A hierarchical Bayesian approach for detecting global microbiome associations.

The human gut microbiome has been shown to be associated with a variety of human diseases, including cancer, metabolic conditions and inflammatory bowel disease. Current approaches for detecting microbiome associations are limited by relying on specific measures of ecological distance, or only allowing for the detection of associations with individual bacterial species, rather than the whole microbiome. In this work, we develop a novel hierarchical Bayesian model for detecting global microbiome associations. Our method is not dependent on a choice of distance measure, and is able to incorporate phylogenetic information about microbial species. We perform extensive simulation studies and show that our method allows for consistent estimation of global microbiome effects. Additionally, we investigate the performance of the model on two real-world microbiome studies: a study of microbiome-metabolome associations in inflammatory bowel disease, and a study of associations between diet and the gut microbiome in mice. We show that we can use the method to reliably detect associations in real-world datasets with varying numbers of samples and covariates.

Delay in loop ileostomy reversal surgery does not impact upon post-operative clinical outcomes. Complications are associated with an increased loss of microflora in the defunctioned intestine.

Loop ileostomy is a common surgical procedure to allow downstream tissue healing, with the aim of re-joining the bowel approximately 12 months later. The reversal procedure is associated with a substantial morbidity up to 40%. Our previous research demonstrated that defunctioned ileum becomes atrophied, with extensive microbial dysbiosis. This study sought to investigate the potential influence of delaying ileostomy reversal surgery upon both clinical and pathological outcomes. Post-operative clinical data was recorded, including routine blood test results, duration of hospital stay, length of time with stoma and incidence of post-operative complications. We measured ileal fibrosis and atrophy and assessed whether these, or dysbiosis, were impacted by the length of time a stoma was in place, or were linked to clinical outcomes. Associations between clinical data were investigated using scatterplot matrix analysis and t-tests. We found no differences in time between ileostomy formation and reversal in patients experiencing complications vs. individuals with no complications. Furthermore, there were no correlations between days with stoma and pathological measures, such as atrophy or fibrosis, and no ongoing increases in collagen production at the time of reversal surgery. This data suggests that the length of time a stoma is in place does not impact on the likelihood of complications. The incidence of complications is associated with increased loss of microbiota in the defunctioned ileum, but importantly, the decrease in bacteria is not linked to time with stoma. Microbiota diversity in the functional and defunctioned limb correlated within an individual, and was not significantly different between those who experienced complications following surgery vs. those that didn't. Microbiota diversity was also not significantly impacted through delay (>365 days) in stoma reversal. We propose that methods to restore intestinal microbiota numbers, and not necessarily their composition, prior to reversal should be explored to improve the clinical outcomes of ileostomy reversal surgery.

A Rare Variant of Pancreatic Sarcoidosis: Diagnostic Challenge.

Pancreatic sarcoidosis is one of the variant of systemic sarcoidosis which is extremely rare in literature and opined as an enigma. Hence, its diagnosis is very challenging as its presentation mimics pancreatic carcinoma. In view of a better understanding, we are presenting a case of pancreatic sarcoidosis to emphasize the above. To clearly distinguish sarcoidosis from malignancy, repeated computed tomography scans, Positron emission tomography scans, fine needle aspiration cytology, endoscopic retrograde cholangio-pancreatography supplemented with histology and relevant blood tests proved it to be a pancreatic sarcoidosis then a malignancy. Over the course, concrete evidence was divulged from lymph node biopsy and histology in clinching the diagnosis which later transformed into a malignancy. Therefore, we concluded it is a rare variant of pancreatic sarcoidosis and careful serial investigations include repeated imaging, histology and blood tests are essential to establish and most importantly differentiate the diagnosis. HOW TO CITE THIS ARTICLE: Khangura T, Uddin G, Davies A, Keating J. A Rare Variant of Pancreatic Sarcoidosis: Diagnostic Challenge. Euroasian J Hepato-Gastroenterol 2015;5(2):118-121.

Proliferation of antigen MIB-1 in metastatic carcinoid tumours removed at liver transplantation: relevance to prognosis.

BACKGROUND: Metastatic carcinoid tumours are difficult to manage. In spite of a multidisciplinary approach, including orthotopic liver transplantation, the recurrence rate is high with a poor prognosis. Histopathology generally fails to provide prognostic information, hence it is essential to try to identify markers of prognosis in these tumours before considering orthotopic liver transplantation. The MIB-1 antibody, which detects cell proliferative activity, has been shown to be a useful prognostic marker for a variety of neoplasms. AIMS: To assess the value of MIB-1 immunostaining as a prognostic marker of the duration to recurrence and the survival of patients undergoing orthotopic liver transplantation for metastatic carcinoid/neuroendocrine tumours of the liver. METHODS: Fourteen patients were included in the study. Formalin-fixed, paraffin-embedded tissue sections of the tumours were stained with routine haematoxylin and eosin and chromogranin. The cell proliferative activity was assessed by MIB-1 antibody labelling using the immunoperoxidase method. Results were correlated with the time of tumour recurrence and the length of patients' survival after transplantation. RESULTS: No correlation was found between MIB-1 labelling index and age, gender, clinical and histological type of tumour (i.e. carcinoid, APUDOMA, secreting or non-secreting). The patients with higher MIB-1 indices ( 5%) showed a trend toward earlier recurrence and poorer survival than those with low MIB-1 indices ( 5%). The predictive value of a MIB-1 index of 2 indicating patient survival of 24 months was 83% (five out of six patients). CONCLUSIONS: The correlation between MIB-1 index and patients' survival suggests that a high proliferative rate, as assessed by MIB-1 immunostaining, may detect those tumours with more aggressive biological behaviour. Prospective studies on a larger number of patients will be needed to determine if, in any individual tumour, this method will provide an additional parameter for a rational approach to therapy.