The Role of Circulating Tumor DNA for Management of Patients With Rectal Cancer: Challenges and Opportunities.

ABSTRACT: Recently, organ preservation with total neoadjuvant therapy resulted in substantial progress in the management of locally advanced rectal cancer (LARC). The PROSPECT trial showed noninferiority of de-escalation of radiotherapy for patients with low-risk LARC who do not need abdominoperineal resection. Although these escalation and de-escalation approaches offer more personalized therapeutic approaches, the current state of care for patients with rectal cancer is far from individualized management. Circulating tumor DNA (ctDNA) is known to be one of the most powerful prognostic factors for early relapse and has been investigated in several interventional clinical trials to offer more precise treatment algorithms. In this review article, we discuss recent updates from studies examining the role of ctDNA for the prediction of treatment response and recurrence for patients with rectal cancer. We also elaborate on the future potential use of ctDNA in treatment escalation and de-escalation approaches for more personalized therapeutic interventions.

Variables impacting prolonged post-anesthesia care unit length of stay in gynecologic cancer patients in the era of same day minimally invasive hysterectomy.

OBJECTIVES: Minimally invasive surgery for treatment of gynecologic malignancies is associated with decreased pain, fewer complications, earlier return to activity, lower cost, and shorter hospital stays. Patients are often discharged the day of surgery, but occasionally stay overnight due to prolonged post-anesthesia care unit (PACU) stays. The objective of this study was to identify risk factors for prolonged PACU length of stay (LOS). METHODS: This is a single institution retrospective review of patients who underwent minimally invasive hysterectomy for gynecologic cancer from 2019 to 2022 and had a hospital stay <24-h. The primary outcome was PACU LOS. Demographics, pre-operative diagnoses, and surgical characteristics were recorded. After Box-Cox transformation, linear regression was used to determine significant predictors of PACU LOS. RESULTS: For the 661 patients identified, median PACU LOS was 5.04 h (range 2.16-23.76 h). On univariate analysis, longer PACU LOS was associated with increased age (ρ = 0.106, p = 0.006), non-partnered status [mean difference (MD) = 0.019, p = 0.099], increased alcohol use (MD = 0.018, p = 0.102), increased Charlson Comorbidity Index (CCI) score (ρ = 0.065, p = 0.097), and ASA class ≥3 (MD = 0.033, p = 0.002). Using multivariate linear regression, increased age (R2 = 0.0011, p = 0.043), non-partnered status (R2 = 0.0389, p < 0.001), and ASA class ≥3 (R2 = 0.0250, p = 0.023) were associated with increased PACU LOS. CONCLUSIONS: Identifying patients at risk for prolonged PACU LOS, including patients who are older, non-partnered, and have an ASA class ≥3, may allow for interventions to improve patient experience, better utilize hospital resources, decrease PACU overcrowding, and limit postoperative admissions and complications. The relationship between non-partnered status and PACU LOS is the most novel relationship identified in this study.

Comparison of outcomes of abdominoperineal resection vs low anterior resection in very-low rectal cancer.

BACKGROUND: The management of very-low rectal cancer is one of the most challenging issues faced by general and colorectal surgeons. Many feel compelled to pursue abdominoperineal resection (APR) over low anterior resection (LAR) to optimize oncologic outcomes. This study aimed to determine differences in long-term oncologic outcomes between patients undergoing APR or LAR for very-low rectal cancer. METHODS: The United States Rectal Cancer Consortium (2010-2016) was queried for adults who underwent either APR or LAR for stage I-III rectal cancers < 5 cm from anorectal junction and met inclusion criteria. The primary outcome was disease-free survival. Secondary outcomes included overall survival, length of stay, complications, recurrence location, and perioperative factors. RESULTS: A total of 431 patients with very-low rectal cancer who underwent APR or LAR were identified; 154 (35.7%) underwent APR. The overall recurrence rate was 19.6%. The median follow-up was 42.5 months. An analysis adjusted for demographics and pathologic stage observed no difference in disease-free survival between operative types (APR-hazard ratio [HR] = 0.90, 95% CI: 0.53-1.52, P = .70). Secondary outcomes demonstrated no significant difference between operation types, including overall survival (HR = 1.29, 95% CI: 0.71-2.32, P = .39), complications (OR = 1.53, 95% CI: 0.94-2.50, P = .12), or length of stay (estimate: 0.04, SE = 0.25, P = .54). CONCLUSION: We observed no significant difference in disease-free survival or overall survival between patients undergoing APR or LAR for very-low rectal cancer. This analysis supports the treatment of very-low rectal cancer, without sphincter involvement, by either APR or LAR.

