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Background: Anastomotic leakage is a severe postoperative complication in colorectal surgery and compromised bowel perfusion is considered a major contributing factor. Conventional methods to assess bowel perfusion have a low predictive value for anastomotic leakage. We therefore aimed to evaluate the efficacy of real-time assessment with near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in the prevention of anastomotic leakage., Methods: This multicentre, randomised, controlled, phase 3 trial was done in eight hospitals in the Netherlands. We included adults (aged >18 years) who were scheduled for laparoscopic or robotic colorectal surgery (with planned primary anastomosis) for benign and malignant diseases. Preoperatively, patients were randomly assigned (1:1) to fluorescence-guided bowel anastomosis (FGBA) or conventional bowel anastomosis (CBA) by variable block randomisation (block sizes 4, 6, and 8) and stratified by site. The operating surgeon and investigators analysing the data were not masked to group assignment. Patients were unmasked after the surgical procedure or after study end. In the FGBA group, surgeons marked anastomosis levels per conventional perfusion assessment and then administered 5 mg of ICG by 2 mL intravenous bolus. They assessed bowel perfusion using NIR fluorescence imaging and adjusted (or kept) transection lines accordingly. Only conventional methods for bowel perfusion assessment were used in the CBA group. The primary outcome was the difference in the rate of clinically relevant anastomotic leakage (ie, requiring active therapeutic intervention but manageable without reoperation [grade B] or requiring reoperation [grade C], per the International Study Group of Rectal Cancer) between the FGBA group and the CBA group within 90 days post-surgery. The primary outcome and safety were assessed in the intention-to-treat population. This study was registered with ToetsingOnline.nl (NL7502) and ClinicalTrials.gov (NCT04712032) and is complete., Findings: Between July 2, 2020, and Feb 21, 2023, 982 patients were enrolled, of whom 490 were assigned to FGBA and 492 were assigned to CBA. After excluding 51 patients, the intention-to-treat population comprised 931 (463 assigned FGBA and 468 assigned CBA). Patients had a median age of 68·0 years (IQR 59·0-75·0) and 485 (52%) were male and 446 (48%) were female. Ethnicity data were not available. The overall 90-day rate of clinically relevant anastomotic leakage was not significantly different between the FGBA group (32 [7%] of 463 patients) and the CBA group (42 [9%] of 468 patients; relative risk 0·77 [95% CI 0·50-1·20]; p=0·24). No adverse events related to ICG use were observed. 313 serious adverse events in 229 (25%) patients were at 90-day follow-up (159 serious adverse events in 113 [24%] patients in the FGBA group and 154 serious adverse events in 116 [25%] patients in the CBA group). 18 (2%) people died by 90 days (ten in the FGBA group and eight in the CBA group)., Interpretation: ICG NIR fluorescence imaging did not reduce 90-day anastomotic leakage rates in this trial across all types of colorectal surgeries. Further research should be done in subgroups, such as rectosigmoid resections, for which evidence suggests ICG NIR might be beneficial., Funding: Olympus Medical, Diagnostic Green, and Intuitive Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Aim: Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including minimally invasive techniques such as lancet sampling or an automated upper arm device (TAP-II), has the potential to replace a significant portion of hospital-based blood sampling, thereby enhancing self-reliance and quality of life. The objectives of this study were to assess the feasibility, reliability and preference for CEA blood collection., Methods: Baseline venous and capillary (by lancet and TAP-II) blood samples were collected from 102 participants, including 20 CRC patients with elevated CEA levels, 60 CRC patients undergoing postoperative outpatient monitoring and 20 healthy volunteers. The second group performed capillary blood collections at home on two consecutive follow-up appointments and subsequently sent them to the hospital. Satisfaction was assessed via patient reported outcome measures on pain, burden, ease of use and preference., Results: The Pearson's correlation test of all usable samples resulted in a linear coefficient of 0.998 (95% CI 0.997-0.998) for the TAP-II method and 0.997 (95% CI 0.996-0.998) for the lancet method, both compared to venipuncture. Following the initial blood collection, 86% of the participants (n = 102) favoured the TAP-II, rating it as the least painful and burdensome option. After two home-based blood samples, the preference for the TAP-II method persisted, with 64% of the patients endorsing its use., Conclusion: This study demonstrated the feasibility of home-based capillary sampling of CEA. The TAP-II blood collection is the most reliable method and is preferred by patients over venipuncture and lancet sampling., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Introduction: Amidst the rising number of cancer survivors and personnel shortages, optimisation of follow-up strategies is imperative, especially since intensive follow-up does not lead to survival benefits. Understanding patient preferences and identifying the associated patient profiles is crucial. Coping style may be a key determinant in achieving this. Our study aims to evaluate preferences, identify coping styles and their associated factors, and explore the association between coping style and patients' preferences in colorectal cancer (CRC) follow-up., Methods: In a prospective multicentre implementation study, patients completed the Threatening Medical Situations Inventory (TMSI) to determine their coping style. Simultaneously patients choose their follow-up preferences for the CRC trajectory regarding frequency of tumour marker determination, location of blood sampling, and manner of contact., Results: A total of 188 patients completed the TMSI questionnaire after inclusion. A more intensive follow-up was preferred by 71.5% of patients. Of all patients, 52.0% had a coping style classified as 'blunting' and 34.0% as 'monitoring'. Variables such as a younger age, female gender, higher educational level, and lower ASA scores were associated with having higher monitoring scores. However, there were no significant associations between follow-up preferences and patients' coping styles., Conclusion: This study suggests that none of the provided options in a patient-led follow-up are unsuitable for patients who underwent curative surgery for primary CRC, based on coping style determined at baseline. Low-intensity surveillance after curative resection of CRC may, therefore, be suitable for a wide range of patients independent of coping styles., (© 2024. The Author(s).)

