Tumour budding as a prognostic biomarker in biopsies and resections of neoadjuvant-treated rectal adenocarcinoma.

BACKGROUND: Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment. METHODS AND RESULTS: A single-centre, retrospective cohort study was conducted. TB was assessed using the hot-spot International Tumour Budding Consortium (ITBCC) method and classified by the revised ITBCC criteria. Haematoxylin and eosin (H&E) and AE1/AE3 cytokeratin (CK) stains for ITB (intratumoural budding) in biopsies with PTB (peritumoural budding) and ITB (intratumoural budding) in resection specimens were compared. Logistic regression assessed budding as predictors of lymph node metastasis (LNM). Cox regression and Kaplan-Meier analyses investigated their utility as a predictor of disease-free (DFS) and overall (OS) survival. A total of 146 patients were included; 91 were male (62.3%). Thirty-seven cases (25.3%) had ITB on H&E and 79 (54.1%) had ITB on CK assessment of biopsy tissue. In univariable analysis, H&E ITB [odds (OR) = 2.709, 95% confidence interval (CI) = 1.261-5.822, P = 0.011] and CK ITB (OR = 2.165, 95% CI = 1.076-4.357, P = 0.030) predicted LNM. Biopsy-assessed H&E ITB (OR = 2.749, 95% CI = 1.258-6.528, P = 0.022) was an independent predictor of LNM. In Kaplan-Meier analysis, ITB identified on biopsy was associated with worse OS (H&E, P = 0.003, CK: P = 0.009) and DFS (H&E, P = 0.012; CK, P = 0.045). In resection specimens, CK PTB was associated with worse OS (P = 0.047), and both CK PTB and ITB with worse DFS (PTB, P = 0.014; ITB: P = 0.019). In multivariable analysis H&E ITB predicted OS (HR = 2.930, 95% CI = 1.261-6.809) and DFS (HR = 2.072, 95% CI = 1.031-4.164). CK PTB grading on resection also independently predicted OS (HR = 3.417, 95% CI = 1.45-8.053, P = 0.005). CONCLUSION: Assessment of TB using H&E and CK may be feasible in rectal cancer biopsy and post-neoadjuvant therapy-treated resection specimens and is associated with LNM and worse survival outcomes. Future management strategies for rectal cancer might be tailored to incorporate these findings.

Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME. METHODS: A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes. RESULTS: A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001). CONCLUSION: NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.

Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials.

BACKGROUND: This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). METHODS: A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. RESULTS: In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. CONCLUSION: This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.

Mechanical bowel preparation and antibiotics in elective colorectal surgery: network meta-analysis.

BACKGROUND: The use of intravenous antibiotics at anaesthetic induction in colorectal surgery is the standard of care. However, the role of mechanical bowel preparation, enemas, and oral antibiotics in surgical site infection, anastomotic leak, and other perioperative outcomes remains controversial. The aim of this study was to determine the optimal preoperative bowel preparation strategy in elective colorectal surgery. METHODS: A systematic review and network meta-analysis of RCTs was performed with searches from PubMed/MEDLINE, Scopus, Embase, and the Cochrane Central Register of Controlled Trials from inception to December 2022. Primary outcomes included surgical site infection and anastomotic leak. Secondary outcomes included 30-day mortality rate, ileus, length of stay, return to theatre, other infections, and side effects of antibiotic therapy or bowel preparation. RESULTS: Sixty RCTs involving 16 314 patients were included in the final analysis: 3465 (21.2 per cent) had intravenous antibiotics alone, 5268 (32.3 per cent) had intravenous antibiotics + mechanical bowel preparation, 1710 (10.5 per cent) had intravenous antibiotics + oral antibiotics, 4183 (25.6 per cent) had intravenous antibiotics + oral antibiotics + mechanical bowel preparation, 262 (1.6 per cent) had intravenous antibiotics + enemas, and 1426 (8.7 per cent) had oral antibiotics + mechanical bowel preparation. With intravenous antibiotics as a baseline comparator, network meta-analysis demonstrated a significant reduction in total surgical site infection risk with intravenous antibiotics + oral antibiotics (OR 0.47 (95 per cent c.i. 0.32 to 0.68)) and intravenous antibiotics + oral antibiotics + mechanical bowel preparation (OR 0.55 (95 per cent c.i. 0.40 to 0.76)), whereas oral antibiotics + mechanical bowel preparation resulted in a higher surgical site infection rate compared with intravenous antibiotics alone (OR 1.84 (95 per cent c.i. 1.20 to 2.81)). Anastomotic leak rates were lower with intravenous antibiotics + oral antibiotics (OR 0.63 (95 per cent c.i. 0.44 to 0.90)) and intravenous antibiotics + oral antibiotics + mechanical bowel preparation (OR 0.62 (95 per cent c.i. 0.41 to 0.94)) compared with intravenous antibiotics alone. There was no significant difference in outcomes with mechanical bowel preparation in the absence of intravenous antibiotics and oral antibiotics in the main analysis. CONCLUSION: A bowel preparation strategy with intravenous antibiotics + oral antibiotics, with or without mechanical bowel preparation, should represent the standard of care for patients undergoing elective colorectal surgery.

