Risk factors for advanced colorectal neoplasia and colorectal cancer detected at surveillance: a nationwide study in the modern era.

AIM: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

The economic impact of anastomotic leakage after colorectal surgery: a systematic review.

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.

Robotic, transanal, and laparoscopic total mesorectal excision for locally advanced mid/low rectal cancer: European multicentre, propensity score-matched study.

BACKGROUND: Total mesorectal excision (TME) is the standard surgery for low/mid locally advanced rectal cancer. The aim of this study was to compare three minimally invasive surgical approaches for TME with primary anastomosis (laparoscopic TME, robotic TME, and transanal TME). METHODS: Records of patients undergoing laparoscopic TME, robotic TME, or transanal TME between 2013 and 2022 according to standardized techniques in expert centres contributing to the European MRI and Rectal Cancer Surgery III (EuMaRCS-III) database were analysed. Propensity score matching was applied to compare the three groups with respect to the complication rate (primary outcome), conversion rate, postoperative recovery, and survival. RESULTS: A total of 468 patients (mean(s.d.) age of 64.1(11) years) were included; 190 (40.6%) patients underwent laparoscopic TME, 141 (30.1%) patients underwent robotic TME, and 137 (29.3%) patients underwent transanal TME. Comparative analyses after propensity score matching demonstrated a higher rate of postoperative complications for laparoscopic TME compared with both robotic TME (OR 1.80, 95% c.i. 1.11-2.91) and transanal TME (OR 2.87, 95% c.i. 1.72-4.80). Robotic TME was associated with a lower rate of grade A anastomotic leakage (2%) compared with both laparoscopic TME (8.8%) and transanal TME (8.1%) (P = 0.031). Robotic TME (1.4%) and transanal TME (0.7%) were both associated with a lower conversion rate to open surgery compared with laparoscopic TME (8.8%) (P < 0.001). Time to flatus and duration of hospital stay were shorter for patients treated with transanal TME (P = 0.003 and 0.001 respectively). There were no differences in operating time, intraoperative complications, blood loss, mortality, readmission, R0 resection, or survival. CONCLUSION: In this multicentre, retrospective, propensity score-matched, cohort study of patients with locally advanced rectal cancer, newer minimally invasive approaches (robotic TME and transanal TME) demonstrated improved outcomes compared with laparoscopic TME.

Surgical quality assessment of critical view of safety in 283 laparoscopic cholecystectomy videos by surgical residents and surgeons.

INTRODUCTION: Surgical quality assessment has improved the efficacy and efficiency of surgical training and has the potential to optimize the surgical learning curve. In laparoscopic cholecystectomy (LC), the critical view of safety (CVS) can be assessed with a 6-point competency assessment tool (CAT), a task commonly performed by experienced surgeons. The aim of this study is to determine the capability of surgical residents to perform this assessment. METHODS: Both surgeons and surgical residents assessed unedited LC videos using a 6-point CVS, a CAT, using an online video assessment platform. The CAT consists of the following three criteria: 1. clearance of hepatocystic triangle, 2. cystic plate, and 3. two structures connect to the gallbladder, with a maximum of 2 points available for each criterion. A higher score indicates superior surgical performance. The intraclass correlation coefficient (ICC) was employed to assess the inter-rater reliability between surgeons and surgical residents. RESULTS: In total, 283 LC videos were assessed by 19 surgeons and 31 surgical residents. The overall ICC for all criteria was 0.628. Specifically, the ICC scores were 0.504 for criterion 1, 0.639 for criterion 2, and 0.719 for the criterion involving the two structures connected to the gallbladder. Consequently, only the criterion regarding clearance of the hepatocystic triangle exhibited fair agreement, whereas the other two criteria, as well as the overall scores, demonstrated good agreement. In 71% of cases, both surgeons and surgical residents scored a total score either ranging from 0 to 4 or from 5 to 6. CONCLUSION: Compared to the gold standard, i.e., the surgeons' assessments, surgical residents are equally skilled at assessing critical view of safety (CVS) in laparoscopic cholecystectomy (LC) videos. By incorporating video-based assessments of surgical procedures into their training, residents could potentially enhance their learning pace, which may result in better clinical outcomes.

Long-term restoration of bowel continuity after rectal cancer resection and the influence of surgical technique: A nationwide cross-sectional study.

