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Karin ATGM Wasmann,1 Charlotte EL Klaver,1 Jarmila DW van der Bilt,1,2 Susan van Dieren,3 Iris D Nagtegaal,4 Cornelis JA Punt,5 Bert van Ramshorst,6 Albert M Wolthuis,2 Johannes HW de Wilt,7 André D’Hoore,2 Hjalmar C van Santvoort,6 Pieter J Tanis11Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, AZ 1105, Amsterdam, The Netherlands; 2Department of Abdominal Surgery, University Hospital Leuven, Leuven 3000, Belgium; 3Clinical Research Unit, Amsterdam University Medical Centre, University of Amsterdam, AZ 1105, Amsterdam, The Netherlands; 4Department of Pathology, Radboud University Medical Centre, GA 6525, Nijmegen, The Netherlands; 5Department of Medical Oncology, Amsterdam University Medical Centre, University of Amsterdam, AZ 1105, Amsterdam, The Netherlands; 6Department of Surgery, St. Antonius Hospital, CM 3435, Nieuwegein, The Netherlands; 7Department of Surgery, Radboud University Medical Centre, GA 6525, Nijmegen, The NetherlandsPurpose: The aim of this study was to evaluate the impact of a laparoscopic approach on long-term oncological outcomes in curative intent surgery for pT4 colon cancer, in both overall and stratified subgroups with distinct clinical entities.Patients and methods: Patients with a pT4N0-2M0 colon cancer from four centers between 2000 and 2014 were included. Laparoscopic and open approaches were compared according to the intention-to-treat principle. Propensity scores were used to adjust for baseline differences between the groups in three manners: i) as a linear predictor in a Cox regression model, ii) to create a 1:1 matched cohort, and iii) to stratify patients into four groups with an increasing chance of receiving laparoscopy.Results: In total, 424 patients were included. After 1:1 matching, a laparoscopic approach correlated with higher rates of radical resection, lower morbidity, and a higher percentage of patients receiving adjuvant chemotherapy. This translated into better 5-year disease-free survival (52% vs 40%, HR 0.70; 95% CI 0.50–0.96) and 5-year overall survival (68% vs 57%, HR 0.66; 95% CI 0.43–0.99). These results were confirmed in the other two propensity score analyses. In the multivariable models, adjuvant chemotherapy remained independently associated with better survival, whereas surgical approach lost significance.Conclusions: In locally advanced colon cancer, an intentional laparoscopic approach in experienced hands seems to decrease morbidity and to increase the proportion of patients receiving adjuvant chemotherapy. Receiving adjuvant chemotherapy was independently associated with improved survival.Keywords: T4 colon cancer, laparoscopy, lower GI

Substantial variability exists in what pathologists consider as pT4a in colorectal cancer when tumor cells are within 1 mm of the free peritoneal surface. This study aimed to determine if the measured sub-millimeter distance between tumor cells and the free peritoneal surface would offer an objective means of stratifying patients according to the risk of developing peritoneal metastases. Histological slides of patients included in the COLOPEC trial, with resectable primary c/pT4N0-2M0 colon cancer, were centrally reassessed. Specific tumor morphological variables were collected, including distance from tumor to free peritoneal surface, measured in micrometers (µm). The primary outcome, 3-year peritoneal metastasis rate, was compared between four groups of patients stratified for relation of tumor cells to the peritoneum: 1) Full peritoneal penetration with tumor cells on the peritoneal surface, 2) 0-99 µm distance to the peritoneum, 3) 100-999 µm to the peritoneum, and 4) ≥1000 µm to the peritoneum, by using Kaplan-Meier analysis. In total, 189 cases were included in the present analysis. Cases with full peritoneal penetration (n = 89), 0-99 µm distance to the peritoneal surface (n = 34), 100-999 µm distance (n = 33), and ≥1000 µm distance (n = 33), showed significantly different 3-year peritoneal metastases rates of 25% vs 29% vs 6% vs 12%, respectively (Log Rank, p = 0.044). N-category did not influence the risk of peritoneal metastases in patients with a tumor distance beyond 100 µm, while only the N2 category seemed to result in an additive risk in patients with a distance of 0-99 µm. The findings of this study suggest that the measured shortest distance between tumor cells and the free peritoneal surface is useful as an objective means of stratifying patients according to the risk of developing peritoneal