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Background: Computerized adaptive testing tailors test items to students' abilities by adapting difficulty level. This more efficient, and reliable assessment form may provide advantages over a conventional medical progress test (PT). Prior to our study, a direct comparison of students' performance on a computer adaptive progress test (CA-PT) and a conventional PT, which is crucial for nationwide implementation of the CA-PT, was missing. Therefore, we assessed the correlation between CA-PT and conventional PT test performance and explored the feasibility and student experiences of CA-PT in a large medical cohort., Methods: In this cross-over study medical students (n = 1432) of three Dutch medical schools participated in both a conventional PT and CA-PT. They were stratified to start with either a conventional PT or CA-PT to determine test performance. Student motivation, engagement and experiences were assessed by questionnaires in students from seven Dutch medical schools. Parallel-forms reliability was assessed using the Pearson correlation coefficient., Results: A strong correlation was found (0.834) between conventional PT and CA-PT test performance. The CA-PT was administered without system performance issues and was completed in a median time of 83 minutes (67-102 minutes). Questionnaire response rate was 31.7% (526/1658). Despite a higher experienced difficulty, most students reported persistence, adequate task management and good focus during the CA-PT., Conclusions: CA-PT provides a reliable estimation of students' ability level in less time than a conventional non-adaptive PT and is feasible in students throughout the entire medical curriculum. Despite the strong correlation between PT scores, students found the CA-PT more challenging., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Introduction: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes for selected patients with colorectal peritoneal metastases (PM), but recurrence rates are high. The aim of this study was to develop a tool to predict recurrence in patients with colorectal PM that undergo CRS-HIPEC., Materials and Methods: For this retrospective cohort study, data of patients that underwent CRS-HIPEC for colorectal PM from four Dutch HIPEC centers were used. Exclusion criteria were perioperative systemic therapy and peritoneal cancer index (PCI) ≥20. Nine previously identified factors were considered as predictors: gender, age, primary tumor characteristics (location, nodal stage, differentiation, and mutation status), synchronous liver metastases, preoperative Carcino-Embryonal Antigen (CEA), and peritoneal cancer index (PCI). The prediction model was developed using multivariable Cox regression and validated internally using bootstrapping. The performance of the model was evaluated by discrimination and calibration., Results: In total, 408 patients were included. During the follow-up, recurrence of disease occurred in 318 patients (78%). Significant predictors of recurrence were PCI (HR 1.075, 95% CI 1.044-1.108) and primary tumor location (left sided HR 0.719, 95% CI 0.550-0.939). The prediction model for recurrence showed fair discrimination with a C-index of 0.64 (95% CI 0.62, 0.66) after internal validation. The model was well-calibrated with good agreement between the predicted and observed probabilities., Conclusion: We developed a prediction tool that could aid in the prediction of recurrence in patients with colorectal PM who undergo CRS-HIPEC., Competing Interests: Declaration of competing interest All 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., (© 2024 Published by Elsevier Ltd.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Whether adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) might prevent peritoneal metastases after curative surgery for high-risk colon cancer is an ongoing debate. This study aimed to determine 5-year oncologic outcomes of the randomized multicenter COLOPEC trial, which included patients with clinical or pathologic T4N0-2M0 or perforated colon cancer and randomly assigned (1:1) to either adjuvant systemic chemotherapy and HIPEC (n = 100) or adjuvant systemic chemotherapy alone (n = 102). HIPEC was performed using a one-time administration of oxaliplatin (460 mg/m 2 , 30 minutes, 42°C, concurrent fluorouracil/leucovorin intravenously), either simultaneously (9%) or within 5-8 weeks (91%) after primary tumor resection. Outcomes were analyzed according to the intention-to-treat principle. Long-term data were available of all 202 patients included in the COLOPEC trial, with a median follow-up of 59 months (IQR, 54.5-64.5). No significant difference was found in 5-year overall survival rate between patients assigned to adjuvant HIPEC followed by systemic chemotherapy or only adjuvant systemic chemotherapy (69.6% v 70.9%, log-rank; P = .692). Five-year peritoneal metastases rates were 63.9% and 63.2% ( P = .907) and 5-year disease-free survival was 55.7% and 52.3% (log-rank; P = .875), respectively. No differences in quality-of-life outcomes were found. Our findings implicate that adjuvant HIPEC should still be performed in trial setting only.

