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Background: Machine learning (ML) has been introduced in various fields of healthcare. In colorectal surgery, the role of ML has yet to be reported. In this systematic review, an overview of machine learning models predicting surgical outcomes after colorectal surgery is provided. Methods: Databases PubMed, EMBASE, Cochrane, and Web of Science were searched for studies using machine learning models for patients undergoing colorectal surgery. To be eligible for inclusion, studies needed to apply machine learning models for patients undergoing colorectal surgery. Absence of machine learning or colorectal surgery or studies reporting on reviews, children, study abstracts were excluded. The Probast risk of bias tool was used to evaluate the methodological quality of machine learning models. Results: A total of 1821 studies were analysed, resulting in the inclusion of 31 articles. A vast proportion of ML algorithms have been used to predict the course of disease and response to neoadjuvant chemoradiotherapy. Radiomics have been applied most frequently, along with predictive accuracies up to 91%. However, most studies included a retrospective study design without external validation or calibration. Conclusions: Machine learning models have shown promising potential in predicting surgical outcomes after colorectal surgery. However, large-scale data is warranted to bridge the gap between calibration and external validation. Clinical implementation is needed to demonstrate the contribution of ML within daily practice. [ABSTRACT FROM AUTHOR]

Purpose: Surgical approach to rectal cancer has evolved in recent decades, with introduction of minimally invasive surgery (MIS) techniques and local excision. Since implementation might differ internationally, this study is aimed at evaluating trends in surgical approach to rectal cancer across different countries over the last 10 years and to gain insight into patient, tumour and treatment characteristics. Methods: Pseudo-anonymised data of patients undergoing resection for rectal cancer between 2010 and 2019 were extracted from clinical audits in the Netherlands (NL), Sweden (SE), England-Wales (EW) and Australia-New Zealand (AZ). Results: Ninety-nine thousand five hundred ninety-seven patients were included (38,413 open, 55,155 MIS and 5416 local excision). An overall increase in MIS was observed from 29.9% in 2010 to 72.1% in 2019, with decreasing conversion rates (17.5–9.0%). The MIS proportion was highly variable between countries in the period 2010–2014 (54.4% NL, 45.3% EW, 39.8% AZ, 14.1% SE, P < 0.001), but variation reduced over time (2015–2019 78.8% NL, 66.3% EW, 64.3% AZ, 53.2% SE, P < 0.001). The proportion of local excision for the two periods was highly variable between countries: 4.7% and 11.8% in NL, 3.9% and 7.4% in EW, 4.7% and 4.6% in AZ, 6.0% and 2.9% in SE. Conclusions: Application and speed of implementation of MIS were highly variable between countries, but each registry demonstrated a significant increase over time. Local excision revealed inconsistent trends over time. [ABSTRACT FROM AUTHOR]

Purpose: Surgical approach to rectal cancer has evolved in recent decades, with introduction of minimally invasive surgery (MIS) techniques and local excision. Since implementation might differ internationally, this study is aimed at evaluating trends in surgical approach to rectal cancer across different countries over the last 10 years and to gain insight into patient, tumour and treatment characteristics. Methods: Pseudo-anonymised data of patients undergoing resection for rectal cancer between 2010 and 2019 were extracted from clinical audits in the Netherlands (NL), Sweden (SE), England-Wales (EW) and Australia-New Zealand (AZ). Results: Ninety-nine thousand five hundred ninety-seven patients were included (38,413 open, 55,155 MIS and 5416 local excision). An overall increase in MIS was observed from 29.9% in 2010 to 72.1% in 2019, with decreasing conversion rates (17.5–9.0%). The MIS proportion was highly variable between countries in the period 2010–2014 (54.4% NL, 45.3% EW, 39.8% AZ, 14.1% SE, P < 0.001), but variation reduced over time (2015–2019 78.8% NL, 66.3% EW, 64.3% AZ, 53.2% SE, P < 0.001). The proportion of local excision for the two periods was highly variable between countries: 4.7% and 11.8% in NL, 3.9% and 7.4% in EW, 4.7% and 4.6% in AZ, 6.0% and 2.9% in SE. Conclusions: Application and speed of implementation of MIS were highly variable between countries, but each registry demonstrated a significant increase over time. Local excision revealed inconsistent trends over time. [ABSTRACT FROM AUTHOR]

Aim Methods and Results Conclusions Recommendations for surveillance after colonoscopy are based on risk factors for metachronous advanced colorectal neoplasia (AN) and colorectal cancer (CRC). The value of these risk factors remains unclear in populations enriched by individuals with a positive faecal immunochemical test and were investigated in a modern setting.This population‐based cohort study included all individuals in the Netherlands of ≥55 years old with a first adenoma diagnosis in 2015. A total of 22,471 patients were included. Data were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were metachronous AN and CRC. Patient and polyp characteristics were evaluated by multivariable Cox regression analyses. During follow‐up, 2416 (10.8%) patients were diagnosed with AN, of which 557 (2.5% from the total population) were CRC. Adenomas with high‐grade dysplasia (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.40–1.83), villous histology (HR 1.91, 95% CI 1.59–2.28), size ≥10 mm (HR 1.12, 95% CI 1.02–1.23), proximal location (HR 1.12, 95% CI 1.02–1.23), two or more adenomas (HR 1.28, 95% CI 1.16–1.41), and serrated polyps ≥10 mm (HR 1.67, 95% CI 1.42–1.97) were independent risk factors for metachronous AN. In contrast, only adenomas with high‐grade dysplasia (HR 2.49, 95% CI 1.92–3.24) were an independent risk factor for metachronous CRC.Risk factors for metachronous AN and CRC were identified for populations with access to a faecal immunochemical test (FIT)‐based screening programme. If only risk factors for metachronous CRC are considered, a reduction in criteria for surveillance seems reasonable. [ABSTRACT FROM AUTHOR]