metastases. This simple measurement is practical and may help in providing a precise definition of pT4a. Trial registration: NCT02231086 (Clinicaltrials.gov)., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background: It was hypothesized that colon cancer with only retroperitoneal invasion is associated with a low risk of peritoneal dissemination. This study aimed to compare the risk of metachronous peritoneal metastases (mPM) between intraperitoneal and retroperitoneal invasion., Methods: In this international, multicenter cohort study, patients with pT4bN0-2M0 colon cancer who underwent curative surgery were categorized as having intraperitoneal invasion (e.g. bladder, small bowel, stomach, omentum, liver, abdominal wall) or retroperitoneal invasion only (e.g. ureter, pancreas, psoas muscle, Gerota's fascia). Primary outcome was 5-year mPM cumulative rate, assessed by Kaplan-Meier analysis., Results: Out of 907 patients with pT4N0-2M0 colon cancer, 198 had a documented pT4b category, comprising 170 patients with intraperitoneal invasion only, 12 with combined intra- and retroperitoneal invasion, and 16 patients with retroperitoneal invasion only. At baseline, only R1 resection rate significantly differed: 4/16 for retroperitoneal invasion only versus 8/172 for intra- +/- retroperitoneal invasion (p = 0.010). Overall, 22 patients developed mPM during a median follow-up of 45 months. Two patients with only retroperitoneal invasion developed mPM, both following R1 resection. The overall 5-year mPM cumulative rate was 13% for any intraperitoneal invasion and 14% for retroperitoneal invasion only (Log Rank, p = 0.878), which was 13% and 0%, respectively, in patients who had an R0 resection (Log Rank, p = 0.235)., Conclusion: This study suggests that pT4b colon cancer patients with only retroperitoneal invasion who undergo an R0 resection have a negligible risk of mPM, but this is difficult to prove because of its rarity. This observation might have implications regarding individualized follow-up., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity., (© 2022. The Author(s).)

Introduction: With evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes., Materials and Methods: From eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS)., Results: In total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23-60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p = 0.005). Independent predictors for metachronous PM were female sex, right-sided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p = 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p = 0.138). Five-year DFS and OS were 54% vs. 62% (p = 0.095) and 63% vs. 68% (p = 0.148) for pT4a vs. pT4b categories, respectively., Conclusion: Patients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The peritoneum is a common site of dissemination in patients with colorectal cancer. In order to identify high-risk patients and improve therapeutic strategies, a better understanding of the peritoneal dissemination process and the reasons behind the high heterogeneity that is observed between patients is required. We aimed to create a murine model to further elucidate the process of peritoneal dissemination and to provide an experimental platform for further studies. We developed an in vivo model to assess patterns of peritoneal dissemination of 15 colorectal cancer cell lines. Immune deficient mice were intraperitoneally injected with 10,000 human colorectal cancer cells. Ten weeks after injection, or earlier in case of severe discomfort, the mice were sacrificed followed by dissection including assessment of the outgrowth and localization of peritoneal metastases. Furthermore, using a color-based clonal tracing method, the clonal dynamics of peritoneal nodules were observed. The different cell lines showed great variation in the extent of peritoneal outgrowth, ranging from no outgrowth to localized or widespread outgrowth of cells. An association between KRAS pathway activation and the formation of peritoneal metastases was identified. Also, cell line specific tumor location preferences were observed, with similar patterns of outgrowth in anatomically related areas. Furthermore, different patterns regarding clonal dynamics were found, varying from monoclonal or polyclonal outgrowth to extensively dispersed polyclonal lesions. The established murine model recapitulates heterogeneity as observed in human peritoneal metastases, which makes it a suitable platform for future (intervention) studies.

