Role of MRI in rectal carcinoma after chemo irradiation therapy with pathological correlation

AbstractRectal cancer is associated with a high risk of metastases and local recurrence; local recurrence rates after surgical treatment being up to 32% (1). Local recurrence is directly related to incomplete tumor resection (2, 3) and also related to the circumferential safety of resection (4, 5). An accurate local staging at the time of initial diagnosis is therefore very important.AimThe aim of this study is to use MRI in comparing the morphologic features of rectal cancer before and after 6weeks of chemo irradiation treatment and to correlate the post treatment MRI appearances with the histological findings in resected tumors.Material and methods68 patients with histopathologically proven rectal adenocarcinoma received standardized 5-week chemo radiation therapy and subjected to MRI before and after treatment for clinical staging. A correlation between pathological response and MRI findings was done.ResultSixty-eight patients with adenocarcinoma rectal cancer were included in the study. Preoperative MRI examination was performed. All patients subsequently underwent operation. The mean time lag between the MRI study and operation was 16.8days.After preoperative chemo-radiotherapy, MRI findings showed that, there is a significant shift toward downstaging. 16/59 (23.5%) patients achieved down-staging from clinical stage III (before therapy) to stage II after therapy (P=0.001) by achieving both tumor (T) downsizing and lymph node downstaging. MR images obtained after radiation therapy with concomitant chemotherapy have (100%) sensitivity, (78.7%) specificity, (100%) NPV in the differentiation of T1–2/T3–4 tumors with MRI, accuracy 80.9% with agreement 70.58% and 100% accuracy for node staging.ConclusionHigh resolution pre treatment MRI of the rectum has a high predictive value of treatment outcome either for neoadjuvant treatment or surgery

The impact of probiotics on gut microbiota and non-alcoholic fatty liver disease (NAFLD) progression based on controlled attenuated parameter (CAP) elastography: Randomized controlled trial

Background: The gut–liver axis has many implications in non-alcoholic fatty liver disease onset as the major contributor of intestinal dysbiosis. Gut microbiota have an important role in intestinal barrier function and reversal of leaky gut. Probiotics may restore intestinal barrier integrity and contribute to hepatic functions recovery and alleviating inflammatory and fibrogenic processes. We aimed to evaluate the impact of probiotics on gut microbiota and non-alcoholic fatty liver disease progression. Results: Sixty non-alcoholic fatty liver disease patients (30 non-alcoholic fatty liver and 30 non-alcoholic steatohepatitis patients) were included in this open label randomized controlled study. Half of the patients of each group were randomized to receive probiotics in addition to classic management. The patients were followed-up for 6 months. The non-alcoholic fatty liver disease patients in the probiotic group experienced significant improvement in their Alanine aminotransferase, triglycerides, liver steatosis, and fibrosis stages, fecal pathological bacterial growth and Lactobacillus acidophilus abundance (P= 0.05, 0.029, 0.012, 0.013, 0.034, <0.001 and 0.005 respectively). Waist circumference and low density lipoprotein improvements were more pronounced in non-alcoholic fatty liver patients. Conclusion: Adding probiotic therapy to classical management of non-alcoholic fatty liver disease may help in improving intestinal dysbiosis, liver steatosis and fibrosis

Nutritional intervention could improve long term outcome post LDLT in limited resources university hospital in Egypt

Introduction: liver transplantation (LT) is considered as salvage therapy for those with irreversible liver failure. Malnutrition is prevalent in transplanted patient’s pre and post transplantation. Objective: to analyze the nutritional status of patients post living donor liver transplantation (LDLT) by using different nutritional assessment tools with nutritional modification in order to improve the outcomes post liver transplantation. Materials and methods: Our prospective cohort study was conducted on 30 who underwent liver transplantation before the study, they were nutritionally assessed through different nutritional scores and anthropometric parameters with application of nutritional modification. Results: ALT and AST decreased significantly and normalized at 6 months with p-value .025, .036; respectively. HbA1c, fasting blood sugar and post prandial blood sugar levels decreased after 6 months. There was statistically significant improvement in lipid profile after 3 and 6 months with nutritional modification. There was significant improvement (p= 0.017) in metabolic syndrome. There is correlation between numbers of years from transplantation and appearance of metabolic syndrome Regarding dyslipidemia, there was significant improvement after 6 months (p< 0.001).CAP study showed improvement (p= 0.014)

LC–MS Profiling of N‑Glycans Derived from Human Serum Samples for Biomarker Discovery in Hepatocellular Carcinoma

Defining clinically relevant biomarkers for early stage hepatocellular carcinoma (HCC) in a high-risk population of cirrhotic patients has potentially far-reaching implications for disease management and patient health. Changes in glycan levels have been associated with the onset of numerous diseases including cancer. In the present study, we used liquid chromatography coupled with electrospray ionization mass spectrometry (LC–ESI-MS) to analyze N-glycans in sera from 183 participants recruited in Egypt and the U.S. and identified candidate biomarkers that distinguish HCC cases from cirrhotic controls. N-Glycans were released from serum proteins and permethylated prior to the LC–ESI-MS analysis. Through two complementary LC–ESI-MS quantitation approaches, global profiling and targeted quantitation, we identified 11 N-glycans with statistically significant differences between HCC cases and cirrhotic controls. These glycans can further be categorized into four structurally related clusters, matching closely with the implications of important glycosyltransferases in cancer progression and metastasis. The results of this study illustrate the power of the integrative approach combining complementary LC–ESI-MS based quantitation approaches to investigate changes in N-glycan levels between HCC cases and patients with liver cirrhosis

LC–MS Based Serum Metabolomics for Identification of Hepatocellular Carcinoma Biomarkers in Egyptian Cohort

Although hepatocellular carcinoma (HCC) has been subjected to continuous investigation and its symptoms are well-known, early stage diagnosis of this disease remains difficult and the survival rate after diagnosis is typically very low (3–5%). Early and accurate detection of metabolic changes in the sera of patients with liver cirrhosis can help improve the prognosis of HCC and lead to a better understanding of its mechanism at the molecular level, thus providing patients with in-time treatment of the disease. In this study, we compared metabolite levels in sera of 40 HCC patients and 49 cirrhosis patients from Egypt by using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from cirrhotic controls are selected by statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. The identities of some of the putative identifications are verified by comparing their MS/MS fragmentation patterns and retention times with those from authentic compounds. Finally, the serum samples are reanalyzed for quantitation of selected metabolites as candidate biomarkers of HCC. This quantitation was performed using isotope dilution by selected reaction monitoring (SRM) on a triple quadrupole linear ion trap (QqQLIT) coupled to UPLC. Statistical analysis of the UPLC-QTOF data identified <b>274</b> monoisotopic ion masses with statistically significant differences in ion intensities between HCC cases and cirrhotic controls. Putative identifications were obtained for <b>158</b> ions by mass based search against databases. We verified the identities of selected putative identifications including glycholic acid (GCA), glycodeoxycholic acid (GDCA), 3β, 6β-dihydroxy-5β-cholan-24-oic acid, oleoyl carnitine, and Phe-Phe. SRM-based quantitation confirmed significant differences between HCC and cirrhotic controls in metabolite levels of bile acid metabolites, long chain carnitines and small peptide. Our study provides useful insight into appropriate experimental design and computational methods for serum biomarker discovery using LC–MS/MS based metabolomics. This study has led to the identification of candidate biomarkers with significant changes in metabolite levels between HCC cases and cirrhotic controls. This is the first MS-based metabolic biomarker discovery study on Egyptian subjects that led to the identification of candidate metabolites that discriminate early stage HCC from patients with liver cirrhosis