Lateral lymph node dissection via robotic surgery: technical feasibility and patterns of lateral lymph node recurrence in rectal cancer.

Purpose: Although total neoadjuvant therapy (TNT) improves outcomes in locally advanced rectal cancer (LARC), patients with proficient mismatch repair (pMMR)/microsatellite stability (MSS) tumors respond poorly to conventional regimens. Patients and Methods: This phase II trial (ESTIMATE) evaluated a novel TNT protocol integrating PD-L1 blockade (envafolimab) in 33 pMMR/MSS LARC patients with tumors located ≤10 cm from the anal verge. The regimen comprised: induction with mFOLFOX6 plus subcutaneous envafolimab (200 mg q2w × 2 cycles), concurrent chemoradiation (50 Gy/25 fractions with capecitabine 825 mg/m 2 plus envafolimab q2w × 3 cycles), and consolidation with mFOLFOX6/Envafolimab ×2 cycles. Patients achieving a clinical complete response (cCR) with undetectable circulating tumor DNA (ctDNA) can opt for watch-and-wait (W&W). Results: The complete response (CR) rate, which integrates pathological complete response (pCR) and cCR, reached 51.5% (17/33), with 21.2% (7/33) achieving organ preservation. Pathological assessment revealed 38.5% pCR (10/26) and 73.1% major response (19/26) after total mesorectal excision (TME). Transcriptomic profiling identified UBD overexpression and RPL21 downregulation as predictive biomarkers. Adverse events occurred in 87.9% (29/33) of the patients, predominantly grade 1–2. Grade 3 neutropenia occurred in 9.1% (3/33) of the patients, and injection-site reaction occurred in 1 patient (3%). With a median follow-up of 27 months (IQR 25-29), the 2-year DFS and OS rates were 90.9% (95% CI: 77.0%–97.6%) and 100% (95% CI: 90.1%–100%), respectively. Distant metastases developed in one of seven patients (14.3%) managed with W&W and two of 26 patients (7.7%) undergoing TME. Conclusions: PD-L1 blockade-enhanced TNT achieves encouraging efficacy, organ preservation, and acceptable tolerability in pMMR/MSS LARC, supported by mechanistically relevant biomarkers.

ASO Visual Abstract: Volume-Outcome Relationships in Total Mesorectal Excision Quality and Grading: A National Cancer Database Study.

Abstract Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision is standard treatment for locally advanced rectal cancer (LARC). This approach allows a subset of patients to achieve a pathological complete response (pCR), thereby improving surgical outcomes, anal preservation rates, and disease‐free survival. An accurate preoperative assessment of pCR is crucial for guiding treatment decisions. Magnetic resonance imaging (MRI), owing to its superior soft‐tissue contrast and spatial resolution, has become the preferred noninvasive modality for assessing nCRT efficacy. Advances in functional MRI (fMRI) techniques include diffusion‐weighted imaging, derived sequences, perfusion‐weighted imaging, and neuro‐fMRI. fMRI sequences provide not only a qualitative assessment but also quantitative parameters derived from various imaging principles, thereby significantly enhancing the clinical utility of MRI. Beyond conventional and functional MRI, this field is rapidly evolving with the integration of radiomics and deep learning approaches. Radiomics involves the high‐throughput extraction of minimal quantitative features from medical images, which can reveal tumor heterogeneity and phenotypic characteristics that are invisible to the human eye. This review summarizes current research and future perspectives on MRI‐based qualitative, quantitative, radiomic, and deep‐learning approaches for assessing nCRT efficacy in patients with LARC.