Background: Anastomotic leakage (AL) remains a burdensome complication following colorectal surgery, with increased morbidity, oncological compromise, and mortality. AL may impose a substantial financial burden on hospitals and society due to extensive resource utilization. Estimated costs associated with AL are important when exploring preventive measures and treatment strategies. The purpose of this study was to systematically review the existing literature on (socio)economic costs associated with AL after colorectal surgery, appraise their quality, compare reported outcomes, and identify knowledge gaps. Methods: Health economic evaluations reporting costs related to AL after colorectal surgery were identified through searching multiple online databases until June 2023. Pairs of reviewers independently evaluated the quality using an adapted version of the Consensus on Health Economic Criteria list. Extracted costs were converted to 2022 euros (€) and also adjusted for purchasing power disparities among countries. Results: From 1980 unique abstracts, 59 full-text publications were assessed for eligibility, and 17 studies were included in the review. The incremental costs of AL after correcting for purchasing power disparity ranged from €2250 (+39.9%, Romania) to €83,633 (+ 513.1%, Brazil). Incremental costs were mainly driven by hospital (re)admission, intensive care stay, and reinterventions. Only one study estimated the economic societal burden of AL between €1.9 and €6.1 million. Conclusions: AL imposes a significant financial burden on hospitals and social care systems. The magnitude of costs varies greatly across countries and data on the societal burden and non-medical costs are scarce. Adherence to international reporting standards is essential to understand international disparities and to externally validate reported cost estimates. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Literature on nationwide long‐term permanent stoma rates after rectal cancer resection in the minimally invasive era is scarce. The aim of this population‐based study was to provide more insight into the permanent stoma rate with interhospital variability (IHV) depending on surgical technique, with pelvic sepsis, unplanned reinterventions and readmissions as secondary outcomes.Patients who underwent open or minimally invasive resection of rectal cancer (lower border below the sigmoid take‐off) in 67 Dutch centres in 2016 were included in this cross‐sectional cohort study.Among 2530 patients, 1470 underwent a restorative resection (58%), 356 a Hartmann's procedure (14%, IHV 0%–42%) and 704 an abdominoperineal resection (28%, IHV 3%–60%). Median follow‐up was 51 months. The overall permanent stoma rate at last follow‐up was 50% (IHV 13%–79%) and the unintentional permanent stoma rate, permanent stoma after a restorative procedure or an unplanned Hartmann's procedure, was 11% (IHV 0%–29%). A total of 2165 patients (86%) underwent a minimally invasive resection: 1760 conventional (81%), 170 transanal (8%) and 235 robot‐assisted (11%). An anastomosis was created in 59%, 80% and 66%, with corresponding unintentional permanent stoma rates of 12%, 24% and 14% (p = 0.001), respectively. When corrected for age, American Society of Anesthesiologists classification, cTNM, distance to the anorectal junction and neoadjuvant (chemo)radiotherapy, the minimally invasive technique was not associated with an unintended permanent stoma (p = 0.071) after a restorative procedure.A remarkable IHV in the permanent stoma rate after rectal cancer resection was found. No beneficial influence of transanal or robot‐assisted laparoscopy on the unintentional permanent stoma rate was found, although this might be caused by the surgical learning curve. A reduction in IHV and improving preoperative counselling for decision‐making for restorative procedures are required. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Evolution of surgical approach to rectal cancer resection: A multinational registry assessment" published in the International Journal of Colorectal Disease. The correction addresses an error in the spelling of a collaborator's name, correcting it from 'Tarik Samour' to 'Tarik Sammour'. The original article has been updated to reflect this correction. The publisher, Springer Nature, maintains a neutral stance on jurisdictional claims and institutional affiliations. The article is authored by multiple individuals from various institutions and countries. [Extracted from the article]

Background: Receiving a stoma significantly impacts patients' quality of life. Coping with this new situation can be difficult, which may result in a variety of physical and psychosocial problems. It is essential to provide adequate guidance to help patients cope with their stoma, as this positively influences self-efficacy in return. Higher self-efficacy reduces psychosocial problems increasing patient's quality of life. This study investigates whether a new mobile application, the Stoma App, improves quality of life. And if personalized guidance, timed support, and peer contact offered as an in-app surplus makes a difference. Methods: A double-blind, randomized controlled trial was conducted between March 2021 and April 2023. Patients aged > 18 years undergoing ileostomy or colostomy surgery, in possession of a compatible smartphone were included. The intervention group received the full version of the app containing personalized and time guidance, peer support, and generic (non-personalized) stoma-related information. The control group received a restricted version with only generic information. Primary outcome was stoma quality of life. Secondary outcomes included psychological adaption, complications, re-admittance, reoperations, and length of hospital stay. Results: The intervention version of the app was used by 96 patients and the control version by 112 patients. After correction for confounding, the intervention group reported a significant 3.1-point improvement in stoma-related quality of life one month postoperatively (p = 0.038). On secondary outcomes, no significant improvements could be retrieved of the intervention group. Conclusion: The Stoma App improves the quality of life of stoma patients. Peer support and personalized guidance are of significant importance in building self-efficacy. It is to be recommended to implement Stoma app—freely available software qualifying as a medical device—in standard stoma care pathways for the benefits of both patients and healthcare providers. [ABSTRACT FROM AUTHOR]

Background: Substantial variation exists when performing a minimally invasive right hemicolectomy (MIRH) due to disparities in training, expertise and differences in implementation of innovations. This study aimed to achieve national consensus on an optimal and standardized MIRH technique for colon cancer and to develop and validate a video-based competency assessment tool (CAT) for MIRH. Method: Statements covering all elements of MIRH were formulated. Subsequently, the Delphi technique was used to reach consensus on a standardized MIRH among 76 colorectal surgeons from 43 different centres. A CAT was developed based on the Delphi results. Nine surgeons assessed the same 12 unedited full-length videos using the CAT, allowing evaluation of the intraclass correlation coefficient (ICC). Results: After three Delphi rounds, consensus (≥80% agreement) was achieved on 23 of the 24 statements. Consensus statements included the use of low intra-abdominal pressure, detailed anatomical outline how to perform complete mesocolic excision with central vascular ligation, the creation of an intracorporeal anastomosis, and specimen extraction through a Pfannenstiel incision using a wound protector. The CAT included seven consecutive steps to measure competency of the MIRH and showed high consistency among surgeons with an overall ICC of 0.923. Conclusion: Nationwide consensus on a standardized and optimized technique of MIRH was reached. The CAT developed showed excellent interrater reliability. These achievements are crucial steps to an ongoing nationwide quality improvement project (the Right study). The Delphi technique was employed to achieve a broad national consensus on 23 statements among 76 colorectal surgeons, defining a standardized MIRH. This standard includes complete mesocolic excision, intracorporeal anastomosis and Pfannenstiel incision using a wound protector. Building upon this consensus, a video-based competency assessment tool was developed, exhibiting excellent reliability. [ABSTRACT FROM AUTHOR]

Background: Improving physical activity, especially in combination with optimizing protein intake, after surgery has a potential positive effect on recovery of physical functioning in patients after gastrointestinal and lung cancer surgery. The aim of this randomized controlled trial is to evaluate the efficacy of a blended intervention to improve physical activity and protein intake after hospital discharge on recovery of physical functioning in these patients. Methods: In this multicenter single-blinded randomized controlled trial, 161 adult patients scheduled for elective gastrointestinal or lung cancer surgery will be randomly assigned to the intervention or control group. The purpose of the Optimal Physical Recovery After Hospitalization (OPRAH) intervention is to encourage self-management of patients in their functional recovery, by using a smartphone application and corresponding accelerometer in combination with coaching by a physiotherapist and dietician during three months after hospital discharge. Study outcomes will be measured prior to surgery (baseline) and one, four, eight, and twelve weeks and six months after hospital discharge. The primary outcome is recovery in physical functioning six months after surgery, and the most important secondary outcome is physical activity. Other outcomes include lean body mass, muscle mass, protein intake, symptoms, physical performance, self-reported limitations in activities and participation, self-efficacy, hospital readmissions and adverse events. Discussion: The results of this study will demonstrate whether a blended intervention to support patients increasing their level of physical activity and protein intake after hospital discharge improves recovery in physical functioning in patients after gastrointestinal and lung cancer surgery. Trial registration: The trial has been registered at the International Clinical Trials Registry Platform at 14–10-2021 with registration number NL9793. Trial registration data are presented in Table 1. [ABSTRACT FROM AUTHOR]