AIM: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases.

Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery in resectable patients shows limited benefit, and novel treatments are urgently needed. The majority of CRC-PMs represent the CMS4 molecular subtype of CRC, and here we queried the vulnerabilities of this subtype in pharmacogenomic databases to identify novel therapies. This reveals the copper ionophore elesclomol (ES) as highly effective against CRC-PMs. ES exhibits rapid cytotoxicity against CMS4 cells by targeting mitochondria. We find that a markedly reduced mitochondrial content in CMS4 cells explains their vulnerability to ES. ES demonstrates efficacy in preclinical models of PMs, including CRC-PMs and ovarian cancer organoids, mouse models, and a HIPEC rat model of PMs. The above proposes ES as a promising candidate for the local treatment of CRC-PMs, with broader implications for other PM-prone cancers.

Towards Equal Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy and Survival in Patients with Isolated Colorectal Peritoneal Metastases: A Nationwide Population-Based Study.

BACKGROUND: Before 2016, patients with isolated synchronous colorectal peritoneal metastases (PMCRC) diagnosed in expert centers had a higher odds of undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and better overall survival (OS) than those diagnosed in referring centers. Nationwide efforts were initiated to increase awareness and improve referral networks. METHODS: This nationwide study aimed to evaluate whether the between-center differences in odds of undergoing CRS-HIPEC and OS have reduced since these national efforts were initiated. All patients with isolated synchronous PMCRC diagnosed between 2009 and 2021 were identified from the Netherlands Cancer Registry. Associations between hospital of diagnosis and the odds of undergoing CRS-HIPEC, as well as OS, were assessed using multilevel multivariable regression analyses for two periods (2009-2015 and 2016-2021). RESULTS: In total, 3948 patients were included. The percentage of patients undergoing CRS-HIPEC increased from 17.2% in 2009-2015 (25.4% in expert centers, 16.5% in referring centers), to 23.4% in 2016-2021 (30.2% in expert centers, 22.6% in referring centers). In 2009-2015, compared with diagnosis in a referring center, diagnosis in a HIPEC center showed a higher odds of undergoing CRS-HIPEC (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.02-2.67) and better survival (hazard ratio [HR] 0.80, 95% CI 0.66-0.96). In 2016-2021, there were no differences in the odds of undergoing CRS-HIPEC between patients diagnosed in HIPEC centers versus referring centers (OR 1.27, 95% CI 0.76-2.13) and survival (HR 1.00, 95% CI 0.76-1.32). CONCLUSION: Previously observed differences in odds of undergoing CRS-HIPEC were no longer present. Increased awareness and the harmonization of treatment for PMCRC may have contributed to equal access to care and a similar chance of survival at a national level.

Neovaginal cancer after sigmoid vaginoplasty: Implications for postoperative cancer surveillance.

Background: Intestinal vaginoplasty can be performed as vaginal reconstruction procedure. Aa pedicled intestinal segment is isolated and transferred to the (neo)vaginal cavity to form the neovaginal lining. Case: A 38-year old patient with Fanconi anemia and congenital vaginal absence, who underwent sigmoid vaginoplasty at the age of one, visited the outpatient clinic with a palpable neovaginal mass. At MRI examination, a neovaginal tumor was observed of approximately 25 × 10 mm without lymphadenopathy, which turned out to be a mucinous adenocarcinoma (T3N0M0). She underwent excision of the total mesocolon, including the sigmoid neovagina, coloanal anastomosis and anus. Summary and Conclusion: Postoperative cancer surveillance seems justified after sigmoid vaginoplasty, even more so in patients with a (genetically) high risk of developing cancer and/or with a history of malignancy.

Oncologic outcomes of screen-detected and non-screen-detected T1 colorectal cancers.