Background: Multivisceral resection for T4b colon cancer constitutes a heterogeneous group of surgical procedures. The purpose of this study was to explore clinically distinct categories of multivisceral resection, with subsequent correlation to postoperative complications and oncological outcomes., Methods: In this multicenter cohort study, all consecutive patients without metastases who underwent multivisceral resection for pT4bN0-2M0 colon cancer between 2000 and 2014 were included. Multivisceral resection was divided into four categories: (i) gastrointestinal (including the stomach), (ii) urologic ((partial) bladder and ureter), (iii) solid organ (spleen, kidney, liver, pancreas, and uterus), and (iv) abdominal wall/omentum/ovaries. The primary outcome was surgical complications and secondary outcomes were 5-year intra-abdominal recurrence, disease-free survival, and overall survival., Results: In total, 130 patients who underwent curative intent resection of pT4 colon cancer were included. Patients who underwent multivisceral resection within multiple categories were assigned to one of the categories based on hierarchy of clinical impact after exploratory analysis. For the primary endpoint, 55 patients were assigned to gastrointestinal, 14 to urologic, 14 to solid organ, and 47 to abdominal wall/omentum/ovaries multivisceral resection. Gastrointestinal multivisceral resection was independently associated with surgical complications (HR 3.9, 95% CI 1.4-10.6). Abdominal wall/omentum/ovaries multivisceral resection was significantly related with intra-abdominal recurrence (HR 7.8, 95% CI 1.0-57.8). The 5-year disease-free survival and overall survival showed no significant differences per multivisceral resection category., Conclusions: Multivisceral resections for T4b colon cancer are heterogeneous procedures considering risk profiles. The proposed multivisceral resection subclassification needs validation, but might improve comparability between studies and hospitals (auditing).

Background: Locoregional recurrence of colon cancer (LRCC) following curative resection is an underreported clinical entity, especially regarding isolated LRCC which is amenable for surgery. The purpose of this study was to review the literature on incidence of LRCC and surgical treatment with corresponding outcome, and to describe an institutional experience with curative-intent surgery, whether or not as part of a multimodality approach., Methods: The PubMed and Medline literature databases 1978-2017 were searched and retrieved articles were assessed for eligibility. Based on a prospectively maintained database since 2010 at a tertiary referral center, original patient files were retrospectively reviewed., Results: Systematic literature review resulted in 11 studies reporting on incidence of LRCC, which ranged from 3.1% to 19.0% before 2010, and from 4.4% to 6.7% in three most recent studies. Twelve identified studies reported on outcome of surgically treated LRCC, with a median survival of 30 and 33 months in the two largest studies. The institutional database entailed 17 patients who underwent resection of isolated LRCC between 2010 and 2018. Median time to recurrence was 19 months. After a median follow-up after resection of LRCC of 20 months, 7 patients had died, 9 patients were alive without evidence of disease and 1 patient with evidence of disease; Median DFS was 36 months and 3-year OS was 65%., Conclusion: Locoregional recurrence of colon cancer occurs in about 5% in most recent series, of whom selected patients are eligible for surgical treatment, with a fair chance of long-term disease control., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Owing to substantial costs and increasing interest in the nonoperative management of appendicitis, the necessity of routine histopathologic examination of appendectomy specimens is being questioned. The aim of this study was to determine whether routine histopathologic examination after appendectomy for suspected appendicitis should still be performed., Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies listing the histopathologic diagnoses after appendectomy for suspected appendicitis. Main outcomes were the incidence of histopathologically proven aberrant findings, the ability of surgeons to recognize unexpected appendiceal pathology intraoperatively, and the percentage of aberrant findings resulting in a change of postoperative management. A meta-analysis was performed using a random-effects model., Results: Twenty-five studies with 57,357 patients were included. The pooled percentage of aberrant findings was 2.52% (95% confidence interval 1.81-3.51). Neoplasms were found in 0.71% (95% confidence interval 0.54-0.94). Findings of the intraoperative assessment by the surgeon were reported for 82 of the 2,718 (3.0%) unexpected diagnoses, with great variation between studies. The impact on postoperative management was described for 237 of 2,718 (8.7%) aberrant findings. Of these, 166 (70.0%) resulted in a change of postoperative management., Conclusion: Based on current evidence, it remains unclear how many of the unexpected appendiceal pathologies with clinical consequences can be identified intraoperatively by the surgeon. Until reliable data on the safety and potential cost savings of a selective policy becomes available, we advise sending appendectomy specimens routinely for histopathologic examination., (Copyright © 2020. Published by Elsevier Inc.)

