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For patients with locally advanced rectal cancer (LARC), a pathological complete response (pCR) after pre-operative chemoradiotherapy (CRT) does not necessarily indicate a cure. Acellular mucin pools are often seen in patients with pCR. However, the clinical significance of acellular mucin pools in this group of patients remains unknown. This was a retrospective analysis of 225 LARC patients who achieved pCR following CRT and total mesorectal resection from 2011 to 2018. The outcomes of 5-year disease-free survival (DFS), 5-year overall survival (OS) and 5-year distant metastasis-free survival (DMFS) were compared in patients with versus without acellular mucin pools. Among 225 pCR patients, acellular mucin pools could be identified in 56 (24.9%) patients, and recurrence occurred in 30 (13.3%) patients at 5 years. Distant recurrence was seen in 13 (23.2%) patients with acellular mucin pools and in 17 (10.1%) patients without acellular mucin pools. Patients with acellular mucin pools versus those without had poorer DFS (76.8 versus 89.9%, P = 0.010) and OS (87.5 versus 97.0%, P = 0.004) at 5 years. The presence of acellular mucin pools was the independent parameter that remained significant for DFS [hazard ratio (HR) = 3.904; 95% confidence interval (CI) = 1.342-11.356; P = 0.047] and OS (HR = 3.850; 95% CI = 1.214-12.213; P = 0.022) on multivariate analysis. A total of 17 patients demonstrated acellular mucin pools in primary tumour and lymph nodes. Subgroup analysis demonstrated that pCR patients with acellular mucin pools in primary tumour and lymph nodes were more likely to develop distant metastasis compared to pCR patients with acellular mucin pools only in primary tumour (47.1 versus 12.8%, P = 0.005). In summary, acellular mucin pools in LARC patients with pCR after CRT might represent a sign of invasive tumour biology and significantly shorten the prognosis of patients, especially in patients with acellular mucin pools in lymph nodes.

Heat shock proteins (HSPs) are a large molecular chaperone family classified by their molecular weights, including HSP27, HSP40, HSP60, HSP70, HSP90, and HSP110. HSPs are likely to have antiapoptotic properties and participate actively in various processes such as tumor cell proliferation, invasion, metastases, and death. In this review, we discuss comprehensively the functions of HSPs associated with the progression of colorectal cancer (CRC) and metastasis and resistance to cancer therapy. Taken together, HSPs have numerous clinical applications as biomarkers for cancer diagnosis and prognosis and potential therapeutic targets for CRC and its related metastases.

Robotic surgery for rectal cancer is gaining popularity, but persuasive evidence on reducing surgical trauma is still lacking. This study compared robotic and laparoscopic abdominoperineal resections (APRs) for the risk of postoperative complications in low rectal cancer.Between December 2013 and 2016, patients with rectal cancer ≤5 cm from anal verge, cT1-T3 N0-1, or ycT1-T3 Nx stage, and no distant metastases were enrolled in a single-center, randomized, controlled trial. Eligible patients were randomly allocated to robotic or laparoscopic APRs at 1:1 ratio. The primary outcome was 30-day postoperative complication rate (Clavien-Dindo grade II or higher) of the intent-to-treat population. The trial registration number is NCT01985698 (http://www.gov).Totally 347 eligible patients were enrolled: 174 in robotic and 173 in laparoscopic group. Robotic APRs significantly reduced postoperative complication rate (13.2% vs. 23.7%, p = 0.013), also reduced open conversion rate (0% vs. 2.9%, p = 0.030), intraoperative hemorrhage (median, 100 vs. 130 ml; p 0.001), 30-day readmission rate (2.3% vs. 6.9%; p = 0.044), postoperative hospital stay (median, 5.0 vs. 7.0 days; p 0.001), and improved urinary and sexual function. No significant difference was observed in long-term oncological outcomes.Compared with laparoscopic APRs, robotic APRs significantly reduced surgical trauma and promoted postoperative recovery.

The aim of this study was to identify risk factors associated with the low anterior resection syndrome (LARS) and to construct a nomogram capable of predicting the risk of LARS in patients who undergo rectal cancer resection.About 538 patients who had undergone anterior resection were recruited as a development set. In addition, 114 patients with rectal cancer were analysed as a validation set to test the new nomogram. Patients in the development set were grouped into two separate cohorts: those with major LARS and those with minor or no LARS. Multiple logistic regression was conducted to detect risk factors for major LARS.The prevalence of major LARS was 40.7%, of minor LARS was 28.6% and the proportion with no LARS was 30.7% in the development set. In multivariate analysis, female gender, preoperative chemoradiation, low tumour height, diverting ileostomy, postoperative anastomotic leakage were shown to be independently associated with major LARS occurring in patients after rectal cancer resection. The area under the curve (AUC) values of the nomogram were 0.726 (95% CI: 0.682-0.769) and 0.750 (95% CI: 0.655-0.845) in the development and validation sets, respectively. The calibration curves and Hosmer-Lemeshow goodness of fit tests showed that the model was acceptably accurate.A nomogram model based on risk factors could be valuable as a predictor of the probability of major LARS after rectal cancer surgery, and provides a guide that clinical staff can use to take preventive measures for high-risk patients.

The aim was to evaluate the efficacy of transanal drainage tube (TDT) placement for preventing anastomotic leakage after low anterior resection for rectal cancer.PubMed, the Cochrane Central Register of Controlled Trials, Embase and ClinicalTrials.gov databases were searched up to October 2021. Studies comparing outcomes following low anterior resection with or without TDT were included. The primary outcomes measured were anastomotic leakage rate, reoperation rate and anastomotic bleed rate.Three randomized controlled trials (RCTs) and 16 observational studies (prospective or retrospective) involving 4560 patients satisfied the basic inclusion criteria. In RCTs, a TDT was associated with no statistically significant differences in anastomotic leakage (OR = 0.67, 95% CI 0.42-1.05, P = 0.08), reduction in reoperation (OR = 0.11, 95% CI 0.03-0.51, P = 0.004) and increased anastomotic bleeding rate (OR = 2.36, 95% CI 1.11-5.01, P = 0.03). In observational studies, a TDT was associated with significant reduction in anastomotic leak (OR = 0.44, 95% CI 0.30-0.64, P 0.0001) and reoperation (OR = 0.47, 95% CI 0.33-0.69, P 0.0001), with no statistically significant differences in anastomotic bleeding (OR = 1.30, 95% CI 0.20-8.30, P = 0.78).In RCTs, a TDT for rectal cancer was correlated with no detectable differences in anastomotic leakage and with an increased risk of anastomotic bleeding. In observational studies, a TDT was correlated with reduction in anastomotic leakage and no detectable differences in anastomotic bleeding. Both RCTs and observational studies demonstrated a comparable reduction in reoperation rate with TDT. These data in aggregate indicated that TDTs may not show superiority but emphasized differences between RCT and observational data.