On the stability of norms and norm-following propensity: a cross-cultural panel study with adolescents.

Norm-based accounts of social behavior in economics typically reflect tradeoffs between maximization of own consumption utility and conformity to social norms. Theories of norm-following tend to assume that there exists a single, stable, commonly known injunctive social norm for a given choice setting and that each person has a stable propensity to follow social norms. We collect panel data on 1468 participants aged 11-15 years in Belfast, Northern Ireland and Bogotá, Colombia in which we measure norms for the dictator game and norm-following propensity twice at 10 weeks apart. We test these basic assumptions and find that norm-following propensity is stable, on average, but reported norms show evidence of change. We find that individual-level variation in reported norms between people and within people across time has interpretable structure using a series of latent transition analyses (LTA) which extend latent class models to a panel setting. The best fitting model includes five latent classes corresponding to five sets of normative beliefs that can be interpreted in terms of what respondents view as "appropriate" (e.g. equality vs. generosity) and how they view deviations (e.g. deontological vs. consequentialist). We also show that a major predictor of changing latent classes over time comes from dissimilarity to others in one's network. Our application of LTA demonstrates how researchers can engage with heterogeneity in normative perceptions by identifying latent classes of beliefs and deepening understanding of the extent to which norms are shared, stable, and can be predicted to change. Finally, we contribute to the nascent experimental literature on the economic behavior of children and adolescents. Supplementary Information: The online version contains supplementary material available at 10.1007/s10683-024-09821-5.

Deprivation and Rurality Mediate Income Inequality's Association with Colorectal Cancer Outcomes.

INTRODUCTION: Income inequality is associated with poor health outcomes, but its association with colorectal cancer is not well-studied. The authors aimed to determine the association between income inequality and colorectal cancer incidence/mortality in U.S. counties, and hypothesized that this association was mediated by deprivation. METHODS: The authors performed a cross-sectional study of U.S. counties from 2015-2019 using statewide cancer registries and the Centers for Disease Control and Prevention WONDER database. Generalized linear negative binomial regression was performed in 2024 to estimate the association between Gini coefficient (income inequality) and colorectal cancer incidence/mortality using incidence rate ratios (IRRs) for the entire cohort and stratified by rurality. RESULTS: A total of 697,981 colorectal cancer cases were diagnosed in the 5-year study period. On adjusted regression, for every 0.1 higher Gini coefficient, there was an 11% higher risk of both colorectal cancer incidence and mortality (IRR 1.11, 95%CI 1.03,1.19 and IRR 1.11, 95%CI 1.05, 1.18 respectively). The association between income inequality and incidence/mortality peaked in more rural counties, however there was not an overall dose-dependent relationship between rurality and these associations. Deprivation mediated the association between income inequality and colorectal cancer incidence (indirect effect B coefficient 0.088, p<0.001) and mortality (B coefficient 0.088, p<0.001). The magnitude and direction of the direct, indirect, and total effects differed in each rurality strata. CONCLUSIONS: Much of income inequality's association with colorectal cancer outcomes operates through deprivation. Rural counties have a stronger association between higher income inequality and higher mortality, which works in tandem with deprivation.

Association of Surgical Approaches and Outcomes in Total Mesorectal Excision and Margin Status for Rectal Cancer.

INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer. METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected from the US Rectal Cancer Consortium database (2007-2017). Quasi-Poisson regression analysis with backward selection was used to investigate the relationship between the surgical approach and outcomes of interest. RESULTS: Among the 664 patients included in the study, the distribution of surgical approaches was as follows: 351 (52.9%) underwent TME via the open approach, 159 (23.9%) via the robotic approach, and 154 (23.2%) via the laparoscopic approach. There were no significant differences in baseline demographics among the three cohorts. The laparoscopic cohort had fewer patients with low rectal cancer (<6 cm from the anal verge) than the robotic and open cohorts (Lap 28.6% versus Rob 59.1% versus Open 45.6%, P = 0.015). Patients who underwent Rob and Lap TME had lower intraoperative blood loss compared with the Open approach (Rob 200 mL [Q1, Q3: 100.0, 300.0] versus Lap 150 mL [Q1, Q3: 75.0, 250.0] versus Open 300 mL [Q1, Q3: 150.0, 600.0], P < 0.001). There was no difference in the operative time (Rob 243 min [Q1, Q3: 203.8, 300.2] versus Lap 241 min [Q1, Q3: 186, 336] versus Open 226 min [Q1, Q3: 178, 315.8], P = 0.309) between the three approaches. Postoperative length of stay was shorter with robotic and laparoscopic approach compared to open approach (Rob 5.0 d [Q1, Q3: 4, 8.2] versus Lap 5 d [Q1, Q3: 4, 8] versus Open 7.0 d [Q1, Q3: 5, 9], P < 0.001). There was no statistically significant difference in the quality of TME between the robotic, laparoscopic, and open approaches (79.2%, 64.9%, and 64.7%, respectively; P = 0.46). The margin positivity rate, a composite of circumferential margin and distal margin, was higher with the robotic and open approaches than with the laparoscopic approach (Rob 8.2% versus Open 6.6% versus Lap 1.9%, P = 0.17), Rob versus Lap (odds ratio 0.21; 95% confidence interval 0.05, 0.83) and Rob versus Open (odds ratio 0.5; 95% confidence interval 0.22, 1.12). There was no difference in long-term survival, including overall survival and recurrence-free survival, between patients who underwent robotic, laparoscopic, or open TME (Figure 1). CONCLUSIONS: In patients undergoing surgery with curative intent for rectal cancer, we did not observe a difference in the quality of TME between the robotic, laparoscopic, or open approaches. Robotic and open TME compared to laparoscopic TME were associated with higher margin positivity rates in our study. This was likely due to the higher percentage of low rectal cancers in the robotic and open cohorts. We also reported no significant differences in overall survival and recurrence-free survival between the aforementioned surgical techniques.

Childhood adversity and mental health admission patterns prior to young person suicide (CHASE): a case-control 36 year linked hospital data study, Scotland UK 1981-2017.

BACKGROUND: Childhood adversity is associated with increased later mental health problems and suicidal behaviour. Opportunities for earlier healthcare identification and intervention are needed. AIM: To determine associations between hospital admissions for childhood adversity and mental health in children who later die by suicide. METHOD: Population-based longitudinal case-control study. Scottish in-patient general and psychiatric records were summarised for individuals born 1981 or later who died by suicide between 1991 and 2017 (cases), and matched controls (1:10), for childhood adversity and mental health (broadly defined as psychiatric diagnoses and general hospital admissions for self-harm and substance use). RESULTS: Records were extracted for 2477 'cases' and 24 777 'controls'; 2106 cases (85%) and 13 589 controls (55%) had lifespan hospitalisations. Mean age at death was 23.7; 75.9% were male. Maltreatment or violence-related childhood adversity codes were recorded for 7.6% cases aged 10-17 (160/2106) versus 2.7% controls (371/13 589), odds ratio = 2.9 (95% CI, 2.4-3.6); mental health-related admissions were recorded for 21.7% cases (458/2106), versus 4.1% controls (560/13 589), odds ratio = 6.5 (95% CI, 5.7-7.4); 80% of mental health admissions were in general hospitals. Using conditional logistic models, we found a dose-response effect of mental health admissions <18y, with highest adjusted odds ratio (aOR) for three or more mental health admissions: aORmale = 8.17 (95% CI, 5.02-13.29), aORfemale = 15.08 (95% CI, 8.07-28.17). We estimated that each type of childhood adversity multiplied odds of suicide by aORmale = 1.90 (95% CI, 1.64-2.21), aORfemale = 2.65 (95% CI, 1.94-3.62), and each mental health admission by aORmale = 2.06 (95% CI, 1.81-2.34), aORfemale = 1.78 (95% CI, 1.50-2.10). CONCLUSIONS: Our lifespan study found that experiencing childhood adversity (primarily maltreatment or violence-related admissions) or mental health admissions increased odds of young person suicide, with highest odds for those experiencing both. Healthcare practitioners should identify and flag potential 'at-risk' adolescents to prevent future suicidal acts, especially those in general hospitals.