Objective: The objective of this systematic review and meta-analysis was to examine the effects of omentoplasty on pelviperineal morbidity following abdominoperineal resection (APR) in patients with cancer., Background: Recent studies have questioned the use of omentoplasty for the prevention of perineal wound complications., Methods: A systematic review of published literature since 2000 on the use of omentoplasty during APR for cancer was undertaken. The authors were requested to share their source patient data. Meta-analyses were conducted using a random-effects model., Results: Fourteen studies comprising 1894 patients (n = 839 omentoplasty) were included. The majority had APR for rectal cancer (87%). Omentoplasty was not significantly associated with the risk of presacral abscess formation in the overall population (RR 1.11; 95% CI 0.79-1.56), nor in planned subgroup analysis (n = 758) of APR with primary perineal closure for nonlocally advanced rectal cancer (RR 1.06; 95% CI 0.68-1.64). No overall differences were found for complicated perineal wound healing within 30 days (RR 1.30; 95% CI 0.92-1.82), chronic perineal sinus (RR 1.08; 95% CI 0.53-2.20), and pelviperineal complication necessitating reoperation (RR 1.06; 95% CI 0.80-1.42) as well. An increased risk of developing a perineal hernia was found for patients submitted to omentoplasty (RR 1.85; 95% CI 1.26-2.72). Complications related to the omentoplasty were reported in 4.6% (95% CI 2.5%-8.6%)., Conclusions: This meta-analysis revealed no beneficial effect of omentoplasty on presacral abscess formation and perineal wound healing after APR, while it increases the likelihood of developing a perineal hernia. These findings do not support the routine use of omentoplasty in APR for cancer.

Clinical significance of the pT4 category in colon cancer is increasing with several therapeutic implications. The aim of this study was to evaluate variability in diagnosing pT4a colon cancer. Twelve pathologists classified 66 preselected scanned Hematoxylin/Eosin-stained slides with tumor cells at a distance of 25-1500 μm (n = 22), 0-25 μm (n = 22), or on (n = 22) the peritoneal surface. Inter- and intraobserver variability were calculated using Kappa statistics. For interlaboratory variability, pathology reports of pT3 and pT4a colon cancer were extracted from the Dutch Pathology Registry between 2012 and 2015. The proportion of pT4a (pT4a/(pT3+pT4a)) was compared between 33 laboratories. Potential risk of understaging was assessed by determining the average number of blocks taken from pT3 and pT4a N0-2M0 tumors with metachronous peritoneal metastasis. Interobserver variability among 12 pathologists was 0.50 (95%CI 0.41-0.60; moderate agreement). Intraobserver variability (8 pathologists) was 0.71 (substantial agreement). A total of 7745 reports with pT3 or pT4aN0-2M0 colon cancer from 33 laboratories were included for interlaboratory analysis. Median percentage of pT4a was 15.5% (range 3.2-24.6%). After adjustment for case mix, 8 labs diagnosed pT4a significantly less or more frequently than the median lab. Metachronous peritoneal metastases were histologically verified in 170 of 6629 pT3 and in 129 of 1116 pT4a tumors, with a mean number of blocks of 4.03(SD 1.51) and 4.78 (SD 1.76) taken from the primary tumors, respectively (p < 0.001). A substantial variability in diagnosing pT4a colon cancer exists, both at pathologist and laboratory level. Diagnosis of pT4a stage appears to be challenging and there is a need for standardizing assessment of this pathological entity.