Neoadjuvant long course chemoradiotherapy (NLCRT) for rectal cancer can result in complete pathological response (pCR). In 2017, we started offering patients who had a complete clinical response (cCR), a choice between total mesorectal excision (TME) and an intensive surveillance or 'watch and wait' (WW) program. We report the early outcomes of this prospective study.All patients undergoing NLCRT from 2017 to 2019 were included. All patients were restaged at 8 weeks, and those who had a cCR were offered TME or WW.Of 59 patients who underwent NLCRT, 55 had restaging. Eleven of these patients had a cCR (20%). Three chose to have TME and all had a pCR. Eight were enrolled in WW. Two patients were diagnosed with local regrowth and underwent TME at 7 and 17 months after NLCRT. A further nine patients, who were surgically unfit or refused TME, and had an excellent response to NLCRT, but one that did not reach criteria for a cCR, were also managed with WW. Of these, two patients developed regrowth with distant metastases. From 2017 to 2019, of the 17 patients who were managed with a WW approach, 13 patients have remained regrowth free after a median of 28 (13-58) months of WW.Preliminary findings suggest management with WW, following cCR, may be a safe alternative to TME. There have so far been no instances of distant failure, and those with cCR that had regrowth, were identified early and successfully managed with salvage TME.

Isolated seminal vesicle invasion is a rare occurrence in patients with locally advanced rectal cancers. This study describes the surgical technique and the perioperative outcomes of minimally invasive 'en-bloc' seminal vesicle excision, preserving the bladder and the prostate.A retrospective review of 23 consecutive patients who underwent minimally invasive, en-bloc resection of seminal vesicles for locally advanced, non-metastatic rectal adenocarcinoma between May 2016 and November 2021. Perioperative outcomes and short-term oncological outcomes were defined.Eighteen patients underwent a laparoscopic procedure while five received a robotic resection. All patients received preoperative radiation with or without consolidation chemotherapy. The median age was 42 years (range 20-64 years) and the median hospital stay was 8 days (range 3-19 days), respectively. Serious complications (Clavien-Dindo ≥ IIIb) were seen in six patients (26.1%). Two patients (8.7%) had an involved circumferential resection margin. At a median follow up of 19 months (range 2-52 months), four patients developed recurrences. The 2-year overall and disease-free survival was 84.4% and 73.6%, respectively.Minimally invasive, en-bloc resection of one or both seminal vesicles for locally advanced rectal adenocarcinoma, is feasible in a select group of patients with acceptable morbidity and short-term outcomes.

There has been limited evaluation of health-related quality of life (HRQOL) in rectal cancer patients receiving neoadjuvant chemoradiotherapy. HRQOL outcomes in the National Surgical Adjuvant Breast and Bowel Project R-04 trial are examined in this article.Between 2004 and 2010, R-04 patients were invited to enroll in the HRQOL substudy, with questionnaires administered before randomization, after completion of chemoradiotherapy, and 1-year after surgery. HRQOL measures included: Functional Assessment of Cancer Therapy for colorectal cancer (FACT-C); Short Form-36v.2 Vitality scale; a treatment-specific symptom scale; and the FACT neurotoxicity scale. A 5-year postsurgery assessment was added to the protocol in 2012. Mixed-effects models examined neoadjuvant therapy treatment effects in the 1-year sample and models that explored associations of host factors and treatment impact on 5-year HRQOL.A total of 1373 patients completed baseline HRQOL and at least one additional assessment. The average age was 58 years (range, 23-85 years), male (68%), and 59% Stage II. There were no statistically significant differences in HRQOL outcomes by treatment arm, but HRQOL worsened from baseline to postneoadjuvant chemoradiotherapy, with statistically significant effect sizes changes ranging from 0.6 (Vitality) to 0.9 (FACT-C Trial Outcome Index). Neurotoxicity was greater in the oxaliplatin-treated groups. Obese/overweight patients had statistically significantly worse FACT-C Trial Outcome Index scores than did underweight/normal weight groups. At 5 years, younger patients and those with normal baseline weight had statistically significantly better physical function scores and older patients had better mental health outcomes.HRQOL did not differ across the four R-04 treatment arms; however, host factors explained significant variation in posttreatment HRQOL.gov: NCT00058474 (https://ClinicalTrials.gov/ct2/show/NCT00058474).This article reports on the health-related quality of life (HRQOL) outcomes of patients treated with four different chemotherapy regimens combined with radiation in rectal cancer patients before definitive surgical treatment. There were no significant differences in HRQOL by treatment regimen, but all patients experienced decreased vitality (energy) and physical functioning. By 1 year after treatment, most patients had returned to pretreatment vitality and physical functioning, with the exception of increased neurotoxicity. In a subsample of patients assessed at 5 years after surgery, physical function was better in those who at pretreatment were younger, normal weight, and had better performance status. Mental function was better in those who at pretreatment were older and had better performance status.