Purpose: Minimally invasive right hemicolectomy (MIRH) is the cornerstone of treatment for patients with right-sided colon cancer. This operation has evolved during recent decades, with many innovations and improvements but this has also resulted in high variability of uptake with subsequent substantial variableness. The aim of this ongoing study is to identify current surgical variations, determine the most optimal and standardised MIRH and nationally train and implement that technique to improve short-term clinical and long-term oncological outcomes. Methods: The Right study is a national multicentre prospective interventional sequential cohort study. Firstly, current local practice was evaluated. Subsequently, a standardised surgical technique for right-sided colon cancer was determined using the Delphi consensus method, and this procedure was trained during hands-on courses. The standardised MIRH will be implemented with proctoring (implementation cohort), after which the performance will be monitored (consolidation cohort). Patients who will receive a minimally invasive (extended) right hemicolectomy for cT1-3N0-2M0 colon cancer will be included. The primary outcome is patient safety reflected in the 90-day overall complication rate according to the Clavien–Dindo classification. Secondary outcomes will include intraoperative complications, 90-day mortality rate, number of resected tumour-positive lymph nodes, completeness of mesocolic excision, surgical quality score, locoregional and distant recurrence and 5-year overall survival. A total number of 1095 patients (365 per cohort) will be included. Discussion: The Right study is designed to safely implement the best surgical practice concerning patients with right-sided colon cancer aiming to standardise and improve the surgical quality of MIRH at a national level. Trial registration: ClinicalTrials.gov: NCT04889456, May 2021. [ABSTRACT FROM AUTHOR]

Malignant lateral lymph nodes (LLNs) in low, locally advanced rectal cancer can cause (ipsi-lateral) local recurrences ((L)LR). Accurate identification is, therefore, essential. This study explored LLN features to create an artificial intelligence prediction model, estimating the risk of (L)LR. This retrospective multicentre cohort study examined 196 patients diagnosed with rectal cancer between 2008 and 2020 from three tertiary centres in the Netherlands. Primary and restaging T2W magnetic resonance imaging and clinical features were used. Visible LLNs were segmented and used for a multi-channel convolutional neural network. A deep learning model was developed and trained for the prediction of (L)LR according to malignant LLNs. Combined imaging and clinical features resulted in AUCs of 0.78 and 0.80 for LR and LLR, respectively. The sensitivity and specificity were 85.7% and 67.6%, respectively. Class activation map explainability methods were applied and consistently identified the same high-risk regions with structural similarity indices ranging from 0.772–0.930. This model resulted in good predictive value for (L)LR rates and can form the basis of future auto-segmentation programs to assist in the identification of high-risk patients and the development of risk stratification models. [ABSTRACT FROM AUTHOR]

Aim: Proper education, guidance and support is crucial before and following creation of a stoma. Patients with a stoma and their close relatives need to adapt to and cope with this new – and sometimes unforeseen – situation, which may result in insecurities and a variety of psychosocial problems. Self‐efficacy is associated both with a reduction in psychosocial problems and with improved quality of life. The main objective of this study was to investigate whether self‐reported quality of life of patients with a stoma can be enhanced by offering personalized and timed guidance, as well as peer contact, in a patient‐centred mobile application. Method: A multicentre, double‐blind, randomized controlled trial will be conducted. Consented adults >18 years of age who will receive an ileostomy or colostomy and possess an eligible smartphone will be included. The intervention group will be given the full version of the application (containing personalized and timed guidance, such as operation‐specific information and information on the associated care pathway) to install on their smartphone. In addition, the intervention group has access to a protected peer‐support platform within the app. The control group will receive a restricted version of the application that contains only generic (non‐personalized) stoma‐related information. The primary outcome is quality of life, 3 months postoperatively. Secondary outcomes are Patient Reported Outcome Measures (PROMs), such as psychological adaption, as well as number of complications, re‐admission and re‐operation rates and the length of hospital stay. Results: Patient enrolment began in March 2021. Data collection was not complete when this protocol was submitted. Conclusion: We hypothesize that patients with a stoma who are supported by the intervention version of the app will report a significantly higher quality of life than patients with a stoma who are supported by the control version of the app (ie, are not offered personalized and timed guidance and information and do not have access to peer support in the app). [ABSTRACT FROM AUTHOR]

Background: Natural orifice transluminal endoscopic surgery (NOTES) is currently gaining a lot of attention. NOTES is expected to further reduce surgical trauma and improve patient care due to eliminating abdominal incisions. The interest in transrectal NOTES has grown slowly, because of concerns of bacterial contamination due to transection of the rectum at the start of the procedure. However, different studies already demonstrated that transanal TME (TaTME) can be performed without major complications. This prospective study focuses on the presence and clinical significance of peritoneal bacterial contamination after TaTME for rectal cancer.Methods: Three bacterial cultures were taken at standardized locations from the pelvic area after completion of the TaTME procedure and before closure of the incisional wounds. The cultures were evaluated for bacterial count and species identification. Furthermore, C-reactive protein and white blood cell count were measured perioperatively, and postoperative complications were recorded.Results: Twenty-three consecutive patients were included between July 2013 and December 2014. Thirty-nine percent (9/23) of the cultures showed gastrointestinal flora. Four of these patients (44 %) developed presacral abscesses. The remaining 61 % (14/23) of the cultures were negative. None of these patients developed infectious complications.Conclusion: Transanal TME procedures are associated with positive cultures in more than one-third of the patients. In these patients, postoperative locoregional infectious complications are more common. [ABSTRACT FROM AUTHOR]

Background: Transanal total mesorectal excision (TaTME) for mid and low rectal cancer has been shown to improve short-term outcomes, mostly due to lower conversion rates and with improved quality of the specimen. However, robust long-term oncological data supporting the encouraging clinical and pathological outcomes are lacking. Methods: All consecutive patients undergoing TaTME with curative intent for mid or low rectal cancer in two referral centers in The Netherlands between January 2012 and April 2016 with a complete and minimum follow-up of 36 months were included. The primary outcome was local recurrence rate. Secondary outcomes were disease-free survival, overall survival and development of metastasis. Results: There were 159 consecutive patients. Their mean age was 66.9 (10.2) years and 66.7% of all patients were men. Pathological analysis showed a complete mesorectum in 139 patients (87.4%), nearly complete in 16 (10.1%) and an incomplete mesorectum in 4 (2.5%). There was involvement of the CRM (< 1 mm) in one patient (0.6%) and no patients had involvement of the distal margin (< 5 mm). Final postoperative staging after neoadjuvant therapy was stage 0 in 11 patients (6.9%), stage I in 73 (45.9%), stage II in 31 (19.5%), stage III in 37 (23.3%) and stage IV in 7 (4.4%). The 3-year local recurrence rate was 2.0% and the 5-year local recurrence rate was 4.0%. Median time to local recurrence was 19.2 months. Distant metastases were found in 22 (13.8%) patients and were diagnosed after a median of 6.9 months (range 1.1–50.4) months. Disease-free survival was 92% at 3 years and 81% at 5 years. Overall survival was 83.6% at 3 years and 77.3% at 5 years. Conclusions: The long-term follow-up of the current cohort confirms the oncological safety and feasibility of TaTME in two high volume referral centers for rectal carcinoma. However, further robust and audited data must confirm current findings before widespread implementation of TaTME. [ABSTRACT FROM AUTHOR]

Background: Quality of surgery has substantial impact on both short- and long-term clinical outcomes. This stresses the need for objective surgical quality assessment (SQA) for education, clinical practice and research purposes. The aim of this systematic review was to provide a comprehensive overview of all video-based objective SQA tools in laparoscopic procedures and their validity to objectively assess surgical performance. Methods: PubMed, Embase.com and Web of Science were systematically searched by two reviewers to identify all studies focusing on video-based SQA tools of technical skills in laparoscopic surgery performed in a clinical setting. Evidence on validity was evaluated using a modified validation scoring system. Results: Fifty-five studies with a total of 41 video-based SQA tools were identified. These tools were used in 9 different fields of laparoscopic surgery and were divided into 4 categories: the global assessment scale (GAS), the error-based assessment scale (EBAS), the procedure-specific assessment tool (PSAT) and artificial intelligence (AI). The number of studies focusing on these four categories were 21, 6, 31 and 3, respectively. Twelve studies validated the SQA tool with clinical outcomes. In 11 of those studies, a positive association between surgical quality and clinical outcomes was found. Conclusion: This systematic review included a total of 41 unique video-based SQA tools to assess surgical technical skills in various domains of laparoscopic surgery. This study suggests that validated SQA tools enable objective assessment of surgical performance with relevance for clinical outcomes, which can be used for training, research and quality improvement programs. [ABSTRACT FROM AUTHOR]