Comparing minimally invasive surgical and open approaches to pelvic exenteration for locally advanced or recurrent pelvic malignancies - Systematic review and meta-analysis.

INTRODUCTION: Pelvic exenteration (PE) is a complex multivisceral surgical procedure indicated for locally advanced or recurrent pelvic malignancies. It poses significant technical challenges which account for the high risk of morbidity and mortality associated with the procedure. Developments in minimally invasive surgical (MIS) approaches and enhanced peri-operative care have facilitated improved long term outcomes. However, the optimum approach to PE remains controversial. METHODS: A systematic literature search was conducted in accordance with PRISMA guidelines to identify studies comparing MIS (robotic or laparoscopic) approaches for PE versus the open approach for patients with locally advanced or recurrent pelvic malignancies. The methodological quality of the included studies was assessed systematically and a meta-analysis was conducted. RESULTS: 11 studies were identified, including 2009 patients, of whom 264 (13.1%) underwent MIS PE approaches. The MIS group displayed comparable R0 resections (Risk Ratio [RR] 1.02, 95% Confidence Interval [95% CI] 0.98, 1.07, p = 0.35)) and Lymph node yield (Weighted Mean Difference [WMD] 1.42, 95% CI -0.58, 3.43, p = 0.16), and although MIS had a trend towards improved towards improved survival and recurrence outcomes, this did not reach statistical significance. MIS was associated with prolonged operating times (WMD 67.93, 95% CI 4.43, 131.42, p < 0.00001) however, this correlated with less intra-operative blood loss, and a shorter length of post-operative stay (WMD -3.89, 955 CI -6.53, -1.25, p < 0.00001). Readmission rates were higher with MIS (RR 2.11, 95% CI 1.11, 4.02, p = 0.02), however, rates of pelvic abscess/sepsis were decreased (RR 0.45, 95% CI 0.21, 0.95, p = 0.04), and there was no difference in overall, major, or specific morbidity and mortality. CONCLUSION: MIS approaches are a safe and feasible option for PE, with no differences in survival or recurrence outcomes compared to the open approach. MIS also reduced the length of post-operative stay and decreased blood loss, offset by increased operating time.

Surgical management of abdominal desmoids: a systematic review and meta-analysis.

BACKGROUND: Desmoid tumours are benign fibromatous tumours arising from dysregulated myofibroblast proliferation within musculoaponeurotic structures. They can occur sporadically but more commonly are associated with genetic syndromes such as familial adenomatous polyposis (Sakorafas et al. in Surg Oncol 16(2):131-142, 2007) (FAP). Mutations in either the Wnt, ß-catenin or APC genes are 'key' triggers for the development of these tumours (Howard and Pollock in Oncol Ther 4(1):57-72, 2016). Classically, these tumours do not metastasise; however, they are associated with significant morbidity and mortality due to their infiltrative pattern and/or local invasion. Historically, surgical resection was the cornerstone of treatment. There remains paucity of data regarding outcomes following the surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity. OBJECTIVES: The aim of this review was to assess the current evidence for surgical management of abdominal desmoid tumours in terms of success, recurrence and morbidity. METHODS: A systematic search of articles in PubMed, EMBASE and The Cochrane Library databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the period from January 2000 to November 2020. RESULTS: Twenty-three studies were included, of which, 749 patients had surgical resection (696 for primary and 53 for recurrent desmoids), 243 patients (18.8%) were medically managed and 353 patients (27.3%) underwent surveillance. Median follow-up was 51.4 months (range 1-372). Six-hundred and ninety-six of the 749 resections (92.9%) underwent primary desmoid resection, with the remaining 53 (7.1%) undergoing resection for recurrence. One-hundred and two surgically managed patients (19%) developed a (re)recurrence, with mesenteric involvement the commonest site for recurrence (55%). When comparing recurrence post-surgery to progression following medical therapy, there was a trend towards better outcomes with surgery, with 25% of surgical patients having a recurrence versus 50.5% having progression with medical therapy [OR 0.40 (95% CI 0.06-2.70), p = 0.35]. Major morbidity following surgery was 4.4% (n = 33) with 2% (n = 14) mortality within 30 days of resection. CONCLUSION: The management of desmoids has considerable heterogeneity. Surgical resection for abdominal desmoids remains a valid treatment option in highly selective cases where negative margins can be obtained, with low major morbidity and/or mortality.

