This thesis consists of two sections. In Section I, (pre)clinical research investigating novel targets for pre- and intraoperative molecular imaging of pancreatic cancer are discussed. In Section... Show moreThis thesis consists of two sections. In Section I, (pre)clinical research investigating novel targets for pre- and intraoperative molecular imaging of pancreatic cancer are discussed. In Section II, various studies are described which lay the groundwork for further investigation into response monitoring and prediction in rectal cancer using various imaging modalities. Show less
There is a lack of knowledge regarding the definition, classification and appropriate treatment of malignant lateral lymph nodes in patients with (locally advanced) rectal cancer. This thesis aimed... Show moreThere is a lack of knowledge regarding the definition, classification and appropriate treatment of malignant lateral lymph nodes in patients with (locally advanced) rectal cancer. This thesis aimed to increase this knowledge and improve treatment practices for this population. Show less
BackgroundAs the survival of patients with rectal cancer has improved in recent decades, more and more patients have to live with the consequences of rectal cancer surgery. An influential factor in... Show moreBackgroundAs the survival of patients with rectal cancer has improved in recent decades, more and more patients have to live with the consequences of rectal cancer surgery. An influential factor in long-term Health-related Quality of Life (HRQoL) is the presence of a stoma. This study aimed to better understand the long-term consequences of a stoma and poor functional outcomes.MethodsPatients who underwent curative surgery for a primary tumor located in the rectosigmoid and rectum between 2013 and 2020 were identified from the nationwide Prospective Dutch Colorectal Cancer (PLCRC) cohort study. Patients received the following questionnaires: EORTC-QLQ-CR29, EORTC-QLQ-C30, and the LARS-score at 12 months, 24 months and 36 months after surgery.ResultsA total of 1,170 patients were included of whom 751 (64.2%) had no stoma, 122 (10.4%) had a stoma at primary surgery, 45 (3.8%) had a stoma at secondary surgery and 252 (21.5%) patients that underwent abdominoperineal resection (APR). Of all patients without a stoma, 41.4% reported major low-anterior resection syndrome (LARS). Patients without a stoma reported significantly better HRQoL. Moreover, patients without a stoma significantly reported an overall better HRQoL.ConclusionThe presence of a stoma and poor functional outcomes were both associated with reduced HRQoL. Patients with poor functional outcomes, defined as major LARS, reported a similar level of HRQoL compared to patients with a stoma. In addition, the HRQoL after rectal cancer surgery does not change significantly after the first year after surgery. Show less
Newly introduced hybrid systems that combine an MRI scanner with a linear accelerator for radiation treatment, called MR-linacs, provide an opportunity for the daily acquisition of quantitative MRI... Show moreNewly introduced hybrid systems that combine an MRI scanner with a linear accelerator for radiation treatment, called MR-linacs, provide an opportunity for the daily acquisition of quantitative MRI (qMRI) without increasing patient burden. This allows for the measurement of changes in quantitative MRI biomarkers over time, that may indicate a response to the radiation treatment. In this thesis, the performance of the Unity MR-linac with regards to several qMRI sequences was characterized, showing results similar to diagnostic systems in terms of accuracy and repeatability. Additionally, we found changes in qMRI parameters in patients early during treatment, which indicates potential as biomarkers for treatment outcome. Show less
IntroductionAlthough optimising rectal cancer treatment has reduced local recurrence rates, many patients develop distant metastases (DM). The current study investigated whether a total neoadjuvant...Show moreIntroductionAlthough optimising rectal cancer treatment has reduced local recurrence rates, many patients develop distant metastases (DM). The current study investigated whether a total neoadjuvant treatment strategy influences the development, location, and timing of metastasesin patients diagnosed with high-risk locally advanced rectal cancer included in the Rectal cancer And Pre-operative Induction therapy followed by Dedicated Operation (RAPIDO) trial.Material and methodsPatients were randomly assigned to short-course radiotherapy followed by 18 weeks of