Pathological reports provide comprehensive insights into the clinical and pathological features of different cancer types. However, extraction of this semi-structured data for research is challenging. To better utilize pathology reports in cancer studies, we developed an efficient natural language processing (NLP) system to automate the extraction of items from pathology reports, facilitating streamlined storage, retrieval, and analysis of clinical data in a centralized database. To determine the optimal model for our study, we conducted a comparative analysis of various deep learning architectures, including long short-term memory, convolutional neural network, and transformer-based models such as bidirectional encoder representations from transformers (BERT), BioBERT, and ClinicalBERT. The proficiency of the ClinicalBERT model in medical terminology and context significantly enhanced the accuracy and efficiency of data extraction from these reports. Among the aforementioned models, ClinicalBERT exhibited the best performance and was selected as the base model. The ClinicalBERT model demonstrated an exceptional performance in accurately classifying variables across multiple cancer types. Regarding stomach cancer, F1 scores (F1 = 1.0) were achieved for variables such as angiolymphatic invasion, and operation name (F1 = 1.0); however, a lower performance was observed for distant metastasis (F1 = 0.3889). Regarding liver cancer, high performance was consistently observed for most variables, with F1 scores above 0.99. Regarding colorectal cancer, F1 scores were achieved for variables such as Dworak's grade, lymph node, operation name, and total mesorectal excision (F1 = 1.0), while slightly lower but acceptable performance was noted for surgical margin (F1 = 0.9259). Regarding breast cancer, F1 scores were achieved for several variables including nipple margin, organ, and superficial margin (F1 = 1.0), while strong performances were noted for lateral and medial margins (F1 > 0.94). This study underscores the efficacy of NLP systems, specifically the ClinicalBERT model, in automating the extraction of important clinical data from pathology reports across various cancer types. This approach can not only simplify the process but also enhance the accuracy of the extracted information.

Transanal total mesorectal excision versus transabdominal laparoscopic Low Hartmann's procedure for rectal cancer: A single-center retrospective analysis of short-term outcomes.

To investigate whether quantitative DWI and qualitative T2WI parameters can predict lymph node involvement in clinical early rectal cancer. This retrospective study included consecutive patients who had rectal MRI from January 1, 2010, to March 31, 2021, showing T1-T2 rectal cancer before undergoing total mesorectal excision without neoadjuvant therapy. Visible mesorectal lymph nodes on DWI were segmented by a junior reader, and ADC values were extracted. Additionally, the junior reader and a senior reader independently recorded qualitative T2WI parameters of the most suspicious lymph node per patient. Histopathology was the reference standard for malignant (pN+) and benign (pN-) lymph node status. Of 69 patients (37 men and 32 women) (median age, 55 years; IQR: 48-66), 23 (33%) had pN+ status; 46 (67%) had pN- status. ADCmean (in × 10-3 mm2/s) of the most suspicious lymph node was not different between the two patient groups (junior reader: 1087 vs. 926, p = 0.31; senior reader: 1178 vs. 1086, p = 0.89). The Dutch criteria, based on the combination of T2WI size and morphologic parameters, showed better diagnostic performance for the senior vs. junior reader: accuracy, sensitivity, specificity, PPV, and NPV of 79.7% (95% CI: 68.3-88.4%), 56.5% (95% CI: 34.5-76.8%), 91.3% (95% CI: 79.2-97.6%), 76.5% (95% CI: 50.1-93.2%), and 80.8% (95% CI: 67.5-90.4%), vs. 69.6% (95% CI: 57.3-80.1%), 26.1% (95% CI: 12.2-48.4%), 91.3% (95% CI: 79.2-97.6%), 60% (95% CI: 26.2-97.8%), and 71.2% (95% CI: 57.9-82.2%). Additional research on alternative and more objective methods for lymph node characterization is needed. Question The performance of MRI for nodal staging in clinical early rectal cancer in particular is a knowledge gap in the literature. Findings The Dutch criteria, based on T2WI size and morphologic parameters, performed better in differentiating metastatic from benign lymph nodes than the quantitative DWI ADC parameter. Clinical relevance Accurate nodal staging in early rectal cancer is crucial for treatment decision-making. Our study highlights the need for additional research on alternative and more objective methods for lymph node characterization.

