Using a retroviral vector system we have established derivatives of the E8 subclone of the human colon cancer cell line SW480 that stably overproduce a full-length rat cDNA encoding the beta 1 isoform of protein kinase C (PKC beta 1). In contrast to vectrol control cells, when treated with the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), the overexpressing cell lines displayed a striking increase in doubling time, and a decrease in saturation density. Western blot analysis indicated that treatment with TPA was also associated with translocation and partial downregulation of the exogenous PKC beta 1 in the over-expressor cell lines. These results extend previous evidence that PKC beta 1 can inhibit the growth of the HT29 human colon cancer cell line. The HT29 cells have a normal c-k-ras oncogene but the SW480 cells used in the present study have an activating mutation in this oncogene. Thus PKC beta 1 can function as a suppressor in both types of colon cancer cells.
Background and study aims Little is known about outcomes of advanced endoscopic resection (ER) for patients with inflammatory bowel disease (IBD) with dysplasia. The aim of our meta-analysis was to estimate the safety and efficacy of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for dysplastic lesions in patients with IBD. Methods We performed a systematic review through Jan 2021 to identify studies of IBD with dysplasia that was treated by EMR or ESD. We estimated the pooled rates of complete ER, adverse events, post-ER surgery, and recurrence. Proportions were pooled by random effect models. Results Eleven studies including 506 patients and 610 lesions were included. Mean lesion size was 23 mm. The pooled rate of complete ER was 97.9 % (95 % confidence interval [CI]: 95.3 % to 99.7 %). The pooled rate of endoscopic perforation was 0.8 % (95 % CI:0.1 % to 2.2 %) while bleeding occurred in 1.6 % of patients (95 %CI:0.4 % to 3.3 %). Overall, 6.6 % of patients (95 %CI:3.6 % to 10.2 %) underwent surgery after an ER. Among 471 patients who underwent surveillance, local recurrence occurred in 4.9 % patients (95 % CI:1.0 % to 10.7 %) and metachronous lesions occurred in 7.4 % patients (95 %CI:1.5 % to 16 %) over a median follow-up of 33 months. Metachronous colorectal cancer (CRC) was detected in 0.2 % of patients (95 %CI:0 % to 2.2 %) during the surveillance period. Conclusions Advanced ER is safe and effective in the management of large dysplastic lesions in IBD and warrants consideration as first-line therapy. Although the risk of developing CRC after ER is low, meticulous endoscopic surveillance is crucial to monitor for local or metachronous recurrence of dysplasia.
Background and Aims The opioid epidemic has become increasingly concerning, with the ever-increasing prescribing of opioid medications in recent years, especially in inflammatory bowel disease [IBD] patients with chronic pain. We aimed to isolate the effect of opioid use disorder [OUD] on 30-day readmission risk after an IBD-related hospitalization. Methods We retrospectively extracted IBD-related adult hospitalizations and 30-day, any-cause, readmissions from the National Readmissions Database [period 2010–2014]. OUD and 30-day readmission trends were calculated. Conventional and exact-matched [EM] logistic regression and time-to-event analyses were conducted among patients who did not undergo surgery during the index hospitalization, to estimate the effect of OUD on 30-day readmission risk. Results In total, 487 728 cases were identified: 6633 [1.4%] had documented OUD And 308 845 patients [63.3%] had Crohn’s disease. Mean age was 44.8 ± 0.1 years, and 54.3% were women. Overall, 30-day readmission rate was 19.4% [n = 94,546], being higher in OUD patients [32.6% vs 19.2%; p < 0.001]. OUD cases have been increasing [1.1% to 1.7%; p-trend < 0.001], while 30-day readmission rates were stable [p-trend = 0.191]. In time-to-event EM analysis, OUD patients were 47% more likely (hazard ratio 1.47; 95% confidence interval [CI]:1.28–1.69; p < 0.001) to be readmitted, on average being readmitted 32% earlier [time ratio 0.68; 95% CI: 0.59–0.78; p < 0.001]. Conclusion OUD prevalence has been increasing in hospitalized IBD patients from 2010 to 2014. On average, one in five patients will be readmitted within 30 days, with up to one in three among the OUD subgroup. OUD is significantly associated with increased 30-day readmission risk in IBD patients and further measures relating to closer post-discharge outpatient follow-up and pain management should be considered to minimize 30-day readmission risk.
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