Nonoperative management protocol for locally advanced rectal cancer.

AIM: The standard treatment for low rectal cancer is preoperative chemoradiotherapy followed by surgery with low anterior resection with diverting ileostomy or abdominoperineal resection, both of which have significant long-term effects on bowel and sexual function. Due to the high morbidity of surgery, there has been increasing interest in nonoperative management for low rectal cancer. The aim of this work is to conduct a pan-Canadian Phase II trial assessing the safety of nonoperative management for low rectal cancer. METHOD: Patients with Stage II or III low rectal cancer completing chemoradiotherapy according to standard of care at participating centres will be assessed for complete clinical response 8-14 weeks following completion of chemoradiotherapy. Subjects achieving a clinical complete response will undergo active surveillance including endoscopy, imaging and bloodwork at regular intervals for 24 months. The primary outcome will be the rate of local regrowth 2 years after chemoradiotherapy. Nonoperative management will be considered safe (i.e. as effective as surgery to achieve local control) if the rate of local regrowth is ≤30% and surgical salvage is possible for all local regrowths. Secondary outcomes will include disease-free and overall survival. CONCLUSION: The results will be highly clinically relevant, as it is expected that nonoperative management will be safe and lead to widespread adoption of nonoperative management in Canada. This change in practice has the potential to decrease the number of patients requiring surgery and the costs associated with surgery and long-term surgical morbidity.

Impact of grade on workup of rectal neuroendocrine tumors: a retrospective cohort study : Grade impact on workup of rectal NETs.

BACKGROUND: Rectal neuroendocrine tumors (RNETs) are often discovered on screening colonoscopy. Indications for staging and definitive resection are inconsistent in current guidelines. We evaluated the role of grade in guiding staging and procedural decision-making. METHODS: Patients with biopsy confirmed RNETs between 2004 and 2015 were reviewed. Baseline characteristics, staging investigations (biochemical and imaging), and endoscopic/surgical treatment were recorded. Associations between grade, preoperative staging, interventions, and survival were determined using Fisher-Freeman-Halton Exact, log-rank, and Kaplan-Meier analysis. RESULTS: Amongst 139 patients with RNETs, 9% were aged ≥ 75 years and 44% female. Tumor grade was: 73% grade 1 (G1), 18%, grade 2 (G2) and 9% grade 3 (G3). Staging investigations were performed in 52% of patients. All serum chromogranin A and 97% of 24-hour urine 5-hydroxyindoleacetic acid tests were normal. The large majority of staging computed tomography (CT) scans were negative (76%) with subgroup analysis showing no G1 patients with CT identified distant disease compared with 38% of G2 and 50% of G3 patients (p < 0.001). G1 patients were more likely to achieve R0/R1 resections compared to G2 (95% vs. 50%, p < 0.001) and G1 patients had significantly better 5-year overall survival (G1: 98%, G2: 67%, G3: 10%, p < 0.001). CONCLUSION: Tumor grade is important in preoperative workup and surgical decision-making. Biochemical staging may be omitted but staging CT should be considered for patients with grade ≥ 2 lesions. Anatomic resections should be considered for patients with grade 2 disease.

Symptom Burden and Time from Symptom Onset to Cancer Diagnosis in Patients with Early-Onset Colorectal Cancer: A Multicenter Retrospective Analysis.

Background: The incidence of colorectal cancer (CRC) is decreasing in individuals >50 years due to organised screening but has increased for younger individuals. We characterized symptoms and their timing before diagnosis in young individuals. Methods: We identified all patients diagnosed with CRC between 1990-2017 in British Columbia, Canada. Individuals <50 years (n = 2544, EoCRC) and a matched cohort >50 (n = 2570, LoCRC) underwent chart review to identify CRC related symptoms at diagnosis and determine time from symptom onset to diagnosis. Results: Across all stages of CRC, EoCRC presented with significantly more symptoms than LoCRC (Stage 1 mean ± SD: 1.3 ± 0.9 vs. 0.7 ± 0.9, p = 0.0008; Stage 4: 3.3 ± 1.5 vs. 2.3 ± 1.7, p < 0.0001). Greater symptom burden at diagnosis was associated with worse survival in both EoCRC (p < 0.0001) and LoCRC (p < 0.0001). When controlling for cancer stage, both age (HR 0.87, 95% CI 0.8-1.0, p = 0.008) and increasing symptom number were independently associated with worse survival in multivariate models. Conclusions: Patients with EoCRC present with a greater number of symptoms of longer duration than LoCRC; however, time from patient reported symptom onset was not associated with worse outcomes.

Local Recurrence-Free Survival After TaTME: A Canadian Institutional Experience.

