Total Mesorectal Excision Research Articles

The diagnosis and oncological outcomes of obturator and internal iliac lymph node metastasis in middle–low rectal cancer: results of a multicenter Lateral Node Collaborative Group study in China

BackgroundLateral lymph node dissection (LLND) can decrease local recurrence to lateral compartments in middle-low rectal cancer, but pathological evidence for optimal surgical indications, especially after neoadjuvant (chemo)radiotherapy (nCRT), is lacking. This study aimed to identify the predictive factors and oncological outcomes for different LLN locations associated with pathological metastasis.MethodIn this multicenter study, patients from 19 centers who underwent total mesorectal excision (TME) with LLND for locally advanced mid-/low rectal cancer from January 2012 to December 2021 were included.ResultsAll 566 included patients underwent TME with LLND surgery; 241 (37.4%) of the largest LLNs were located in the obturator area, and 403 (62.6%) of the largest LLNs were located in the internal iliac area. Multivariate analysis revealed that a short-axis size of 9 mm for the obturator area and 6 mm for internal iliac nodes constituted a reliable indicator of pathological LLN metastasis in non-CRT patients. In nCRT patients, a short-axis node size of 7 mm for obturator nodes and 4 mm for internal iliac nodes could be used to accurately predict pathological LLN metastasis. In contrast to pathological internal iliac node metastasis, pathological obturator node metastasis was associated with lower distant metastasis-free survival (DMFS) (P = 0.001), cancer-specific survival (CSS) (P = 0.043), and overall survival (OS) (P = 0.009), but lower lateral local recurrence-free survival (LRFS) (P > 0.05) was not statistically significant.ConclusionsThe obturator and internal iliac nodes may be two completely different types of LLNs, and the optimal cutoff value for predicting pathological LLN metastasis is inconsistent regardless of nCRT.Clinical trial registration The protocol of the current study was registered on ClinicalTrials.gov (NCT04850027), and the protocols were in accordance with the standards set by the World Medical Association Declaration of Helsinki.

Deformable Mapping of Rectal Cancer Whole-Mount Histology with Restaging MRI at Voxel Scale: A Feasibility Study.

Purpose To develop a radiology-pathology coregistration method for 1:1 automated spatial mapping between preoperative rectal MRI and ex vivo rectal whole-mount histology (WMH). Materials and Methods This retrospective study included consecutive patients with rectal adenocarcinoma who underwent total neoadjuvant therapy followed by total mesorectal excision with preoperative rectal MRI and WMH from January 2019 to January 2022. A gastrointestinal pathologist and a radiologist established three corresponding levels for each patient at rectal MRI and WMH, subsequently delineating external and internal rectal wall contours and the tumor bed at each level and defining eight point-based landmarks. An advanced deformable image coregistration model based on the linearized iterative boundary reconstruction (LIBR) approach was compared with rigid point-based registration (PBR) and state-of-the-art deformable intensity-based multiscale spectral embedding registration (MSERg). Dice similarity coefficient (DSC), modified Hausdorff distance (MHD), and target registration error (TRE) across patients were calculated to assess the coregistration accuracy of each method. Results Eighteen patients (mean age, 54 years ± 13 [SD]; nine female) were included. LIBR demonstrated higher DSC versus PBR for external and internal rectal wall contours and tumor bed (external: 0.95 ± 0.03 vs 0.86 ± 0.04, respectively, P < .001; internal: 0.71 ± 0.21 vs 0.61 ± 0.21, P < .001; tumor bed: 0.61 ± 0.17 vs 0.52 ± 0.17, P = .001) and versus MSERg for internal rectal wall contours (0.71 ± 0.21 vs 0.63 ± 0.18, respectively; P < .001). LIBR demonstrated lower MHD versus PBR for external and internal rectal wall contours and tumor bed (external: 0.56 ± 0.25 vs 1.68 ± 0.56, respectively, P < .001; internal: 1.00 ± 0.35 vs 1.62 ± 0.59, P < .001; tumor bed: 2.45 ± 0.99 vs 2.69 ± 1.05, P = .03) and versus MSERg for internal rectal wall contours (1.00 ± 0.35 vs 1.62 ± 0.59, respectively; P < .001). LIBR demonstrated lower TRE (1.54 ± 0.39) versus PBR (2.35 ± 1.19, P = .003) and MSERg (2.36 ± 1.43, P = .03). Computation time per WMH slice for LIBR was 35.1 seconds ± 12.1. Conclusion This study demonstrates feasibility of accurate MRI-WMH coregistration using the advanced LIBR method. Keywords: MR Imaging, Abdomen/GI, Rectum, Oncology Supplemental material is available for this article. © RSNA, 2024.