Whether minimally invasive surgery (MIS) is safe and effective for patients with N2M0 colorectal cancer (CRC) remains controversial. This study aimed to compare short- and long-term outcomes between MIS and open surgery (Open) groups for patients with pathological (p)N2M0 CRC, and evaluate the oncological outcomes of MIS for pN2M0 CRC.We retrospectively analyzed 125 consecutive patients with pN2M0 CRC who underwent curative surgery between 2010 and 2017, using propensity score-matching (PSM) analysis.Median follow-up was 59.4 months. After PSM, we enrolled 68 patients (n = 34 in each group). The conversion rate was 9.6% for the entire patient cohort and 5.9% for the matched cohort. In colon cancer (CC), short-term outcomes were similar between groups. On the other hand, in rectal cancer (RC), estimated blood loss, rate of anastomosis leakage, and length of postsurgical stay were lower in the MIS group than the Open group. R0 resection was achieved in all patients with MIS. No surgical mortality was encountered in any group. No significant differences were found between groups in terms of 3-year local recurrence rate, overall survival, cancer-specific survival, or recurrence-free survival among the entire patient cohort or the matched cohort, regardless of the primary tumor site (CC or RC). Surgical approach (MIS vs Open) had no significant influence on survival outcomes.MIS is a safe and effective option for patients with pN2M0 CRC, with acceptable short- and long-term outcomes comparable to the open approach. MIS can be considered for patients with pN2M0 CRC.

Obesity is a growing global public health problem. More than half the European and North American population is overweight or obese. Colon and rectum cancers are still the second leading cause of cancer death worldwide, and epidemiological data support an association between obesity and colorectal cancers (CRCs).To review the literature on CRC epidemiology in obese subjects, assessing the effects of obesity, including childhood or maternal obesity, on CRC, diagnosis, management, and prognosis, and discussing targeted prophylactic measures.We searched PubMed for obesity/overweight/metabolic syndrome and CRC. Other key words included 'staging', 'screening', 'treatment', 'weight loss', 'bariatric surgery' and 'chemotherapy'.In Europe, about 11% of CRCs are attributed to overweight and obesity. Epidemiological data suggest that obesity is associated with a 30%-70% increased risk of colon cancer in men, the association being less consistent in women. Visceral fat or abdominal obesity seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/mDespite a growing body of evidence linking obesity to CRC, many questions remain unanswered, including whether we should screen patients with obesity earlier or propose prophylactic bariatric surgery for certain patients with obesity.

Total mesorectal excision (TME) is the gold standard treatment for rectal cancer. Although TME has managed to decrease the rates of local recurrence after rectal cancer resection, local recurrence is still recorded at varying rates. The present study aimed to validate the PREDICT score in the prediction of local recurrence of rectal cancer after TME with curative intent.This was a retrospective multicenter study on patients with nonmetastatic low or middle rectal cancer who underwent TME. The total PREDICT score was calculated for every patient and related to the onset of local recurrence. According to the final score, patients were allocated to one of three risk groups: low, moderate, and high, and the rates of local recurrence in each group were calculated and compared.The present study included 262 patients (50.4% males) with a mean age of 47.1 years. The overall local recurrence rate was 12.6%. 29.4% of patients were in the low-risk group, 63.7% in the moderate-risk group, and 6.9% in the high-risk group. The local recurrence rate was 3.9% (95% confidence interval [CI]: 0.8-10.9) in the low-risk group, 13.2% (95% CI: 8.4-19.3) in the moderate risk group, and 44.4% (95% CI: 21.5-69.2) in the high-risk group (p 0.0001). The sensitivity of the PREDICT score was 72.7%, the specificity was 88.1%, and the accuracy was 86.3%.The PREDICT score had good diagnostic accuracy in the prediction of local recurrence after TME and a good discriminatory ability in the differentiation between patients at different risks to develop local recurrence.

Recent studies showed the potential of MRI-based deep learning (DL) for assessing treatment response in rectal cancer, but the role of MRI-based DL in evaluating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation remains unclear.To develop a DL method based on T2-weighted imaging (T2WI) and clinical factors for noninvasively evaluating KRAS mutation in rectal cancer.Retrospective.A total of 376 patients (108 women [28.7%]) with histopathology-confirmed rectal adenocarcinoma and KRAS mutation status.A 3 T, turbo spin echo T2WI and single-shot echo-planar diffusion-weighted imaging (b = 0, 1000 sec/mmA clinical model was constructed with clinical factors (age, gender, carcinoembryonic antigen level, and carbohydrate antigen 199 level) and MRI features (tumor length, tumor location, tumor stage, lymph node stage, and extramural vascular invasion), and two DL models based on modified MobileNetV2 architecture were evaluated for diagnosing KRAS mutation based on T2WI alone (image model) or both T2WI and clinical factors (combined model). The clinical usefulness of these models was evaluated through calibration analysis and decision curve analysis (DCA).Mann-Whitney U test, Chi-squared test, Fisher's exact test, logistic regression analysis, receiver operating characteristic curve (ROC), Delong's test, Hosmer-Lemeshow test, interclass correlation coefficients, and Fleiss kappa coefficients (P 0.05 was considered statistically significant).All the nine clinical-MRI characteristics were included for clinical model development. The clinical model, image model, and combined model in the testing cohort demonstrated good calibration and achieved areas under the curve (AUCs) of 0.668, 0.765, and 0.841, respectively. The combined model showed improved performance compared to the clinical model and image model in two cohorts. DCA confirmed the higher net benefit of the combined model than the other two models when the threshold probability is between 0.05 and 0.85.The proposed combined DL model incorporating T2WI and clinical factors may show good diagnostic performance. Thus, it could potentially serve as a supplementary approach for noninvasively evaluating KRAS mutation in rectal cancer.3 TECHNICAL EFFICACY: Stage 2.

Collagen in the tumor microenvironment is recognized as a potential biomarker for predicting treatment response. This study investigated whether the collagen features are associated with pathological complete response (pCR) in locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (nCRT) and develop and validate a prediction model for individualized prediction of pCR. The prediction model was developed in a primary cohort (353 consecutive patients). In total, 142 collagen features were extracted from the multiphoton image of pretreatment biopsy, and the least absolute shrinkage and selection operator (Lasso) regression was applied for feature selection and collagen signature building. A nomogram was developed using multivariable analysis. The performance of the nomogram was assessed with respect to its discrimination, calibration, and clinical utility. An independent cohort (163 consecutive patients) was used to validate the model. The collagen signature comprised four collagen features significantly associated with pCR both in the primary and validation cohorts (p 0.001). Predictors in the individualized prediction nomogram included the collagen signature and clinicopathological predictors. The nomogram showed good discrimination with area under the ROC curve (AUC) of 0.891 in the primary cohort and good calibration. Application of the nomogram in the validation cohort still gave good discrimination (AUC = 0.908) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. In conclusion, the collagen signature in the tumor microenvironment of pretreatment biopsy is significantly associated with pCR. The nomogram based on the collagen signature and clinicopathological predictors could be used for individualized prediction of pCR in LARC patients before nCRT.