BACKGROUND: Transanal total mesorectal excision is a novel surgical treatment for mid to low rectal cancers. Norwegian population data have raised concerns about local recurrence in patients treated with transanal total mesorectal excision. OBJECTIVE: This study aimed to analyze local recurrence and disease-free survival in patients treated by transanal total mesorectal excision for rectal cancer at a high-volume tertiary center. DESIGN: This retrospective study used a prospectively maintained institutional transanal total mesorectal excision database. Patient demographics, treatment, and outcomes data were analyzed. Local recurrence, disease-free survival, and overall survival were analyzed using Kaplan-Meier analysis. SETTINGS: The study was conducted at a single academic institution in Vancouver, Canada. PATIENTS: All patients treated by transanal total mesorectal excision for rectal adenocarcinoma between 2014 and 2022 were included. MAIN OUTCOME MEASURES: The primary outcome was local recurrence-free survival. RESULTS: Between 2014 and 2022, 306 patients were treated by transanal total mesorectal excision at St. Paul's Hospital. Of these, 279 patients met the inclusion criteria. The mean age was 62 years (SD ± 12.3), and 66.7% of patients were men. Restorative resection was achieved in 97.5% of patients, with a conversion rate from laparoscopic to open surgery of 6.8%. The composite optimal pathological outcome was 93.9%. The median follow-up was 26 months (interquartile range, 12-47), and 82.8% of patients achieved reestablishment of GI continuity to date. The overall local recurrence rate was 4.7% (n = 13). The estimated 2-year local recurrence-free survival rate was 95.0% (95% CI, 92-98) and the estimated 5-year local recurrence-free survival rate was 94.5% (95% CI, 91-98). LIMITATIONS: Limitations include the retrospective nature of the study and the generalizability of a Canadian population. CONCLUSIONS: Recent European data have challenged the presumed oncologic safety of transanal total mesorectal excision. Although the learning curve for this procedure is challenging and poor outcomes are associated with low volume, this high-volume single-center study confirms acceptable oncologic outcomes consistent with the current standard. See Video Abstract . SOBREVIDA SIN RECIDIVA DESPUS DE TATME EXPERIENCIA INSTITUCIONAL CANADIENSE: ANTECEDENTES:La excisión total del mesorecto por vía transanal es un tratamiento quirúrgico novedoso para los cánceres de recto medio a bajo. Estudios sobre la población noruega han generado preocupación debido a la recidiva local en pacientes tratados con excisión total del mesorecto por vía transanal.OBJETIVO:Nuestra finalidad fué de analizar la recidiva local y la sobrevida libre de enfermedad en pacientes tratados mediante la excisión total del mesorecto por vía transanal, debido a un cáncer de recto en un centro terciario de alto volúmen.DISEÑO:El presente estudio retrospectivo, utiliza una base de datos institucional sobre la excisión total del mesorecto por vía transanal mantenida prospectivamente. Se analizaron los datos demográficos, de tratamiento y los resultados de los pacientes sometidos a la técnica mencionada. La recidiva local, la sobrevida libre de enfermedad y la sobrevida global se analizaron mediante el modelo de Kaplan-Meier.AJUSTES:El estudio se llevó a cabo en una sola institución académica en Vancouver, Canadá.PARTICIPANTES:Se incluyeron todos los pacientes tratados mediante excisión total del mesorecto por vía transanal causado por adenocarcinomas de recto entre 2014 y 2022.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la sobrevida libre de recidiva local.RESULTADOS:Entre 2014 y 2022, 306 pacientes fueron tratados mediante la excisión total del mesorecto por vía transanal en el Hospital St. Paul. De estos, 279 pacientes cumplieron los criterios de inclusión. La edad media fue de 62 años (DE ± 12,3) y el 66,7% de los pacientes eran varones. La resección restauradora se logró en el 97,5% de los pacientes con una tasa de conversión de cirugía laparoscópica en laparotomía del 6,8%. El resultado patológico óptimo combinado fué del 93,9%. La mediana de seguimiento fue de 26 meses (rango intercuartil 12-47) y el 82,8% logró el restablecimiento de la continuidad gastrointestinal hasta la fecha. La tasa global de recidiva local fué del 4,7% (n = 13). La sobrevida libre de recidiva local estimada a los 2 años fué del 95,0% (IC del 95%: 92-98) y del 94,5% a los 5 años (IC del 95%: 91-98).LIMITACIONES:Las limitaciones incluyen la naturaleza retrospectiva del estudio y la generalización de una población canadiense.CONCLUSIONES:Datos europeos recientes han cuestionado la supuesta seguridad oncológica de la excisión total del mesorecto por vía transanal. Si bien la curva de aprendizaje de este procedimiento es muy desafiante y los malos resultados se asocian con un volumen bajo, el presente estudio, unicéntrico de gran volumen confirma los resultados oncológicos aceptables consistentes con el estándar actual. (Traducción-Dr. Xavier Delgadillo ).

Preparing for colorectal surgery: a feasibility study of a novel web-based multimodal prehabilitation programme in Western Canada.