The Use of CellCollector Assay to Detect Free Cancer Cells in the Peritoneal Cavity of Colorectal Cancer Patients: An Experimental Study.

Colorectal cancer (CRC) is associated with high incidence and mortality rates globally. The presence of intraperitoneal free cancer cells (IFCCs) is recognized as an independent prognostic factor for CRC patients. However, a clinical gold standard for IFCCs detection is lacking. The GILUPI CellCollector has demonstrated high sensitivity and specificity in detecting free cancer cells, yet its application for CRC IFCCs detection remains unreported. We selected CRC and normal cell lines to evaluate the CellCollector's ability to detect tumor cells. A total of 70 CRC patients and 17 patients with benign disease undergoing laparoscopic procedures were investigated. Peritoneal lavage fluid was collected pre- and post-operation, and both real-time PCR (CEA mRNA) and CellCollector detection were performed. We compared the sensitivity and specificity of these two methods. CellCollector can distinguish well between CRC and normal cells in cell line experiments. CellCollector detects IFCCs better than real-time PCR (CEA) in CRC patients in different TNM Stages. The sensitivity of CellCollector was higher than that of real-time PCR (84.6% vs. 48.4%), and the specificity of CellCollector was also higher than real-time PCR (79.1% vs. 60.4%). There was no significant difference in the results of IFCCs detected by CellCollector before and after total mesorectal excision (TME) or complete mesocolic excision (CME) radical colorectomy (p > 0.05), but there was a significant difference in real-time PCR detection (p < 0.05). The CellCollector demonstrates superior sensitivity and specificity compared to real-time PCR for detecting IFCCs in CRC patients, suggesting its potential as a clinical tool for IFCCs detection. ClinicalTrials.gov identifier: NCT01978444.

Neoadjuvant chemoradiation for down staging of locally-advanced rectal cancer, and assessment of clinical response with digital rectal examination, magnetic resonance imaging and colonoscopy

Background: In this era of total neoadjuvant treatment (TNT) followed by rectal preservation non-operative management (NOM) or wait and watch (WW) approach for non-metastatic locally-advanced rectal cancer (LARC), reliable and reproducible response evaluation to neoadjuvant therapies forms the cornerstone. Through this study, we try to evaluate clinical response of locally-advanced rectal cancer to neoadjuvant chemoradiation (CRT) in terms of downstaging and total mesorectal excision (TME), and the accuracy of digital rectal examination (DRE), magnetic resonance imaging (MRI) and colonoscopy in the assessment of clinical response to neoadjuvant CRT. Methods: Histologically proven locally advanced rectal adenocarcinoma patients, after pretreatment evaluation, were considered for neoadjuvant chemoradiation, i.e., intensity-modulated radiation therapy (IMRT) with 5-fluorouracil (5-FU) and leucovorin-based concurrent chemotherapy. Patients were evaluated 6-8 weeks after completion of CRT and clinical response assessed by means of DRE, colonoscopy and MRI of pelvis. Following surgery, pathological response was assessed on the final histopathological examination (HPE). Results: Twenty-two patients were accrued for this protocol, of which, 15 (68.2%) were male and 7 (31.8%) were female. Downstaging and TME was achieved in 90.9% of the patients. The sensitivity of DRE, colonoscopy and MRI to detect a complete response was 66.67% and specificity was 94.74%. There were no severe toxicities or deaths reported. Conclusions: Neoadjuvant concurrent chemoradiotherapy with bolus 5-FU and leucovorin is an accepted modality of treatment for locoregionally-advanced rectal cancer, which offers higher rates of downstaging and TME. Digital rectal examination, colonoscopy and MRI together can be reliably used to assess response following neoadjuvant CRT.

