Intersphincteric resection (ISR) enables radical sphincter-preserving surgery in a subset of low rectal tumors impinging on the anal sphincter complex (ASC). Excellent anatomical knowledge is... Show moreIntersphincteric resection (ISR) enables radical sphincter-preserving surgery in a subset of low rectal tumors impinging on the anal sphincter complex (ASC). Excellent anatomical knowledge is essential for optimal ISR. This study describes the role of the longitudinal muscle (LM) in the ASC and implications for ISR and other low rectal and anal pathologies. Six human adult en bloc cadaveric specimens (three males, three females) were obtained from the University of Leeds GIFT Research Tissue Programme. Paraffin-embedded mega blocks containing the ASC were produced and serially sectioned at 250 mu m intervals. Whole mount microscopic sections were histologically stained and digitally scanned. The intersphincteric plane was shown to be potentially very variable. In some places adipose tissue is located between the external anal sphincter (EAS) and internal anal sphincter (IAS), whereas in others the LM interdigitates to obliterate the plane. Elsewhere the LM is (partly) absent with the intersphincteric plane lying on the IAS. The LM gave rise to the formation of the submucosae and corrugator ani muscles by penetrating the IAS and EAS. In four of six specimens, striated muscle fibers from the EAS curled around the distal IAS reaching the anal submucosa. The ASC formed a complex structure, varying between individuals with an inconstant LM affecting the potential location of the intersphincteric plane as well as a high degree of intermingling striated and smooth muscle fibers potentially further disrupting the plane. The complexity of identifying the correct pathological staging of low rectal cancer is also demonstrated. Clin. Anat., 2019. (c) 2019 Wiley Periodicals, Inc. Show less
Background: Decreased cancer specific survival in older colorectal patients is mainly due to mortality in the first year, emphasizing the importance of the first postoperative year. This study aims... Show moreBackground: Decreased cancer specific survival in older colorectal patients is mainly due to mortality in the first year, emphasizing the importance of the first postoperative year. This study aims to gain an overview and time trends of short-term mortality in octogenarians (>= 80 years) with colorectal cancer across four North European countries.Methods: Patients of 80 years or older, operated for colorectal cancer (stage I-Ill) between 2005 and 2014, were included. Population-based cohorts from Belgium, Denmark, the Netherlands, and Sweden were collected. Separately for colon- and rectal cancer, 30-day, 90-day, one-year, and excess one-year mortality were calculated. Also, short-term mortality over three time periods (2005-2008, 2009-2011, 2012-2014) was analyzed.Results: In total, 35,158 colon cancer patients and 10,144 rectal cancer patients were included. For colon cancer, 90-day mortality rate was highest in Denmark (15%) and lowest in Sweden (8%). For rectal cancer, 90-day mortality rate was highest in Belgium (11%) and lowest in Sweden (7%). One-year excess mortality rate of colon cancer patients decreased from 2005 to 2008 to 2012-2014 for all countries (Belgium: 17%-11%, Denmark: 21%-15%, the Netherlands: 18%-10%, and Sweden: 10%-8%). For rectal cancer, from 2005 to 2008 to 2012-2014 one-year excess mortality rate decreased in the Netherlands from 16% to 7% and Sweden: 8%-2%).Conclusions: Short-term mortality rates were high in octogenarians operated for colorectal cancer. Short-term mortality rates differ across four North European countries, but decreased over time for both colon and rectal cancer patients in all countries. (C) 2019 Published by Elsevier Ltd. Show less
Background A multicentre cohort study was performed to analyse the motivations for surgical referral of patients with benign colorectal lesions, and to evaluate the endoscopic and pathological... Show moreBackground A multicentre cohort study was performed to analyse the motivations for surgical referral of patients with benign colorectal lesions, and to evaluate the endoscopic and pathological characteristics of these lesions as well as short-term surgical outcomes. Methods Patients who underwent surgery for a benign colorectal lesion in 15 Dutch hospitals between January 2014 and December 2017 were selected from the pathology registry. Lesions were defined as complex when at least one of the following features was present: size at least 40 mm, difficult location according to the endoscopist, previous failed attempt at resection, or non-lifting sign. Results A total of 358 patients were included (322 colonic and 36 rectal lesions). The main reasons for surgical referral of lesions in the colon and rectum were large size (33 center dot 5 and 47 per cent respectively) and suspicion of invasive growth (31 center dot 1 and 58 per cent). Benign lesions could be categorized as complex in 80 center dot 6 per cent for colonic and 80 per cent for rectal locations. Surgery consisted of local excision in 5 center dot 9 and 64 per cent of colonic and rectal lesions respectively, and complicated postoperative course rates were noted in 11 center dot 2 and 3 per cent. In the majority of patients, no attempt was made to resect the lesion endoscopically (77 center dot 0 per cent of colonic and 83 per cent of rectal lesions). Conclusion The vast majority of the benign lesions referred for surgical resection could be classified as complex. Considering the substantial morbidity of surgery for benign colonic lesions, reassessment for endoscopic resection by another advanced endoscopy centre seems to be underused and should be encouraged. Show less