Many patients are confronted with low anterior resection syndrome after rectal surgery. The perspectives of both healthcare professionals and patients on the impact of bowel problems may differ. This study aimed to explore experiences of healthcare professionals on how to provide, organise and optimise care for patients with low anterior resection syndrome from an interprofessional perspective.An explorative qualitative design was used. Healthcare professionals were recruited in October 2018 in one general teaching hospital and one university hospital. Twenty one healthcare professionals from different professions caring for patients with low anterior resection syndrome were included in three focus group interviews.Healthcare professionals confirmed a lack of focus on patients who are confronted with low anterior resection syndrome and stated a need for a standardised approach of care. Additionally, three levels for care optimization emerged from the data: information before surgery with strong emphasis on the timing of informing, counselling of patients when confronted with low anterior resection syndrome and organisation of care.Healthcare professionals find it important to adopt the moment and amount of information to the coping mechanism and timing of the trajectory. Counselling and follow-up of patients with LARS should be organised proactively and should not remain restricted to pharmacological and nutritional advice. A possible strategy is to develop and implement late effects nurse-led clinics coordinated by the clinical nurse specialist.

Locally invasive T4 rectal cancer often requires neoadjuvant treatment followed by multi-visceral surgery to achieve a radical resection (R0), and referral to a specialized exenteration quaternary centre is typically recommended. The aim of this study was to explore regional variance in treatment and outcomes of patients with locally advanced rectal cancer in Australia and New Zealand (ANZ).Data were collected from the Bi-National Colorectal Cancer Audit (BCCA) database. Rectal cancer patients treated between 2007 and 2019 were divided into six groups based on region (state/country) using patient postcode. A subset analysis of patients with T4 cancer was performed. Primary outcomes were positive circumferential resection margin (CRM+), and positive circumferential and/or distal resection margin (CRM/DRM+).A total of 9385 patients with rectal cancer were identified, with an overall CRM+ rate of 6.4% and CRM/DRM+ rate of 8.6%. There were 1350 patients with T4 rectal cancer (14.4%). For these patients, CRM+ rate was 18.5%, and CRM/DRM+ rate was 24.1%. Significant regional variation in CRM+ (range 13.4-26.0%; p = 0.025) and CRM/DRM+ rates (range 16.1-29.3%; p = 0.005) was identified. In addition, regions with higher CRM+ and CRM/DRM+ rates reported lower rates of multi-visceral resections: range 24.3-26.8%, versus 32.6-37.3% for regions with lower CRM+ and CRM/DRM+ rates (p 0.0001).Positive resection margins and rates of multi-visceral resection vary between the different regions of ANZ. A small subset of patients with T4 rectal cancer are particularly at risk, further supporting the concept of referral to specialized exenteration centres for potentially curative multi-visceral resection.

Management of advanced or recurrent pelvic cancer has evolved dramatically over the past few decades. Patients who were previously considered inoperable are now candidates for potentially curative surgery and avoid suffering with intractable symptoms. Up to 10% of primary rectal cancers present with isolated advanced local disease and between 10% and 15% of patients develop localized recurrence following proctectomy. Advances in surgical technique, reconstruction and multidisciplinary involvement have led to a reduction in mortality and morbidity and culminated in higher R0 resection rates with superior longer-term survival outcomes. Recent studies boast over 50% 5-year survival for rectal with an R0 resection. Exenteration has cemented itself as an important treatment option for advanced primary/recurrent pelvic tumours, however, there are still a few controversies. This review will discuss some of these issues, including: limitations of resection and the approach to high/wide tumours; the role of acute exenteration; re-exenteration; exenteration in the setting of metastatic disease and palliation; the role of radiotherapy (including intra-operative and re-irradiation); management of the empty pelvis; and the impact on quality of life and function.

Total neoadjuvant therapy (TNT) for rectal cancer is the preoperative delivery of radiation or chemoradiotherapy as well as systemic chemotherapy for the purpose of improving treatment completion rates and decreasing toxicity, maximizing the primary tumor response, and improving survival for patients with rectal cancer. This review summarizes the data surrounding TNT, including several recent randomized controlled trials. Moreover, it reviews the literature regarding high-quality surgery and the role of radiation and chemotherapy in the treatment of rectal cancer in the modern era. Finally, it presents an evidence-based protocol for the selective use of TNT in the treatment of patients with rectal cancer.

There have been reports about robotic surgery for rectal cancer with chemoradiotherapy (CRT), but only a few studies have compared the use of robotic surgery with and without neoadjuvant chemotherapy (NAC). The aim of our study was to compare the perioperative outcomes of robotic surgery with and without NAC for lower rectal cancer and to examine the effects of NAC on robotic surgery.From January 2016 to July 2021, we compared the short-term outcomes of 45 patients who did not undergo NAC and 55 patients who underwent NAC.The rate of sphincter-preserving surgeries was higher in the NAC group than in the non-NAC group (P = .024). The total operative time was significantly longer in the NAC group than in the non-NAC group (P .001). The rate of lateral lymph node dissection was significantly higher in the NAC group than in the non-NAC group (P .001). No significant differences were identified in the rate of incisional surgical site infections (SSI), organ/space SSI postoperative bleeding, small bowel obstruction, anastomotic leakage, urinary dysfunction, or urinary infections between the groups. There were eight incidences of lateral lymph node metastasis (15%) and two cases with positive resection margins (4.0%) in the NAC group.Robotic surgery after NAC has few complications and a higher sphincter-preserving rate that without NAC.

