Paul Mustacchia

Gastrointestinal Stromal Tumors: A Review of Case Reports, Diagnosis, Treatment, and Future Directions

Gastrointestinal stromal tumor (GIST) is a nonepithelial, mesenchymal tumor first described by Mazur and Clark in 1983. Since then, its molecular biology has been studied in great detail. Special interest in the role of tyrosine kinase in its regulation has been the target by different drug research. Mutation in c-kit exons 9, 11, 13, 17 and PDGFRA mutation in exons 12, 14, 18 are responsible for activation of gene signaling system resulting in uncontrolled phosphorylation and tissue growth. However, 5 to 15% of GISTs does not harbor these mutations, which raises additional questions in another alternate signaling pathway mutation yet to be discovered. Diagnosis of GISTs relies heavily on KIT/CD117 immunohistochemical staining, which can detect most GISTs except for a few 3% to 5% that harbors PDGFRA mutation. Newer staining against PKC theta and DOG-1 genes showed promising results but are not readily available. Clinical manifestation of GISTs is broad and highly dependent on tumor size. Surgery still remains the first-line treatment for GISTs. The advancement of molecular biology has revolutionized the availability of newer drugs, Imatinib and Sunitinib. Together with its advancement is the occurrence of Imatinib/Sunitinib drug resistance. With this, newer monoclonal antibody drugs are being developed and are undergoing clinical trials to hopefully improve survival in patients with GISTs.

Hepatic sarcoidosis presenting as portal hypertension and liver cirrhosis: case report and review of the literature.

Systemic sarcoidosis is a disease of unknown etiology, with the liver being the third most commonly affected organ. Most cases of hepatic sarcoidosis are not clinically apparent, but a few can progress to liver cirrhosis, portal hypertension and ultimately liver failure. The diagnosis of hepatic sarcoidosis is difficult, considering that no single laboratory test or radiographic finding can definitively diagnose this systemic disease. Diagnosis of hepatic sarcoidosis relies heavily on histopathologic evaluation of two or more organs, a diagnostic modality that is invasive and may not be applicable to all patients. The treatment of hepatic sarcoidosis is challenging, with no large randomized controlled trials done to date. Physicians must be aware of the complications of hepatic sarcoidosis, and must include the same in the differential diagnosis of liver cirrhosis. We present a case of hepatic sarcoidosis complicated by portal hypertension and liver cirrhosis.

Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis

Objectives: Caffeine consumption is reported to be associated with reduced hepatic fibrosis in patients with chronic liver diseases. We performed a systematic review and meta-analysis to assess the association between caffeine consumption and prevalence or hepatic fibrosis of nonalcoholic fatty liver disease (NAFLD) in observational studies. Methods: We searched the literature of all languages from PubMed, EMBASE, and the Cochrane library from 1 January 1980 through 10 January 2015. Total caffeine consumption was defined as the daily intake of caffeine (mg/day) from all caffeine-containing products. Combined and subgroup analyses stratified by study designs, study locations, and type of caffeine intake were performed. Results: Four cross-sectional and two case control studies with a total of 20,064 subjects were included in the meta-analysis. Among these, three studies with 18,990 subjects were included in the analysis for prevalence of NAFLD while the other three studies with 1074 subjects were for hepatic fibrosis. Total caffeine consumption (mg/day) was not significantly associated with either the prevalence [pooled mean difference (MD) 2.36; 95% confidence interval (CI) −35.92 to 40.64] or hepatic fibrosis (higher versus lower stages; pooled MD −39.95; 95% CI −132.72 to 52.82) of NAFLD. Subgroup analyses stratified by study designs and locations were also not significant. However, after stratifying by type of caffeine intake, regular coffee caffeine intake (mg/day) was significantly associated with reduced hepatic fibrosis of NAFLD (pooled MD −91.35; 95% CI −139.42 to −43.27; n = 2 studies). Conclusion: Although total caffeine intake is not associated with the prevalence or hepatic fibrosis of NAFLD, regular coffee caffeine consumption may significantly reduce hepatic fibrosis in patients with NAFLD.

Eosinophilic Gastrointestinal Diseases: Review and Update

Eosinophilic gastrointestinal disorders (EGIDs) are a progressively more frequent diverse group of intestinal diseases. The intention of this paper is to present the newest developments in the care of patients with EGIDs and to sum up a rising literature defining the clinical features and mechanistic elements of eosinophils and their intricate associations with the gastrointestinal tract. Clinicians ought to stay sensitive to EGIDs as a diagnostic likelihood for patients with general gastrointestinal symptoms. Further research is warranted to establish various methods leading to dysfunction coupled with eosinophilic gastrointestinal inflammation.

Association between nonalcoholic fatty liver disease and colorectal adenoma: a systemic review and meta-analysis

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome (MetS) and the most common chronic liver disease worldwide. The association between NAFLD and colorectal adenoma has been investigated in multiples studies but the results have been conflicting. We performed a systematic review and meta-analysis to evaluate this in asymptomatic patients who underwent screening colonoscopy. METHODS We searched the literatures of all languages from PubMed, EMBASE and the Cochrane library from January 1, 1980 through July 15, 2014. Combined and subgroup analyses stratified by study designs, study locations, characteristics of adenoma (location, size, number, and advanced adenoma) were performed. RESULTS Four cross-sectional and one cohort studies with a total of 6,263 subjects were included in the meta-analysis. NAFLD was significantly associated with colorectal adenoma [pooled odds ratio (OR) 1.74, 95% confidence interval (CI): 1.53-1.97]. The association was more significant in Asian population (pooled OR =1.77, 95% CI: 1.52-2.05, n=3 studies), compared to European/North American population (pooled OR =1.42, 95% CI: 0.75-2.67, n=2 studies). NAFLD was significantly associated with the number of colorectal adenoma (pooled OR =1.78, 95% CI: 1.10-2.86, n=2 studies), but not the location, size, or presence of advanced adenoma. CONCLUSIONS Our results suggest NAFLD is significantly associated with the presence of colorectal adenoma in asymptomatic patients undergoing screening colonoscopy. This finding provides additional risk stratifications for applying colorectal cancer (CRC) screening strategies. However, more studies of western population are needed to further investigate the ethnic disparity.

