Vegetal diamine oxidase alleviates histamine-induced contraction of colonic muscles

Excess of histamine in gut lumen generates a pronounced gastrointestinal discomfort, which may include diarrhea and peristalsis dysfunctions. Deleterious effects of histamine can be alleviated with antihistamine drugs targeting histamine receptors. However, many antihistamine agents come with various undesirable side effects. Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Mammalian intestinal mucosa contains an endogenous DAO, yet possessing lower activity compared to that of vDAO preparation. Moreover, in several pathological conditions such as inflammatory bowel disease and irritable bowel syndrome, this endogenous DAO enzyme can be lost or inactivated. Here, we tested the therapeutic potential of vDAO by focusing on the well-known effect of histamine on gut motility. Using ex vivo and in vitro assays, we found that vDAO is more potent than commercial anti-histamine drugs at inhibiting histamine-induced contraction of murine distal colon muscles. We also identified pyridoxal 5′-phosphate (the biologically active form of vitamin B6) as an effective enhancer of vDAO antispasmodic activity. Furthermore, we discovered that rectally administered vDAO can be retained on gut mucosa and remain active. These observations make administration of vDAO in the gut lumen a valid alternative treatment for histamine-induced intestinal dysfunctions

Laparoscopic conversion in colorectal cancer surgery; is there any improvement over time at a population level?

Conversion of laparoscopic colorectal cancer resection has been associated with worse outcome, but this might have been related to a learning curve effect. This study aimed to evaluate incidence, predictive factors and outcomes of laparoscopic conversion after the implementation phase of laparoscopic surgery at a population level. Patients undergoing elective resection of non-locally advanced, non-metastatic colorectal cancer between 2011 and 2015 were included. Data were extracted from the Dutch Surgical Colorectal Audit. Patients were grouped as laparoscopic completed (LR), laparoscopic converted (CONV) with further specification of timing (within or after 30 min) as registered in the DSCA, and open resection (OR). Uni- and multi-variate analyses were used to determine predictors of conversion and outcome (complicated course and mortality), with evaluation of trends over time. A total of 23,044 patients with colon cancer and 11,324 with rectal cancer were included. Between 2011 and 2015, use of laparoscopy increased from 55 to 84% in colon cancer, and from 49 to 89% in rectal cancer. Conversion rates decreased from 11.8 to 8.6% and from 13 to 8.0%, respectively. Laparoscopic hospital volume was independently associated with conversion rate. Only for colon cancer, the rate of complicated course was significantly higher after CONV compared to OR (adjusted odds ratio 1.486; 95% CI 1.298-1.702), and significantly higher after late (> 30 min) compared to early conversion (adjusted odds ratio 1.341; 1.046-1.719). There was no impact of CONV on mortality in both colon and rectal cancer. The use of laparoscopic colorectal cancer surgery increased to more than 80% at a national level, accompanied by a decrease in conversion which is significantly related to the laparoscopic hospital volume. Conversion was only associated with complicated course in colon cancer, especially when the reason for conversion consisted of an intra-operative complication, without affecting mortalit

Definition of the Rectum: An International, Expert-based Delphi Consensus

Mini: A radiological, anatomic distinction between the rectum and sigmoid colon was agreed by consensus of international experts in rectal cancer using the Delphi Technique. Use of this landmark, “the sigmoid take-off,” may harmonize efforts in research and clinical practice to improve patient outcomes. Background: The wide global variation in the definition of the rectum has led to significant inconsistencies in trial recruitment, clinical management, and outcomes. Surgical technique and use of preoperative treatment for a cancer of the rectum and sigmoid colon are radically different and dependent on the local definitions employed by the clinical team. A consensus definition of the rectum is needed to standardise treatment. Methods: The consensus was conducted using the Delphi technique with multidisciplinary colorectal experts from October, 2017 to April, 2018. Results: Eleven different definitions for the rectum were used by participants in the consensus. Magnetic resonance imaging (MRI) was the most frequent modality used to define the rectum (67%), and the preferred modality for 72% of participants. The most agreed consensus landmark (56%) was “the sigmoid take-off,” an anatomic, image-based definition of the junction of the mesorectum and mesocolon. In the second round, 81% of participants agreed that the sigmoid take-off as seen on computed tomography or MRI achieved consensus, and that it could be implemented in their institution. Also, 87% were satisfied with the sigmoid take-off as the consensus landmark. Conclusion: An international consensus definition for the rectum is the point of the sigmoid take-off as visualized on imaging. The sigmoid take-off can be identified as the mesocolon elongates as the ventral and horizontal course of the sigmoid on axial and sagittal views respectively on cross-sectional imaging. Routine application of this landmark during multidisciplinary team discussion for all patients will enable greater consistency in tumour localisation

International evaluation of circumferential resection margins after rectal cancer resection: insights from the Swedish and Dutch audits

