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Background: Pre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial., Patients and Methods: Patients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT- group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT ≥75% group) were compared with patients who did not receive pCT (pCT-/- group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression., Results: In total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT- and pCT-/- groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT-), and 0.5 and 0.8 (pCT ≥75% versus pCT-/-). However, all 95% confidence intervals included 1., Conclusions: These data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes., Methods: Patients with low cT3-4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response., Results: More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease., Conclusion: Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purposes: To describe current practice in the management of rectal cancer, to identify uncertainties that usually arise in the multidisciplinary team (MDT)'s discussions ('grey zones') and propose next generation studies which may provide answers to them., Materials and Methods: A questionnaire on the areas of controversy in managing T2, T3 and T4 rectal cancer was drawn up and distributed to the Rectal-Assisi Think Tank Meeting (ATTM) Expert European Board. Less than 70% agreement on a treatment option was indicated as uncertainty and selected as a 'grey zone'. Topics with large disagreement were selected by the task force group for discussion at the Rectal-ATTM., Results: The controversial clinical issues that had been identified within cT2-cT3-cT4 needed further investigation. The discussions focused on the role of (1) neoadjuvant therapy and organ preservation on cT2-3a low-middle rectal cancer; (2) neoadjuvant therapy in cT3 low rectal cancer without high risk features; (3) total neoadjuvant therapy, radiotherapy boost and the best chemo-radiotherapy schedule in T4 tumors. A description of each area of investigation and trial proposals are reported., Conclusion: The meeting successfully identified 'grey zones' and, in the light of new evidence, proposed clinical trials for treatment of early, intermediate and advanced stage rectal cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: The aim of this EURECCA international comparison is to compare oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer between European countries., Material and Methods: Population-based national cohort data from the Netherlands (NL), Belgium (BE), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), Spain (ES), and single-centre data from Lithuania (LT) were obtained. All operated patients with (y)pTNM stage I-III rectal cancer diagnosed between 2004 and 2009 were included. Oncologic treatment strategies and relative survival were calculated and compared between neighbouring countries., Results: We included 57,120 patients. Treatment strategies differed between NL and BE (p < 0.001), DK and SE (p < 0.001), and ENG and IE (p < 0.001). More preoperative radiotherapy as single treatment before surgery was administered in NL compared with BE (59.7% vs. 13.1%), in SE compared with DK (55.1% vs. 10.4%), and in ENG compared with IE (15.2% vs. 9.6%). Less postoperative chemotherapy was given in NL (9.6% vs. 39.1%), in SE (7.9% vs. 14.1%), and in IE (12.6% vs. 18.5%) compared with their neighbouring country. In ES, 55.1% of patients received preoperative chemoradiation and 62.3% postoperative chemotherapy. There were no significant differences in relative survival between neighbouring countries., Conclusion: Large differences in oncologic treatment strategies for patients with (y)pTNM I-III rectal cancer were observed across European countries. No clear relation between oncologic treatment strategies and relative survival was observed. Further research into selection criteria for specific treatments could eventually lead to individualised and optimal treatment for patients with non-metastasised rectal cancer., (Copyright © 2018. Published by Elsevier Ltd.)

Background: In a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years., Methods: Patients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible. Follow-up data were collected for all patients enrolled in the trial. Overall and recurrence-free survival were calculated using the Kaplan-Meier method., Results: Follow-up data were available for all 50 patients. After a median follow-up time of 8.1 years (range 6.0-9.8), 16 patients (32.0%) were still alive and 14 (28%) were disease-free. The median overall survival was 3.8 years (range 0.5-9.4). From the 36 patients who received radical treatment, two (5.6%) had a local recurrence and 29 (80.6%) had a distant recurrence., Conclusions: Long-term survival can be achieved in patients with primary metastatic rectal cancer after neoadjuvant radio- and chemotherapy. Despite a high number of recurrences, 32% of patients were alive after a median follow-up time of 8.1 years.

Aim: Dissection of the perineal body (PB) during abdominoperineal excision (APE) for low rectal cancer is often difficult due to the lack of a natural plane of dissection. Understanding the PB and its relation to the anorectum is essential to permit safe dissection during the perineal phase of the operation and avoid damage to the anorectum and urogenital organs. This study describes the anatomy and histology of the PB relevant to APE., Method: Six human adult cadaver pelvic exenteration specimens (three male, three female) from the Leeds GIFT Research Tissue Programme were studied. Paraffin-embedded mega-blocks were produced and serially sectioned at 50- and 250-μm intervals. Sections were stained by immunohistochemistry to show collagen, elastin and smooth muscle., Results: The PB was cylindrically shaped in the male specimens and wedge-shaped in the female ones. Although centrally located between the anal and urogenital triangles, it was nearly completely formed by muscle fibres derived from the rectal muscularis propria. Thick bundles of smooth muscle, mostly arising from the longitudinal muscle, inserted into the PB and levator ani muscle (LAM). The recto-urethralis muscle originated from the PB and separated the anterolateral PB from the urogenital organs., Conclusion: Smooth muscle fibres derived from the rectal muscularis propria extend into the PB and LAM and appear to fix the anorectum. Dissection of the PB during APE is safe only when the smooth muscle fibres that extend into the PB are divided., (Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.)