Aim: Chemoradiotherapy (CRT) has great potential to downstage rectal cancer. Response assessment has been investigated in locally advanced rectal cancer but not in early stage rectal cancer. The aim is to characterize the diagnostic accuracy of endoscopy performed by surgical endoscopists compared to (diffusion-weighted, DWI) MRI only and a multimodal approach combining (DWI-)MRI and endoscopic information both analysed by an abdominal radiologist for response assessment in early rectal cancer after neoadjuvant CRT., Materials and Methods: Patients treated with neoadjuvant CRT for early distal rectal cancer (cT1-3 N0) followed by transanal endoscopic microsurgery were included. Three separate reassessment groups were analysed for response assessment using endoscopic evaluation alone versus (DWI-)MRI alone versus the combination of endoscopy with (DWI-)MRI with a focus on sensitivity and specificity and analysis using receiver operating characteristic curves., Results: Three cohorts (N = 36, N = 25 and N = 25, respectively) were analysed for response assessment. Of the endoscopy cohort, 16 of the 36 patients had a complete response. Area under the curve was 0.69 (0.66-0.74; pooled sensitivity 55.3%, pooled specificity 80.0%). Agreement for scoring separate endoscopic features was poor to moderate. Of the (DWI-)MRI cohort, 11 of the 25 patients had a complete response. Area under the curve for (DWI-)MRI alone was 0.55 (sensitivity 72.7%, specificity 42.9%). The areas under the receiver operating characteristic curve improved to 0.68 (sensitivity 90.9%, specificity 75.0%) when (DWI-)MRI was combined with endoscopic information, with 11 out of 25 patients with a complete response. The most accurate response assessment was made by combining endoscopy and (DWI-)MRI with a high negative predictive value (90.9%)., Conclusion: Good and complete responders after chemoradiation of early stage rectal cancer can be best assessed using a multimodality approach combining endoscopy and (DWI-)MRI., (© 2022 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal metastases (PM) from colorectal carcinoma (CRC). Because of considerable morbidity, optimal patient selection is essential. This study was designed to determine the impact of the onset of PM (synchronous vs. metachronous) on survival outcomes after CRS-HIPEC., Methods: Patients undergoing CRS-HIPEC for colorectal PM in two academic centers in the Netherlands between 2010 and 2020 were eligible for inclusion. Patients were classified as synchronous (s-PM, i.e., diagnosis at time of presentation, staging, or primary surgery) or metachronous onset (m-PM, i.e., diagnosis during follow-up) of colorectal PM. Survival outcomes were compared between groups by Kaplan-Meier survival and Cox regression analyses., Results: Of 390 included patients, 179 (45.9%) had synchronous onset of colorectal PM. These patients more often presented with higher TN-stage and poor differentiation/signet cell histology. Treatment with perioperative chemotherapy was more common in s-PM patients. m-PM patients experienced more serious postoperative complications (Clavien-Dindo ≥ III). There was no significant difference in disease-free survival (DFS) between s-PM (median 9 months, interquartile range [IQR] 5-15) and m-PM patients (median 8 months, IQR 5-17). Overall survival (OS) was significantly shorter for s-PM (median 28 months, IQR 11-48) versus m-PM patients (median 33 months, IQR 18-66, p = 0.049). Synchronous onset of PM was not independently associated with OS in a multivariable analysis., Conclusions: Synchronous onset of colorectal PM was associated with poor tumor characteristics and more advanced disease, but was not an independent predictor of survival outcomes after CRS-HIPEC., (© 2022. The Author(s).)