Surgery for synchronous and metachronous colorectal cancer: segmental or extensive colectomy?

PURPOSE: To assess the impact of surgical approach on morbidity, mortality, and the oncological outcomes of synchronous (SC) and metachronous (MC) colorectal cancer (CRC). METHODS: All patients undergoing resection for double location CRC (SC or MC) between 2006 and 2020 were included. The exclusion criteria were polyposis or SC located on the same side. RESULTS: Sixty-seven patients (age, 64.8 years; male, 78%) with SC (n = 41; 61%) or MC (n = 26; 39%) were included. SC was treated with segmental colectomy (right and left colectomy/proctectomy; n = 19) or extensive colectomy (subtotal/total colectomy or restorative proctocolectomy with pouch; n = 22). Segmental colectomy was associated with a higher incidence of anastomotic leakage (47.4 vs. 13.6%; p = 0.04) and a higher rate of medical morbidity (47.4 vs. 16.6%; p = 0.04). The mean number of lymph nodes harvested was similar. For MC, the second cancer was treated by iterative colectomy (n = 12) or extensive colectomy (n = 14) and there was no significant difference in postoperative outcomes between the two surgical approaches. The median follow-up period was 42.4 ± 29.1 months. The 5-year overall and disease-free survival of the SC and MC groups did not differ to a statistically significant extent. CONCLUSIONS: Extensive colectomy should be preferred for SC to reduce morbidity and improve the prognosis. In contrast, iterative colectomy can be performed safely for patients with MC.

A fundamental change emerging in locally advanced rectal cancer management: a case report.

Treatment of locally advanced rectal cancer remains a challenge in colorectal surgery. It has had an evolving landscape over the past three decades. Implementation of total neoadjuvant therapy (TNT) as a novel approach to management has begun globally but long-term outcomes and data analysis to identify optimal schedules are eagerly awaited. We report a case of locally advanced rectal cancer management in a young male with a complete pathological response to TNT.

The role of bariatric surgery in liver transplantation: timing and type.

INTRODUCTION: The rise in obesity worldwide has shifted the indications for liver transplantation (LT), with non-alcoholic steatohepatitis (NASH) being the second most common indication for transplantation. There remains an underestimation of cirrhosis being attributed to NASH. Bariatric surgery (BS) is a reliable solution to overcome obesity and its associated comorbidities. The role of BS in LT has been investigated by different studies; however, the type of BS and timing of LT need further investigation. METHODS: A systemic review examining the role of BS in LT patients was performed. After selection of the studies based on inclusion and exclusion criteria, data extraction was performed by two independent reviewers. Primary outcomes included patient and graft survival. RESULTS: From a total of 2374 articles, five met the prefined criteria. One hundred sixty-two patients had both BS + LT and 1426 underwent LT alone. The percentage of female patients in the BS + LT and LT cohorts was 75% and 35% respectively. The average age in BS + LT and LT cohorts was 43.05 vs. 56.22 years respectively. Patients undergoing BS had comparable outcomes in terms of overall patient survival, graft survival and post-operative morbidity compared to LT alone. When comparing BMI change in patients with prior versus simultaneous BS + LT, no significant difference was found. CONCLUSION: BS and LT patients achieve comparable outcomes to general LT populations. Further studies examining simultaneous BS + LT are needed to answer questions concerning patient selection and timing of surgery.

Risk of pancreatic ductal adenocarcinoma associated with carriage of BRCA1 and/or BRCA2 mutation: A systematic review and meta-analysis.

