Summary Background Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy, to potentially avoid morbidity and side-effects ...of rectal excision. The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer. Methods We did a prospective, randomised, open-label, multicentre, phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer. Patients aged 18 years and older with stage T2T3 lower rectal carcinoma, of maximum size 4 cm, who had a good clinical response to neoadjuvant chemoradiotherapy (residual tumour ≤2 cm) were centrally randomly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery. Randomisation, which was done via the internet, was not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was required if tumour stage was ypT2–3. The primary endpoint was a composite outcome of death, recurrence, morbidity, and side-effects at 2 years after surgery, to show superiority of local excision over total mesorectal excision in the modified intention-to-treat (ITT) population (expected proportions of patients having at least one event were 25% vs 60% for superiority). This trial was registered with ClinicalTrials.gov , number NCT00427375. Findings From March 1, 2007, to Sept 24, 2012, 186 patients received chemoradiotherapy and were enrolled in the study. 148 good clinical responders were randomly assigned to treatment, three were excluded (because they had metastatic disease, tumour >8 cm from anal verge, and withdrew consent), and 145 were analysed: 74 in the local excision group and 71 in the total mesorectal excision group. In the local excision group, 26 patients had a completion total mesorectal excision. At 2 years in the modified ITT population, one or more events from the composite primary outcome occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62–2·86; p=0·43). In the modified ITT analysis, there was no difference between the groups in all components of the composite outcome, and superiority was not shown for local excision over total mesorectal excision. Interpretation We failed to show superiority of local excision over total mesorectal excision, because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects, and compromised the potential advantages of local excision. Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy. Funding National Cancer Institute of France, Sanofi, Roche Pharma.
BACKGROUND:Restoration of bowel continuity is a major goal after surgical treatment of rectal cancer. Intersphincteric resection allows sphincter preservation in low rectal cancer but may have poor ...functional results, including frequent bowel movements, urgency, and incontinence.
OBJECTIVE:This study aimed to evaluate long-term functional outcome after intersphincteric resection to identify factors predictive of good continence.
DESIGN:Descriptive observational study.
SETTING:Follow-up of surgery in tertiary care university hospital.
PATIENTS:Eligible patients were without recurrence 1 year or more after surgery for low rectal cancer.
INTERVENTION:Intersphincteric resection.
MAIN OUTCOME MEASURES:Bowel function was assessed with a standardized questionnaire sent to patients. Functional outcome was considered as good if the Wexner score was 10 or less. Univariable and multivariable regression analyses were used to evaluate impact of age, gender, body mass index, tumor stage, tumor location, distance of the tumor from the anal verge and from the anal ring, type of surgery, colonic pouch, height of the anastomosis, pelvic sepsis, and preoperative radiotherapy on functional outcome.
RESULTS:Of 125 eligible patients, 101 responded to the questionnaire. Median follow-up was 51 (range, 13–167) months. In multivariate analyses, the only independent predictors of good continence were distance of the tumor greater than 1 cm from the anal ring (OR, 5.88; 95% CI, 1.75–19.80; P = .004) and anastomoses higher than 2 cm above the anal verge (OR, 6.59; 95% CI, 1.12–38.67; P = .037).
LIMITATIONS:The study is limited by its retrospective, observational design and potential bias due to possible differences between those who responded to the questionnaire and those who did not.
CONCLUSIONS:Patient characteristics do not appear to influence functional outcome at long-term follow-up after intersphincteric resection. The risk of fecal incontinence depends mainly on tumor level and height of the anastomosis.
Purpose
Improvements in neoadjuvant therapy for locally advanced cT4 rectal cancer have led to improved tumour response and thus a variety of suitable management strategies. The aim of this study was ...to report management and outcomes of patients with cT4 rectal cancer undergoing a spectrum of treatment strategies from organ preservation (OP) to pelvic exenteration (PE).
Methods
Patients who underwent elective treatment for cT4 rectal cancer between 2016 and 2021 were included. All patients were treated with curative intent. Surgical management was adapted to tumour response. Kaplan–Meier curves were generated to compare 3-year overall survival (3y-OS), local recurrence (3y-LR) and distant metastases (3y-DM) between different strategies.
Results
Among 152 patients included, 13 (8%) underwent OP, 71 (47%) TME and 68 (45%) APR/PE. The median follow-up was 31.3 months. Patients undergoing OP had a lower tumour pretreatment (
p
< 0.001). Compared to patients with TME, those with APR/PE had a higher rate of ypT4 (
p
= 0.001) with a lower R0 rate (
p
= 0.044). The 3y-OS and 3y-DM were 78% and 15.1%, respectively, without significant differences. The 3y-LR was 6.6%, and patients with OP had a significantly worse 3y-local regrowth compared to 3y-LR in patients with TME and APR/PE (30.2% vs. 5.4% vs. 2%,
p
= 0.008).