Background: Decision-making after local resection of T1 colorectal cancer (T1CRC) is often complex and calls for optimal information provision as well as active patient involvement., Objective: The aim was to evaluate the perceptions of patients with T1CRC on information provision and therapeutic decision-making., Methods: This multicenter cross-sectional study included patients who underwent endoscopic or local surgical resection as initial treatment. Information provision was assessed using the EORTC QLQ-INFO25 questionnaire. In patients with high-risk T1CRC, we evaluated decisional involvement and satisfaction regarding the choice as to whether to undergo additional treatment after local resection, and the level of decisional conflict using the Decisional Conflict Scale., Results: Ninety-eight patients with T1CRC were included (72% response rate; 79/98 endoscopic and 19/98 local surgical resection; 45/98 high-risk T1CRC). Median time since local resection was 28 months (IQR 18); none had developed recurrence. Unmet information needs were reported by 29 patients (30%; 18 low-risk, 11 high-risk), mostly on post-treatment related topics (follow-up visits, recovery time, recurrence prevention). After local resection, 24 of the 45 high-risk patients (53%) underwent additional treatment, while others were subjected to surveillance. Higher-educated patients were more often actively involved in decision-making (93% vs. 43%, p = 0.002) and more frequently underwent additional treatment (79% vs. 40%, p = 0.02). Decisional conflict (p = 0.19) and satisfaction (p = 0.78) were comparable between higher- and lower-educated high-risk patients., Conclusion: Greater attention should be given to the post-treatment course during consultations following local T1CRC resection. The differences in decisional involvement and selected management strategies between higher- and lower-educated high-risk patients warrant further investigation., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy., Methods: The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging ( 99m Tc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump., Results: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%., Conclusion: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In colorectal liver metastases (CRLM) patients, combination of liver resection and ablation permit a more parenchymal-sparing approach. This study assessed trends in use of combined resection and ablation, outcomes, and overall survival (OS)., Methods: This population-based study included all CRLM patients who underwent liver resection between 2014 and 2022. To assess OS, data was linked to two databases containing date of death for patients treated between 2014 and 2018. Hospital variation in the use of combined minor liver resection and ablation versus major liver resection alone in patients with 2-3 CRLM and ≤3 cm was assessed. Propensity score matching (PSM) was applied to evaluate outcomes., Results: This study included 3593 patients, of whom 1336 (37.2%) underwent combined resection and ablation. Combined resection increased from 31.7% in 2014 to 47.9% in 2022. Significant hospital variation (range 5.9-53.8%) was observed in the use of combined minor liver resection and ablation. PSM resulted in 1005 patients in each group. Major morbidity was not different (11.6% vs. 5%, P = 1.00). Liver failure occurred less often after combined resection and ablation (1.9% vs. 0.6%, P = 0.017). Five-year OS rates were not different (39.3% vs. 33.9%, P = 0.145)., Conclusion: Combined resection and ablation should be available and considered as an alternative to resection alone in any patient with multiple metastases., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae , Bifidobacterium animalis , and Adlercreutzia equolifaciens , while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies., Competing Interests: Author AO was employed by the company Pathan BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vietsch, Latifi, Verheij, van der Oost, de Wilde, Haen, van den Boom, Koerkamp, Doornebosch, van Verschuer, Ooms, Mohammad, Willemsen, Aerts, Krog, de Miranda, van den Bosch, Mueller, Katsikis and van Eijck.)

Introduction: Colorectal cancer (CRC) is the third most common type of cancer in the Netherlands. Approximately 90% of patients can be treated with surgery, which is considered potentially curative. Postoperative surveillance during the first 5 years after surgery pursues to detect metastases in an early, asymptomatic and treatable stage. Multiple large randomised controlled trials have failed to show any (cancer-specific) survival benefit of intensive postoperative surveillance compared with a minimalistic approach in patients with CRC. This raises the question whether an (intensive) in-hospital postoperative surveillance strategy is still warranted from both a patient well-being and societal perspective. A more modern, home-based surveillance strategy could be beneficial in terms of patients' quality of life and healthcare costs., Methods and Analysis: The multicentre, prospective FUTURE-primary study implements a patient-led home-based surveillance after curative CRC treatment. Here, patients are involved in the choice regarding three fundamental aspects of their postoperative surveillance. First regarding frequency, patients can opt for additional follow-up moments to the minimal requirement as outlined by the current Dutch national guidelines. Second regarding the setting, both in-hospital or predominantly home-based options are available. And third, concerning patient-doctor communication choices ranging from in-person to video chat, and even silent check-ups. The aim of the FUTURE-primary study is to evaluate if such a patient-led home-based follow-up approach is successful in terms of quality of life, satisfaction and anxiety compared with historic data. A successful implementation of the patient-led aspect will be assessed by the degree in which the additional, optional follow-up moments are actually utilised. Secondary objectives are to evaluate quality of life, anxiety, fear of cancer recurrence and cost-effectiveness., Ethics and Dissemination: Ethical approval was given by the Medical Ethics Review Committee of Erasmus Medical Centre, The Netherlands (2021-0499). Results will be presented in peer-reviewed journals., Trial Registration Number: NCT05656326., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014-2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017-2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery.

