To assess the relevance of peritoneal reflection involvement in long-term oncological outcomes in patients with rectal cancer.

Prospective observational study from a specialized colorectal unit that included a consecutive series of patients undergoing mesorectal excision for rectal cancer. Peritoneal reflection (PR) involvement was evaluated on pathological examination using Shepherd's classification. Overall survival (OS), disease-free survival (DFS), and local recurrence (LR) were assessed.

One hundred sixty patients were included in the present analysis. Peritoneal involvement was present in 28.2% of the 85 tumors above or at the level of PR. There were no differences in OS, DFS, or LR according to tumor's height location. The 5-year OS, DFS, and LR for tumors involving PR were 58.3%, 61.7%, and 30.3%, respectively. Patients with peritoneal involvement had a higher LR rate (p = 0.02) and shorter OS (p = 0.04). Shepherd's grade 4 peritoneal involvement was an independent risk factor for OS (HR 2.9; 95% CI 1.1-9.5, p = 0.04) and LR (HR 4.2; 95% CI 1.2-16.9, p = 0.04).

After rectal cancer resection, peritoneal involvement is an independent risk factor for local recurrence and poor survival.

Depending on the extent of the tumor, the treatment strategies for rectal cancer include primary surgical resection or, in the case of locally advanced carcinoma, neoadjuvant chemo(radio)therapy (C[R]Tx) or total neoadjuvant therapy (TNT), usually followed by surgical treatment. During resection, it is important to find a balance between radicality and preservation of function. Current data show that shorter safety margins are possible for patients who received neoadjuvant treatment without compromising the oncological outcome. This enables continence-preserving surgery in many patients with low rectal cancer. In these cases in particular, intraoperative frozen section diagnostics play a central role in confirming tumor-free margins. However, frozen section diagnostics also play an important role in the transanal resection of early carcinomas or in the therapy of recurrent rectal cancer. It should not be performed routinely, but rather in a targeted maner for specific questions and the corresponding therapeutic consequences. The informative value of frozen section diagnostics in neoadjuvant treated rectal cancer may be limited, so that the final assessment of the resection status and thus the determination of further therapy must be based on paraffin-embedded sections.

Intra-operative electron radiotherapy (IOERT) directly delivers a large fraction of radiation to at-risk margins during surgery. However, the precise benefit of IOERT in patients with locally advanced and locally recurrent colorectal cancer (LACC/LRCC) is unclear. This study aimed to provide an updated summary of the current evidence available regarding IOERT as part of multi-modality treatment of LACC and LRCC.

This systematic review update was prospectively registered on PROSPERO (CRD42023438184). An electronic literature search was carried out using Ovid (MEDLINE), EMBASE, Web of Science, and the Cochrane Library databases for studies from July 2011 to April 2024. The inclusion criteria were adult patients who received IOERT as part of multi-modal treatment for LACC or LRCC. The primary outcome was overall survival (OS), disease free survival (DFS) and local control (LC) at 5 years. Secondary outcomes included post-operative complications.

16 new studies were identified since the previous analysis, and included (study population 1912 patients) of which two were prospective. High heterogeneity prevented meta-analysis of outcomes except for 5-year OS which suggested a non-significant benefit favouring IOERT. Significant methodological concerns were identified making interpretations challenging, however patients with LACC or LRCC with an R1 resection margin showed a favourable 5-year OS (40 % and 18 % respectively) when compared to current evidence.

Although limited by a lack of appropriately conducted randomised evidence, IOERT-containing multi-modality treatment may improve oncological outcomes in LACC and LRCC patients with R1 resections.

In the last two decades, robotic technology has fundamentally transformed the field of colorectal surgery by providing surgeons with unprecedented levels of precision and control. Nevertheless, robotic surgery presents certain challenges such as prolonged operating times, high costs, limited accessibility, and the necessity for specialized training.

This comparative review analyzes the impact of robotic platforms on colorectal surgery and its outcomes, with the expanding market of this technology. The major databases including PubMed, Scopus, and Google Scholars were searched using the key term 'robotic assisted surgery,' 'robotic platforms,' and 'colorectal surgery' to identify relevant articles as of August 2024. The most utilized robotic platforms currently available on the market - Da Vinci, Versius, Senhance, and Revo-I - are compared through their peri- and post-operative outcomes, including operative duration, blood loss, hospitalization period, oncological outcomes, and cost, providing a comprehensive insight into the future of robotic-assisted colorectal surgery.

Robotic surgery significantly improves patient outcomes, including shorter postoperative recovery times and effective cancer resection margins. However, challenges faced with these platforms include longer intraoperative times, arm clashing, the need for bedside assistance, and cost. Nevertheless, with the evolution toward managing more complex rectal cancer cases and more challenging dissection planes, the need for robotic platforms will only grow.

Surgical start time is considered to influence the quality of surgery due to surgeon fatigue. High-quality studies on middle and low rectal cancer are lacking. The analysis aims to find out the influence of surgical start time on the quality of surgery for middle and low rectal cancer, and whether robotic surgery could avoid the influence.

This study was a post hoc analysis of the REAL (robotic vs. laparoscopic surgery for middle and low rectal cancer) study, a multicenter, randomized, controlled, unblinded, parallel group, superiority trial. This analysis included the modified intention-to-treat population of the REAL study, who were divided into Group I (the surgeon's first surgery of the day), Group II (the surgeon's second surgery of the day), and Group III (the surgeon's third and subsequent surgeries of the day) based on surgical information registered in the REAL study. The primary outcome was the percentage of patients with a positive circumferential resection margin. The second outcomes were the macroscopic completeness of resection the incidence of intraoperative complications and 30-day postoperative complications.

