Jasbir Makker

Genetic epidemiology of irritable bowel syndrome

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder characterized by presence of abdominal pain or discomfort associated with altered bowel habits. It has three main subtypes - constipation predominant IBS (C-IBS), diarrhea predominant IBS (D-IBS) and IBS with mixed features of both diarrhea as well as constipation (M-IBS). Its pathophysiology and underlying mechanisms remain elusive. It is traditionally believed that IBS is a result of multiple factors including hypersensitivity of the bowel, altered bowel motility, inflammation and stress. Initial studies have shown familial aggregation of IBS suggesting shared genetic or environmental factors. Twin studies of IBS from different parts of world have shown higher concordance rates among monozygotic twins than dizygotic twins, and thus suggesting a genetic component to this disorder. Multiple studies have tried to link single-nucleotide polymorphisms (SNPs) to IBS but there is little evidence that these SNPs are functional. Various molecules have been studied and investigated by the researchers. Serotonin, a known neurotransmitter and a local hormone in the enteric nervous system, has been most extensively explored. At this time, the underlying gene pathways, genes and functional variants linked with IBS remain unknown and the promise of genetically-determined risk prediction and personalize medicine remain unfulfilled. However, molecular biological technologies continue to evolve rapidly and genetic investigations offer much promise in the intervention, treatment and prevention of IBS.

Incidental finding of esophageal pneumatosis

Pneumatosis of the gastrointestinal tract is a rare condition characterized by the presence of air filled cavities in the gastrointestinal tract wall. Its occurrence has been described throughout the gastrointestinal tract from the esophagus to the rectum, however it is most commonly reported in the small intestine. Despite multiple case reports in literature, its pathogenesis still remains unclear. Pneumatosis may be idiopathic or associated with a variety of disorders namely peptic ulcer disease, jejunoileal bypass, intestinal obstruction and non-gastrointestinal disorders like asthma, chronic obstructive pulmonary disease, systemic lupus erythematosus, infectious enteritis, etc. We here present a rare case of pneumatosis of the esophagus diagnosed incidentally at an esophagogastroduodenoscopy (EGD). A 78-year-old asymptomatic woman underwent EGD and colonoscopy at our hospital for evaluation of anemia. Few months prior to EGD, she had undergone excision of laryngocele at our hospital. EGD revealed extensive submucosal blebs distributed throughout the esophagus, otherwise unremarkable stomach and duodenum. Colonoscopy showed a tubular adenomatous polyp. Since our patient was asymptomatic she did not require any surgical intervention. Management of pneumatosis depends on the underlying cause.

Strongyloidiasis: A case with acute pancreatitis and a literature review

Strongyloides stercoralis, a soil transmitted helminth infection, affects millions with varying prevalence worldwide. A large number of affected hosts are asymptomatic. Symptoms pertaining to pulmonary and gastrointestinal involvement may be present. Manifestations of involvement beyond lung and intestine can be seen with dissemination of infection and lethal hyperinfection. Immunosuppression secondary to use of steroids or other immunosuppressants and coexistence of human T-lymphotropic virus type-1 are the known risk factors for dissemination and hyperinfection. Diagnostic modalities comprise stool examination, serology and molecular testing. Stool tests are inexpensive but are limited by low sensitivity, whereas serologic and molecular tests are more precise but at the expense of higher cost. Treatment with Ivermectin or Albendazole as an alternative is safe and efficacious. We present a rare case of acute pancreatitis secondary to Strongyloides. High index of suspicion in patients specifically from endemic countries of origin and lack of other common etiologies of acute pancreatitis may help in early diagnosis and prompt treatment of this potentially fatal infection.

Ascaris lumbricoides: To Expect the Unexpected during a Routine Colonoscopy

Ascaris lumbricoides is a common nematode infecting humans worldwide with increased prevalence in tropical and subtropical areas of less developed countries. Recently, it has been estimated that over one billion individuals are infected with ascariasis worldwide with 7% in USA. Although most of these cases are due to increasing immigration and travel outside America it is worth recognizing that prevalence of ascariasis is high in southeastern parts of USA due to their temperate climate. Infections of A. lumbricoides are largely asymptomatic, and hence a large population of people carrying this worm remains undetected for years until they develop some symptoms. Due to a large group of asymptomatic individuals with intestinal ascariasis, these worms are occasionally and unexpectedly identified during routine endoscopic procedures. Here, we present a case of an intestinal ascariasis found during routine colonoscopy in an African-American man from the Bronx with perianal itching. He denied any history of travel outside USA but reported frequent visits to South Carolina. This case illustrates the fact that ascariasis should be suspected even if immigration or travel outside USA is not involved. It should be suspected even in cases of travel within USA to the south east where endemic cases are reported.

