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.

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.

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.

CRP/Albumin Ratio: An Early Predictor of Steroid Responsiveness in Acute Severe Ulcerative Colitis.

INTRODUCTION: Identifying hospitalized patients with acute severe ulcerative colitis (ASUC) who will be refractory to corticosteroid therapy and require rescue therapy remains difficult. Hypoalbuminemia worsens with time during hospitalization and is associated with rapid clearance of and reduced response to infliximab (IFX) rescue. Early use of rescue therapy may therefore be more effective. Simple clinical and laboratory predictors of corticosteroid responsiveness would facilitate earlier use of rescue therapy. MATERIALS AND METHODS: Retrospective study of a prospectively maintained database of 3600 patients attending a single center was conducted. Patients with histologically confirmed ulcerative colitis admitted with ASUC over a 5-year period from January 2010 to December 2014 were identified. All patients initially received intravenous corticosteroids. Patient demographics were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during admission. Receiver operating characteristic statistics were used to determine the optimal stool frequency, CRP, albumin, and CRP/albumin ratio (CAR) to predict steroid response. RESULTS: A total of 124 ASUC patients were admitted during a 5-year period. Median follow-up was 2.3 years. A total of 62 patients (50%) were steroid responsive, 55 patients (44%) received rescue IFX, 22 patients (18%) required colectomy within 30 days of admission, whereas a further 14 (11%) required colectomy during follow-up. By receiver operating characteristic statistics, day 3 CAR was a more accurate marker of steroid responsiveness than day 3 CRP or day 3 albumin alone [area under curve=0.75 (P<0.001)]. The optimal CAR to predict response to steroids on day 3 was 0.85 (sensitivity 70%, specificity 76%). When combined with D3 stool frequency, specificity improved to 83%. If at day 3, CAR was >0.85 and stool frequency was >3, the relative risk of steroid nonresponse was significantly raised at 3.9 (95% confidence interval, 2.1-7.2). CONCLUSIONS: Raised D3 CAR is an early predictor of steroid-refractory ASUC. When combined with D3 stool frequency, its predictive ability improves. In patients with predicted steroid nonresponse, early introduction of rescue IFX at this stage may be more effective, before serum albumin falls profoundly.

Impact of preoperative immunosuppressive agents on postoperative outcomes in Crohn's disease.

BACKGROUND: Immunosuppressive agents are essential in the management of Crohn's disease. Their safety before surgery, however, is still controversial. OBJECTIVE: The aim of this study is to evaluate whether the preoperative use of immunosuppressive agents is associated with increased postoperative complications in Crohn's disease. DATA SOURCES: A literature search of PubMed, EMBASE, and The Cochrane Library was undertaken in February 2013. STUDY SELECTION: All studies describing postoperative outcomes of patients undergoing bowel resections for Crohn's disease were included if they reported data comparing patients on preoperative immunosuppressive agents with an appropriate control group. INTERVENTIONS: All immunosuppressive agents used to manage Crohn's disease were studied. MAIN OUTCOME MEASURES: The main outcomes measured were total overall complications and total infectious complications. RESULTS: Twenty-one eligible studies (20 retrospective and 1 prospective) with 6899 patients were included. When individual studies were examined, only 2/14 (14%), 4/13 (31%), and 1/8 (13%) studies found an association between postoperative complications and preoperative anti-tumor necrosis factor agents, corticosteroids, and thiopurines. In meta-analyses, patients on anti-tumor necrosis factor agents (risk ratio, 1.29; 95% CI, 1.07-1.55), and corticosteroids (risk ratio, 1.55; 95% CI, 1.23-1.95) were found to have a higher risk of postoperative infectious complications. The use of anti-tumor necrosis factor agents was also significantly associated with wound infection (risk ratio, 1.62; 95% CI, 1.12-2.34) and septic shock (risk ratio, 1.81; 95% CI, 1.03-3.17). There was no association between the use of thiopurines or combined immunomodulator drugs and postoperative complications. LIMITATIONS: Most studies were retrospectively designed, and there were large variations in the patient populations and outcome definitions. CONCLUSIONS: Patients with Crohn's disease on preoperative immunosuppressive agents are at higher risk for complications. Both corticosteroids and anti-tumor necrosis factor agents may increase the risk of infections and septic shock. A preoperative drug-free interval, when feasible, might be considered to reduce the risk of infections. The adoption of any operative strategies that modify these outcomes may additionally counter these risks.

Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients.

BACKGROUND: Ileal pouch anal anastomosis (IPAA) is the treatment of choice for chronic, medically refractory mucosal ulcerative colitis, indeterminate colitis, familial adenomatous polyposis (FAP), and a select group of patients with Crohn's disease. AIM: : We report outcomes, complications, and quality of life (QOL) in a cohort of 3707 patients treated at our institution from January 1984 to March 2010. METHODS: Data were collected from a prospectively maintained database and chart review of 3707 consecutive primary IPAA cases. Patient demographics, postoperative complications, functional outcomes, and QOL data were available. Follow-up consisted of clinical examination with assessment of pouch function and QOL. RESULTS: A total of 3707 patients underwent primary pouch and 328 underwent redo pouch surgery. Postoperative histopathological diagnoses were mucosal ulcerative colitis (n = 2953, 79.7%), indeterminate colitis (n = 63, 1.7%), FAP (n = 223, 6%), Crohn's disease (n = 150, 4%), cancer/dysplasia (n = 97, 2.6%), and others (n = 221, 6.0%). Early perioperative complications were encountered in 33.5% of patients with a mortality rate of 0.1%. Excluding pouchitis, late complications were experienced by 29.1% of patients. Of those patients who had IPAA at our institution, pouch failure occurred in 197 patients (5.3%). During a median follow-up of 84 months, 119 patients (3.2%) required excision of the pouch, 32 (0.8%) had a nonfunctioning pouch, and 46 patients (1.2%) had redo IPAA. Functional outcomes and QOL were good or excellent in 95% of patients and similar in each histopathological subgroup. CONCLUSIONS: IPAA is an excellent option for patients with MUC, IC, FAP, and select patients with Crohn's disease.

Restorative procedures in colonic crohn disease.

Surgical management for refractory Crohn colitis often involves creation of a temporary or permanent stoma. Traditionally, the procedure of choice has been a total proctocolectomy with permanent ileostomy. However, restorative procedures that help to avoid a permanent stoma are being used with more frequency. In this article, the authors will address these procedures, including colocolonic anastomosis, ileorectal anastomosis, ileal pouch rectal anastomosis, and ileal pouch anal anastomosis. Factors that may influence one's decision to perform these procedures, such as patient age and nutritional status, medical comorbidities, sphincter function, desire to avoid a permanent ostomy, and prior medical therapy, will be discussed. Functional outcomes regarding these procedures will also be described. One should keep in mind that surgery does not cure Crohn disease and that postoperative long-term management is essential in preventing progression or recurrence of disease.

The Impact of Bariatric Surgery on the Incidence of Colorectal Cancer in Patients with Obesity-a Systematic Review and Meta-analysis of Registry Data.

PURPOSE: Cancer and obesity represent two of the most significant global health concerns. The risk of malignancy, including colorectal cancer (CRC), increases with obesity. The aim of this study was to perform a systematic review and meta-analysis to determine the value of bariatric surgery in reducing CRC risk in patients with obesity using registry data. MATERIALS AND METHODS: A systematic review and meta-analysis were performed as per PRISMA guidelines. The risk of CRC was expressed as a dichotomous variable and reported as odds ratios (OR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. A multi-treatment comparison was performed, examining the risk reduction associated with existing bariatric surgery techniques. Analysis was performed using RevMan, R packages, and Shiny. RESULTS: Data from 11 registries including 6,214,682 patients with obesity were analyzed. Of these, 14.0% underwent bariatric surgery (872,499/6,214,682), and 86.0% did not undergo surgery (5,432,183/6,214,682). The mean age was 49.8 years, and mean follow-up was 5.1 years. In total, 0.6% of patients who underwent bariatric surgery developed CRC (4,843/872,499), as did 1.0% of unoperated patients with obesity (54,721/5,432,183). Patients with obesity who underwent bariatric surgery were less likely to develop CRC (OR: 0.53, 95% CI: 0.36-0.77, P < 0.001, I2 = 99%). Patients with obesity undergoing gastric bypass surgery (GB) (OR: 0.513, 95% CI: 0.336-0.818) and sleeve gastrectomy (SG) (OR: 0.484, 95% CI: 0.307-0.763) were less likely to develop CRC than unoperated patients. CONCLUSION: At a population level, bariatric surgery is associated with reduced CRC risk in patients with obesity. GB and SG are associated with the most significant reduction in CRC risk. PROSPERO REGISTRATION: CRD42022313280.