A total of 1171 patients from the REAL study were included and divided into three groups: 547 (46.7%) in Group I (the surgeon's first surgery), 420 (35.9%) in Group II (the surgeon's second surgery), and 204 (17.4%) in Group III (the surgeon's third and subsequent surgeries). There was a lower percentage of circumferential resection margin (CRM)-positive patients in Group I (3.9%) than in Group II (6.6%, unadjusted P = 0.069) and Group III (8.1%, unadjusted P = 0.027, adjusted P = 0.081). Group I also had fewer intraoperative complications (5.3%) than Group II (8.3%, unadjusted P = 0.060) and Group III (9.3%, unadjusted P = 0.046, adjusted P = 0.138). Macroscopic completeness of resection was not significantly different among the three groups (complete rate: Group I vs. Group II, 94.9% vs. 92.4%, unadjusted P = 0.254; Group I vs. Group III, 94.9% vs. 92.6%, unadjusted P = 0.334; Group II vs. Group III, 92.4% vs. 92.6%, unadjusted P = 0.488). The incidence of 30-day postoperative complications showed no significant difference among the three groups (Group I vs. Group II, 18.5% vs. 20.0%, unadjusted P = 0.547; Group I vs. Group III, 18.5% vs. 22.1%, unadjusted P = 0.268; Group II vs. Group III, 20.0% vs. 22.1%, unadjusted P = 0.551). The quality of robotic surgery was not significantly influenced by surgical start time. For laparoscopic surgery, Group I had a lower CRM positivity rate (4.3%) than Group II (9.4%, unadjusted P = 0.029, adjusted P = 0.087) and Group III (10.4%, unadjusted P = 0.031, adjusted P = 0.047).

According to this post hoc analysis of the REAL study, for middle and low rectal cancer surgery, surgical start time could influence surgical quality by affecting surgeon fatigue. Surgeries start later in a day bring worse quality compared to those early in a day. Robotic surgery could reduce this influence to some extent, while laparoscopic surgery is more susceptible.

Complete resection of advanced rectal cancer is challenging, with local recurrence rates ranging from 4% to 12%. Local recurrence is often categorized as central, anastomotic, or lateral, with lateral lymph node (LLN) metastasis being the primary driver of lateral recurrence. Although preoperative radiotherapy effectively manages nonlateral recurrences, it is less effective for lateral recurrences, and LLN dissection significantly reduces lateral recurrence rates. This study aimed to clarify the clinicopathological characteristics associated with lateral and nonlateral recurrences.

We retrospectively analyzed 232 patients (156 males and 76 females; median age, 64 years) who underwent preoperative radiotherapy followed by curative-intent surgery for clinical T3/4 rectal adenocarcinoma located below the peritoneal reflection between April 2010 and December 2017. In total, 40% of the patients underwent LLN dissection. Univariate and multivariate analyses of clinicopathological data were performed to identify the independent risk factors for lateral and nonlateral recurrences.

Local recurrence occurred in 19 (8%) patients: 7 had lateral recurrence, 13 had nonlateral recurrence, and 1 had both. Multivariate analysis identified mesorectal lymph node metastasis as a significant risk factor for lateral recurrence, whereas positive circumferential resection margin was a significant risk factor for nonlateral recurrence.

The identification of different risk factors for lateral and nonlateral recurrence suggests that lateral recurrence is more strongly associated with lymphatic permeation than nonlateral recurrence. These findings highlight the importance of LLN dissection in minimizing the risk of lateral recurrence.

A positive pathologic retroperitoneal surgical resection margin in the retroperitonealized colon is reported to predict distant metastases. However, no studies have investigated retroperitoneal surgical resection margin positivity on computed tomography colonography and its prognostic significance.

Patients who underwent primary resection for ascending or descending colon cancer at our institution between 2013 and 2018 were retrospectively evaluated (n = 206). Retroperitoneal surgical resection margin on computed tomography colonography was defined on the basis of the relationship between the advanced tumor area and the retroperitoneum. The relationship between retroperitoneal surgical resection margin on computed tomography colonography and relapse-free survival was analyzed by dividing the patients into positive and negative retroperitoneal surgical resection margin on computed tomography colonography groups.

Two doctors independently evaluated the images. The interobserver agreement rate was 93.7% with a kappa coefficient of 0.78 (95% confidence interval, 0.66-0.90). Retroperitoneal surgical resection margin on computed tomography colonography positivity was observed in 32 of the 206 patients (15.5%). Univariate analysis showed that a positive retroperitoneal surgical resection margin on computed tomography colonography was a poor prognostic factor for relapse-free survival (hazard ratio, 7.07; 95% confidence interval, 2.77-18.0, P < .001). Multivariate analysis with carcinoembryonic antigen, clinical T and N stage as covariates (all P < .10 in univariate analysis) identified only retroperitoneal surgical resection margin on computed tomography colonography positive as a significant independent poor prognostic factor for relapse-free survival (hazard ratio, 3.99; 95% confidence interval, 1.30-12.3, P = .02).

In conclusion, this study revealed that retroperitoneal surgical resection margin on computed tomography colonography positivity is a poor prognostic factor. In cases in which retroperitoneal surgical resection margin on computed tomography colonography is positive, it is recommended not only to secure a wider margin, such as by resecting the Gerota fascia, but also to consider retroperitoneal surgical resection margin on computed tomography colonography positivity as a potential indication for preoperative chemotherapy.

Microscopically positive resection margins (R1) are associated with poorer outcomes in colon cancer. While the sequalae of a positive margin related to the primary tumour (R1Tumour) are relatively well known, comparatively less is known when the positive margin pertains to a metastatic lymph node (R1LNM). The aim of this study is to confirm the significance and impact of R1LNM margins in colon cancer patients.

A retrospective, observational study of patients treated for American Joint Committee on Cancer Stage 3 colon cancer with potentially curative surgical intervention during a 10-year study period was performed. Patients were stratified into three groups (R0, R1Tumour, R1LNM). Outcomes measured were disease-specific survival (DSS), local recurrence-free survival (LRFS) and systemic recurrence-free survival (SRFS). Cox multivariable analysis and sensitivity analyses (time-stratified, competing-risk and propensity-matched analyses) were performed to determine the independent importance of R1LNM.

A total of 801 patients were included. The R1 resection rate was 6.6% and the R1LNM resection rate was 4.7%. Compared with R0 resection, R1LNM margins had significantly lower 5-year DSS [R1LNM 53.8% (95% CI 37.4%-77.3%) vs. R0 74.2%], LRFS [R1LNM 61% (95% CI 41.7%-89.1%) vs. R0 80.5%] and SRFS [R1LNM 39.5% (95% CI 24.2%-63.8%) vs. R0 70%]. R1LNM was not independently associated with the above outcomes following traditional, time-stratified and competing-risk multivariable analyses, nor following propensity matching.

R1LNM positivity may reflect other poor-prognosis variables, which themselves play a more substantial role in determining disease outcomes.

This study aims to examine why we encounter a pathological circumferential resection margin (pCRM)-positive specimen whose preoperative MRI indicates negative mesorectal fascia involvement in middle to low rectal cancer.

