Practice Patterns for Organ Preservation in US Patients With Rectal Cancer, 2006-2020.

Importance: In March 2023, the National Comprehensive Cancer Network endorsed watch and wait for those with complete clinical response to total neoadjuvant therapy. Neoadjuvant therapy is highly efficacious, so this recommendation may have broad implications, but the current trends in organ preservation in the US are unknown. Objective: To describe organ preservation trends among patients with rectal cancer in the US from 2006 to 2020. Design, Setting, and Participants: This retrospective, observational case series included adults (aged ≥18 years) with rectal adenocarcinoma managed with curative intent from 2006 to 2020 in the National Cancer Database. Exposure: The year of treatment was the primary exposure. The type of therapy was chemotherapy, radiation, or surgery (proctectomy, transanal local excision, no tumor resection). The timing of therapy was classified as neoadjuvant or adjuvant. Main Outcomes and Measures: The primary outcome was the absolute annual proportion of organ preservation after radical treatment, defined as chemotherapy and/or radiation without tumor resection, proctectomy, or transanal local excision. A secondary analysis examined complete pathologic responses among eligible patients. Results: Of the 175 545 patients included, the mean (SD) age was 63 (13) years, 39.7% were female, 17.4% had clinical stage I disease, 24.7% had stage IIA to IIC disease, 32.1% had stage IIIA to IIIC disease, and 25.7% had unknown stage. The absolute annual proportion of organ preservation increased by 9.8 percentage points (from 18.4% in 2006 to 28.2% in 2020; P < .001). From 2006 to 2020, the absolute rate of organ preservation increased by 13.0 percentage points for patients with stage IIA to IIC disease (19.5% to 32.5%), 12.9 percentage points for patients with stage IIIA to IIC disease (16.2% to 29.1%), and 10.1 percentage points for unknown stages (16.5% to 26.6%; all P < .001). Conversely, patients with stage I disease experienced a 6.1-percentage point absolute decline in organ preservation (from 26.4% in 2006 to 20.3% in 2020; P < .001). The annual rate of transanal local excisions decreased for all stages. In the subgroup of 80 607 eligible patients, the proportion of complete pathologic responses increased from 6.5% in 2006 to 18.8% in 2020 (P < .001). Conclusions and Relevance: This case series shows that rectal cancer is increasingly being managed medically, especially among patients whose treatment historically relied on proctectomy. Given the National Comprehensive Cancer Network endorsement of watch and wait, the increasing trends in organ preservation, and the nearly 3-fold increase in complete pathologic responses, international professional societies should urgently develop multidisciplinary core outcome sets and care quality indicators to ensure high-quality rectal cancer research and care delivery accounting for organ preservation.

New Onset Geriatric Syndromes and One-year Outcomes Following Elective Gastrointestinal Cancer Surgery.

OBJECTIVE: To assess whether older adults who develop geriatric syndromes following elective gastrointestinal surgery have poorer 1-year outcomes. BACKGROUND: Within 10 years, 70% of all cancers will occur in older adults ≥65 years old. The rise in older adults requiring major surgery has brought attention to age-related complications termed geriatric syndromes. However, whether postoperative geriatric syndromes are associated with long-term outcomes is unclear. METHODS: A population-based retrospective cohort study using the New York State Cancer Registry and the Statewide Planning and Research Cooperative System was performed including patients >55 years with pathologic stage I-III esophageal, gastric, pancreatic, colon, or rectal cancer who underwent elective resection between 2004 and 2018. Those aged 55 to 64 served as the reference group. The exposure of interest was a geriatric syndrome [fracture, fall, delirium, pressure ulcer, depression, malnutrition, failure to thrive, dehydration, or incontinence (urinary/fecal)] during the surgical admission. Patients with any geriatric syndrome within 1 year of surgery were excluded. Outcomes included incident geriatric syndrome, 1-year days alive and out of the hospital, and 1-year all-cause mortality. RESULTS: In this study, 37,998 patients with a median age of 71 years without a prior geriatric syndrome were included. Of those 65 years or more, 6.4% developed a geriatric syndrome. Factors associated with an incident geriatric syndrome were age, alcohol/tobacco use, comorbidities, neoadjuvant therapy, ostomies, open surgery, and upper gastrointestinal cancers. An incident geriatric syndrome was associated with a 43% higher risk of 1-year mortality (hazard ratio, 1.43; 95% confidence interval, 1.27-1.60). For those aged 65+ discharged alive and not to hospice, a geriatric syndrome was associated with significantly fewer days alive and out of hospital (322 vs 346 days, P < 0.0001). There was an indirect relationship between the number of geriatric syndromes and 1-year mortality and days alive and out of the hospital after adjusting for surgical complications. CONCLUSIONS: Given the increase in older adults requiring major surgical intervention, and the establishment of geriatric surgery accreditation programs, these data suggest that morbidity and mortality metrics should be adjusted to accommodate the independent relationship between geriatric syndromes and long-term outcomes.