A Novel Digital Health Platform With Health Coaches to Optimize Surgical Patients: Feasibility Study at a Large Academic Health System.

BACKGROUND: Pip is a novel digital health platform (DHP) that combines human health coaches (HCs) and technology with patient-facing content. This combination has not been studied in perioperative surgical optimization. OBJECTIVE: This study's aim was to test the feasibility of the Pip platform for deploying perioperative, digital, patient-facing optimization guidelines to elective surgical patients, assisted by an HC, at predefined intervals in the perioperative journey. METHODS: We conducted an institutional review board-approved, descriptive, prospective feasibility study of patients scheduled for elective surgery and invited to enroll in Pip from 2.5 to 4 weeks preoperatively through 4 weeks postoperatively at an academic medical center between November 22, 2022, and March 27, 2023. Descriptive primary end points were patient-reported outcomes, including patient satisfaction and engagement, and Pip HC evaluations. Secondary end points included mean or median length of stay (LOS), readmission at 7 and 30 days, and emergency department use within 30 days. Secondary end points were compared between patients who received Pip versus patients who did not receive Pip using stabilized inverse probability of treatment weighting. RESULTS: A total of 283 patients were invited, of whom 172 (60.8%) enrolled in Pip. Of these, 80.2% (138/172) patients had ≥1 HC session and proceeded to surgery, and 70.3% (97/138) of the enrolled patients engaged with Pip postoperatively. The mean engagement began 27 days before surgery. Pip demonstrated an 82% weekly engagement rate with HCs. Patients attended an average of 6.7 HC sessions. Of those patients that completed surveys (95/138, 68.8%), high satisfaction scores were recorded (mean 4.8/5; n=95). Patients strongly agreed that HCs helped them throughout the perioperative process (mean 4.97/5; n=33). The average net promoter score was 9.7 out of 10. A total of 268 patients in the non-Pip group and 128 patients in the Pip group had appropriate overlapping distributions of stabilized inverse probability of treatment weighting for the analytic sample. The Pip cohort was associated with LOS reduction when compared to the non-Pip cohort (mean 2.4 vs 3.1 days; median 1.9, IQR 1.0-3.1 vs median 3.0, IQR 1.1-3.9 days; mean ratio 0.76; 95% CI 0.62-0.93; P=.009). The Pip cohort experienced a 49% lower risk of 7-day readmission (relative risk [RR] 0.51, 95% CI 0.11-2.31; P=.38) and a 17% lower risk of 30-day readmission (RR 0.83, 95% CI 0.30-2.31; P=.73), though these did not reach statistical significance. Both cohorts had similar 30-day emergency department returns (RR 1.06, 95% CI 0.56-2.01, P=.85). CONCLUSIONS: Pip is a novel mobile DHP combining human HCs and perioperative optimization content that is feasible to engage patients in their perioperative journey and is associated with reduced hospital LOS. Further studies assessing the impact on clinical and patient-reported outcomes from the use of Pip or similar DHPs HC combinations during the perioperative journey are required.

Drivers of inappropriate use of antimicrobials in South Asia: A systematic review of qualitative literature.

Antimicrobial resistance is a global public health crisis. Effective antimicrobial stewardship requires an understanding of the factors and context that contribute to inappropriate use of antimicrobials. The goal of this qualitative systematic review was to synthesize themes across levels of the social ecological framework that drive inappropriate use of antimicrobials in South Asia. In September 2023, we conducted a systematic search using the electronic databases PubMed and Embase. Search terms, identified a priori, were related to research methods, topic, and geographic location. We identified 165 articles from the initial search and 8 upon reference review (n = 173); after removing duplicates and preprints (n = 12) and excluding those that did not meet eligibility criteria (n = 115), 46 articles were included in the review. We assessed methodological quality using the qualitative Critical Appraisal Skills Program checklist. The studies represented 6 countries in South Asia, and included data from patients, health care providers, community members, and policy makers. For each manuscript, we wrote a summary memo to extract the factors that impede antimicrobial stewardship. We coded memos using NVivo software; codes were organized by levels of the social ecological framework. Barriers were identified at multiple levels including the patient (self-treatment with antimicrobials; perceived value of antimicrobials), the provider (antimicrobials as a universal therapy; gaps in knowledge and skills; financial or reputational incentives), the clinical setting (lack of resources; poor regulation of the facility), the community (access to formal health care; informal drug vendors; social norms), and policy (absence of a regulatory framework; poor implementation of existing policies). This study is the first to succinctly identify a range of norms, behaviors, and policy contexts driving inappropriate use of antimicrobials in South Asia, emphasizing the importance of working across multiple sectors to design and implement approaches specific to the region.