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for patients with colorectal peritoneal metastases (CRPM). Patient selection is key to optimizing outcomes after CRS/HIPEC. The aim of this study was to determine the prognostic value of ascites diagnosed on preoperative imaging., Methods: A prospective database of patients eligible for CRS/HIPEC between 2010 and 2020 was retrospectively analyzed. The presence of ascites, postoperative complications, overall survival (OS), disease-free survival (DFS), and completeness of cytoreduction were assessed. Univariable and multivariable logistic regression was performed to identify independent predictors for outcome., Results: Of the 235 included patients, 177 (75%) underwent CRS/HIPEC while 58 (25%) were not eligible for CRS/HIPEC. In 42 of the 177 patients (24%) who underwent CRS/HIPEC, ascites was present on preoperative computed tomography (CT) imaging. Peritoneal Cancer Index (PCI) score was significantly higher in patients with preoperative ascites compared with patients without (11 [range 2-30] vs. 9 [range 0-28], respectively; p = 0.011) and complete cytoreduction was more often achieved in patients without ascites (96.3% vs. 85.7%; p = 0.007). There was no significant difference in median DFS and OS after CRS/HIPEC between patients with and without ascites {10 months (95% confidence interval [CI] 7.1-12.9) vs. 9 months (95% CI 7.2-10.8), and 25 months (95% 9.4-40.6) vs. 27 months (95% CI 22.4-31.6), respectively}., Conclusions: Ascites on preoperative imaging was not associated with worse survival in CRS/HIPEC patients with CRPM. Therefore, excluding patients from CRS/HIPEC based merely on the presence of ascites is not advisable., (© 2022. The Author(s).)

In patients with colorectal peritoneal metastases scheduled for cytoreductive surgery, accurate preoperative estimation of tumor burden and subsequent intraoperative detection of all tumor deposits remains challenging. In this study (ClinicalTrials.gov NCT03699332) we describe the results of a phase I clinical trial evaluating [ 111 In]In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-carcinoembryonic antigen (anti-CEA) antibody conjugate that enables both preoperative imaging and intraoperative radioguidance and fluorescence imaging. Primary study outcomes are safety and feasibility of this multimodal imaging approach. Secondary outcomes are determination of the optimal dose, correlation between tracer uptake and histopathology and effects on clinical strategy. Administration of [ 111 In]In-DOTA-labetuzumab-IRDye800CW is well-tolerated and enables sensitive pre- and intraoperative imaging in patients who receive 10 or 50 mg of the tracer. Preoperative imaging revealed previously undetected lymph node metastases in one patient, and intraoperative fluorescence imaging revealed four previously undetected metastases in two patients. Alteration of clinical strategy based on multimodal imaging occurred in three patients. Thus, multimodal image-guided surgery after administration of this dual-labeled tracer is a promising approach that may aid in decision making before and during cytoreductive surgical procedures., (© 2022. The Author(s).)

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) leads to increased survival rates in patients with peritoneal carcinomatosis, but is associated with considerable morbidity and mortality rates. Prehabilitation, a process to optimize a patient's preoperative functional capacity, has a positive impact on recovery after colorectal surgery. The impact of prehabilitation in patients undergoing HIPEC is scarcely investigated. This scoping review and narrative synthesis aims to summarize and evaluate what is currently reported about the effect of prehabilitation on postoperative outcomes after HIPEC., Methods: A literature search of studies reporting on the effect of prehabilitation on outcomes after HIPEC was performed (August 2020). Study characteristics, patient demographics, composition of prehabilitation programs, and reported outcomes used to quantify the effect of prehabilitation were recorded., Results: The literature search did not yield any studies on the effect of prehabilitation programs on outcomes after HIPEC. As an alternative, studies identifying modifiable risk factors for poor postoperative outcomes after HIPEC that can be targeted by prehabilitation were reviewed to evaluate starting points for prehabilitation. Fourteen studies identify the following preoperative factors: poor nutritional status, poor performance status, low health related quality of life and an history of smoking., Conclusion: No research has been published on the effect of prehabilitation prior to HIPEC. This review demonstrates that preoperative modifiable risk factors for outcomes in patients undergoing HIPEC are multifactorial. A multimodal prehabilitation program prior to HIPEC, including nutritional support, psychical exercise, psychological support and smoking cessation, might therefore be a promising approach to improve postoperative outcomes., 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 © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM)., Objective: To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment., Design, Setting, and Participants: An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment., Interventions: Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles., Main Outcomes and Measures: Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm)., Results: In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively., Conclusions and Relevance: In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial., Trial Registration: ClinicalTrials.gov Identifier: NCT02758951.