Risks of Organ Preservation in Rectal Cancer: Data From Two International Registries on Rectal Cancer.

Organ preservation has become an attractive alternative to surgery (total mesorectal excision [TME]) among patients with rectal cancer after neoadjuvant therapy who achieve a clinical complete response (cCR). Nearly 30% of these patients will develop local regrowth (LR). Although salvage resection is frequently feasible, there may be an increased risk for development of subsequent distant metastases (DM). The aim of this study is to compare the risk of DM between patients with LR after Watch and Wait (WW) and patients with near-complete pathologic response (nPCR) managed by TME at the time of reassessment of response. Data from patients enrolled in the International Watch & Wait Database (IWWD) with cCR managed by WW and subsequent LR were compared with patients managed by TME (with ≤10% cancer cells-nPCR) from the Spanish Rectal Cancer Project (VIKINGO project). The primary end point was DM-free survival at 3 years from decision to WW or TME. The secondary end point was possible risk factors associated with DM. Five hundred and eight patients with LR were compared with 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among LRs (22.8% v 10.2%; P ≤ .001). Independent risk factors for DM included LR (v TME at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery. 3-year DM-free survival was significantly worse for patients with LR (75% v 87%; P = .001). When stratified for pathologic stage, patients with LR did significantly worse through all stages (P ≤ .009). Patients with LR appear to have a higher risk for subsequent DM development than patients with nPCR managed by TME at restaging irrespective of final pathology. Leaving the primary undetectable tumor in situ until development of LR may result in worse oncologic outcomes.

Tailored Approaches and Patient-centered Care: The Current Landscape of Neoadjuvant Therapy in Rectal Cancer

Colorectal cancer (CRC) is the third most diagnosed cancer in Canada and worldwide. Although mortality rates have declined, it remains the second most lethal malignancy worldwide. For patients with locally advanced rectal cancer (LARC), several new concepts have been introduced in recent years for treatment sequencing and de-escalation. The use of pelvic magnetic resonance imaging (MRI) for initial staging and neoadjuvant therapy response assessment has become a key part of the workup for LARC, utilizing the expertise of specialist radiologists. High-volume rectal cancer centers have adopted total neoadjuvant therapy (TNT) as a preferred approach for many patients with LARC. There is rising interest in shortening the duration of chemotherapy or radiation, or even omitting radiation altogether for select patients, to reduce the burden of long-term toxicities. For patients who achieve clinical complete or near-complete responses (cCR or nCR) to neoadjuvant therapies, nonoperative management (NOM) has emerged as an option to avoid the complications of a total mesorectal excision (TME). This paradigm shift has resulted in numerous treatment options for many patients with rectal cancer, enabling a more individualized, multidisciplinary approach to care. Clinicians must understand how to interpret the evidence around these new concepts to successfully implement them into clinical practice. This review summarizes the recent evidence for neoadjuvant therapy approaches in rectal cancer to provide a context for this paradigm shift to a tailored therapeutic strategy.