Conclusion
cT4 tumours may be suitable for the full spectrum of rectal cancer management from organ preservation to pelvic exenteration depending on tumour response to neoadjuvant therapy. However, careful attention is required in OP as local regrowth in up to 30% of cases reinforces the need for sustained active surveillance in Watch&Wait programmes.
The pathological nodal stage, determination of which requires examination of ≥ 12 lymph nodes, is one of the main prognostic factors in rectal cancer. Neoadjuvant chemoradiotherapy (CRT) may reduce ...the number of both lymph nodes retrieved and positive lymph nodes. Induction chemotherapy before CRT aimed at reducing the rate of distant metastases. However, the impact of this new treatment on number of lymph nodes retrieved and positive lymph nodes is unknown. This study was performed to evaluate the effects of neoadjuvant chemotherapy on lymph nodes in locally advanced rectal cancer treated by CRT. We retrospectively included patients with T2 – 4 Nx M0 rectal cancer and compared those receiving neoadjuvant chemotherapy plus CRT with those receiving CRT alone. From 2012 to 2019, 85 patients were treated with neoadjuvant chemotherapy + CRT and 189 with CRT alone. The number of lymph nodes retrieved (19 vs. 17, respectively,
P
= 0.434), the rate of specimens with ≥ 12 lymph nodes (92% vs. 88%, respectively,
P
= 0.397), and the median number of positive lymph nodes (1 vs. 2, respectively,
P
= 0.878) were similar between the two groups. However, the rate of pN0 was higher after neoadjuvant chemotherapy + CRT compared to CRT (75% vs. 62%, respectively,
P
= 0.030). Neoadjuvant chemotherapy before CRT for locally advanced rectal cancer did not modify the number of lymph nodes retrieved or the number of positive lymph nodes compared to CRT alone. However, it significantly increased the rate of tumors without any positive lymph nodes (ypN0).
Opinion statement
Since total neoadjuvant treatment achieves almost 30% pathologic complete response, organ preservation has been increasingly debated for good responders after neoadjuvant treatment ...for patients diagnosed with rectal cancer. Two organ preservation strategies are available: a
watch and wait
strategy and a local excision strategy including patients with a near clinical complete response. A major issue is the selection of patients according to the initial tumor staging or the response assessment. Despite modern imaging improvement, identifying complete response remains challenging. A better selection could be possible by radiomics analyses, exploiting numerous image features to feed data characterization algorithms. The subsequent step is to include baseline and/or pre-therapeutic MRI, PET-CT, and CT radiomics added to the patients’ clinicopathological data, inside machine learning (ML) prediction models, with predictive or prognostic purposes. These models could be further improved by the addition of new biomarkers such as circulating tumor biomarkers, molecular profiling, or pathological immune biomarkers.
Graphical Abstract
Surgeons are experiencing difficulties implementing recommendations not only owing to incomplete, confusing or conflicting information but also to the increasing involvement of patients in decisions ...relating to their health. This study sought to establish which common factors including heuristic factors guide surgeons' decision-making in colon and rectal cancers. We conducted a systematic literature review of surgeons' decision-making factors related to colon and rectal cancer treatment. Eleven of 349 identified publications were eligible for data analyses. Using the IRaMuTeQ (Interface of R for the Multidimensional Analyses of Texts and Questionnaire), we carried out a qualitative analysis of the significant factors collected in the studies reviewed. Several validation procedures were applied to control the robustness of the findings. Five categories of factors (i.e. patient, surgeon, treatment, tumor and organizational cues) were found to influence surgeons' decision-making. Specifically, all decision criteria including biomedical (e.g. tumor information) and heuristic (e.g. surgeons' dispositional factors) criteria converged towards the factor 'age of patient' in the similarity analysis. In the light of the results, we propose an explanatory model showing the impact of heuristic criteria on medical issues (i.e. diagnosis, prognosis, treatment features, etc.) and thus on decision-making. Finally, the psychosocial complexity involved in decision-making is discussed and a medico-psycho-social grid for use in multidisciplinary meetings is proposed.
Circulating tumor cell (CTC) detection and numeration are becoming part of the common clinical practice, especially for breast, colon, and prostate cancer. However, their paucity in peripheral blood ...samples is an obstacle for their identification. Several groups have tried to improve CTC recovery rate by developing highly sensitive cellular and molecular detection methods. However, CTCs are still difficult to detect in peripheral blood. Therefore, their recovery rate could be increased by obtaining blood samples from vessels close to the drainage territories of the invaded organ, when the anatomical situation is favorable. This approach has been tested mostly during tumor resection surgery, when the vessels nearest to the tumor are easily accessible. Moreover, radiological (including echo‐guided based and endovascular techniques) and/or endoscopic routes could be utilized to obtain CTC samples close to the tumor in a less invasive way than conventional biopsies. The purpose of this article is to summarize the available knowledge on CTC recovery from blood samples collected close to the tumor (i.e., in vessels located in the drainage area of the primary tumor or metastases). The relevance of such an approach for diagnostic and prognostic evaluations will be discussed, particularly for pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and non‐small‐cell lung cancer.