Background: In search of improvement of patient assessment in the postoperative phase, C-reactive protein (CRP) is increasingly being studied as an early marker for postoperative complications following major abdominal surgery. Several studies reported an attenuated immune response in minimally invasive surgery, which might affect interpretation of postoperative CRP levels. The aim of the present study was to compare the value of CRP as a predictor for major postoperative complications in patients undergoing open versus laparoscopic colorectal surgery.Methods: A subgroup analysis from a randomized clinical trial (LAFA-trial) was performed, including all patients with non-metastasized colorectal cancer. In the LAFA trial, patients were randomized to open or laparoscopic segmental colectomy. In a subgroup of 79 patients of the LAFA trial, postoperative assessment of CRP levels was conducted routinely preoperatively and 1, 2, 24 and 72 h after surgery.Results: Thirty-seven patients were randomized to the open group and 42 patients to the laparoscopic group. Major complications occurred in 19% of laparoscopic procedures and 13.5% of open procedures (p = 0.776). CRP levels rise following surgical procedures. In uncomplicated cases, the rise in CRP levels was significantly lower at 24 and 72 h following laparoscopic resection in comparison to open resection. No differences in CRP levels were observed when comparing open and laparoscopic resection in patients with major complications.Conclusion: In patients with an uncomplicated postoperative course, CRP levels were lower following minimally invasive resection, possibly due to decreased operative trauma. No differences in CRP were observed stratified for surgical technique in patients with major complications. These results suggest that CRP may be applied as a marker for major postoperative complications in both open and minimally invasive colorectal surgery. Future research should aim to assess the role of standardized postoperative CRP measurements. [ABSTRACT FROM AUTHOR]

Background: The role of diverting ileostomy in total mesorectal excision (TME) for rectal cancer with primary anastomosis is debated. The aim of this study is to gain insight in the clinical consequences of a diverting ileostomy, with respect to stoma rate at one year and stoma-related morbidity. Methods: Patients undergoing TME with primary anastomosis for rectal cancer between 2015 and 2017 in eleven participating hospitals were included. Retrospectively, two groups were compared: patients with or without diverting ileostomy construction during primary surgery. Primary endpoint was stoma rate at one year. Secondary endpoints were severity and rate of anastomotic leakage, overall morbidity rate within thirty days and stoma (reversal) related morbidity. Results: In 353 out of 595 patients (59.3%) a diverting ileostomy was constructed during primary surgery. Stoma rate at one year was 9.9% in the non-ileostomy group and 18.7% in the ileostomy group (p = 0.003). After correction for confounders, multivariate analysis showed that the construction of a diverting ileostomy during primary surgery was an independent risk factor for stoma at one year (OR 2.563 (95%CI 1.424–4.611), p = 0.002). Anastomotic leakage rate was 17.8% in the non-ileostomy group and 17.2% in the ileostomy group (p = 0.913). Overall 30-days morbidity rate was 37.6% in the non-ileostomy group and 56.1% in the ileostomy group (p < 0.001). Stoma reversal related morbidity rate was 17.9%. Conclusions: The stoma rate at one year was higher in patients with ileostomy construction during primary surgery. The incidence and severity of anastomotic leakage were not reduced by construction of an ileostomy. The morbidity related to the presence and reversal of a diverting ileostomy was substantial. [ABSTRACT FROM AUTHOR]

Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) aims to treat microscopic disease left after CytoReductive Surgery (CRS). Thermal enhancement depends on the temperatures achieved. Since the location of microscopic disease is unknown, a homogeneous treatment is required to completely eradicate the disease while limiting side effects. To ensure homogeneous delivery, treatment planning software has been developed. This study compares simulation results with clinical data and evaluates the impact of nine treatment strategies on thermal and drug distributions. For comparison with clinical data, three treatment strategies were simulated with different flow rates (1600-1800mL/min) and inflow temperatures (41.6–43.6 °C). Six additional treatment strategies were simulated, varying the number of inflow catheters, flow direction, and using step-up and step-down heating strategies. Thermal homogeneity and the risk of thermal injury were evaluated. Simulated temperature distributions, core body temperatures, and systemic chemotherapeutic concentrations compared well with literature values. Treatment strategy was found to have a strong influence on the distributions. Additional inflow catheters could improve thermal distributions, provided flow rates are kept sufficiently high (>500 mL/min) for each catheter. High flow rates (1800 mL/min) combined with high inflow temperatures (43.6 °C) could lead to thermal damage, with CEM 43 10 values of up to 27 min. Step-up and step-down heating strategies allow for high temperatures with reduced risk of thermal damage. The planning software provides valuable insight into the effects of different treatment strategies on peritoneal distributions. These strategies are designed to provide homogeneous treatment delivery while limiting thermal injury to normal tissue, thereby optimizing the effectiveness of HIPEC. [ABSTRACT FROM AUTHOR]

Introduction: Total mesorectal excision (TME) is an essential component of surgical management of rectal cancer. Both open and laparoscopic TME have been proven to be oncologically safe. However, it remains a challenge to achieve complete TME with clear circumferential resections margin (CRM) with the conventional transabdominal approach, particularly in mid and low rectal tumours. Transanal TME (TaTME) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer.Methods: An international, multicentre, superiority, randomised trial was designed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas. The primary endpoint is involved CRM. Secondary endpoints include completeness of mesorectum, residual mesorectum, morbidity and mortality, local recurrence, disease-free and overall survival, percentage of sphincter-saving procedures, functional outcome and quality of life. A Quality Assurance Protocol including centralised MRI review, histopathology re-evaluation, standardisation of surgical techniques, and monitoring and assessment of surgical quality will be conducted.Discussion: The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME. TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas. [ABSTRACT FROM AUTHOR]

