Ghulamullah Shahzad

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.

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.

Cancers of the Appendix: Review of the Literatures

Cancers of the appendix are rare. Most of them are found accidentally on appendectomies performed for appendicitis. When reviewed, majority of the tumors were carcinoid, adenoma, and lymphoma. Adenocarcinomas of appendix are only 0.08% of all cancers and the treatment remains controversial. Here we are reporting a 46-year-old male presented with symptoms of appendicitis, diagnosed with adenocarcinoma of the appendix. The patient was treated with appendectomy and refused further surgical intervention to complete hemicolectomy. Up to date, he remains asymptomatic. We performed literature review of the tumors of the appendix. Most of the benign conditions are treated with surgery alone. Lymphomas require CHOP-like chemotherapy and carcinoid syndrome treatment with somatostatin analogues. It is generally recommended that right hemicolectomy is the preferred treatment for adenocarcinoma of appendix. The role of chemotherapy is unclear due to lacking randomized trials but seems to be accepted if there is lymph node involvement or peritoneal seeding.

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 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 relationship of vitamin D status, smoking, and colorectal adenoma: A retrospective study in an ethnically diverse community

OBJECTIVEnCirculating 25-hydroxyvitamin D (25OHD) level is suggested to be negatively correlated with risk of colorectal cancer (CRC) and colorectal adenoma (CRA), but most of the epidemiological data were originated amongst Caucasians and African Americans. This study aimed to investigate the relationship between vitamin D status, smoking and CRA in an ethnically diverse community with a high Hispanic density.nnnMETHODSnIn this retrospective study, we included 233 patients who underwent complete colonoscopies from 2009 to 2011, and their serum 25OHD levels in the winter season had been measured. Among them, 65 adenoma cases and 168 adenoma-free controls were identified and evaluated for the association of CRA with smoking, ethnicity and serum 25OHD level using unstratified and stratified multivariate logistic regression analyses.nnnRESULTSnIn our study participants, the mean serum 25OHD level and the percentage of Hispanics were lower in the adenoma group versus the control group, while no black-white difference was noted in the CRA prevalence. When adjusted for 25OHD level, the lower rate of adenoma in Hispanics compared to non-Hispanics was attenuated and became statistically insignificant. A mild protective effect of vitamin D (6% reduction) on the CRA risk was found significant for active smokers, but not for non-smokers. A detrimental impact of smoking in the CRA risk was only shown among non-Hispanic patients, but not among Hispanics irrespective of vitamin D status.nnnCONCLUSIONSnOur data suggest a marked distinction between Hispanics and non-Hispanics in the risk of CRA. The reduced adenoma prevalence among Hispanics vs. non-Hispanics could be partially explained by vitamin D status, cigarette smoking and their interactions. Future larger-sized multi-center studies on vitamin D status and ethnicity, as well as dietary, behavioral, genetic factors and their interactions for CRA and CRC are needed. This article is part of a Special Issue entitled Vitamin D Workshop.

Rectal ulcers and massive bleeding after hemorrhoidal band ligation while on aspirin

Endoscopic hemorrhoidal band ligation is a well-established nonoperative method for treatment of bleeding internal hemorrhoids (grade 1 to 3). It is a safe and effective technique with a high success rate. Complications with this procedure are uncommon. Although rectal ulceration due to band ligation is a rare complication, it can cause life-threatening hemorrhage especially when patients are on medications which impair hemostasis like aspirin or non steroidal anti-inflammatory drugs. We present 2 cases of massive lower gastro-intestinal bleeding in patients who had a band ligation procedure performed 2 wk prior to the presentation and were on aspirin at home. Both the patients were hemodynamically unstable requiring resuscitation. They required platelet and blood transfusions and were found to have rectal ulcers on colonoscopy done subsequently. The rectal ulcers corresponded to the site of band ligation. The use of aspirin by these patients would have caused defects in the hemostasis and may have predisposed them to massive bleeding in the presence of rectal ulcers occurring after the band ligation procedure. Managing aspirin before and after the ligation may be difficult especially since adequate guidelines are unavailable. Stopping aspirin in all the cases might not be safe and the decision should be individualized.

Eosinophilic Enterocolitis Diagnosed by Means of Upper Endoscopy and Colonoscopy with Random Biopsies Treated with Budenoside: A Case Report and Review of the Literature

Intense infiltration of gastrointestinal and colonic mucosa with eosinophils or acidophilic gastroenteritis (EG) is a relatively uncommon picture for a pathologist endoscopist especially outside the pediatric age group and is highly suggestive of an ongoing chronic inflammatory process. Existing literature projected a hypothetical association with allergy but the exact pathophysiology is still unknown. Association with malabsorption, protein losing enteropathy, and refractory ulcers with gastrointestinal bleeding makes the clinical presentation more complicated. We present a unique case of diarrhea and abdominal pain in the clinical presentation with associated peripheral eosinophilia, asthma, and gastroesophageal reflux disease (GERD). The patients symptoms abated after initiation of budesonide.

Role of Mucosal Inflammation in Eosinophilic Esophagitis: Review of the Literature

Eosinophilic esophagitis (EE) is increasingly recognized in adults. It is an inflammatory disease of the esophageal mucosa, with variable presentation, unresponsive to acid suppression therapy. The diagnosis requires histological confirmation of intense eosinophilic infiltration on esophageal biopsy specimen, however exact criteria required to make a diagnosis of EE is still being debated and a clear differentiation from gastroesophageal reflux disease (GERD) is important. Allergen elimination or anti-inflammatory therapy may be effective in such patients. The imperfect diagnostic criteria for EE mandate an understanding of the immunology and the pathophysiology of the disease. It may facilitate the introduction of novel treatment modalities in an individual unresponsive to acid suppression therapy. This paper describes basic elements of the immune-mediated injury to the esophageal mucosa and management aspects to provide a better understanding of the condition.

Germ cell cancer presenting as gastrointestinal bleeding and developing brain metastases: case report and review of the literature

This paper describes a rare case of germ cell cancer with duodenum, brain and lung metastases. The patient presented with melena and left testicle enlargement. Orchiectomy revealed mixed germ cell cancer, enteroscopy revealed duodenal choriocarcinoma, and chest x-ray and computed tomography (CT) showed bilateral lung metastases. The patient received and tolerated cisplatinum-based chemotherapy, and responded well. However, he developed seizures 3 months later. MRI showed brain metastases and he was treated with whole-brain radiation. One month later, he developed progressive dyspnea. Chest CT showed worsening lung metastases. He received second-line chemotherapy, but died due to multiorgan failure. Germ cell cancer with nonpulmonary metastases has poor prognosis and the management of these patients requires a multimodal approach. Head CT should be considered as routine screening for all germ cell cancer patients on initial diagnosis and brain MRI should be considered for high-risk patients (with an embryo- or choriocarcinoma histology, dramatically elevated β-human chorionic gonadotropin and lung involvement).