Intestinal Oxalate Absorption, Enteric Hyperoxaluria, and Risk of Urinary Stone Formation in Patients with Crohn's Disease.

Nephrolithiasis is a common urologic manifestation of Crohn's disease. The purpose of this study was to investigate the clinical characteristics, intestinal oxalate absorption, and risk factors for urinary stone formation in these patients. In total, 27 patients with Crohn's disease and 27 healthy subjects were included in the present study. Anthropometric, clinical, and 24 h urinary parameters were determined, and the [13C2]oxalate absorption test was performed. Among all patients, 18 had undergone ileal resection, 9 of whom had a history of urinary stones. Compared to healthy controls, the urinary excretion values of calcium, magnesium, potassium, sulfate, creatinine, and citrate were significantly lower in patients with Crohn's disease. Intestinal oxalate absorption, the fractional and 24 h urinary oxalate excretion, and the risk of calcium oxalate stone formation were significantly higher in patients with urolithiasis than in patients without urolithiasis or in healthy controls. Regardless of the group, between 83% and 96% of the [13C2]oxalate was detected in the urine within the first 12 h after ingestion. The length of ileum resection correlated significantly with the intestinal absorption and urinary excretion of oxalate. These findings suggest that enteric hyperoxaluria can be attributed to the hyperabsorption of oxalate following extensive ileal resection. Oral supplementation of calcium and magnesium, as well as alkali citrate therapy, should be considered as treatment options for urolithiasis.

Use of the lactose-[13C]ureide breath test for diagnosis of small bowel bacterial overgrowth: comparison to the glucose hydrogen breath test.

PURPOSE: The glucose hydrogen breath test (GHBT) is commonly used as a noninvasive test to diagnose small bowel bacterial overgrowth (SBBO) but its validity has been questioned. Our aim was to evaluate the lactose-[(13)C]ureide breath test (LUBT) to diagnose SBBO and to compare it with the GHBT, using cultures of intestinal aspirates as a gold standard. METHODS: In 22 patients with suspected SBBO (14 male, age range 18-73 years) aspirates were taken from the region of the ligament of Treitz under sterile conditions and cultured for bacterial growth. More than 10(6) colony-forming units/mL fluid or the presence of colonic flora was defined as culture positive (c+). After oral intake of 50 g glucose and 2 g of lactose-[(13)C]ureide, end-expiratory breath samples were obtained up to 120 min. The (13)C/(12)C ratio in breath CO(2) was determined by isotope ratio-mass spectrometry and hydrogen concentration in breath was analyzed electrochemically. RESULTS: After analyzing receiver operating characteristic curves of the LUBT results, total label recovery of >0.88% at 120 min was considered positive. The test had a sensitivity of 66.7% and a specificity of 100% to predict c+. In the GHBT, an increase of the signal of > or =12 ppm from baseline was considered positive. The sensitivity and specificity of the test were 41.7 and 44.4%, respectively. CONCLUSIONS: The new stable isotope-labeled LUBT has excellent specificity but suboptimal sensitivity. In contrast, the standard GHBT lacks both high sensitivity and specificity. The LUBT is superior to the GHBT for detecting SBBO.

Multiple novel alterations in Kit tyrosine kinase in patients with gastrointestinally pronounced systemic mast cell activation disorder.

OBJECTIVE: Sequencing efforts to discover mutations in the tyrosine kinase Kit related to systemic mast cell disorders have so far been focused mainly on only a few of the 21 exons of the encoding gene c-kit, thus considerably limiting the possibility to quantitatively reveal pathogenetic relationships. The purpose of this study was to analyze and compare the total sequence of Kit tyrosine kinase at the level of the mRNAs obtained from patients with clear systemic signs of a pathologically increased mast cell mediator release and those from healthy volunteers. MATERIAL AND METHODS: Kit encoding mRNA isolated from mast cell progenitors in peripheral blood from 17 patients with a mast cell activation disorder and from 5 healthy volunteers as well as from the human mast cell leukemia cell line HMC1 was analyzed for alterations. RESULTS: Multiple novel point mutations and six isoforms of Kit which are due to alternative mRNA splicing were detected. One isoform, the insertion of a glutamine residue at amino acid position 252, was found to be a new splice variant expressed in all patients but in none of the healthy volunteers. CONCLUSIONS: Systemic mast cell activation disorder was pathogenetically characterized by two or more alterations in the Kit tyrosine kinase providing not only a means of confirming the diagnosis, but also of assessing prognosis and of starting adequate therapeutic interventions. The insertion of Q252 appears to be pathognomic for that disease, providing a novel means for the identification of chronic non-specific gastrointestinal symptoms as manifestations of a systemic mast cell activation disorder.

Phase II study of photodynamic therapy and metal stent as palliative treatment for nonresectable hilar cholangiocarcinoma.

BACKGROUND: The combination of photodynamic therapy and biliary drainage by plastic endoprosthesis insertion has produced promising results in the treatment of nonresectable hilar cholangiocarcinoma. The feasibility and efficacy of intraductal photodynamic therapy with subsequent biliary drainage by self-expandable metal stent insertion were evaluated in a prospective phase II study. METHODS: Twenty-four patients were treated with photodynamic therapy after sensitization with porfimer sodium. A plastic endoprosthesis was inserted immediately thereafter and replaced by a metal stent 4 weeks later. A retrospectively analyzed group of 20 patients treated only with biliary drainage served as a historical control group. RESULTS: In 19 of the 24 patients, insertion of a metal stent was technically feasible. The 30-day and 60-day mortality rates were 0%. A significant decrease in serum bilirubin was noted in all patients and quality of life remained stable throughout follow-up. Mean and median survival were, respectively, 15.9(3.1) and 9.9: 95% CI [6.4, 13.4] months after photodynamic therapy. In the control group, mean and median survival were, respectively, 12.5(3.4) and 5.6: 95% CI [3.7, 7.6] months, which was not statistically significantly different from the photodynamic therapy group. CONCLUSIONS: Photodynamic therapy with consecutive biliary drainage by insertion of a self-expandable metal stent is feasible. With respect to the small benefit in overall survival, randomized controlled trials are warranted.