Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy.

Focal splenic lesions (FSL) occur in Gaucher disease type I (GD1), but their clinical significance is not known. Previous studies estimated the prevalence of FSL at 4% (pediatric) to 33% (adult) of GD1 patients and reported an association with splenomegaly. We tested the hypothesis that the presence of FSL is associated with suboptimal response to macrophage-directed enzyme replacement therapy (ERT). Additionally we investigated whether FSL were associated with other phenotypic features of GD1. The splenic parenchyma was assessed by MRI performed for routine evaluation of GD1 in 239 consecutive GD1 patients with intact spleens. The prevalence of FSL was 18.4% (44/239). Following a mean of 3.5 years of ERT, platelet response was inferior among patients with FSL (80,700 ± 9,600 to 90,100 ± 7,200/mm(3) , P = 0.2) compared to patients without FSL in whom there was a robust platelet response: 108,600 ± 5,670 to 150,200 ± 6,710/mm(3), P < 0.001. Compared to patients without FSL, patients harboring FSL had worse thrombocytopenia (platelet count: 83,700 ± 8,800 vs. 112,100 ± 4,200/mm(3), P = 0.004), greater frequency of pre-ERT splenomegaly, and greater post-ERT splenomegaly (8.5 ± 0.77 vs. 4.8 ± 0.25× normal, P < 0.001). Additionally, the prevalence of osteonecrosis was higher among patients with FSL compared to patients without FSL (38 vs. 20.7%, P = 0.026). FSL appear to be a determinant of response to ERT, suggesting studies comparing relative efficacy of newly emerging therapies for GD1 should adjust for this factor. Moreover, occurrences of FSL coincide with more severe manifestations of GD1 such as avascular osteonecrosis.

Bilhemia after trans-jugular intra-hepatic porto-systemic shunt and its management with biliary decompression.

Bilhemia or bile mixing with blood is a rare clinical problem. The clinical presentation is usually transient self-resolving hyperbilirubinemia, progressive and rapidly rising conjugated hyperbilirubinemia, or recurrent cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) plays an important role in diagnosis and management. Biliary decompression with endoscopic sphincterotomy is useful in treating these patients. If not recognized and treated in time, the condition can be fatal in a significant proportion of patients. This usually occurs after blunt or penetrating hepatic trauma due to a fistulous connection between the biliary radicle and portal or hepatic venous radical. Cases have been described due to iatrogenic trauma such as liver biopsy and percutaneous biliary drainage. However, the occurrence after trans-jugular intra-hepatic porto-systemic shunt (TIPS) is very rare. We report a case of bilhemia presenting as rapidly rising bilirubin after TIPS. The patient was managed successfully with ERCP and removal of a blood clot from the common bile duct.

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.

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.

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.