Transanal versus robotic total mesorectal excision for mid- and low-rectal cancer: A single-center comparative cohort of 109 patients.

Development and validation of a predictive model for postoperative urinary dysfunction following robotic total mesorectal excision in mid-low rectal cancer.

TME, generally interpreted as total mesorectal excision, has been adopted globally as standard of care in rectal cancer. TME originated from a 1982 publication, though neither title nor content implied that total was needed for all. The paper stated that patients with upper rectal cancer could have mesorectal trans-section, tailored to the individual patient. Nevertheless, the concept figure suggested total mesorectal excision with a denuded rectal stump, which could result in higher anastomotic leakage rates. The current update reports that the "T" represents "Total", or "Tailored "mesorectal excision. The basic principles of "The TME concept" revolve around precision surgery for both distal and circumferential, cancer margin clearance.

Total mesorectal excision (TME) is the surgical standard for mid-to-low rectal cancer, and the Commission on Cancer Standard 5.7 requires documentation of TME grade. The aim of our study was to describe national variation in TME grading and quality. This was a multicenter retrospective cohort of 5033 patients within the National Cancer Database who underwent TME for rectal adenocarcinoma in 2022, the first year TME quality is available. The exploratory outcomes were TME reporting and completeness by institution volume, assessed by quartiles and by the Leapfrog Group's standard of 16 proctectomies/year, and the associations of TME grades with surgical approach, lymph node yield, and surgical margins. There were significant differences in likelihood of TME reporting (p < 0.001) and in TME grades (p < 0.001) by facility volume quartile. Meeting the Leapfrog minimum of 16 annual proctectomies was associated with a higher likelihood of reporting TME grade (p = 0.02) but not with more complete TME grades (p = 0.68). Robotic-assisted approaches had the highest rate of complete TME among surgical approaches (p < 0.001) and lower rates of conversion to open than did laparoscopic approaches (4.6% vs 14.6%, p < 0.001). Complete TME was more likely to have at least 12 lymph nodes (p = 0.001), no residual tumor (p < 0.001), and negative circumferential resection margins (p < 0.001) than nearly complete and incomplete TME. High-volume institutions were more likely to report TME grades and achieve complete TME, which was associated with higher rates of adequate lymph node yield and negative margins. Robotic-assisted approaches were associated with the highest rates of complete TME grades.

Advances in surgical techniques, together with the widespread use of neoadjuvant and adjuvant therapies, have markedly improved disease-free and overall survival in patients with rectal cancer. Nevertheless, urogenital dysfunction remains a significant source of postoperative morbidity, primarily due to the anatomical location of the rectum and its close relationship with the autonomic pelvic nerves. Although the incidence of urological complications has declined to below 10%, sexual dysfunction continues to affect approximately one-quarter of patients. Nerve-sparing total mesorectal excision, performed without compromising oncological principles, has therefore become a critical component of contemporary rectal cancer surgery. Minimally invasive video-assisted techniques, offering magnified visualization and enhanced precision during pelvic dissection, facilitate the accurate identification and preservation of autonomic nerve structures. However, current evidence indicates that awareness and consistent application of nerve-sparing principles remain suboptimal, even among experienced colorectal surgeons. This video systematically demonstrates the key anatomical landmarks and stepwise surgical maneuvers required for effective nerve preservation during total mesorectal excision, aiming to reduce urogenital functional morbidity.