CAPOX or FOLFOX4 before surgery (EXP), or long-course chemoradiotherapy with optional postoperative chemotherapy (SC-G). Assessments for metastatic disease were performed pre- and post-treatment, during surgery, and 6, 12, 24, 36, and 60 months postoperatively. From randomisation, differences in the occurrence of DM and first site of metastasis were evaluated.ResultsIn total, 462 patients were evaluated in the EXP and 450 patients in the SC-G groups. The cumulative probability of DM at 5 years after randomisation was 23% [95% CI 19–27] and 30% [95% CI 26–35] (HR 0.72 [95% CI 0.56–0.93]; P = 0.011) in the EXP and SC-G, respectively. The median time to DM was 1.4 (EXP) and 1.3 years (SC-G). After diagnosis of DM, median survival was 2.6 years [95% CI 2.0–3.1] in the EXP and 3.2 years [95% CI 2.3–4.1] in the SC-G groups (HR 1.39 [95% CI 1.01–1.92]; P = 0.04). First occurrence of DM was most often in the lungs (60/462 [13%] EXP and 55/450 [12%] SC-G) or the liver (40/462 [9%] EXP and 69/450 [15%] SC-G). A hospital policy of postoperative chemotherapy did not influence the development of DM.ConclusionsCompared to long-course chemoradiotherapy, total neoadjuvant treatment with short-course radiotherapy and chemotherapy significantly decreased the occurrence of metastases, particularly liver metastases. Show less
BACKGROUND: Nearly 30% of patients with rectal cancer develop local regrowth after initial clinical complete response managed by watch and wait. These patients might be at higher risk for distant... Show moreBACKGROUND: Nearly 30% of patients with rectal cancer develop local regrowth after initial clinical complete response managed by watch and wait. These patients might be at higher risk for distant metastases.OBJECTIVE: This study aimed to investigate risk factors for distant metastases using time-dependent analyses.DESIGN: Data from an international watch and wait database were retrospectively reviewed. Cox regression analysis was used to determine risk factors for worse distant metastases-free survival. Conditional survival modeling was used to investigate the impact of risk factors on the development of distant metastases.SETTING: Retrospective, multicenter database.PATIENTS: A total of 793 patients (47 institutions) with rectal cancer and clinical complete response to neoadjuvant treatment from the International Watch & Wait Database were included.MAIN OUTCOME MEASURES: Distant metastases-free survival.RESULTS: Of the 793 patients managed with watch and wait (median follow-up 55.2 mo)‚ 85 patients (10.7%) had distant metastases. Fifty-one of 85 patients (60%) had local regrowth at any time. Local regrowth was an independent factor associated with worse distant metastases-free survival in the multivariable model. Using conditional estimates, patients with local regrowth without distant metastases for 5 years (from decision to watch and wait) remained at higher risk for development of distant metastases for 1 subsequent year compared to patients without local regrowth (5-year conditional distant metastases-free survival 94.9% vs 98.4%).LIMITATIONS: Lack of information on adjuvant chemotherapy, salvage surgery for local regrowth, and heterogeneity of individual surveillance/follow-up strategies used may have affected results.CONCLUSIONS: In patients with clinical complete response managed by watch and wait, development of local regrowth at any time is a risk factor for distant metastases. The risk of distant metastases remains higher for 5 years after development of local regrowth. Show less
Objectives The presence and size of lateral lymph nodes (LLNs) are important factors influencing treatment decisions for rectal cancer. Awareness of the clinical relevance and describing LLNs in... Show moreObjectives The presence and size of lateral lymph nodes (LLNs) are important factors influencing treatment decisions for rectal cancer. Awareness of the clinical relevance and describing LLNs in MRI reports is therefore essential. This study assessed whether LLNs were mentioned in primary MRI reports at a national level and investigated the concordance with standardised re-review. Methods This national, retrospective, cross-sectional cohort study included 1096 patients from 60 hospitals treated in 2016 for primary cT3-4 rectal cancer <= 8 cm from the anorectal junction. Abdominal radiologists re-reviewed all MR images following a 2-h training regarding LLNs. Results Re-review of MR images identified that 41.0% of enlarged (>= 7 mm) LLNs were not mentioned in primary MRI reports. A contradictory anatomical location was stated for 73.2% of