Paradigm Shift in the Surveillance and Management of Dysplasia in Inflammatory Bowel Disease (West).

Patients with long-standing inflammatory bowel disease (IBD) colitis have a 2.4-fold higher risk of developing colorectal cancer (CRC) than the general population, for both ulcerative colitis (UC) and Crohn's disease (CD) colitis. Surveillance colonoscopy is recommended to detect early CRC and dysplasia. Most dysplasia discovered in patients with IBD is actually visible. Recently published SCENIC (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations) consensus statements provide unifying recommendations for the optimal surveillance and management of dysplasia in IBD. SCENIC followed the prescribed processes for guideline development from the Institute of Medicine (USA), including systematic reviews, full synthesis of evidence and deliberations by panelists, and incorporation of the GRADE methodology. The new surveillance paradigm involves high-quality visual inspection of the mucosa, using chromoendoscopy and high-definition colonoscopy, with endoscopic recognition of colorectal dysplasia. Lesions are described according to a new classification, which replaces the term 'dysplasia associated lesion or mass (DALM)' and its derivatives. Targeted biopsies are subsequently done on areas suspicious for dysplasia, and resections are carried out for discrete, resectable lesions.

Phase I evaluation of TNFerade biologic plus chemoradiotherapy before esophagectomy for locally advanced resectable esophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by surgery is the primary treatment option for patients with locally advanced esophageal cancer. This multicenter phase I trial examined intratumoral injection of TNFerade biologic, an adenoviral vector that expresses the human tumor necrosis factor-α gene, with chemoradiotherapy in locally advanced esophageal cancer. OBJECTIVES: To assess pathologic complete response (pCR), time to disease progression, progression-free survival, survival, and safety and tolerance in patients treated with preoperative chemoradiation combined with endoscopy or EUS-guided intratumoral injection of TNFerade biologic. DESIGN/INTERVENTION: Five weekly injections of TNFerade biologic, dose-escalated logarithmically from 4 × 10(8) to 4 × 10(11) particle units (PU), were given in combination with cisplatin 75 mg/m(2) and intravenous 5-fluorouracil 1000 mg/m(2)/d for 96 hours on days 1 and 29, and concurrent radiation therapy to 45 Gy. Surgery was performed 9 to 15 weeks after treatment. SETTING: U.S. multicenter study. PATIENTS: Patients with stage II and III esophageal cancer were enrolled. MAIN OUTCOME MEASUREMENTS: Primary outcome measures were safety, feasibility, tolerability, and rate of pCR. Secondary outcome measures were overall survival (OS) and disease-free survival. RESULTS: Twenty-four patients with a median age of 61 years were enrolled; 88% of the patients were men, 21% were stage II, and 79% were stage III. Six (29%) had a pCR, observed among 21 patients (20 who underwent esophagectomy and 1 at autopsy). Dose-limiting toxicities were not observed. The most frequent potentially related adverse events were fatigue (54%), fever (38%), nausea (29%), vomiting (21%), esophagitis (21%), and chills (21%). At the top dose of 4 × 10(11) PU, thromboembolic events developed in 5 of 8 patients. The median OS was 47.8 months. The 3- and 5-year OS rates and disease-free survival rates were 54% and 41% and 38% and 38%, respectively. LIMITATIONS: We included primarily adenocarcinoma. CONCLUSIONS: Preoperative TNFerade, in combination with chemoradiotherapy, is active and safe at doses up to 4 × 10(10) PU and is associated with long survival. This regimen warrants additional studies.