Aim: The number of examined lymph nodes (NLN) was associated with survival of stages II and III colorectal cancer (CRC) patients. Guidelines recommend examining at least 12 lymph nodes. This study investigated the influence of surgical specimen length on lymph node harvest and compliance with international guidelines., Materials and Methods: This population-based study included 4,724 cases of surgically treated CRC that were diagnosed from 2002 to 2008. Multivariate analyses were performed for the main study variables (age, gender, diagnosis at screening or in symptomatic patients, cancer site, staging, grading, number of positive nodes, neo-adjuvant treatment for rectal cancer, hospital were surgery was performed). Fractional polynomial models investigated the relationship between continuous variables and outcomes., Results: The NLN increased over time reaching ≥12 NLN in 64% of cases at the end of the study period. More NLN were associated with young age, right colon cancer, pT3-T4 disease, stages II and III and high grade. Fewer NLN were associated with short surgical specimen length and neo-adjuvant treatment in rectal cancer patients. Use of laparoscopy increased sharply over time., Conclusions: NLN increased over time in accordance with international guidelines. Surgical specimen length correlated with NLN which may determine therapeutic choices, particularly in stage II colon cancer. When harvested lymph nodes are under 10 in number and all are negative, chemotherapy is always recommended. As specimen lengths <20 cm were associated with a high risk of inadequate NLN counts, patients are at risk of over-treatment., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Excellent understanding of fasciae and nerves surrounding the rectum is necessary for total mesorectal excision (TME). However, fasciae anterolateral to the rectum and surrounding the low rectum are still poorly understood. We studied the perirectal fascia enfolding the extraperitoneally located part of the rectum in en-bloc cadaveric specimens and the University Medical Center Utrecht (UMCU) pelvic dataset, and describe implications for TME., Methods: Four donated human adult cadaveric specimens (two males, two females) were obtained through the Leeds GIFT Research Tissue Programme. Paraffin-embedded blocks were produced and serially sectioned at 50 and 250 μm intervals. Whole mount sections were stained with haematoxylin & eosin, Masson's trichrome and Millers' elastin. Additionally, the UMCU pelvic dataset including digitalised cryosections of a female pelvis in three axes was studied., Results: The mid and lower rectum were surrounded by a multi-layered perirectal fascia, of which the mesorectal fascia (MRF) and parietal fascia bordered the 'holy plane'. There was no extra constant fascia forming a potential surgical plane. Nerves ran laterally to the MRF. More caudally, the mesorectal fat strongly reduced and the MRF approached the rectal muscularis propria. The MRF had a variable appearance in terms of thickness and completeness, most prominently at the anterolateral lower rectum., Conclusion: Dissection onto the MRF allows nerve preservation in TME. Rectal surgeons are challenged in doing so as the MRF varies in thickness and shows gaps, most prominently at the anterolateral lower rectum. At this site, the risk of entering the mesorectum is great and may result in an incomplete specimen., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: High-dose-rate brachytherapy (HDRBT) appears to be associated with less treatment-related toxicity compared with external beam radiotherapy in patients with rectal cancer. The present study compared the effect of preoperative treatment strategies on overall survival, cancer-specific deaths, and local recurrences between a Dutch and Canadian expert center with different preoperative treatment strategies., Patients and Methods: We included 145 Dutch and 141 Canadian patients with cT3, non-metastasized rectal cancer. All patients from Canada were preoperatively treated with HDRBT. The preoperative treatment strategy for Dutch patients consisted of either no preoperative treatment, short-course radiotherapy, or chemoradiotherapy. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) comparing overall survival. We adjusted for age, cN stage, (y)pT stage, comorbidity, and type of surgery. Primary endpoint was overall survival. Secondary endpoints were cancer-specific deaths and local recurrences., Results: Five-year overall survival was 70.9% (95% CI 62.6%-77.7%) in Dutch patients compared with 86.9% (80.1%-91.6%) in Canadian patients, resulting in an adjusted HR of 0.70 (95% CI 0.39-1.26; p = 0.233). Of 145 Dutch patients, 6.9% (95% CI 2.8%-11.0%) had a local recurrence and 17.9% (95% CI 11.7%-24.2%) patients died of rectal cancer, compared with 4.3% (95% CI 0.9%-7.5%) local recurrences and 10.6% (95% CI 5.5%-15.7%) rectal cancer deaths out of 141 Canadian patients., Conclusion: We did not detect statistically significant differences in overall survival between a Dutch and Canadian expert center with different treatment strategies. This finding needs to be further investigated in a randomized controlled trial., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Excellent anatomical knowledge of the rectum and surrounding structures is essential for total mesorectal excision (TME). Denonviliers' fascia (DVF) has been frequently studied, though the optimal anterior plane in TME is still disputed. The relationship of the lateral edges of DVF to the autonomic nerves and mesorectal fascia is unclear. We studied whole mout microscopic sections of en-bloc cadaveric pelvic exenteration and describe implications for TME., Methods: Four donated human adult cadaveric specimens (two males, two females) were obtained from the Leeds GIFT Research Tissue Programme. Paraffin-embedded mega blocks were produced and serially sectioned at 50 and 250 μm intervals. Sections were stained with haematoxylin & eosin, Masson's trichrome and Millers' elastin. Additionally, a series of eleven human fetal specimens (embryonic age of 9-20 weeks) were studied., Results: DVF consisted of multiple fascial condensations of collagen and smooth muscle fibres and was indistinguishable from the anterior mesorectal fascia and the prostatic fascia or posterior vaginal wall. The lateral edges of DVF appeared fan-shaped and the most posterior part was continuous with the mesorectal fascia. Fasciae were not identified in fetal specimens., Conclusion: DVF is adherent to and continuous with the mesorectal fascia. Optimal surgical dissection during TME should be carried out anterior to DVF to ensure radical removal, particularly for anterior tumours. Autonomic nerves are at risk, but can be preserved by closely following the mesorectal fascia along the anterolateral mesorectum. The lack of evident fasciae in fetal specimens suggested that these might be formed in later developmental stages., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: In many European countries, short-term 5 × 5 Gy radiotherapy has become the standard preoperative treatment of patients with resectable rectal cancer. Individualized risk assessment might allow a better selection of patients who will benefit from postoperative treatment and intensified follow-up., Patients and Methods: From patient's data from three European rectal cancer trials (N = 2881), we developed multivariate cox nomograms reflecting the risk for local recurrence (LR), distant metastases (DM) and overall survival (OS). Evaluated variables were age, gender, tumour distance from the anal verge, the use of radiotherapy, surgical technique (total mesorectal excision/conventional surgery), surgery type (low anterior resection/abdominoperineal resection), time from randomization to surgery, residual disease (R0 versus R1 + 2), pT-stage, pN-stage and surgical complications., Results: Pathological T- and N-status are of vital importance for an accurate prediction of LR, DM and OS. Short-course radiotherapy reduces the rate of LR. The developed nomograms are capable of predicting events with a validation c-index of 0.79 (LR), 0.76 (DM) and 0.75 (OS). The proposed stratification in risk groups allowed significant distinction between Kaplan-Meier curves for outcome., Conclusion: The developed nomograms can contribute to better individual risk prediction for LR, DM and OS for patients operated on rectal cancer. The practicality of the defined risk groups makes decision support in the consulting room feasible, assisting physicians to select patients for adjuvant therapy or intensified follow-up., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME)., Patients and Methods: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival., Results: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39)., Conclusion: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual., Registration Number: Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Several studies have shown remarkable differences in colorectal cancer survival across Europe. Most of these studies lacked information about stage and treatment. In this study we compared short-term survival as well as differences in tumour stage and treatment strategies between five European countries: Norway, Sweden, Denmark, Belgium, and the Netherlands. For this retrospective cohort study all patients aged 18 years or older and operated on adenocarcinoma of the rectum without distant metastases and diagnosed in 2008 and 2009 were selected in national audit registries from Norway, Sweden, Denmark, Belgium, and the Netherlands. Differences in pre-operative treatment between the countries were compared using univariable and multivariable logistic regression. One year relative survival and one year relative excess risk of death (RER) were compared between the five countries. Large variation in the use of preoperative radiotherapy and chemoradiation was found between the countries. Even though, there was little variation in relative survival between the countries, except Sweden, which had a significant better one year RER of death among the elderly patients after adjustment. The differences in survival are expected to be caused by differences in peri-operative care, selection of patients, and especially management of elderly patients. The effects of preoperative treatment are expected to be seen on long term follow-up., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate whether the abdominoperineal excision (APE) is associated with an increased risk of circumferential resection margin (CRM) involvement after rectal cancer surgery in comparison with low anterior resection (LAR)., Background: The oncologic inferiority of the APE technique in comparison with LAR has been widely reported in literature. However, because of large evolvement in rectal cancer care, outcomes after APE may have improved since then., Methods: The population-based dataset of the Dutch Surgical Colorectal Audit was used selecting 5017 patients with primary rectal cancer undergoing surgery in 2010 to 2011. Propensity scores were calculated for the likelihood of performing an APE given relevant patient and tumor characteristics, and used in the multivariate analysis of CRM involvement., Results: The APE was associated with a slight, nonsignificant, increased risk of CRM involvement [odds ratio (OR) = 1.33; confidence interval (CI) = 0.93-1.90]. Absolute percentages of CRM involvement were 8% and 12% after LAR and APE, respectively.In the subgroup analysis, advanced rectal tumors (cT3-4) were associated to a higher risk of CRM involvement after APE (OR = 1.61; CI = 1.05-1.90), whereas smaller tumors (cT1-2) were not (OR = 0.62; CI = 0.27-1.40)., Conclusions: The results suggest that on a national level the APE procedure itself is not a strong predictor anymore for CRM involvement after rectal cancer surgery. However, in advanced tumors, results after APE are inferior to LAR.