Background: Nearly a quarter of patients with locally advanced (T4 stage) or perforated colon cancer are at risk of developing peritoneal metastases, often without curative treatment options. We aimed to determine the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with locally advanced colon cancer., Methods: This multicentre, open-label trial was done in nine hospitals that specialised in HIPEC in the Netherlands. Patients with clinical or pathological T4N0-2M0-stage tumours or perforated colon cancer were randomly assigned (1:1), with a web-based randomisation application, before resection of the primary tumour, to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy (experimental group) or to adjuvant systemic chemotherapy alone (control group). Patients were stratified by tumour characteristic (T4 or perforation), age (<65 years or ≥65 years), and surgical approach of the primary tumour resection (laparoscopic or open). Key eligibility criteria included age between 18 and 75 years, adequate clinical condition for HIPEC, and intention to start adjuvant systemic chemotherapy. Patients with metastatic disease were ineligible. Adjuvant HIPEC consisted of fluorouracil (400 mg/m 2 ) and leucovorin (20 mg/m 2 ) delivered intravenously followed by intraperitoneal delivery of oxaliplatin (460 mg/m 2 ) for 30 min at 42°C, delivered simultaneously or within 5-8 weeks after primary tumour resection. In all patients without evidence of recurrent disease at 18 months, a diagnostic laparoscopy was done. The primary endpoint was peritoneal metastasis free-survival at 18 months, measured in the intention-to-treat population, with the Kaplan-Meier method. Adverse events were assessed in all patients who received assigned treatment. This study is registered with ClinicalTrials.gov, number NCT02231086., Findings: Between April 1, 2015, and Feb 20, 2017, 204 patients were randomly assigned to treatment (102 in each group). In the HIPEC group, two patients withdrew consent after randomisation. In this group, 19 (19%) of 100 patients were diagnosed with peritoneal metastases: nine (47%) during surgical exploration preceding intentional adjuvant HIPEC, eight (42%) during routine follow-up, and two (11%) during diagnostic laparoscopy at 18-months. In the control group, 23 (23%) of 102 patients were diagnosed with peritoneal metastases, of whom seven (30%) were diagnosed by laparoscopy at 18-months and 16 during regular follow-up (therefore making them ineligible for diagnostic laparoscopy). In the intention-to-treat analysis (n=202), there was no difference in peritoneal-free survival at 18-months (80·9% [95% CI 73·3-88·5] for the experimental group vs 76·2% [68·0-84·4] for the control group, log-rank one-sided p=0·28). 12 (14%) of 87 patients who received adjuvant HIPEC developed postoperative complications and one (1%) encapsulating peritoneal sclerosis., Interpretation: In patients with T4 or perforated colon cancer, treatment with adjuvant HIPEC with oxaliplatin did not improve peritoneal metastasis-free survival at 18 months. Routine use of adjuvant HIPEC is not advocated on the basis of this trial., Funding: Organization for Health Research and Development and the Dutch Cancer Society., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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

Introduction: Patients with pT4 colon cancer are at risk of developing intra-abdominal recurrence. Infectious complications have shown to negatively influence disease free survival (DFS) and overall survival (OS) in stage I-III colon cancer. The aim of this study was to determine whether surgical site infections (SSIs) also increase the risk of intra-abdominal recurrence in pT4 colon cancer patients., Methods: All consecutive patients with pT4N0-2M0 colon cancer from four centres between January 2000 and December 2014 were included. Patients were categorized into 2 groups; with and without a postoperative (<30 days) SSIs. SSIs included both deep incisional as well as organ/space SSIs. The primary outcome was intra-abdominal recurrence (including local/incisional recurrence, peritoneal metastases) and was assessed using Kaplan-Meier and Cox regression analyses. Secondary outcome measures were DFS and OS., Results: Out of 420 patients, 62 (15%) developed a SSI. The 5-year intra-abdominal recurrence rates were 44% and 27% for patients with and without a SSI, respectively (p = 0.011). After multivariate analysis, SSI was independently associated with intra-abdominal recurrence (HR 1.807 (1.091-2.992)), worse DFS (HR 1.788 (1.226-2.607)), and worse OS (HR 1.837 (1.135-2.973)). Other independent risk factors for intra-abdominal recurrence were a R1 resection (HR 2.616 (1.264-5.415)) and N2-stage (HR 2.096 (1.318-3.332))., Conclusion: SSIs after resection of a pT4N0-2M0 colon cancer are associated with an increased risk of intra-abdominal recurrence and worse survival. This finding supports the hypothesis that infection-based immunologic pathways play a role in colon cancer cell dissemination and outgrowth., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: When a colorectal or coloanal anastomosis fails because of persistent leakage or stenosis, or the anastomosis has to be resected for recurrent cancer, constructing a new anastomosis might be an option in selected patients. This is a rare and complex type of redo surgery., Objective: The aim of this review was to evaluate the current literature on redo anastomosis for complicated colorectal or coloanal anastomosis., Data Sources: A systematic literature search of MEDLINE, EMBASE, the Cochrane Library, the PROSPERO register, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform database was performed., Study Selection: Two reviewers independently screened the available literature. All studies reporting on redo surgery and aiming at reconstruction of a prior low colorectal or coloanal anastomosis for any indication were included., Main Outcome Measures: Primary outcome was successful restoration of continuity. Secondary outcomes were postoperative morbidity, pelvic sepsis, incontinence, and mortality., Results: Nine studies were included, comprising 291 patients, of whom 76% had index surgery for colorectal cancer. Pooled proportions showed an overall success rate of 79% (95% CI, 69-86), with a pooled incidence of major postoperative morbidity of 16% (95% CI, 10-24). The pooled pelvic sepsis rate was 16% (95% CI, 9-27), and the pooled surgical reintervention and readmission rates were 11% (95% CI, 8-17) and 7% (95% CI, 3-15). Five studies reported on incontinence, with a pooled proportion of 17% (95% CI, 10-26)., Limitations: The limitations of this review are the lack of randomized controlled trials and high-quality studies, and the small sample sizes and heterogeneous patient populations in the included studies., Conclusions: Redo surgery is a valuable treatment option for the complicated colorectal or coloanal anastomosis with 79% successful restoration of bowel continuity in the published literature from experienced tertiary centers.