Background: First described by Carl Toldt in the late 19th century, the mesorectum has since been a topic of anatomical and surgical debate. Its clinical importance was redefined by Heald's introduction of Total Mesorectal Excision (TME), nowadays the golden standard in oncologic rectal surgery. This study aims to elucidate the embryological development and adult anatomy of the mesorectum and the mesorectal fascia, with a focus on clinically significant relations, particularly the peritoneum, and components of the hypogastric plexuses. Methods: We performed anatomical dissections on four 12-15-week-old human fetuses and eight formalin-fixed adult cadavers. In addition, a transverse pelvic section was examined to assess the spatial organization of mesorectal and fascial structures. Results: Our findings confirm the presence of a dorsal mesentery at the rectal level during fetal development, illustrating its transformation into the adult mesorectum. We identified the mesorectal contents in the fetus and examined the course and relations of the superior rectal vessels, hypogastric nerves, and pelvic splanchnic nerves, in both fetal and adult specimens. Conclusions: The observed fetal and adult configurations provide a continuous morphological description of the mesorectum and its compartmental organization within the pelvis. This study enhances the understanding of the mesorectum's embryology, structure, and vital surgical landmarks. By delineating the so-called 'Holy plane' of Heald (the natural avascular plane between the mesorectal and presacral fasciae used during total mesorectal excision) and the delicate connective fibers known surgically as 'angel's hair', which become visible when this plane is correctly entered, rectal and presacral fasciae, and neurovascular elements, provides a comprehensive anatomical framework that may inform surgical plane identification and support future clinical investigations into nerve-sparing rectal surgery.

To evaluate the value of magnetic resonance imaging (MRI) in identifying the pathologic complete response (pCR) of patients with locally advanced rectal cancer (LARC) after neoadjuvant therapy (NAT). This retrospective study included 152 patients with LARC who underwent NAT followed by total mesorectal excision (TME) at our hospital between January 2019 and November 2024. The response to NAT was assessed using MRI. At first, the response was assessed according to MRI-based tumor regression grade (mrTRG), which was only on the basis of T2 weighted imaging (T2WI). Then, diffusion weighted imaging (DWI) was added to construct biparametric MRI-based tumor regression grade (BPmrTRG), followed by multiparametric MRI-based tumor regression grade (MPmrTRG) consisting of T2WI, DWI and contrast-enhanced T1-weighted imaging (CE-T1WI). The diagnostic efficacy of the three methods for identifying pCR was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC), positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity. The DeLong test was used to compare the AUCs of different methods. Of the 152 patients, 27 (17.8%) were obtained pCR at surgical histopathological analysis. Among the three different MRI-based TRG methods, MPmrTRG archived the highest AUC of 0.891 (95% CI: 0.814-0.957) to identify pCR after NAT, followed by an AUC of 0.840 (95%CI: 0.745-0.916) for BPmrTRG and 0.729 (95% CI: 0.630-0.818) for mrTRG. Paired comparisons showed that AUC of MPmrTRG was higher than that of mrTRG with statistically significant after Bonferroni correction (p = 0.007), as well as the sensitivity (0.815 vs. 0.481, p = 0.008). After adding DWI and CE-T1WI, the multiparametric MRI approach could improve diagnosis performance for identifying pCR after NAT in patients with LARC, which could facility clinicians' decision and patients' consultation for the watch and wait strategy to forgo the surgery and preserve the organ.

BackgroundThe optimal neoadjuvant strategy for high-risk locally advanced rectal cancer (LARC) remains a matter of debate. This study evaluated the efficacy and safety of neoadjuvant FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, irinotecan) plus bevacizumab without radiotherapy in patients with magnetic resonance imaging-defined high-risk LARC.MethodsA prospective, multicentre, single arm phase II trial was conducted in four Japanese Institutions between 2018 and 2024, enrolling patients with rectal adenocarcinoma and at least one high-risk criterion: clinical T4, lateral pelvic lymph node metastasis, mesorectal fascia involvement, or positive extramural vascular invasion. Patients received four cycles of FOLFOXIRI plus bevacizumab, followed by two cycles of FOLFOXIRI alone, before total mesorectal excision. The primary endpoint was pathological complete response (pCR); secondary endpoints included the R0 resection rate, local recurrence (LR), recurrence-free survival (RFS), overall survival (OS), and safety.ResultsOF 50 eligible patients, 31 were enrolled before early trial closure due to a slow accrual (accrual rate 62%). All patients underwent surgery. The pCR rate was 10% (3 of 31) and R0 resection was achieved in 97% (30 of 31) of patients. The median follow-up was 36.7 months. The 3-year cumulative LR rate was 3%, with 3-year RFS and OS rates of 73 and 81%, respectively. Grade ≥ 3 neutropenia occurred in 29% of patients, with acceptable toxicity overall. No cases of gastrointestinal perforation were observed. Grade ≥ III postoperative complications occurred in seven patients (23%), with the most frequent events being anastomotic leakage in two patients (7%).ConclusionsIn this phase II trial, although recruitment was suboptimal, neoadjuvant FOLFOXIRI plus bevacizumab achieved good local control without radiotherapy in patients with high-risk LARC. Although the pCR rate was modest compared with radiotherapy-based regimens, this chemotherapy-only approach may represent a reasonable option for select patients who are not suitable candidates for pelvic radiotherapy. Registration number: UMIN000037367 (https://www.umin.ac.jp/english/).