Background: Floxuridine's high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to quantify the systemic exposure of floxuridine., Methods: Patients undergoing continuous hepatic arterial infusion pump (HAIP) floxuridine after resection of colorectal liver metastases (CRLM) in two centres underwent six cycles of floxuridine at start dose 0.12 mg/kg/day. No concomitant systemic chemotherapy was administered. Peripheral venous blood samples were drawn during the first two cycles: pre-dose (only in the second cycle), 30 min, 1 h, 2 h, 7 h, and 15 days after floxuridine infusion. Foxuridine concentration in the residual pump reservoir was measured on day 15 of both cycles. A floxuridine assay with a lower boundary of detection of 0.250 ng/mL was developed., Results: 265 blood samples were collected in the 25 patient included in this study. Floxuridine was mostly measurable at day 7 and day 15 (86 % and 88 % of patients respectively). The median dose corrected concentrations were 0.607 ng/mL [IQR: 0.472-0.747] for cycle 1 day 7, 0.579 ng/mL [IQR: 0.470-0.693] for cycle 1 day 15, 0.646 ng/mL [IQR: 0.463-0.8546] for cycle 2 day 7, and 0.534 ng/mL [IQR: 0.4257-0.7075] for cycle 2 day 15. One patient had remarkably high floxuridine concentrations reaching up to 44 ng/mL during the second cycle, without a clear explanation. The floxuridine concentration in the pump decreased by 14.7 % (range 0.5 %-37.8 %) over a period of 15 days (n = 18)., Conclusion: Overall, negligible systemic concentrations of floxuridine were detected. However, remarkably increased levels were detected in one patient. Floxuridine concentration in the pump decreases over time., Competing Interests: Conflict of Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background & Aims: In contrast to mismatch repair deficient colorectal carcinoma (CRC), MMR proficient (pMMR) CRC does not respond to immune checkpoint blockade. We studied immune checkpoint stimulation via glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) on ex vivo functionality of human tumor-infiltrating lymphocytes (TIL) isolated from pMMR primary CRC and liver metastases (CRLM)., Methods: Using lymphocytes from resected tumor, adjacent tissues, and peripheral blood mononuclear cells (PBMC) of 132 pMMR primary CRC or CRLM patients, we determined GITR expression and the in vitro T-cell agonistic activity of recombinant GITR ligation., Results: Here, we show that GITR was overexpressed on TIL when compared with other stimulatory immune checkpoints (4-1BB, OX40). Its expression was enhanced in TIL compared with PBMC and adjacent tissues. Among CD4 + TIL, GITR expression was primarily expressed by CD45RA - FoxP3 hi activated regulatory T cells. Within CD8 + TIL, GITR was predominantly expressed on functionally exhausted and putative tumor-reactive CD103 + CD39 + TIL. Strikingly, recombinant GITRL reinvigorated ex vivo TIL responses by significantly enhancing CD4 + and CD8 + TIL numbers. Dual treatment with GITRL and nivolumab (anti-PD1) enhanced CD8 + TIL expansion compared with GITRL monotherapy. Moreover, GITRL/anti-PD1 dual therapy further improved anti-PD1-mediated reinvigoration of interferon gamma secretion by exhausted CD8 TIL from primary CRC., Conclusions: GITR is overexpressed on CD4 + and CD8 + TIL from pMMR CRC and CRLM. Agonistic targeting of GITR enhances ex vivo human TIL functionality and may therefore be a promising approach for novel monotherapy or combined immunotherapies in primary pMRR CRC and CRLM., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A growing proportion of patients with early rectal cancer is treated by local excision only. The aim of this study was to evaluate long-term oncological outcomes and the impact of local recurrence on overall survival for surgical local excision in pT1 rectal cancer., Methods: Patients who only underwent local excision for pT1 rectal cancer between 1997 and 2014 in two Dutch tertiary referral hospitals were included in this retrospective cohort study. The primary outcome was the local recurrence rate. Secondary outcomes were distant recurrence, overall survival and the impact of local recurrence on overall survival., Results: A total of 150 patients (mean age 68.5 ± 10.7 years, 57.3% males) were included in the study. Median length of follow-up was 58.9 months (range 6-176 months). Local recurrence occurred in 22.7% (n = 34) of the patients, with a median time to local recurrence of 11.1 months (range 2.3-82.6 months). The vast majority of local recurrences were located in the lumen. Five-year overall survival was 82.0%, and landmark analyses showed that local recurrence significantly impacted overall survival at 6 and 36 months of follow-up (6 months, p = 0.034, 36 months, p = 0.036)., Conclusions: Local recurrence rates after local excision of early rectal cancer can be substantial and may impact overall survival. Therefore, clinical decision-making should be based on patient- and tumour characteristics and should incorporate patient preferences., (© 2022. The Author(s).)