Objective: To test the reliability and validity of the Chinese version of the colostomy impact score (CIS) among patients with a permanent colostomy in China. Methods: A total of 218 patients completed the survey either in the clinic or remotely and mailed their responses. Reliability was estimated based on test-retest reliability. Validity was evaluated based on content validity, construct validity, and discriminative validity. The sensitivity and specificity of the score were analysed. The area under the curve was analysed by drawing the receiver-operating characteristic (ROC) curve; the optimal cutoff point was calculated to assess the impact of a stoma on domestic patients. Results: The test-retest reliability of the CIS was 0.967. The content validity was 0.98, and the construct and discriminative validities were good; sensitivity, specificity, and area under the ROC curve were 100, 48.53, and 0.806%, respectively. The optimal cutoff point for the Chinese version of the Colostomy Impact Score was 11.5. Conclusions: The Chinese version of the CIS indicated good reliability and validity, making it suitable for the evaluation of the impact of a permanent colostomy.

AIM: The sigmoid take-off (STO), the point on imaging where the sigmoid sweeps ventral from the sacrum, was chosen as the definition of the rectum during an international Delphi consensus meeting and has been incorporated into the Dutch guidelines since October 2019. The aim of this study was to evaluate the implementation of this landmark 1 year after the guideline implementation and to perform a quality assessment of the STO training. METHOD: Dutch radiologists, surgeons, surgical residents, interns, PhD students and physician assistants were asked to complete a survey and classify 20 tumours on MRI as 'below', 'on' or 'above' the STO. Outcomes were agreement with the expert reference, inter-rater variability and accuracy before and after the training. RESULTS: Eighty-six collaborators participated. Six radiologists (32%) and 11 surgeons (73%) used the STO as the standard landmark to distinguish between rectal and sigmoidal tumours during multidisciplinary meetings. Overall agreement with the expert reference improved from 53% to 70% (p

The development of chemotherapy and treatment strategies for metastatic colorectal cancer (mCRC) have provided patients with significant survival benefits. Currently, molecular targeting agents and late-line treatment with regorafenib and trifluridine/tipiracil (FTD/TPI) are available. However, the impact of this increase in drug availability on overall survival (OS) in mCRC remains a clinical question.We retrospectively collected data on consecutive mCRC patients who were treated at three institutions in Japan. We divided the patients into three cohorts: patients who initiated first-line treatment from Jan 2005 to Dec 2006 (cohort A: only cytotoxic drugs available), Jan 2007 to Dec 2011 (cohort B: molecular targeting drugs available), and Jan 2012 to Sep 2016 (cohort C: late-line treatment available).A total of 1409 consecutive patients were analyzed. The median survival time (MST) in cohorts A, B, and C was 18.6, 25.4, and 26.4 months, respectively. The hazard ratio (HR) for cohort B versus A was 0.81 (95% CI 0.68-0.97), for cohort C versus A was 0.74 (95% CI 0.61-0.89), and for cohort C versus B was 0.92 (0.81-1.03). The median number of administered drugs (range) was 3 (1-5) in cohort A, 4 (1-7) in cohort B, and 4 (1-7) in cohort C. The increase in drug availability extended the MST from 15.5 months in patients treated with ≤3 drugs to 36.0-37.3 months in patients treated with six to seven drugs.The development of chemotherapy including late-line treatments could improve the prognosis of mCRC patients.

This study investigated male voiding dysfunction (VD) or lower urinary tract function in rectal cancer (RC) patients after laparoscopic or open total mesorectal excision with pelvic autonomic nerve preservation (PANP).One hundred and eighty-seven male RC patients admitted between January 2016 and May 2019 were enrolled in this study, 112 of whom underwent laparoscopic total mesorectal excision (LTME) and 75 underwent open total mesorectal excision (OTME). The International Prostatic Symptom Score (IPSS) was compared between the two groups.The postoperative IPSS in patients with RC was elevated on day 7 and gradually decreased during the first month after surgery. Compared with the OTME group, the IPSS scores decreased less in the LTME group at week 1, and months 1 and 3 postoperatively (6.82 ± 2.13 vs 10.15 ± 3.86, 5.70 ± 2.45 vs 7.21 ± 2.0, and 5.01 ± 2.09 vs 5.75 ± 2.55, respectively; P 0.05). The VD rate was significantly lower in the LTME group than the OTME group at 1, 2, and 3 weeks postoperatively (21.4% vs 26.8%,13.4% vs 25.3%, and 9.8% vs18.6%, respectively; P 0.05); however, there was no major difference in the incidence of VD 6 months postoperatively between the two groups (P 0.05). VD was more frequent in the OTME group than the LTME group 6 months postoperatively, but the difference was not statistically significant (odds ratio = 1.857, 95% CI, 0.964-3.645, P = 0.064).LTME may be superior to OTME with respect to PANP of lower urinary tract function in males with RC.

The relationship between metastatic colorectal cancer (mCRC) and venous thromboembolism (VTE) is poorly defined in the modern era. Our objective was to examine impact of putative risk factors including newer treatments and anti-angiogenic therapy on VTE incidence and survival in a modern older mCRC cohort.This is a SEER-Medicare cohort analysis of mCRC patients diagnosed in 2004-2009. Risk factor analysis was conducted using Cox models adjusted for sex, diagnosis age, race, primary tumor location, comorbidity, and prior VTE history, with cancer treatments as time-varying covariates. Main outcomes were VTE incidence and overall survival.Ten thousand nine hundred and seventy six mCRC cases with mean age 77.9 years (range 65-107), 49.7% women, 83.5% white. There were 1306 VTE cases corresponding to 13.7% incidence at 1 year and 20.3% at 3 years. Independent VTE predictors included female sex (HR 1.27; 95% CI 1.14-1.42), African American race (HR 1.49; 1.27-1.73), prior VTE history (HR 16.3; 12.1-22.1), and right sided cancers (HR 1.16; 1.04-1.29). After adjustment, any therapy and bevacizumab (HR 0.68, 0.58-0.78) in particular were protective. Overall survival was 40.1% (39.4-41.3) at 1 year but improved significantly with any treatment. VTE following diagnosis of mCRC was associated with inferior OS (HR 1.09; 1.02-1.15).In this large contemporary mCRC cohort, effective systemic therapy including anti-angiogenic treatment was associated with lower VTE risk. Overall survival was poor, and modestly worse if a patient had a VTE at any time during treatment.