Generalization of a positive-feature interoceptive morphine occasion setter across the rat estrous cycle.

INTRODUCTION: Interoceptive stimuli elicited by drug administration acquire conditioned modulatory properties of the induction of conditioned appetitive behaviours by exteroceptive cues. This effect may be modeled using a drug discrimination task in which the drug stimulus is trained as a positive-feature (FP) occasion setter (OS) that disambiguates the relation between an exteroceptive light conditioned stimulus (CS) and a sucrose unconditioned stimulus (US). We previously reported that females are less sensitive to generalization of a FP morphine OS than males, so we investigated the role of endogenous ovarian hormones in this difference. METHODS: Male and female rats received intermixed injections of 3.2 mg/kg morphine or saline before each daily training session. Training consisted of 8 presentations of the CS, each followed by access to sucrose on morphine, but not saline sessions. Following acquisiton, rats were tested for generalization of the morphine stimulus to 0, 1.0, 3.2, and 5.4 mg/kg morphine. Female rats were monitored for estrous cyclicity using vaginal cytology throughout the study. RESULTS: Both sexes acquired stable drug discrimination. A gradient of generalization was measured across morphine doses and this behaviour did not differ by sex, nor did it differ across the estrous cycle in females. CONCLUSIONS: Morphine generalization is independent of fluctuations in levels of sex and endogenous gonadal hormones in females under these experimental conditions.

Disruption of positive- and negative-feature morphine interoceptive occasion setters by dopamine receptor agonism and antagonism in male and female rats.

RATIONALE: Internally perceived stimuli evoked by morphine administration can form Pavlovian associations such that they can function as occasion setters (OSs) for externally perceived reward cues in rats, coming to modulate reward-seeking behaviour. Though much research has investigated mechanisms underlying opioid-related reinforcement and analgesia, neurotransmitter systems involved in the functioning of opioids as Pavlovian interoceptive discriminative stimuli remain to be disentangled despite documented differences in the development of tolerance to analgesic versus discriminative stimulus effects. OBJECTIVES: Dopamine has been implicated in many opioid-related behaviours, so we aimed to investigate the role of this neurotransmitter in expression of morphine occasion setting. METHODS: Male and female rats were assigned to positive- (FP) or negative-feature (FN) groups and received an injection of morphine or saline before each training session. A 15-s white noise conditioned stimulus (CS) was presented 8 times during every training session; offset of this stimulus was followed by 4-s access to liquid sucrose on morphine, but not saline, sessions for FP rats. FN rats learned the reverse contingency. Following stable discrimination, rats began generalization testing for expression of morphine-guided sucrose seeking after systemic pretreatment with different doses of the non-selective dopamine receptor antagonist, flupenthixol, and the non-selective dopamine receptor agonist, apomorphine, combined with training doses of morphine or saline in a Latin-square design. RESULTS: The morphine discrimination was acquired under both FP and FN contingencies by males and females. Neither flupenthixol nor apomorphine at any dose substituted for morphine, but both apomorphine and flupenthixol disrupted expression of the morphine OS. This inhibition was specific to sucrose seeking during CS presentations rather than during the period before CS onset and, in the case of apomorphine more so than flupenthixol, to trials on which access to sucrose was anticipated. CONCLUSIONS: Our findings lend support to a mechanism of occasion setting involving gating of CS-induced dopamine release rather than by direct dopaminergic modulation by the morphine stimulus.

Prophylactic defunctioning stomas improve clinical outcomes of anastomotic leak following rectal cancer resections: An analysis of the US Rectal Cancer Consortium.