Introduction: Colorectal cancer (CRC) follow-up has a major impact on outpatient services. The aim was to examine patient acceptability and costs of a new remote follow-up regimen for patients with CRC., Material and Methods: All patients with stage I-III CRC and having completed at least one-year of follow-up at Radboud University Medical Center located in Nijmegen, The Netherlands, were considered for remote follow-up. Enrolled patients received the EORTC-C30 (Quality of Life, QoL), Cancer Worry Scale (Fear of Cancer Recurrence, FCR), (e)Health literacy and patient satisfaction questionnaires. Follow-up use and costs were evaluated., Results: A total of 118 patients with stage I-III CRC have been followed according to the new remote follow-up regimen. Median length of follow-up at start of remote follow-up was 34 months (interquartile range of 24-41) and all patients were sufficiently health literate. Overall satisfaction towards remote follow-up at 6-and 12-months was rated 7.8 and 7.5 out of 10. Satisfaction with the online self-management information was rated 8 out of 10. Over a one-year period, QoL remained high and patients experienced low FCR. More than 70% of the patients self-organized their care, while the others sought contact by telephone, MyChart or hospital visits. Remote follow-up for the total cohort led to €22,408 cost-savings over one-year compared to standard hospital follow-up., Conclusions: Implementation of remote follow-up for patients with stage I-III CRC is feasible, comes with high patient satisfaction and considerable cost-savings. Short-term results did not show differences in QoL or FCR during the course of remote follow-up., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The value of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneally metastasized goblet-cell carcinoids (GCCs) and mixed adenoneuroendocrine carcinomas (MANECs) is currently unclear. We compared outcomes of CRS-HIPEC to surgery alone for peritoneally metastasized GCCs and MANECs., Patients and Methods: Two cohorts were obtained from the Netherlands Cancer Registry (n = 569): patients with peritoneally metastasized GCCs and MANECs treated with CRS-HIPEC in Dutch and Belgian centers (n = 45), and patients treated with surgery alone. Primary outcome was overall survival (OS). Secondary outcomes were morbidity and hospital mortality. After propensity score matching, OS was compared in univariate and multivariate analyses. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from database inception to June 25, 2018., Results: After matching for sex, tumor stage, lymph node stage, and liver metastases, CRS-HIPEC was associated with improved median OS in the combined GCC and MANEC group and the separate GCC subgroup in univariate (GCC + MANEC: 39 vs. 12 months, P < .001; GCC: 39 vs. 12 months, P = .017) and multivariate analysis (GCC + MANEC: hazard ratio 4.27, 95% confidence interval 1.88-9.66, P = .001; GCC: hazard ratio 2.77, 95% confidence interval 1.06-7.26, P = .038). Acceptable grade III-IV morbidity (17.5%) and mortality (0) were seen after CRS-HIPEC. The literature review supported these findings., Conclusion: CRS-HIPEC is associated with substantial survival benefit in patients with peritoneally metastasized GCCs and MANECs compared to surgery alone and is a safe treatment option. These data support centralized care of GCC and MANEC patients with peritoneal spread in expert centers offering CRS-HIPEC., (Copyright © 2020. Published by Elsevier Inc.)

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.

Purpose: In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored., Methods: Ten patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations., Results: Peritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04)., Conclusion: In this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments. The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.

Preoperative chemotherapy followed by surgery was applied in three patients, aged 68 years (male), 48 years (female), and 80 years (male) with locally advanced cancer of the colon with bladder invasion. Achieving a resection with free margins (R0) is essential in colon-cancer surgery, but the role of preoperative chemotherapy in colon cancer remains unknown. When a tumour is presumed to be unresectable, guidelines recommend discussing the case and possibly referring the patient to an oncological expertise centre, where each patient will be individually assessed for the most suitable preoperative treatment and surgery during a multidisciplinary tumour board meeting. All three patients showed that preoperative chemotherapy led to down-staging and reduction of the tumour size, although removal of the bladder was still necessary in one patient. All patients underwent a complete resection, which resulted in long-term disease-free and overall survival.