Evidence has emerged that a pretreatment immune profile in rectal cancer is associated with response to chemoradiotherapy (CRT) and recurrence after CRT. However, few studies have evaluated the immune profile differences after CRT regarding recurrence and nonrecurrence.We included patients with advanced rectal cancer treated with CRT and surgery with recurrence within 1 year in a recurrence group. After sex and age matching with the recurrence group, patients with no recurrence for 3 years after CRT were included in a nonrecurrence group. We extracted the immune profile, including CD3 and CD8, from the surgical specimen after CRT using multispectral fluorescence immunohistochemistry and compared the two groups.The immune profiles of 65 patients with rectal cancer were assessed; 30 were included in the recurrence group and 35 were included in the nonrecurrence group. CD3Vigorous CD3

Distal resection margin (DRM) is closely associated with sphincter-preserving surgery and oncological safety for patients with mid-low rectal cancers. However, the optimal DRM has not been determined.Data of 378 rectal cancer patients who underwent laparoscopic-assisted sphincter-preserving surgery from 2009 to 2015 were retrospectively analysed. Patients were divided into two groups based on DRM: ≤1 cm (n = 74) and1 cm (n = 304). To minimize the differences between the two groups, propensity-score matching on baseline features was performed.Before propensity-score matching, no significant differences in 5-year disease-free survival (DFS) (92.8% versus 81.3%, P = 0.128) and 5-year overall survival (OS) (83.7% versus 82.2%, P = 0.892) were observed in patients with DRMs of ≤1 cm (n = 74) and1 cm (n = 304), respectively. After propensity-score matching (1:1), there were also no significant differences in DFS (88.1% versus 78.2%, P = 0.162) and OS (84.5% versus 84.9%, P = 0.420) between the DRM of ≤1 cm group (n = 65) and1 cm group (n = 65), respectively. A total of 44 patients received preoperative chemoradiotherapy (CRT). In this cohort, the 5-year local recurrence (LR) rates (P = 0.118) and the 5-year DFS rates (P = 0.298) were not significantly different between the two groups. A total of 334 patients received surgery without neoadjuvant CRT. There were also no significant differences in the 5-year LR rates (P = 0.150) and 5-year DFS rates (P = 0.172) between the two groups.When aiming to achieve at least a 1-2 cm distal clinical resection margin, a histological resection margin of1 cm on the DRM gave equivalent clinical outcomes to a DRM of1 cm.

Anastomotic leak (AL) is the anathema of colorectal surgery, with well-documented adverse impacts on patient morbidity and mortality. The long-term consequences of AL on bowel function and quality of life (QoL) is less well-defined after minimally invasive surgery. By omitting a temporary diverting ileostomy (TDI), it is postulated that the minimally invasive approach will lead to early diagnosis and expedient management of AL.This retrospective and cross-sectional study included patients who underwent minimally invasive restorative rectal surgery with a low pelvic colorectal anastomosis and without a TDI at two tertiary hospitals in Brisbane, Australia between 2004 and 2018. Surgical management of AL is described and long-term functional outcomes were evaluated through validated questionnaires.Two hundred and twenty-four patients met inclusion criteria. AL was associated with lesion proximity to the anal verge (P = 0.011), total mesorectal excision (TME) (P 0.001) and advanced malignant disease (P = 0.019). Twenty-four patients experienced an AL (11%) diagnosed at a median of 5.5 days post-operative. Survey responders (n = 99, 62%) included 10 (10%) AL and 89 (90%) non-AL patients, with a median follow-up of 4 and 6.4 years. SF-36 and FISI scores were comparable between groups, however AL patients had worse LARS scores (P = 0.028). Patients undergoing TME, irrespective of AL, had poorer low anterior resection syndrome (LARS) (P 0.001) and FISI scores (P = 0.001).AL in patients undergoing minimally invasive low pelvic colorectal anastomosis without a TDI does not impact long term QoL. The occurrence of LARS is dependent on the extent of resection, rather than the occurrence of AL.

Transanal total mesorectal excision (TaTME) avoids the difficulty of laparoscopic dissection of the lower part of the rectum. The need for stoma is associated with many stoma-related complications. The objective was to compare TaTME with immediate coloanal anastomosis and protective ileostomy (TaTME-IA) versus Turnbull-Cutait delayed coloanal anastomosis (TaTME-TC).A retrospective cohort study included patients with low rectal cancer at least 1 cm above the top of the anal sphincter. Patients had either TaTME-IA or TaTME-TC. Primary outcome measures were anastomotic and stoma-related complications. Secondary outcomes included rate of permanent stomas, local recurrence, continence, and quality of life (QOL).TaTME-IA was done in 25 patients versus 20 who had TaTME-TC. TaTME-IA had significantly longer mean operative time (p = 0.04) and shorter length of stay (LOS) (4.5 vs. 11.4 days; p = 0.0001) compared to TaTME-TC. Anastomotic leak was reported in two patients of TaTME-IA versus one patient of TaTME-TC (p = 0.77). Anastomotic stenosis was reported in one patient in each group. No significant difference between groups as regard continence, local recurrence, and QOL.TaTME-TC is a safe option that can be offered for patients with low rectal cancer who refuse or are not amenable to a temporary stoma. Anastomotic complications were similar in both groups. LOS was much longer in TaTME-TC, however, it avoids stoma complications. Both groups had similar functional oncologic outcomes and QOL.

Rectal cancer is a challenging disease process to manage, with a rising incidence in young adults. Several clinical advances have been made in the past decade with regards to optimal treatment strategies in early-stage (T1-2, node negative tumours) and locally advanced cancers (T3-4 and/or nodal positivity) utilizing a multimodal approach of surgery, neoadjuvant chemoradiotherapy, and adjuvant chemotherapy, all aiming to optimize oncological outcomes, while minimizing associated morbidity. This narrative review aimed to summarize trial level evidence apropos the management of early and locally advanced rectal cancer. All relevant prospective clinical trials were identified through a computer-assisted search of PubMed, EMBASE, Medline databases between 1990 and 30 June 2021. With regards to early rectal cancer, there is limited trial-level evidence in the literature. Total mesorectal excision (TME) is the current standard of care, but local excision could be considered in select patients with pT1 tumours, or patients with near or complete clinical response to neoadjuvant CRT. As for locally advanced rectal cancer, the current standard of care consists of long-course chemotheradiotherapy or short-course radiotherapy, followed by TME. However, the role of total neoadjuvant therapy is promising, with respect to both oncological outcomes, as well as in reducing toxicity. Both induction and consolidation chemotherapy treatment approaches have been described in literature, with encouraging early results. The optimal management of rectal cancer is constantly evolving. More research is needed to investigate the long-term oncological and functional outcomes following new multimodal therapies in the management of early-stage and locally advanced rectal cancer.