Background: We evaluated the clinical prognostic value of methylation of two non-coding repeat sequences, long interspersed element 1 (LINE-1) and Alu, in rectal tumour tissues. In addition to DNA methylation, expression of histone modifications H3K27me3 and H3K9Ac was studied in this patient cohort., Methods: LINE-1 and Alu methylation were assessed in DNA extracted from formalin-fixed paraffin-embedded tissues. A pilot (30 tumour and 25 normal tissues) and validation study (189 tumour and 53 normal tissues) were performed. Histone modifications H3K27me3 and H3K9Ac were immunohistochemically stained on tissue microarrays of the study cohort., Results: In early-stage rectal cancer (stage I-II), hypomethylation of LINE-1 was an independent clinical prognostic factor, showing shorter patient survival (P=0.014; HR: 4.6) and a higher chance of tumour recurrence (P=0.001; HR: 9.6). Alu methylation did not show any significant correlation with clinical parameters, suggesting an active role of LINE-1 in tumour development. Expression of H3K27me3 (silencing gene expression) and H3K9Ac (activating gene expression) in relation to methylation status of LINE-1 and Alu supported this specific role of LINE-1 methylation., Conclusion: The epigenetic status of LINE-1, but not of Alu, is prognostic in rectal cancer, indicating an active role for LINE-1 in determining clinical outcome.