Background: Worldwide, acute cholecystitis is a common disease. The current standard of treatment is according to the Tokyo Guidelines established in 2018. Conservative management with various combinations of analgesics, anti-inflammatory drugs, and percutaneous drainage are sometimes used to avoid or delay surgery, especially in frail patients, but little is known about the efficacy and safety of these strategies. Therefore, we evaluated the effect of antibiotic agents, with or without gallbladder drainage, or symptomatic treatment alone in patients with acute cholecystitis who were considered unfit for acute surgery. Patients and Methods: All patients whose initial treatment for cholecystitis was conservative who were admitted between 2014 and 2016 were included in this study. Patients were divided into three groups: those treated with antibiotic agents, those who received antibiotic agents in combination with percutaneous gallbladder drainage and those whose treatment was only symptomatic. Demographic characteristics, comorbidities, Tokyo Severity Classification, length of stay, re-admission rates, secondary treatment (delayed drainage or surgery), and complication rates were retrieved from their medical records. Results: Initially 33 were treated with conservative methods in this period. Fifteen patients were treated initially with antibiotic agents, 12 patients with antibiotic agents in combination with percutaneous drainage, and 6 patients received symptomatic treatment only. One patient had mild cholecystitis (Tokyo Severity Classification grade I) and the other 32 patients had moderate to severe (grade II or III) cholecystitis. Eventually, 25 patients (76%) underwent cholecystectomy, 2 of whom (8%) were emergency operations because of disease progression. Twelve patients (36%) were re-admitted, of whom the majority (83%) was re-admitted before cholecystectomy. Conclusion: Treatment of cholecystitis with antibiotic agents, drainage, or analgesic agents is feasible. However, it should be regarded as a bridge to surgery rather than a definitive solution because of frequent recurrence. Occasionally, an emergency operation could not be avoided as a result of disease progression under conservative treatment.

Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111 In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts ( p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies.

Background: Selected patients with colorectal peritoneal metastases are treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The concentration of intraperitoneal chemotherapy reflects the administered dose and perfusate volume. The aim of this study was to calculate intraperitoneal chemotherapy concentration during HIPEC and see whether this was related to clinical outcomes., Methods: An observational multicentre study included consecutive patients with colorectal peritoneal metastases who were treated with CRS-HIPEC between 2010 and 2018 at three Dutch centres. Data were retrieved from prospectively developed databases. Chemotherapy dose and total circulating volumes of carrier solution were used to calculate chemotherapy concentrations. Postoperative complications, disease-free and overall survival were correlated with intraoperative chemotherapy concentrations. Univariable and multivariable logistic regression, Cox regression and survival analyses were performed., Results: Of 320 patients, 220 received intraperitoneal mitomycin C (MMC) and 100 received oxaliplatin. Median perfusate volume for HIPEC was 5·0 (range 0·7-10·0) litres. Median intraperitoneal chemotherapy concentration was 13·3 (range 7·0-76·0) mg/l for MMC and 156·0 (91·9-377·6) mg/l in patients treated with oxaliplatin. Grade III or higher complications occurred in 75 patients (23·4 per cent). Median overall survival was 36·9 (i.q.r. 19·5-62·9) months. Intraperitoneal chemotherapy concentrations were not associated with postoperative complications or survival., Conclusion: CRS-HIPEC was performed with a wide variation in intraperitoneal chemotherapy concentrations that were not associated with complications or survival., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Colorectal cancer is a common disease and patient follow-up can overwhelm outpatient services. Cancer patients are followed to provide (psychological) support, and to identify and treat disease recurrence and complications. This article describes our thoughts on, and first experience with the development and implementation of an alternative, remote follow-up plan for colorectal cancer patients. Within remote follow-up, patients have access to test results, and are supported with self-management information. They have access to telemedicine applications such as video-consultation, text messaging, and telephone services to contact their physician and nurse practitioner. Routine outpatient clinical visits are abandoned. Currently, 66 patients are being followed remotely. Application of telemedicine within cancer follow-up has several advantages. Patients do not have to travel back and forth, sparing time, costs and efforts. Second, telemedicine applications increase patient empowerment. If applied safely, remote follow-up may become a viable alternative to clinical follow-up., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: To evaluate whether PET/CT could be used to assess the extent of colorectal peritoneal metastases., Methods: All patients who underwent a PET/CT scan before a CRS-HIPEC procedure between January 1, 2010 and December 31, 2013 were retrospectively included (n = 35). Two nuclear medicine physicians (observer 1 and observer 2) separately reviewed the scans on intraperitoneal abnormalities. A simplified PCI was used to compare the extent of rPCI versus sPCI., Results: Included patients had a median age of 60.6 years. Histology of primary tumors were 51.5% adenocarcinomas, 37.1% mucinous adenocarcinoma, and 11.4% SRCC. Median sPCI was 9.5 (5.0-11.8) and median rPCI was 5.0 (3.0-7.0) for observer 1 and 4.0 (3.0-6.0) for observer 2 (p = 0.02 and p = 0.01, respectively). When compared to the surgical data, PET/CT showed a poor correlation for assessing the extent of PC for both adenocarcinoma (observer 1 rho - 0.17, p = 0.51 and observer 2 rho 0.13, p = 0.61) as well as mucinous carcinoma or SRCC (observer 1 rho 0.44, p = 0.08 and observer 2 rho 0.38, p = 0.14)., Conclusion: PET/CT underestimates the extent of PC during surgery in both mucinous and non-mucinous CRC and is not recommended for intraperitoneal tumor scoring.

