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G A A b st ra ct s 1 year of BE diagnosis in THIN and histology report confirmation in IPCI. Age-and sexspecific incidence rates (IRs) were calculated for both BE and EAC. IRs were also calculated in relation to the total number of upper GI endoscopies. Survival analysis was used to evaluate EAC-free survival since incident BE diagnosis. Results: From the study population of 6,885,420 subjects in UK we identified 12,312 incident BE and subsequent 40 (0.3%) incident EAC cases. Among 1,487,191 subjects in NL 1,383 incident BE and 5 (0.4%) incident EAC cases occurred. The IR of BE increased linearly with age: IR was 15.6/100,000 PYs (UK) and 23.7/100,000 PYs (NL) for patients aged 40-44 years, increasing to 85.6/ 100,000 PYs (UK) and 87.0/100,000 PYs (NL) for 70-74 years. In both UK and NL, the IR of BE was 2-4 times higher in males than females across all age groups. With respect to calendar time, the IR of BE increased by 35% (UK) and 41% (NL) from 2000 to 2003, after which IRs remained stable until 2012. Sensitivity analysis with different case definitions did not yield major differences; THIN; overall IR decreased from 27.7/100,000 PYs to 26.0/ 100,000 PYs, and IPCI: overall IR decreased from 31.4/100,000 PYs to 15.2/100,000 PYs. In UK, the IR of BE per 1,000 upper GI endoscopies increased from 29.1 in 2000 up to 38.5 in 2011. In NL the IR of BE increased from 24.0/1,000 upper GI endoscopies in 2000 to 30.3/1,000 in 2002 and decreased thereafter up to 11.4/1,000 endoscopies in 2012. The one-year risk of EAC was 0.086% (95% CI: 0.04-0.17) overall, 0.11% (95% CI: 0.05-0.23) for males and 0.06% (95% CI: 0.02-0.24) for females. Male subjects had a higher risk of EAC development than females (Log-rank p=0.0027). Conclusion: Incidence rates of BE in the UK and NL increased until 2003, but have remained stable thereafter. Around 0.3% of patients with BE developed EAC at least one year after BE diagnosis, yielding a one-year risk of EAC of 0.09%. IRs of both BE and EAC increase with advancing age, particularly in males aged >65 years. Male subjects were at higher risk to develop EAC. These findings may help tailor endoscopic surveillance strategies among patients with BE.

Background: Helicobacter pylori (H.pylori) infection plays an important role in gastric carcinogenesis and exemplifies the strong association between inflammation and cancer. DARPP-32 (Dopamine and cAMP-regulated phosphoprotein, Mr 32000) is a novel cancer gene. The aim of this study was to investigate the role of inflammation and H.pylori in regulating DARPP-32 expression. Methods: Immunohistochemistry (IHC) were used to determine protein expression. DARPP-32 promoter activity was measured by a luciferase reporter system. The mRNA and protein levels were evaluated by quantitative real-time PCR and Western blot analysis. Results: The IHC analysis demonstrated overexpression of p-NFκB and DARPP-32 in the early stages of human gastric cancer. Therefore, we examined the relationship between NF-kB and DARPP-32, and found that DARPP-32 does not regulate the transcriptional activity of NF-κB as measured by pNF-κB luciferase reporter and western blot analysis. On the other hand, we found that TNF-α treatment leads to activation of NFκB and mediates upregulation of mRNA and protein levels of DARPP-32 in several gastric cancer cell lines (P 10-fold, P

Background: Recently a new anus-preserving operation of intersphincteric resection (ISR) has been introduced for very low rectal cancer. Here, we have clinically analyzed the oncologic and functional outcomes of ISR to prove the validity of the new operative procedure. Patients and Methods: Since 1982, a total of 206 patients received abdominoperineal resection (APR). We have histologically evaluated the tumor spread in very low rectal cancer treated with APR to clarify the potential indication of ISR with or without external sphincter muscle resection (ESR). Then, ISR has been performed in 83 patients based on the histologic theory since 2000. Histologic results: When the lowest edge of a tumor was located above the dentate line (defined as Pa cancer), the invasion and/or metastasis was rarely beyond the internal sphincter muscle. When the lowest edge was located at or below the dentate line (defined as Pb cancer), invasion and/or metastasis tended to extend into the levator muscle (29%), intersphincteric space (43%), external sphincter muscles (20%) and into the intermuscular groove (21%). Clinical results: Preoperative chemoradiation therapy was not performed. ISR was performed in 44 (68%) of 65 patients with Pa cancer and ESR, in 32%. In 18 patients with Pb cancer, ESR was performed in 61% and ISR, 39% (p=0.0514). Morbidity developed in 24% including anastomotic leakage (4.8%), colonic necrosis (2.4%), ileus (2.4%), and others. Curative operation was accomplished in 80 patients. There were 21 patients with Stage 0-1, 29 patients with Stage 2, and 24 patients with Stage 3. Radial margin (RM) < 1 mm was found in 9 (11%). Total recurrence rate was 20%. Distant metastasis developed in 10%. Local recurrence including pelvic node metastasis developed in 12.5% with no significant difference between ISR and ESR patients. Multivariate Cox regression analysis showed that RM < 1 mm was the most powerful independent risk factor of local recurrence (HR:10.057, 95%CI:2.274-44.476, p=0.0023). Both recurrence-free and cancer-specific 5-year survivals showed no significant difference between ISR and ESR patients (72% vs 82%, p=0.3412, 86% vs 96%, p=0.2051). Anal function showed good continence (Wexner score < 6, Kirwan grade 1-2,) in 60-70% of ISR patients and in 4050% of ESR patients. Multivariate logistic regression analysis showed that the resected volume of external sphincter muscles was the most powerful independent adverse factor affecting anal function. Conclusion: Both ISR and ESRwere acceptable techniques of anus-preservation for very low rectal cancer. However, appropriate preoperative treatments including neoadjuvant chemotherapy are necessary before operation to keep RM safe and to control local recurrence. Some ideal procedures are required to improve anal function.