Forty-four consecutive patients included in this study had c(yc)T1-3 primary rectal adenocarcinoma without mesorectal fascia involvement and underwent laparoscopic total mesorectal excision (TME) with curative intent in the Department of Gastrointestinal Surgery of Kansai Medical University Hospital from January 2014 to April 2018. We adopted three checkpoints to investigate the misleading point causing positive pCRM (≤ 1 mm). (1) c(yc)CRM diagnosis by two radiologists with more than 20 and 15 years of experience in rectal cancer MRI diagnosis. (2) The specimen was assessed using the TME score presented by Nagtegaal. (3) We compared the standard sectioning according to UK guidelines (group A; n = 26) with the specimen MRI image navigation-based section (group B; n = 18) in terms of estimation of pCRM by c(yc)CRM.

We achieved a "complete" resection specimen in all cases. A simple correlation coefficient in group B revealed a significant correlation between c(yc)CRM and pCRM (r = 0.663, p = 0.00513); this correlation was not significant in group A (r = 0.261, p = 0.19824). However, tests for differences between linear regression coefficients in groups A and B showed no significant differences (p = 0.12596). There were five cases of pCRM ≤ 1 mm: three in group A and two in group B. An anterior lesion caused pCRM ≤ 1 mm in three cases; the tumor deposits or extramural vascular invasion caused the other cases.

The cause of misleading pCRM was the inaccurate preoperative MRI diagnosis of c(yc)CRM.

Total neoadjuvant treatment (TNT) with induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) has improved long-term outcomes for patients with locally advanced rectal cancer (LARC). However, long-term outcomes have not been investigated for patients with incomplete (R1) resection separately. This study investigates overall survival (OS), disease-free survival (DFS) and local and distant recurrence rates in patients with R1 resection after preoperative treatment with ICT and CRT or CRT.

From the NORD database 689 patients with LARC who received treatment between 2006 and 2017 were screened for inclusion. All patients with R1 resection were included. ICT consisted of at least 1 cycle of capecitabine and oxaliplatin (CAPOX) and was followed by radiotherapy concomitant with capecitabine.

Among 46 patients with R1 resection, 27 (59%) received both ICT and CRT, and 19 (41%) patients received CRT. The 5-year OS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 37% (95% CI, 15%-59%) (CRT) (P = .25) and 5-year DFS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 32% (95% CI, 11%-53%) (CRT) (P = .22). The local recurrence rates showed a small nonstatistical significant difference in local control in the ICT group: 15% compared to 26% in the CRT group (P = .22). Distant recurrence rates were similar: 41% (ICT + CRT) versus 47% (CRT) (P = .48).

There was no significant difference in OS, DFS or local and distant recurrence rates between patients who received ICT + CRT versus patients who received CRT only.

Rectal cancer's prevalence increases with an aging population, disproportionately affecting the elderly. The suitability of surgical interventions for this demographic is contentious due to underrepresentation during surgery. This study examines the practicality of utilizing Da Vinci surgery for rectal cancer patients who are 70 years and older. Information was gathered from PubMed, Embase, Scopus and the Cochrane Library, with a focus on English-language publications. Statistical analysis was performed using RevMan 5.4, presenting outcomes for categorical variables in risk ratios. Out of 890 patients across 5 studies, 240 were categorized as elderly, while 650 fell into the younger age group. Notable distinctions were noted in harvested lymph nodes, BMI, and postoperative outcomes, whereas factors like the length of hospital stay, Clavien-Dindo classification, and radial resection margin did not display significance. Although age increases postoperative risk, evidence emphasizes frailty, not age alone, as the primary determining factor.

Background and Objective: Colorectal cancer (CRC) is the third most common cancer worldwide, with colon cancer accounting for approximately 60% of all CRC cases. Surgery remains the primary and most effective treatment. Robotic-assisted surgery (RAS) has emerged as a promising approach for colon cancer resection. This retrospective study compares RAS and laparoscopic-assisted surgery (LSS) for stage I-III colon cancer resections at a single medical center in East Asia. Methods: Between 1 January 2018, and 29 February 2024, patients undergoing colectomy were classified into right-side and left-side colectomies. Propensity score matching was conducted based on age group, gender, ASA score, and BMI to ensure comparability between groups. After matching, there were 50 RAS and 200 LSS cases for right colectomy (RC), and 129 RAS and 258 LSS cases for left colectomy (LC). Perioperative outcomes were compared between the two surgical approaches. The primary outcomes were recovery milestones, while secondary outcomes included complications and postoperative pain scores. Results: RAS demonstrated faster recovery milestones compared to LSS (hospital stay: 6.5 vs. 10.2 days, p = 0.005 for RC; 5.5 vs. 8.2 days, p < 0.001 for LC). RAS also resulted in lower rates of ileus (14% vs. 26%, p = 0.064 for RC; 6.2% vs. 15.9%, p = 0.007 for LC) and higher lymph node yields (31.4 vs. 26.8, p = 0.028 for RC; 25.8 vs. 23.9, p = 0.066 for LC). Major complication rates showed no significant difference between RAS and LSS (4.0% vs. 7.0%, p = 0.746 for RC; 4.7% vs. 3.1%, p = 0.563 for LC). Patients in the RAS group experienced earlier diuretic phases and reported significantly lower postoperative pain scores (3.0 vs. 4.1, p = 0.011 for RC; 2.9 vs. 4.1, p < 0.001 for LC). Conclusions: Robotic-assisted surgery is associated with faster recovery, lower rates of ileus (LC), higher lymph node yield (RC) and reduced postoperative pain compared to laparoscopic-assisted surgery for colon cancer resection.

While total mesorectal excision is the gold standard for rectal cancer, the optimal surgical approach to achieve adequate oncological outcomes remains controversial. This network meta-analysis aims to compare the histopathological outcomes of robotic (R-RR), transanal (Ta-RR), laparoscopic (L-RR), and open (O-RR) resections for rectal cancer.

MEDLINE, Embase, and the Cochrane Library were screened from inception to June 2024. Of the 4186 articles screened, 27 RCTs were selected. Pairwise comparisons and Bayesian network meta-analyses applying random effects models were performed.

