BACKGROUND: Changes in the treatment of rectal cancer during the past decades have led to an increase in sphincter preservation with a consecutive decline in abdominoperineal resection rates. OBJECTIVE: The aim of this study was to analyze the cumulative incidence of permanent stoma in patients undergoing sphincter-preserving resection of mid and low rectal cancer. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a tertiary referral cancer hospital. PATIENTS: From 2003 to 2010, 125 patients with primary mid and low rectal cancer who underwent sphincter-preserving low anterior resection were included. MAIN OUTCOME MEASURES: The occurrence of a permanent stoma over time was investigated by using a Cox proportional hazards regression model and competing-risk models, with death as a competing risk. The risk factors were assessed by computing HRs and a Cox proportional hazards regression. RESULTS: After a median follow-up time of 61 months (range, 22–113), 15 of 125 patients ended up with a permanent stoma, accounting for a 5-year cumulative incidence of 6% (95% CI, 4%–11%). The reasons for obtaining a permanent stoma were anastomotic leakage (60%, 9/15), intractable fecal incontinence (27%, 4/15), and local recurrence (13%, 2/15). The Cox proportional hazards regression identified anastomotic leakage (HR, 6.10; 95% CI, 2.23–16.71; p = 0.0004) and coloanal anastomosis (HR, 4.31; 95% CI, 1.49–12.47; p = 0.007) as statistically significant risk factors. LIMITATIONS: Because of the small number of events in this sample, further investigations with a larger number of patients are required. Fecal incontinence was assessed by patient self-reported data without the use of a validated score. CONCLUSION: The 5-year cumulative incidence of a permanent stoma was 6%. Anastomotic leakage and coloanal anastomosis were identified as risk factors. These details should be considered before sphincter-preserving surgery.
Background: There is a rapidly growing literature available on right hemicolectomy comparing the short- and long-term outcomes of robotic right colectomy (RRC) to that of laparoscopic right colectomy (LRC). The aim of this meta-analysis is to revise current comparative literature systematically. Methods: A systematic review of comparative studies published between 2000 to 2021 in PubMed, Scopus and Embase was performed. The primary endpoint was postoperative morbidity, mortality and long-term oncological results. Secondary endpoints consist of blood loss, conversion rates, complications, time to first flatus, hospital stay and incisional hernia rate. Results: 25 of 322 studies were considered for data extraction. A total of 16,099 individual patients who underwent RRC (n = 1842) or LRC (n = 14,257) between 2002 and 2020 were identified. Operative time was significantly shorter in the LRC group (LRC 165.31 min ± 43.08 vs. RRC 207.38 min ± 189.13, MD: −42.01 (95% CI: −51.06−32.96), p < 0.001). Blood loss was significantly lower in the RRC group (LRC 63.57 ± 35.21 vs. RRC 53.62 ± 34.02, MD: 10.03 (95% CI: 1.61–18.45), p = 0.02) as well as conversion rate (LRC 1155/11,629 vs. RRC 94/1534, OR: 1.65 (1.28–2.13), p < 0.001) and hospital stay (LRC 6.15 ± 31.77 vs. RRC 5.31 ± 1.65, MD: 0.84 (95% CI: 0.29–1.38), p = 0.003). Oncological long-term results did not differ between both groups. Conclusion: The advantages of robotic colorectal procedures were clearly demonstrated. RRC can be regarded as safe and feasible. Most of the included studies were retrospective with a limited level of evidence. Further randomized trials would be suitable.
Histone deacetylases (HDACs) play a key role in epigenetic mechanisms in health and disease and their dysfunction is implied in several cancer entities. Analysis of expression patterns in pancreatic neuroendocrine tumors (pNETs) indicated HDAC5 to be a potential target for future therapies. As a first step towards a possible treatment, the aim of this study was to evaluate the in vitro cellular and molecular effects of HDAC5 inhibition in pNET cells. Two pNET cell lines, BON-1 and QGP-1, were incubated with different concentrations of the selective class IIA HDAC inhibitor, LMK-235. Effects on cell viability were determined using the resazurin-assay, the caspase-assay, and Annexin-V staining. Western Blot and immunofluorescence microscopy were performed to assess the effects on HDAC5 functionality. LMK-235 lowered overall cell viability by inducing apoptosis in a dose- and time-dependent manner. Furthermore, acetylation of histone-H3 increased with higher LMK-235 concentrations, indicating functional inhibition of HDAC4/5. Immunocytochemical analysis showed that proliferative activity (phosphohistone H3 and Ki-67) decreased at highest concentrations of LMK-235 while chromogranin and somatostatin receptor 2 (SSTR2) expression increased in a dose-dependent manner. HDAC5 expression was found to be largely unaffected by LMK-235. These findings indicate LMK-235 to be a potential therapeutic approach for the development of an effective and selective pNET treatment.