Background: Transanal endoscopic microsurgery (TEM) has gained wide-spread acceptance as a safe and useful technique for the resection of rectal adenomas and selected T1 malignant lesions. If the lesion appears >T1 rectal cancer after resection with TEM, a completion TME resection is recommended. The aim of this study was to investigate the results of TME surgery after TEM for rectal cancer., Methods: In four tertiary referral hospitals for TEM, all patients with completion TME surgery after initial TEM were selected. All eligible patients who were treated with 5 × 5 Gy radiotherapy followed by TME surgery from the Dutch TME trial were selected as reference group. A multivariate logistic regression model was used to calculate odds ratio's (OR) for colostomies and for colo- and ileostomies combined. Local recurrence and survival rates were compared in hazard ratio's (HR) using the multivariate Cox proportional hazard model., Results: Fifty-nine patients were included in the TEM-COMPLETION group and 881 patients from the TME trial. In the TEM-COMPLETION group, 50.8% of the patients had a colostomy compared to 45.9% in the TME trial, OR 2.51 (p < 0.006). There is no significant difference when ileo- and colostomies are analyzed together. In the TEM-COMPLETION group, 10.2% developed a local recurrence compared to 5.2% in the TME trial, HR 6.8 (p < 0.0001)., Conclusions: Completion TME surgery after TEM for unexpected rectal adenocarcinoma results in more colostomies and higher local recurrence rates compared to one stage TME surgery preceded with preoperative 5 × 5 Gy radiotherapy. Pre-operative investigations must be optimized to distinguish malignant and benign lesions and prevent avoidable local recurrence and colostomies., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aim: The purpose of this multicenter cohort study was to evaluate whether a differentiated treatment of primary rectal cancer based on magnetic resonance imaging (MRI) can reduce the number of incomplete resections and local recurrences and improve recurrence-free and overall survival., Methods: From February 2003 until January 2008, 296 patients with rectal cancer underwent preoperative MRI using a lymph node specific contrast agent to predict circumferential resection margin (CRM), T- and N-stage. Based on expert reading of the MRI, patients were stratified in: (a) low risk for local recurrence (CRM>2mm and N0 status), (b) intermediate risk and (c) high risk (close/involved CRM, N2 status or distal tumours). Mainly based on this MRI risk assessment patients were treated with (a) surgery only (TME or local excision), (b) preoperative 5 × 5 Gy+TME and (c) a long course of chemoradiation therapy followed by surgery after a 6-8 week interval., Results: Overall 228 patients underwent treatment with curative intent: 49 with surgery only, 86 with 5 × 5 Gy and surgery and 93 with chemoradiation and surgery. The number of complete resections (margin>1mm) was 218 (95.6%). At a median follow-up of 41 months the three-year local recurrence rate, disease-free survival rate and overall survival rate is 2.2%, 80% and 84.5%, respectively., Conclusion: With a differentiated multimodality treatment based on dedicated preoperative MR imaging, local recurrence is no longer the main problem in rectal cancer treatment. The new challenges are early diagnosis and treatment, reducing morbidity of treatment and preferably prevention of metastatic disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The last decade there has been an increased awareness of the problem of anastomotic leakage after low anterior resection for rectal cancer, which may have led to more defunctioning stomas. In this study, current use of defunctioning stomas was assessed and compared to the use of defunctioning stomas at the time of the TME-trial together with associated outcomes., Methods: Eligible patients with rectal cancer undergoing low anterior resection were selected from the Dutch Surgical Colorectal Audit (DSCA, n = 988). Similar patients were selected from the TME-trial (n = 891). The percentages of patients with a defunctioning stoma, anastomotic leakage and postoperative mortality rates were studied. Multivariable models were used to study possible confounding on the outcomes., Results: At the time of the TME-trial, 57% of patients received a defunctioning stoma. At the time of the DSCA, 70% of all patients received a defunctioning stoma (p < 0.001). Anastomotic leakage rates were similar (11.4% and 12.1%; p = 0.640). The postoperative mortality rate differed (3.9% in the TME-trial vs. 1.1% in the DSCA; p < 0.001), but was not associated with a more frequent use of a stoma (OR 1.80, 95% CI 0.91-3.58)., Conclusion: In current surgical practice, 70% of patients undergoing LAR for rectal cancer receives a defunctioning stomas. This percentage seems increased when compared to data from the TME-trial. Clinically relevant anastomotic leakage rates remained similar. Therefore, current routine use of defunctioning stomas should be questioned., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer., Patients and Methods: Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m(2), day 1) intravenously and capecitabine (1000 mg/m(2) twice daily orally, days 1-14) for up to six cycles. Surgery was carried out 6-8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated., Results: Of 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%-90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%-84.5%). Toxic effects were tolerable. No treatment-related deaths occurred., Conclusions: Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab-capecitabine-oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.

Background: Magnetic resonance imaging (MRI) methods for chemoradiotherapy (CRT) response assessment of rectal cancer include posttreatment T staging (ymrT), tumor regression grading (mrTRG), volume reduction posttreatment, and modified RECIST measurement. We compared these methods in identifying good versus poor responders with the histopathological standards of T stage (ypT) and tumor regression grading (TRG)., Methods: A total of 86 patients underwent CRT in a prospective phase II trial for MRI-defined locally advanced rectal cancer. Two readers independently assessed MRIs for ymrT, mrTRG, volume change, and RECIST. Parameters for each case were categorized as good or poor response and analyzed against ypT and TRG by univariate logistic regression., Results: A total of 83 patients had evaluable imaging, and 78 had final pathology (five did not undergo surgery). Of these, 34 patients had good response (ypT0-3a) and 44 had poor response (>ypT3a). Also, 27 patients had favorable pathologic TRG (predominant fibrosis) and 51 had unfavorable TRG (predominant tumor). Good mrTRG and ymr 80 % showed an OR of 3.23 (95 % CI: 1.14-9.17), 4.25 (95 % CI: 0.92-15.45), respectively, for a good ypT score (P = 0.028), but there was no association for histopathological TRG., Conclusion: Favorable and unfavorable histopathology are predicted by both ymrT and mrTRG, and we recommend these parameters for post-treatment assessment of rectal cancers treated with CRT.

Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients., Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998-2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure., Results: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63-0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50-0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46-0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79-1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70-2.20; P<0.001)., Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of a placebo-controlled trial that investigates the role of aspirin as adjuvant treatment in colon cancer patients.

Colorectal cancer is the cancer with the second highest cancer incidence in Europe. Roughly, 1 out of 3 patients with a colorectal malignancy has a rectal carcinoma. Surgery is the cornerstone in the curative treatment of rectal cancer. In the 1980s with conventional surgery, the 5-year local recurrence rate was over 20% and the 5-year overall survival rate around 50%. In the Swedish Rectal Cancer trial, in which 1,168 patients were included, preoperative radiotherapy in addition to conventional surgery resulted in a reduction of more than 50% in the 5-year local recurrence rate in comparison to conventional surgery alone (11 vs. 27%; p < 0.001). In addition, the 5-year overall survival rate improved from 48 to 58% if patients were treated with preoperative radiotherapy in addition to conventional surgery (p = 0.004). With total mesorectal excision (TME), by which the rectum with its mesorectum and visceral fascia are dissected sharply and under direct vision, local recurrence rates dropped and overall survival improved. In the Dutch TME trial, 5 × 5 Gy preoperative radiotherapy in combination with TME surgery was compared to TME surgery alone (1,861 patients). In this trial, the 5-year local recurrence rate for patients treated with TME surgery alone was similar to patients treated in the Swedish Rectal Cancer trial with blunt dissection in combination with preoperative 5 × 5 Gy radiotherapy (11%). If preoperative radiotherapy was added to TME surgery, the 5-year local recurrence rate was reduced to 5.6%. The overall survival rate at 5 years was 64% for both patients treated with TME surgery alone and patients treated with preoperative radiotherapy followed by TME surgery, compared to 48% for patients treated with blunt dissection alone in the previously mentioned Swedish trial. TME surgery is now considered the standard surgical procedure for rectal cancer. However, even if TME surgery is performed, surgical quality varies. First, these results indicate that improvements in the surgical procedure itself can result in major progress regarding long-term oncological outcome, such as decreased local recurrence rates and improved overall survival. Second, it illustrates that variation in surgical quality could lead to large differences in outcome. Recently, it was shown that surgical variation is not only important for patients with rectal cancer, but also plays an important role for the outcome of patients with colon cancer., (Copyright © 2012 S. Karger AG, Basel.)