Background: The risk of lymph node metastasis associated with deep submucosal invasion should be balanced against the mortality and morbidity of total mesorectal excision (TME). Dissection through the submucosa hinders radical deep resection, and full-thickness resection may influence the outcome of completion TME. Endoscopic intermuscular dissection (EID) in between the circular and longitudinal part of the muscularis propria could potentially provide an R0 resection while leaving the rectal wall intact.Methods: In this prospective cohort study, the data of patients treated with EID for suspected deep submucosal invasive rectal cancer between 2018 and 2020 were analyzed. Study outcomes were the percentages of technical success, R0 resection, curative resection, and adverse events.Results: 67 patients (median age 67 years; 73 % men) were included. The median lesion size was 25 mm (interquartile range 20-33 mm). The rates of overall technical success, R0 resection, and curative resection were 96 % (95 %CI 89 %-99 %), 81 % (95 %CI 70 %-89 %), and 45 % (95 %CI 33 %-57 %). Only minor adverse events occurred in eight patients (12 %).Conclusion: EID for deep invasive T1 rectal cancer appears to be feasible and safe, and the high R0 resection rate creates the potential of rectal preserving therapy in 45 % of patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the impact of open or laparoscopic resection of primary colorectal cancer (CRC) on the development of metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. Materials and methods: This was a retrospective, population-based study of CRC patients who underwent open or laparoscopic resection of the primary tumour in the Netherlands between January 1st and June 30th 2015. Patients with synchronous metastases were excluded. CPM were considered metachronous if diagnosed ≥ 90 days after resection of primary CRC. Multivariable cox regression analysis was performed to correct for tumour location, histology, differentiation, and stage, nodal stage, tumour perforation, primary surgery type, and unclear resection margins. Results: In total, 1516 CRC patients underwent open resection and 3236 CRC patients underwent laparoscopic resection, with a 3-year cumulative incidence of metachronous CPM of 7.3% and 3.7%, respectively (p < 0.001), after median follow-up of 42 months. Open surgical approach was significantly associated with the development of metachronous CPM: HR 1.4 [95%CI 1.1–1.8]. Other prognostic factors were mucinous adenocarcinoma histology (HR 1.6, 95%CI 1.0–2.5), T4 stage (HR 3.2, 95%CI 2.3–4.5), N1 stage (HR 2.9, 95%CI 2.1–4.0), and N2 stage (HR 4.2, 95%CI 2.9–6.1). Conclusions: Patients treated with open resection had a significantly higher risk to develop metachronous CPM than patients treated with laparoscopic resection. The mechanisms underlying this phenomenon remain unknown but might be related to differences in per-operative specimen handling, tumour spill, surgical trauma and pro-inflammatory response. This finding might imply the need for a personalized follow-up after primary resection of CRC. [ABSTRACT FROM AUTHOR]

Background: Promoting physical activity (PA) in patients during and/or after an inpatient stay appears important but challenging. Interventions using activity trackers seem promising to increase PA and enhance recovery of physical functioning. Objective: To review the effectiveness of physical activity interventions using activity trackers on improving PA and physical functioning, compared to usual care in patients during and/or after inpatient care. In addition, it was determined whether the following intervention characteristics increase the effectiveness of these interventions: the number of behaviour change techniques (BCTs) used, the use of a theoretical model or the addition of coaching by a health professional. Design: Systematic review and meta-analysis. Data Sources: PubMed, EMBASE, Cinahl, SportDiscus and Web of Science databases were searched in March 2020 and updated in March 2021. Eligibility criteria for selecting studies: Randomized controlled trials (RCTs) including interventions using activity trackers and feedback on PA in adult patients during, or less than 3 months after, hospitalization or inpatient rehabilitation. Methods: Following database search and title and abstract screening, articles were screened on full text for eligibility and then assessed for risk of bias by using the Physiotherapy Evidence Database (PEDro) scale. Meta-analyses, including subgroup analysis on intervention characteristics, were conducted for the outcomes PA and physical functioning. Results: Overall, 21 RCTs totalling 2355 patients were included. The trials covered a variety of clinical areas. There was considerable heterogeneity between studies. For the 13 studies that measured PA as an outcome variable(N = 1435), a significant small positive effect in favour of the intervention was found (standardized mean difference (SMD) = 0.34; 95%CI 0.12–0.56). For the 13 studies that measured physical functioning as an outcome variable (N = 1415) no significant effect was found (SMD = 0.09; 95%CI -0.02 - 0.19). Effectiveness on PA seems to improve by providing the intervention both during and after the inpatient period and by using a theoretical model, multiple BCTs and coaching by a health professional. Conclusion: Interventions using activity trackers during and/or after inpatient care can be effective in increasing the level of PA. However, these improvements did not necessarily translate into improvements in physical functioning. Several intervention characteristics were found to increase the effectiveness of PA interventions. Trial registration: Registered in PROSPERO (CRD42020175977) on March 23th, 2020. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate interobserver variability between individual pathologists and a panel of pathologists in the histopathological assessment of advanced colorectal neoplasms in the Dutch bowel cancer screening population. Methods and results: Histological slides of adenomas with high‐grade dysplasia and early colorectal carcinomas (CRC) from 20 different laboratories were reviewed by the pathology panel of the Dutch bowel screening programme. Interobserver variability was reported by descriptive statistics. In addition, potential clinical consequences of discrepancies were evaluated. A total of 104 cases of adenomas with high‐grade dysplasia and 83 early CRCs were reviewed. Discrepancies were observed in 41 of 104 (39.4%) adenoma cases, which potentially had clinical consequences in 16 (15.4%) cases. For CRC, discrepancies were shown in 44 of 83 cases (53.0%) and would have potentially led to alternative treatment strategies in 25 (30.1%) cases. Most frequently, discrepancies were observed in the assessment of lymphovascular invasion (23 of 73 cases, 31.5%). Conclusion: This study showed that considerable interobserver variability is present in the histopathological assessment of advanced colorectal neoplasia, which may impact upon treatment choices. Additional stains and education, as well as intercollegial consultation, might decrease this variability. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study evaluates the incidence of delirium and risk factors associated with delirium in elderly patients admitted to a general surgical ward. METHODS: Patients aged over 60 years who were admitted with an acute or elective general surgical diagnosis were eligible for this prospective cohort study. Risk factors associated with delirium were analyzed using univariate and multivariate analysis to identify those independently associated with delirium. RESULTS: A total of 209 patients were included in the study. The incidence of delirium was 16.9% (23.2% for acute admission, P <.001). Variables associated with delirium were dementia, presence of an urinary catheter, cognitive decline at admission measured with the mini-mental state examination, white blood cell count >10.0 × 109/L, and urea >7.5 mmol/L. Median length of hospital stay was 13 days (range 3-85) for patients with delirium versus 7 (range 1-54) for patients without (P 5=002). CONCLUSIONS: The incidence of delirium is high in elderly patients, especially after an acute admission, leading to an increase in length of hospital stay. To minimize delirium, associated risk factors must be identified and, if possible, treated. [ABSTRACT FROM AUTHOR]

Kinases are pivotal regulators of cellular physiology. The human genome contains more than 500 putative kinases, which exert their action via the phosphorylation of specific substrates. The determinants of this specificity are still only partly understood and as a consequence it is difficult to predict kinase substrate preferences from the primary structure, hampering the understanding of kinase function in physiology and prompting the development of technologies that allow easy assessment of kinase substrate consensus sequences. Hence, we decided to explore the usefulness of phosphorylation of peptide arrays comprising of 1176 different peptide substrates with recombinant kinases for determining kinase substrate preferences, based on the contribution of individual amino acids to total array phosphorylation. Employing this technology, we were able to determine the consensus peptide sequences for substrates of both c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8, two highly homologous kinases with distinct signalling roles in cellular physiology. The results show that although consensus sequences for these two kinases identified through our analysis share important chemical similarities, there is still some sequence specificity that could explain the different biological action of the two enzymes. Thus peptide arrays are a useful instrument for deducing substrate consensus sequences and highly homologous kinases can differ in their requirement for phosphorylation events. [ABSTRACT FROM AUTHOR]