all LLNs and a different size (>=/< 7 mm) for 41.7%. In total, 49.4% of all cases did not mention LLNs in primary MRI reports. Reporting LLNs was associated with stage (cT3N0 44.3%, T3N+/T4 52.8%, p = 0.013), cN stage (N0 44.1%, N1 48.6%, N2 59.5%, p < 0.001), hospital type (non-teaching 34.6%, teaching 52.2%, academic 53.2% p = 0.006) and annual rectal cancer resection volumes (low 34.8%, medium 47.7%, high 57.3% p < 0.001). For LLNs present according to original MRI reports (n = 226), 64.2% also mentioned a short-axis size, 52.7% an anatomical location and 25.2% whether it was deemed suspicious. Conclusions Almost half of the primary MRI reports for rectal cancer patients treated in the Netherlands in 2016 did not mention LLNs. A significant portion of enlarged LLNs identified during re-review were also not mentioned originally, with considerable discrepancies for location and size. These results imply insufficient awareness and indicate the need for templates, education and training. Show less
Background Surgical resection is the mainstay of curative treatment for rectal cancer. Post-operative complications, low anterior resection syndrome (LARS), and the presence of a stoma may... Show moreBackground Surgical resection is the mainstay of curative treatment for rectal cancer. Post-operative complications, low anterior resection syndrome (LARS), and the presence of a stoma may influence the quality of life after surgery. This study aimed to gain more insights into the long-term trade-off between stoma and anastomosis. Methods All patients who underwent sphincter-sparing surgical resection for rectal cancer in the Leiden University Medical Center and the Reinier de Graaf Gasthuis between January 2012 and January 2016 were included. Patients received the following questionnaires: EORTC-QLQ-CR29, EORTC-QLQ-C30, EQ-5D-5L, and the LARS score. A comparison was made between patients with a stoma and without a stoma after follow-up. Results Some 210 patients were included of which 149 returned the questionnaires (70.9%), after a mean follow-up of 3.69 years. Overall quality of life was not significantly different in patients with and without stoma after follow-up using the EORTC-QLQ-C30 (p = 0.15) or EQ-5D-5L (p = 0.28). However, after multivariate analysis, a significant difference was found for the presence of a stoma on global health status (p = 0.01) and physical functioning (p < 0.01). Additionally, there was no difference detected in the quality of life between patients with major LARS or a stoma. Conclusion This study shows that after correction for possible confounders, a stoma is associated with lower global health status and physical functioning. However, no differences were found in health-related quality of life between patients with major LARS and patients with a stoma. This suggests that the choice between stoma and anastomosis is mainly preferential and that shared decision-making is required. Show less
Background: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision ... Show moreBackground: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs.Methods: PubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed.Results: Seven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3-15%) compared to LLND- (11-27%; RR = 0.40, 95%CI [0.25-0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61-78% vs. 46-79% for LLND-; RR = 0.72, 95%CI [0.51-1.02], p = 0.143), and neither was five-year OS (range 69-91% vs. 72-80%; RR = 0.72, 95%CI [0.45-1.14], p = 0.163).Conclusion: In rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND. Show less
Argillander, T.E.; Hulst, H.C. van der; Zaag-loonen, H.J. van der; Duijvendijk, P. van; Dekker, J.W.T.; Bol, J.M. van der; ... ; Munster, B.C. van 2022
Introduction: Older patients have a higher risk for complications after rectal cancer surgery. Although screening for geriatric impairments may improve risk prediction in this group, it has not... Show moreIntroduction: Older patients have a higher risk for complications after rectal cancer surgery. Although screening for geriatric impairments may improve risk prediction in this group, it has not been studied previously. Methods: We retrospectively investigated patients >= 70 years with elective surgery for non-metastatic rectal cancer between 2014 and 2018 in nine Dutch hospitals. The predictive value of six geriatric parameters in combination with standard preoperative predictors was studied for postoperative complications, delirium, and length of stay (LOS) using logistic regression analyses. The geriatric parameters included the four