Aims: Optimal staging in rectal cancer is indispensable for the decision on further treatment and estimation of prognosis. This study assesses the prognostic capacity of the metastatic lymph node ratio (LNR) in addition to the new TNM classification., Methods: LNR was determined, in stage III patients from the Dutch TME-trial. Six year median follow up data from the trial database were used to analyse the relation of LNR to overall survival (OS) and local recurrence (LR). The relation of LNR to lymph node yield was assessed and appropriate cut off values of LNR for clinical use were determined., Results: 605 patients were analyzed. 278 underwent pre-operative radiotherapy. 82 patients developed a local recurrence and 289 distant metastases. LNR was an independent risk factor for OS, hazard ratio (HR) 2.10 (95% CI 1.35-3.27) (in addition to age >= 65 years, involved circumferential resection margin (CRM) and new TNM stage) and LR, HR 2.25 (95% CI 1.02-4.56) (in addition to pre-operative radiotherapy and involved CRM). LNR is predictive of OS and LR from a lymph node yield of more than one and more than five respectively. A LNR value of 0.60 offers the best cut off to identify high risk patients (5-years OS was 61 vs. 32%, HR 2.45 (95% CI 1.96-3.08) and 5-years LR rate 12.6 versus 16.3%, HR 1.65 (95% CI 1.03-2.64))., Conclusions: LNR is an independent risk factor for OS and LR in addition to the 7th edition of the TNM classification. It can aid in predicting prognosis and identifying patients that should be considered for adjuvant treatment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to obtain detailed anatomical information about the lateral lymph nodes, in order to determine whether they might play a role in presacral local recurrence of rectal cancer after total mesorectal excision without lateral lymph node dissection., Methods: Ten serially sectioned human fetal pelvises were studied at high magnification and a three-dimensional reconstruction of the fetal pelvis was made., Results: Examination of the histological sections and the three-dimensional reconstruction showed that lateral lymph node tissue comprises a major proportion of the pelvic tissue volume. There were no lymph nodes located in the presacral area. Connections between the mesorectal and extramesorectal lymph node system were found in all fetal pelvises, located below the peritoneal reflection on the anterolateral side of the fetal rectum. At this site middle rectal vessels passed to and from the mesorectum, and branches of the autonomic nervous system bridge to innervate the rectal wall., Conclusion: The findings of this study support the hypothesis that tumour recurrence might arise from lateral lymph nodes.

Background: Aim of this study was to describe treatment patterns and outcome according to region and hospital type and volume among patients with rectal cancer in the Netherlands., Methods: All patients with rectal carcinoma diagnosed in the period 2001-2006 were selected from the Netherlands Cancer Registry. Logistic regression analyses were performed to examine the influence of relevant factors on the odds of receiving preoperative radiotherapy and on the odds of postoperative mortality. Relative survival analysis was used to estimate relative excess risk of dying according to hospital type and volume., Results: In total, 16 039 patients were selected. Patients diagnosed in a teaching or university hospital had a lower odds (OR 0.85; 95% CI 0.73-0.99 and OR 0.70; 95% CI 0.52-0.92) and patients diagnosed in a hospital performing >50 resections per year had a higher odds (OR 1.95; 95% CI 1.09-1.76) of receiving preoperative radiotherapy. A large variation between individual hospitals in rates of preoperative radiotherapy and between Comprehensive Cancer Centre-regions in the administration of preoperative chemoradiation was revealed. Postoperative mortality was not correlated to hospital type or volume. Patients with T1-M0 tumours diagnosed in a hospital with >50 resections per year had a better survival compared to patients diagnosed in a hospital with <25 resections per year (RER 0.11; 95% CI 0.02-0.78)., Conclusion: This study demonstrated variation in treatment and outcome of patients with rectal cancer in the Netherlands, with differences related to hospital volume and hospitals teaching or academic status. However, variation in treatment patterns between individual hospitals proved to be much larger than could be explained by the investigated characteristics. Future studies should focus on the reasons behind these differences, which could lead to a higher proportion of patients receiving optimal treatment for their stage of the disease., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT)., Patients and Methods: A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo)radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied., Results: Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor-node-metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC., Conclusions: Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.

Aim of the Study: In patients from the Dutch TME trial patterns of local recurrence (LR) in rectal cancer were studied. The purpose was to reconstruct the most likely mechanisms of LR and the effect of preoperative radiotherapy., Methods: 1417 patients were analyzed; 713 were randomized into preoperative radiotherapy and total mesorectal excision (RT + TME), 704 into TME alone. Of the 114 patients with LR, the subsites of LR were determined and related to tumor and treatment factors., Results: Overall 5-year LR-rate was 4.6% in the RT + TME group and 11.0% in the TME group. Presacral local recurrences occurred most in both groups. Radiotherapy reduced anastomotic LR significantly, except when after low anterior resection (LAR) distal margins were less than 5 mm. Abdominoperineal resection (APR) mainly resulted in presacral LR. Even after resection with a negative circumferential resection margin, LR-rates were high. Thirty percent of the patients had advanced tumors, which resulted in 58% of all LRs. Lateral LR comprised 20% of all LR. Presacral and lateral LR resulted in a poor prognosis, in contrast to anterior or anastomotic LRs with a relatively good prognosis., Conclusions: RT reduces LR in all subsites and is especially effective in preventing anastomotic LR after LAR. APR-surgery mainly results in presacral LR, which may be prevented by a wider resection. In the TME trial many advanced tumors were included, rather requiring chemoradiotherapy instead of RT. Currently, with good imaging techniques, better selection can take place. Especially lateral LR might be a problem in the future., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: In the Netherlands, the Total Mesorectal Excision (TME) surgical technique for rectal cancer was introduced together with pre-operative radiotherapy in a quality controlled manner within the framework of the TME trial (1996-1999). The aim of this study is to examine the effects of the structural changes in rectal cancer care on survival compared to colon cancer for patients treated before, during and after the TME trial., Method: We compared overall survival of all patients with curatively resected colon (n = 15,266) and rectal cancer (n = 5839) in the regions of Comprehensive Cancer Centres South and West between 1990 and 2005, adjusting for prognostic variables., Results: In the pre-trial period, rectal cancer had a significant lower survival compared to colon cancer (HR 1.248, P < 0.01). However, in the post-trial period, survival after rectal cancer was similar to colon cancer (HR 0.987, n.s.)., Conclusion: Although survival improved significantly for both colon and rectal cancer in the last 15 years, the substantially worse results after rectal cancer have been eliminated. This study shows the lasting effects that structural surgical training and quality assurance can have on survival outcome., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Background: Anastomotic leakage represents a major complication after anterior resection of the rectum. The incidence of anastomotic leakage varies considerably among clinical studies in part owing to the lack of a standardized definition of this complication. The aim of the present article was to propose a definition and severity grading of anastomotic leakage after anterior rectal resection., Methods: After a literature review a consensus definition and severity grading of anastomotic leakage was developed within the International Study Group of Rectal Cancer., Results: Anastomotic leakage should be defined as a defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- and extraluminal compartments. Severity of anastomotic leakage should be graded according to the impact on clinical management. Grade A anastomotic leakage results in no change in patients' management, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy., Conclusion: The proposed definition and clinical grading is applicable easily in the setting of clinical studies. It should be applied in future reports to facilitate valid comparison of the results of different studies., (Copyright 2010 Mosby, Inc. All rights reserved.)