A Scoping Review of Quality-of-Life Assessments Employed in Abdominal Wall Reconstruction.

INTRODUCTION: Surgeons use several quality-of-life instruments to track outcomes following abdominal wall reconstruction (AWR); however, there is no universally agreed upon instrument. We review the instruments used in AWR and report their utilization trends within the literature. METHODS: This scoping review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews guidelines using the PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane databases. All published articles in the English language that employed a quality-of-life assessment for abdominal wall hernia repair were included. Studies which focused solely on aesthetic abdominoplasty, autologous breast reconstruction, rectus diastasis, pediatric patients, inguinal hernia, or femoral hernias were excluded. RESULTS: Six hernia-specific tools and six generic health tools were identified. The Hernia-Related Quality-of-Life Survey and Carolinas Comfort Scale are the most common hernia-specific tools, while the Short-Form 36 (SF-36) is the most common generic health tool. Notably, the SF-36 is also the most widely used tool for AWR outcomes overall. Each tool captures a unique set of patient outcomes which ranges from abdominal wall functionality to mental health. CONCLUSIONS: The outcomes of AWR have been widely studied with several different assessments proposed and used over the past few decades. These instruments allow for patient assessment of pain, quality of life, functional status, and mental health. Commonly used tools include the Hernia-Related Quality-of-Life Survey, Carolinas Comfort Scale, and SF-36. Due to the large heterogeneity of available instruments, future work may seek to determine or develop a standardized instrument for characterizing AWR outcomes.

Metabolic syndrome and surgical complications: a systematic review and meta-analysis of 13 million individuals.

BACKGROUND: Metabolic syndrome (MetS) is characterised by the presence of at least three of the five following components: insulin resistance, obesity, chronic hypertension, elevated serum triglycerides, and decreased high-density lipoprotein cholesterol concentrations. It is estimated to affect 1 in 3 people around the globe and is reported to affect 46% of surgical patients. For people with MetS who undergo surgery, an emerging body of literature points to significantly poorer postoperative outcomes compared with nonaffected populations. The aim of this study is to review the current evidence on the risks of surgical complications in patients with MetS compared to those without MetS. METHODS: Systematic review and meta-analysis using PRISMA and AMSTAR reporting guidelines. RESULTS: The meta-analysis included 63 studies involving 1 919 347 patients with MetS and 11 248 114 patients without MetS. Compared to individuals without the condition, individuals with MetS were at an increased risk of mortality (OR 1.75 95% CI: 1.36-2.24; P <0.01); all surgical site infection types as well as dehiscence (OR 1.64 95% CI: 1.52-1.77; P <0.01); cardiovascular complications (OR 1.56 95% CI: 1.41-1.73; P <0.01) including myocardial infarction, stroke, cardiac arrest, cardiac arrythmias and deep vein thrombosis; increased length of hospital stay (MD 0.65 95% CI: 0.39-0.9; P <0.01); and hospital readmission (OR 1.55 95% CI: 1.41-1.71; P <0.01). CONCLUSION: MetS is associated with a significantly increased risk of surgical complications including mortality, surgical site infection, cardiovascular complications, increased length of stay, and hospital readmission. Despite these risks and the high prevalence of MetS in surgical populations there is a lack of evidence on interventions for reducing surgical complications in patients with MetS. The authors suggest prioritising interventions across the surgical continuum that include (1) preoperative screening for MetS; (2) surgical prehabilitation; (3) intraoperative monitoring and management; and (4) postoperative rehabilitation and follow-up.