The 27 RCTs included a total of 8696 patients. Bayesian pairwise meta-analysis revealed significantly lower odds of non-complete mesorectal excision with Ta-RR (Odds Ratio, OR, 0.60; 95%CI, 0.33, 0.92; P = .02; I2:11.7 %) and R-RR (OR, 0.68; 95%CI, 0.46, 0.94; P = .02; I2:41.7 %) compared with laparoscopy. Moreover, lower odds of positive CRMs were observed in the Ta-RR group than in the L-RR group (OR, 0.36; 95%CI, 0.13, 0.91; P = .02; I2:43.9 %). The R-RR was associated with more lymph nodes harvested compared with L-RR (Mean Difference, MD, 1.24; 95%CI, 0.10, 2.52; P = .03; I2:77.3 %). Conversely, Ta-RR was associated with a significantly lower number of lymph nodes harvested compared with all other approaches. SUCRA plots revealed that Ta-RR had the highest probability of being the best approach to achieve a complete mesorectal excision and negative CRM, followed by R-RR, which ranked the best in lymph nodes retrieved.

When comparing the effectiveness of the available surgical approaches for rectal cancer resection, Ta-RR and R-RR are associated with better histopathological outcomes than L-RR.

The relative benefits of robotic surgery and laparoscopic surgery are controversial in rectal cancer. This study compared the short- and long-term outcomes of robotic surgery with those of laparoscopic surgery in patients with rectal cancer using propensity score analysis.

This study analyzed consecutive patients who underwent minimally invasive surgery for stage I-III rectal cancer between April 2014 and October 2020. After propensity score matching (PSM), short-term outcomes, relapse-free survival, and overall survival were compared between the robotic surgery (RS) group and the laparoscopic surgery (LS) group.

During the study period, 251 patients underwent laparoscopic surgery and 193 underwent robotic surgery. PSM resulted in 160 matched pairs (After PSM, the percentages of patients with stage I, II, and III disease were respectively 56%, 19%, and 24% in the LS group and 49%, 23%, and 28% in the RS group (P = 0.462). Median operation time was 239 min in the LS group and 284 min in the RS group (P = 0.001). The C-reactive protein level on postoperative day 3 was significantly lower in the RS group (4.63 mg/mL vs. 5.86 mg/mL, P = 0.013). Postoperative complications, including ileus and Clavien-Dindo grade II or higher complications, were 6% vs. 1% (P = 0.006) and 21% vs. 12% (P = 0.024) in the LS and RS groups, respectively. The 5-year relapse-free survival rate was 88.5% in the LS group and 90.5% in the RS group (P = 0.525); the respective 5-year overall survival rates were 97.3 and 93.8% (P = 0.283). The 5-year cumulative local and distant recurrence rates were 3.3% vs. 3.3% (P = 0.665) and 9.7% vs. 7.7% (P = 0.464) in the LS and RS groups, respectively CONCLUSION: Robotic surgery can be a feasible treatment modality for rectal cancer, with lower frequencies of postoperative ileus and Clavien-Dindo grade II or higher complications than laparoscopic surgery and no difference in long-term outcomes.

To create and validate nomograms predicting overall survival and recurrence in treatment-naïve rectal cancer (RC) patients who underwent upfront surgery.

Although multidisciplinary treatment is standard for locally advanced RC, understanding surgical efficacy is important for determining indications for perioperative adjuvant therapy.

RC patients who underwent upfront surgery at the Japanese Society for Cancer of the Colon and Rectum institutions were analyzed. A training cohort (n = 1925) of treatment-naïve patients who underwent surgery between 2007 and 2008 was analyzed to construct prognostic models predicting postoperative survival and recurrence. Discrimination and calibration were performed using an external validation cohort (n = 2957; Japanese colorectal cancer registry, procedures in 2005-2006). Effects of adjuvant chemotherapy on survival were evaluated based on nomogram prediction and Surveillance, Epidemiology, and End Results (SEER) data (n = 10,482; upfront surgery for RC in 2010-2015).

In the training cohort, age predicted survival, venous invasion predicted recurrence, and sex, tumor location, histological type, preoperative carcinoembryonic antigen, invasion depth, lymphatic invasion, positive radial margin, and numbers of metastatic nodes and examined nodes predicted both. Internal and external validated Harrell's C-index values were respectively 0.77 and 0.75 for survival and 0.75 and 0.74 for recurrence. RC patients who underwent upfront surgery in the SEER database were stratified into 3 risk levels by nomogram score. Adjuvant chemotherapy did not improve 5-year survival in low-risk patients, but did so for middle-risk (62.4% vs 76.8%) and high-risk (39.4% vs 63.5%) patients.

These nomograms could predict survival and recurrence after upfront curative resection of RC and identify cases expected to benefit more from adjuvant chemotherapy.

Neoadjuvant chemoradiotherapy (nCRT) is employed for the local control of locally advanced rectal cancer; however, its prognostic impact is limited and often impairs pelvic organ function. Therefore, careful patient selection is essential. This study aimed to investigate the impact of nCRT on relapse-free survival (RFS) by stratifying patients according to MRI detected circumferential resection margin (mrCRM) or extramural vascular invasion (mrEMVI), as the ability of MRI findings to identify patients who will have beneficial outcomes from nCRT is uncertain.

We retrospectively analyzed patients with clinical stage II-III lower rectal cancer who underwent surgical resection with or without nCRT between 2010 and 2011 at 69 hospitals in Japan. The impact of nCRT on RFS was evaluated using multivariable Cox regression models in the entire cohort and in subgroups stratified by mrCRM or mrEMVI status.

In the entire cohort (nCRT, n = 172; surgery alone, n = 503), nCRT showed a trend toward improved RFS, although the difference was not statistically significant (HR, 0.74; 95 % CI, 0.54-1.03; P = 0.074). Among mrCRM-negative and mrEMVI-negative patients, there were no significant differences in RFS between the nCRT and surgery-alone groups. Among mrCRM-positive patients, nCRT tended to improve the RFS (HR, 0.70; 95 % CI, 0.46-1.06; P = 0.089). Among mrEMVI-positive patients, nCRT significantly prolonged the RFS (HR, 0.62; 95 % CI, 0.38-1.00; P = 0.048).

Compared to surgery alone, nCRT did not significantly improve RFS in the overall population but significantly improved RFS in mrEMVI-positive patients.