Background: T1 rectal cancer (RC) patients are increasingly being treated by local resection alone but uniform surveillance strategies thereafter are lacking. To determine whether different local resection techniques influence the risk of recurrence and cancer-related mortality, a meta-analysis was performed., Methods: A systematic search was conducted for T1RC patients treated with local surgical resection. The primary outcome was the risk of RC recurrence and RC-related mortality. Pooled estimates were calculated using mixed-effect logistic regression. We also systematically searched and evaluated endoscopically treated T1RC patients in a similar manner., Results: In 2585 unique T1RC patients (86 studies) undergoing local surgical resection, the overall pooled cumulative incidence of recurrence was 9.1% (302 events, 95% CI 7.3-11.4%; I 2  = 68.3%). In meta-regression, the recurrence risk was associated with histological risk status (p < 0.005; low-risk 6.6%, 95% CI 4.4-9.7% vs. high-risk 28.2%, 95% CI 19-39.7%) and local surgical resection technique (p < 0.005; TEM/TAMIS 7.7%, 95% CI 5.3-11.0% vs. other local surgical excisions 10.8%, 95% CI 6.7-16.8%). In 641 unique T1RC patients treated with flexible endoscopic excision (16 studies), the risk of recurrence (7.7%, 95% CI 5.2-11.2%), cancer-related mortality (2.3%, 95% CI 1.1-4.9), and cancer-related mortality among patients with recurrence (30.0%, 95% CI 14.7-49.4%) were comparable to outcomes after TEM/TAMIS (risk of recurrence 7.7%, 95% CI 5.3-11.0%, cancer-related mortality 2.8%, 95% CI 1.2-6.2% and among patients with recurrence 35.6%, 95% CI 21.9-51.2%)., Conclusions: Patients with T1 rectal cancer may have a significantly lower recurrence risk after TEM/TAMIS compared to other local surgical resection techniques. After TEM/TAMIS and endoscopic resection the recurrence risk, cancer-related mortality and cancer-related mortality among patients with recurrence were comparable. Recurrence was mainly dependent on histological risk status., (© 2022. The Author(s).)

Introduction: Local excision is increasingly used as an alternative treatment for radical surgery in patients with early stage clinical T1 (cT1) rectal cancer. This study provides an overview of incidence, staging accuracy and treatment strategies in patients with cT1 rectal cancer in the Netherlands., Materials and Methods: Patients with cT1 rectal cancer diagnosed between 2005 and 2018 were included from the Netherlands Cancer Registry. An overview per time period (2005-2009, 2010-2014 and 2015-2018) of the incidence and various treatment strategies used, e.g. local excision (LE) or major resection, with/without neoadjuvant treatment (NAT), were given and trends over time were analysed using the Chi Square for Trend test. In addition, accuracy of tumour staging was described, compared and analysed over time., Results: In total, 3033 patients with cT1 rectal cancer were diagnosed. The incidence of cT1 increased from 540 patients in 2005-2009 to 1643 patients in 2015-2018. There was a significant increased use of LE. In cT1N0/X patients, 9.2% received NAT, 25.5% were treated by total mesorectal excision (TME) and 11.4% received a completion TME (cTME) following prior LE. Overall accuracy in tumour staging (cT1 = pT1) was 77.3%, yet significantly worse in cN1/2 patients, as compared to cN0 patients (44.8% vs 77.9%, respectively, p < 0.001)., Conclusion: Over time, there was an increase in the incidence of cT1 tumours. Both the use of neoadjuvant therapy and TME surgery in clinically node negative patients decreased significantly. Clinical accuracy in T1 tumour staging improved over time, but remained significantly worse in clinical node positive patients., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The use of cytokines for immunotherapy shows clinical efficacy but is frequently accompanied by severe adverse events caused by excessive and systemic immune activation. Here, we set out to address these challenges by engineering a fusion protein of a single, potency-reduced, IL15 mutein and a PD1-specific antibody (anti-PD1-IL15m). This immunocytokine was designed to deliver PD1-mediated, avidity-driven IL2/15 receptor stimulation to PD1 + tumor-infiltrating lymphocytes (TIL) while minimally affecting circulating peripheral natural killer (NK) cells and T cells. Treatment of tumor-bearing mice with a mouse cross-reactive fusion, anti-mPD1-IL15m, demonstrated potent antitumor efficacy without exacerbating body weight loss in B16 and MC38 syngeneic tumor models. Moreover, anti-mPD1-IL15m was more efficacious than an IL15 superagonist, an anti-mPD-1, or the combination thereof in the B16 melanoma model. Mechanistically, anti-PD1-IL15m preferentially targeted CD8 + TILs and single-cell RNA-sequencing analyses revealed that anti-mPD1-IL15m treatment induced the expansion of an exhausted CD8 + TIL cluster with high proliferative capacity and effector-like signatures. Antitumor efficacy of anti-mPD1-IL15m was dependent on CD8 + T cells, as depletion of CD8 + cells resulted in the loss of antitumor activity, whereas depletion of NK cells had little impact on efficacy. The impact of anti-hPD1-IL15m on primary human TILs from patients with cancer was also evaluated. Anti-hPD1-IL15m robustly enhanced the proliferation, activation, and cytotoxicity of CD8 + and CD4 + TILs from human primary cancers in vitro , whereas tumor-derived regulatory T cells were largely unaffected. Taken together, our findings showed that anti-PD1-IL15m exhibits a high translational promise with improved efficacy and safety of IL15 for cancer immunotherapy via targeting PD1 + TILs. See related Spotlight by Felices and Miller, p. 1110 ., (©2021 American Association for Cancer Research.)