Aim: This study aimed to determine predictive factors for the circumferential resection margin (CRM) within two northern European countries with supposed similarity in providing rectal cancer care. Method: Data for all patients undergoing rectal resection for clinical tumour node metastasis (TNM) stage I–III rectal cancer were extracted from the Swedish ColoRectal Cancer Registry and the Dutch ColoRectal Audit (2011–2015). Separate analyses were performed for cT1–3 and cT4 stage. Predictive factors for the CRM were determined using univariable and multivariable logistic regression analyses. Results: A total of 6444 Swedish and 12 089 Dutch patients were analysed. Over time the number of hospitals treating rectal cancer decreased from 52 to 42 in Sweden, and 82 to 79 in the Netherlands. In the Swedish population, proportions of cT4 stage (17% vs 8%), multivisceral resection (14% vs 7%) and abdominoperineal excision (APR) (37% vs 31%) were higher. The overall proportion of patients with a positive CRM (CRM+) was 7.8% in Sweden and 5.4% in the Netherlands. In both populations with cT1–3 stage disease, common independent risk factors for CRM+ were cT3, APR and multivisceral resection. No common risk factors for CRM+ in cT4 stage disease were found. An independent impact of hospital volume on CRM+ could be demonstrated for the cT1–3 Dutch population. Conclusion: Within two northern European countries with implemented clinical auditing, rectal cancer care might potentially be improved by further optimizing the treatment of distal and locally advanced rectal cancer

International evaluation of circumferential resection margins after rectal cancer resection: insights from the Swedish and Dutch audits

Aim: This study aimed to determine predictive factors for the circumferential resection margin (CRM) within two northern European countries with supposed similarity in providing rectal cancer care. Method: Data for all patients undergoing rectal resection for clinical tumour node metastasis (TNM) stage I–III rectal cancer were extracted from the Swedish ColoRectal Cancer Registry and the Dutch ColoRectal Audit (2011–2015). Separate analyses were performed for cT1–3 and cT4 stage. Predictive factors for the CRM were determined using univariable and multivariable logistic regression analyses. Results: A total of 6444 Swedish and 12 089 Dutch patients were analysed. Over time the number of hospitals treating rectal cancer decreased from 52 to 42 in Sweden, and 82 to 79 in the Netherlands. In the Swedish population, proportions of cT4 stage (17% vs 8%), multivisceral resection (14% vs 7%) and abdominoperineal excision (APR) (37% vs 31%) were higher. The overall proportion of patients with a positive CRM (CRM+) was 7.8% in Sweden and 5.4% in the Netherlands. In both populations with cT1–3 stage disease, common independent risk factors for CRM+ were cT3, APR and multivisceral resection. No common risk factors for CRM+ in cT4 stage disease were found. An independent impact of hospital volume on CRM+ could be demonstrated for the cT1–3 Dutch population. Conclusion: Within two northern European countries with implemented clinical auditing, rectal cancer care might potentially be improved by further optimizing the treatment of distal and locally advanced rectal cancer

Nationwide analysis of hospital variation in preoperative radiotherapy use for rectal cancer following guideline revision

Introduction: The revised Dutch colorectal cancer guideline (2014), led to an overall decrease in preoperative radiotherapy (RT) use. This study evaluates hospital variation in RT use for resectable rectal cancer and the influence of guideline revision, including the nationwide impact of changing RT application on short term outcomes. Methods: Data of surgically resected rectal cancer patients registered in the Dutch ColoRectal Audit were extracted between 2011 and 2017. Patients were divided into groups based on time of guideline revision (<2014 and ≥ 2014). Primary outcome was guideline adherence at hospital level regarding RT application, stratified for three stage groups. Secondary outcomes included positive circumferential resection (CRM+) and 30-day complicated postoperative course. Results: The groups consisted of 7364 and 12,057 patients, respectively. In total, 6772 patients did not receive RT (17.6% (<2014) vs. 45.7% (≥2014), p < 0.001). The largest increase of surgery alone was observed for cT1-2N0 stage rectal cancer (35.1% vs. 91.8%, p < 0.001), with a substantial decrease in hospital variation (IQR 22.2–50.0% vs. IQR 87.6–98.0%). For cT1-3N1MRF- stage rectal cancer, a substantial amount of hospital variation in short course RT remained after guideline revision (IQR 26.8–54.1% vs. IQR 26.2–50.0%). A significant decrease in CRM+ (5.8% vs. 4.2%, p < 0.001) and complicated course (22.5% vs. 18.5%, p < 0.001) was observed. Conclusions: Radiotherapy for early-stage rectal cancer was uniformly abandoned after guideline revision, while substantial hospital variation remained for intermediate risk resectable rectal cancer in the Netherlands. The substantial nationwide decrease in the use of RT for rectal cancer treatment did not negatively impact CRM involvement