Postoperative MRI Findings Following Conventional and Extralevator Abdominoperineal Excision in Low Rectal Cancer

Aim: The disparity in outcomes for low rectal cancer may reflect differences in operative approach and quality. The extralevator abdominoperineal excision (ELAPE) was developed to reduce margin involvement in low rectal cancers by widening the excision of the conventional abdominoperineal excision (c-APE) to include the posterior pelvic diaphragm. This study aimed to determine the prevalence and localization of inadvertent residual pelvic diaphragm on postoperative MRI after intended ELAPE and c-APE. Methods: A total of 147 patients treated with c-APE or ELAPE for rectal cancer were included. Postoperative MRI was performed on 51% of the cohort (n = 75) and evaluated with regard to the residual pelvic diaphragm by a radiologist trained in pelvic MRI. Patient records, histopathological reports, and standardized photographs were assessed. Pathology and MRI findings were evaluated independently in a blinded fashion. Additionally, preoperative MRIs were evaluated for possible risk factors for margin involvement. Results: Magnetic resonance imaging-detected residual pelvic diaphragm was identified in 45 (75.4%) of 61 patients who underwent ELAPE and in 14 (100%) of 14 patients who underwent c-APE. An increased risk of margin involvement was observed in anteriorly oriented tumors with 16 (22%) of 73 anteriorly oriented tumors presenting with margin involvement vs. 7 (9%) of 74 non-anteriorly oriented tumors (p = 0.038). Conclusion: Residual pelvic diaphragm following abdominoperineal excision can be depicted by postoperative MRI. Inadvertent residual pelvic diaphragm (RPD) was commonly found in the series of patients treated with the ELAPE technique. Anterior tumor orientation was a risk factor for circumferential resection margin (CRM) involvement regardless of surgical approach.</p

Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer

Objective: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients. Methods: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients. Results: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12–2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22–5.03) and Stage II (OR = 1.76, 95%CI: 1.11–2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44–1.53) patients. Conclusion: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell

Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer

BackgroundMultiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a ‘low-ctDNA-shedding’ and ‘less-aggressive’ subgroup.MethodsctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722).ResultsAfter adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2–0.8, Cohort#2: OR: 0.7, 95%CI: 0.5–0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3–1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4–1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1–0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2–0.6).ConclusionsOur study suggests that asymptomatic patients are enriched for a ‘low-ctDNA-shedding-low-recurrence-risk’ subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients

Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection:an international, multi-centre, prospective audit

Introduction: The optimal bowel preparation strategy to minimise the risk of anastomotic leak is yet to be determined. This study aimed to determine whether oral antibiotics combined with mechanical bowel preparation (MBP+Abx) was associated with a reduced risk of anastomotic leak when compared to mechanical bowel preparation alone (MBP) or no bowel preparation (NBP). Methods: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 Left Sided Colorectal Resection audit was performed. Patients undergoing elective left sided colonic or rectal resection with primary anastomosis between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. Results: Of 3676 patients across 343 centres in 47 countries, 618 (16.8%) received MBP+ABx, 1945 MBP (52.9%) and 1099 patients NBP (29.9%). Patients undergoing MBP+ABx had the lowest overall rate of anastomotic leak (6.1%, 9.2%, 8.7% respectively) in unadjusted analysis. After case-mix adjustment using a mixed-effects multivariable regression model, MBP+Abx was associated with a lower risk of anastomotic leak (OR 0.52, 0.30–0.92, P&nbsp;=&nbsp;0.02) but MBP was not (OR 0.92, 0.63–1.36, P&nbsp;=&nbsp;0.69) compared to NBP. Conclusion: This non-randomised study adds ‘real-world’, contemporaneous, and prospective evidence of the beneficial effects of combined mechanical bowel preparation and oral antibiotics in the prevention of anastomotic leak following left sided colorectal resection across diverse settings. We have also demonstrated limited uptake of this strategy in current international colorectal practice

Evaluating the incidence of pathological complete response in current international rectal cancer practice

The mainstay of management for locally advanced rectal cancer is chemoradiotherapy followed by surgical resection. Following chemoradiotherapy, a complete response may be detected clinically and radiologically (cCR) prior to surgery or pathologically after surgery (pCR). We aim to report the overall complete pathological response (pCR) rate and the reliability of detecting a cCR by conventional pre-operative imaging.A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients treated by elective rectal resection were included. A pCR was defined as a ypT0 N0 EMVI negative primary tumour; a partial response represented any regression from baseline staging following chemoradiotherapy. The primary endpoint was the pCR rate. The secondary endpoint was agreement between post-treatment MRI restaging (yMRI) and final pathological staging.Of 2572 patients undergoing rectal cancer surgery in 277 participating centres across 44 countries, 673 (26.2%) underwent chemoradiotherapy and surgery. The pCR rate was 10.3% (67/649), with a partial response in 35.9% (233/649) patients. Comparison of AJCC stage determined by post-treatment yMRI with final pathology showed understaging in 13% (55/429) and overstaging in 34% (148/429). Agreement between yMRI and final pathology for T-stage, N-stage, or AJCC status were each graded as 'fair' only (n = 429, Kappa 0.25, 0.26 and 0.35 respectively).The reported pCR rate of 10% highlights the potential for non-operative management in selected cases. The limited strength of agreement between basic conventional post-chemoradiotherapy imaging assessment techniques and pathology suggest alternative markers of response should be considered, in the context of controlled clinical trials

Diagnostic performance of MRI and endoscopy for assessing complete response in rectal cancer after neoadjuvant chemoradiotherapy: a systematic review of the literature

Background The diagnostic performance of magnetic resonance imaging (MRI) modalities and/or endoscopy for assessing complete response in rectal cancer after neoadjuvant chemoradiotherapy (nCRT) is unclear. Purpose To summarize existing evidence on the diagnostic performance of diffusion-weighted MRI, perfusion-weighted MRI, T2-weighted MR tumor regression grade, and/or endoscopy for assessing complete tumor response after nCRT. Material and Methods MEDLINE and Embase databases were searched. The PRISMA guidelines were followed. Sensitivity, specificity, negative predictive, and positive predictive values were retrieved from included studies. Results In total, 81 studies were eligible for inclusion. Evidence suggests that combined use of MRI and endoscopy tends to improve the diagnostic performance compared to single imaging modality. The positive predictive value of a complete response varies substantially between studies. There is considerable heterogeneity between studies. Conclusion Combined re-staging tends to improve diagnostic performance compared to single imaging modality, but the vast majority of studies fail to offer true clinical value due to the study heterogeneity. </jats:sec

sj-docx-1-acr-10.1177_02841851211065925 - Supplemental material for Diagnostic performance of MRI and endoscopy for assessing complete response in rectal cancer after neoadjuvant chemoradiotherapy: a systematic review of the literature

Supplemental material, sj-docx-1-acr-10.1177_02841851211065925 for Diagnostic performance of MRI and endoscopy for assessing complete response in rectal cancer after neoadjuvant chemoradiotherapy: a systematic review of the literature by Nicolai Egholt Munk, Peter Bondeven and Bodil Ginnerup Pedersen in Acta Radiologica</p