Background: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands., Method: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups., Results: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004)., Conclusion: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© 2021 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Objective: To investigate differences in postoperative outcomes between short-course radiotherapy and delayed surgery (SCRT-delay) and chemoradiation (CRT) in patients with locally advanced rectal cancer (LARC)., Background: Previous trials suggest that SCRT-delay could serve as an adequate neoadjuvant treatment for LARC. Therefore, in frail LARC patients SCRT-delay is recommended as an alternative to CRT. However, data on postoperative outcomes after SCRT-delay in comparison to CRT is scarce., Methods: This was an observational study with data from the Dutch ColoRectal Audit (DCRA). LARC patients who underwent surgery (2014-2017) after an interval of ≥6 weeks were included. Missing values were replaced by multiple imputation. Propensity score matching (PSM), using age, Charlson Comorbidity Index, cT-stage and surgical procedure, was applied to create comparable groups. Differences in postoperative outcomes were analyzed using Chi-square test for categorical variables, independent sample t-test for continuous variables and Mann-Whitney U test for non-parametric data., Results: 2926 patients were included. In total, 288 patients received SCRT-delay and 2638 patients underwent CRT. Patients in the SCRT-delay group were older and had more comorbidities. Also, ICU-admissions and permanent colostomies were more common, as well as pulmonic, cardiologic, infectious and neurologic complications. After PSM, both groups comprised 246 patients with equivalent age, comorbidities and tumor stage. There were no differences in postoperative complications., Conclusion: Postoperative complications were not increased in LARC patients undergoing SCRT-delay as neoadjuvant treatment. Regarding treatment-related complications, SCRT-delay is a safe alternative neoadjuvant treatment option for frail LARC patients., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Several factors are included in decision making for treatment of patients with locally advanced rectal cancer, including a trade-off between risks and gains of both clinical and functional outcomes. However, it is largely unknown which outcomes are most important to patients and whether this differs between patients and clinicians., Methods: Both clinicians and patients treated for locally advanced rectal cancer were invited to fill out an online questionnaire, including a choice-based conjoint experiment. Participants were presented 14 comparisons of two hypothetical case presentations, characterized by different treatments and outcomes of care (6 attributes) and were asked to select the case with the best outcome at that moment. Hierarchical Bayes Estimation was used to calculate the relative importance (RI) of each of the six attributes., Results: In total, 94 patients and 128 clinicians completed the questionnaire. For patients, avoiding surgery with permanent stoma was most important (RI 24.4, 95%CI 21.88-26.87) and a 2-year difference in disease-free survival was least important (RI 5.6, 95%CI 4.9-6.2). Clinicians assigned highest importance to avoiding severe and daily worries about cancer recurrence (RI 30.7, 95%CI 29.1-32.4), while this was ranked 4th by patients (RI 17.9, 95%CI 16.5-19.4, p < 0.001)., Conclusion: When confronted with different outcomes within one case description, patients find the duration of disease free survival the least important. In addition, considerable differences were found between the importance assigned by patients and clinicians to clinical and functional outcomes, most notably in avoiding surgery with permanent stoma and worries about recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Abdominoperineal resection (APR) for rectal cancer is associated with high morbidity of the perineal wound, and controversy exists about the optimal closure technique. Primary perineal wound closure is still the standard of care in the Netherlands. Biological mesh closure did not improve wound healing in our previous randomised controlled trial (BIOPEX-study). It is suggested, based on meta-analysis of cohort studies, that filling of the perineal defect with well-vascularised tissue improves perineal wound healing. A gluteal turnover flap seems to be a promising method for this purpose, and with the advantage of not having a donor site scar. The aim of this study is to investigate whether a gluteal turnover flap improves the uncomplicated perineal wound healing after APR for rectal cancer., Methods: Patients with primary or recurrent rectal cancer who are planned for APR will be considered eligible in this multicentre randomised controlled trial. Exclusion criteria are total exenteration, sacral resection above S4/S5, intersphincteric APR, biological mesh closure of the pelvic floor, collagen disorders, and severe systemic diseases. A total of 160 patients will be randomised between gluteal turnover flap (experimental arm) and primary closure (control arm). The total follow-up duration is 12 months, and outcome assessors and patients will be blinded for type of perineal wound closure. The primary outcome is the percentage of uncomplicated perineal wound healing on day 30, defined as a Southampton wound score of less than two. Secondary outcomes include time to perineal wound closure, incidence of perineal hernia, the number, duration and nature of the complications, re-interventions, quality of life and urogenital function., Discussion: The uncomplicated perineal wound healing rate is expected to increase from 65 to 85% by using the gluteal turnover flap. With proven effectiveness, a quick implementation of this relatively simple surgical technique is expected to take place., Trial Registration: The trial was retrospectively registered at Clinicaltrials.gov NCT04004650 on July 2, 2019.

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.

Background: Transanal total mesorectal excision (TaTME) is a new complex technique with potential to improve the quality of surgical mesorectal excision for patients with mid and low rectal cancer. The procedure is technically challenging and has shown to be associated with a relative long learning curve which might hamper widespread adoption. Therefore, a national structured training pathway for TaTME has been set up in the Netherlands to allow safe implementation. The aim of this study was to monitor safety and efficacy of the training program with 12 centers., Methods: Short-term outcomes of the first ten TaTME procedures were evaluated in 12 participating centers in the Netherlands within the national structured training pathway. Consecutive patients operated during and after the proctoring program for rectal carcinoma with curative intent were included. Primary outcome was the incidence of intraoperative complications, secondary outcomes included postoperative complications and pathological outcomes., Results: In October 2018, 12 hospitals completed the training program and from each center the first 10 patients were included for evaluation. Intraoperative complications occurred in 4.9% of the cases. The clinicopathological outcome reported 100% for complete or nearly complete specimen, 100% negative distal resection margin, and the circumferential resection margin was positive in 5.0% of patients. Overall postoperative complication rate was 45.0%, with 19.2% Clavien-Dindo ≥ III and an anastomotic leak rate of 17.3%., Conclusions: This study shows that the nationwide structured training program for TaTME delivers safe implementation of TaTME in terms of intraoperative and pathology outcomes within the first ten consecutive cases in each center. However, postoperative morbidity is substantial even within a structured training pathway and surgeons should be aware of the learning curve of this new technique.