Development and validation of multivariable predictive models for recurrence and mortality following nonoperative management of sigmoid volvulus.

AIM: Sigmoid volvulus is a challenging condition, and deciding between elective surgery or expectant management can be complex. The aim of this study was to develop a tool for predicting the risk of recurrent sigmoid volvulus and all-cause mortality within 1 year following initial nonoperative management. METHOD: This is a retrospective cohort study using Medicare claims data from 2016 to 2018 of beneficiaries admitted urgently/emergently for volvulus, undergoing colonic decompression and discharged alive without surgery (excluding those discharged to hospice). The primary outcomes were recurrent sigmoid volvulus and all-cause mortality within 1 year. Proportional hazards models and logistic regression were employed to identify risk factors and develop prediction equations, which were subsequently validated. RESULTS: Among the 2078 patients managed nonoperatively, 36.1% experienced recurrent sigmoid volvulus and 28.6% died within 1 year. The prediction model for recurrence integrated age, sex, race, palliative care consultations and four comorbidities, achieving area under the curve values of 0.63 in both the training and testing samples. The model for mortality incorporated age, palliative care consultations and nine comorbidities, with area under the curve values of 0.76 in the training and 0.70 in the testing sample. CONCLUSION: This study provides a straightforward predictive tool that utilizes easily accessible data to estimate individualized risks of recurrent sigmoid volvulus and all-cause mortality for older adults initially managed nonoperatively. The tool can assist clinicians and patients in making informed decisions about such risks. While the accuracy of the calculator was validated, further confirmation through external validation and prospective studies would enhance its clinical utility.

Is there an outcome benefit? Patient engagement technology in addition to the electronic medical record patient portal following elective colorectal surgery.

BACKGROUND: Patient engagement technologies (PET) are an area of growing innovation and investment, but whether PET use in the setting of electronic medical record (EMR) supported patient portals are associated with improved outcomes is unknown. Therefore, we assessed PET and EMR activation among patients undergoing elective colorectal surgery on an enhanced recovery pathway. METHODS: We identified adults undergoing elective colorectal surgery between 1/2017 and 7/2021. EMR activations were assessed and patients were considered PET users if they used a proprietary PET application. Multivariable logistic regression was used to identify factors associated with PET use and determine whether the level of engagement (percentage of messages read by the patient) was associated with 30-day outcomes. RESULTS: 484 patients (53.5% PET users, 81.6% with an activated EMR patient portal, 30.8% ≥ 70 years of age) were included. PET users were younger, more likely to have their EMR portal activated and had decreased odds of prolonged length of stay [odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4-0.8]. Among patients ≥ 70 years, PET users had reduced odds of readmissions (OR 0.2, 95% CI 0.1-0.9) compared to PET non-users. The most engaged PET users had decreased morbidity (OR 0.2, 95% CI 0.1-0.8) and readmissions (OR 0.3, 95% CI 0.1-0.8) compared to the least engaged PET users. CONCLUSION: When controlling for EMR activation, patients who use PET, specifically those with higher levels of engagement or aged ≥ 70, have improved outcomes following elective colorectal surgery. Interventions aimed at increasing the adoption of PET among older adults may be warranted.

Are postoperative opioid stewardship protocols sustainable? Results from a 2-year quality improvement project.

