The Icahn School of Medicine at Mount Sinai, on behalf of GN, MO, and NSD, has filed patents covering composition of matter on the small molecules disclosed herein for the treatment of human cancer and other diseases (international application numbers: PCT/US15/19770, PCT/US15/19764; and US Patent: US 9,540,358 B2). RAPPTA Therapeutics LLC has licensed this intellectual property for the clinical and commercial development of this series of small molecule PP2A activators. GN, MO, and MDG have an ownership interest in RAPPTA Therapeutics LLC.

Discussion: Mantle cell lymphoma is a subtype of non-Hodgkins lymphoma (NHL) making up about 7% of NHL in adults. MCL predominantly presents with advanced disease. Gastrointestinal involvement during endoscopic evaluation is rarely the presenting sign, as in this patient, which most commonly manifests as diffuse lymphomatous polyposis. Recognizing this endoscopic finding is important as it can expedite diagnosis by appropriately analyzing tissue obtained through biopsy and attaining further imaging to confirm the suspicion of lymphoma.[2033] Figure 1. A. Nodular ileocecal valve with surrounding polypoid colonic mucosa B. Polypoid mucosa in the terminal ileum C. Lymphoma cells with irregular nuclear contours, irregular chromatin, inconspicuous nucleolus, and moderate amount of cytoplasm. D. CT scan showing 5.0cm ileocecal valve.

INTRODUCTION: Oral chemotherapy with Vismodegib for locally advanced Basal Cell Carcinoma (BCC) is widely used by dermatologists. In several isolated case reports, rare hepatotoxicity has been reported, but no consumer safety notifications have been issued by the manufacturer or the FDA to date. CASE DESCRIPTION/METHODS: A 62-year-old Caucasian female presented to emergency room with profound jaundice of her skin and scleral icterus that began two weeks after completion of Vismodegib oral chemotherapy for BCC of the left lateral forehead (Figure 1). Her past medical history was only significant for hypertension and pyrosis. The patient reports that she did not take any prescription or over-the-counter medications, herbal supplements, and had no history of alcohol use. Admission labs revealed AST of 37, ALT of 287, alkaline phosphatase of 522, total bilirubin 11.2, direct bilirubin 6.9, and indirect bilirubin of 4.3. A prompt liver biopsy revealed findings consistent with drug-related injury, including bile ductular reaction associated with portal inflammation consisting of lymphocytes, eosinophils, and neutrophils (Figure 2). She was stabilized and discharged with a plan for weekly outpatient monitoring. However, she presented two weeks later with complaints of right upper quadrant pain and melanotic stools for two days. Admission labs revealed a hemoglobin of 8.4, decreased from 12.0 on previous discharge. She was transfused appropriately and an upper endoscopy (EGD) revealed bleeding from the papillary orifice, indicative of hemobilia (Figure 3), warranting selective angiography and coil embolization for successful hemostasis. Jaundice resolved fully in four weeks and hemoglobin and liver function tests (LFTs) normalized in two months at follow-up. DISCUSSION: As noted in our case, gastroenterologists are bound to see an array of iatrogenic life-threatening complications from outpatient oral therapy for cosmetic lesions. Our case involved not only the hepatotoxic effects from Vismodegib, but a rare iatrogenic complication from the biopsy with bleeding requiring further interventions. Fatalities have been reported with this drug. Therefore, heightened awareness in medical community and mandated patient safety notifications by the manufacturer and the FDA are necessary to improve outcomes.

INTRODUCTION: Disaccharidase assay for evaluating abdominal pain has been well studied in the pediatric population. Deficiency of lactase or sucrase-isomaltase can present with chronic diarrhea, flatulence, abdominal pain, and bloating in such patients. However, the prevalence of disaccharidase deficiencies in adult populations with such symptoms has not been well delineated. METHODS: Distal duodenal specimens from 100 patients with above symptoms, who underwent an upper endoscopy (EGD) at an outpatient facility were submitted for disaccharidase assay. Standardized laboratory cut off values were used to determine disaccharidase levels that were outside the normal range. Statistical analysis was done to determine the frequencies of abnormal disaccharidases. Analysis of the group, with normal or low lactase/sucrase and presenting clinical features, was performed. RESULTS: Mean age of study patients was 52 years and 46% of the patients were male. The racial distribution was as follows: 45% White, 23% Hispanic, 18% Asian, 6% Black, 8% other. Table 1 shows the frequencies of normal and low values for these patients. 84% of the cohort had low lactase, 21% had low sucrase, and 11% had all 4 values in normal range. Figure 2 shows the distribution of the remaining patients who had at least 1 abnormal disaccharide. CONCLUSION: The association between abdominal symptoms and carbohydrate malabsorption in adults is widely recognized, but testing is rarely performed by gastroenterologists in clinical practice. Dietary recommendations are often made empirically. We investigated the prevalence of low disaccharidase levels in the adult population with above symptoms. Besides lactase deficiency, a significant number of patients also had deficiency of sucrase, maltase and palatinase. While this study cannot establish a causal relationship between low levels noted and patient symptoms, this information can be used to recommend appropriate diets or the use of lactase and sucrase enzyme supplements offering a more selective approach in patient care.

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