Aim: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection., Method: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1β), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted., Results: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78)., Conclusion: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool., (© 2019 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the implementation and outcome of MILS on a nationwide scale., Methods: Electronic patient files were reviewed in all Dutch liver surgery centers and all patients undergoing MILS between 2011 and 2016 were selected. Operative outcomes were stratified based on extent of the resection and annual MILS volume., Results: Overall, 6951 liver resections were included, with a median annual volume of 50 resections per center. The overall use of MILS was 13% (n = 916), which varied from 3% to 36% (P < 0.001) between centers. The nationwide use of MILS increased from 6% in 2011 to 23% in 2016 (P < 0.001). Outcomes of minor MILS were comparable with international studies (conversion 0-13%, mortality <1%). In centers which performed ≥20 MILS annually, major MILS was associated with less conversions (14 (11%) versus 41 (30%), P < 0.001), shorter operating time (184 (117-239) versus 200 (139-308) minutes, P = 0.010), and less overall complications (37 (30%) versus 58 (42%), P = 0.040)., Conclusion: The nationwide use of MILS is increasing, although large variation remains between centers. Outcomes of major MILS are better in centers with higher volumes., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Aim: This subgroup analysis of a prospective multicentre cohort study aims to compare postoperative morbidity between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME)., Method: The study was designed as a subgroup analysis of a prospective multicentre cohort study. Patients undergoing TaTME or LaTME for rectal cancer were selected. All patients were followed up until the first visit to the outpatient clinic after hospital discharge. Postoperative complications were classified according to the Clavien-Dindo classification and the comprehensive complication index (CCI). Propensity score matching was performed., Results: In total, 220 patients were selected from the overall prospective multicentre cohort study. After propensity score matching, 48 patients from each group were compared. The median tumour height for TaTME was 10.0 cm (6.0-10.8) and for LaTME was 9.5 cm (7.0-12.0) (P = 0.459). The duration of surgery and anaesthesia were both significantly longer for TaTME (221 vs 180 min, P < 0.001, and 264 vs 217 min, P < 0.001). TaTME was not converted to laparotomy whilst surgery in five patients undergoing LaTME was converted to laparotomy (0.0% vs 10.4%, P = 0.056). No statistically significant differences were observed for Clavien-Dindo classification, CCI, readmissions, reoperations and mortality., Conclusion: The study showed that TaTME is a safe and feasible approach for rectal cancer resection. This new technique obtained similar postoperative morbidity to LaTME., (© 2019 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Anastomotic leak after rectal surgery is reported in 9% (range 3-28%) of patients. The aim of our study was to evaluate the effectiveness of endosponge therapy for anastomotic. Endpoints were the rate of restored continuity and the functional bowel outcome after anastomotic leakage., Methods: This was a multicenter retrospective observational cohort study. All patients with symptomatic anastomotic leakage after rectal surgery who had endosponge therapy between January 2012 and August 2017 were included. Functional bowel outcome was measured using the low anterior resection syndrome (LARS) score system., Results: Twenty patients were included. Eighteen patients had low anterior resection (90%) for rectal cancer. A diverting ileostomy was performed at primary surgical intervention in 14 patients (70%). Fourteen patients (70%) were treated with neoadjuvant (chemo-)radiotherapy. The median time between primary surgical intervention and first endosponge placement was 21 (5-537) days. The median number of endosponge changes was 9 (2-28). The success rate of the endosponge treatment was 88% and the restored gastrointestinal continuity rate was 73%. A chronic sinus occurred in three patients (15%). All patients developed LARS, of which 77% reported major LARS., Conclusions: Endosponge therapy is an effective treatment for the closure of presacral cavities with high success rate and leading to restored gastrointestinal continuity in 73%. However, despite endosponge therapy many patients develop major LARS.

Background: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM., Methods: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone., Discussion: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival., Trial Registration: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.