BACKGROUND: Opioid stewardship protocols reduce opioid overprescription, but many require corrective action within 1 year. Because there are limited data on the sustainability of opioid reduction protocols, we sought to evaluate prescribing trends beyond 1 year. METHODS: We reviewed prescribing data from a tertiary care center to establish a consensus discharge opioid-prescribing guideline. Subsequently, we performed a prospective quality-improvement study for patients on an enhanced recovery protocol undergoing elective colectomies, proctectomies, and stoma-related procedures. We gathered process (protocol compliance), balance (rates of patient-controlled analgesia and nerve blocks, inpatient opioid utilization, pain scores within 48 hours of discharge), and clinical measures (median discharge opioid pills, postdischarge day 7 satisfaction). RESULTS: In total, 1,049 patients with similar ages, operative indications, and rates of substance use pre- and postintervention were included. Over 2 years, compliance was 88.6%, and there was a 43.6% reduction in the total discharge number of opioid pills. Phone calls for opioid refills were stable (10.2% pre- vs 7.8% postintervention, P = .16), and the following all decreased significantly: intraoperative nerve blocks, patient-controlled analgesia use, and final 48-hour and total median inpatient opioid use. There was a clinically negligible, statistically significant reduction in pain scores within 48 hours of discharge. Fifty patients provided satisfaction data, and 92% were satisfied or somewhat satisfied with their analgesia. CONCLUSION: Over 2 years, reduced opioid prescribing was maintained without escalating resources. Sustainability suggests that after successfully implementing an opioid reduction protocol, institutions may safely redeploy quality improvement resources elsewhere.

New insights into the responder/nonresponder divide in rectal cancer: Damage-induced Type I IFNs dictate treatment efficacy and can be targeted to enhance radiotherapy.

Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal cancer patients often results in individuals that respond well to therapy and those that respond poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide. Our major aim is to identify what factors in the tumor microenvironment drive a fraction of rectal cancer patients to respond to radiotherapy. We also sought to distinguish potential biomarkers that would indicate a positive response to therapy and design combinatorial therapeutics to enhance radiotherapy efficacy. To address this, we developed an orthotopic murine model of rectal cancer treated with short course radiotherapy that recapitulates the bimodal response observed in the clinic. We utilized a robust combination of transcriptomics and protein analysis to identify differences between responding and nonresponding tumors. Our mouse model recapitulates human disease in which a fraction of tumors respond to radiotherapy (responders) while the majority are nonresponsive. We determined that responding tumors had increased damage-induced cell death, and a unique immune-activation signature associated with tumor-associated macrophages, cancer-associated fibroblasts, and CD8+ T cells. This signature was dependent on radiation-induced increases of Type I Interferons (IFNs). We investigated a therapeutic approach targeting the cGAS/STING pathway and demonstrated improved response rate following radiotherapy. These results suggest that modulating the Type I IFN pathway has the potential to improve radiation therapy efficacy in RC.

Epidemiology and healthcare utilization for rectal foreign bodies in United States adults, 2012-2021.

INTRODUCTION: Presentations to the emergency department for rectal foreign bodies are common, but there is little epidemiologic information on this condition. This limits the ability to provide evidence-based education to trainees regarding the populations affected, the types and frequency of foreign bodies, and factors associated with hospitalization. To address this, we analyzed national estimates of emergency department presentations for rectal foreign bodies from 2012 to 2021 in the US. METHODS: We queried the National Electronic Injury Surveillance System for any injury to the 'pubic region' or 'lower trunk' with an accompanying diagnosis of foreign body, puncture, or laceration. Two authors manually reviewed all clinical narratives to identify cases of rectal foreign bodies. National estimates were determined using weighting and strata variables, incidence rates calculated using census data, trends assessed by linear regression, and factors associated with hospitalization identified by multivariable logistic regression. RESULTS: From 885 cases, there were an estimated 38,948 (95% CI, 32,040-45,856) emergency department visits for rectal foreign bodies among individuals ≥15 years from 2012 to 2021. The average age was 43, 77.8% were male, 55.4% of foreign bodies were sexual devices, and 40.8% required hospitalization. The annual incidence of presentations for rectal foreign bodies increased from 1.2 in 2012 to 1.9 per 100,000 persons in 2021 (R2 = 0.84, p < 0.01). Males have a bimodal age distribution peaking in the fifth decade, while females have a right-skewed age distribution peaking in the second decade. Female sex (odds ratio [OR] 0.4; 95% confidence interval [CI], 0.2-0.6) and, compared to sexual devices, balls/marbles (OR 0.2; 95% CI, 0.05-0.6) or drugs/paraphernalia (OR 0.1; 95% CI, 0.05-0.4) are associated with a reduced odds of hospitalization. CONCLUSIONS: Presentations to the emergency department for rectal foreign bodies increased for males and females from 2012 to 2021 in the United States. These epidemiologic estimates for a complex form of anorectal trauma provide preclinical information for emergency medicine, surgery, and radiology trainees.