AIM: Prehabilitation for colorectal cancer has focused on exercise-based interventions that are typically designed by clinicians; however, no research has yet been patient-oriented. The aim of this feasibility study was to test a web-based multimodal prehabilitation intervention (known as PREP prehab) consisting of four components (physical activity, diet, smoking cessation, psychological support) co-designed with five patient partners. METHOD: A longitudinal, two-armed (website without or with coaching support) feasibility study of 33 patients scheduled for colorectal surgery 2 weeks or more from consent (January-September 2021) in the province of British Columbia, Canada. Descriptive statistics analysed a health-related quality of life questionnaire (EQ5D-5L) at baseline (n = 25) and 3 months postsurgery (n = 21), and a follow-up patient satisfaction survey to determine the acceptability, practicality, demand for and potential efficacy in improving overall health. RESULTS: Patients had a mean age of 52 years (SD 14 years), 52% were female and they had a mean body mass index of 25 kg m-2 (SD 3.8 kg m-2). Only six patients received a Subjective Global Assessment for being at risk for malnutrition, with three classified as 'severely/moderately' malnourished. The majority (86%) of patients intended to use the prehabilitation website, and nearly three-quarters (71%) visited the website while waiting for surgery. The majority (76%) reported that information, tools and resources provided appropriate support, and 76% indicated they would recommend the PREP prehab programme. About three-quarters (76%) reported setting goals for lifestyle modification: 86% set healthy eating goals, 81% aimed to stay active and 57% sought to reduce stress once a week or more. No patients contacted the team to obtain health coaching, despite broad interest (71%) in receiving active support and 14% reporting they received 'active support'. CONCLUSION: This web-based multimodal prehabilitation programme was acceptable, practical and well-received by all colorectal surgery patients who viewed the patient-oriented multimodal website. The feasibility of providing active health coaching support requires further investigation.

Direct Medical Spending on Young and Average-Age Onset Colorectal Cancer before and after Diagnosis: a Population-Based Costing Study.

BACKGROUND: Despite a better understanding of the increasing incidence of young-onset colorectal cancer (yCRC; age at diagnosis <50 years), little is known about its economic burden. Therefore, we estimated direct medical spending on yCRC before and after diagnosis. METHODS: We used linked administrative health databases in British Columbia, Canada, to create a study population of yCRC and average-age onset colorectal cancer (aCRC; age at diagnosis ≥50 years) cases, along with cancer-free controls. Over the 1-year period preceding a colorectal cancer diagnosis, we estimated direct medical spending on hospital visits, healthcare practitioners, and prescription medications. After diagnosis, we calculated cost attributable to yCRC and aCRC, which additionally included the cost of cancer treatments (e.g., chemotherapy and radiotherapy) across phases of care. RESULTS: We included 1,058 yCRC (45.4% females; age at diagnosis 42.4 ± 6.2 years) and 12,619 aCRC (44.8% females; age at diagnosis of 68.1 ± 9.2 years) cases. Direct medical spending on the average yCRC and aCRC case during the year before diagnosis was $6,711 and $8,056, respectively. After diagnosis, the overall average annualized cost attributable to yCRC significantly differed in comparison with aCRC for the initial ($50,216 vs. $37,842; P < 0.001), continuing ($8,361 vs. $5,014; P < 0.001), and end-of-life cancer phase ($86,125 vs. $61,512; P < 0.001) but not end-of-life non-cancer phase ($77,273 vs. $23,316; P = 0.372). CONCLUSIONS: Reported cost estimates may be used as inputs for future economic evaluations pertaining to yCRC. IMPACT: We provided comprehensive cost estimates for healthcare spending on young-onset colorectal cancer.

Surgical Outcomes in Total Neoadjuvant Therapy for Rectal Cancer Versus Standard Long-course Chemoradiation: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This systematic review and meta-analysis seeks to evaluate the impact of total neoadjuvant therapy (TNT) for rectal cancers on surgical complications and surgical pathology when compared with standard long-course chemoradiotherapy (LCRT). BACKGROUND: The oncological benefits of TNT are well published in previous meta-analyses, but there is little synthesized information on how it affects surgical outcomes. A recent study has suggested an increase in local recurrence and higher rates of breached total mesorectal excision (TME) plane in TNT patients. METHODS: This study conformed to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A search was performed in Medline (via PubMed), Cochrane databases, EMBASE and CINAHL to identify relevant randomized controlled trials (RCTs) comparing outcomes between TNT and LCRT. Meta-analyses of pooled proportions between TNT and LCRT were performed, comparing primary outcomes of surgical mortality, morbidity and all reported complications; surgical-pathology differences, namely mesorectal quality, R0 resection rates, circumferential resection margin positive rates, and sphincter preservation rates. Death and progression of disease during neoadjuvant treatment period was also compared. Risk of bias of RCTs was performed using the Cochrane risk-of-bias tool by 2 independent reviewers. RESULTS: A total of 3185 patients with rectal cancer from 11 RCTs were included in the analysis: 1607 received TNT and 1578 received LCRT, of which 1422 (TNT arm) and 1391 (LCRT arm) underwent surgical resection with curative intent. There was no significant difference in mortality [risk ratio (RR)=0.86, 95% CI: 0.13-5.52, P =0.88, I2 =52%] or major complications (RR=1.04, 95% CI: 0.86-1.26, P =0.70, I2 =0%) between TNT and LCRT. There was a significantly higher risk of breached TME in TNT group on pooled analysis (RR=1.49, 95% CI: 1.03-12.16, P =0.03, I2 =0%), and on subgroup analysis there is higher risk of breached TME in those receiving extended duration of neoadjuvant treatment (>17 weeks from start of treatment to surgery) when compared with LCRT (RR=1.61, 95% CI: 1.06-2.44, P =0.03). No difference in R0 resection rates (RR=0.85, 95% CI: 0.66-1.10, P =0.21, I2 =15%), circumferential resection margin positive rates (RR=0.87, 95% CI: 0.65-1.16, P =0.35, I2 =10%) or sphincter preservation rates (RR=1.02, 95% CI: 0.83-1.25, P =0.88, I2 =57%) were observed. There was a significantly lower risk of progression of disease to an unresectable stage during the neoadjuvant treatment period in TNT patients (RR=0.60, 95% CI: 0.39-0.92, P =0.03, I2 =18%). On subgroup analysis, it appears to favor those receiving extended duration of neoadjuvant treatment (RR=0.44, 95% CI: 0.26-0.80, P =0.002), and those receiving induction-type chemotherapy in TNT (RR=0.25, 95% CI: 0.07-0.88, P =0.03). CONCLUSIONS: TNT increases rates of breached TME which can contribute to higher local recurrence rates. TNT, however, improves systemic control by reducing early progression of disease during neoadjuvant treatment period. Further research is warranted to identify patients that will benefit from this strategy.