Association between aspirin use and the prevalence of nonalcoholic fatty liver disease: a cross‐sectional study from the Third National Health and Nutrition Examination Survey

Many basic mechanistic studies found that aspirin inhibited multiple pathways involved in non‐alcoholic fatty liver disease (NAFLD) development.

The association of H. pylori and colorectal adenoma: does it exist in the US Hispanic population?

BACKGROUND Although data on the association between colorectal adenomas and Helicobacter pylori (H. pylori) exists in White and Black patients, there is no data on this association in a US Hispanic population. Our aim was to study the association of adenoma detection and biopsy proven H. pylori infection in a cohort of US Hispanics. METHODS Data were collected from Nassau University Medical Center, a 530-bed tertiary care teaching hospital in East Meadow, New York. Patients who underwent both an esophagogastroduodenoscopy (EGD) and colonoscopy from July 2009 to March 2011 were pulled from an electronic database. A total of 1,737 patients completed colonoscopies during this time with 95 excluded: 17 inflammatory bowel disease, 12 malignancy, 22 prior history of colorectal adenoma, and 44 incomplete. Among the colonoscopies, 799 patients had EGDs performed prior to colonoscopies that were eligible for our study. RESULTS H. pylori prevalence was highest in Hispanics 40.9%, followed by Blacks 29.1% (OR 0.59, 95% CI: 0.42-0.84), then Whites 7.9% (OR 0.12, 95% CI: 0.06-0.24). The adenoma detection rate was significantly higher in Whites 23.2% and Blacks 21.8% compared to Hispanics 14.5%, P=0.0002 respectively. Smoking and alcohol were lower in the H. pylori group, 18.6% (n=44) vs. 26.1% (n=147) for smoking (P=0.02) and 14.4% (n=34) vs. 19% (n=107) for alcohol (P=0.12), respectively. There was no evidence in the Hispanics for an association between adenoma detection and H. pylori infection. Furthermore size, location, and multiple polyps did not differ between the two groups. CONCLUSIONS While data has shown an association between H. pylori and colorectal adenomas, we did not find this in our Hispanic population. With the growing population of Hispanics in the U.S, large scale studies are needed to conclusively characterize the role of H. pylori infection in colorectal adenoma and adenocarcinoma in this group of patients.

Transient Psychotic Episode Induced by Helicobacter pylori Triple Therapy Treatment.

The term ‘antibiomania’ refers to manic episodes that occur after a patient starts taking antibiotics. We report the case of a 49-year-old male who developed acute psychosis secondary to initiation of triple therapy for Helicobacter pylori eradication. Unlike with proton pump inhibitors, there have been several reported cases of central nervous system side effects and psychiatric consequences due to amoxicillin, however evidence points to clarithromycin as the likely culprit. On average onset of symptoms occurred within 1–5 days of initiating therapy. In all cases, symptoms resolved upon cessation of clarithromycin, mostly within 1–3 days. Unfortunately, the mechanism through which clarithromycin causes neurotoxicity remains unclear. Clinicians should be cognizant of psychiatric side effects secondary to clarithromycin, and discontinuation should be prompt for rapid recovery of mental status.

Esophageal Sarcoidosis: A Review of Cases and an Update

Sarcoidosis is a chronic disorder that can virtually affect any organ system in the body. Histologically, it is characterized by the presence of T lymphocytes, mononuclear phagocytes, and noncaseating granulomas. Most commonly affected are the intrathoracic structures, with 90% of the reported cases involving the lungs. Esophageal involvement in sarcoidosis is extremely rare. Dysphagia is the most common presentation in these patients and can be attributed to various mechanisms such as direct esophageal wall infiltration, extrinsic compression, cranial neuropathy, and brainstem involvement. A thorough online literature review revealed only 23 reported cases of esophageal involvement in sarcoidosis. This paper reviews these reported cases in detail along with newer diagnostic and treatment options, including direction of future therapy.

Gastrobronchial fistula following laparoscopic sleeve gastrectomy.

Acquired fistulas between the tracheobronchial tree and the gastrointestinal tract are rare but serious complications of laparoscopic sleeve gastrectomies with significant morbidity and mortality. With the rising popularity and widespread acceptance of bariatric surgery techniques, the occurrence of gastrobronchial fistulas is being increasingly recognised. We present the case of a 26-year-old woman who underwent laparoscopic sleeve gastrectomy for morbid obesity and presented later with a history of chronic productive cough. Upper gastrointestinal series showed the presence of a communicating fistula between the stomach and the lung, with extravasation of contrast into the lung. The aim of this paper is to highlight the importance of considering the diagnosis of a gastrobronchial fistula in cases of persistent respiratory infections in the postoperative period following bariatric surgery and to review its incidence, clinical manifestations and treatment.