Cancer prevention in ulcerative colitis: long-term outcome following fluorescence-guided colonoscopy.

BACKGROUND: Patients with long-standing ulcerative colitis require repeated endoscopies for early detection of neoplasias, which, however, are frequently missed by standard colonoscopy. Fluorescence-guided colonoscopy is known to improve the detection rate but the long-term effects of fluorescence-guided colonoscopy are unknown. METHODS: Colitis patients with negative findings at index fluorescence-guided colonoscopy entered a prospective long-term study with conventional colonoscopies at 2-year intervals. Risk and time to progression were evaluated. The positive predictive value was assessed in patients with neoplasias at index fluorescence-guided colonoscopy who underwent immediate total colectomy. RESULTS: Thirty-one patients with negative fluorescence-guided colonoscopy were surveyed for a mean of 7.8 ± 0.9 years. Neoplasia was observed in only two of them (6%) after 7 and 8 years of follow-up, respectively. Neoplasia at index fluorescence-guided colonoscopy was observed in 10 patients. In all of them, multiple flat low-grade intraepithelial neoplasia was diagnosed. At immediate colectomy performed in eight of them, the diagnosis of flat low-grade intraepithelial neoplasia was confirmed, corresponding to a positive predictive value of 100%. However, synchronous more advanced neoplasia was detected in three of the eight patients (38%). All patients, those with and those without neoplasia, were alive at the end of the study. CONCLUSIONS: Fluorescence-guided colonoscopy misses, in contrast to standard colonoscopy, few, if any, patients with neoplasia. Most neoplasia-negative patients remain negative during prolonged follow-up. However, when low-grade dysplasia is diagnosed by fluorescence-guided colonoscopy, colectomy is recommended because more than a third of the patients harbor synchronous, more advanced neoplasia.

Wireless capsule pH monitoring: does it fulfil all expectations?

pH monitoring has been used as a diagnostic tool in gastro-oesophageal reflux disease (GERD) for many years. Recent studies have shown that wireless capsule pH monitoring is better tolerated and interferes less with daily activities as compared to traditional catheter-based pH monitoring. Moreover, prolonged recording time (48 h instead of 24 h) is possible with wireless pH monitoring. The main secondary effect of wireless capsule pH monitoring is induction of thoracic discomfort in 10-65% of the patients, which can vary from mild foreign body sensation to severe chest pain. Sensitivity and specificity of wireless capsule monitoring is comparable to that of traditional pH monitoring. It has not been proven yet that better tolerability and a longer recording time increases the diagnostic yield of wireless capsule monitoring in GERD.

Reduced medication dependency and improved symptoms and quality of life 12 months after enteryx implantation for gastroesophageal reflux.

BACKGROUND: The need is well recognized for additional data on endoluminal therapies for gastroesophageal reflux disease (GERD). This prospective multicenter clinical trial was designed to assess safety and effectiveness of Enteryx, a nonresorbable copolymer implanted into the lower esophagus, in reducing usage of proton pump inhibitors (PPIs) and improving reflux symptoms and quality of life. METHODS: Enteryx implantation was performed under fluoroscopic visualization without general anesthesia in 93 patients with symptomatic GERD responsive to and relapsing upon cessation of PPI therapy. Subjective and objective data were collected up to 12 months postprocedure. The criterion for treatment success was reduction in PPI dosage of > or =50%. RESULTS: At 12 months, treatment success was attained in 86% (confidence interval, 77%-93%) of 74 evaluable patients and elimination of PPI therapy in 65% (confidence interval, 53%-76%). The treatment success rate by intent-to-treat analysis was 69% (confidence interval, 58%-78%). Reflux-related heartburn (P < 0.0001), regurgitation symptoms (P = 0.0005), and physical (P < 0.0001) and mental quality of life (P = 0.0012) scores improved. The most frequent complications were chest pain (77%), dysphagia/odynophagia (27%), and sensation of fever (26%). CONCLUSIONS: Enteryx implantation provides an effective and safe alternative for management of gastroesophageal reflux, reducing medication dependency and symptoms and enhancing quality of life.

Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study.