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.

Intestinal stomas: indications, management, and complications.

The ability to appropriately construct and care for an ostomy is crucial to good colorectal surgical practice. Enterostomal therapy is critical to the successful management of ostomies and their complications. Although associated with morbidity, a well-constructed ostomy can provide our patients with a good, durable QoL.

Treatment for Constipation-An Online Search. Readability and Quality of Online Patient Resources.

Aim: To evaluate the readability and quality of online patient information regarding treatment for constipation in the English language. Methods: By utilizing the Google © website, the keyword "treatment for chronic constipation" was searched. Each webpage was assessed by 2 authors independently for readability using both the Gunning Fog Index (GFI) and the Flesch Reading Ease Score (FRES). The quality of the information produced on each individual website was assessed using the DISCERN instrument. Other parameters that were recorded included the country of origin, the organization type, and whether or not the website was issued a Health on the Net (HoN) certificate. Results: This study identified a mean GFI score of 13.2 and a mean FRES score of 48.9. This result indicates poor overall readability. A mean DISCERN score of 37.9 was produced, indicating an overall weak quality of online information on this topic. This study indicated that parameters such as website organization type and the presence or absence of HoN certification impacted the quality of the information websites on this topic. Conclusion: This study indicated a poor level of quality and readability of online information on the topic of chronic constipation treatment. Further resources should be directed towards improving website readability and quality. Patients may be advised that if they wish to access online information on this topic, websites that display HoN accreditation will likely produce higher quality information.

Surgical Strategies to Reduce Postoperative Recurrence of Crohn's Disease After Ileocolic Resection.

Postoperative recurrence after ileocaecal resection for fibrostenotic terminal ileal Crohn's disease is a significant issue for patients as it can result in symptom recurrence and requirement for further surgery. There are very few modifiable factors, aside from smoking cessation, that can reduce the risk of postoperative recurrence. Until relatively recently, the surgical technique used for resection and anastomosis had little or no impact on postoperative recurrence rates. Novel surgical techniques such as the Kono-S anastomosis and extended mesenteric excision have shown promise as ways to reduce postoperative recurrence rates. This manuscript will review and discuss the evidence regarding a range of surgical techniques and their potential role in reducing disease recurrence. Some of the techniques have been shown to be associated with significant benefits for patients and have already been integrated into the routine clinical practice of some surgeons, while other techniques remain under investigation. Current techniques such as resection of the mesentery close to the intestine and stapled side to side anastomosis are being challenged. It is looking more likely that surgeons will have a major role to play when it comes to reducing recurrence rates for patients undergoing ileocaecal resection for Crohn's disease.

A systematic review and meta-analysis comparing surgical and oncological outcomes of upper rectal, rectosigmoid and sigmoid tumours.

AIM: Management paradigms for tumours from the sigmoid colon to the lower rectum vary significantly. The upper rectum (UR) represents the transition point both anatomically and in treatment protocols. Above the UR is clearly defined and managed as colon cancer and below is managed as rectal cancer. This study compares outcomes between sigmoid, rectosigmoid and UR tumours to establish if differences exist in operative and oncological outcomes. METHODS: Electronic databases were searched for published studies with comparative data on peri-operative and oncological outcome for upper rectal and sigmoid/rectosigmoid (SRS) tumours treated without neoadjuvant radiation. The search adhered to PRISMA guidelines (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models. RESULTS: Seven comparative series examined outcomes in 4355 patients. There was no difference in ASA grade (OR, 1.28; 95% CI, 0.99-1.67; P = 0.06), T3/T4 tumours (OR, 1.24; 95% CI, 0.95-1.63; P = 0.12), or lymph node positivity (OR, 0.97; 95% CI, 0.70-1.36; P = 0.87). UR cancers had higher rates of operative morbidity (OR, 0.72; 95% CI, 0.55-0.93; P = 0.01) and anastomotic leak (OR, 0.47; 95% CI, 0.31-0.71; P = 0.0004). There was no difference in local recurrence (OR, 0.63; 95% CI, 0.37-1.08; P = 0.10). SRS tumours had lower rates of distant recurrence (OR, 0.83; 95% CI, 0.68-1.0; P = 0.05). Rectosigmoid operative and cancer outcomes were closer to UR than sigmoid. CONCLUSIONS: Based on existing data, UR and rectosigmoid tumours have higher morbidity, leak rates and distant recurrence than more proximal tumours.