Aim: Transanal total mesorectal excision (TaTME) has been suggested as a potential solution for the resection of challenging mid and low rectal cancer. This relatively complex procedure has been implemented in many centres over the last years, despite the absence of long‐term safety data. Recently, concern has arisen because of an increase in local recurrence in the implementation phase. The aim of this study was to assess the correlation between accumulated experience and local recurrences. Method: An independent clinical researcher performed an external audit of consecutive series of all TaTME procedures in six centres in the Netherlands. Kaplan–Meier estimated local recurrence rates were calculated and multivariate Cox proportional hazards regression analysis performed to assess risk factors for local recurrence. Primary outcome was the local recurrence rate in the initial implementation (cases 1–10), continued adoption (cases 11‐40) and prolonged experience (case 41 onward). Results: Six hundred and twenty‐four consecutive patients underwent TaTME for rectal cancer with a median follow‐up of 27 months (range 1–82 months). The estimated 2‐ and 3‐year local recurrence rates were 4.6% and 6.6%, respectively. Cox proportional hazards regression revealed procedural experience to be an independent factor in multivariate analysis next to advanced stage (ycMRF+, pT3‐4, pN+) and pelvic sepsis. Corrected analysis projected the 3‐year local recurrence rates to be 9.7%, 3.3% and 3.5% for the implementation, continued adoption and prolonged experience cohorts, respectively. Conclusion: This multicentre study shows a high local recurrence rate (12.5%) after implementation of TaTME which lowers to an acceptable rate (3.4%) when experience increases. Therefore, intensified proctoring and further precautions must be implemented to reduce the unacceptably high risk of local recurrence at units starting this technique. [ABSTRACT FROM AUTHOR]

Background: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden.Methods: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior.Discussion: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future.Trial Registration: Netherlands Trial Register, NL7083 , 06 July 2018. [ABSTRACT FROM AUTHOR]

Background: For surgical endometriosis, treatment key is to properly identify the peritoneal lesions. The aim of this clinical study was to investigate if advanced imaging improves the detection rate by comparing narrow-band imaging (NBI), near-infrared imaging with indocyanine green (NIR-ICG), or three-dimensional white-light imaging (3D), to conventional two-dimensional white-light imaging (2D) for the detection of peritoneal endometriotic lesions.Methods: This study was a prospective, single-center, randomized within-subject, clinical trial. The trial was conducted at Amsterdam UMC-Location VUmc, a tertiary referral hospital for endometriosis. 20 patients with ASRM stage III-IV endometriosis, scheduled for elective laparoscopic treatment of their endometriosis, were included. During laparoscopy, the pelvic region was systematically inspected with conventional 2D white-light imaging followed by inspection with NBI, NIR-ICG, and 3D imaging in a randomized order. Suspected endometriotic lesions and control biopsies of presumably healthy peritoneum were taken for histological examination. The pathologist was blinded for the method of laparoscopic detection. Sensitivity and specificity rates of the enhanced imaging techniques were analyzed. McNemar's test was used to compare sensitivity to 2D white-light imaging and Method of Tango to assess non-inferiority of specificity.Results: In total, 180 biopsies were taken (117 biopsies from lesions suspected for endometriosis; 63 control biopsies). 3D showed a significantly improved sensitivity rate (83.5% vs. 75.8%, p = 0.016) and a non-inferior specificity rate (82.4% vs. 84.7%, p = 0.009) when compared to 2D white-light imaging. The single use of NBI or NIR-ICG showed no improvement in the detection of endometriosis. Combining the results of 3D and NBI resulted in a sensitivity rate of 91.2% (p < 0.001).Conclusion: Enhanced laparoscopic imaging with 3D white light, combined with NBI, improves the detection rate of peritoneal endometriosis when compared to conventional 2D white-light imaging. The use of these imaging techniques enables a more complete laparoscopic resection of endometriosis. [ABSTRACT FROM AUTHOR]

Background: Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes.Methods: This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0-10 or 11-20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician's discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates.Discussion: This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM.Trial Registration: Clinicaltrials.gov/ NCT02758951 , NTR/ NTR6301 , ISRCTN/ ISRCTN15977568 , EudraCT/ 2016-001865-99 . [ABSTRACT FROM AUTHOR]

Background: Approximately 20-30% of patients with pT4 colon cancer develop metachronous peritoneal metastases (PM). Due to restricted accuracy of imaging modalities and absence of early symptoms, PM are often detected at a stage in which only a quarter of patients are eligible for curative intent treatment. Preliminary findings of the COLOPEC trial (NCT02231086) revealed that PM were already detected during surgical re-exploration within two months after primary resection in 9% of patients with pT4 colon cancer. Therefore, second look diagnostic laparoscopy (DLS) to detect PM at a subclinical stage may be considered an essential component of early follow-up in these patients, although this needs confirmation in a larger patient cohort. Furthermore, a third look DLS after a negative second look DLS might be beneficial for detection of PM occurring at a later stage.Methods: The aim of this study is to determine the yield of second look DLS and added value of third look DLS after negative second look DLS in detecting occult PM in pT4N0-2 M0 colon cancer patients after completion of primary treatment. Patients will undergo an abdominal CT at 6 months postoperative, followed by a second look DLS within 1 month if no PM or other metastases not amenable for local treatment are detected. Patients without PM will subsequently be randomized between routine follow-up including 18 months abdominal CT, or an experimental arm with a third look DLS provided that PM or incurable metastases are absent at the 18 months abdominal CT. Primary endpoint is the proportion of PM detected after a negative second look DLS and will be determined at 20 months postoperative.Discussion: Second look DLS is supposed to result in 10% occult PM, and third look DLS after negative second look DLS is expected to detect an additional 10% of PM compared to routine follow-up alone in patients with pT4 colon cancer. Detection of PM at an early stage will likely increase the proportion of patients eligible for curative intent treatment and subsequently improve survival, given the uniformly reported direct association between the extent of peritoneal disease and survival.Trial Registration: ClinicalTrials.gov: NCT03413254 , January 2018. [ABSTRACT FROM AUTHOR]

Background: Transanal total mesorectal excision (TaTME) is a safe alternative to laparoscopic TME for mid and low rectal cancer. TaTME allows improved visualization of the surgical planes and margins, and may potentially improve oncological outcomes. However, functional results after total mesorectal excision (TME) are variable and there are currently only a few published studies that include functional data related to the outcomes of TaTME.Methods: Fifty-four consecutive patients were included in this study: one group included 27 patients who underwent laparoscopic low anterior and the other included 27 patients who underwent TaTME. All patients were asked to complete five questionnaires related to quality of life (QOL) and function [EQ-5D-3L, EORTC-QLQ C30, EORTC-QLQ C29, Low Anterior Resection Syndrome score (LARS), and International Prostate Symptom Score IPSS]. All TaTME patients were operated on at The Gelderse Vallei Hospital by a single surgeon and had a follow-up of at least 6.6 months.Results: The EORTC-QLQ C30 and EQ-5D-3L questionnaires showed comparable outcomes in terms of QOL between the two groups. Almost all items evaluated by the EORTC-QLQ C29, including sexual outcomes, were similar between the two groups. One item concerning fecal incontinence, however, was scored worse for TaTME. There were no significant differences between the groups in terms of LARS symptoms or urinary function.Conclusions: Patients undergoing laparoscopic or transanal TME showed comparable functional and QOL outcomes. Although the TaTME technique is still evolving, this study indicates that this technique is a safe alternative to laparoscopic surgery in terms of functional outcomes for mid and low rectal cancers. [ABSTRACT FROM AUTHOR]