Purpose: After total mesorectal excision (TME) for rectal cancer, pathology is standardized with margin status as a predictor for recurrence. This has yet to be implemented after transanal endoscopic microsurgery (TEM) and was investigated prospectively for T1 rectal adenocarcinomas., Patients and Methods: Eighty patients after TEM were compared to 75 patients after TME. The study protocol included standardized pathology. TEM patients were eligible when excision margins were negative., Results: TEM was safer than TME as reflected by operating time, blood loss, hospital stay, morbidity, re-operation rate and stoma formation (all P<0.001). Mortality after TEM was 0% and after TME 4%. At 5 years after TEM and TME, both overall survival (TEM 75% versus TME 77%, P=0.9) and cancer-specific survival (TEM 90% versus TME 87%, P=0.5) were comparable. Local recurrence rate after TEM was 24% and after TME 0% (HR 79.266, 95% CI, 1.208 to 5202, P<0.0001)., Conclusion: For T1 rectal adenocarcinomas TEM is much saver than TME and survival is comparable. After TEM local recurrence rate is substantial, despite negative excision margins.

Background: The association between diverting stomas and symptomatic anastomotic leakage after rectal cancer surgery was studied, as well as the impact of leakage on local recurrence, distant metastasis, and disease-free, overall and cancer-specific survival., Methods: Data from the Swedish Rectal Cancer Trial, Dutch TME trial, CAO/ARO/AIO-94 trial, EORTC 22921 trial and Polish Rectal Cancer Trial were pooled (n = 5187). All eligible patients without distant metastases at the time of low anterior resection were selected (n = 2726); overall survival was studied in patients aged 75 years or less (n = 2480). Multivariable models were used to study the association between diverting stomas and anastomotic leakage, and between leakage and recurrence or survival., Results: Some 9.7 per cent of patients were diagnosed with a symptomatic anastomotic leak; diverting stomas were negatively associated with leakage (11.6 per cent without and 7.8 per cent with a stoma; P = 0.002). Anastomotic leakage was negatively associated with overall survival in the multivariable analysis (hazard ratio (HR) 1.29 (95 per cent confidence interval 1.02 to 1.63); P = 0.034), but not with cancer-specific survival (HR 1.12 (0.83 to 1.52); P = 0.466)., Conclusion: Diverting stomas were associated with less symptomatic anastomotic leakage. Oncological outcome was not significantly influenced by leakage, but overall survival was reduced., ((c) 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background and Purpose: During the first decade of the 21st century a number of important European randomized studies were published. In order to help shape clinical practice based on best scientific evidence from the literature, the International Conference on 'Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), and European Society of Therapeutic Radiation Oncology (ESTRO)., Methods: Consensus was achieved using the Delphi method. The document was available to all Committee members as a web-based document customized for the consensus process. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by a topic, and a series of statements were developed. Each member commented and voted, sentence by sentence thrice. Sentences upon which an agreement was not reached after voting round # 2 were openly debated during a Consensus Conference in Perugia (Italy) from 11 December to 13 December 2008. A hand-held televoting system collected the opinions of both the Committee members and the audience after each debate. The Executive Committee scored percentage consensus based on three categories: "large consensus", "moderate consensus", and "minimum consensus"., Results: The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of the members. All chapters were voted on by at least 75% of the members, and the majority was voted on by >85%., Conclusions: This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe.

This study aimed to identify risk factors for long-term sexual dysfunction (SD) after rectal cancer treatment. Patients with resectable rectal cancer were randomised to total mesorectal excision with or without preoperative radiotherapy (PRT). Preoperatively and at 3, 6, 12, 18 and 24 months postoperatively, SD scores were filled out in questionnaires. Possible risk factors for postoperative deterioration of sexual functioning, including patients' demographics, tumour-specific factors and treatment-related variables, were investigated with univariate and multivariable regression analyses. Increase in general SD, erectile dysfunction and ejaculatory problems were reported by 76.4, 79.8 and 72.2 percent of the male patients, respectively. Risk factors were nerve damage, blood loss, anastomotic leakage, PRT and the presence of a stoma. In female patients, increase in general SD, dyspareunia and vaginal dryness were reported by 61.5, 59.1 and 56.6 percent, respectively. This was associated with PRT and the presence of a stoma. SD occurs frequently after rectal cancer treatment and is caused by surgical (nerve) damage with an additional effect of PRT. Patients should be informed preoperatively, and education of surgeons in neuroanatomy may provide the key to the improvement of functional outcome.

In 1908, William Ernest Miles published his article in the Lancet, introducing the basis of modern rectal cancer surgery. He established the basis for curative cancer treatment by combining the knowledge of anatomy and biological behaviour with improved surgical options as a result of better anaesthesiological techniques. Miles' contribution comprised the introduction of the concept of lymphatic spread of cancer cells and his consequent radical surgical resection, removing all primary lymph nodes en bloc. Miles' concept has dominated the minds of surgeons throughout the 20th century and his abdominoperineal resection has been the golden standard for several decades. However, his concept of downward spread of rectal cancer was proven wrong, which initiated the historical shift from radical abdominoperineal resection to the use of sphincter-saving surgery. Since the introduction of total mesorectal excision, abdominoperineal excision has been performed in only a minority of patients. Further improvement in surgical technique consisted of autonomic nerve preservation, improving functional outcome. From a historical overview, it can be concluded that the management of rectal cancer has been progressed tremendously over the past 100 years, mainly because of an increased understanding of the pathology and natural history of the disease, which has been initiated by Miles.