Transanal total mesorectal excision: Understanding indications, managing complications, and effective prevention methods

AbstractTransanal total mesorectal excision (TaTME) has emerged as a surgical method for treating rectal malignancies in the middle and lower third of the rectum over the past 15 years. This approach was adopted because of the challenges encountered in secure total mesorectal excision (TME). Patient selection criteria and the rationale for TaTME have evolved, leading to improved oncological outcomes and patient quality of life. The procedure includes inserting a unique platform through the anus, forming a purse‐string closure, and endoscopically sealing the lower rectum. The mesorectum is then removed laparoscopically following a ‘down‐to‐up’ approach, finalised with a transabdominal laparoscopic phase and anastomosis. Pelvic anatomy complexity poses challenges, including potential injuries to the urinary tract, surgical site leakage, sinus damage, sagittal vein harm, nerve injury, carbon dioxide embolism, bowel function disturbance, sphincter mechanism issues, and rectal abscess formation. Proficient anatomy knowledge, precise surgical techniques, and advanced technologies contribute to their prevention. In conclusion, TaTME offers a promising approach to rectal surgery with satisfactory oncological outcomes. However, vigilance is required to eliminate potential complications.

Total Mesorectal Excision with New Robotic Platforms: A Scoping Review

Total Mesorectal Excision with New Robotic Platforms: A Scoping Review

Short-term outcomes of 47 selective laparoscopic lymph node dissection for rectal cancer: A retrospective study.

This study aims to analyze the safety, feasibility, and short-term oncology outcomes of selective laparoscope lateral lymph node dissection (LLND) with total mesorectal excision surgery. Between December 2019 and May 2023, LLND with total mesorectal excision surgery was performed in 47 selected patients with advanced rectal cancer. Surgical complications and 2-year oncology survival outcomes were analyzed in the study. All 47 procedures were technically successful without converting conversion to open surgery. The mean operation time was 200.6 minutes (135-321 minutes), and the mean estimated blood loss was 92.9 mL (range 10-2000 mL). The most common postoperative complications were anastomotic (8.5%, n = 4), ileus (6.4%, n = 3), and chyle leakage (4.3%, n = 2). Lateral pelvic lymph node metastases were found in 19 (40.4%) patients. When divided into lateral pelvic lymph node positive and negative groups, there was no significant impact on overall survival (94.4% vs 100%, Log-rank P = .596) and local recurrence-free survival (LFRS) (76.7% vs 89.6%, Log-rank P = .210), except disease-free survival (DFS) (58.3% vs 90.2%, Log-rank P = .005). Subgroup analysis showed similar short-term survival outcomes between the pN+ group and the internal iliac metastasis group (Log-rank P of overall survival, LFRS, and DFS were all ˃.05). LRFS and DFS in the obturator or external iliac metastasis group were worse than those in the internal iliac metastasis group when the follow-up time was extended (Log-rank P of LFRS and DFS were .05 and .063). Selective laparoscopy LLND for rectal cancer is safety and feasibility, and its complications are manageable. Oncology survival outcomes for lateral pelvic lymph node metastases limited to the internal iliac are similar to the pN+ stage; therefore, it should be treated positively.

Prognostic Impact of Skip Metastasis to the Lateral Lymph Nodes in Lower Rectal Cancer.

Some patients with lower rectal cancer develop "skip metastasis," in which lymph node metastasis occurs in the lateral but not the mesenteric lymph nodes. However, the prognostic impact of skip metastasis is unclear. This study aimed to determine the long-term prognosis of skip metastasis in lower rectal cancer. This retrospective study included patients with stage I-III lower rectal cancer who underwent total mesorectal excision and lateral lymph node dissection at our institution between 2000 and 2019. We investigated the association of lymph node metastasis with relapse-free and overall survival. Multivariate analyses were performed using Cox proportional hazards regression models. Of a total of 371 patients, 183 (49%) were negative for lymph node metastasis, 115 (31%) were positive for mesenteric lymph nodes only, 18 (5%) were positive for lateral lymph nodes only (skip metastasis), and 55 (15%) were positive for both mesenteric and lateral lymph nodes; the 5-year relapse-free survival rates were respectively 79.9%, 60.0%, 68.3%, and 32.7%, and 5-year overall survival rates were 96.6%, 90.0%, 85.6%, and 57.3%. Multivariable analysis revealed significant differences in relapse-free and overall survival between those positive for both mesenteric and lateral lymph nodes and those positive for lateral lymph nodes only (relapse-free survival, hazard ratio 2.30, p=0.048; overall survival, hazard ratio 3.50, p=0.030). In patients with lower rectal cancer who underwent total mesorectal excision and lateral lymph node dissection, those with skip metastasis had better relapse-free and overall survival than those with both mesenteric and lateral lymph node metastases.