Aim: Transanal endoscopic microsurgery (TEM) is used for the resection of large rectal adenomas and well or moderately differentiated T1 carcinomas. Due to difficulty in preoperative staging, final pathology may reveal a carcinoma not suitable for TEM. Although completion total mesorectal excision is considered standard of care in T2 or more invasive carcinomas, this completion surgery is not always performed. The purpose of this article is to evaluate the outcome of patients after TEM-only, when completion surgery would be indicated. Methods: In this retrospective multicenter, observational cohort study, outcome after TEM-only (n = 41) and completion surgery (n = 40) following TEM for a pT2–3 rectal adenocarcinoma was compared. Results: Median follow-up was 29 months for the TEM-only group and 31 months for the completion surgery group. Local recurrence rate was 35 and 11% for the TEM-only and completion surgery groups respectively. Distant metastasis occurred in 16% of the patients in both groups. The 3-year overall survival was 63% in the TEM-only group and 91% in the completion surgery group respectively. Three-year disease-specific survival was 91 versus 93% respectively. Conclusions: Although local recurrence after TEM-only for pT2–3 rectal cancer is worse compared to the recurrence that occurs after completion surgery, disease-specific survival is comparable between both groups. The lower unadjusted overall survival in the TEM-only group indicates that TEM-only may be a valid alternative in older and frail patients, especially when high morbidity of completion surgery is taken into consideration. Nevertheless, completion surgery should always be advised when curation is intended. [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility of intraoperative use of indocyanine green (ICG) fluorescent angiography in laparoscopic intestinal vaginoplasty to determine intestinal segment perfusion and viability.Design: Intestinal vaginoplasty may be performed as a vaginal (re)construction procedure. During surgery, a pedicled intestinal segment is transferred caudally to line the neovaginal cavity. Most commonly, a sigmoid or ileal segment is used. In obtaining adequate mobility of the segment, arterial structures sometimes have to be sacrificed, with possible detrimental effects on segment perfusion and subsequently viability. ICG may be used as an aid to assess segment perfusion. We present a case series of six consecutive patients who underwent intestinal vaginoplasty with intraoperative use of ICG.Setting: Tertiary university hospital.Patient(s): Six transgender women undergoing laparoscopic sigmoid vaginoplasty with intraoperative use of ICG from October 2017 to October 2018.Intervention(s): Intraoperative use of ICG in laparoscopic sigmoid vaginoplasty to determine sigmoid segment perfusion and viability.Main Outcome Measure(s): Value and feasibility of ICG in this reconstructive procedure.Result(s): Intraoperative use of ICG demonstrated segment viability in five patients. In one patient, vascularization of the segment was deemed to be inadequate and reconstruction was aborted.Conclusions: ICG fluorescent angiography may be used intraoperatively to assess perfusion of the pedicled sigmoid segment during sigmoid vaginoplasty. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic right hemicolectomy for colon cancer is associated with substantial morbidity despite the introduction of enhanced recovery protocols and laparoscopic surgery. Laparoscopic right hemicolectomy with an intracorporeal anastomosis (IA) is less invasive than laparoscopic assisted hemicolectomy, possibly leading to further decrease in post-operative morbidity and faster recovery. The current standard technique includes an extracorporeal anastomosis with mobilization of the colon, mesenteric traction and a extraction wound located in the mid/upper abdomen with relative more post-operative morbidity compared to extraction wounds located in the lower abdomen.Methods: A systematic review of PubMed and Embase databases was performed on studies comparing the intracorporeal versus the extracorporeal performed anastomosis in laparoscopic right hemicolectomy. Primary outcomes were mortality, short-term morbidity and length of stay. For quality assessment, the MINORS checklist was used. Meta-analysis was performed using a random-effects model, and a subgroup analysis was performed for data regarding short-term morbidity and length of stay in studies published in 2012≥.Results: A total of 2692 papers were identified, 12 non-randomized comparative studies were included in the analysis with a total number of 1492 patients. No significant change in mortality was found (OR 0.36, 95 % CI 0.09-1.46; I 2 = 0 %). Short-term morbidity decreased significantly in favour of IA (OR 0.68, 95 % CI 0.49-0.93; I 2 = 20 %). Length of stay was decreased, but with serious risk of heterogeneity (MD -0.77 days, 95 % CI -1.46 to -0.07; I 2 = 81 %). Subgroup analysis for papers published in 2012≥ resulted in an even larger decrease in short-term morbidity (OR 0.65, 95 % CI 0.50-0.85; I 2 = 0 %) and a significant decrease in length of stay with low risk of heterogeneity (MD -0.77 days, 95 % CI -1.17 to -0.37; I 2 = 4 %).Conclusion: Intracorporeal anastomosis in laparoscopic right hemicolectomy is associated with reduced short-term morbidity and decreased length of hospital stay suggesting faster recovery as shown in this meta-analysis. [ABSTRACT FROM AUTHOR]

Background: Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC).Methods: Using gene expression databases we investigated ADAM12 expression in CRC and delineated the source of ADAM12 expression. The clinical value of ADAM12 was retrospectively assessed in the CAIRO2 trial in metastatic CRC with 235 patients (31% of total cohort), and an independent rectal cancer cohort (n = 20).Results: ADAM12 is expressed by activated CRC associated fibroblasts. In the CAIRO2 trial cohort, ADAM12 serum levels were prognostic (ADAM12 low versus ADAM12 high; median OS 25.3 vs. 17.1 months, HR 1.48 [95% CI 1.11-1.96], P = 0.007). The prognostic potential was specifically high for metastatic rectal cancer (HR 1.78 [95% CI 1.06-3.00], P = 0.030) and mesenchymal subtype tumors (HR 2.12 [95% CI 1.25-3.60], P = 0.004). ADAM12 also showed potential for predicting recurrence in an exploratory analysis of non-metastatic rectal cancers.Conclusions: Here we describe a non-invasive marker for activated stroma in CRC which associates with poor outcome, especially for primary cancers located in the rectum. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to test and validate a novel noninvasive method for intraoperative visualization of extrahepatic bile ducts during laparoscopic cholecystectomy. Injury to the common bile duct (CBD) is a rare but major complication of laparoscopic cholecystectomy. Most injuries occur when anatomy is unclear due to the presence of anatomic variations, acute inflammation, or adhesions. Patients and Methods: Thirty patients were included, and each received an intravenous injection of 0.05 mg/kg of indocyanine green (ICG) (ICG-Pulsion®; PULSION Medical Systems AG, Munich, Germany) prior to the start of surgery. Laparoscopic cholecystectomy was performed according to standard procedures. The CBD and cystic duct (CD) were visualized before and during dissection of the liver hilus using a conventional laparoscopic camera and a recently developed near-infrared (NIR) camera (Olympus, Tokyo, Japan). Results: Using ICG-NIR, the CBD and CD could be visualized 11 minutes ( P=.008) and 8.6 minutes ( P=.001) earlier than with a conventional camera. Both early (20/30 patients) and late (26/30 patients) identification of the CBD with ICG-NIR was significantly more frequent compared with conventional images (2/30 and 10/30, respectively; P<.001). One postoperative bilioma required re-admission and endoscopic retrograde cholangiopancreatography with stent placement. Conclusions: Identification of the CBD and CD using a low dose of ICG and the NIR camera was both faster and more frequent compared with conventional laparoscopic images during elective laparoscopic cholecystectomy. [ABSTRACT FROM AUTHOR]

Background Reducing the incidence of anastomotic leakages would benefit both patients and health care in general. Attempts to solve this problem have been disappointing thus far. Sylys® Surgical Sealant was developed as an extraluminal adjunct to standard closure techniques for bowel anastomosis procedures. We describe the results of a first-in-man study in which Sylys® Surgical Sealant is used. The aim of this study was to evaluate the safety of Sylys® Surgical Sealant in stoma reversal procedures. Methods This prospective, multicenter, non-randomized, first-in-man industry initiated study was performed in two independent hospitals in the Netherlands. The study population consisted of adults who were scheduled for an open ileostomy reversal procedure. Exclusion critera were: patients with severe co-morbidities, patients receiving antibiotics, immunosuppressive agents or steroids for pre-existing conditions. Follow up was conducted during 3 months after surgery at the outpatient clinic. Results Sixteen patients were eligible for inclusion. Twenty adverse events were recorded in 12 of the 16 treated patients (75%). None of these events were considered to be related to Sylys® Surgical Sealant. No clinical signs of anastomotic leakage were reported. Conclusions In conclusion, this first-in-man application of Sylys® Surgical Sealant as an adjunct to standard bowel anastomosis closure techniques did not show any adverse effects in relation to the sealant in 16 patients. [ABSTRACT FROM AUTHOR]