BACKGROUND: The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program. METHODS: Data from T1 CRC patients diagnosed between 2014 and 2017 were collected from 12 hospitals in the Netherlands. The presence of lymph node metastasis (LNM) at diagnosis was compared between screen-detected and non-screen-detected patients using multivariable logistic regression. Cox proportional hazard regression was used to analyze differences in the time to recurrence (TTR), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival. Additionally, the performance of conventional risk factors for LNM was evaluated across the groups. RESULTS: 1803 patients were included (1114 [62%] screen-detected), with median follow-up of 51 months (interquartile range 30). The proportion of LNM did not significantly differ between screen- and non-screen-detected patients (12.6% vs. 8.9%; odds ratio 1.41; 95%CI 0.89-2.23); a prediction model for LNM performed equally in both groups. The 3- and 5-year TTR, MFS, and CSS were similar for patients within and outside the screening program. However, overall survival was significantly longer in screen-detected T1 CRC patients (adjusted hazard ratio 0.51; 95%CI 0.38-0.68). CONCLUSIONS: Screen-detected and non-screen-detected T1 CRCs have similar stage distributions and oncologic outcomes and can therefore be treated equally. However, screen-detected T1 CRC patients exhibit a lower rate of non-CRC-related mortality, resulting in longer overall survival.

Evolution of surgical approach to rectal cancer resection: A multinational registry assessment.

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.

Better stoma care using the Stoma App: does it help? A first randomized double-blind clinical trial on the effect of mobile healthcare on quality of life in stoma patients.

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.

Challenging case of deficient mismatch repair right-sided locally advanced adenocarcinoma of the ascending colon with duodenal involvement: A case report including step-by-step video of operation.

INTRODUCTION AND IMPORTANCE: Irresectable colon cancer presents a complex clinical challenge. Neoadjuvant immunotherapy has shown potential in improving resectability. Additionally, advancements in surgical techniques, including complete mesocolic excision (CME) with central vascular ligation (CVL), have contributed to better outcomes for right-sided colon cancer. This case report aims to demonstrate the successful laparoscopic resection of initial appearing irresectable colon cancer with suspected duodenal involvement. CASE PRESENTATION: A 70-year-old female presented with an irresectable mismatch repair deficient (dMMR) adenocarcinoma of the ascending colon with suspected duodenal ingrowth. Neoadjuvant treatment with pembrolizumab and ataluren resulted in a significant response, allowing for surgical resection. A laparoscopic right hemicolectomy with CME, including CVL, intracorporeal anastomosis and extraction through a Pfannenstiel incision, was performed. Additionally, the serosal layer of the duodenum was shaved after observing the absence of intraluminal invasion. Postoperatively, transient gastroparesis occurred, but overall outcomes were favourable. CLINICAL DISCUSSION: This case emphasizes the potential of immunotherapy in improving resectability for irresectable dMMR colon cancer with suspected involvement of surrounding organs. The combination of neoadjuvant therapy and advanced surgical techniques, such as CME with CVL, shows promise in achieving favourable clinical outcomes. However, further studies are needed to validate the effectiveness and safety of this combined approach in a larger cohort of patients. CONCLUSION: The successful laparoscopic resection of initially irresectable dMMR colon cancer with duodenal involvement, following neoadjuvant immunotherapy, demonstrated promising outcomes. This case advocates for further exploration of neoadjuvant treatments' efficacy, coupled with advanced surgical techniques, in managing locally advanced right-sided colon cancer.

Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes.

Importance: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014. Objective: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level. Design, Setting, and Participants: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022. Main Outcomes and Measures: The main outcomes were 4-year local recurrence and overall survival rates. Results: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001). Conclusions and Relevance: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

Nationwide standardization of minimally invasive right hemicolectomy for colon cancer and development and validation of a video-based competency assessment tool (the Right study).

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).

Allogeneic NK cells induce monocyte-to-dendritic cell conversion, control tumor growth, and trigger a pro-inflammatory shift in patient-derived cultures of primary and metastatic colorectal cancer.