Transanal total mesorectal excision (taTME) has become a promising surgical approach for anus-preserving surgery of mid-low rectal cancer (RC). This study aimed to compare the long-term oncological outcomes of taTME and laparoscopic total mesorectal excision (lapTME). Of 233 patients who were treated for mid-low RC from July 2017 to August 2020, 110 underwent taTME and 123 received lapTME. Propensity score matching (PSM) was performed to balance the baseline characteristics between the taTME and lapTME groups. After PSM, 61 patients were included in each group. Prior to PSM, the 5-year overall survival (OS) and disease-free survival (DFS) rates were comparable between the taTME and lapTME groups (72.7% vs. 69.1%, p = 0.617; 72% vs. 69%, p = 0.576, respectively). After PSM, there was no statistically significant difference in the 5-year OS and DFS rates between groups (64.2% vs. 64.4%, p = 0.936; 66.1% vs. 66.1%, p = 0.947, respectively). As compared to lapTME, taTME achieved comparable oncological safety for patients with mid-low RC.

Achieving complete total mesorectal excision (TME) is considered an important indicator of surgical quality in rectal cancer surgery. However, the impact of TME quality on overall survival (OS) remains controversial. This study aimed to evaluate the association between TME quality and OS in patients undergoing rectal cancer surgery. A retrospective analysis was conducted on 171 patients who underwent elective low anterior resection or abdominoperineal resection for rectal cancer between 2021 and 2022. OS was compared between patients with incomplete TME and those with near-complete or complete TME. In addition, clinical and pathological factors associated with TME quality were assessed. Incomplete TME was independently associated with worse OS [hazard ratio (HR)=2.53, 95% confidence interval (CI) 1.15-5.59, p=0.021], while undergoing a Hartmann procedure showed the strongest negative impact on OS (HR=4.60, 95% CI 2.04-10.38, p<0.001). At 36 months, OS was 86.3% in the near-complete/complete TME group versus 68.3% in the incomplete group (log-rank p=0.008). Factors associated with incomplete TME included lower preoperative albumin levels, larger tumor size, previous abdominal surgery, tumors located closer to the anal verge, lymphovascular invasion, and positive circumferential resection margins. Incomplete TME was associated with significantly worse OS in patients undergoing rectal cancer surgery. These findings highlight the importance of achieving optimal TME quality. Larger prospective studies are warranted to validate these results.