Summary: Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define the transcriptional program underlying angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4 signaling. Extensive analysis of multiple cancer types demonstrates significant upregulation of ELTD1 in tumor-associated endothelial cells, with a higher expression correlating with favorable prognosis. Importantly, ELTD1 silencing impairs endothelial sprouting and vessel formation in vitro and in vivo, drastically reducing tumor growth and greatly improving survival. Collectively, these results provide insight into the regulation of tumor angiogenesis and highlight ELTD1 as key player in blood vessel formation. [ABSTRACT FROM AUTHOR]

Simple Summary: Strategies to enhance the preferential accumulation and activation of Natural Killer (NK) cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based cancer immunotherapy. In this study, we report that a bispecific single domain antibody (VHH) that targets CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells can be used to target and enhance cytolysis of cancer cells. The bispecific VHH enhanced NK cell activation and cytotoxicity in an EGFR- and CD16-dependent and KRAS-independent manner. Moreover, the bispecific VHH induced stronger activity of cancer patient-derived NK cells and resulted in tumor control in a co-culture of metastatic colorectal cancer cells and either autologous peripheral blood mononuclear cells or allogeneic CD16+ NK cells. We believe that this novel approach could represent a valid therapeutic strategy either alone or in combination with other NK cell-based therapies. The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches. [ABSTRACT FROM AUTHOR]

Colon cancer is a clinically diverse disease. This heterogeneity makes it difficult to determine which patients will benefit most from adjuvant therapy and impedes the development of new targeted agents. More insight into the biological diversity of colon cancers, especially in relation to clinical features, is therefore needed. We demonstrate, using an unsupervised classification strategy involving over 1,100 individuals with colon cancer, that three main molecularly distinct subtypes can be recognized. Two subtypes have been previously identified and are well characterized (chromosomal-instable and microsatellite-instable cancers). The third subtype is largely microsatellite stable and contains relatively more CpG island methylator phenotype-positive carcinomas but cannot be identified on the basis of characteristic mutations. We provide evidence that this subtype relates to sessile-serrated adenomas, which show highly similar gene expression profiles, including upregulation of genes involved in matrix remodeling and epithelial-mesenchymal transition. The identification of this subtype is crucial, as it has a very unfavorable prognosis and, moreover, is refractory to epidermal growth factor receptor-targeted therapy. [ABSTRACT FROM AUTHOR]

Despite the presence of mutations in APC or β-catenin, which are believed to activate the Wnt signalling cascade constitutively, most colorectal cancers show cellular heterogeneity when β-catenin localization is analysed, indicating a more complex regulation of Wnt signalling. We explored this heterogeneity with a Wnt reporter construct and observed that high Wnt activity functionally designates the colon cancer stem cell (CSC) population. In adenocarcinomas, high activity of the Wnt pathway is observed preferentially in tumour cells located close to stromal myofibroblasts, indicating that Wnt activity and cancer stemness may be regulated by extrinsic cues. In agreement with this notion, myofibroblast-secreted factors, specifically hepatocyte growth factor, activate β-catenin-dependent transcription and subsequently CSC clonogenicity. More significantly, myofibroblast-secreted factors also restore the CSC phenotype in more differentiated tumour cells both in vitro and in vivo. We therefore propose that stemness of colon cancer cells is in part orchestrated by the microenvironment and is a much more dynamic quality than previously expected that can be defined by high Wnt activity. [ABSTRACT FROM AUTHOR]

Simple Summary: Efficacy of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assists in designing potentially more effective treatment protocols and clinical trials. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In total, 60 articles were included in this study. The selected articles were screened on the HIPEC parameters. Recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for patients with peritoneal metastasis (PM) of various origins which aims for cure in combination with cytoreductive surgery (CRS). Efficacy of CRS-HIPEC depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assist in designing potentially more effective treatment protocols and clinical trials. The different methodologies for peritoneal disease and HIPEC are variable. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In this review, recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments. [ABSTRACT FROM AUTHOR]

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) may be curative for colorectal cancer patients with peritoneal metastases (PMs) but it has a high rate of morbidity. Accurate preoperative patient selection is therefore imperative, but is constrained by the limitations of current imaging techniques. In this pilot study, we explored the feasibility of circulating tumor (ct) DNA analysis to select patients for CRS-HIPEC. Thirty patients eligible for CRS-HIPEC provided blood samples preoperatively and during follow-up if the procedure was completed. Targeted Next-Generation Sequencing (NGS) of DNA from PMs was used to identify bespoke mutations that were subsequently tested in corresponding plasma cell-free (cf) DNA samples using droplet digital (dd) PCR. CtDNA was detected preoperatively in cfDNA samples from 33% of patients and was associated with a reduced disease-free survival (DFS) after CRS-HIPEC (median 6.0 months vs median not reached, p = 0.016). This association could indicate the presence of undiagnosed systemic metastases or an increased metastatic potential of the tumors. We demonstrate the feasibility of ctDNA to serve as a preoperative marker of recurrence in patients with PMs of colorectal cancer using a highly sensitive technique. A more appropriate treatment for patients with preoperative ctDNA detection may be systemic chemotherapy in addition to, or instead of, CRS-HIPEC. [ABSTRACT FROM AUTHOR]

Background: Transanal total mesorectal excision (TaTME) is a relatively new and demanding technique for rectal cancer treatment. Results from national datasets are absent and comparative data with laparoscopic TME (lapTME) are scarce. Therefore, this study aimed to evaluate the initial TaTME experience in the Netherlands, by comparing outcomes with conventional lapTME.Study Design: Patients with rectal cancer who underwent curative TaTME or lapTME were selected from the nationwide and mandatory Dutch ColoRectal Audit (DCRA), between January 2015 and December 2017. Primary outcome was circumferential resection margin (CRM) involvement. Secondary outcomes included operative details and short-term (<30 days) clinical course. Propensity score matching was performed for 7 factors.Results: There were 3,777 patients included for analysis (TaTME, n = 416, lapTME, n = 3361). Transanal TME was performed in 38 hospitals and lapTME in 90 hospitals. Before matching, the patient category within the TaTME group was technically more challenging in terms of tumor height and preoperative threatened margins. After 1:1 matching, 396 patients were included in each group, with comparable baseline characteristics. Circumferential resection margin involvement was 4.3% after TaTME and 4.0% after lapTME (p = 1.000). Conversion rate was significantly lower in TaTME (1.5% vs 8.6%, p < 0.001). Anastomotic leak rate was not significantly different (16.5% vs 12.2%, p = 0.116). Other postoperative outcomes were also comparable between the groups. Significant independent risk factors for CRM involvement in TaTME were preoperative threatened margin on MRI (odds ratio [OR] 5.48, 95% CI 1.33 to 22.54) and conversion (OR 30.12, 95% CI 3.70 to 245.20).Conclusions: This first nationwide study shows early experience with adoption of TaTME in the Netherlands. Considering that current data represent initial TaTME experience, acceptable short-term outcomes were demonstrated when compared with the well-established lapTME. [ABSTRACT FROM AUTHOR]