Genomic landscape of platinum resistant and sensitive testicular cancers

While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertook undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combined this with published genomic data on an additional 624 TGCTs. We integrated analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide the first support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised

Sleep disorders and gastrointestinal symptoms: chicken, egg or vicious cycle?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75369/1/j.1365-2982.2008.01254.x.pd

Dietary guidelines for irritable bowel syndrome are important for gastroenterologists, dietitians and people with irritable bowel syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134108/1/jhn12413_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134108/2/jhn12413.pd

Review article: current and emerging therapies for functional dyspepsia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74835/1/j.1365-2036.2006.03005.x.pd

American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73792/1/j.1572-0241.2007.01393.x.pd

The utility of diagnostic tests in irritable bowel syndrome patients: a systematic review

The aim of this study was to determine the pretest probability of organic GI disease and the accuracy of diagnostic tests for organic GI disease in patients who meet symptom-based criteria for irritable bowel syndrome (IBS). METHODS : After a comprehensive literature search for studies examining the accuracy of diagnostic tests for organic GI disease among patients who meet symptom-based criteria for IBS, two independent observers qualitatively assessed the methodology of selected studies and extracted data. Data on the pretest probability of organic GI disease in this population and the accuracy of currently recommended diagnostic tests were converted to descriptive tables. RESULTS : Among patients meeting symptom-based criteria for IBS, the pretest probability of inflammatory bowel disease, colorectal cancer, or infectious diarrhea is less than 1%. Currently recommended diagnostic tests rarely identify organic GI disease in patients fulfilling symptom-based criteria for IBS. However, the pretest probability of celiac disease in patients meeting symptom-based criteria for IBS was 10 times higher than the prevalence of celiac disease in the general population. CONCLUSION : There is insufficient evidence to recommend the routine performance of a standardized battery of diagnostic tests in patients who meet symptom-based criteria for IBS. Based upon the increased pretest probability of celiac disease, routine performance of serological tests for celiac disease may be useful in this patient population, though additional study is needed in this area.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72511/1/j.1572-0241.2002.07027.x.pd

Pharmacologic and Complementary and Alternative Medicine Therapies for Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by episodic abdominal pain or discomfort in association with altered bowel habits (diarrhea and/or constipation). Other gastrointestinal symptoms, such as bloating and flatulence, are also common. A variety of factors are believed to play a role in the development of IBS symptoms, including altered bowel motility, visceral hypersensitivity, psychosocial stressors, altered brain-gut interactions, immune activation/low grade inflammation, alterations in the gut microbiome, and genetic factors. In the absence of biomarkers that can distinguish between IBS subgroups on the basis of pathophysiology, treatment of this condition is predicated upon a patient's most bothersome symptoms. In clinical trials, effective therapies have only offered a therapeutic gain over placebos of 7-15%. Evidence based therapies for the global symptoms of constipation predominant IBS (IBS-C) include lubiprostone and tegaserod; evidence based therapies for the global symptoms of diarrhea predominant IBS (IBS-D) include the probiotic Bifidobacter infantis, the nonabsorbable antibiotic rifaximin, and alosetron. Additionally, there is persuasive evidence to suggest that selected antispasmodics and antidepressants are of benefit for the treatment of abdominal pain in IBS patients. Finally, several emerging therapies with novel mechanisms of action are in development. Complementary and alternative medicine therapies including probiotics, herbal therapies and acupuncture are gaining popularity among IBS sufferers, although concerns regarding manufacturing standards and the paucity of high quality efficacy and safety data remain

Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor-Refractory Symptoms

Background & aimsThere are few data on the prevalence of gastroesophageal reflux disease (GERD) in the United States. We performed a population-based study to determine the prevalence of GERD symptoms and persistent GERD symptoms despite use of proton pump inhibitors (PPIs).MethodsWe conducted the National Gastrointestinal Survey in 2015 using MyGiHealth, an app that guides participants through National Institutes of Health gastrointestinal Patient-Reported Outcomes Measurement Information System surveys. Primary outcomes were prevalence of GERD symptoms in the past and persistence of GERD symptoms (heartburn or regurgitation 2 or more days in past week) among participants taking PPIs. Population weights were applied to the data and multivariable regression was used to adjust for confounding.ResultsAmong 71,812 participants, 32,878 (44.1%) reported having had GERD symptoms in the past and 23,039 (30.9%) reported having GERD symptoms in the past week. We also found that 35.1% of those who had experienced GERD symptoms were currently on therapy (55.2% on PPIs, 24.3% on histamine-2 receptor blockers, and 24.4% on antacids). Among 3229 participants taking daily PPIs, 54.1% had persistent GERD symptoms. Younger individuals, women, Latino individuals, and participants with irritable bowel syndrome or Crohn's disease were more likely to have continued symptoms, even when taking PPIs.ConclusionsUsing a population-based survey, we found GERD symptoms to be common: 2 of 5 participants have had GERD symptoms in the past and 1 of 3 had symptoms in the past week. We also found that half of PPI users have persistent symptoms. Given the significant effect of GERD on quality of life, further research and development of new therapies are needed for patients with PPI-refractory GERD symptoms

Appropriate timing of the 14 C-urea breath test to establish eradication of Helicobacter pylori infection

The aim of this study was to determine the performance characteristics of the 14 C-urea breath test (UBT) performed 2 wk after the completion of therapy for Helicobacter pylori using a 4 to 6 wk study as the gold standard. METHODS : Patients with active Helicobacter pylori infection at four medical centers received proton pump inhibitor-based triple or quadruple therapy for 10–14 days. Patients underwent the 14 C-UBT 2 and 4–6 wk after the completion of therapy. A positive test was defined as 14 CO 2 excretion of >200 dpm, a negative test as 50 but <200 dpm. Performance characteristics of the 2-wk UBT were calculated using the 4 to 6-wk result as a gold standard. RESULTS : Eighty-five patients were enrolled and 82 patients (mean ± SD age, 62 ± 15 yr; 15 women) completed the protocol. Four patients had equivocal UBT results and were excluded from the analysis. Of the 78 patients, 68 (87%) had a negative 4 to 6-wk UBT. The 2-week UBT yielded a sensitivity of 90% (95% confidence interval 72–100%), specificity of 99% (97–100%), and accuracy of 97% (93–100%). In patients with a persistently positive UBT, 14 CO 2 excretion at 2 wk was significantly lower than at 4–6 wk after therapy ( p = 0.03 ). CONCLUSIONS : A UBT performed 2 wk after therapy yielded results comparable to 4 to 6 wk testing. Further studies to evaluate the optimal time of confirmatory testing in the age of more effective proton pump inhibitor-based triple therapies are warranted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73434/1/j.1572-0241.2000.02005.x.pd