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.

Tumor Budding and PDC Grade Are Stage Independent Predictors of Clinical Outcome in Mismatch Repair Deficient Colorectal Cancer.

Mismatch repair deficient (dMMR) colorectal cancer (CRC) despite its association with poor histologic grade often has improved prognosis compared with MMR proficient CRC. Tumor budding and poorly differentiated clusters (PDCs) may predict metastatic potential of colorectal adenocarcinoma (CRC). In addition, their assessment may be more reproducible than the evaluation of other histopathologic parameters. Therefore, we wished to determine their potential as prognostic indicators in a cohort of dMMR CRC patients relative to histologic grade. We investigated the predictive value of conventional WHO grade, budding, PDC grade and other histopathologic parameters on the presence of lymph node metastasis (LNM) and clinical outcome in 238 dMMR CRCs. MMR status was determined by immunohistochemistry for the mismatch repair proteins hMLH1, hMSH2, hMSH6, and hPMS2. Tumor budding and PDCs were highly correlated (r=0.701; P<0.000). Both budding and PDC grade were associated with WHO grade, perineural invasion, lympho-vascular invasion, and extramural vascular invasion, and the presence of LNM in dMMR CRC (P<0.009). Independent predictors of LNM were PDC grade (odds ratio, 4.12; 95% confidence interval [CI], 1.69-10.04; P=0.011) and EMVI (odds ratio, 3.81; 95% CI, 1.56-9.19; P<0.000). Only pTstage (hazard ratio [HR], 4.11; 95% CI, 1.48-11.36; P=0.007) and tumor budding (HR, 2.99; 95% CI, 1.72-5.19; P<0.000) were independently associated with worse disease-free survival (DFS). If tumor budding was excluded from the model, PDC grade became significant for DFS (HR, 2.34; 95% CI, 1.34-4.09; P=0.003). WHO Grade does not independently correlate with clinical outcome in dMMR CRC. PDC grade and extramural vascular invasion are independent predictors of LNM. Tumor budding and pTstage are the best predictors of DFS. If tumor budding cannot be assessed, PDC grade may be used as a prognostic surrogate.

Inclusion of the Mesentery in Ileocolic Resection for Crohn's Disease is Associated With Reduced Surgical Recurrence.

BACKGROUND AND AIMS: Inclusion of the mesentery during resection for colorectal cancer is associated with improved outcomes but has yet to be evaluated in Crohn's disease. This study aimed to determine the rate of surgical recurrence after inclusion of mesentery during ileocolic resection for Crohn's disease. METHODS: Surgical recurrence rates were compared between two cohorts. Cohort A [n = 30] underwent conventional ileocolic resection where the mesentery was divided flush with the intestine. Cohort B [n = 34] underwent resection which included excision of the mesentery. The relationship between mesenteric disease severity and surgical recurrence was determined in a separate cohort [n = 94]. A mesenteric disease activity index was developed to quantify disease severity. This was correlated with the Crohn's disease activity index and the fibrocyte percentage in circulating white cells. RESULTS: Cumulative reoperation rates were 40% and 2.9% in cohorts A and B [P = 0.003], respectively. Surgical technique was an independent determinant of outcome [P = 0.007]. Length of resected intestine was shorter in cohort B, whilst lymph node yield was higher [12.25 ± 13 versus 2.4 ± 2.9, P = 0.002]. Advanced mesenteric disease predicted increased surgical recurrence [Hazard Ratio 4.7, 95% Confidence Interval: 1.71-13.01, P = 0.003]. The mesenteric disease activity index correlated with the mucosal disease activity index [r = 0.76, p < 0.0001] and the Crohn's disease activity index [r = 0.70, p < 0.0001]. The mesenteric disease activity index was significantly worse in smokers and correlated with increases in circulating fibrocytes. CONCLUSIONS: Inclusion of mesentery in ileocolic resection for Crohn's disease is associated with reduced recurrence requiring reoperation.