A study of genomic aberrations in gastric adenocarcinoma

Master'sMASTER OF SCIENC

One year changes in QCT and DXA bone densities following bariatric surgery in a multiethnic Asian cohort

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The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

<p>Abstract</p> <p>Background</p> <p>Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints.</p> <p>Methods</p> <p>Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation.</p> <p>Results</p> <p>By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (<it>p </it>< 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated.</p> <p>Conclusion</p> <p>This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.</p

Clinical features of paraduodenal hernia

Paraduodenal hernia (PDH), though uncommon, is a surgical emergency associated with high risk of strangulation and incarceration. Diagnosis of PDH remains challenging due to its non-specific presentation. We report the presentation and management of PDH in our hospital. All PDHs diagnosed from 2003 to 2014 were identified from a hospital database. Diagnosis of PDH was based on either radiological imaging or intraoperative surgical findings. Eight PDHs were identified during the study period. Median age was 48.5 (24–63) years and five occurred in females. All were left-sided PDHs. Six patients experienced recurrent symptoms prior to presentation. The commonest presenting symptoms were recurrent abdominal pain (four patients) and intestinal obstruction (four patients). Five patients were treated conservatively either because they had no obstructive symptoms or they declined surgery. All of them remained well up to a median of 27 (16–45) months’ follow-up. In contrast, three patients with obstructive symptoms underwent surgical repair (laparotomy, hernia repair and adhesiolysis). One patient had sub-acute intestinal obstruction after surgical repair and required re-exploratory surgery. All three PDH patients with obstructive symptoms remained well on follow-up (median 61 (range: 27–114) months) after surgery. In conclusion, PDH is an uncommon cause of intestinal obstruction. A high index of suspicion is required to diagnose PDH

Molecular Genetics of Gastric Adenocarcinoma

Gastric carcinoma is the second leading cause of cancer deaths in the world. Its aetiology is closely linked to the bacterial pathogen Helicobacter pylori which is believed to induce a state of chronic inflammation that predisposes to a cascade of molecular and cellular alterations leading to carcinogenesis. Although the exact process of gastric carcinogenesis has yet to be elucidated fully, the interaction of the genetic factors with environmental factors is likely to be a significant consideration. Numerous genes and molecular pathways have been discovered to be associated with gastric adenocarcinoma and more importantly, it is now becoming possible to use some of these as means of prognostication and targeted therapy. This review will outline our current understanding of the aetiology and molecular genetics of gastric adenocarcinoma and its current clinical applications

Small hiatal hernia and postprandial reflux after vertical sleeve gastrectomy: A multiethnic Asian cohort.

BackgroundLaparoscopic vertical sleeve gastrectomy (LSG) is a popular bariatric procedure performed in Asia, as obesity continues to be on the rise in our population. A major problem faced is the development of de novo gastroesophageal reflux disease (GERD) after LSG, which can be chronic and debilitating. In this study, we aim to assess the relationship between the presence of small hiatal hernia (HH) and the development of postoperative GERD, as well as to explore the correlation between GERD symptoms after LSG and timing of meals. In doing so, we hope to gain a better understanding about the type of reflux that occurs after LSG and take a step closer towards effectively managing this difficult to treat condition.MethodsWe retrospectively reviewed data collected from patients who underwent LSG in our hospital from Dec 2008 to Dec 2016. All patients underwent preoperative upper GI endoscopy, during which the identification of hiatal hernia takes place. Patients' information and reflux symptoms are recorded using standardized questionnaires, which are administered preoperatively, and again during postoperative follow up visits.ResultsOf the 255 patients, 125 patients (74%) developed de novo GERD within 6 months post-sleeve gastrectomy. The rate of de novo GERD was 57.1% in the group with HH, and 76.4% in the group without HH. Adjusted analysis showed no significant association between HH and GERD (RR = 0.682; 95% CI 0.419 to 1.111; P = 0.125). 88% of the patients who developed postoperative GERD reported postprandial symptoms occurring only after meals, and the remaining 12% of patients reported no correlation between the timing of GERD symptoms and meals.ConclusionThere is no direct correlation between the presence of small hiatal hernia and GERD symptoms after LSG. Hence, the presence of a small sliding hiatal hernia should not be exclusion for sleeve gastrectomy. Electing not to perform concomitant hiatal hernia repair also does not appear to result in higher rates of postoperative or de novo GERD