Phase 1/2a, dose-escalation, safety, pharmacokinetic and preliminary efficacy study of intratumoral administration of BC-819 in patients with unresectable pancreatic cancer.

BC-819 is a DNA plasmid that was developed to target the expression of diphtheria-toxin gene under the control of H19 regulatory sequences. BC-819 has the potential to treat pancreatic cancer that overexpresses the H19 gene. The objectives were to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of BC-819 administered intratumorally in subjects with unresectable, locally advanced, non-metastatic pancreatic cancer. Nine patients with unresectable pancreatic adenocarcinoma were enrolled in an open-label, dose-escalation trial. Subjects were entered into one out of two cohorts with escalating doses of BC-819. Each cohort received 2 weeks of twice weekly intratumoral injection of BC-819 under computerized tomography (CT) (n = 3) or endoscopic ultrasound (EUS) (n = 6) guidance. Patients were assessed by CT or positron emission tomography (PET)/CT during week 4 for tumor response. The maximum tolerated dose of BC-819 was not reached in this study at the highest dose. Asymptomatic elevation of lipase, which was considered as an adverse event with dose-limiting toxicity, occurred in only one subject in the high-dose group and was resolved spontaneously. The tumors did not increase in size 4 weeks after initiating treatment. Two weeks after completing the treatment, the two subjects who went on to receive subsequent chemotherapy or chemoradiation therapy, pancreatic tumors were downstaged and considered surgically resectable. Remarkably, three of the six subjects in cohort no. 2 evaluated at month 3 had a partial response. BC-819 can be safely administered intratumorally via EUS- or CT-guided injection at a dose of at least 8 mg per injection weekly twice. BC-819 given locally in combination with systemic chemotherapy may provide an additional therapeutic benefit for the treatment of pancreatic cancer.

Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy.

BACKGROUND AND STUDY AIMS: A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. PATIENTS AND METHODS: In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. RESULTS: 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). CONCLUSIONS: The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Retroperitoneal perforation during endoscopic sphincterotomy: imaging findings.

BACKGROUND: Endoscopic retrograde cholangiopancreatography with sphincterotomy has become an important technique in the diagnosis and treatment of biliary and pancreatic diseases. Serious complications, although rare, may occur, and their early recognition and treatment are of the utmost importance. We encountered several such cases. This study reviews the imaging findings in patients with retroperitoneal perforation detected after the procedure. METHODS: Of 796 patients who had endoscopic sphincterotomy at our institution during a 9-year period, retroperitoneal perforation occurred in nine (1.13%). Imaging findings and clinical outcome were assessed. RESULTS: In eight patients, routine abdominal radiographs taken during the procedure disclosed retroperitoneal air, associated with extravasation of contrast material in six patients. This was further confirmed on computed tomography (CT) in three patients. In the ninth patient, the diagnosis was established by an emergent abdominal CT performed a day after the sphincterotomy, because of severe abdominal pain. Two patients died of overwhelming sepsis. CONCLUSIONS: Retroperitoneal perforation during endoscopic sphincterotomy is a rare complication, which occurred in 1.13% of our patients. It can be usually clearly recognized radiographically by an abdominal film and in doubtful cases by CT. We emphasize the importance of recognizing this potentially serious complication with imaging studies.

Budesonide versus prednisone in the treatment of active Crohn's disease. The Israeli Budesonide Study Group.

BACKGROUND & AIMS: Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohn's disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon. METHODS: Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded. RESULTS: One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohn's Disease Activity Index of <150 at completion was 51% and 52.5% for the BUD and PRED groups, respectively. Twice as many responded to treatment with no side effects in the BUD compared with the PRED group (30% vs. 14%) (P = 0.006). Most of the decrease in CDAI scores occurred during the first 2 weeks. CONCLUSIONS: BUD is as effective as PRED in the treatment of CD involving the terminal ileum and right colon. BUD has significantly fewer steroid-related adverse reactions.

Tolerability of iron: a comparison of bis-glycino iron II and ferrous sulfate.

The tolerability of supplemental iron in the chelated form of bis-glycino iron II was compared with that of ferrous sulfate in a randomized, double-blind, cross-over trial. Both iron formulations were prepared to deliver 50 mg elemental iron in each capsule; the capsules for both formulations were identical in appearance and weight. Each supplement was taken once daily before breakfast for two weeks. The incidence and severity of adverse side effects were not statistically different for the two preparations. However, of the 38 women evaluated, 14 (37%) experienced moderate-to-severe side effects only while taking the sulfate formulation compared to eight (21%) who experienced similar side effects only while taking the chelate formulation; the remaining 16 women had the same symptom profile with both preparations. This tendency for the chelate to be better tolerated was observed for the symptoms of bloating, constipation, and nausea. In addition, a significant (P less than 0.05) number of women preferred the chelate to the sulfate formulation. This preference appeared to be related to the lower number of side effects experienced with the chelate.

Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn's disease and intestinal resection.

We compared the intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with Crohn's disease and resections of the small bowel. Patients were subgrouped into those with small (less than 100 cm), intermediate (100-300 cm), and large (greater than 300 cm) resections. [3H]cholecalciferol or [3H]25-hydroxycholecalciferol were given orally and serial blood samples were taken for measurement of plasma radiolabeled vitamin. Absorption of both forms of the vitamin decreased with extent of resection but 25-hydroxycholecalciferol absorption was always greater than that of cholecalciferol. When compared with normal control subjects, 25-hydroxycholecalciferol absorption in these patients was better maintained than that of cholecalciferol. These data indicate that vitamin D malabsorption reflects the extent of distal small-bowel resection in Crohn's disease. Treatment with oral cholecalciferol is sufficient in those with small or moderate resections but oral 25-hydroxycholecalciferol supplementation may be preferred in those with a severe short-bowel syndrome.

Two point analysis 15-minute 14C-urea breath test for diagnosing Helicobacter pylori infection.

The value of a two point analysis (double sample) 14C-urea breath test in diagnosing Helicobacter pylori (HP) infection in patients with suspected acid peptic disease has been studied and compared to histology and to a rapid agar plate urease test in 76 patients. Using the histological finding of HP as the gold standard, the 14C-breath test was positive in 59 of the 61 histologically confirmed infected patients and in 3 of the 15 noninfected ones, giving a sensitivity of 97% and specificity of 80%. In 12 patients, a smaller dose of 3 mu Ci 14C-urea was used. The results correlated well with those in whom the higher dose of 10 mu Ci was used. We conclude that a two point 14C-urea breath test with analysis at 5 and 15 min is effective in diagnosing HP infection thus obviating the need for endoscopy and biopsy.

Endoscopic treatment of suture line bleeding ulcer caused by nonabsorbable suture material in postvagotomy patients.

Two postvagotomy patients with upper gastrointestinal bleeding, which appeared several months after operation, are reported. Endoscopy showed the pyloroplasty suture line to be ulcerated and bleeding, with a few strands of silk protruding from edematous mucosa. The history of suture line ulceration and the contribution of endoscopy to its diagnosis and treatment are reviewed.

[Instrumental dilatation of esophageal and gastric stenoses using Gruntzig's catheter and Celestin's dilator. Preliminary results]. / Dilatation instrumentale des sténoses oesophagiennes et gastriques à l'aide du cathéter de Grüntzig et du dilatateur de Celestin. Résultats préliminaires.

The aim of this study was to present the technique of endoscopic dilatation and the preliminary results obtained with 2 new instruments, the Grüntzig balloon catheter, and the Celestin dilator, in patients with esophageal or gastric strictures. The Grüntzig balloon catheter was used 11 times in 7 patients (6 adults and one child aged 1 1/2 year), for the dilatation of severe or irregular strictures of the esophagus (5 cases), the stomach (1 case) and the pylorus (1 case). Partial (4 cases) or complete relief (2) were observed and allowed subsequent use of the Celestin bougies (2 cases), or the introduction of an esophageal prosthesis (1 case). In the child with caustic stricture of the esophagus, dilatation with the Grüntzig balloon-catheter was complicated twice by perforation. In the second case, the perforation was related to the technique used in dilatation and was treated by conservation measures. Endoscopic dilatations with the Celestin bougies were performed in 27 patients with benign (including 9 peptic strictures) or malignant strictures (14 cases, 7 related to esophageal cancer, and 7 to cancer of the cardia). A total of 74 dilatations were performed, attaining a maximum diameter of 16 or 18 mm in one session, in 21 patients (78 p. 100 of the cases). In the case of peptic stricture, the anatomical result was excellent in 8 patients and the functional result good in 7 of 9 cases. In case of malignant stricture, the result was conditioned by the evolution of the tumor; recurrence of dysphagia called for either repeated dilatations (8 cases) or the introduction of an esophageal prosthesis (5 cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Collagenous colitis. Report of a case.

A 50-year-old woman presented with a long history of nausea, abdominal pain, weight loss, and intermittent watery diarrhea. All investigations were negative except for the finding, on five separate colonoscopic biopsies, of a layer of band-like collagen beneath the surface epithelium, diagnostic of collagenous colitis.

[Conn's adenoma after prolonged treatment with estro-progestins. 2 cases]. / Adénomes de Conn après prise prolongée d'estro-progestatifs. 2 observations.

PIP: As it appears from the 2 cases presented in this brief article hypertension caused by OC (oral contraception) does not necessarily regress after interruption of treatment. Such observation brings the authors to discuss the hypothesis of a relationship between OC and Conn adenoma caused by hyperaldosteronism after prolonged use of oral contraception.^ieng