Anastomotic leak (AL) is the anathema of colorectal surgery. Early diagnosis is an essential segue to early intervention. A temporary diverting ileostomy (TDI) does not prevent an AL and presents inherent complications of its own. Numerous drain fluid biomarkers (BM) have been studied in colorectal surgery and extravasated intraluminal substances (EILS) such as amylase have shown promise. The aim of this study was to assess drain fluid amylase (DFA) as a BM of AL after minimally invasive rectal resection without a TDI.A single centre prospective cohort study performed from 2018 to 2021. The primary outcome was DFA measured daily whilst the drain was in situ. Rectal tube amylase was also measured for the first two post-operative days to quantitate the intra-luminal levels of the enzyme. DFA was compared between patients who experienced AL and those who did not.Of the 62 patients studied, six (9.7%) experienced AL. There was a statistically significant difference in DFA between patients who experienced AL (Median:1373.5 U/L; IQR: 306-7953) and patients who did not experience an AL (Median: 27.0 U/L; IQR: 16-38); p 0.0001.The measurement of drain fluid amylase is a highly sensitive BM of early clinical anastomotic leak in patients undergoing a rectal resection with an extraperitoneal anastomosis and when a TDI is not incorporated. This simple, inexpensive and non-invasive test should be considered in all patients as an adjunct to the clinical diagnosis and differentiation of AL from other postoperative complications.

Previous studies have concluded that colorectal cancer patients with deficient mismatch repair (dMMR) usually have a good prognosis. However, some studies have suggested that the prognosis of rectal cancer patients with dMMR appears to be worse. Our aim was to investigate chemoradiotherapy resistance in dMMR rectal tumors.A retrospective study of 217 patients with locally advanced rectal adenocarcinoma treated with chemoradiotherapy and total mesorectal excision surgery was conducted using immunohistochemistry to determine MMR status and propensity score matching models to reduce potential confounders. Kaplan-Meier analysis, log-rank test, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups.The 3-year DFS rates were 77.1% and 56.7% in the pMMR and dMMR groups, respectively. The pMMR group had significantly better DFS than the dMMR group (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.10-3.91; p = 0.019). However, there was no significant difference in OS between the two groups (45.7 [interquartile range, IQR], 39.3-72.1] vs. 47.5 [IQR, 29.5-72.1]) (HR, 1.39; 95% CI, 0.70-2.77; p = 0.35). Neither OS nor DFS was significantly different between the neoadjuvant chemoradiotherapy and postoperative chemoradiotherapy groups.Locally advanced dMMR rectal adenocarcinoma exhibits greater chemoradiotherapy resistance than pMMR.

Diffusion weighted imaging (DWI) at multiple b-values has been used to predict the pathological complete response (pCR) to neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Non-Gaussian models fit the signal decay of diffusion by several physical values from different approaches of approximation.To develop a deep learning method to analyze DWI data scanned at multiple b-values independent on Gaussian or non-Gaussian models and to apply to a rectal cancer neoadjuvant chemoradiotherapy model.Retrospective.A total of 472 participants (age: 56.6 ± 10.5 years; 298 males and 174 females) with locally advanced adenocarcinoma were enrolled and chronologically divided into a training group (n = 200; 42 pCR/158 non-pCR), a validation group (n = 72; 11 pCR/61 non-pCR) and a test group (n = 200; 44 pCR/156 non-pCR).A 3.0 T MRI scanner. DWI with a single-shot spin echo-planar imaging pulse sequence at 12 b-values (0, 20, 50, 100, 200, 400, 600, 800, 1000, 1200, 1400, and 1600 sec/mmDWI signals from manually delineated tumor region were converted into a signature-like picture by concatenating all histograms from different b-values. Pathological results (pCR/non-pCR) were used as the ground truth for deep learning. Gaussian and non-Gaussian methods were used for comparison.Analysis of variance for age; Chi-square for gender and pCR/non-pCR; area under the receiver operating characteristic (ROC) curve (AUC); DeLong test for AUC. P 0.05 for significant difference.The AUC in the test group is 0.924 (95% CI: 0.866-0.983) for the signature-like pictures converted from 35 bins, and it is 0.931 (95% CI: 0.884-0.979) for the signature-like pictures converted from 70 bins, which is significantly (Z = 3.258, P 0.05) larger than DThe proposed signature-like pictures provide more accurate pretreatment prediction of the response to neoadjuvant chemoradiotherapy than the fitted methods for locally advanced rectal cancer.3 TECHNICAL EFFICACY: Stage 2.

Adoption of multimodality treatment approach for rectal cancer has resulted in significant improvements in oncologic outcomes. The roles of chemotherapy, radiation, and surgery in rectal cancer treatment are continuously evolving with the goal of achieving the best possible oncologic and functional outcome while minimizing treatment toxicity. The aim of this review is to summarize the most recent trials focusing on organ-sparing treatment strategies and the optimal selection of patients for neoadjuvant radiation therapy.

Comparative bowel functional outcomes between ultralow anterior resections (ULAR) and inter-sphincteric resection (ISR) for similar tumour and patient characteristics is not known.Single centre study of low rectal caners (5cm from anal verge) with 1:1 propensity matching of age, sex, body mass index, prior radiation, and surgical approach (open vs. minimally invasive) was performed for the ULAR and ISR groups. Primary outcome measure was Wexner Incontinence scores and Low Anterior Resection Syndrome (LARS) score at a single time point after stoma reversal.Seventy-two matched patients were included. Median Wexner scores were five and eight for the ULAR and ISR cohorts (p = 0.006). Major incontinence (Wexner11) was found in 5.6% versus 33% after ULAR and ISR, respectively. Major LARS (score29) was demonstrated in 11% versus 25% in ULAR versus ISR (p = 0.293). Majority in both groups has no LARS (score20), that is, 72.2% versus 63.9% in ULAR against ISR. Besides these, stool fragmentation (p0.001), nocturnal defecation (p0.001) and use of anti-diarrhoeal medications (p = 0.023) were significantly more after ISR.Bowel continence was relatively inferior after ISR as compared to an ULAR for low rectal cancers in matched cohorts. Major LARS in ISR was twice as prevalent without statistical differences.

