured. Serum and rectal tissue nitrite levels increased in Group 3 rats. Both i.p. and i.r. L-NAME treatment significantly reduced serum and rectal tissue nitrite levels, but no effect on MPO activity and histologic damage score was observed. Under the present conditions we concluded i.r. and i.p. L-NAME treatment, applied at the dosage of 50 mg/kg/day, does not have any protective effect on the colonic injury.

Type 1 gastric carcinoid tumor: another extrahepatic manifestation of hepatitis C virus infection?

A 67 year-old female with a 10-year history of cirrhosis due to hepatitis C virus who developed a gastric carcinoid tumor of the corpus is described. Carcinoid tumor was identified during her last routine gastroscopic evaluation for portal hypertension. In the case, serum parietal cell antibodies, hypergastrinemia and atrophic gastritis were also found. Chronic hepatitis C virus infection is known to induce clinical and laboratory signs of autoimmunity. But the question of whether hepatitis C virus plays a pathogenic role in the development of gastric carcinoid tumor is unknown. As far as we know, this is the first report describing gastric carcinoid tumor in hepatitis C virus induced chronic liver disease. We suggest that the possibility of the development of autoimmune atrophic gastritis and carcinoid tumors should be considered in patients with chronic hepatitis C that coexists with autoimmune diseases and has positive parietal cell antibodies.

Groove (paraduodenal) pancreatitis: Report of two cases.

"Groove" pancreatitis is a rare segmental form of chronic pancreatitis that involves the area located between the common bile duct, head of the pancreas and duodenum. It is more common in middle-aged males who have a history of alcohol abuse. The differential diagnosis varies from anatomic variants to malignancies. The most relevant differential diagnosis of groove pancreatitis is adenocarcinoma of the head of the pancreas. Most of the cases were diagnosed after pancreatic resection. Thus, the correct diagnosis of this rarely seen disease is very important to avoid unnecessary tests or procedures and to determine the definitive treatment.

Intrahepatic cholestasis of pregnancy: correlation of preterm delivery with bile acids.

BACKGROUND/AIMS: The aim of this study was to determine the incidence, obstetrical and fetal complication rates of intrahepatic cholestasis of pregnancy in patients managed actively around 38 weeks and evaluate the correlation of these results with liver function tests and bile acids. MATERIAL AND METHODS: In this cohort study 3710 women were booked for delivery, of which 32 pregnant women were diagnosed as intrahepatic cholestasis of pregnancy. All data concerning obstetric- medical history, laboratory results, symptom onset time, pruritus degree, treatment response, and delivery time and infants information were recorded in the study protocol. Statistical analyses were conducted with SPSS 12.0 version and correlations were assessed by Spearman Rank correlation analysis. RESULTS: The incidence of intrahepatic cholestasis of pregnancy was 0.86%. The symptoms appeared around 32 weeks. 16.6% multiparas had a previously affected pregnancy and 21.8% of intrahepatic cholestasis of pregnancy patients had family history of intrahepatic cholestasis of pregnancy. Symptom onset varied according to season (p<0.05). Most patients (69.5%) were diagnosed in winter and the beginning of spring. There were no reported cases of clinical maternal jaundice, bleeding tendency or stillbirth. Pruritus was decreased by ursodeoxycholic acid treatment. Total bile acids tended to be higher in patients with preterm delivery (r=0.409, p=0.038). CONCLUSION: Total bile acids are correlated with preterm delivery. An attempt to deliver at around 38 weeks may improve perinatal outcome.

Actinomycotic hepatic abscess.

Actinomycotic hepatic abscess was diagnosed in a 46-year-old male driver from Ukraine presenting with the symptoms of malaise, loss of appetite, upper right quadrant pain, weight loss, and night sweats which had been present for last 2 months. Computed tomography (CT) of the abdomen revealed a hypodense mass in the left liver lobe which was suspected as hepatocellular carcinoma. Histopathological examination of the CT guided biopsy specimen yielded a diagnosis of actinomycotic abscess of the liver. Treatment with intravenous penicillin for 6 weeks followed by a course of oral penicillin for 14 weeks resulted in complete cure as evidenced by clinical improvement and radiological disappearance of the lesion.

Toxoplasmic hepatitis in an immunocompetent patient.

Acquired toxoplasmosis is more frequently an unrecognized disease. Immunocompetent adults and adolescents with primary infection are generally asymptomatic, or symptoms observed may include malaise, fever, and lymphadenopathy. In contrast, immunocompromised patients may experience severe manifestation including encephalitis and multi system organ failure. We report a case of toxoplasmic hepatitis presenting with hepatomegaly in an immunocompetent patient.

CT findings and serum ca 125 levels in malignant peritoneal mesothelioma: report of 11 new cases and review of the literature.

The aim of this study was to review and reappraise the clinical and CT features of malignant peritoneal mesothelioma (MPM), and to discuss differential diagnosis. The history, clinical, and laboratory data, and imaging studies of 11 patients with a histologically proven diagnosis of MPM, were retrospectively reviewed. Our patients consisted of 7 women and 4 men, with a median age of 48 years (age range 40-55 years). There was a definite history of significant asbestos exposure in 6 patients. Abdominal swelling (9 of 11) was the most common presenting symptom. The mean serum CA-125 (normal value 1.2-32 U/ml) level was 230 U/ml (range 19-1000 U/ml). The most common radiological findings were extensive or moderate amounts ascites (11 of 11), irregular or nodular peritoneal thickening (11 of 11), omental involvement (10 of 11), mesentery involvement (9 of 11), pleural thickening, plaques or calcification (7 of 11), pleural effusion (6 of 11), and bowel wall thickening (5 of 11). Two patients had large upper abdominal masses. Computed tomography findings of MPM are nonspecific and inadequate to pinpoint specific diagnosis. The diagnosis requires histological demonstration which is commonly made by an image or laparoscopic-guided biopsy. Pleural changes suggesting asbestosis combined with CT findings and high CA-125 levels can suggest, but are not diagnostic of, mesothelioma. Suggesting the diagnosis of MPM is important because histological and immunohistochemical tests are needed for diagnostic accuracy.

Acute liver failure due to Hodgkin's lymphoma.

OBJECTIVE: To describe an unusual case of acute liver failure due to Hodgkin's lymphoma. CASE PRESENTATION AND INTERVENTION: A 37-year-old man was admitted with jaundice and abdominal distension. Physical examination showed tender hepatosplenomegaly, ascites, grade I encephalopathy, left cervical (2 x 1 cm) and axillary (1 x 1 cm) lymph nodes. The laboratory data revealed elevated serum bilirubin, transaminases, lactate dehydrogenase, and coagulation defects. Initially, primary liver disease was considered, but a liver biopsy revealed infiltration of the liver by Hodgkin's lymphoma that was confirmed by lymph node biopsy. Hodgkin's lymphoma was of lymphocyte depletion type. CONCLUSION: This case demonstrates that in the presence of lymphadenopathy involving acute liver failure, hematological malignancies should be taken into consideration. Liver and lymph node biopsies should be performed as early as possible.

Successful ivermectin treatment of hepatic strongyloidiasis presenting with severe eosinophilia.

A 49-year-old, previously healthy nurse presented with hepatic lesions and severe peripheral eosinophilia due to strongyloidiasis. Imaging studies of the abdomen showed predominantly peripheral, confluent hepatic lesions. The hepatic lesions and eosinophilia did not show any improvement with albendazole, but completely resolved with ivermectin treatment. Our findings suggest that Strongyloides stercoralis can present with isolated focal hepatic lesions and severe eosinophilia, and resolves with ivermectin treatment.