INTRODUCTION: Natural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly lyse tumor cells without inducing graft-versus-host disease. As NK cells are also able to influence the function of other immune cells (most notably dendritic cells (DC)), a better understanding of the effects of allogeneic NK cell products on the host immune system is required. In this study, we analyzed the effects of an allogeneic off-the-shelf NK cell product, on the tumor microenvironment (TME) of primary and metastatic colorectal cancer (pCRC and mCRC, respectively). Moreover, we explored if the combination of NK cells with R848, a toll-like receptors 7/8 ligand, could further enhance any pro-inflammatory effects. METHODS: Ex vivo expanded umbilical cord blood stem cell derived NK cells were co-cultured with pCRC or mCRC single-cell suspensions in the presence or absence of R848 for 5 days, during and after which flow cytometry and cytokine release profiling were performed. RESULTS: NK cells efficiently induced lysis of tumor cells in both pCRC and mCRC single-cell suspensions and thereby controlled growth rates during culture. They also induced differentiation of infiltrating monocytic cells to an activated DC phenotype. Importantly, this NK-mediated myeloid conversion was also apparent in cultures after tumor cell depletion and was further enhanced by combining NK cells with R848. Moreover, NK cells, and to a greater extent, the combination of NK cells and R848, triggered CD8+ and CD4+ T-cell activation as well as a reduction in activated regulatory T cell rates. Finally, the combination of NK cells and R848 induced a pro-inflammatory shift in the cytokine release profile resulting in higher levels of interferon (IFN)-γ, interleukin (IL)-2, IL-12p70, and IFN-α as well as a reduction in IL-6, in both pCRC and mCRC cultures. CONCLUSION: Allogeneic NK cells engaged in favorable myeloid crosstalk, displayed effective antitumor activity and, when combined with R848, induced a pro-inflammatory shift of the CRC TME. These findings prompt the investigation of NK cells and R848 as a combination therapy for solid tumors.

Best Evidence for Each Surgical Step in Minimally Invasive Right Hemicolectomy: A Systematic Review.

Objective: The aim of this study was to systematically review the literature for each surgical step of the minimally invasive right hemicolectomy (MIRH) for non-locally advanced colon cancer, to define the most optimal procedure with the highest level of evidence. Background: High variability exists in the way MIRH is performed between surgeons and hospitals, which could affect patients' postoperative and oncological outcomes. Methods: A systematic search using PubMed was performed to first identify systematic reviews and meta-analyses, and if there were none then landmark papers and consensus statements were systematically searched for each key step of MIRH. Systematic reviews were assessed using the AMSTAR-2 tool, and selection was based on highest quality followed by year of publication. Results: Low (less than 12 mmHg) intra-abdominal pressure (IAP) gives higher mean quality of recovery compared to standard IAP. Complete mesocolic excision (CME) is associated with lowest recurrence and highest 5-year overall survival rates, without worsening short-term outcomes. Routine D3 versus D2 lymphadenectomy showed higher LN yield, but more vascular injuries, and no difference in overall and disease-free survival. Intracorporeal anastomosis is associated with better intra- and postoperative outcomes. The Pfannenstiel incision gives the lowest chance of incisional hernias compared to all other extraction sites. Conclusion: According to the best available evidence, the most optimal MIRH for colon cancer without clinically involved D3 nodes entails at least low IAP, CME with D2 lymphadenectomy, an intracorporeal anastomosis and specimen extraction through a Pfannenstiel incision.

Patients' perspectives and the perceptions of healthcare providers in the treatment of early rectal cancer; a qualitative study.

BACKGROUND: Shared decision-making has become of increased importance in choosing the most suitable treatment strategy for early rectal cancer, however, clinical decision-making is still primarily based on physicians' perspectives. Balancing quality of life and oncological outcomes is difficult, and guidance on patients' involvement in this subject in early rectal cancer is limited. Therefore, this study aimed to explore preferences and priorities of patients as well as physicians' perspectives in treatment for early rectal cancer. METHODS: In this qualitative study, semi-structured interviews were performed with early rectal cancer patients (n = 10) and healthcare providers (n = 10). Participants were asked which factors influenced their preferences and how important these factors were. Thematic analyses were performed. In addition, participants were asked to rank the discussed factors according to importance to gain additional insights. RESULTS: Patients addressed the following relevant factors: the risk of an ostomy, risk of poor bowel function and treatment related complications. Healthcare providers emphasized oncological outcomes as tumour recurrence, risk of an ostomy and poor bowel function. Patients perceived absolute risks of adverse outcome to be lower than healthcare providers and were quite willing undergo organ preservation to achieve a better prospect of quality of life. CONCLUSION: Patients' preferences in treatment of early rectal cancer vary between patients and frequently differ from assumptions of preferences by healthcare providers. To optimize future shared decision-making, healthcare providers should be aware of these differences and should invite patients to explore and address their priorities more explicitly during consultation. Factors deemed important by both physicians and patients should be expressed during consultation to decide on a tailored treatment strategy.

A Deep Learning Framework with Explainability for the Prediction of Lateral Locoregional Recurrences in Rectal Cancer Patients with Suspicious Lateral Lymph Nodes.

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.