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., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: According to Dutch guidelines, locally excised, low-risk, pT1 or ypT0-1 rectal cancer should not necessarily be followed by completion total mesorectal excision (cTME) in contrast to rectal cancers with higher T stages or unfavorable features. This study evaluated cTME after local excision at a national level with possible determinants for decision-making. Methods: All patients in the Dutch Colorectal Audit (DCRA) who underwent local excision of rectal cancer between 2012 and 2015 were included. Guideline adherence for performing cTME was determined with univariate and multivariate analyses to identify factors related to noncompliance. Results: According to the guidelines, of 530 included patients, cTME was indicated in 283 (53%), and among those, was performed in 82 (29%). Guideline adherence for performing cTME improved significantly ( P <.001), from 10% in 2012 to 44% in 2015. Lower Charlson comorbidity index in patients with high-risk pT1 rectal cancer and younger patients (aged 61-70 years vs ≥80 years) with pT≥2 rectal cancer were associated with increased performance of cTME (odds ratio [OR], 13.50; 95% CI, 1.39-131.32, and OR, 6.25; 95% CI, 1.83-21.31, respectively). Conclusions: In this population-based study from the Netherlands, only a minority of patients underwent cTME after local excision of rectal cancer with pathologic features indicating the need for further treatment according to the guidelines. Although the percentage of patients undergoing cTME increased over time, the study indicated a tendency toward rectal-preserving treatment with potential oncologic risks., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Background: The aim of this study was to investigate the effect of age on CAL and its associated mortality., Methods: Data were derived from the Dutch ColoRectal Audit. All patients undergoing resection for colorectal cancer in the Netherlands between January 2011 and December 2016 were included. Univariable and multivariable logistic regressions were performed to test the effect of age on CAL and its associated mortality., Results: In total, 45 488 patients were included. The incidence of CAL was 6.4% in patients <60 years old, 5.5% in patients 60-69 years old, 5.4% in patients 70-80 years old, and 4.9% in patients ≥80 years old (P < 0.001). Multivariate analysis showed that age was protective for CAL (OR 0.965 per 5 years, 95% CI 0.941-0.985, P < 0.001). Mortality after CAL was 1.3% in patients <60 years old, 4.8% in patients 60-69 years old, 12.3% in patients 70-80 years old, and 27.0% in patients >80 years old (P < 0.001). Older age was associated with mortality following CAL (OR 1.497 per 5 years 95% CI 1.364-1.647, P < 0.001)., Conclusions: This population-based study suggests a protective effect of increased age on CAL after colorectal cancer resection. However, older age is strongly associated with mortality after CAL., (© 2018 Wiley Periodicals, Inc.)

Objective: Non-randomised studies suggest that endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM), but EMR might be more cost-effective and safer. This trial compares the clinical outcome and cost-effectiveness of TEM and EMR for large rectal adenomas., Design: Patients with rectal adenomas ≥3 cm, without malignant features, were randomised (1:1) to EMR or TEM, allowing endoscopic removal of residual adenoma at 3 months. Unexpected malignancies were excluded postrandomisation. Primary outcomes were recurrence within 24 months (aiming to demonstrate non-inferiority of EMR, upper limit 10%) and the number of recurrence-free days alive and out of hospital., Results: Two hundred and four patients were treated in 18 university and community hospitals. Twenty-seven (13%) had unexpected cancer and were excluded from further analysis. Overall recurrence rates were 15% after EMR and 11% after TEM; statistical non-inferiority was not reached. The numbers of recurrence-free days alive and out of hospital were similar (EMR 609±209, TEM 652±188, p=0.16). Complications occurred in 18% (EMR) versus 26% (TEM) (p=0.23), with major complications occurring in 1% (EMR) versus 8% (TEM) (p=0.064). Quality-adjusted life years were equal in both groups. EMR was approximately €3000 cheaper and therefore more cost-effective., Conclusion: Under the statistical assumptions of this study, non-inferiority of EMR could not be demonstrated. However, EMR may have potential as the primary method of choice due to a tendency of lower complication rates and a better cost-effectiveness ratio. The high rate of unexpected cancers should be dealt with in further studies., Competing Interests: Competing interests: Dr. Dijkgraaf reports grants from The Netherlands Organisation for Health Research and Development, during the conduct of the study. Dr. Fockens reports personal fees from Covidien, personal fees from Fujifilm, personal fees from Olympus, outside the submitted work. Dr. Jansen reports personal fees from MSD, personal fees from Abbvie, personal fees from Takeda and personal fees from Hospira, outside the submitted work. Dr. Schoon reports personal fees from Boston-Scientific, personal fees from Medtronic, personal fees from Olympus, outside the submitted work. Furthermore, we declare no competing interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Aims: Large non-pedunculated rectal polyps are most commonly resected by endoscopic mucosal resection (EMR) or transanal endoscopic microsurgery (TEM). Despite pre-procedural diagnostics, unexpected rectal cancer is incidentally encountered within the resected specimen. This study aimed to compare the diagnostic assessment and procedural characteristics of lesions with and without unexpected submucosal invasion., Methods: A post-hoc analysis of a multicenter randomized trial (TREND study) was performed in which patients with a non-pedunculated rectal polyp of ≥3 cm without endoscopic suspicion of invasive growth were randomized between EMR and TEM., Results: Unexpected rectal cancer was detected in 13% (27/203) of patients; 15 after EMR and 12 after TEM. Most consisted of low-risk T1 cancers (78%, n = 18). There were no differences in the diagnostic assessment between lesions with and without unexpected submucosal invasion. Diagnostic biopsies revealed similar rates of high-grade dysplasia (28% [7/25] vs 18% [26/144]). When compared with EMR of adenomas, EMR procedures of unexpected cancers had a lower success rate of submucosal lifting (60% vs 93%, P < .001), were more often assessed as endoscopically incomplete (33% vs 10%, P = .01), and were more frequently terminated prematurely (60% vs 8%, P = .001)., Conclusions: Diagnostic assessment of large non-pedunculated rectal polyps revealed similar characteristics between unexpected cancers and adenomas. Unexpected cancers during EMR were non-lifting in 40%, endoscopically assessed as incomplete in 33%, and terminated prematurely in 60%. In treatment-naive patients, these factors should raise suspicion of malignancy and need discussion in a multidisciplinary team meeting for decision on further treatment strategies., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: McKittrick Wheelock Syndrome (MKWS) is a rare syndrome characterized by secretory diarrhea, dehydration, prerenal acute kidney injury, and severe electrolyte abnormalities caused by a large hypersecretory villous adenoma located in the rectum or rectosigmoid junction. Transabdominal (laparoscopic) procedures are the most described procedures in the treatment of MKWS. We report an alternative surgical approach, transanal minimally invasive surgery (TAMIS), to solve this syndrome., Materials and Methods: All patients who underwent transanal endoscopic microsurgery or TAMIS were included in a prospectively collected database in our center. Between 1996 and 2015, 3 patients were found to have MKWS and treated by TAMIS. Demographics, characteristics of the adenoma, surgery-related data, and outcome were analyzed., Results: The first patient had a villous adenoma 0-12 cm from the anal verge. After TAMIS, she complained of a stenosis that was successfully treated by dilatation. The second patient had an impressive bulky tumor in the rectum. An endoscopic mucosal resection was attempted twice, but incompletely. Pathology analysis showed villous adenoma with high-grade dysplasia and intramucosal carcinoma. One year after TAMIS, a recurrence was detected and treated by an abdominal-perineal resection. A TAMIS was performed in the third patient because of a giant villous circular adenoma, but because of high mucus and fluid production, no proper overview could be obtained. Together with opening of the peritoneum, this prompted us to convert to a laparoscopic Hartmann procedure. Besides this technical difficulty, the patient recovered uneventful., Conclusions: MKWS is a rare syndrome and missed diagnosis could result in life-threatening situations. Different endoscopic and surgical treatments are described to solve this syndrome. TAMIS should be considered as a rectum-preserving surgical treatment option for such extensive adenomas.