Rare case of dysphagia, skin blistering, missing nails in a young boy.

Epidermolysis bullosa is a group of genetic disorders with an autosomal dominant or an autosomal recessive mode of inheritance and more than 300 mutations. The disorder is characterized by blistering mucocutaneous lesions and has several varying phenotypes due to anchoring defect between the epidermis and dermis. The variation in phenotypic expression depends on the involved structural protein that mediates cell adherence between different layers of the skin. Epidermolysis bullosa can also involve extra-cutaneous sites including eye, nose, ear, upper airway, genitourinary tract and gastrointestinal tract. The most prominent feature of the gastrointestinal tract involvement is development of esophageal stricture. The stricture results from recurrent esophageal mucosal blistering with consequent scarring and most commonly involves the upper esophagus. Here we present a case of a young boy with dominant subtype of dystrophic epidermolysis bullosa who presented with dysphagia, extensive skin blistering and missing nails. Management of an esophageal stricture eventually requires dilatation of the stricture or placement of a gastrostomy tube to keep up with the nutritional requirements. Gastrostomy tube also provides access for esophageal stricture dilatation in cases where antegrade approach through the mouth has failed.

Dysmetabolic Hyperferritinemia: All Iron Overload Is Not Hemochromatosis

Disturbances in iron metabolism can be genetic or acquired and accordingly manifest as primary or secondary iron overload state. Organ damage may result from iron overload and manifest clinically as cirrhosis, diabetes mellitus, arthritis, endocrine abnormalities and cardiomyopathy. Hemochromatosis inherited as an autosomal recessive disorder is the most common genetic iron overload disorder. Expert societies recommend screening of asymptomatic and symptomatic individuals with hemochromatosis by obtaining transferrin saturation (calculated as serum iron/total iron binding capacity × 100). Further testing for the hemochromatosis gene is recommended if transferrin saturation is >45% with or without hyperferritinemia. However, management of individuals with low or normal transferrin saturation is not clear. In patients with features of iron overload and high serum ferritin levels, low or normal transferrin saturation should alert the physician to other - primary as well as secondary - causes of iron overload besides hemochromatosis. We present here a possible approach to patients with hyperferritinemia but normal transferrin saturation.

Cytomegalovirus related fatal duodenal diverticular bleeding: Case report and literature review

Involvement of gastrointestinal tract by cytomegalovirus (CMV) is common. CMV infections mainly run their course without any clinical signs in immunocompetent hosts. In contrast, CMV can cause severe infections with serious consequences in a immunocompromised state typically associated with organ transplants, highly immunosuppressive cancer chemotherapy, advanced HIV infection or treatment with corticosteroids. The incidence and severity of these manifestations of CMV is directly proportional with the degree of cellular immune dysfunction, i.e., CD8+ Cytotoxic T-cell response. Clinical manifestations of CMV can become apparent in different situations including reactivation of CMV from latency, primary infection in a seronegative host, or exposure of a seropositive host to a new strain of CMV. As the clinical signs of CMV in immunodeficient patients are usually sparse, physicians should be highly vigilant about CMV infection, a treatable condition that otherwise is associated with significant mortality. Here we report a rare case of severe gastrointestinal CMV infection with sustained immunodeficiency secondary to treatment with steroids manifesting as fatal duodenal diverticular bleeding.