Germline BRCA1/2 mutations lead to malfunction of DNA damage repair pathways and predispose to pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to synthesise the available research on this topic. Four studies reporting risk ratio (RR) were included in the final meta-analysis to minimise misrepresenting our results by combining separate risk estimates. Our meta-analysis revealed a statistically significant increased risk of PDAC in BRCA carriers overall (RR: 2.65, 95% confidence interval: 1.43-4.91, p = 0.002).

Postoperative outcomes after laparoscopic or open gastrectomy. A national cohort study of 10,343 patients.

BACKGROUND: Laparoscopy for gastric cancer has not been as popular compared with other digestive surgeries, with conflicting reports on outcomes. The aim of this study focuses on the surgical techniques comparing open and laparoscopy by assessing the morbi-mortality and long-term complications after gastrectomy. METHODS: A retrospective study (2013-2018) was performed on a prospective national cohort (PMSI). All patients undergoing resection for gastric cancer with a partial gastrectomy (PG) or total gastrectomy (TG) were included. Overall morbidity at 90 post-operative days and long-term results were the main outcomes. The groups (open and laparoscopy) were compared using a propensity score and volume activity matching after stratification on resection type (TG or PG). RESULTS: A total of 10,343 patients were included. The overall 90-day mortality and morbidity were 7% and 45%, with reintervention required in 9.1%. High centre volume was associated with improved outcomes. There was no difference in population characteristics between groups after matching. An overall benefit for a laparoscopic approach after PG was found for morbidity (Open = 39.4% vs. Laparoscopy = 32.6%, p = 0.01), length of stay (Open = 14[10-21] vs. Laparoscopy = 11[8-17] days, p<0.0001). For TG, increased reintervention rate (Open = 10.8% vs. Laparoscopy = 14.5%, p = 0.04) and increased oesophageal stricture rate (HR = 2.54[1.67-3.85], p<0.001) were encountered after a laparoscopic approach. No benefit on mortality was found for laparoscopic approach in both type of resections after adjusted analysis. CONCLUSIONS: Laparoscopy is feasible for PG with a substantial benefit on morbidity and length of stay, however, laparoscopic TG should be performed with caution, with of higher rates of reintervention and oesophageal stricture.

Functional outcomes of patients undergoing successful redo surgery after failed primary colorectal or coloanal anastomosis for rectal cancer.

BACKGROUND: After a failure of a colorectal or coloanal anastomosis, redo anastomotic surgery aims to avoid the risk of permanent stoma but, overall, to provide a satisfactory functional result and quality of life. Very limited data exist regarding the long-term results after a successful redo anastomosis. The present study aimed to report the long-term functional outcomes and quality of life in patients after a successful redo colorectal anastomosis or coloanal anastomosis. METHODS: Between 2007 and 2018, all patients who had a successful restoration of bowel continuity after a failed primary anastomosis performed for a rectal cancer were included. Functional outcomes and quality of life were assessed using the low anterior rectal syndrome score and the Gastrointestinal Quality of Life Index. RESULTS: One hundred and twenty-seven patients were eligible for inclusion in this study, with long-term functional outcomes assessed in 73 patients (57%). After a median follow-up of 69 months, 31 patients presented no or minor low anterior rectal syndrome (42%), whereas 31 patients reported a major low anterior rectal syndrome (42%). A definitive stoma was confectioned in 11 patients (15%), despite the technical success of redo anastomosis due to poor functional results. Only operative interval <36 months was associated with a poor functional outcome (P = .001), whereas all other factors such as pelvic radiotherapy were not (P = .848). An absence of major low anterior rectal syndrome was the only factor associated with improved quality of life (P = .001). CONCLUSION: After successful redo colorectal anastomosis or coloanal anastomosis, good functional outcomes can be achieved in almost half of patients with a well-preserved quality of life but requires a prolonged postoperative period of rehabilitation.

Surgical approach for rectal cancer: A network meta-analysis comparing open, laparoscopic, robotic and transanal TME approaches.

