Advitya Malhotra

The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients

Mutations in GBA1 gene that encodes lysosomal glucocerebrosidase result in Type 1 Gaucher Disease (GD), the commonest lysosomal storage disorder; the most prevalent disease mutation is N370S. We investigated the heterogeneity and natural course of N370S GD in 403 patients. Demographic, clinical, and genetic characteristics of GD at presentation were examined in a cross‐sectional study. In addition, the relative risk (RR) of cancer in patients compared with age‐, sex‐, and ethnic‐group adjusted national rates of cancer was determined. Of the 403 patients, 54% of patients were homozygous (N370S/N370S) and 46% were compound heterozygous for the N370S mutation (N370S/other). The majority of N370S/N370S patients displayed a phenotype characterized by late onset, predominantly skeletal disease, whereas the majority of N370S/other patients displayed early onset, predominantly visceral/hematologic disease, P < 0.0001. There was a striking increase in lifetime risk of multiple myeloma in the entire cohort (RR 25, 95% CI 9.17–54.40), mostly confined to N370S homozygous patients. The risk of other hematologic malignancies (RR 3.45, 95% CI 1.49–6.79), and overall cancer risk (RR 1.80, 95% CI 1.32–2.40) was increased. Homozygous N370S GD leads to adult‐onset progressive skeletal disease with relative sparing of the viscera, a strikingly high risk of multiple myeloma, and an increased risk of other cancers. High incidence of gammopathy suggests an important role of the adaptive immune system in the development of GD. Adult patients with GD should be monitored for skeletal disease and cancers including multiple myeloma. Am. J. Hematol., 2009.

Colonoscopic full-thickness resection of the colon in a porcine model as a prelude to endoscopic surgery of difficult colon polyps: a novel technique (with videos)

BACKGROUND Colonoscopic full-thickness resection (CFTR) of the colon may obviate the need for surgical resection of benign lesions. OBJECTIVE To develop an animal model for CFTR of the colon followed by endoscopic suture closure with through-the-endoscope devices. DESIGN Pilot study. SETTING University medical center. ANIMALS Twenty pigs. INTERVENTIONS A 2-cm circular area was resected on the antimesenteric side of the colon (phase 1, n = 10) and on the mesenteric side (phase 2, n = 10) by using an insulated tip knife cut followed by the use of a grasping forceps and a snare to resect and retrieve the specimen. The tissue apposition system was used to close the defect. MAIN OUTCOME MEASUREMENTS Resection and closure times were recorded. The animals were euthanized at 2 weeks and examined for peritonitis, adhesions, wound healing, and T-tag injury to adjacent viscera. RESULTS The CFTR was successful in all 20 attempts. The median resection time was 6 minutes (range 2.5-35 minutes). Suture closure was successful in 19 animals. It took a median time of 41 minutes (range 21-125 minutes) and 4 sutures to close the defect. Eighteen animals survived without clinical signs of distress; there was a well-healed scar without peritonitis or distant adhesions on necropsy at 2 weeks. One animal failed to thrive, and necropsy revealed mild peritonitis, small abscesses, distant adhesions, and a 2-mm hole at the suture site. Two of the 132 T-tags were inserted in the adjacent viscera. LIMITATIONS Colon resection in the proximal colon was not studied. CONCLUSIONS In this animal model, CFTR of the colon followed by suture closure can be accomplished successfully by using through-the-endoscope devices.

Clinical Challenges and Images in GI

C uestion: A 40-year-old Hispanic woman with unremarkble past medical history presented to the emergency deartment (ED) with generalized fatigue and dyspnea on xertion. Her symptoms started about 3 months ago. There as no history of weight loss or anorexia. She denied menrrhagia, melena, hematochezia, and hematemesis. On hysical examination, she was normotensive, tachypneic, nd tachycardic with a heart rate of 116. Examination of the onjunctiva revealed marked pallor. The rest of the physical xamination was unremarkable, except for a positive guaiac est. Laboratory data revealed a hemoglobin 6.2 g/dl (noral range, 11.5–15.5) and a mean corpuscular volume of 67 (normal range, 80–96). Patient underwent esophagogasroduodenoscopy (EGD) and colonoscopy to evaluate the ource of blood loss. EGD revealed numerous, red-colored, yperemic, smooth, polypoid lesions in the body and the ntrum of the stomach (Figure A). Multiple polyps were esected using snare cautery and sent for pathology. All the esected polyps exhibited the same histopathological feaures as shown in Figure B (hematoxylin and eosin; original agnification, 20x).

Giant Trichobezoar and Gastric Perforation in a Normal Healthy Woman

We present a case report of a mentally healthy woman who had gastric trichobezoar leading to perforation. A pertinent review of literature is included.