VMS -questionnaire items pertaining to functional impairment, fall risk, delirium risk, and malnutrition, as well as mobility problems and polypharmacy. Standard predictors included age, sex, body mass index, American Society of Anesthesiologists (ASA)-classification, comorbidities, tumor stage, and neoadjuvant therapy. Changes in model performance were evaluated by comparing Area Under the Curve (AUC) of the regression models with and without geriatric parameters. Results: We included 575 patients (median age 75 years; 32% female). None of the geriatric parameters improved risk prediction for complications or LOS. The addition of delirium risk to the standard preoperative prediction model improved model performance for predicting postoperative delirium (AUC 0.75 vs 0.65, p = 0.03). Conclusions: Geriatric parameters did not improve risk prediction for postoperative complications or LOS in older patients with rectal cancer. Delirium risk screening using the VMS-questionnaire improved risk prediction for delirium. Older patients undergoing rectal cancer surgery are a pre-selected group with few impairments. Geriatric screening may have additional value earlier in the care pathway before treatment decisions are made. Show less
Survival of patients with colorectal cancer improved markedly over the past decades, as a result of advances in screening, staging procedures, treatment, and surveillance. However, still about 20%... Show moreSurvival of patients with colorectal cancer improved markedly over the past decades, as a result of advances in screening, staging procedures, treatment, and surveillance. However, still about 20% of patients with colorectal cancer develop metachronous metastases and 20% of all patients with colorectal cancer have metastatic disease at diagnosis. Several treatment modalities, such as total mesorectal excision (TME) and preoperative (chemo)radiotherapy for rectal cancer, as well as adjuvant chemotherapy for stage III colon cancer, have been studied extensively and showed to improve cancer-related outcomes. On the contrary, the effectiveness of other treatment modalities including adjuvant chemotherapy for rectal cancer and for stage II colon cancer, and surgery of the primary tumour in incurable metastatic colorectal cancer are still subject of debate. Moreover, there is considerable short-term and long-term morbidity after (chemo)radiotherapy or surgery which should be taken into account. Further defining optimal treatment strategies is therefore of great importance. This thesis focused on improving evidence for treatment modalities that are currently subject of debate for patients with colorectal cancer. This was done using data from randomised controlled trials as well as cancer registry data. Show less
This thesis describes the use of high-dose-rate endorectal brachytherapy as a boost to external beam radiotherapy in patients with rectal cancer. With 60% clinical complete response in the HERBERT... Show moreThis thesis describes the use of high-dose-rate endorectal brachytherapy as a boost to external beam radiotherapy in patients with rectal cancer. With 60% clinical complete response in the HERBERT study, this treatment is very promising for use in organ preservation studies. Both toxicity of external beam radiotherapy as toxicity of brachytherapy are addressed and further improvements to the brachytherapy technique are suggested to increase tumor control while limiting toxicity. Show less
By implementation of MRI-based staging, selective preoperative radiotherapy and surgical resection according to the TME-principle, the outcomes for patients with locally advanced rectal cancer have... Show moreBy implementation of MRI-based staging, selective preoperative radiotherapy and surgical resection according to the TME-principle, the outcomes for patients with locally advanced rectal cancer have improved considerably over the last decades. This has led to an increased focus on quality of life, functional outcomes and shared decision making. In this thesis, novel treatment options for patients with locally advanced rectal cancer are evaluated, including watch and wait for patients with a complete response after chemoradiotherapy as well as a total neoadjudant therapy (TNT) approach. Also quality of life and the importance patients assign to several outcome measures after ungoqing treatment for rectal cancer themselves are described. Show less
Ende, R.P.J. van den; Ercan, E.; Keesman, R.; Kerkhof, E.M.; Marijnen, C.A.M.; Heide, U.A. van der 2020