A cohort of patients operated at the National Cancer Center Hospital in Tokyo for rectal carcinoma, at or below the peritoneal reflection, was reviewed retrospectively. The purpose was to study the risk factors for local relapse and the patterns of local recurrence. Three hundred fifty-one patients operated between 1993 and 2002 for rectal carcinoma, at or below the peritoneal reflection, were analyzed. One hundred forty-five patients, with preoperatively staged T1 or T2 tumors without suspected lymph nodes, underwent total mesorectal excision (TME). Lateral lymph node dissection (LLND) was performed in suspected T3 or T4 disease, or when positive lymph nodes were seen; 73 patients received unilateral LLND and 133 patients received bilateral LLND. Of the 351 patients 6.6% developed local recurrence after 5 years. TME only resulted in 0.8% 5-year local recurrence. In lymph-node-positive patients, 33% of the unilateral LLND group had local relapse, significantly more (p = 0.04) than in the bilateral LLND group with 14% local recurrence. Local recurrence in the lateral, presacral, perineal, and anastomotic subsites was lower in the bilateral LLND group as compared with in the unilateral LLND group. We conclude that, in selected patients, surgery without LLND has a very low local recurrence rate. Bilateral LLND is more effective in reducing the chance of local recurrence than unilateral LLND. Either surgical approach, with or without LLND, requires reliable imaging during work-up.

Background: Urinary dysfunction (UD) is common after rectal cancer treatment, but the contribution of each treatment component (surgery and radiotherapy) to its development remains unclear. This study aimed to evaluate UD during 5 years after total mesorectal excision (TME) and to investigate the influence of preoperative radiotherapy (PRT) and surgical factors., Methods: Patients with operable rectal cancer were randomized to TME with or without PRT. Questionnaires concerning UD were completed by 785 patients before and at several time points after surgery. Possible risk factors, including PRT, demographics, tumour location, and type and extent of resection, were investigated by multivariable regression analysis., Results: Long-term incontinence was reported by 38.1 per cent of patients, of whom 72.0 per cent had normal preoperative function. Preoperative incontinence (relative risk (RR) 2.75, P = 0.001) and female sex (RR 2.77, P < 0.001) were independent risk factors. Long-term difficulty in bladder emptying was reported by 30.6 per cent of patients, of whom 65.0 per cent had normal preoperative function. Preoperative difficulty in bladder emptying (RR 2.94, P < 0.001), peroperative blood loss (RR 1.73, P = 0.028) and autonomic nerve damage (RR 2.82, P = 0.024) were independent risk factors. PRT was not associated with UD., Conclusion: UD is a significant clinical problem after rectal cancer treatment and is not related to PRT, but rather to surgical nerve damage., (Copyright (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Knowledge of the biology and management of rectal cancer continues to improve. A multidisciplinary approach to a patient with rectal cancer by an experienced expert team is mandatory, to assure optimal diagnosis and staging, surgery, selection of the appropriate neo-adjuvant and adjuvant strategy and chemotherapeutic management. Moreover, optimal symptom management also requires a dedicated team of health care professionals. The introduction of total mesorectal excision has been associated with a decrease in the rate of local failure after surgery. High quality surgery and the achievement of pathological measures of quality are a prerequisite to adequate locoregional control. There are now randomized data in favour of chemoradiotherapy or short course radiotherapy in the preoperative setting. Preoperative chemoradiotherapy is more beneficial and has less toxicity for patients with resectable rectal cancer than postoperative chemoradiotherapy. Furthermore chemoradiotherapy leads also to downsizing of locally advanced rectal cancer. New strategies that decrease the likelihood of distant metastases after initial treatment need be developed with high priority. Those involved in the care for patients with rectal cancer should be encouraged to participate in well-designed clinical trials, to increase the evidence-based knowledge and to make further progress. Health care workers involved in the care of rectal cancer patients should be encouraged to adopt quality control processes leading to increased expertise.

Aim: To elicit surgery preferences of patients who have experience with either low anterior resection (LAR) or abdominoperineal resection (APR) and its outcomes, to support decision-making in future patients with resectable rectal cancer., Methods: One hundred and twenty-two patients were interviewed. Surgery preference was assessed in two ways. In the treatment trade-off method, the certainty of a stoma was hypothetically weighed against the risk of incontinence. In the time trade-off method, remaining life expectancy was traded off to avoid a permanent stoma or faecal incontinence., Results: To avoid APR, LAR patients accepted a much higher risk of incontinence than APR patients. In fact, 71% of the LAR patients chose LAR if they would certainly suffer monthly incontinence, and still 32% if they would certainly suffer daily incontinence. Nevertheless, APR patients would give up less remaining life years to be without a permanent stoma than LAR patients to be without monthly incontinence., Conclusions: Most patients preferred LAR above APR, even if LAR involved a risk of faecal incontinence. This seems to justify that LAR, if surgically possible, is performed in the first instance. However, since APR patients could live well with a permanent stoma, we recommend clearly informing patients before surgery about the surgical options and their potential outcomes.

Background: Low anterior resection (LAR) may result in faecal incontinence. This study aimed to identify risk factors for long-term faecal incontinence after total mesorectal excision (TME) with or without preoperative radiotherapy (PRT)., Methods: Between 1996 and 1999, patients with operable rectal cancer were randomized to TME with or without PRT. Eligible patients who underwent LAR were studied retrospectively at 2 years (399 patients) and 5 years (339) after TME., Results: At 5 years after surgery faecal incontinence was reported by 61.5 per cent of patients who had PRT and 38.8 per cent of those who did not (P < 0.001). Excessive blood loss and height of the tumour were associated with long-term faecal incontinence, but only in patients treated with PRT., Conclusion: Faecal incontinence is likely to occur after PRT and TME, especially when the perineum is irradiated., (Copyright (c) 2007 British Journal of Surgery Society Ltd.)