Postoperative Morbidity and Factors Predicting the Development of Lymphoceles Following Lateral Pelvic Node Dissection for Rectal Cancer: A Cohort Study.

Lateral pelvic node dissection (LPLND) is indicated inthe surgical management of clinically significant pelvic lymphadenopathy associated with rectal malignancies. However, procedure-related morbidity, including the incidence and predisposing factors for lymphoceles arising in this setting have not been adequately evaluated. This retrospective single-institution study included 183 patients with nonmetastatic, lateral node-positive rectal cancer undergoing total mesorectal excision with LPLND between June 2014 and May 2023 to determine the incidence and severity of postoperative complications using the Clavien-Dindo system, with logistic regression performed to model a relationship between lymphocele-development and potentially-predictive variables. In this cohort, mean age was 45.3 ± 12.81 years, 62.8% were male, and 27.9% had body mass index ≥ 25kg/m2. Median tumor-distance from the verge was 3.0 (interquartile range [IQR] 1.0-5.0)cm. Following radiotherapy in 86.9%, all patients underwent surgery: 30.1% had open resection and 26.2% had bilateral LPLND. Median nodal-yield was 6 (IQR 4-8) per side. Postoperatively, 45.3% developed complications, with 18% consideredclinically significant. Lymphoceles, detected in 21.3%, comprised the single-most common sequelae following LPLND, 46.2%arising within 30 days of surgery and 33.3% requiring intervention. On multivariate analyses, obesity (hazard ratio [HR] 2.496; 95% confidence interval [CI] 1.094-5.695), receipt of preoperative radiation (HR 10.026; 95% CI 1.225-82.027), open surgical approach (HR 2.779; 95% CI 1.202-6.425), and number of harvested nodes (HR 1.105; 95% CI 1.026-1.190) were significantly associated with lymphocele-development. Pelvic lymphoceles and its attendant complications represent the most commonly encountered morbidity following LPLND for rectal cancer, with obesity, neoadjuvant radiotherapy, open surgery, and higher nodal-yield predisposing to their development.

Modified FOLFOX6 with Cetuximab versus with Radiotherapy in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: A Single-Center, Prospective, Randomized Controlled Trial.

In this trial, the feasibility and efficacy of neoadjuvant chemotherapy with targeted agents in the treatment of patients with locally advanced rectal cancer were evaluated. In this single-center, prospective, randomized controlled trial, we randomly assigned (1 : 1) patients with locally advanced rectal cancer with wild-type RAS/BRAF gene to two groups: 5 cycles of modified leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin combination regimen (modified FOLFOX6, mFOLFOX6) concurrent with 25 times radiotherapy or 5 cycles of mFOLFOX6 plus cetuximab, all with subsequent total mesorectal excision (TME) resection and adjuvant chemotherapy. We performed a random assignment by a computer-generated random number sequence. The primary end point was the R0 resection rate. The secondary end points were rates of pathologic complete response, downstaging, adverse events, postoperative complications, preventive enterostomy and low anterior resection syndrome. From January 6, 2020 to October 28, 2022, 80 patients were assigned and evaluated. In the mFOLFOX6-RT and mFOLFOX6-Cet groups, the rate of R0 resection was 96.7 and 96.9% (p = 1.000); the rate of pathological complete response (pCR) was 23.3 and 21.9% (p = 0.891); and the rate of downstaging (ypStage 0 to 1) was 53.3 and 53.1% (p = 1.000), respectively. No statistical differences between the two groups were observed in the incidence of adverse events and postoperative complications. Additionally, lower rates of preventive enterostomy and low anterior resection syndrome were shown in the mFOLFOX6-Cet group compared to the mFOLFOX6-RT group. The neoadjuvant treatment strategy of mFOLFOX6 with cetuximab is feasible and promising for patients with locally advanced rectal cancer, even superior to mFOLFOX6 with radiotherapy.