PURPOSE: The individual channels in an endorectal applicator for high-dose-rate endorectal brachytherapy are not visible on standard MRI sequences. The aim of this study was to test whether an... Show morePURPOSE: The individual channels in an endorectal applicator for high-dose-rate endorectal brachytherapy are not visible on standard MRI sequences. The aim of this study was to test whether an ultrashort echo time (UTE) MRI sequence could be used to visualize the individual channels to enable MR-only treatment planning for rectal cancer.METHODS AND MATERIALS: We used a radial three-dimensional (3D) UTE pulse sequence and acquired images of phantoms and two patients with rectal cancer. We rigidly registered a UTE image and CT scan of an applicator phantom, based on the outline of the applicator. One observer compared channel positions on the UTE image and CT scan in five slices spaced 25 mm apart. To quantify geometric distortions, we scanned a commercial 3D geometric quality assurance phantom and calculated the difference between detected marker positions on the UTE image and corresponding marker positions on two 3D T-1-weighted images with opposing readout directions.RESULTS: On the UTE images, there is sufficient contrast to discern the individual channels. The difference in channel positions on the UTE image compared with the CT was on average -0.1 +/- 0.1 mm (left-right) and 0.1 +/- 0.3 mm (anteroposterior). After rigid registration to the 3D T-1-weighted sequences, the residual 95th percentile of the geometric distortion inside a 550-mm-diameter sphere was 1.0 mm (left-right), 0.9 mm (anteroposterior), and 0.9 mm (craniocaudal).CONCLUSIONS: With a UTE sequence, the endorectal applicator and individual channels can be adequately visualized in both phantom and patients. The geometrical fidelity is within an acceptable range. (C) 2020 The Authors. Published by Elsevier Inc. on behalf of American Brachytherapy Society. Show less
Introduction: Several factors are included in decision making for treatment of patients with locally advanced rectal cancer, including a trade-off between risks and gains of both clinical and... Show moreIntroduction: Several factors are included in decision making for treatment of patients with locally advanced rectal cancer, including a trade-off between risks and gains of both clinical and functional outcomes. However, it is largely unknown which outcomes are most important to patients and whether this differs between patients and clinicians.Methods: Both clinicians and patients treated for locally advanced rectal cancer were invited to fill out an online questionnaire, including a choice-based conjoint experiment. Participants were presented 14 comparisons of two hypothetical case presentations, characterized by different treatments and outcomes of care (6 attributes) and were asked to select the case with the best outcome at that moment. Hierarchical Bayes Estimation was used to calculate the relative importance (RI) of each of the six attributes.Results: In total, 94 patients and 128 clinicians completed the questionnaire. For patients, avoiding surgery with permanent stoma was most important (RI 24.4, 95%CI 21.88-26.87) and a 2-year difference in disease-free survival was least important (RI 5.6, 95%CI 4.9-6.2). Clinicians assigned highest importance to avoiding severe and daily worries about cancer recurrence (RI 30.7, 95%CI 29.1-32.4), while this was ranked 4th by patients (RI 17.9, 95%CI 16.5-19.4, p < 0.001).Conclusion: When confronted with different outcomes within one case description, patients find the duration of disease free survival the least important. In addition, considerable differences were found between the importance assigned by patients and clinicians to clinical and functional outcomes, most notably in avoiding surgery with permanent stoma and worries about recurrence. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Background In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is... Show moreBackground In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. Methods Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. Discussion This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for theen blocresection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. Show less
Valk, M.J.M. van der; Marijnen, C.A.M.; Etten, B. van; Dijkstra, E.A.; Hilling, D.E.; Kranenbarg, E.M.K.; ... ; Collaborative Investigators 2020
Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. Adjuvant chemotherapy is advised in... Show moreBackground: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. Adjuvant chemotherapy is advised in several international guidelines, although the survival benefit remains unclear and compliance is poor. The current multidisciplinary approach has led to major improvements in local control, yet the occurrence of distant metastases has not decreased accordingly. The combination of short-course radiotherapy (SCRT) and chemotherapy in the waiting period before surgery might have several benefits, including higher compliance, downstaging and better effect of systemic therapy.Methods: This is an investigator-initiated, international multicentre randomized phase III trial. High-risk rectal cancer patients were randomized to SCRT followed by chemotherapy (6 cycles CAPOX or alternatively 9 cycles FOLFOX4) and subsequent surgery, or long-course radiotherapy (25-28 x 2-1.8 Gy) with concomitant capecitabine followed by surgery and optional postoperative chemotherapy (8 cycles CAPOX or 12 cycles FOLFOX4) according to local institutions' policy. The primary endpoint is time to disease related treatment failure. Here, we report the compliance, toxicity and postoperative complications in both study groups.Findings: Between June 2011 and June 2016, 920 patients were enrolled. Of these, 901 were evaluable (460 in the experimental arm and 441 in the standard arm). All patients in the experimental arm received 5 x 5 Gy radiotherapy, and 84% of all patients received at least 75% of the prescribed chemotherapy. In the standard arm, the compliance for CRT was 93% and 58% for postoperative chemotherapy. Toxicity >= grade 3 occurred in 48% of patients in the experimental arm, compared to 25% of patients in the standard arm during preoperative treatment and 35% of patients during postoperative chemotherapy. No statistically significant differences in surgical procedures or postoperative complications were observed.Interpretation: High compliance (84%) of preoperative systemic treatment could be achieved with the experimental approach. Although considerable toxicity was observed during preoperative therapy, this did not lead to differences in surgical procedures or postoperative complications. Longer follow-up time is needed to assess the primary endpoint and related outcomes. (c) 2020 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 147 (2020) 75-83 Show less
Background Anastomotic leak after rectal cancer surgery is a severe complication associated with poorer oncologic outcome and quality of life. Preoperative assessment of the risk for anastomotic... Show moreBackground Anastomotic leak after rectal cancer surgery is a severe complication associated with poorer oncologic outcome and quality of life. Preoperative assessment of the risk for anastomotic leak is a key component of surgical planning, including the opportunity to create a defunctioning stoma. Objective The purpose of this study was to identify and quantify the risk factors for anastomotic leak to minimize risk by either not restoring bowel continuity or protecting the anastomosis with a temporary diverting stoma. Methods Potentially relevant studies were identified from the following databases: PubMed, Embase and Cochrane Library. This meta-analysis included studies on transabdominal resection for rectal cancer that reported data about anastomotic leak. The risk for anastomotic leak after rectal cancer surgery was investigated. Preoperative, intraoperative, and postoperative factors were extracted and used to compare anastomotic leak rates. All variables demonstrating a p value < 0.1 in the univariate analysis were entered into a multivariate logistic regression model to determine the risk factors for anastomotic leak. Results Twenty-six centers provided individual data on 9735 patients. Selected preoperative covariates (time before surgery, age, gender, smoking, previous abdominal surgery, BMI, diabetes, ASA, hemoglobin level, TNM classification stage, anastomotic distance) were used as independent factors in a logistic regression model with anastomotic leak as dependent variable. With a threshold value of the receiver operating characteristics (ROC) curve corresponding to 0.0791 in the training set, the area under the ROC curve (AUC) was 0.585 (p < 0.0001). Sensitivity and specificity of the model's probability > 0.0791 to identify anastomotic leak were 79.1% and 32.9%, respectively. Accuracy of the threshold value was confirmed in the validation set with 77.8% sensitivity and 35.2% specificity. Conclusions We trust that, with further refinement using prospective data, this nomogram based on preoperative risk factors may assist surgeons in decision making. The score is now available online (). Show less