Background: Findings show T4 colorectal cancer (CRC) to be a risk factor for the development of peritoneal metastases (PM). Heterogeneity regarding peritoneal involvement of T4 tumors might explain the wide range of reported PM incidences (8-50%). Hyperplastic and mesothelial inflammatory reactions complicate evaluation of the exact primary tumor involvement of the peritoneal layer. This retrospective cohort study aimed to assess the association between either inflammatory peritoneal reaction or peritoneal involvement of the primary tumor and the risk of PM., Methods: Since 2010, pathologists at UZ Leuven have systematically categorized peritoneal involvement in peritoneal reaction with tumor less than 1 mm from the peritoneal surface or true peritoneal penetration. All patients undergoing resection of CRC between January 2010 and July 2013 who fulfilled either of these pathologic criteria were included in this study., Results: The study enrolled 159 CRC patients. Peritoneal reaction with tumor less than 1 mm from the peritoneal surface was present in 43 patients and true peritoneal penetration in 116 patients. Overall, 29 patients (18%) had synchronous PM, and 30 patients (23%) had metachronous PM. In the multivariable analysis, true peritoneal penetration, in contrast to peritoneal reaction with tumor less than 1 mm from the peritoneum, was associated with greater risk of PM (odds ratio [OR], 2.518; range, 1.038-6.111; p = 0.041) and lymph node involvement (N1: OR, 1.572; range, 0.651-3.797 vs N2: OR, 4.046; range, 1.549-10.569; p = 0.014)., Conclusion: Histologically confirmed true peritoneal penetration by CRC, rather than inflammatory peritoneal reaction constitutes a high risk for PM. With evolving treatment strategies that aim to treat PM in an earlier phase, identification of high-risk patients becomes highly important clinically.

Background: In colon cancer, T4 stage is still assumed to be a relative contraindication for laparoscopic surgery considering the oncological safety. The aim of this systematic review with meta-analysis was to evaluate short- and long-term oncological outcomes after laparoscopic surgery for T4 colon cancer, and to compare these with open surgery., Methods: Using systematic review of literature, studies reporting on radicality of resection, disease-free survival (DFS), and/or overall survival (OS) after laparoscopic surgery for T4 colon cancer were identified, with or without a control group of open surgery. Pooled proportions and risk ratios were calculated using an inverse variance method., Results: Thirteen observational cohort studies published between 2012 and 2017 were included, together consisting of 1217 patients that received laparoscopic surgery and 1357 with an open procedure. The proportion of multivisceral resections was larger in the open group in five studies. Based on 11 studies, the pooled proportion of R0 resection was 0.96 (95% CI: 0.91-0.99) and 0.96 (95% CI: 0.90-0.98) after laparoscopic and open surgery, respectively. Analysing (mainly) T4a subgroups in 6 evaluable studies revealed pooled R0 resection rates of 0.94 in both groups. No significant differences were found between laparoscopic and open surgery for any survival measure: RR 1.07 (95% CI: 0.96-1.20) for 3-year DFS, RR 1.04 (95% CI: 0.95-1.15) for 5-year DFS, RR 1.07 (95% CI: 0.99-1.14) for 3-year OS, and RR 1.05 (95% CI: 0.98-1.12) for 5-year OS., Conclusion: Literature on laparoscopic surgery for T4 colon cancer is restricted to non-randomized comparisons with substantial allocation bias. Laparoscopic surgery for T4a tumours might be safe, whereas for T4b colon cancer requiring multivisceral resection it should be applied with caution.

