Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases.

BACKGROUND: Helicobacter pylori (H. pylori) is a significant human pathogen that is responsible for a variety of illnesses, including mucosa-associated lymphoid tissue lymphoma, gastric cancer, peptic ulcers, and gastritis. AIM: To investigate the frequency of H. pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H. pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen. METHODS: H. pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H. pylori infection. The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction. The patients underwent 14 d of triple-therapy treatment. The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation. RESULTS: The intention-to-treat eradication rate was 59.2% (95%CI: 48.2%-70.3%). Rates of H. pylori resistance to clarithromycin, amoxicillin, and metronidazole were 52.8%, 81.9%, and 100%, respectively. Successful eradication of H. pylori was more significantly associated with vacA s1-positive strains [adjusted odds ratio (aOR) = 0.507, 95%CI: 0.175-0.822]. A significant association was found between failed eradication rate and H. pylori strains resistant to clarithromycin (aOR = 0.204, 95%CI: -0.005 to 0.412) and amoxicillin (aOR = 0.223, 95%CI: 0.026-0.537). CONCLUSION: This study's low H. pylori eradication rate following 14-d triple therapy is concerning and worrying. H. pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin, amoxicillin, and clarithromycin in this research is challenging and of great concern.

MET canonical transcript expression is a predictive biomarker for chemo-sensitivity to MET-inhibitors in hepatocellular carcinoma cell lines.

PURPOSE: Long interspersed nuclear element 1 (LINE-1 or L1) is a dominant non-long terminal repeat (non-LTR) retrotransposon in the human genome that has been implicated in the overexpression of MET. Both the canonical MET and L1-MET transcripts are considered to play a role in hepatocellular carcinoma (HCC) development. The aim of this study was to assess the utility of canonical MET, L1-MET, and MET protein expressions as predictive biomarkers for chemo-sensitivity to MET-inhibitors in HCC cell lines in vitro. Additionally, we assessed their expression in tumour tissues from Egyptian HCC patients. METHODS: MET and L1-MET expressions were assessed by qRT-PCR in six liver cancer cell lines (SNU-387, SNU-475, SK-HEP-1, PLC/PRF/5, SNU-449 and SNU-423) and 47 HCC tumour tissues. MET protein expression was measured by western blot in cell lines and immunohistochemistry in the tumours. Cell proliferation assay was used to assess the effect of crizotinib and tivantinib on the six liver cancer cell lines in correlation with the expression of MET, L1-MET and MET. RESULTS: The antitumor effect of crizotinib and tivantinib correlated with MET gene expression but not with L1-MET transcript or MET protein expressions. No significant difference was observed between HCC tumours and non-tumour samples in MET and L1-MET transcripts expression. There were no significant correlations between the 2-year overall survival rate and the MET, L1-MET transcripts and the MET protein expression. CONCLUSION: MET RNA expression could be useful biomarker for tivantinib and crizotinib targeted therapy in HCC. The value of assessment of MET protein expression is limited.

Predictors of Outcome of Living Donor Liver Transplantation for Hepatocellular Carcinoma.

The aim of this work is to study the different factors that affect the outcome of living donor liver transplantation for patients with hepatocellular carcinoma (HCC). Between April 2003 to November 2014, 62 patients with liver cirrhosis and HCC underwent living donor liver transplantation (LDLT) in the National Liver Institute, Menoufia University, Egypt. The preoperative, operative, and postoperative data were analyzed. After studying the pathology of explanted liver; 44 (71 %) patients were within the Milan criteria, and 18 (29 %) patients were beyond Milan; 13 (21.7 %) of patients beyond the Milan criteria were also beyond the University of California San Francisco criteria (UCSF) criteria. Preoperative ablative therapy for HCC was done in 22 patients (35.5 %), four patients had complete ablation with no residual tumor tissues. Microvascular invasion was present in ten patients (16 %) in histopathological study. Seven (11.3 %) patients had recurrent HCC post transplantation. The 1, 3, 5 years total survival was 88.7, 77.9, 67.2 %, respectively, while the tumor-free survival was 87.3, 82.5, 77.6 %, respectively. Expansion of selection criteria beyond Milan and UCSF had no increased risk effect on recurrence of HCC but had less survival rate than patients within the Milan criteria. Microvascular invasion was an independent risk factor for tumor recurrence.

The Differential Immunohistochemical Expression of p53, c-Jun, c-Myc, and p21 Between HCV-related Hepatocellular Carcinoma With and Without Cirrhosis.

Hepatocellular carcinoma (HCC) constitutes 70.48% of all liver tumors among Egyptians with multifactorial etiology and complex pathogenesis. HCV infection is the most common risk factor of HCC in Egypt, which commonly develops on top of cirrhosis (HCC-C); however, 15% to 20% of HCC are reported to arise in noncirrhotic livers (HCC-NC). This study aimed to explore the differences in the immunohistochemical expression of p53, c-Jun, c-Myc, and p21 between HCC-C and HCC-NC to verify the underlying molecular pathways and to study their role in hepatocarcinogenesis. This study investigated 103 cases of HCC (86 cases of HCC-C and 17 cases HCC-NC including tumorous and nontumorous tissues) together with 10 cases of chronic hepatitis and 10 cases of pure cirrhosis as control groups. Zero, 100%, 100%, and 50% of chronic hepatitis cases were positive for p53, c-Jun, c-Myc, and p21, respectively. All cirrhotic cases were negative for p53 and c-Jun, whereas they were all positive for c-Myc and p21. A total of 41%, 11.65%, 86.4%, and 57.3% of HCC cases showed p53, c-Jun, c-Myc, and p21 expression, respectively. The only difference between HCC-C and HCC-NC was the H-score values of p21 expression, which were higher in HCC-C compared with HCC-NC (P=0.03). HCV-related HCC commonly develops on top of cirrhosis with a minority develops on top of noncirrhotic liver. Only p21 pathway appears to be upregulated in favor of HCC-C than HCC-NC. p53 is considered as a late-event molecular carcinogen, whereas p21 and c-Myc may serve as early-event molecular carcinogen in HCC. The oncogenic role of p21 may be related to its cytoplasmic localization and its promotion of c-Myc expression. Progressive increase in the intensity of c-Myc expression from chronic hepatitis to cirrhosis to HCC may refer to its role as a multistep regulator of hepatocarcinogenesis. The marked reduction of c-Jun in HCC may refer to its tumor suppressor activity.