Could meeting the standards of the National Accreditation Program for Rectal Cancer in the National Cancer Database improve patient outcomes?

AIM: The National Accreditation Program for Rectal Cancer (NAPRC) was developed to improve rectal cancer patient outcomes in the United States. The NAPRC consists of a set of process and outcome measures that hospitals must meet in order to be accredited. We aimed to assess the potential of the NAPRC by determining whether achievement of the process measures correlates with improved survival. METHODS: The National Cancer Database was used to identify patients undergoing curative proctectomy for non-metastatic rectal cancer from 2010 to 2014. NAPRC process measures identified in the National Cancer Database included clinical staging completion, treatment starting <60 days from diagnosis, carcinoembryonic antigen level measured prior to treatment, tumour regression grading and margin assessment. RESULTS: There were 48 669 patients identified with a mean age of 62 ± 12.9 years and 61.3% of patients were men. The process measure completed most often was assessment of proximal and distal margins (98.4%) and the measure completed least often was the serum carcinoembryonic antigen level prior to treatment (63.8%). All six process measures were completed in 23.6% of patients. After controlling for age, gender, comorbidities, annual facility resection volume, race and pathological stage, completion of all process measures was associated with a statistically significant mortality decrease (Cox hazard ratio 0.88, 95% CI 0.81-0.94, P < 0.001). CONCLUSION: Participating institutions provided complete datasets for all six process measures in less than a quarter of patients. Compliance with all process measures was associated with a significant mortality reduction. Improved adoption of NAPRC process measures could therefore result in improved survival rates for rectal cancer in the United States.

Implementation of a new definition for acute kidney injury in the National Surgical Quality Improvement Project: What is the impact?

BACKGROUND: The National Surgical Quality Improvement Project is the preeminent surgical quality database, but it undercaptures acute kidney injury. Recently, the National Surgical Quality Improvement Project lowered the thresholds for acute kidney injury for the first time, so we assessed the impact of implementing the definition change on the rate of acute kidney injuries. METHODS: For this interrupted time series analysis, we assembled 2 institutional National Surgical Quality Improvement Project files to identify adults undergoing inpatient noncardiac nonvascular surgery. The acute kidney injury definition changed on July 1, 2021, so patients were stratified by their operative date into 12-month pre and post groups. Weighted covariate propensity score matching and logistic regression were used to balance the periods and compare outcomes. RESULTS: In total, 4,784 adults were eligible (55% pre and 45% post change). The overall rate of postoperative outcomes was similar, aside for acute kidney injury (pre 0.3%, post 5.6%, P < .0001). Regardless of the period, patients with acute kidney injuries had significantly longer lengths of stay and morbidity and mortality rates compared to those without an acute kidney injury. After the definition change, 81% of acute kidney injuries were stage I, and none were identified by urine output alone. After matching, surgery after the definition change was associated with an increased weighted odds of an acute kidney injury compared to surgery before the change (odds ratio 26.2; 95% confidence interval, 12.1-56.8). CONCLUSION: In the year after the definition change, there was a 1,700% relative increase in the rate of reported acute kidney injuries. Newly identified acute kidney injuries are associated with high complication rates, and this definition change has implications for patient counseling, research, and quality reporting.

A Novel Use for Pelvic MRI Scans to Estimate Lean Body Mass and Screen for Sarcopenia in Patients With Rectal Cancer.