Introduction: The incidence of rectal cancer is highest in elderly patients. However, these patients are often underrepresented in randomised studies. Therefore, it is not clear whether results of rectal cancer studies are equally applicable to both elderly and younger patients. In this paper, the Dutch Total Mesorectal Excision (TME) study is revisited, focused on patients aged 75 years and above. The rectal cancer databases of the Comprehensive Cancer Centres (CCC) South and West were combined to analyse the effect of the TME-study in three different periods: before (1990-1995), during (1996-1999) and after (2000-2002) the trial., Results: Implementation of preoperative radiotherapy, as investigated in the TME trial, and the introduction of TME surgery resulted in improved 5 year survival during the subsequent periods, in patients younger than 75 years, of 60% (1990-1995) to 67% (1996-1999) and 70% (2000-2002) (log rank p<0.0001). The older patients did not improve and remained at 41%, 40% and 43% at 5 years in the respective periods. Furthermore, mortality during the first 6-month period after treatment is significantly raised compared to younger patients: 14% in the elderly, compared to 3.9% in the younger TME-study patient (p<0.0001 X2). In the CCC database these figures were confirmed at 16% and 3.9% (p<0.0001 X2)., Conclusion: Overall survival was not improved in the elderly rectal cancer patient after introduction of preoperative radiotherapy and TME-surgery. Non-cancer related mortality is a significant problem in the first 6 months after surgery.

Preoperative radiotherapy (PRT) in resectable rectal cancer improves local control but increases probability of faecal incontinence and sexual dysfunction. Consensus was reached in 2001 in the Netherlands on a guideline advising PRT to new patients. Purpose was to assess at what benefit oncologists and rectal cancer patients prefer PRT followed by surgery to surgery alone, and how oncologists and patients value various treatment outcomes. Sixty-six disease-free patients and 60 oncologists (surgical, radiation, medical) were interviewed. Minimally desired benefit from PRT (local control) was assessed using the Treatment Tradeoff Method. Importance of survival, local control, faecal incontinence, and sexual dysfunction in determining treatment outcome preferences was assessed using Adaptive Conjoint Analysis. The range of required benefit from PRT varied widely within participant groups. Seventeen percent of patients would choose PRT at a 0% benefit; 11% would not choose PRT for the maximum benefit of 11%. Mean minimally desired benefit excluding these two groups was 4%. For oncologists, the required benefit was 5%. Also, how strongly participants valued treatment outcomes varied widely within groups. Of the four outcomes, participants considered incontinence most often as most important. Relative treatment outcome importance differed between specialties. Patients considered sexual functioning more important than oncologists. Large differences in treatment preferences exist between individual patients and oncologists. Oncologists should adequately inform their patients about the risks and benefits of PRT, and elicit patient preferences regarding treatment outcomes.

Objective: Total mesorectal excision (TME) is the gold standard in rectal cancer, if curation is intended. Transanal endoscopic microsurgery (TEM) is a much safer technique and seems to have comparable survival in early rectal cancer. The impact of both procedures on quality of life has never been compared. In this study we compared quality of life after TEM and TME., Method: Fifty-four patients underwent TEM for a T1 carcinoma. Only patients without known locoregional or distant recurrences were included, resulting in 36 eligible patients in whom quality of life after TEM was studied. The questionnaires used included the EuroQol EQ-5D, EQ-VAS, EORTC QLQ-C30 and EORTC QLQ-CR38. The results were compared with a sex-and age-matched sample of T+N0 rectal cancer patients who had undergone sphincter saving surgery by TME and a sex- and age matched community-based sample of healthy persons., Results: Thirty-one patients after TEM returned completed questionnaires (overall response rate 86%). Quality of life was compared with 31 TME patients and 31 healthy controls. From the patients' and social perspective quality of life did not differ between the three groups. Compared with TEM, significant defecation problems were seen after TME (P < 0.05). A trend towards better sexual functioning after TEM, compared with TME, was seen, especially in male patients, although it did not reach statistical significance., Conclusion: Transanal endoscopic microsurgery and TME do not seem to differ in quality of life postoperatively, but defecation disorders are more frequently encountered after TME. This difference could play a role in the choice of surgical therapy in (early) rectal cancer. Further prospective studies are needed to confirm our conclusions.

Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. To identify genetic changes that might correlate with tumour stage and could lead to optimized treatment selection we performed a genome-wide chromosomal instability search in a homogeneous, clinical cohort of rectal tumours. 78 rectal tumours during different clinical stages were analysed with 10K single nucleotide polymorphism (SNP) arrays. Logistic regression was performed to build a quantitative model of specific chromosomal aberrations. Overall, most cases (95%) had one or more chromosomal aberrations. We observed a clear correlation between the total number of aberrations and the different tumour stages. Specifically, the chromosomal events: gain of 8q22-24, 13q and 20q, and loss of 17p and 18q12-22, were far more abundant in carcinoma than in adenoma. In adenoma fractions from cases with a carcinoma (infiltrating at least in the submucosa), twice the amount of such 'malignant aberrations' was observed, compared to pure adenomas. Furthermore, combined aberrations such as gain of 13q and loss of 18q were only found in adenomatous fractions of carcinomas and not in benign lesions. Based on these five genomic events associated with carcinoma, a clear distinction between adenoma and carcinoma tissue could be made. These data should be validated further in order that they may be used in preoperative staging of rectal tumours., (Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will neither rise during follow-up. This study investigates this relationship., Method: Data were derived from a study initiated to evaluate treatment regimes for rectal carcinoma (Dutch TME trial, n=1861) from which 954 were eligible for analysis. Recurrent disease occurred in 272 of these patients (29.5%). The pre-operative CEA value was compared to CEA values during follow-up, using threshold values of 2.5 and 5.0 ng/ml., Results: Normal pre-operative CEA values were present in 63% (CEA<5.0) and 39% (CEA<2.5) of patients with recurrent disease. Patients with a normal pre-operative CEA and recurrent disease had elevated CEA values during follow-up in 41% (CEA<5.0), 50% (CEA<2.5) and in 60% with both threshold values when the last measurement was done within 3 months before recurrent disease was diagnosed., Conclusion: A normal pre-operative CEA is common in patients with rectal carcinoma. CEA does rise due to recurrent disease in at least 50% of patients with normal pre-operative values. Serial post-operative CEA testing cannot be discarded based on a normal pre-operative serum CEA.