Locally recurrent rectal cancer (LRRC), which occurs in 6-12% of patients previously treated with surgery, with or without pre-operative chemoradiation therapy, represents a complex and heterogeneous disease profoundly affecting the patient's quality of life (QoL) and long-term survival. Its management usually requires a multidisciplinary approach, to evaluate the several aspects of a LRRC, such as resectability or the best approach to reduce symptoms. Surgical treatment is more complex and usually needs high-volume centers to obtain a higher rate of radical (R0) resections and to reduce the rate of postoperative complications. Multiple factors related to the patient, to the primary tumor, and to the surgery for the primary tumor contribute to the development of local recurrence. Accurate pre-treatment staging of the recurrence is essential, and several classification systems are currently used for this purpose. Achieving an R0 resection through radical surgery remains the most critical factor for a favorable oncologic outcome, although both chemotherapy and radiotherapy play a significant role in facilitating this goal. If a R0 resection of a LRRC is not feasible, palliative treatment is mandatory to reduce the LRRC-related symptoms, especially pain, minimizing the effect of the recurrence on the QoL of the patients. The aim of this manuscript is to provide a comprehensive narrative review of the literature regarding the management of LRRC.

Concerns persist regarding the effectiveness of robotic proctectomy compared with open proctectomy for locally advanced rectal cancer with a high risk of circumferential resection margin involvement.

Comparison of surrogate cancer outcomes after robotic versus open proctectomy in this subpopulation.

Retrospective cohort study.

Three academic hospitals (Mayo Clinic Arizona, Florida, and Rochester) with data available through the Mayo Data Explorer platform.

Patients at high risk of circumferential resection margin involvement were selected on the basis of the MRI-based definition from the MERCURY I and II trials.

Rate of pathologic circumferential resection margin involvement (≤1 mm), mesorectal grading, and rate of distal margin involvement.

Out of 413 patients, 125 (30%) underwent open and 288 (70%) underwent robotic proctectomy. Open proctectomy was significantly associated with a greater proportion of cT4 tumors (39.3% vs 24.8%, p = 0.021), multivisceral/concomitant resections (40.8% vs 18.4%, p < 0.001), and less frequent total neoadjuvant therapy use (17.1% vs 47.1%, p = 0.001). Robotic proctectomy was less commonly associated with pathologic circumferential resection margin involvement (7.3% vs 17.6%, p = 0.002), including after adjustment for cT stage, neoadjuvant therapy, and multivisceral resection (OR 0.326; 95% CI, 0.157-0.670, p = 0.002). Propensity score matching for 66 patients per group and related multivariable analysis no longer indicated any reduction of circumferential positive margin rate associated with robotic surgery ( p = 0.86 and p = 0.18). Mesorectal grading was comparable (incomplete mesorectum in 6% robotic proctectomy patients vs 11.8% open proctectomy patients, p = 0.327). All cases had negative distal resection margins.

Retrospective design.

In patients with locally advanced rectal cancer at high risk of circumferential resection margin involvement, robotic proctectomy is an effective approach and could be pursued when technically possible as an alternative to open proctectomy. See Video Abstract .

ANTECEDENTES:Persisten preocupaciones con respecto a la efectividad de la proctectomía robótica en comparación con la proctectomía abierta en casos de cáncer de recto localmente avanzado con un alto riesgo de margen de resección circunferencial positivo.OBJETIVO:Comparar los resultados en la subpoblación de portadores de cáncer luego de una proctectomía robótica versus una proctectomía abierta.DISEÑO:Estudio retrospectivo de cohortes.AJUSTE:Realizado en tres hospitales académicos (Mayo Clinic de Arizona, Florida y Rochester) a través de la plataforma Mayo Data Explorer.PACIENTES:Fueron seleccionados aquellos pacientes con alto riesgo de compromiso sobre el margen de resección circunferencial, según la definición de los Estudios Mercury I-II basada en la Imágen de Resonancia Magnética.MEDIDAS DE RESULTADO PRINCIPALES Y SECUNDARIAS:La tasa de compromiso patológico sobre el margen de resección circunferencial (≤1 mm), la clasificación mesorrectal y la tasa del compromiso del margen distal.RESULTADOS:De 413 pacientes, 125 (30%) fueron sometidos a una proctectomía abierta y 288 (70%) a proctectomía robótica. La proctectomía abierta se asoció significativamente con una mayor proporción de tumores cT4 (39,3% frente a 24,8%, p = 0,021), las resecciones multiviscerales/concomitantes fueron de 40,8% frente a 18,4%, p < 0,001 y una adminstración menos frecuente de terapia neoadyuvante total (17,1). % vs 47,1%, p = 0,001).La proctectomía robótica se asoció con menos frecuencia con la presencia de una lesión sobre el margen de resección circunferencial patológico (7,3% frente a 17,6%, p = 0,002), incluso después del ajuste por estadio cT, de la terapia neoadyuvante y de resección multivisceral (OR 0,326, IC 95% 0,157-0,670, p = 0,002). El apareado de propensión por puntuación en 66 pacientes por grupo y el análisis multivariable relacionado, no mostraron ninguna reducción en la tasa de margen positivo circunferencial asociado con la cirugía robótica ( p = 0,86 y p = 0,18). La clasificación mesorrectal fue igualmente comparable (mesorrecto incompleto en el 6% de los pacientes con RP frente al 11,8% de los pacientes con OP, p = 0,327). Todos los casos tuvieron márgenes de resección distal negativos.LIMITACIÓN:Diseño retrospectivo.CONCLUSIÓN:En pacientes con cáncer de recto localmente avanzado con alto riesgo de compromiso del margen de resección circunferencial, la proctectomía robótica es un enfoque eficaz y podría realizarse cuando sea técnicamente posible como alternativa a la proctectomía abierta. (Traducción-Dr. Xavier Delgadillo ).

The incidence of rectal neuroendocrine tumors (RNETs) has witnessed a significant surge, with a notable proportion being amenable to endoscopic removal. However, the clinical significance of positive resection margin for RNETs patients following endoscopic resection remain unknown, resulting in a lack of consensus regarding the appropriateness of implementing salvage treatment.

In this large, multicenter, retrospective cohort study, we analyzed the medical records of individuals who underwent endoscopic resection for RNETs and classified them into two groups: the positive resection margin and the negative resection margin group. The overall survival (OS) and disease-free survival (DFS) were compared among two group. The independent variables were identified using univariate and multivariate logistic regression analyses to predict positive resection margin. Then, the model was established to predict the patients with positive resection margin using multivariate logistic regression.

181 RNETs patients (34.3 %) represented positive margin after endoscopic resection. Following a median follow-up period of 72 months, tumor recurrence manifested in 12 out of 527 patients (2.2 %) and the presence of positive resection margin was associated with worse DFS. Independent factors correlating with positive resection margin included endoscopic resection method choice, RNETs located in the low rectum, NLR >4.44 and tumor size exceeding 14.89 mm. A prediction model was therefore established with high predictive accuracy and excellent clinical applicability determined by calibration curves and DCA curve. Among RNETs patients with positive margin following endoscopic resection, implementing salvage treatment was beneficial for improving DFS and salvage endoscopic resection offer equal efficiency compared with salvage radical resection.