PURPOSE: Anastomotic leak (AL) is a complication of low anterior resection (LAR) that results in substantial morbidity. There is immense interest in evaluating immediate postoperative and long-term oncologic outcomes in patients who undergo diverting loop ileostomies (DLI). The purpose of this study is to understand the relationship between fecal diversion, AL, and oncologic outcomes. METHODS: This is a retrospective multicenter cohort study using patient data obtained from the US Rectal Cancer Consortium database compiled from six academic institutions. The study population included patients with rectal adenocarcinoma undergoing LAR. The primary outcome was the incidence of AL among patients who did or did not receive DLI during LAR. Secondary outcomes included risk factors for AL, receipt of adjuvant therapy, 3-year overall survival, and 3-year recurrence. RESULTS: Of 815 patients, 38 (4.7%) suffered AL after LAR. Patients with AL were more likely to be male, have unintentional preoperative weight loss, and are less likely to undergo DLI. On multivariable analysis, DLI remained protective against AL (p < 0.001). Diverted patients were less likely to undergo future surgical procedures including additional ostomy creation, completion proctectomy, or pelvic washout for AL. Subgroup analysis of 456 patients with locally advanced disease showed that DLI was correlated with increased receipt of adjuvant therapy for patients with and without AL on univariate analysis (SHR:1.59; [95% CI 1.19-2.14]; p = 0.002), but significance was not met in multivariate models. CONCLUSION: Lack of DLI and preoperative weight loss was associated with anastomotic leak. Fecal diversion may improve the timely initiation of adjuvant oncologic therapy. The long-term outcomes following routine diverting stomas warrant further study.

Predictors of recurrence and long-term patient reported outcomes following surgical repair of anal fistula, a retrospective analysis.

PURPOSE: Surgery for anal fistulas can result in devastating complications, including reoperations and fecal incontinence. There is limited contemporary evidence comparing outcomes since the adoption of the ligation of intersphincteric fistula tract procedure into mainstream practice. The purpose of this study is to compare recurrence rates and long-term outcomes of anal fistula following repair. METHODS: Data was collected from the electronic medical records or patient reported outcomes from patients aged 18 or older with a primary or recurrent cryptoglandular anal fistula. Primary outcome was recurrence defined as the identification of at least one fistula os or a high clinical suspicion of anal fistula. Secondary outcomes included fecal incontinence and postoperative quality of life. RESULTS: A total of 171 patients underwent definitive surgical repairs for their anal fistula. So 66.5% had a simple fistula, and 33.5% had a complex fistula. Of the 171 patients, 12.5% had a recurrence. The recurrence rates were 5.9% for simple fistula and 25.4% for complex fistula. Predictors of recurrence included diabetes mellitus, history of anorectal abscess, complex fistula, and sphincter sparing surgery. LIFT or plug/biologic procedures were both associated with a 50% or greater recurrence rate. No significant differences were found in fecal incontinence or associated quality of life between sphincter sparing or non-sphincter sparing surgical resections. CONCLUSION: The study provides insights into the long-term outcomes of surgical repair for anal fistula. We demonstrate that sphincter sparing operations are associated with increased recurrence, meanwhile, non-sphincter sparing surgeries did not increase the risk of fecal incontinence or worsen quality of life.

Association of omental pedicled flap with anastomotic leak following low anterior resection for rectal cancer.

BACKGROUND AND OBJECTIVES: Anastomotic leak following colorectal anastomosis adversely impacts short-term, oncologic, and quality-of-life outcomes. This study aimed to assess the impact of omental pedicled flap (OPF) on anastomotic leak among patients undergoing low anastomotic resection (LAR) for rectal cancer using a multi-institutional database. METHODS: Adult rectal cancer patients in the US Rectal Cancer Consortium, who underwent a LAR for stage I-III rectal cancer with or without an OPF were included. Patients with missing data for surgery type and OPF use were excluded from the analysis. The primary outcome was the development of anastomotic leaks. Multivariable logistic regression was used to determine the association. RESULTS: A total of 853 patients met the inclusion criteria and OPF was used in 106 (12.4%) patients. There was no difference in age, sex, or tumor stage of patients who underwent OPF versus those who did not. OPF use was not associated with an anastomotic leak (p = 0.82), or operative blood loss (p = 0.54) but was associated with an increase in the operative duration [ß = 21.42 (95% confidence interval = 1.16, 41.67) p = 0.04]. CONCLUSIONS: Among patients undergoing LAR for rectal cancer, OPF use was associated with an increase in operative duration without any impact on the rate of anastomotic leak.

Teaching by texting to promote positive health behaviours in pregnancy: a protocol for a randomised controlled trial of SmartMom.