Impact of the COVID-19 Pandemic on Access to Cancer Surgery: Analysis of Surgical Wait Times in British Columbia, Canada.

OBJECTIVE: As coronavirus disease 2019 (COVID-19) spread, efforts were made to preserve resources for the anticipated surge of COVID-19 patients in British Columbia, Canada. However, the relationship between COVID-19 hospitalizations and access to cancer surgery is unclear. In this project, we analyze the impact of COVID-19 patient volumes on wait time for cancer surgery. METHODS: We conducted a retrospective study using population-based datasets of regional surgical wait times and COVID-19 patient volumes. Weekly median wait times for urgent, nonurgent, cancer, and noncancer surgeries, and maximum volumes of hospitalized patients with COVID-19 were studied. The results were qualitatively analyzed. RESULTS: A sustained association between weekly median wait time for priority and other cancer surgeries and increase hospital COVID-19 patient volumes was not qualitatively discernable. In response to the first phase of COVID-19 patient volumes, relative to pre-COVID-19 pandemic levels, wait time were shortened for urgent cancer surgery but increased for nonurgent surgeries. During the second phase, for all diagnostic groups, wait times returned to pre-COVID-19 pandemic levels. During the third phase, wait times for all surgeries increased. CONCLUSION: Cancer surgery access may have been influenced by other factors, such as policy directives and local resource issues, independent of hospitalized COVID-19 patient volumes. The initial access limitations gradually improved with provincial and institutional resilience, and vaccine rollout.

Association of Reducing the Recommended Colorectal Cancer Screening Age With Cancer Incidence, Mortality, and Costs in Canada Using OncoSim.

Importance: Recent US guideline updates have advocated for colorectal cancer (CRC) screening to begin at age 45 years in average-risk adults, whereas Canadian screening programs continue to begin screening at age 50 years. Similarities in early-onset CRC rates in Canada and the US warrant discussion of earlier screening in Canada, but there is a lack of Canadian-specific modeling data to inform this. Objective: To estimate the association of a lowered initiation age for CRC screening by biennial fecal immunochemical test (FIT) with CRC incidence, mortality, and health care system costs in Canada. Design, Setting, and Participants/Exposures: This economic evaluation computational study used microsimulation modeling via the OncoSim platform. Main Outcomes and Measures: Modeled rates of CRC incidence, mortality, and health care costs in Canadian dollars. Results: This analysis included 4 birth cohorts (1973-1977, 1978-1982, 1983-1987, and 1988-1992) representative of the Canadian population accounting for previously documented effects of increasing CRC incidence in younger birth cohorts. Screening initiation at age 45 years resulted in a net 12 188 fewer CRC cases, 5261 fewer CRC deaths, and an added 92 112 quality-adjusted life-years (QALYs) to the cohort population over a 40-year period relative to screening from age 50 years. Screening initiation at age 40 years yielded 18 135 fewer CRC cases, 7988 fewer CRC deaths, and 150 373 QALYs. The cost per QALY decreased with younger birth cohorts to a cost of $762 per QALY when Canadians born in 1988 to 1992 began screening at age 45 years or $2622 per QALY with screening initiation at age 40 years. Although costs associated with screening and resulting therapeutic interventions increased with earlier screening, the overall health care system cost of managing CRC decreased. Conclusions and Relevance: This economic evaluation study using microsimulation modeling found that earlier screening may reduce CRC disease burden and add life-years to the Canadian population at a modest cost. Guideline changes suggesting earlier CRC screening in Canada may be justified, but evaluation of the resulting effects on colonoscopy capacity is necessary.

Patient, hospital and environmental costs of unnecessary bloodwork: capturing the triple bottom line of inappropriate care in general surgery patients.