Arezzo, A.; Migliore, M.; Chiaro, P.; Arolfo, S.; Filippini, C.; Cuonzo, D. di; ... ; REAL Score Collaborators 2019
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
Cell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer'. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood... Show moreCell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer'. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood. Here we developed an approach to evaluate fragmentation patterns of cell-free DNA across the genome, and found that profiles of healthy individuals reflected nucleosomal patterns of white blood cells, whereas patients with cancer had altered fragmentation profiles. We used this method to analyse the fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric or bile duct cancer and 245 healthy individuals. A machine learning model that incorporated genome-wide fragmentation features had sensitivities of detection ranging from 57% to more than 99% among the seven cancer types at 98% specificity, with an overall area under the curve value of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation-based cell-free DNA analyses detected 91% of patients with cancer. The results of these analyses highlight important properties of cell-free DNA and provide a proof-of-principle approach for the screening, early detection and monitoring of human cancer. Show less
Background: The decision to perform surgery for patients with T1 colorectal cancer hinges on the estimated risk of lymph node metastasis, residual tumour and risks of surgery. The aim of this... Show moreBackground: The decision to perform surgery for patients with T1 colorectal cancer hinges on the estimated risk of lymph node metastasis, residual tumour and risks of surgery. The aim of this observational study was to compare surgical outcomes for T1 colorectal cancer with those for more advanced colorectal cancer.Methods: This was a population-based cohort study of patients treated surgically for pT1 -3 colorectal cancer between 2009 and 2016, using data from the Dutch ColoRectal Audit. Postoperative complications (overall, surgical, severe complications and mortality) were compared using multivariable logistic regression. A risk stratification table was developed based on factors independently associated with severe complications (reintervention and/or mortality) after elective surgery.Results: Of 39 813 patients, 5170 had pT1 colorectal cancer. No statistically significant differences were observed between patients with pT1 and pT2-3 disease in the rate of severe complications (8.3 versus 9.5 per cent respectively; odds ratio (OR) 0.89, 95 per cent c.i. 0.80 to 1.01, P=0.061), surgical complications (12.6 versus 13.5 per cent; OR 0.93, 0.84 to 1.02, P = 0.119) or mortality (1.7 versus 2.5 per cent; OR 0.94, 0.74 to 1.19, P=0.604). Male sex, higher ASA grade, previous abdominal surgery, open approach and type of procedure were associated with a higher severe complication rate in patients with pT1 colorectal cancer.Conclusion: Elective bowel resection was associated with similar morbidity and mortality rates in patients with pT1 and those with pT2-3 colorectal carcinoma. Show less
Tumor-specific fluorescent imaging agents are moving towards the clinic, supporting surgeons with real-time intraoperative feedback about tumor locations. The epithelial cell adhesion molecule ... Show moreTumor-specific fluorescent imaging agents are moving towards the clinic, supporting surgeons with real-time intraoperative feedback about tumor locations. The epithelial cell adhesion molecule (EpCAM) is considered as one of the most promising tumor-specific proteins due its high overexpression on epithelial-derived cancers. This study describes the development and evaluation of EpCAM-F800, a novel fluorescent anti-EpCAM antibody fragment, for intraoperative tumor imaging. Fab production, conjugation to the fluorophore IRDye 800CW, and binding capacities were determined and validated using HPLC, spectrophotometry and cell-based assays. In vivo, dose escalation-, blocking-, pharmacokinetic- and biodistribution studies (using both fluorescence and radioactivity) were performed, next to imaging of clinically relevant orthotopic xenografts for breast and colorectal cancer. EpCAM-F800 targets EpCAM with high specificity in vitro, which was validated using in vivo blocking experiments with a 10x higher dose of unlabeled Fab. The optimal dose range for fluorescence tumor detection in mice was 1-5 nmol (52-260 mu g), which corresponds to a human equivalent dose of 0.2-0.8 mg/kg. Biodistribution showed high accumulation of EpCAM-F800 in tumors and metabolizing organs. Breast and colorectal tumors could clearly be visualized within 8h post-injection and up to 96 h, while the agent already showed homogenous tumor distribution within 4 h. The blood half-life was 4.5 h. This study describes the development and evaluation of a novel EpCAM-targeting agent and the feasibility to visualize breast and colorectal tumors by fluorescence imaging during resections. EpCAM-F800 will be translated for clinical use, considering its abundance in a broad range of tumor types. Show less
Claassen, Y.H.M.; Bastiaannet, E.; Hartgrink, H.H.; Dikken, J.L.; Steur, W.O. de; Slingerland, M.; ... ; Velde, C.J.H. van de 2019
