The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Fistula closure is achieved by using the anal fistula plug in approximately 54% of patients without Crohn's disease. The anal fistula plug has not been adequately evaluated in the Crohn's population.

The development of Barrett's epithelium is frequent after esophagectomy, is time-related, reflecting chronic acid and bile exposure, and is not specific for adenocarcinoma or the presence of previous Barrett's epithelium. This model may represent a useful in vivo model of the pathogenesis of Barrett's metaplasia and tumorigenesis.

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Background The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long‐course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6–8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. Methods A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8‐week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence‐free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta‐analysis was performed using the Mantel–Haenszel method. Results Twenty‐six publications, including four RCTs, with 25 445 patients were identified. A minimum 8‐week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). Conclusion A minimum 8‐week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence‐free survival without compromising surgical morbidity.

Objective:To examine the expression of the transcription factor nuclear factor kappa B (NF-B) in Barrett's epithelium and adenocarcinoma and the impact of NF-B expression on tumor stage and response to neoadjuvant chemotherapy and radiation therapy. Summary Background Data: Progression of Barrett's esophagus to adenocarcinoma is associated with a wide range of cellular and molecular abnormalities. Nuclear factor-kappa B (NF-B) regulates several genes involved in inflammatory, immune and apoptotic responses, but its role in esophageal inflammation and tumorigenesis has not been reported. Methods: Mobility shift assay was used to measure NF-B activity in nuclear extracts of fresh-frozen biopsies from tumor and uninvolved tissues (n ϭ 30) and esophageal cell lines OE33, SKGT-4, and OE21. RelA expression was assessed by immunohistochemical staining (n ϭ 97). The NF-B/RelA and IB protein expressions were also examined by Western blotting. Results: NF-B was not expressed in normal esophageal squamous epithelium, in contrast to increased expression in 40% of patients with Barrett's epithelium. Sixty-one percent of resected tumors (n ϭ 97) displayed NF-B immunoreactivity, and 87.5% of the NF-Bpositive tumors were Stage IIb and III compared with only 12.5% of patients with Stage I and IIa disease (P Ͻ 0.05). The expression of NF-B inversely correlated with major or complete pathologic responses to neoadjuvant chemotherapy and radiation therapy, with 15/20 (75%) responders in the NF-B-negative group compared with 7/38 (18%) in the NF-B-positive group (P Ͻ 0.00001). Moreover, incubation of esophageal cell lines OE33, SKGT-4, and OE21 with deoxycholic acid or low pH induced NF-B expression.

Ileorectal anastomosis is an appropriate operation for selected patients with Crohn's colitis with sparing of the rectum. However, patients must be counseled that the reoperation rate and/or proctectomy rate is approximately 30%.

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