OBJECTIVE: To characterise the extent of unnecessary care in general surgery inpatients using a triple bottom line approach. DESIGN: Patients with uncomplicated acute surgical conditions were retrospectively evaluated for unnecessary bloodwork according to the triple bottom line, quantifying the impacts on patients, healthcare costs and greenhouse gas emissions. The carbon footprint of common laboratory investigations was estimated using PAS2050 methodology, including emissions generated from the production, transport, processing and disposal of consumable goods and reagents. SETTING: Single-centre tertiary care hospital. PARTICIPANTS: Patients admitted with acute uncomplicated appendicitis, cholecystitis, choledocholithiasis, gallstone pancreatitis and adhesive small bowel obstruction were included in the study. 304 patients met inclusion criteria and 83 were randomly selected for in-depth chart review. MAIN OUTCOME MEASURES: In each patient population, the extent of over-investigation was determined by comparing ordered laboratory investigations against previously developed consensus recommendations. The quantity of unnecessary bloodwork was measured by number of phlebotomies, tests and blood volume in addition to healthcare costs and greenhouse gas emissions. RESULTS: 76% (63/83) of evaluated patients underwent unnecessary bloodwork resulting in a mean of 1.84 phlebotomies, 4.4 blood vials, 16.5 tests and 18 mL of blood loss per patient. The hospital and environmental cost of these unnecessary activities was $C5235 and 61 kg CO2e (974 g CO2e per person), respectively. The carbon footprint of a common set of investigations (complete blood count, differential, creatinine, urea, sodium, potassium) was 332 g CO2e. Adding a liver panel (liver enzymes, bilirubin, albumin, international normalised ratio/partial thromboplastin time) resulted in an additional 462 g CO2e. CONCLUSIONS: We found considerable overuse of laboratory investigations among general surgery patients admitted with uncomplicated acute surgical conditions resulting in unnecessary burden to patients, hospitals and the environment. This study identifies an opportunity for resource stewardship and exemplifies a comprehensive approach to quality improvement.

Local versus radical surgery for early rectal cancer with or without neoadjuvant or adjuvant therapy.

BACKGROUND: Total mesorectal excision is the standard of care for stage I rectal cancer. Despite major advances and increasing enthusiasm for modern endoscopic local excision (LE), uncertainty remains regarding its oncologic equivalence and safety relative to radical resection (RR). OBJECTIVES: To assess the oncologic, operative, and functional outcomes of modern endoscopic LE compared to RR surgery in adults with stage I rectal cancer. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science - Science Citation Index Expanded (1900 to present), four trial registers (ClinicalTrials.gov, ISRCTN registry, the WHO International Clinical Trials Registry Platform, and the National Cancer Institute Clinical Trials database), two thesis and proceedings databases, and relevant scientific societies' publications in February 2022. We performed handsearching and reference checking and contacted study authors of ongoing trials to identify additional studies. SELECTION CRITERIA: We searched for randomized controlled trials (RCTs) in people with stage I rectal cancer comparing any modern LE techniques to any RR techniques with or without the use of neo/adjuvant chemoradiotherapy (CRT). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We calculated hazard ratios (HR) and standard errors for time-to-event data and risk ratios for dichotomous outcomes, using generic inverse variance and random-effects methods. We regrouped surgical complications from the included studies into major and minor according to the standard Clavien-Dindo classification. We assessed the certainty of evidence using the GRADE framework. MAIN RESULTS: Four RCTs were included in data synthesis with a combined total of 266 participants with stage I rectal cancer (T1-2N0M0), if not stated otherwise. Surgery was performed in university hospital settings. The mean age of participants was above 60, and median follow-up ranged from 17.5 months to 9.6 years. Regarding the use of co-interventions, one study used neoadjuvant CRT in all participants (T2 cancers); one study used short-course radiotherapy in the LE group (T1-T2 cancers); one study used adjuvant CRT selectively in high-risk patients undergoing RR (T1-T2 cancers); and the fourth study did not use any CRT (T1 cancers). We assessed the overall risk of bias as high for oncologic and morbidity outcomes across studies. All studies had at least one key domain with a high risk of bias. None of the studies reported separate outcomes for T1 versus T2 or for high-risk features. Low-certainty evidence suggests that RR may result in an improvement in disease-free survival compared to LE (3 trials, 212 participants; HR 1.96, 95% confidence interval (CI) 0.91 to 4.24). This would translate into a three-year disease-recurrence risk of 27% (95% CI 14 to 50%) versus 15% after LE and RR, respectively. Regarding sphincter function, only one study provided objective results and reported short-term deterioration in stool frequency, flatulence, incontinence, abdominal pain, and embarrassment about bowel function in the RR group. At three years, the LE group had superiority in overall stool frequency, embarrassment about bowel function, and diarrhea. Local excision may have little to no effect on cancer-related survival compared to RR (3 trials, 207 participants; HR 1.42, 95% CI 0.60 to 3.33; very low-certainty evidence). We did not pool studies for local recurrence, but the included studies individually reported comparable local recurrence rates for LE and RR (low-certainty evidence). It is unclear if the risk of major postoperative complications may be lower with LE compared with RR (risk ratio 0.53, 95% CI 0.22 to 1.28; low-certainty evidence; corresponding to 5.8% (95% CI 2.4% to 14.1%) risk for LE versus 11% for RR). Moderate-certainty evidence shows that the risk of minor postoperative complications is probably lower after LE (risk ratio 0.48, 95% CI 0.27 to 0.85); corresponding to an absolute risk of 14% (95% CI 8% to 26%) for LE compared to 30.1% for RR. One study reported an 11% rate of temporary stoma after LE versus 82% in the RR group. Another study reported a 46% rate of temporary or permanent stomas after RR and none after LE. The evidence is uncertain about the effect of LE compared with RR on quality of life. Only one study reported standard quality of life function, in favor of LE, with a 90% or greater probability of superiority in overall quality of life, role, social, and emotional functions, body image, and health anxiety. Other studies reported a significantly shorter postoperative period to oral intake, bowel movement, and off-bed activities in the LE group. AUTHORS' CONCLUSIONS: Based on low-certainty evidence, LE may decrease disease-free survival in early rectal cancer. Very low-certainty evidence suggests that LE may have little to no effect on cancer-related survival compared to RR for the treatment of stage I rectal cancer. Based on low-certainty evidence, it is unclear if LE may have a lower major complication rate, but probably causes a large reduction in minor complication rate. Limited data based on one study suggest better sphincter function, quality of life, or genitourinary function after LE. Limitations exist with respect to the applicability of these findings. We identified only four eligible studies with a low number of total participants, subjecting the results to imprecision. Risk of bias had a serious impact on the quality of evidence. More RCTs are needed to answer our review question with greater certainty and to compare local and distant metastasis rates. Data on important patient outcomes such as sphincter function and quality of life are very limited. Results of currently ongoing trials will likely impact the results of this review. Future trials should accurately report and compare outcomes according to the stage and high-risk features of rectal tumors, and evaluate quality of life, sphincter, and genitourinary outcomes. The role of neoadjuvant or adjuvant therapy as an emerging co-intervention for improving oncologic outcomes after LE needs to be further defined.