INTRODUCTION Trends in the use of short-course radiation therapy (RT) for rectal cancer in Australia are unknown. The purpose of this study was to compare short-course RT and long-course chemoradiation (CRT) utilisation in the neoadjuvant treatment of rectal cancer in New South Wales (NSW). METHODS Patients who received neoadjuvant RT (2009-2014) for rectal cancer were identified from the NSW Central Cancer Registry. Univariate and multivariable analyses were performed to investigate factors associated with receipt of short-course RT. RESULTS A total of 1196 (81%) patients received long-course CRT, and 274 (19%) patients received short-course RT. Receipt of short-course RT was associated with older age: 54% in patients ≥80 years, and 11% in patients

Aim: Reviewing outcomes of regorafenib use in metastatic colorectal cancer using real-world data from the South Australian Metastatic Colorectal Cancer Registry. Methods: A retrospective review of the characteristics and outcomes of patients who received regorafenib in the Registry up to December 2018. The registry started in February 2006. Results: Fifty-three patients received regorafenib therapy since approved by the therapeutic goods administration in November 2013. The median age was 66 (range 34–82). 66% were male, 66% had stage IV disease at diagnosis, 53% had liver only involvement, whereas 13% had liver and lung disease and 6% had lung only involvement. 75% had left-sided primary. KRAS was available in 35/53 patients with 49% of them being WT. BRAF status was known in 8/53 with 25% of them having a mutated variant. MSI testing was known in 14 patients in whom 21% of them had MSI-High tumors. Prior lines of treatment received: one line 4%, two 9%, three 23%, four 26%, >four 37%. Prior biological use: bevacizumab 72%, anti-EGFR 100% (for RAS WT). Median survival from diagnosis was 3.3 years (95% CI, 2.8–3.8 years). Median survival from the start of regorafenib was 7.1 months (95% CI, 4.8–9.4 months) and the 12-month survival rate was 28%. Conclusion: The survival outcome for those patients from our population-based registry who access regorafenib is in keeping with reports from large, randomized trials. Thus, clinicians can quote local real world data when discussing efficacy and access to regorafenib therapy for mCRC patients. Refereed/Peer-reviewed

Background Delineation of clinical target volume (CTV) for radiotherapy is a time‐consuming and labor‐intensive work. This study aims to propose a novel convolutional neural network (CNN)‐based model for fast auto‐segmentation of CTV. To evaluate its performance and clinical utility, a blind randomized validation method was used. Methods Our proposed model was based on the generally accepted U‐Net architecture using computed tomography slices with CTV contours delineated by experienced radiation clinicians from 135 rectal patients receiving neoadjuvant radiotherapy. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) were used to measure segmentation performance. The validated dataset of additional 20 patients for clinical evaluation by 10 experienced oncology clinicians from 7 centers was randomly and blindly divided into two groups for clinicians' scoring and Turing test, respectively. Second evaluation was performed with different randomization after 2 weeks. Results The mean DSC and 95HD values of the proposed model were 0.90 ± 0.02 and 8.11 ± 1.93 mm for CTV of rectal cancer patients, respectively. The average time for automatic segmentation in the validation groups was 15 s per patient. By clinicians' scoring, the AI model performed better than manually delineating, though the differences were not significant (Week 0: 2.59 vs. 2.52, p = 0.086; Week 2: 2.55 vs. 2.47, p = 0.115). Additionally, the mean positive rates in the Turing test were 40.5% in Week 0 and 45.2% in Week 2, which demonstrated the great intelligence of our model. Conclusions Our proposed model can be used clinically for assisting contouring of CTVs in rectal cancer patients receiving neoadjuvant radiotherapy, which improves the efficiency and consistency of radiation clinicians' work., This study first developed an auto‐segmentation system using U‐Net deep learning architecture in patients receiving neoadjuvant radiotherapy and obtained great measurement performance. Besides, we first reported a blind system for clinical evaluation, including clinicians' scoring and Turing test by multicenter radiologists, which can eliminate inter‐ and intra‐observer discrepancy as much as possible. Our proposed methods may be helpful for the assessment of AI‐assisted models in clinical practice.

Aim Positron emission tomography (PET)/CT can be used to monitor the metabolic changes that occur after intensified treatment with induction chemotherapy and chemo(re)irradiation for locally recurrent rectal cancer (LRRC). This study aimed to analyse the correlation between the PET/CT response and final histopathological outcomes. Methods All LRRC patients who underwent induction chemotherapy prior to surgery between January 2010 and July 2020 and were monitored with pretreatment and post-treatment PET/CT were included. Visual qualitative analysis was performed, and patients were scored as having achieved a complete metabolic response (CMR), partial metabolic response (PMR) or no response (NR). The histopathological response was assessed according to the Mandard tumour regression (TRG) score and categorized as major (TRG 1-2), partial (TRG 3) or poor (TRG 4-5). The PET/CT and TRG categories were compared, and possible confounders were analysed. Results A total of 106 patients were eligible for analysis; 24 (23%) had a CMR, 54 (51%) had a PMR and 28 (26%) had NR. PET/CT response was a significant predictor of the negative resection margin rate, achieving 96% for CMR, 69% for PMR and 50% for NR. The overall accuracy between PET score and pathological TRG was 45%, and the positive predictive value for CMR was 63%. A longer interval between post-treatment PET/CT and surgery negatively influenced the predictive value. Conclusion Metabolic PET/CT response evaluation after neoadjuvant treatment proves to be a complementary diagnostic tool to standard MRI in assessing tumour response, and may play a role for treatment planning in LRRC patients.