Circulating tumor cell (CTC) detection and numeration are becoming part of the common clinical practice. However, their paucity in peripheral blood samples is an obstacle for their identification. Therefore, their recovery rate could be increased by obtaining blood samples from vessels close to the drainage territories of the invaded organ, when the anatomical situation is favorable.
•Endoscopic submucosal dissection with countertraction for laterally spreading lesions is more cost effective than a selective ESD or a piece-meal EMR strategy.•Endoscopic submucosal dissection for ...all laterally spreading lesions is the cheapest strategy and avoids the greatest number of surgeries.•CONECCT classification is the best classification to select high risk lesions for endoscopic submucosal dissection.•Depending to the reimbursement scheme, a selective endoscopic submucosal strategy according to CONECCT optical diagnosis classification could be the most cost effective.
Endoscopic management is preferred to surgical management for large superficial colorectal lesions. However, the optimal endoscopic resection strategy (piecemeal endoscopic mucosal resection pEMR or endoscopic submucosal dissection ESD) is still debated from an economical point of view. To date, in France, there is no Health Insurance reimbursement rate for the hospital stays related to ESD. We searched to estimate the global cost of colorectal ESD and to define the most cost-effectiveness endoscopic strategy.
A model was created to compare the cost-effectiveness of ESD and pEMR according to optical diagnosis (Japan NBI Expert Team JNET, laterally spreading tumour LST, CONECCT). We distinguished three groups from the same multicentre ESD cohort and compared the medical and economic outcomes: real-life ESD data (Universal-ESD or U-ESD) compared to modelled selective ESD (S-ESD JNET; S-ESD LST; S-ESD CONECCT) and exclusive pEMR strategies (Universal-EMR or U-EMR).
The en-bloc, R0, and curative resection rates were 97.5%, 86.5%, and 82.6%, respectively in the real life French ESD cohort of 833 colorectal lesions. U-ESD was the least-expensive strategy, with a global cost of 2,858,048.17 €, i.e. 3,431.03 €/patient and was also the most effective strategy because it avoided 774 surgeries, which was more than any other strategy. It outperformed S-ESD CONNECT (global cost = 2,951,411.44 €, and 3,543.11 €/patient, 765 surgeries avoided, S-ESD LST (global cost = 3,055,951.53 €, and 3,668.61 €/patient, 749 surgeries avoided), and S-ESD JNET (global cost = 3,547,426.97 € and 4,258.62 €/patient, 704 surgeries avoided) and U-EMR (global cost = 4,060,547.62 € and 4,874.61 €/patient, 620 surgeries avoided). Even though a model which optimized pEMR results (0% technical failure, 0% primary surgery), U-EMR strategy remained the most expansive strategy and the one that avoided the least surgeries.
ESD for all LSTs upper than 20 mm is more cost-effective than pEMR, and S-ESD.
Objective Tissue engineering may provide new operative tools for colorectal surgery in elective indications. The aim of this study was to define a suitable bioscaffold for colorectal tissue ...engineering. Methods We compared 2 bioscaffolds with in vitro and in vivo experiments: porcine small intestinal submucosa (SIS) versus chitosan hydrogel matrix. We assessed nontoxicity of the scaffold in vitro by using human adipose–derived stem cells (hADSC). In vivo, a 1 × 2-cm colonic wall defect was created in 16 rabbits. Animals were divided randomly into 2 groups according to the graft used, SIS or chitosan hydrogel. Graft area was explanted at 4 and 8 weeks. The end points of in vivo experiments were technical feasibility, behavior of the scaffold, in situ putative inflammatory effect, and the quality of tissue regeneration, in particular smooth muscle layer regeneration. Results In vitro, hADSC attachment and proliferation occurred on both scaffolds without a substantial difference. After proliferation, hADSCs kept their mesenchymal stem cell characteristics. In vivo, one animal died in each group. Eight weeks after implantation, the chitosan scaffold allowed better wound healing compared with the SIS scaffold, with more effective control of inflammatory activity and an integral regeneration of the colonic wall including the smooth muscle cell layer. Conclusion The outcomes of in vitro experiments did not differ greatly between the 2 groups. Macroscopic and histologic findings, however, revealed better wound healing of the colonic wall in the chitosan group suggesting that the chitosan hydrogel could serve as a better scaffold for colorectal tissue engineering.
PDF