The management of low rectal cancer, particularly tumors of the lower third, presents a persistent surgical challenge centered on the balance between oncological radicality and the preservation of continence and quality of life. Organ preservation strategies have emerged as a paradigm shift, moving beyond the historical standard of abdominoperineal resection. This comprehensive review examines the integrated role of intensive neoadjuvant chemoradiation therapy (nCRT) regimens and total transanal mesorectal excision (TaTME) in facilitating sphincter-preserving resection for distal rectal carcinomas. We synthesize current evidence on the induction of pathological complete response (pCR) through dose-escalated radiation and concurrent chemotherapy, and its critical impact on surgical planning. The focus is on how the TaTME technique, with its enhanced distal visualization and precision in the deep pelvis, enables a more reliable assessment of tumor response and a technically optimized intersphincteric dissection. This manuscript analyzes the synergistic potential of these two approaches—aggressive nonsurgical cytoreduction and refined surgical access—to achieve clear circumferential and distal margins while preserving the sphincter complex. We discuss the implications of pCR as a surrogate for favorable long-term oncological outcomes and review the stringent patient selection, response assessment protocols, and functional considerations inherent to this multidisciplinary model. The evolving landscape of non-operative management is contextualized alongside definitive TaTME resection, providing a nuanced overview of contemporary organ-preserving pathways.

PurposeCurrent international guidelines recommend neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) for locally advanced rectal cancer (LARC). Although nCRT reduces the risk of local recurrence, it has not demonstrated a survival advantage and increases the likelihood of preoperative overtreatment. This study investigated whether upfront TME could be offered without compromising oncologic outcomes.MethodsFrom January 2015 to December 2020, patients with stage II/III LARC who underwent either upfront TME or nCRT followed by TME were analyzed using propensity score matching. Long-term survival outcomes were compared between the 2 groups. The primary endpoint was 5-year disease-free survival. Secondary endpoints included 5-year local recurrence-free survival, distant metastasis-free survival, and overall survival.ResultsA total of 348 patients were included, of whom 138 (39.7%) underwent upfront TME. The upfront TME group showed significantly higher 5-year disease-free survival (63.3% vs. 43.9%) and distant metastasis-free survival (88.1% vs. 70.3%). However, after excluding patients with preoperative mesorectal fascia (MRF) involvement, no significant differences were observed in long-term oncologic outcomes. Following 1:1 propensity score matching, 47 patients from each group were compared. Kaplan-Meier survival analysis revealed no significant differences in any endpoints. Cox regression analysis of the matched cohort indicated that preoperative MRF involvement, positive extramural vascular invasion, and tumor deposits were not independent prognostic factors.ConclusionUpfront TME may represent a viable treatment option for selected patients with LARC, particularly those without MRF involvement, providing comparable oncologic outcomes to the standard nCRT approach.

The incidence of early-onset colorectal cancer (EO-CRC), defined as a diagnosis before 50 years of age, is increasing worldwide. However, its clinical characteristics and outcomes compared to average-onset colorectal cancer (AO-CRC) remain under debate, especially in the setting of locally advanced rectal cancer (LARC). This study aimed to compare clinical characteristics, treatment responses, and survival outcomes between patients with early-onset and average-onset locally advanced rectal cancer. A multicenter retrospective cohort study. We retrospectively analysed 305 patients with stage II-III rectal cancer treated between 2012 and 2022 across three Italian oncology centrers. Patients were categorised as EO-RC (⩽50 years) or AO-RC (>50 years). All patients underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision. Pathological and radiological responses were evaluated, and survival outcomes were assessed through Kaplan-Meier methods. Early-onset patients accounted for 10.5% of the cohort. Clinical and pathological characteristics were broadly similar between groups, although EO-RC patients had a higher prevalence of proficient mismatch repair status. Radiological and pathological response rates were comparable. After a median follow-up of 120 months, the 10-year overall survival (OS) was 73.3% in EO-RC and 91.9% in AO-RC (HR 7.60, 95% CI 2.22-26.06; p = 0.0012). Disease-free survival (DFS) at 10 years was 57.1% in EO-RC and 70.9% in AO-RC (HR 1.80, 95% CI 0.86-3.78; p = 0.1177). Early-onset rectal cancer patients exhibit similar response rates and DFS compared to older patients, but appear to have worse OS. Further studies are needed to explore biological factors and post-recurrence treatment strategies that may influence these outcomes.