BACKGROUND: Sarcopenia, the combination of low lean body mass and decreased muscle strength, is associated with significant morbidity and mortality among patients with colorectal cancer. Standard methods for assessing lean body mass and muscle strength, such as bioelectric impedance analysis and handgrip dynamometry, are rarely obtained clinically. Per National Cancer Center Network recommendations, pelvic MRI is routinely collected for staging and surveillance among patients with rectal cancer. However, there are no data assessing the relationship of pelvic MRI lean body mass measurements at the fifth lumbar vertebrae with bioelectric impedance analysis, handgrip strength, or abdominal CT in patients with rectal cancer. Therefore, we aimed to assess whether pelvic MRI lean body mass correlates with a standard for lean body mass measurement (bioelectric impedance analysis), muscle function (handgrip strength), and an imaging modality frequently used in the literature to identify sarcopenia (abdominal CT at the third lumbar vertebrae). IMPACT OF INNOVATION: Lean body mass measurements from routinely collected pelvic MRI at the fifth lumbar vertebrae accurately and reproducibly estimate lean body mass and modestly correlate with handgrip strength. Rectal cancer pelvic MRI may be repurposed for identifying sarcopenia without increasing inconvenience, ionizing radiation exposure, or expenditure to patients with rectal cancer. TECHNOLOGY, MATERIALS, AND METHODS: Patients with locally advanced rectal cancer with pretreatment bioelectric impedance analysis and handgrip strength measurements within 3 months of their staging pelvic MRI were eligible. Axial skeletal muscle areas were segmented using T1-weighted series pelvic MRI at the fifth lumbar vertebrae and abdominal CT at the third lumbar vertebrae using Slice-O-Matic (Tomovision, Montreal, Canada). Lean body mass (kilograms) was derived from skeletal muscle area with standard equations. Handgrip strength (kilograms) was the maximum of 3 dominant hand attempts in the standing anatomical position. The primary outcome was the agreement between lean body mass measured by pelvic MRI (at the fifth lumbar vertebrae) and bioelectric impedance analysis. Secondary outcomes included the concordance of pelvic MRI lean body mass (at the fifth lumbar vertebrae) with abdominal CT (at the third lumbar vertebrae) and handgrip strength. Additionally, the intra- and interobserver validity, internal consistency, and the mean difference (bias) between lean body mass measurements by pelvic MRI and bioelectric impedance analysis were evaluated. PRELIMINARY RESULTS: Sixteen patients were eligible. The average lean body mass was similar and consistent across 2 observers between bioelectric impedance analysis and pelvic MRI. There was a strong correlation between lean body mass measured on pelvic MRI, bioelectric impedance analysis, and abdominal CT. The reliability of 2 pelvic MRI lean body mass measurements (2 weeks apart by blinded observers) and the correlation of lean body mass between pelvic MRI and bioelectric impedance analysis was strong. Inter- and intraobserver correlation, reliability, and internal consistency were strong for the entire cohort. There was a moderate correlation between pelvic MRI lean body mass and handgrip strength. CONCLUSIONS: Lean body mass measured at the fifth lumbar vertebrae on pelvic MRI is reproducible and correlates strongly with measurements from bioelectric impedance analysis (standard) and abdominal CT at the third lumbar vertebrae and modestly with handgrip strength. These data suggest that MRI lean body mass measurements may be a method to screen patients with rectal cancer for sarcopenia. FUTURE DIRECTIONS: Future studies may evaluate changes in lean body mass on serial pelvic MRI studies among patients with rectal cancer.

Low Preoperative Serum Creatinine is Common and Associated With Poor Outcomes After Nonemergent Inpatient Surgery.

OBJECTIVE: To assess the association between low preoperative serum creatinine and postoperative outcomes. BACKGROUND: The association between low creatinine and poor surgical outcomes is not well understood. METHODS: We identified patients with creatinine in the 7 days preceding nonemergent inpatient surgery in the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2020. Multivariable logistic regression was used to examine the association between creatinine and 30-day mortality and major complications. RESULTS: Of 1,809,576 patients, 27.8% of males and 23.5% of females had low preoperative serum creatinine, 14.6% experienced complications, and 1.2% died. For males, compared with the reference creatinine of 0.85 to 1.04, those with serum creatinine ≤0.44 had 55% increased odds of mortality [ adjusted odds ratio (aOR), 1.55; 95% CI, 1.29-1.86] and 82% increased odds of major complications (aOR, 1.82; 95% CI, 1.69-1.97). Similarly, for females, compared with the reference range of 0.65 to 0.84, those with serum creatinine ≤0.44 had 49% increased odds of mortality (aOR, 1.49; 95% CI, 1.32-1.67) and 76% increased odds of major complications (aOR, 1.76; 95% CI, 1.70-1.83). These associations persisted for the total cohort, among those with mildly low albumin, and for those with creatinine values measured 8 to 30 days preoperatively. CONCLUSIONS: A low preoperative creatinine is common and associated with poor outcomes after nonemergent inpatient surgery. A low creatinine may help identify high-risk patients who may benefit from further evaluation and optimization.