Background: The precise content and frequency of follow-up of patients with colorectal cancer (CRC) is variable and guideline adherence is low. The aim of this study was to assess the view of colorectal surgeons on their local follow-up schedule and to clarify their opinions about risk-stratification and organ preserving therapies. Equally important, adherence to the Dutch national guidelines was determined., Methods: Colorectal surgeons were invited to complete a web-based survey about the importance and interval of clinical follow-up, CEA monitoring and the use of imaging modalities. Furthermore, the opinions regarding physical examination, risk-stratification, organ preserving strategies, and follow-up setting were assessed. Data were analyzed using quantitative and qualitative analysis methods., Results: A total of 106 colorectal surgeons from 52 general and 5 university hospitals filled in the survey, yielding a hospital response rate of 74% and a surgeon response rate of 42%. The follow-up of patients with CRC was mainly done by surgeons (71%). The majority of the respondents (68%) did not routinely perform physical examination during follow-up of rectal patients. Abdominal ultrasound was the predominant modality used for detection of liver metastases (77%). Chest X-ray was the main modality for detecting lung metastases (69%). During the first year of follow-up, adherence to the minimal guideline recommendations was high (99-100%). The results demonstrate that, within the framework of the guidelines, some respondents applied a more intensive follow-up and others a less intensive schedule. The majority of the respondents (77%) applied one single follow-up imaging schedule for all patients that underwent treatment with curative intent., Conclusions: Dutch colorectal surgeons' adherence to minimal guideline recommendations was high, but within the guideline framework, opinions differed about the required intensity and content of clinical visits, the interval of CEA monitoring, and the importance and frequency of imaging techniques. This national survey demonstrates current follow-up practice throughout the Netherlands and highlights the follow-up differences of curatively treated patients with CRC.

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

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.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care in the treatment of patients with peritoneal carcinomatosis of colorectal origin. The use of oxaliplatin for HIPEC has gained popularity. Although the HIPEC procedure is adopted throughout the world, major differences exist between treatment protocols regarding the carrier solution, perfusate volume, use of an open or closed technique, duration of the perfusion and application of additional flushing. These differences can influence the pharmacokinetics and pharmacodynamics of oxaliplatin and might thereby have an impact on the efficacy and/or safety of the treatment. Clinicians should be aware of the clinical importance of oxaliplatin pharmacology when performing HIPEC surgery. This review adds new insights into the complex field of the pharmacology of HIPEC and highlights an important worldwide problem: the lack of standardization of the HIPEC procedure., (© 2018 The British Pharmacological Society.)

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with considerable postoperative morbidity, including ileus and infectious complications. Perioperative care is believed to be an important factor for the development and treatment of postoperative morbidity., Patients and Methods: Data on case-matched patients from a retrospective database of 2 Dutch HIPEC centres was compared. Patient selection and procedures were identical in both hospitals although perioperative management items differ slightly. In centre B, immediate total parenteral nutrition (TPN), suprapubic urine bladder catheter placement (SPCs) and selective decontamination of the digestive-tract are standard care for CRS-HIPEC patients, while in centre A, they are not., Results: From a total of 223 patients, 68 consecutive patients from centre B were compared to 68 matched patients from centre A. TPN was administered to 54.4% of patients in centre A because of prolonged ileus, whereas it was standard of care in centre B. In all, 105 (77.2%) patients experienced postoperative complications including 17.6% who had a grades III-IV complication. The incidence of grade III-V complications was 18 (26.4%) in centre A and 8 (11.8%) in centre B (p = 0.03). Median hospital stay was 12 days (7-84) in A and 11(6-80) in centre B (p = 0.546)., Conclusions: Gastrointestinal recovery after CRS-HIPEC seems to take longer as compared to other surgical procedures. Between the 2 centres, a significant difference in severe complications was found, while standard TPN, selective bowel decontamination and SPCs were the only identified differences in perioperative care., (The Author(s). Published by S. Karger AG, Basel.)

