Cyclooxygenase-2 expression in polyps from a patient with juvenile polyposis syndrome with mutant BMPR1A.

OBJECTIVES: Cyclooxygenase-2 (COX-2) expression is increased in colorectal cancers and has been reported to be upregulated in Peutz-Jeghers polyps. To determine whether germline and somatic loss of BMPR1A in polyps from a patient with juvenile polyposis syndrome have altered COX-2 expression, we characterized a patient with juvenile polyposis syndrome for BMPR1A germline mutations and examined the polyps for BMPR1A expression and COX-2 expression. PATIENTS AND METHODS: DNA analysis for BMPR1A was performed on a patient with juvenile polyposis syndrome. Multiple polypectomies were performed, and several polyps showed adenomatous change. Genomic DNA was extracted from polyp material for loss of heterozygosity (LOH) analyses with microsatellite markers. Immunohistochemistry was performed on sections using antibodies for BMPR1A and COX-2. RESULTS: The kindred possessed a germline BMPR1A missense mutation. In polyp domains containing cystic and adenomatous epithelium, no LOH was observed using markers near the BMPR1A locus. Immunostaining indicated decreased expression of phospho-SMAD1 (pSMAD1), functionally downstream of the mutant BMPR1A receptor in the cystic epithelium, with further reduction in adenomatous portions within the polyp. COX-2 protein, normally not expressed in the colon, was present and increased in polyp epithelium. CONCLUSIONS: Decreased expression of pSMAD1 in the cystic epithelium with further reduction in the adenomatous area, and increase in COX-2 expression within polyps from the BMPR1A heterozygote, suggest a potential mechanism for adenomatous pathogenesis in these hamartomatous polyps. This may imply that COX-2 inhibitors could be a means for chemoprevention in this syndrome.

Total pancreatectomy and islet cell autotransplantation as a means of treating patients with genetically linked pancreatitis.

BACKGROUND: For patients with severe chronic pancreatitis, total or completion pancreatectomy with islet cell autotransplantation (IAT) can alleviate pain and avoid the complications of diabetes. Several genetic mutations, specifically, PRSS1, CFTR, and SPINK1, are associated with chronic pancreatitis. Few reports have focused on the benefit of this operation for this subset of patients. METHODS: Between February 2000 and July 2009, 118 patients were treated with total pancreatectomy and IAT for chronic pancreatitis. Patients with known genetic mutations were then selected for further analysis. RESULTS: Of the 188 patients, 16 (13.6%) patients were identified as having genetic mutations, including CFTR (n = 10), PRSS1 (n = 4), and SPINK1 (n = 2) mutations. Mean patient age was 31.4 years (range, 15-59) with an equal male-to-female ratio (50:50). Preoperatively, patients required an average of 185 ± 60 morphine equivalents (MEQ) (median, 123 MEQ) for preoperative pain control. No patients were taking insulin before operation. After resection with IAT, patients were discharged from the hospital with a daily average of 22 ± 4 units of insulin with 6 (38%) patients requiring fewer than 15 units of insulin at the time of discharge. At a mean follow-up of 22 months, mean insulin requirements decreased to 15 U/d (P = .0172). A total of 7 (44%) patients required 15 or fewer units daily, and 4 (25%) patients were completely insulin-independent. Average daily narcotic usage at most recent follow-up decreased to 70 MEQ (median, 0) with 10 (63%) patients currently narcotic-independent. Analyses of the 36-item short-form health survey and the McGill Pain Questionnaire demonstrated a significant improvement in quality-of-life parameters and pain assessment. CONCLUSION: In patients who suffer from genetically linked chronic pancreatitis, pancreatic resection with IAT should be considered as an early therapeutic option to decrease chronic abdominal pain while preserving endogenous endocrine function.

Prevalence of irritable bowel syndrome and depression in fibromyalgia.

The purpose of this study was to determine the point prevalence of depressive symptoms, using the PRIME-MD questionnaire, and irritable bowel syndrome (IBS), while comparing the Rome II to the Rome I criteria, in patients with fibromyalgia (FM) and rheumatologic controls in an outpatient setting. The prevalence of IBS in FM patients (n = 105) was 63% by Rome I and 81% by Rome II criteria. The prevalence of IBS in controls (n = 62) was 15% by Rome I and 24% by Rome II criteria (FM vs. control; P < 0.001). Depressive symptoms were met in 40% of FM patients and 8% of controls (P < 0.001). The coexistence of IBS and depressive symptoms in the FM patients was 31% (Rome I) and 34% (Rome II). The prevalence of IBS and depressive symptoms was higher in FM patients compared to the control population. Identification of IBS and depressive symptoms in FM patients might enable clinicians to better meet the needs of this patient population.

Pyogenic and amebic liver abscesses.

Pyogenic and amebic liver abscesses are the two most common hepatic abscesses. Amebic abscesses are more common in areas where Entamoeba histolytica is endemic, whereas pyogenic abscesses are more common in developed countries. Pyogenic abscess severity is dependent on the bacterial source and the underlying condition of the patient. Amebic liver abscess is more prevalent in individuals with suppressed cell-mediated immunity, men, and younger people. The right lobe of the liver is the most likely site of infection in both types of hepatic abscess. Patients usually present with a combination of fever, right-upper-quadrant abdominal pain, and hepatomegaly. Jaundice is more common in the pyogenic abscess. The diagnosis is often delayed and is usually made through a combination of radiologic imaging and microbiologic, serologic, and percutaneous techniques. Treatment involves antibiotics along with percutaneous drainage or surgery.