A study of intersphincteric resection rate following robotic-assisted total mesorectal excision versus laparoscopic-assisted total mesorectal excision for patients with middle and low rectal cancer: study protocol for a multicenter randomized clinical trial

IntroductionRobotic-assisted complete mesorectal excision (RATME) is increasingly being used by colorectal surgeons. Most surgeons consider RATME a safe method, and believe it can facilitate total mesorectal excision (TME) in rectal cancer, and may potentially have advantages over intersphincteric resection (ISR) and anus preservation. Therefore, this trial was designed to investigate whether RATME has technical advantages and can increase the ISR rate compared with laparoscopic-assisted TME (LATME) in patients with middle and low rectal cancer.Methods and analysisThis is a multicenter, superiority, randomized controlled trial designed to compare RATME and LATME in middle and low rectal cancer. The primary endpoint is the ISR rate. The secondary endpoints are coloanal anastomosis (CAA) rate, conversion to open surgery, conversion to transanal TME (TaTME), abdominoperineal resection (APR) rate, postoperative morbidity and mortality within 30 days, pathological outcomes, long-term survival outcomes, functional outcomes, and quality of life. In addition, certain measurements will be conducted to ensure quality and safety, including centralized photography review and semiannual assessment.DiscussionThis trial will clarify if RATME improves ISR and promotes anus preservation in patients with mid- and low-rectal cancer. Furthermore, this trial will provide evidence on the optimal treatment strategies for RATME and LATME in patients with mid- and low-rectal cancer regarding improved operational safety.Trial registrationClinicalTrials.gov NCT06105203. Registered on October 27, 2023.

Optimised treatment of patients with enlarged lateral lymph nodes in rectal cancer: protocol of an international, multicentre, prospective registration study after extensive multidisciplinary training (LaNoReC)

IntroductionInadequate treatment of enlarged lateral lymph nodes (LLNs) in rectal cancer patients is associated with an increased lateral local recurrence (LLR) risk, despite neoadjuvant treatment and total mesorectal excision (TME)...

From Insight to Impact: Improving Mesorectal Evaluation Standards through Resident Educational Intervention

Abstract Introduction/Objective The completeness of total mesorectal excision (TME) and involvement of the circumferential radial margin (CRM) significantly impact local recurrence and survival rates in rectal cancer. Accurate gross examination to assess mesorectal status is crucial, not only for patient prognosis but also for evaluating surgical quality. Methods/Case Report We implemented a quality assurance initiative to enhance mesorectal quantification and CRM assessment by pathology trainees. Low anterior resection specimens received between January 2022 and December 2023 were included, with 2022 as the pre-intervention period and 2023 post-intervention. In December 2022, an educational session was conducted, emphasizing rectal resection specimens’ types and the importance of mesorectal and CRM assessment. Periodic reminder emails reinforced these concepts. Results (if a Case Study enter NA) We identified a total of 35 cases in the study: 20 pre-intervention arm and 15 post-intervention arm. Mesorectal quantification and CRM assessment and documentation improved significantly post- education, rising from 70% (14 of 20 cases) to 93% (14 of 15 cases) (p &amp;lt; 0.0001). Conclusion In conclusion, our study underscores the critical role of meticulous gross examination in assessing mesorectal status, serving not only as a prognostic indicator but also in guiding surgical precision and rectal cancer management. Further, our findings emphasize the transformative potential of education-driven interventions in enhancing the quality of mesorectal evaluation, reinforcing the pivotal role of pathologists and pathology trainees in shaping therapeutic strategies and ultimately improving rectal cancer patient care.

Outcomes of Distal Rectal Cancer Patients Who Did Not Qualify for Watch-and-Wait: Comparison of Intersphincteric Resection Versus Abdominoperineal Resection.