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.)

Importance: Treatment of rectal cancer is shifting toward organ preservation aiming to reduce surgery-related morbidity. Short-term outcomes of organ-preserving strategies are promising, but long-term outcomes are scarce in the literature., Objective: To explore long-term oncological outcomes and health-related quality of life (HRQL) in patients with cT1-3N0M0 rectal cancer who underwent neoadjuvant chemoradiotherapy (CRT) followed by transanal endoscopic microsurgery (TEM)., Design, Setting, and Participants: In this multicenter phase II feasibility study, patients with cT1-3N0M0 rectal cancer admitted to referral centers for rectal cancer throughout the Netherlands between February 2011 and September 2012 were prospectively included. These patients were to be treated with neoadjuvant CRT followed by TEM in case of good response. An intensive follow-up scheme was used to detect local recurrences and/or distant metastases. Data from validated HRQL questionnaires and low anterior resection syndrome questionnaires were collected. Data were analyzed from February 2011 to April 2017., Main Outcomes and Measures: The primary study outcome of the study was the number of ypT0-1 specimens by performing TEM. Secondary outcome parameters were locoregional recurrences and HRQL., Results: Of the 55 included patients, 30 (55%) were male, and the mean (SD) age was 64 (39-82) years. Patients were followed up for a median (interquartile range) period of 53 (39-57) months. Two patients (4%) died during CRT, 1 (2%) stopped CRT, and 1 (2%) was lost to follow-up. Following CRT, 47 patients (85%) underwent TEM, of whom 35 (74%) were successfully treated with local excision alone. Total mesorectal excision was performed in 16 patients (4 with inadequate responses, 8 with completion after TEM, and 4 with salvage for local recurrence). The actuarial 5-year local recurrence rate was 7.7%, with 5-year disease-free and overall survival rates of 81.6% and 82.8%, respectively. Health-related quality of life during follow-up was equal to baseline, with improved emotional well-being in patients treated with local excision (mean score at baseline, 72.0; 95% CI, 67.1-80.1; mean score at follow-up, 86.9; 95% CI, 79.2-94.7; P = .001). Major, minor, and no low anterior resection syndrome was experienced in 50%, 28%, and 22%, respectively, of patients with successful organ preservation., Conclusions and Relevance: In early-stage rectal cancer (cT1-3N0M0), CRT enables organ preservation with additional TEM surgery in approximately two-thirds of patients with good long-term oncological outcome and HRQL. This multimodality treatment triggers a certain degree of bowel dysfunction, and one-third of patients still undergo radical surgery and are overtreated by CRT.

Over the past 5 years, cancer has replaced coronary heart disease as the leading cause of death in the Netherlands. It is thus paramount that medical doctors acquire a knowledge of cancer, since most of them will face many patients with cancer. Studies, however, have indicated that there is a deficit in knowledge of oncology among medical students, which may be due not only to the content but also to the structure of the curriculum. In this study, we compared students' knowledge acquisition in four different undergraduate medical programs. Further, we investigated possible factors that might influence students' knowledge growth as related to oncology. The participants comprised 1440 medical students distributed over four universities in the Netherlands. To measure students' knowledge of oncology, we used their progress test results from 2007 to 2013. The progress test consists of 200 multiple-choice questions; this test is taken simultaneously four times a year by all students. All questions regarding oncology were selected. We first compared the growth of knowledge of oncology using mixed models. Then, we interviewed the oncology coordinator of each university to arrive at a better insight of each curriculum. Two schools showed similar patterns of knowledge growth, with a slight decrease in the growth rate for one of them in year 6. The third school had a faster initial growth with a faster decrease over time compared to other medical schools. The fourth school showed a steep decrease in knowledge growth during years 5 and 6. The interviews showed that the two higher-scoring schools had a more focused semester on oncology, whereas in the others, oncology was scattered throughout the curriculum. Furthermore, the absence of a pre-internship training program seemed to hinder knowledge growth in one school. Our findings suggest that curricula have an influence on students' knowledge acquisition. A focused semester on oncology and a pre-internship preparatory training program are likely to have a positive impact on students' progress in terms of knowledge of oncology.