BACKGROUND & AIMS: In nonrandomized trials, photodynamic therapy (PDT) had a promising effect on nonresectable cholangiocarcinoma (NCC). This prospective, open-label, randomized, multicenter study with a group sequential design compared PDT in addition to stenting (group A) with stenting alone (group B) in patients with NCC. METHODS: In patients with histologically confirmed cholangiocarcinoma, endoscopic or percutaneous double stenting was performed. Patients fulfilling inclusion criteria were randomized to group A (stenting and subsequent PDT) and group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt was injected intravenously 2 days before intraluminal photoactivation (wavelength, 630 nm; light dose, 180 J/cm(2)). Further treatments were performed in cases of residual tumor in the bile duct. The primary outcome parameter was survival time. Secondary outcome parameters were cholestasis and quality of life. RESULTS: PDT resulted in prolongation of survival (group A: n = 20, median 493 days; group B: n = 19, median 98 days; P < 0.0001). It also improved biliary drainage and quality of life. CONCLUSIONS: PDT, given in addition to best supportive care, improves survival in patients with NCC. The study was terminated prematurely because PDT proved to be so superior to simple stenting treatment that further randomization was deemed unethical.

Promoter methylation of INK4a/ARF as detected in bile-significance for the differential diagnosis in biliary disease.

PURPOSE: There is a need to enhance endobiliary cytotechniques by molecular marker lesions. This is of special significance for patients with primary sclerosing cholangitis, a disease predisposing for the development of cholangiocarcinoma. The INK4a/ADP ribosylation factor (ARF) locus encodes two tumor suppressor genes: p16INK4a and p14ARF. p16INK4a has been shown to be of major significance in cholangiocarcinoma. EXPERIMENTAL DESIGN: In an effort to evaluate the potential diagnostic role of p16INK4a and p14ARF promoter methylation in biliary disease, endoscopical obtained bile specimens of 71 patients were analyzed (26 choledocholithiasis, 6 with normal results, 23 bile duct carcinoma, 5 gall bladder carcinoma). Eleven patients with primary sclerosing cholangitis were enrolled. RESULTS: Merely 6% of specimens (2 of 32) obtained from patients without evidence for malignant biliary disease but 53.5% of malignancies (15 of 28) showed p16 promoter methylation (p14: 3 and 46.2%, respectively). The concordance of methylation rates detected in either bile or tissue specimens was high. In primary sclerosing cholangitis, a similar prevalence of methylation was detected as in malignant disease. CONCLUSIONS: This study demonstrates: (a) a high frequency and specificity of INK4a/ARF methylation in malignant biliary disease compared with mere cholangitis; and (b) the capability to detect these alterations reliably in endoscopically obtained bile. Thus, INK4a/ARF's promoter methylation status represents a candidate marker for the endoscopic diagnosis of biliary disease.

Mucosal flora in inflammatory bowel disease.

BACKGROUND & AIMS: Microorganisms that directly interact with the intestinal mucosa are obscured by fecal flora and poorly characterized. METHODS: We investigated the mucosal flora of washed colonoscopic biopsies of 305 patients with bowel inflammation and 40 controls. The microbial cultures were validated by quantitative polymerase chain reaction with subsequent cloning and sequencing, fluorescence in-situ hybridization, and electron microscopy. RESULTS: We found high concentrations of mucosal bacteria in patients with bowel inflammation, but not in controls. The concentrations of mucosal bacteria increased progressively with the severity of disease, both in inflamed and non-inflamed colon. In patients with >10,000 cfu/microL, a thick bacterial band was attached to the intact mucosa without signs of translocation. Patients with inflammatory bowel disease (IBD) and concentrations of mucosal bacteria >50,000 cfu/microL had characteristic inclusions of multiple polymorphic bacteria within solitary enterocytes located next to the lamina propria, without or having no contact with the fecal stream. The identified bacteria were of fecal origin. CONCLUSIONS: Our findings suggest that the changes in the mucosal flora in IBD are not secondary to inflammation, but a result of a specific host response. We hypothesize that the healthy mucosa is capable of holding back fecal bacteria and that this function is profoundly disturbed in patients with IBD.