Rare Presentation of Gastroesophageal Carcinoma with Rectal Metastasis: A Case Report

Patient: Female, 60 Final Diagnosis: Gastroesophageal carcinoma with rectal metastasis Symptoms: Bloating • constipation • weight loss Medication: — Clinical Procedure: Endoscopy • flexible sigmoidoscopy • lower endoscopic ultrasound Specialty: Gastroenterology and Hepatology Objective: Unusual clinical course Background: Gastroesophageal cancers, previously considered rare, are rapidly increasing worldwide. We present here a unique case of gastroesophageal carcinoma with metastasis to the rectum. Case Report: A 60-year-old female patient presented with constipation, bloating, and weight loss of 4-month duration. She had undergone sleeve gastrectomy 6 years before. Endoscopies performed revealed a friable-looking mucosa in the lower esophagus and a polypoid rectal mass. Histopathological examination from both the esophageal and rectal lesions revealed poorly differentiated adenocarcinoma cells. Immunohistochemistry stain from both specimens was positive for CK7 supporting the gastric site primary with metastasis to the rectum. Further evaluation also revealed metastasis to bone and malignant pleural effusion. Chemotherapy with palliative intent was initiated. Conclusions: Colorectal metastasis is commonly seen from cancers of the breast, stomach, melanoma, kidney, prostate, and ovaries. However, colorectal metastasis from gastroesophageal cancer has never been reported in the medical literature. Diagnosis relies on histopathologic examination and immunohistochemical staining of the tumor. Treatment depends on the tumor stage. Tumors with widespread metastatic disease are candidates for palliative chemotherapy.

Predicting the presence of adenomatous polyps during colonoscopy with National Cancer Institute Colorectal Cancer Risk-Assessment Tool

AIM To evaluate the National Cancer Institute (NCI) Colorectal Cancer (CRC) Risk Assessment Tool as a predictor for the presence of adenomatous polyps (AP) found during screening or surveillance colonoscopy. METHODS This is a retrospective single center observational study. We collected data of adenomatous polyps in each colonoscopy and then evaluated the lifetime CRC risk. We calculated the AP prevalence across risk score quintiles, odds ratios of the prevalence of AP across risk score quintiles, area under curves (AUCs) and Youden’s indexes to assess the optimal risk score cut off value for AP prevalence status. RESULTS The prevalence of AP gradually increased throughout the five risk score quintiles: i.e., 27.63% in the first and 51.35% in the fifth quintile. The odd ratios of AP prevalence in the fifth quintile compared to the first and second quintile were 2.76 [confidence interval (CI): 1.71-4.47] and 2.09 (CI: 1.32-3.30). The AUC for all patients was 0.62 (CI: 0.58-0.66). Youden’s Index indicated the optimal risk score cutoff value discriminating AP prevalence status was 3.60. CONCLUSION Patients with the higher NCI risk score have higher risk of AP and subsequent CRC; therefore, measures to increase the effectiveness of CRC detection in these patients include longer withdrawal time, early surveillance colonoscopy, and choosing flexible colonoscopy over other CRC screening modalities.

Recurrent Mantle Cell Lymphoma Presenting as Gastrointestinal Bleeding

Mantle cell lymphoma is a rare and aggressive subtype of B-cell non-Hodgkin lymphomas. Mantle cell lymphoma frequently involves extranodal sites, and gastrointestinal tract is involved microscopically and macroscopically in more than 80% of cases. We present two cases of recurrent mantle cell lymphoma presenting with lower and upper gastrointestinal bleeding, respectively. A 58-year-old woman with a history of recurrent mantle cell lymphoma treated with chemotherapy and stem cell transplantation presented with left-sided abdominal pain and hematochezia. Colonoscopy showed a mass-like lesion in the ascending colon, polyps in the ascending colon, and splenic flexure. A 68-year-old man with a history of mantle cell lymphoma treated with chemotherapy presented with epigastric pain and melena. Esophagogastroduodenoscopy showed a large polypoidal ulcerated mass with oozing in the duodenal bulb. Biopsies in both patients were suggestive of mantle cell lymphoma. Patients with mantle cell lymphoma could be asymptomatic or may present with abdominal pain, obstruction, diarrhea, or gastrointestinal bleeding. In patients presenting with gastrointestinal symptoms, endoscopy must be pursued and biopsies must be taken for any suspicious lesions as well as normal mucosa to exclude mantle cell lymphoma as an etiology for the lesion or symptoms. Even though there are no standard guidelines for endoscopic screening of gastrointestinal tract in asymptomatic patients, one should be aware of involvement of gastrointestinal tract in the early course of disease or recurrent disease. Although mantle cell lymphoma is initially responsive to chemotherapy, it eventually becomes refractory with a median survival of 3–5 years.