Radiation Therapy Exacerbates Tumor-Promoting Innervation and Nerve Signaling in Rectal Cancer.

PURPOSE: Many solid tumors present with perineural invasion (PNI), and innervation correlates with worsened prognosis. The effects that commonly administered therapies such as radiation therapy (RT) have on PNI status remain unknown. We investigated the contribution of RT on the nervous system and elucidated the implications that increased nerve signaling can have on tumor burden using our previously developed orthotopic murine model of rectal cancer (RC) and our targeted and clinically relevant short-course RT (SCRT) regimen. METHODS: Medical charts for patients with RC treated at the Wilmot Cancer Institute were obtained and PNI status was analyzed. Human data were accompanied by an orthotopic murine model of RC. Briefly, luciferase-expressing murine colon-38 (MC38-luc) tumor cells were injected orthotopically into the rectal wall of C57BL6 mice. Targeted SCRT (5 gray (Gy) per fraction for 5 consecutive fractions) was administered to the tumor. Intratumoral innervation was determined by immunohistochemistry (IHC), local norepinephrine (NE) concentration was quantified by enzyme-linked immunosorbent assay (ELISA), and ß2-adrenergic receptor (B2AR) expression was assessed by flow cytometry. Chronic NE signaling was mirrored by daily isoproterenol treatment, and the effect on tumor burden was determined by overall survival, presence of metastatic lesions, and tumor size. Isoproterenol signaling was inhibited by administration of propranolol. RESULTS: Human RC patients with PNI have decreased overall survival compared with patients without PNI. In our mouse model, SCRT induced the expression of genes involved in neurogenesis, increased local NE secretion, and upregulated B2AR expression. Treating mice with isoproterenol resulted in decreased overall survival, increased rate of metastasis, and reduced SCRT efficacy. Interestingly, the isoproterenol-induced decrease in SCRT efficacy could be abrogated by blocking the BAR through the use of propranolol, suggesting a direct role of BAR stimulation on impairing SCRT responses. CONCLUSIONS: Our results indicate that while SCRT is a valuable treatment, it is accompanied by adverse effects on the nervous system that may impede the efficacy of therapy and promote tumor burden. Therefore, we could speculate that therapies aimed at targeting this signaling cascade or impairing nerve growth in combination with SCRT may prove beneficial in future cancer treatment.

Sigmoid volvulus: Evaluating identification strategies and contemporary multicenter outcomes.

BACKGROUND: There is limited epidemiologic data on sigmoid volvulus (SV) from non-endemic regions. Therefore, we performed a multicenter study to report contemporary outcomes and appraise literature-based methods that pair diagnostic and procedural codes to identify SV. METHOD: Using an automated search for patients with 'volvulus' in our system from 2011 to 2021, we reviewed electronic charts to clarify the diagnosis, automatically replicate three strategies to identify SV, and retrieved 6-month outcomes. RESULTS: Of 895 patients, 109 had SV. Literature-based strategies poorly identified SV. At the index admission, patients underwent endoscopic reduction alone (33%), emergent (16.5%), semi-elective (34%), or elective (16.5%) surgery. Endoscopic reduction alone had high recurrence rates and delayed surgery was associated with worse outcomes. CONCLUSION: Literature-based strategies to identify SV suffer from misclassification bias which affects patient counseling. In this large series, one-third of patients do not undergo during their index admission despite improved outcomes with earlier surgery.

An assessment of left-digit bias in the treatment of older patients with potentially curable rectal cancer.