INTRODUCTION: Prenatal education is associated with positive health behaviours, including optimal weight gain, attendance at prenatal care, acceptance of routine screening tests, smoking cessation, decreased alcohol consumption and breast feeding. Adoption of these behaviours has been associated with reduced rates of caesarean birth, preterm birth and low birth weight. Barriers to prenatal class attendance faced by parents in Canada include geography, socioeconomic status, age, education, and, among Indigenous peoples and other equity-deserving groups, stigma. To address the need for easily accessible and reliable information, we created 'SmartMom', Canada's first prenatal education programme delivered by short message service text messaging. SmartMom provides evidence-based information timed to be relevant to each week of pregnancy. The overall goal of SmartMom is to motivate the adoption of positive prenatal health behaviours with the ultimate goal of improving health outcomes among women and their newborns. METHODS AND ANALYSIS: We will conduct a two-arm single-blinded randomised controlled trial. Blinding of participants to trial intervention will not be possible as they will be aware of receiving the intervention, but data analysts will be blinded. Our primary research questions are to determine if women experiencing uncomplicated pregnancies randomly assigned to receive SmartMom messages versus messages addressing general topics related to pregnancy but without direction for behaviour change, have higher rates of: (1) weight gain within ranges recommended for prepregnancy body mass index and (2) adherence to Canadian guidelines regarding attendance at prenatal care appointments. ETHICS AND DISSEMINATION: The study has been granted a Certificate of Approval, number H22-00603, by the University of British Columbia Research Ethics Board. To disseminate our findings, we are undertaking both integrated and end-of-grant knowledge translation, which will proactively involve potential end-users and stakeholders at every phase of our project. TRIAL REGISTRATION NUMBER: NCT05793944.

Short-course radiation with consolidation chemotherapy does not increase operative morbidity compared to long-course chemoradiation: A retrospective study of the US rectal cancer consortium.

BACKGROUND AND OBJECTIVES: Neoadjuvant short-course radiation and consolidation chemotherapy (SC TNT) remains less widely used for rectal cancer in the United States than long-course chemoradiation (LCRT). SC TNT may improve compliance and downstaging; however, a longer radiation-to-surgery interval may worsen pelvic fibrosis and morbidity with total mesorectal excision (TME). A single, US-center retrospective analysis has shown comparable risk of morbidity after neoadjuvant short-course radiation with consolidation chemotherapy (SC TNT) and long-course chemoradiation (LCRT). Validation by a multi-institutional study is needed. METHODS: The US Rectal Cancer Consortium database (2010-2018) was retrospectively reviewed for patients with nonmetastatic, rectal adenocarcinoma treated with neoadjuvant LCRT or SC TNT before TME. The primary endpoint was severe postoperative morbidity. Cohorts were compared by univariate analysis. Multivariable logistic regression modeled the odds of severe complication. RESULTS: Of 788 included patients, 151 (19%) received SC TNT and 637 (81%) LCRT. The SC TNT group had fewer distal tumors (33.8% vs. 50.2%, p < 0.0001) and more clinical node-positive disease (74.2% vs. 47.6%, p < 0.0001). The intraoperative complication rate was similar (SC TNT 5.3% vs. 4.4%, p = 0.65). There was no difference in overall postoperative morbidity (38.4% vs. 46.3%, p = 0.08). Severe morbidity was similar with low anterior resection (9.1% vs. 15.3%, p = 0.10) and abdominoperineal resection (24.4% vs. 29.7%, p = 0.49). SC TNT did not increase the odds of severe morbidity relative to LCRT on multivariable analysis (OR 0.64, 95% CI 0.37-1.10). CONCLUSIONS: SC TNT does not increase morbidity after TME for rectal cancer relative to LCRT. Concern for surgical complications should not discourage the use of SC TNT when aiming to increase the likelihood of complete clinical response.

Use of Perioperative Intravenous Lidocaine as Part of an Abdominal Surgery Enhanced Recovery Pathway Does Not Significantly Impact Postoperative Pain.