Breast-Conserving Therapy is Associated with Improved Survival Without an Increased Risk of Locoregional Recurrence Compared with Mastectomy in Both Clinically Node-Positive and Node-Negative Breast Cancer Patients.

INTRODUCTION: Randomized trials demonstrated equivalent survival between breast-conserving surgery combined with radiotherapy (BCT) and mastectomy alone. Contemporary retrospective studies using pathological stage have reported improved survival with BCT. However, pathological information is unknown before surgery. To mimic real-world surgical decision-making, this study assesses oncological outcomes by using clinical nodal status. METHODS: Female patients aged 18-69 years who were treated with upfront BCT or mastectomy between 2006 and 2016 for T1-3N0-3 breast cancer were identified by using prospective, provincial database. The patients were divided into clinically node-positive (cN+) and node-negative (cN0) strata. Multivariable logistic regression was used to assess the effect of local treatment type on overall survival (OS), breast cancer-specific survival (BCSS), and locoregional recurrence (LRR). RESULTS: Of 13,914 patients, 8228 had BCT and 5686 had mastectomy. Mastectomy patients had higher-risk clinicopathological factors: pathologically positive axillary staging was 21% in BCT and 38% in mastectomy groups. Most patients received adjuvant systemic therapy. For cN0 patients, 7743 had BCT and 4794 had mastectomy. On multivariable analysis, BCT was associated with improved OS (hazard ratio [HR] 1.37, p < 0.001) and BCSS (HR 1.32, p < 0.001), whereas LRR was not different between the groups (HR 0.84, p = 0.1). For cN+ patients, 485 had BCT and 892 had mastectomy. On multivariable analysis, BCT was associated with improved OS (HR 1.46, p = 0.002) and BCSS (HR 1.44, p = 0.008), whereas LRR was not different between the groups (HR 0.89, p = 0.7). CONCLUSIONS: In the era of contemporary systemic therapy, BCT was associated with better survival than mastectomy, without an increased risk of locoregional recurrence for both cN0 and cN+ presentations.

Detection of viral RNAs at ambient temperature via reporter proteins produced through the target-splinted ligation of DNA probes.

Nucleic acid assays are not typically deployable in point-of-care settings because they require costly and sophisticated equipment for the control of the reaction temperature and for the detection of the signal. Here we report an instrument-free assay for the accurate and multiplexed detection of nucleic acids at ambient temperature. The assay, which we named INSPECTR (for internal splint-pairing expression-cassette translation reaction), leverages the target-specific splinted ligation of DNA probes to generate expression cassettes that can be flexibly designed for the cell-free synthesis of reporter proteins, with enzymatic reporters allowing for a linear detection range spanning four orders of magnitude and peptide reporters (which can be mapped to unique targets) enabling highly multiplexed visual detection. We used INSPECTR to detect a panel of five respiratory viral targets in a single reaction via a lateral-flow readout and ~4,000 copies of viral RNA via additional ambient-temperature rolling circle amplification of the expression cassette. Leveraging synthetic biology to simplify workflows for nucleic acid diagnostics may facilitate their broader applicability at the point of care.

Treatment Patterns and Outcomes of Preoperative Neoadjuvant Radiotherapy in Patients with Early-onset Rectal Cancer.