BACKGROUND: Patient age is associated with poorer rectal cancer treatment compliance. However, it is unknown whether left-digit bias (disproportionate influence of leftmost age digit) influences this association. METHODS: The patients diagnosed with stage I-III rectal cancer between 2006 to 2017 in the National Cancer Database were identified. The association between age and receipt of guideline-adherent care was assessed using mixed-effects multivariable analyses. RESULTS: Among 97,960 patients, 46.2% received guideline-adherent overall treatment and 73.3% underwent guideline-adherent surgical resection. Of those who underwent guideline-adherent surgery, 86.4% received guideline-adherent radiotherapy and 56.6% received guideline-adherent chemotherapy. After risk-adjustment, each decade increase in age was associated with 36% decreased odds of guideline-adherent therapy (odds ratio = 0.64, 95% confidence interval = 0.63-0.65). Patients aged 58 to 59 (odds ratio = 1.15, 95% confidence interval = 1.02-1.27) and 78 to 79 (odds ratio = 1.28, 95% confidence interval = 1.08-1.51) had higher odds of guideline-adherent overall treatment compared with patients aged 60 and 80, respectively. However, there were no significant differences in the receipt of guideline-adherent treatment between patients aged 60 vs 61-62 and 80 vs 81-82. CONCLUSION: Older patients with rectal cancer are less likely to receive guideline-adherent care, and a left-digit bias is present. Geriatric assessment-guided treatment decisions could help mitigate this bias.

Association of Time Elapsed Since Ischemic Stroke With Risk of Recurrent Stroke in Older Patients Undergoing Elective Nonneurologic, Noncardiac Surgery.

Importance: Perioperative strokes are a major cause of death and disability. There is limited information on which to base decisions for how long to delay elective nonneurologic, noncardiac surgery in patients with a history of stroke. Objective: To examine whether an association exists between the time elapsed since an ischemic stroke and the risk of recurrent stroke in older patients undergoing elective nonneurologic, noncardiac surgery. Design, Setting, and Participants: This cohort study used data from the 100% Medicare Provider Analysis and Review files, including the Master Beneficiary Summary File, between 2011 and 2018 and included elective nonneurologic, noncardiac surgeries in patients 66 years or older. Patients were excluded if they had more than 1 procedure during a 30-day period, were transferred from another hospital or facility, were missing information on race and ethnicity, were admitted in December 2018, or had tracheostomies or gastrostomies. Data were analyzed May 7 to October 23, 2021. Exposures: Time interval between a previous hospital admission for acute ischemic stroke and surgery. Main Outcomes and Measures: Acute ischemic stroke during the index surgical admission or rehospitalization for stroke within 30 days of surgery, 30-day all-cause mortality, composite of stroke and mortality, and discharge to a nursing home or skilled nursing facility. Multivariable logistic regression models were used to estimate adjusted odds ratios (AORs) to quantify the association between outcome and time since ischemic stroke. Results: The final cohort included 5 841 539 patients who underwent elective nonneurologic, noncardiac surgeries (mean [SD] age, 74.1 [6.1] years; 3 371 329 [57.7%] women), of which 54 033 (0.9%) had a previous stroke. Patients with a stroke within 30 days before surgery had higher adjusted odds of perioperative stroke (AOR, 8.02; 95% CI, 6.37-10.10; P < .001) compared with patients without a previous stroke. The adjusted odds of stroke were not significantly different at an interval of 61 to 90 days between previous stroke and surgery (AOR, 5.01; 95% CI, 4.00-6.29; P < .001) compared with 181 to 360 days (AOR, 4.76; 95% CI, 4.26-5.32; P < .001). The adjusted odds of 30-day all-cause mortality were higher in patients who underwent surgery within 30 days of a previous stroke (AOR, 2.51; 95% CI, 1.99-3.16; P < .001) compared with those without a history of stroke, and the AOR decreased to 1.49 (95% CI, 1.15-1.92; P < .001) at 61 to 90 days from previous stroke to surgery but did not decline significantly, even after an interval of 360 or more days. Conclusions and Relevance: The findings of this cohort study suggest that, among patients undergoing nonneurologic, noncardiac surgery, the risk of stroke and death leveled off when more than 90 days elapsed between a previous stroke and elective surgery. These findings suggest that the recent scientific statement by the American Heart Association to delay elective nonneurologic, noncardiac surgery for at least 6 months after a recent stroke may be too conservative.