Positive resection margin following endoscopic resection may indicate negative prognosis. Salvage treatment can improve the prognosis of RNETs patients with positive resection margin. Notably, salvage local resection exhibited similar efficacy compared with radical surgery in term of survival benefit.

Esophageal cancer presents a clinical challenge due to its high incidence and unfavorable prognosis. The prognostic role of the circumferential resection margin (CRM) remains highly controversial, potentially due to its temporal dynamics coupled with variability in follow-up durations across studies. We aimed to explore the time-dependent prognostic significance of CRM in T3 esophageal squamous cell carcinomas (ESCCs). We systematically reviewed literature from 1990 to 2023 to determine how follow-up duration influences the prognostic role of CRM in esophageal cancer. Concurrently, we performed a retrospective examination of 354 patients who underwent treatment at the National Cancer Center between 2015 and 2018. Integrating a time interaction term in the Cox regression analyses enabled us to not only identify independent risk factors affecting overall survival (OS) but also to specifically scrutinize the potential temporal variations in CRM's prognostic impact. Our literature review suggested that CRM's influence on prognosis diminishes with longer follow-up durations for both classifications, namely the Royal College of Pathologists (RCP) (β = -0.003, P < 0.001) and the College of American Pathologists (CAP) (β = -0.007, P < 0.001). Time-dependent multivariate Cox regression analysis emphasized the evolving nature of CRM's prognostic effect, and the inclusion of the time interaction term enhanced model accuracy. In conclusion, CRM is an independent prognostic factor for T3 thoracic ESCC patients. Its influence appears to decrease over extended follow-up periods, shedding light on the heterogeneity seen in previous studies. With the time interaction term, CRM becomes a more precise post-operative prognostic indicator for esophageal cancer.

Robotic-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.

This 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.

This 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.

ClinicalTrials.gov NCT06105203. Registered on October 27, 2023.

The clinical value of different modes of CRM involvement in rectal cancer patients is unclear. This study aims to determine the clinical impact of different modes of circumferential resection margin (CRM) involvement in patients with a locally advanced rectal carcinoma.

A cohort of patients who were diagnosed with stage III rectal cancer between June 2014 and June 2020 was selected from the prospective Dutch nationwide pathology databank (PALGA). Histopathological and clinical data were analyzed according to the nature of CRM involvement (via primary tumor invasion, lymph node metastasis, tumor deposit, multiple factors) and analyses on recurrence and overall survival (OS) were performed.

3020 patients were included, of whom 12.4 % had a positive CRM. The majority of these patients (63.2 %) had CRM involvement by primary tumor invasion and in 9 % of patients multiple factors caused the positive CRM. The rates of local recurrence and distant metastasis were related to the nature of the CRM involvement, with lowest rate for lymph node metastasis and highest rate for multiple factors. On multivariate analysis, CRM involvement by primary tumor invasion, tumor deposits and multiple factors, but not by lymph node metastasis, were associated with poor OS.

This nationwide population based study highlights the clinical importance of reporting the nature of CRM involvement in rectal cancer patients. Lymph node metastasis involving the CRM does not bear the same risks for local recurrence, distant metastases and OS as CRM involvement by primary tumor invasion or CRM involvement by multiple factors.

To investigate whether robotic surgery (RS) decreases the risk of circumferential resection margin (CRM) positivity compared with conventional laparoscopic surgery (LS) in patients with rectal cancer (RC) undergoing mesorectal excision (ME).

Although it is well known that CRM positivity affects postoperative outcomes in patients with RC undergoing ME, few studies have investigated whether RS is superior to conventional LS for the risk of CRM positivity.

We performed a comprehensive electronic search of the literature up to December 2022 to identify studies that compared the risk of CRM positivity between patients with RC undergoing robotic and conventional laparoscopic surgery. A meta-analysis was performed using random-effects models to calculate risk ratios (RRs) and 95 % confidence intervals (CIs), and heterogeneity was analyzed using I2 statistics.

Eighteen studies, consisting of 4 randomized controlled trials (RCTs) and 14 propensity score matching (PSM) studies, involved a total of 9203 patients with RC who underwent ME were included in this meta-analysis. The results demonstrated that RS decreased the overall risk of CRM positivity (RR, 0.82; 95 % CI, 0.73-0.92; P = 0.001; I2 = 0 %) compared with conventional LS. Results of a meta-analysis of the 4 selected RCTs also showed that RS decreased the risk of CRM positivity (RR, 0.62; 95 % CI, 0.43-0.91; P = 0.01; I2 = 0 %) compared with conventional LS.

This meta-analysis revealed that RS is associated with a decreased risk of CRM positivity compared with conventional LS in patients with RC undergoing ME.

There is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins.

Patients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival.

A total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion.

In patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group.

This study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN).

Patients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local-regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan-Meier method and log-rank tests.

A total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109).

Our study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.

Colorectal cancer is a common malignancy and various methods have been introduced to decrease the possibility of recurrence. Early recurrence (ER) is related to worse prognosis. To date, few observational studies have reported on the analysis of rectal cancer. Hence, we reported on the timing and risk factors for the ER of resectable rectal cancer at our institute.

To analyze a cohort of patients with local and/or distant recurrence following the radical resection of the primary tumor.

Data were retrospectively collected from the institutional database from March 2011 to January 2021. Clinicopathological data at diagnosis, perioperative and postoperative data, and first recurrence were collected and analyzed. ER was defined via receiver operating characteristic curve. Prognostic factors were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling.

We included 131 patients. The optimal cut off value of recurrence-free survival (RFS) to differentiate between ER (n = 55, 41.9%) and late recurrence (LR) (n = 76, 58.1%) was 8 mo. The median post-recurrence survival (PRS) of ER and LR was 1.4 mo and 2.9 mo, respectively (P = 0.008) but PRS was not strongly associated with RFS (R² = 0.04). Risk factors included age ≥ 70 years [hazard ratio (HR) = 1.752, P = 0.047], preoperative concurrent chemoradiotherapy (HR = 3.683, P < 0.001), colostomy creation (HR = 2.221, P = 0.036), and length of stay > 9 d (HR = 0.441, P = 0.006).