Background: Colorectal peritoneal carcinomatosis (PC) is preferably treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Peritoneal recurrence of disease after treatment can occur without distant metastases, with a variety of treatment options., Objective: This study aimed to evaluate the management of isolated peritoneal recurrence after primary CRS-HIPEC., Methods: In two tertiary referral centers, all patients who underwent CRS-HIPEC for colorectal PC between 2004 and 2015 and who developed isolated peritoneal recurrences were retrospectively evaluated. Location, treatment of peritoneal recurrences, and curative or palliative treatment intent were reported, and univariable and multivariable Cox regression analysis and survival analyses were performed., Results: Of 414 patients treated with CRS-HIPEC for colorectal PC, 106 patients (26%) developed isolated peritoneal recurrence. Forty-three patients (41%) were treated with curative intent and 63 (59%) were treated with palliative intent. Median overall survival (OS) in the patients treated with curative intent was 24.7 months (interquartile range [IQR] 12.1-61.7), compared with 7.6 months (IQR 2.5-15.9) in those treated with palliative intent (p < 0.001). In the patients treated with curative CRS (n = 17) and curative second CRS-HIPEC (n = 15), median OS was 51.7 months (IQR 14.4-NA) and 29.0 months (IQR 18.1-63.0), respectively (p = 0.620). The latter group had a significantly higher region count (median 1 vs. 3; p < 0.001). Postoperative complications and hospital stay did not significantly differ between first and second CRS-HIPEC., Conclusion: After CRS-HIPEC for colorectal cancer, approximately one of four patients will develop isolated peritoneal recurrences. A substantial amount of these patients can be safely treated with curative intent yielding long-term survival.

Background: Almost 50% of women who have had rectal surgery subsequently develop vaginal discharge. Due to the recurrent and unexpected nature of this heavy discharge, they often experience it as very distressing. Many of these women undergo extensive diagnostic tests that are mainly focused on identifying fistula formation. If no fistula is found, in most cases no other cause for severe vaginal discharge can be demonstrated., Case Description: In our practice, we saw three patients (49-, 54- and 74-years-old, respectively) with similar severe vaginal discharge after rectal surgery and in whom no explanation for the vaginal discharge could be found. For this reason we conducted a literature search into this condition., Conclusion: Anatomical changes appear to be responsible for heavy vaginal discharge following rectal surgery. Changes in pelvic floor muscles and compression of the distal part of the vagina may lead to pooling of fluid in the proximal part of the vagina, resulting in severe discharge. Symptomatic treatment may reduce the symptoms.

Aim: To evaluate a step up approach: Taking macrobiopsies and performing excision biopsies in patients with suspected rectal cancer in which biopsies taken though the flexible endoscope showed benign histology., Methods: Patients with a rectal neoplasm who underwent flexible endoscopy and biopsies were included. In case of benign biopsies rigid rectoscopy and macrobiopsies were employed. If this failed to prove malignancy, transanal endoscopic microsurgery (TEM) was used in a final effort to establish a certain preoperative diagnosis. The preoperative results were compared with the findings after surgical excision and follow up to calculate the reliability of this algorithm., Results: One hundred and thirty-two patients were included. One hundred and ten patients with a carcinoma and 22 with an adenoma. Seventy-five of 110 carcinomas were proven malignant after flexible endoscopy. With the addition of rigid endoscopy and taking of macrobiopsies, this number increased to 89. Performing TEM excision biopsies further enlarged the number of proven malignancies to 100., Conclusion: The step-up approach includes taking macrobiopsies through the rigid rectoscope and performing excision biopsies using transanal endoscopic microsurgery in addition to flexible endoscopy. This approach, reduced the number of missed preoperative malignant diagnoses from 32% to 9%., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.