Total mesorectal excision (TME) with intersphincteric resection and handsewn coloanal anastomosis (ISR-CAA) has been shown to be oncologically safe in patients with distal rectal cancer treated with preoperative chemoradiation. The introduction of the watch-and-wait (WW) strategy for rectal cancer patients with a clinical complete response to neoadjuvant therapy is changing the profile of patients undergoing TME surgery immediately following neoadjuvant treatment. The outcomes of ISR-CAA for patients with locally advanced rectal cancers not qualifying for WW have not been investigated. We conducted a retrospective analysis comparing the outcomes of ISR-CAA and abdominoperineal resection (APR) in patients with distal rectal cancer treated with neoadjuvant therapy and not qualifying for WW, at a comprehensive cancer center with an established WW program. The primary outcome was local recurrence-free survival. Sixty-seven patients had ISR-CAA and 79 had APR. Median follow-up was 61.1 months. The two groups were similar in sex, tumor stage, grade, and distance from the anal verge, but patients in the APR group were older on average. An R0 resection was achieved in 94% of ISR-CAA patients and 91% of APR patients. Patients in the ISR-CAA group had a lower 5-year rate of local recurrence-free survival (79% vs. 93%; p = 0.038) compared with the APR group; however, 5-year disease-free survival did not differ significantly between groups (67% for ISR-CAA and 64% for APR; p = 0.19). The local recurrence rate after ISR-CAA may be higher than after APR for patients without a clinical complete response to neoadjuvant therapy requiring TME surgery.

Node-sparing modified short-course Radiotherapy Combined with CAPOX and Tislelizumab for locally Advanced MSS of Middle and low rectal Cancer (mRCAT): an open-label, single-arm, prospective, multicentre clinical trial

BackgroundNeoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC.MethodsThis was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed.DiscussionIn our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer.Trial registrationThis study was registered at www.clinicaltrials.gov. Trial registration number: NCT05972655. Date of registration: 31 July 2023.

Local excision versus total mesorectal excision for rectal cancer patients with clinical complete or near-complete response after neoadjuvant chemoradiotherapy

PurposeLocal excision is an effective approach for managing rectal cancer exhibiting substantial regression after neoadjuvant chemoradiotherapy. The purpose of this study is to compare the outcomes between local excision and total mesorectal excision in rectal cancer patients achieving clinical complete or near-complete response after neoadjuvant chemoradiotherapy.MethodsThis is a retrospective cohort study that includes a consecutive series of rectal cancer patients who responded well to neoadjuvant chemoradiotherapy followed by surgery. A total of 180 rectal cancer patients at a single institution during a 12-year period are included. The main outcomes include short-term outcomes, oncological outcomes, and functional outcomes between the two groups.ResultsA total of 180 patients were included in the study. Sixty-one (33.9%) received local excision and 119 (66.1%) received total mesorectal excision. The baseline characteristics were generally balanced between the two groups. The local excision group demonstrated a significantly shorter operative time, less blood loss, and shorter hospital stay (p < 0.001). 3-year overall survival rates were 97.5% (95% CI, 0.93–1.00) and 95.5% (95% CI, 0.91–1.00) between the two groups (p = 0.38). The local excision group exhibited significantly higher 3-year local recurrence rates 15.7% (95% CI, 0.74–0.97) vs 4.2% (95% CI, 0.92–1.00) (p = 0.017), yet lower 3-year distant metastasis rates 9.6% (95% CI, 0.82–1.00) vs 12.6% (95% CI, 0.81–0.94) (p = 0.33) and lower 3-year disease-free survival rates 76.8% (95% CI, 0.64–0.92) vs 84.7% (95% CI, 0.78–0.92) (p = 0.56) comparing with the total mesorectal excision group. The local excision group demonstrated significantly better functional outcomes compared with the total mesorectal excision group (p < 0.001).ConclusionPatients who achieve either clinical complete or near-complete response after neoadjuvant chemoradiotherapy are suitable candidates for local excision. The local excision group demonstrated superior short-term and functional outcomes, and the oncological outcomes were not compromised.