RFS of 8 mo was the optimal cut-off value. Although ER was not associated with PRS, it was still related to prognosis; thus, intense surveillance is recommended.

This study aimed to develop nomograms that combine clinical factors and MRI tumour regression grade to predict the pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy.

The retrospective study included 204 patients who underwent neoadjuvant chemoradiotherapy and surgery between January 2013 and December 2021. Based on pathological tumour regression grade, patients were categorized into four groups: complete pathological response (pCR, n=45), non-complete pathological response (non-pCR; n=159), good pathological response (pGR, n=119), and non-good pathological response (non-pGR, n=85). The patients were divided into a training set and a validation set in a 7:3 ratio. Based on the results of univariate and multivariate analyses in the training set, two nomograms were respectively constructed to predict complete and good pathological responses. Subsequently, these predictive models underwent validation in the independent validation set. The prognostic performances of the models were evaluated using the area under the curve (AUC).

The nomogram predicting complete pathological response incorporates tumour length, post-treatment mesorectal fascia involvement, white blood cell count, and MRI tumour regression grade. It yielded an AUC of 0.787 in the training set and 0.716 in the validation set, surpassing the performance of the model relying solely on MRI tumour regression grade (AUCs of 0.649 and 0.530, respectively). Similarly, the nomogram predicting good pathological response includes the distance of the tumour's lower border from the anal verge, post-treatment mesorectal fascia involvement, platelet/lymphocyte ratio, and MRI tumour regression grade. It achieved an AUC of 0.754 in the training set and 0.719 in the validation set, outperforming the model using MRI tumour regression grade alone (AUCs of 0.629 and 0.638, respectively).

Nomograms combining MRI tumour regression grade with clinical factors may be useful for predicting pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. The proposed models could be applied in clinical practice after validation in large samples.

The objective of the study is to compare 2 techniques for histological handling of rectal cancer specimens, namely whole-mount in a large block vs conventional sampling using small blocks, for mesorectal pathological assessment of circumferential resection margin status and depth of tumor invasion into the mesorectal fat.

This is a prospective study including 27 total mesorectal excision specimens of rectal cancer from patients treated for primary rectal carcinoma between 2020 and 2022 in a specialized multidisciplinary Colorectal Unit. For each total mesorectal excision specimen, 2 contiguous representative tumoral slices were selected and comparatively analyzed with whole-mount and small blocks macroscopic dissection techniques, enabling comparison between them in the same surgical specimen. The agreement between the 2 techniques to assess the distance of the tumor from the circumferential resection margin as well as the depth of tumor invasion was evaluated with the Student's t-test for paired samples, Pearson's correlation coefficient, and the Bland-Altman method comparison analysis.

Complete mesorectal excision was observed in 8% of cases. Circumferential resection margin involvement was observed in only one case (4 %). The whole-mount and small block techniques obtained similar results when we assessed the distance to the circumferential resection margin (t-test P = 0.8, r = 0.92) and the depth of mesorectal infiltration (t-test P = 0.6, r = 0.95).

Both gross dissection techniques (whole-mount vs multiple small cassettes) are equivalent and reliable to assess the distance to circumferential resection margin and the depth of mesorectal infiltration in the mesorectal fat in rectal cancer staging.

Endoanal ultrasound (EAUS) is a valuable imaging modality for the evaluation of anal and perianal pathologies. It provides detailed information about the anatomy and physiology of the anorectal region and has been used in pre-and post-operative settings of anorectal pathologies. EAUS is not only useful in the evaluation of benign pathologies but also in loco-regional staging of anal and rectal tumors. EAUS has several advantages over MRI, including reduced cost, better patient tolerance, and improved scope of application in patients with contraindications to MRI. Despite its benefits, EAUS is not widely performed in many centers across the globe. This article aims to educate radiologists, trainees, and surgeons about the indications, contraindications, patient preparation, imaging technique, and findings of EAUS. We will also highlight the technical difficulties, diagnostic challenges, and procedural complications encountered during EAUS, along with a comparative analysis of EAUS with other imaging approaches.

This study aimed to review the historical transition of rectal cancer surgery and recent evidence regarding transanal total mesorectal excision (TaTME). Additionally, it outlined the anatomical landmarks and technical considerations essential for successful TaTME. Anatomical studies and surgical techniques were analyzed to identify key landmarks and procedural steps crucial for TaTME. TaTME offers improved visibility and maneuverability even in the deep and narrow pelvis and is expected to contribute to tumor radical cure rates. By securing the circumferential resection margin and distal margin while preserving pelvic autonomic nerve function, TaTME holds promise for maintaining postoperative urinary and sexual functions. Key anatomical landmarks include the endopelvic fascia posteriorly, the S4-pelvic splanchnic nerve laterally, and the prostate or posterior vaginal wall anteriorly. Selecting the appropriate dissection layer based on tumor depth and ensuring precise incision of the tendinous arch of the pelvic fascia contributes to successful TaTME outcomes. TaTME represents a significant advancement in rectal cancer surgery, offering improved outcomes through meticulous attention to anatomical detail and precise dissection techniques. Understanding the historical context of rectal cancer surgery alongside recent evidence on TaTME is essential for optimizing patient outcomes and expanding the safe implementation of this innovative approach.

Total mesorectal excision (TME) has greatly improved rectal cancer surgery outcomes by reducing local recurrence and enhancing patient survival. This review outlines essential knowledge and techniques for performing TME. TME emphasizes the complete resection of the mesorectum along embryologic planes to minimize recurrence. Key anatomical insights include understanding the rectal proper fascia, Denonvilliers fascia, rectosacral fascia, and the pelvic autonomic nerves. Technical tips cover a step-by-step approach to pelvic dissection, the Gate approach, and tailored excision of Denonvilliers fascia, focusing on preserving pelvic autonomic nerves and ensuring negative circumferential resection margins. In Korea, TME has led to significant improvements in local recurrence rates and survival with well-adopted multidisciplinary approaches. Surgical techniques of TME have been optimized and standardized over several decades in Korea, and minimally invasive surgery for TME has been rapidly and successfully adopted. The review emphasizes the need for continuous research on tumor biology and precise surgical techniques to further improve rectal cancer management. The ultimate goal of TME is to achieve curative resection and function preservation, thereby enhancing the patient's quality of life. Accurate TME, multidisciplinary-based neoadjuvant therapy, refined sphincter-preserving techniques, and ongoing tumor research are essential for optimal treatment outcomes.

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).

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.

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).

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.