Preoperative radiotherapy for early-stage rectal cancer has risks and benefits that may impact treatment choice in young patients. We reviewed radiotherapy use and outcomes for rectal cancer by age. Patients with early-stage rectal cancer in the Canadian province of British Columbia from 2002 to 2016 were identified (n = 6,232). Baseline characteristics, treatment response, overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and locoregional recurrence rate (LRR) were compared between patients <50 (early-onset; n = 532) and ≥50 years old (average-onset; n = 5,700). Early-onset patients were more likely to receive preoperative chemoradiotherapy than short-course radiotherapy [OR, 2.20; 95% confidence interval (CI), 1.67-2.89; P < 0.0001], but also had higher nodal (P = 0.00096) and overall clinical staging (P = 0.033). Cancer downstaging and pathologic complete response rates were similar in those receiving neoadjuvant chemoradiotherapy by age. Early-onset and average-onset patients had similar DSS (P = 0.91) and DFS (P = 0.27) in multivariate analysis unless non-colorectal deaths, which were higher in older patients, were censored in the DFS model (HR, 1.30; 95% CI, 1.01-1.68; P = 0.042). LRR also did not differ between age groups (P = 0.88). Outcomes did not differ based on radiotherapy type. Young patients with rectal cancer are more likely to present with higher staging and receive long-course chemoradiotherapy. DSS did not differ by age group; however, young patients had worse DFS when we censored competing risks of death in older patients. Significance: This population-based study suggests younger patients are more likely to receive chemoradiotherapy, potentially due to higher stage at diagnosis, and response is comparable by age.

Weak-anchoring effects in a thin pinned ridge of nematic liquid crystal.

A theoretical investigation of weak-anchoring effects in a thin two-dimensional pinned static ridge of nematic liquid crystal resting on a flat solid substrate in an atmosphere of passive gas is performed. Specifically, we solve a reduced version of the general system of governing equations recently derived by Cousins et al. [Proc. R. Soc. A 478, 20210849 (2022)10.1098/rspa.2021.0849] valid for a symmetric thin ridge under the one-constant approximation of the Frank-Oseen bulk elastic energy with pinned contact lines to determine the shape of the ridge and the behavior of the director within it. Numerical investigations covering a wide range of parameter values indicate that the energetically preferred solutions can be classified in terms of the Jenkins-Barratt-Barbero-Barberi critical thickness into five qualitatively different types of solution. In particular, the theoretical results suggest that anchoring breaking occurs close to the contact lines. The theoretical predictions are supported by the results of physical experiments for a ridge of the nematic 4^{'}-pentyl-4-biphenylcarbonitrile (5CB). In particular, these experiments show that the homeotropic anchoring at the gas-nematic interface is broken close to the contact lines by the stronger rubbed planar anchoring at the nematic-substrate interface. A comparison between the experimental values of and the theoretical predictions for the effective refractive index of the ridge gives a first estimate of the anchoring strength of an interface between air and 5CB to be (9.80±1.12)×10^{-6}Nm^{-1} at a temperature of (22±1.5)^{∘}C.

Oncological Outcomes of Transanal Endoscopic Surgery for the Surgical Management of T2 and T3 Rectal Cancer.