TOpClass Class 4 Perineal Crohn's Disease: A Systematic Review and Meta-analysis of Perineal Wound Complication After Proctectomy in Crohn's Patients.

Nonhealing perineal wounds have been reported to be common after proctectomy for Crohn's disease (CD). We performed a systematic review and meta-analysis of perineal wound healing after proctectomy for CD and assessed the risk factors for nonhealing. A comprehensive literature search was conducted in PubMed, Embase, and Scopus databases from 2010 to 2023, and articles reporting perineal wound healing rates after proctectomy for CD were included. Data on study characteristics and proportion of healed wounds, and risk factors, were extracted. Random-effects meta-analysis was performed to estimate the pooled proportion and 95% CIs using the "meta" package in R. Heterogeneity was assessed using the I2 statistic. We identified 501 articles, of which 252 remained after de-duplication. After screening, 4 retrospective cohort studies involving 333 patients were included. Across the 4 studies, the pooled proportion of completely healed perineal wounds at 6 months was 65% (95% CI 52%-80%), and 70% (95% CI 60%-83%) at 12 months. Significant heterogeneity was found between studies (I2 = 86% at 6 months). Three studies examined risk factors for impaired healing after proctectomy. One study identified preoperative perineal sepsis as the only independent factor associated with impaired healing (P = .001) on multivariable analysis. In 1 study, male sex, shorter time from diversion to proctectomy, and higher preoperative C-reactive protein levels were all associated with delayed healing in univariate analysis. Another study found that close rectal dissection was associated with significantly lower healing rates than total mesorectal excision (P = .01). Prior use of tumor necrosis factor inhibitors was not associated with wound healing outcomes. This meta-analysis revealed complete perineal healing in only 70% of patients 12 months after proctectomy for CD. This highlights knowledge gaps, including the identification of modifiable risk factors and methods for preventing or as rescue therapy, such as vacuum-assisted closure and flap reconstruction, for nonhealing perineal wounds after proctectomy for CD. Poor perineal wound healing outcomes are likely related to imperfectly understood underlying inflammatory dysregulation and systemically impaired wound healing in patients with CD.

Current perioperative care in patients undergoing a beyond total mesorectal excision procedure for rectal cancer: What are the differences with the colorectal enhanced recovery after surgery protocol?

Patients requiring a beyond total mesorectal excision (bTME) procedure for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) will probably benefit from enhanced recovery after surgery (ERAS) protocols. However, implementation of ERAS protocols in such groups of patients is considered challenging. The aims of this study were to evaluate ERAS-related outcomes of patients with LARC or LRRC undergoing bTME and to investigate the possibility of designing a tailored ERAS protocol. This study was divided into four phases. Phase one consisted of a literature study to compare functional recovery and postoperative outcomes in patients undergoing bTME. In phase two, outcomes on ERAS care elements in bTME were retrospectively evaluated. In phase three, differences in ERAS-related outcomes and compliance of the colorectal ERAS protocol in patients who had undergone bTME were studied. In phase four, multidisciplinary team meetings were held to develop an ERAS protocol for bTME patients. Seven studies reported on ERAS-related outcomes in patients undergoing bTME. Median length of hospital stay was 9-19 days, median stay in the intensive care unit was 2-4 days and 30-day postoperative major complication rates were 22.6%-61.3%. Seventy-five bTME patients were included for retrospective analysis. In these patients, length of stay was 9.0 days and major postoperative complications were observed in 40.0%. The overall ERAS compliance was 44.4%. Compared with the colorectal ERAS protocol, the largest differences in management were observed in the use of epidural anaesthesia, the postoperative use of urethral catheters, oral intake and mobilization. Patients undergoing bTME for LARC or LRRC are substantially different from patients treated with the colorectal ERAS protocol, regarding ERAS-related outcomes. A tailored, multimodal ERAS protocol with specific modifications was developed by an expert multidisciplinary team for patients undergoing bTME for LARC or LRRC.