In Japan, the hinotori™ Surgical Robot System obtained pharmaceutical approval for use in colorectal cancer surgery in October 2022. This system has an operating arm with eight axes, adjustable arm base, and flexible three-dimensional viewer, which are expected to be advantageous in colorectal cancer surgery. A 55-year-old man presented to our hospital with melena and was diagnosed with cStage IIA (cT3N0M0) rectal cancer. The patient underwent intersphincteric resection using hinotori™ Surgical Robot System. Appropriate port placement was available for rectal manipulation, lymph node dissection, and arm base angle adjustment. Herein, we report the world's first rectal cancer surgery using the hinotori™ Surgical Robot System with TaTME by two teams.

Stroma AReactive Invasion Front Areas (SARIFA) is a recently identified haematoxylin & eosin (H&E)based histopathologic biomarker in gastrointestinal cancers, including colorectal cancer (CRC), defined as direct contact between tumour cells and adipocytes at the tumour invasion front. The current study aimed at validating the prognostic relevance of SARIFA in a large population-based CRC series as well as at investigating the relationship between SARIFA-status and previously established Warburg-subtypes, both surrogates of the metabolic state of the tumour cells.

SARIFA-status (positive versus negative) was determined on H&E slides of 1,727 CRC specimens. Warburg-subtype (high versus moderate versus low) data was available from our previous study. The associations between SARIFA-status, Warburg-subtype, clinicopathological characteristics and CRC-specific as well as overall survival were investigated.

28.7% (n=496) CRC were SARIFA-positive. SARIFA-positivity was associated with more advanced disease stage, higher pT category, and more frequent lymph node involvement (all p<0.001). SARIFA-positivity was more common in Warburg-high CRC. 44.2% (n=219) of SARIFA-positive CRCs were Warburg-high compared to 22.8% (n=113) being Warburg-low and 33.1% (n=164) being Warburg-moderate (p<0.001). In multivariable-adjusted analysis, patients with SARIFA-positive CRCs had significantly poorer CRC-specific (HRCRC-specific 1.65; 95% CI 1.41-1.93) and overall survival (HRoverall survival 1.46; 95% CI 1.28-1.67) independent of clinically known risk factors and independent of Warburg-subtype. Combining the SARIFA-status and the Warburg-subtype to a combination score (SARIFA-negative/Warburg-high versus SARIFA-positive/Warburg-low versus SARIFA-positive/Warburg-high, and so on) did not improve the survival prediction compared to the use of SARIFA-status alone (SARIFA-negative + Warburg-high: HRCRC-specific 1.08; 95% CI 0.84-1.38; SARIFA-positive + Warburg-low: HRCRC-specific 1.79; 95% CI 1.32-2.41; SARIFA-positive + Warburg-high: HRCRC-specific 1.58; 95% CI 1.23-2.04).

Our current study is the by far largest external validation of SARIFA-positivity as a novel independent negative prognostic H&E-based biomarker in CRC. In addition, our study shows that SARIFA-positivity is associated with the Warburg-high subtype. Further research is warranted to provide a more mechanistic understanding of the underlying tumour biology. Based on our data, we conclude SARIFA-status should be implemented in pathologic routine practice to stratify CRC patients.

Colorectal cancer remains a leading cause of mortality worldwide. Significant variation in response to treatment and survival is evident among patients with similar stage disease. Molecular profiling has highlighted the heterogeneity of colorectal cancer but has had limited impact in daily clinical practice. Biomarkers with robust prognostic and therapeutic relevance are urgently required. Ideally, biomarkers would be derived from H&E sections used for routine pathological staging, have reliable sensitivity and specificity, and require minimal additional training. The biomarker targets would capture key pathological features with proven additive prognostic and clinical utility, such as the local inflammatory response and tumour microenvironment. The Glasgow Microenvironment Score (GMS), first described in 2014, combines assessment of peritumoural inflammation at the invasive margin with quantification of tumour stromal content. Using H&E sections, the Klintrup-Mäkinen (KM) grade is determined by qualitative morphological assessment of the peritumoural lymphocytic infiltrate at the invasive margin and tumour stroma percentage (TSP) calculated in a semi-quantitative manner as a percentage of stroma within the visible field. The resulting three prognostic categories have direct clinical relevance: GMS 0 denotes a tumour with a dense inflammatory infiltrate/high KM grade at the invasive margin and improved survival; GMS 1 represents weak inflammatory response and low TSP associated with intermediate survival; and GMS 2 tumours are typified by a weak inflammatory response, high TSP, and inferior survival. The prognostic capacity of the GMS has been widely validated while its potential to guide chemotherapy has been demonstrated in a large phase 3 trial cohort. Here, we detail its journey from conception through validation to clinical translation and outline the future for this promising and practical biomarker.

Fluorescence-guided surgery (FGS) can play a key role in improving radical resection rates by assisting surgeons to gain adequate visualization of malignant tissue intraoperatively. Designed ankyrin repeat proteins (DARPins) possess optimal pharmacokinetic and other properties for in vivo imaging. This study aims to evaluate the preclinical potential of epithelial cell adhesion molecule (EpCAM)-binding DARPins as targeting moieties for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of cancer.

EpCAM-binding DARPins Ac2, Ec4.1, and non-binding control DARPin Off7 were conjugated to IRDye 800CW and their binding efficacy was evaluated on EpCAM-positive HT-29 and EpCAM-negative COLO-320 human colon cancer cell lines. Thereafter, NIRF and PA imaging of all three conjugates were performed in HT-29_luc2 tumor-bearing mice. At 24 h post-injection, tumors and organs were resected and tracer biodistributions were analyzed.

Ac2-800CW and Ec4.1-800CW specifically bound to HT-29 cells, but not to COLO-320 cells. Next, 6 nmol and 24 h were established as the optimal in vivo dose and imaging time point for both DARPin tracers. At 24 h post-injection, mean tumor-to-background ratios of 2.60 ± 0.3 and 3.1 ± 0.3 were observed for Ac2-800CW and Ec4.1-800CW, respectively, allowing clear tumor delineation using the clinical Artemis NIRF imager. Biodistribution analyses in non-neoplastic tissue solely showed high fluorescence signal in the liver and kidney, which reflects the clearance of the DARPin tracers.

Our encouraging results show that EpCAM-binding DARPins are a promising class of targeting moieties for pan-carcinoma targeting, providing clear tumor delineation at 24 h post-injection. The work described provides the preclinical foundation for DARPin-based bimodal NIRF/PA imaging of cancer.