BACKGROUND: The optimal approach for total mesorectal excision (TME) of rectal cancer remains controversial. AIM: To compare short- and long-term outcomes after open (OpTME), laparoscopic (LapTME), robotic (RoTME) and transanal TME (TaTME). METHODS: A systematic search of electronic databases was performed up to January 1, 2020 for randomized controlled trials (RCTs) comparing at least 2 TME strategies. A Bayesian arm-based random effect network meta-analysis (NMA) was performed, specifically, a mixed treatment comparison (MTC). RESULTS: 30 RCTs (and six updates) of 5586 patients with rectal cancer were included. No significant differences were identified in recurrence rates or survival rates. Operating time was shorter with OpTME (surface under the cumulative ranking curve [SUCRA] 0.96) compared to LapTME, RoTME and TaTME. Although OpTME was associated with the most blood loss (SUCRA 0.90) and had a slower recovery with increased length of stay (SUCRA 0.90) compared to the minimally invasive techniques, there was no difference in postoperative morbidity. OpTME was associated with a more complete TME specimen compared to LapTME (Risk Ratio [RR] 1.05, 95% Credible Interval [CrI] 1.01, 1.11), and TaTME had less involved CRMs (RR 0.173, 95% CrI 0.02, 0.76) versus LapTME. There were no differences between the modalities in terms of deep TME defects, DRM distance, or lymph node yield. CONCLUSIONS: While OpTME was the most effective TME modality for short term histopathological resection quality, there was no difference in long-term oncologic outcomes. Minimally invasive approaches enhance postoperative recovery, at the cost of longer operating times. Technique selection should be based on individual tumour characteristics and patient expectations, as well as surgeon and institutional expertise.

Laparoscopic rectal dissection preserves erectile function after ileal pouch-anal anastomosis: a two-centre study.

AIM: Few studies have been published on erectile function after ileal pouch-anal anastomosis (IPAA) and, unlike in women, male fertility after IPAA has never been assessed. The primary objective was to assess the impact of IPAA on erectile function. The secondary objective was to assess the impact of IPAA on male fertility. METHODS: All of the male patients who underwent IPAA in two university care centres between 2003 and 2017, aged 70 years or less at the time of operation, were included. Forty-eight per cent of the patients responded to the international index of erectile function, the Jorge-Wexner score and a fertility questionnaire. All demographic and perioperative data were prospectively collected. Fertility results were compared with those of a control group undergoing appendectomy, matched for age at the time of operation, desire for paternity and length of follow-up. RESULTS: One hundred and thirty-nine patients were included, among which 46 (33%) presented with erectile dysfunction and 14 (10%) with severe erectile dysfunction. Age older than 50 years (OR 0.27, 95% CI 0.12-0.62, P = 0.002) and rectal dissection performed by open surgery (OR 4.16, 95% CI 1.62-10.65, P = 0.003) were independent risk factors for erectile dysfunction. There was no infertility after IPAA compared with controls: indeed, 23 (16%) IPAA patients presented with pregnancy in their couple versus 27 (22%) controls (P = 0.29), whereas 36 (26%) IPAA patients and 34 (28%) controls (P = 0.80) expressed paternity desire. CONCLUSION: A total laparoscopic approach, including rectal dissection, should be preferred to preserve erectile function. Male fertility is not impaired after IPAA.

Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm.

Approximately one-third of all newly diagnosed colorectal cancer (CRC) is composed of rectal cancer, with the incidence rising in younger patients. The principal neoadjuvant treatments consist of neoadjuvant short-course radiotherapy and long-course chemoradiation. Locally advanced rectal cancer (LARC) is particularly challenging to manage given the anatomical constrictions of the pelvis and the risk for local recurrence. In appropriately treated patients, 5- and 10-year overall survival is estimated at 60 and 50%, respectively. The prognosis for LARC has improved in recent years with more access to screening, advances in surgical techniques, and perioperative care. Furthermore, the refinement of the multidisciplinary team with combined-modality management strategies has improved outcomes. These advancements have been augmented by significant improvements in the understanding of the underlying tumor biology. However, there are many instances where patient outcomes do not match those for their tumor stage and accurate prognostic information for individual patients can be difficult to estimate owing to the heterogeneous nature of LARC. Many new combinations of chemotherapy with radiotherapy, including total neoadjuvant therapy with targeted therapies that aim to diminish toxicity and increase survival, are being evaluated in clinical trials. Despite these advances, local recurrence and distant metastasis remain an issue, with one-third of LARC patients dying within 5 years of initial treatment. Although much of the new pathological, molecular genetics, and immunological biomarkers allow refinement in the classification and prognostication of CRC, the relative importance of each of these factors with regards to the development and progression of LARC remains incompletely understood. These factors are often insufficiently validated and seldom consider the individual characteristics of the host, the tumor and its location, the local available expertise, or the probable location of recurrence. Appreciating the mechanisms behind these differences will allow for a more comprehensive, personalized approach and more informed treatment options, leading to ultimately superior outcomes. This review aims to first outline the current multidisciplinary context in which LARC care should be delivered and then discuss how some key prognosticators, including novel histopathological, molecular genetics, and immunological biomarkers, might fit into the wider context of personalized LARC management in the coming years.