BACKGROUND: The utility of perioperative intravenous lidocaine in improving postoperative pain control remains unclear. We aimed to compare postoperative pain outcomes in ERP abdominal surgery patients who did vs did not receive intravenous lidocaine. We hypothesized that patients receiving lidocaine would have lower postoperative pain scores and consume fewer opioids. METHODS: We performed a retrospective cohort study of patients undergoing elective abdominal surgery at a single institution via an ERP from 2017 to 2018. Patients who received lidocaine in the 6 months prior to a lidocaine shortage were compared to those who did not receive lidocaine for 6 months following the shortage. The primary outcome measures were pain scores as measured on the visual analogue scale and opioid consumption as measured by oral morphine equivalents (OME). RESULTS: We identified 1227 consecutive ERP abdominal surgery patients for inclusion (519 patients receiving lidocaine and 708 patients not receiving lidocaine). Demographics between the two cohorts were similar, with the following exceptions: more females, and more patients with a history of psychiatric diagnoses in the group that did not receive lidocaine. Adjusted, mixed linear models for both OME (P = .23) and pain scores (P = .51) found no difference between the lidocaine and no lidocaine groups. DISCUSSION: In our study of ERP abdominal surgery patients, perioperative intravenous lidocaine did not offer improvement in postoperative pain scores or OME consumed. We therefore do not recommend the use of intravenous lidocaine as part of an ERP multimodal pain management strategy in abdominal surgery patients.

Adolescent restraint stress enhances adult nicotine reinforcement in male and female rats.

Adolescent stress is a risk factor for the initiation of nicotine use, but whether adolescent stress can enhance nicotine reinforcement when it is initiated later in adulthood is unknown, and it is unclear whether males and females are equally impacted. Therefore, this study assessed physiological responses (body weight and blood serum corticosterone - CORT) to restraint stress (RS) during adolescence (P28-55) or during adulthood (P70-96) in male and female Sprague-Dawley rats. When all subjects reached adulthood (P69 or 110; 2 weeks after termination of stress exposure), they were tested on sucrose preference and intravenous single-dose nicotine (0.03 mg/kg/infusion) self-administration. It was found that all rats displayed a significant CORT response to RS. Importantly, stress during adolescence, but not during adulthood, enhanced subsequent acquisition of nicotine intake tested in adulthood. Although this effect was observed in both sexes, only males displayed reduced body weight gain and adult sucrose preference. Moreover, regardless of stress exposure, females were more stimulated by nicotine, consumed more nicotine overall, and displayed enhanced nicotine seeking. These results suggest that adolescence is a period of heightened sensitivity to the enhancing effect of repeated stress on the susceptibility to develop nicotine dependence later in life in both sexes.

REMAP Periop: a randomised, embedded, multifactorial adaptive platform trial protocol for perioperative medicine to determine the optimal enhanced recovery pathway components in complex abdominal surgery patients within a US healthcare system.

INTRODUCTION: Implementation of enhanced recovery pathways (ERPs) has resulted in improved patient-centred outcomes and decreased costs. However, there is a lack of high-level evidence for many ERP elements. We have designed a randomised, embedded, multifactorial, adaptive platform perioperative medicine (REMAP Periop) trial to evaluate the effectiveness of several perioperative therapies for patients undergoing complex abdominal surgery as part of an ERP. This trial will begin with two domains: postoperative nausea/vomiting (PONV) prophylaxis and regional/neuraxial analgesia. Patients enrolled in the trial will be randomised to arms within both domains, with the possibility of adding additional domains in the future. METHODS AND ANALYSIS: In the PONV domain, patients are randomised to optimal versus supraoptimal prophylactic regimens. In the regional/neuraxial domain, patients are randomised to one of five different single-injection techniques/combination of techniques. The primary study endpoint is hospital-free days at 30 days, with additional domain-specific secondary endpoints of PONV incidence and postoperative opioid consumption. The efficacy of an intervention arm within a given domain will be evaluated at regular interim analyses using Bayesian statistical analysis. At the beginning of the trial, participants will have an equal probability of being allocated to any given intervention within a domain (ie, simple 1:1 randomisation), with response adaptive randomisation guiding changes to allocation ratios after interim analyses when applicable based on prespecified statistical triggers. Triggers met at interim analysis may also result in intervention dropping. ETHICS AND DISSEMINATION: The core protocol and domain-specific appendices were approved by the University of Pittsburgh Institutional Review Board. A waiver of informed consent was obtained for this trial. Trial results will be announced to the public and healthcare providers once prespecified statistical triggers of interest are reached as described in the core protocol, and the most favourable interventions will then be implemented as a standardised institutional protocol. TRIAL REGISTRATION NUMBER: NCT04606264.