Background: The high morbidity associated with radical resection for rectal cancer is an incentive for surgeons to adopt strategies aimed at organ preservation, particularly for early disease. There are a number of different approaches to achieve this. In this study we have collated current national and international guidelines to produce a synopsis to support this changing practice., Methods: The databases PubMed, Embase, Trip database, national guideline clearinghouse, BMJ Best practice were interrogated. Guidelines published before 2010 were excluded. The AGREE-II tool was used for quality assessment., Results: 24 guidelines were drawn from 2278 potential publications. A consensus exists for local excision for "low risk" T1 rectal cancer but there is no agreement how to stratify the risk of treatment failure. There is a low level of agreement for rectal preservation for more advanced disease but when mentioned is recommended for unfit patients or in th context of a clinical trial. Guidelines are inconsistent with respect to surveillance in node negative disease and after, complete response to chemoradiotherapy CONCLUSION: According to current guidelines and consensus statements organ preservation for rectal cancer beyond low risk T1, is still considered experimental and only indicated in patients unsuitable for radical surgery.. Follow up strategies and cN0 staging deserve attention and highlight the need for high quality clinical trials. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Objective: To determine the effect of biological mesh closure on perineal wound healing after extralevator abdominoperineal resection (eAPR)., Background: Perineal wound complications frequently occur after eAPR with preoperative radiotherapy for rectal cancer. Cohort studies have suggested that biological mesh closure of the pelvic floor improves perineal wound healing., Methods: Patients were randomly assigned to primary closure (standard arm) or biological mesh closure (intervention arm). A non-cross-linked porcine acellular dermal mesh was sutured to the pelvic floor remnants in the intervention arm, followed by a layered closure of the ischioanal and subcutaneous fat and skin similar to the control intervention. The outcome of the randomization was concealed from the patient and perineal wound assessor. The primary endpoint was the rate of uncomplicated perineal wound healing defined as a Southampton wound score of less than 2 at 30 days postoperatively. Patients were followed for 1 year., Results: In total, 104 patients were randomly assigned to primary closure (n = 54; 1 dropouts) and biological mesh closure (n = 50; 2 dropouts). Uncomplicated perineal wound healing rate at 30 days was 66% (33/50; 3 not evaluable) after primary closure, which did not significantly differ from 63% (30/48) after biological mesh closure [relative risk 1.056; 95% confidence interval (CI) 0.7854-1.4197; P = 0.7177). Freedom from perineal hernia at 1 year was 73% (95% CI 60.93-85.07) versus 87% (95% CI 77.49-96.51), respectively (P = 0.0316)., Conclusions: Perineal wound healing after eAPR with preoperative radiotherapy for rectal cancer was not improved when using a biological mesh. A significantly lower 1-year perineal hernia rate after biological mesh closure is a promising secondary finding that needs longer follow-up to determine its clinical relevance.

Objective: Early detection of peritoneal metastases (PM) of colorectal cancer (CRC) is difficult and treatment options at a clinically overt stage are limited. Potentially, adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) is of value. The aim of this study was to present long term oncological outcomes of a pilot study on adjuvant HIPEC to reduce development of PMCRC, with systematic review of literature., Methods: Long term oncological outcomes of ten patients who underwent laparoscopic HIPEC within eight weeks after resection of primary CRC in the pilot study were retrospectively collected. A systematic search of literature was performed on studies describing the use of HIPEC in patients with CRC at high risk of developing PM., Results: The median follow-up was 54 months (range 49-63). All patients were alive at the last follow-up moment and none of them had developed PM. Two patients had developed pulmonary metastases. Systematic review revealed five small cohort studies, including two matched comparisons. Peritoneal recurrences were found in 0% to 9% after adjuvant HIPEC, which was 28% and 43% in the two control groups, respectively. Disease free and overall survival were significantly higher in favour of HIPEC., Conclusion: Long term follow-up of ten patients included in a pilot study on adjuvant HIPEC revealed no peritoneal recurrences. This result is in line with other published pilot studies, a promising observation. However, the outcomes of the Dutch randomized COLOPEC trial and similar trials worldwide should be awaited for definitive conclusions on the effectiveness of adjuvant HIPEC., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.