Background: Stapled anopexy is a safe technique for the treatment of hemorrhoids but carries a higher risk of recurrence, which might be caused due to the limited volume of resected tissue. In this study, we investigated the introduction of a high-volume circular stapling device; in particular whether an increased amount of resected tissue could affect patients' short-term postoperative outcome., Methods: Between 2011 and 2015, stapled anopexy was performed for hemorrhoids and/or anal prolapse in 141 patients (n = 25 conventional PPH-3©-stapler versus n = 116 high-volume CHEX©-stapler). In this prospectively collected dataset, operation details and short-term postoperative outcome were compared., Results: With the high-volume stapler, a significantly higher amount of tissue was resected: 9.8 g (range 6.2-11.4) vs. 6.4 g (range 4.9-8.8) with the conventional stapler, p < 0.01. Postoperative short-term outcome did not differ in terms of readmission and complication rates. In all 5 patients who underwent a redo operation for residual hemorrhoids or prolapse, the high-volume stapler was used in the primary operation., Conclusion: A high-volume stapling device for stapled anopexy was introduced safely with a significantly higher amount of resected tissue without a worse short-term outcome. However, it remains unclear whether higher stapling volumes may lead to improved long-term outcome with less reinterventions., (© 2017 S. Karger AG, Basel.)

Objective: Abdominoperineal resection (APR) is associated with high incidence of surgical wound infections. The use of incisional negative-pressure wound therapy (iNPWT) is known to reduce wound infections for several surgical indications. The aim of this pilot study was to investigate the potential of a new portable negative-pressure therapy device on perineal wound healing in patients undergoing APR. Approach: A new single-use incisional negative-pressure therapy device was applied in 10 patients. A negative pressure of -80 mmHg was continued for 7 days postsurgery. Incidence of wound complications and time to wound healing were compared with a historical control group of 10 patients undergoing APR in 2014, treated with conventional wound care. Results: Patient characteristics were comparable in both groups. Mean 1.6 dressings were used per patient. A wound complication was diagnosed in seven patients versus six in the control group. Wound infections were diagnosed median 11.5 days after surgery, compared with 10.5 days in the control group. Duration of wound healing was shorter in the study group (median 8.5 weeks vs. 13 weeks). Innovation: This is the first study to report on the use of this iNPWT device for patients who underwent APR for rectal cancer. Conclusion: In this study, iNPWT did not reduce wound complications. Wound infections occurred slightly later and seemed to have a less severe clinical course. After treatment with iNPWT, the duration of wound healing was shorter., Competing Interests: No competing financial interests exist. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article.

Background: Long-term complications of previous rectal surgery (e.g., enterovisceral fistula, anastomotic stricture, rectal stenosis) can be challenging problems for which transabdominal or transperineal surgery with or without definitive fecal diversion is often required. Transanal endoscopic surgery (TES) might allow for local treatment of these complications, thereby saving patients from otherwise major surgery., Patients and Methods: All patients undergoing TES in the IJsselland Hospital (NL) since 1996 were recorded in a prospective database, of which twenty patients were treated for complications after previous rectal surgery. Data on prior treatment, surgical techniques, outcomes, and need for additional surgery were collected., Results: Twenty patients were identified from the database (rectourinary fistula n = 3, rectovaginal fistula n = 5, anastomotic stricture n = 8, and rectal stenosis n = 4). One of the three (33 %) rectourinary fistulas and two of five (40 %) rectovaginal fistulas were successfully treated with TES. Anastomotic strictures were successfully treated in 5/8 (63 %) patients. Strictures after local excision of rectal tumors were successfully treated in 3/4 (75 %) patients. No minor complication and one major complication occurred (rectovaginal fistula after stenoplasty eventually requiring Hartmann's procedure)., Conclusions: Transanal treatment of anastomotic strictures, rectal stenosis, and fistula after prior rectal surgery is safe and effective in a large proportion of patients. TES should be considered as a first step in all patients presenting with these late complications after rectal surgery.