Prognostic value of tumor deposits in rectal cancer: A monocentric series of 505 patients.

BACKGROUND AND OBJECTIVES: It has been suggested that tumor deposits (TDs) may have a worse prognosis in rectal cancer compared with colonic cancer. The aim of this study was to assess TDs prognosis in rectal cancer. METHODS: Patients who underwent total mesorectum excision for rectal adenocarcinoma (2011-2016) were included. A case-matched analysis was performed to assess the accurate impact of TDs for each pN category after exclusion of synchronous metastasis. RESULTS: A total of 505 patients were included. TDs were observed in 99 (19.6%) patients, (pN1c = 37 [7.3%]). TDs were associated with pT3-T4 stage (P = .037), synchronous metastasis (P = .003), lymph node (LN) invasion (P = .041), vascular invasion (P = .001), and perineural invasion (P < .001). TD was associated with a worse 3-year disease-free survival (DFS) among pN0 (51.2% vs 79.8%; P < .001); pN1 patients (35.2% vs 70.1%; P = .004) but not among pN2 patients (37.5% vs 44.7%; P = .499). After matching, pN1c patients had a worse 3-year DFS compared with pN0 patients (58.6% vs 82.4%; P = .035) and a tendency toward a worse DFS among N1 patients (40.1% vs 64.2%; P = .153). DFS was worse when one TD was compared with one invaded LN (40.8% vs 81.3%; P < .001). CONCLUSION: In rectal cancer, TDs have a metastatic risk comparable to a pN2 stage which may lead to changes in adjuvant treatment.

Advanced colonic cancer with clinically suspected bladder invasion: Outcomes and prognosis from a multicentric study of 117 patients from the FRENCH research group.

BACKGROUND: Bladder invasion by colon cancer is rare; however, its management is still controversial. Our objective was to report outcomes and identify risk factors for local recurrence in colon cancer with clinically suspected bladder invasion. METHODS: We conducted a retrospective study in 23 centers in France. All patients who underwent colon surgery with bladder resection (2010-2017) were included. Metastatic and recurrent colon cancers were excluded. RESULTS: One hundred and seventeen patients (men = 73) were included. Partial cystectomy occurred in 108 patients (92.3%), with a total cystectomy occurring in 9 patients (7.7%). Neoadjuvant treatment was given to 31 patients (26.5%). Major morbidity was 20.5%. R0 resection rates were 87.2%. Histologically confirmed bladder invasion was present in 47%. Thirty-four patients were pN+, while 60 patients (51.3%) received adjuvant chemotherapy. Mean follow-up was 33.8 months. Three-year overall survival and disease-free survival were 82.9% and 59.5%. Rates of local recurrence and distant recurrence were 14.5% and 18.8%, respectively; the local recurrences (11/17; 65%) were in the bladder, while 4 of these patients had a bladder recurrence despite not having histologically confirmed bladder invasion at the index surgery. The rate of bladder recurrence after histologic bladder invasion was 13% (7/55), while the rate of bladder recurrence without primary bladder invasion was 7% (4/62) (P = .343). Neoadjuvant therapy, type of cystectomy, and adjuvant therapy did not influence local recurrence (P > .445 each). R1 bladder resections, when compared with a R0 bladder resections, were associated with an increased rate of local recurrence (63% vs 10%; P < .0001). CONCLUSION: Clinically suspected bladder invasion increases local recurrence even in the absence of histologically confirmed bladder invasion. Only complete resections with R0 margins decrease local recurrence. Careful, detailed postoperative surveillance is required, even without pathologic bladder invasion.

The Role of Exenterative Surgery in Advanced Urological Neoplasms.

Pelvic exenterative surgery is both complex and challenging, especially in the setting of locally recurrent disease. In recent decades, improved surgical techniques have facilitated more extensive resection of both locally advanced and recurrent pelvic malignancies, but its role in urological cancer surgery is highly selective. However, it remains an important part of the armamentarium for the management of bladder and prostate cancer cases where there is local invasion into adjacent organs or localized recurrence. Better diagnostics, reconstructive options and centralized care have reduced associated morbidity considerably, and it is still used rarely in palliative settings. Despite this, there is sparse prospective evidence reporting on long-term oncological or quality of life outcomes.