BACKGROUND: Transanal endoscopic surgery is an organ-sparing treatment for early rectal cancer. Patients with advanced lesions are recommended for total mesorectal excision. However, some patients have prohibitive comorbidities or refuse major surgery. OBJECTIVE: To assess the cancer outcomes of patients with T2 or T3 rectal cancers who received transanal endoscopic surgery as their sole surgical treatment. DESIGN: This study used a prospectively maintained database. SETTING: A tertiary hospital in Canada. PATIENTS: Patients who underwent transanal endoscopic surgery for pathology-confirmed T2 or T3 rectal adenocarcinomas from 2007-2020 were included. MAIN OUTCOME MEASURES: Disease-free survival and overall survival, stratified by tumor stage and reason for transanal endoscopic surgery. RESULTS: Among the included 132 patients (T2, n = 96; T3, n = 36), average follow-up was 22 months. Twenty-eight decline oncologic resection, whereas 104 had preclusive comorbidities. Fifteen patients (11.4%) had disease recurrence (4 local, 11 metastatic). Three-year disease-free survival was 86.5% (95% CI, 77.1-95.9) for T2 and 67.9% (95% CI, 46.3-89.5) for T3 tumors. Mean disease-free survival was longer for T2 (75.0 mo; 95% CI, 67.8-82.1) compared to T3 cancers (50 mo; 95% CI, 37.7-62.3; p = 0.037). Three-year disease-free survival for patients who declined radical excision was 84.0% (95% CI, 67.1-100) versus 80.7% (95% CI, 69.7-91.7) in patients too comorbid for surgery. Three-year overall survival rate was 84.9% (95% CI, 73.9-95.9) for T2 and 49.0% (95% CI, 26.7-71.3) for T3 tumors. Patients who declined radical resection had similar 3-year overall survival (89.7%; 95% CI, 76.2-100) compared to patients who were unable to undergo excision because of medical comorbidities (98.1%; 95% CI, 95.6-100). LIMITATIONS: Small sample, single institution, and surgeon experience. CONCLUSIONS: Oncologic outcomes are compromised in patients treated by transanal endoscopic surgery for T2 and T3 rectal cancer. Transanal endoscopic surgery remains an option for informed patients who prefer to avoid radical resection. See Video Abstract at http://links.lww.com/DCR/C200 . RESULTADOS ONCOLGICOS DE LA CIRUGA ENDOSCPICA TRANSANAL PARA EL MANEJO QUIRRGICO DEL CNCER DE RECTO T Y T: ANTECEDENTES:La cirugía endoscópica transanal es un tratamiento de conservación de órganos para el cáncer de recto en estadio temprano. A los pacisentes con lesiones avanzadas se les recomienda la escisión total del mesorrecto. Sin embargo, algunos pacientes tienen comorbilidades prohibitivas o rechazan una cirugía mayor.OBJETIVO:Evaluar los resultados del cáncer de pacientes con cáncer de recto T2 o T3 que recibieron cirugía endoscópica transanal como único tratamiento quirúrgico.DISEÑO:Este estudio utilizó una base de datos mantenida prospectivamente.ENTORNO CLINICO:Un hospital terciario en CanadáPACIENTES:Aquellos que se sometieron a cirugía endoscópica transanal por adenocarcinomas rectales T2 o T3 confirmados por patología de 2007-2020. Se excluyeron los pacientes cuya cirugía se realizó por recurrencia del cáncer o posteriormente fueron sometidos a resección radical.PRINCIPALES MEDIDAS DE VALORACIÓN:Supervivencia libre de enfermedad y supervivencia global, estratificada por estadio del tumor y motivo de la cirugía endoscópica transanal.RESULTADOS:Se incluyeron 132 pacientes (T2, n = 96; T3, n = 36). El seguimiento medio fue de 22 meses (DE ± 23,4). 104 pacientes tenían comorbilidades significativas, mientras que 28 rechazaron la resección oncológica. Quince pacientes (11,4%) tuvieron recurrencia de la enfermedad (4 locales, 11 metastásicos). La supervivencia libre de enfermedad a los tres años para los tumores T2 fue del 86,5 % (IC del 95%: 77,1-95,9) y del 67,9% (IC del 95%: 46,3-89,5) para los tumores T3. La supervivencia libre de enfermedad media fue más prolongada para los cánceres T2 (75,0 meses, IC del 95%: 67,8 a 82,1) en comparación con los cánceres T3 (50 meses, IC del 95%: 37,7 a 62,3, p = 0,037). La supervivencia sin enfermedad a los tres años para los pacientes que rechazaron la escisión mesorrectal total fue del 84,0% (IC del 95%: 67,1-100), mientras que los pacientes con demasiada comorbilidad médica para la cirugía tuvieron una supervivencia sin enfermedad a los tres años del 80,7% (IC del 95%: 69.7-91.7). La supervivencia general a los tres años fue del 84,9% (IC del 95%: 73,9 a 95,9) para los tumores T2 y del 49,0% (IC del 95%: 26,7 a 71,3) para los tumores T3. Los pacientes que rechazaron la resección radical tuvieron una supervivencia general similar a los tres años (89,7%, IC del 95%: 76,2-100), en comparación con los pacientes que no pudieron someterse a una escisión mesorrectal total debido a comorbilidades médicas (98,1%, IC del 95%: 95,6-100).LIMITACIONES:Muestra pequeña, institución única, experiencia del cirujano.CONCLUSIONES:Los resultados oncológicos están comprometidos en pacientes tratados con cirugía endoscópica transanal por cáncer de recto T2 y T3. Sin embargo, la cirugía endoscópica transanal sigue siendo una opción para pacientes informados que prefieren evitar la resección radical. Consulte Video Resumen en http://links.lww.com/DCR/C200 . (Traducción-Dr. Ingrid Melo ).

Management of rectal neuroendocrine tumours by transanal endoscopic microsurgery.

AIM: The objective of this study was to evaluate the safety and effectiveness of transanal endoscopic microsurgery for rectal neuroendocrine tumours. METHOD: A retrospective cohort study of all pathology-confirmed rectal neuroendocrine tumours treated by transanal endoscopic microsurgery from April 2007 to December 2020 at a tertiary care centre was performed. Demographic, clinical, radiographic and pathological data were collected. Characteristics of patients with recurrence were examined. Descriptive statistics were performed. RESULTS: There were 58 patients treated by transanal endoscopic microsurgery excision. Referrals were for primary excision (15, 25.9%), completion re-excision after incomplete endoscopic removal (38, 65.5%) or locally recurrent rectal neuroendocrine tumours (5, 8.6%). The mean age of patients was 56.4 ± 11.9 years and 26 patients were women (44.8%). Mean tumour size was 7.4 ± 3.8 mm (range 1.0-15.0 mm). Most (86.4%) were Grade 1 tumours. Mean operative time was 37.2 ± 17.2 min and 56 patients (96.6%) were discharged on the same day. All patients had negative margins on final pathology. Of the 38 patients who were referred for completion re-excision after incomplete endoscopic removal, eight (21.1%) had residual tumour on final pathology. Three recurrences were diagnosed at 2.1, 4.5 and 12.5 years after excision. All recurrences were from Grade 1 or 2 primary tumours, less than 2 cm, and diagnosed radiographically. CONCLUSION: To date, this is the largest North American study looking at transanal endoscopic microsurgery for rectal neuroendocrine tumours. This technique is effective in managing primary, incompletely excised and recurrent tumours with good clinical and oncological outcomes.