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Background: Natural orifice transluminal endoscopic surgery (NOTES), a recent development in the field of minimally invasive surgery, provides theoretical advantages over open and laparoscopic surgery. Challenges with the use of NOTES for colon resections include the need to extract a large specimen and perform an intestinal anastomosis. A transanal single-port laparoscopic proctectomy uses the potential advantages of NOTES yet provides easy specimen extraction and anastomosis.Methods: Fresh frozen then thawed human cadavers were used. Access was obtained via transanal mucosectomy, and a transanal endoscopic microsurgery (TEM) system was used to perform the proctectomy once the procedure was above the pelvic floor. After the peritoneal cavity was entered, a hand port was placed through the sphincter and above the pelvic floor. The left colon was mobilized using two 5-mm working ports and a 10-mm camera port for the flexible-tipped laparoscope that were placed through the hand port. The specimen was removed transanally.Results: The critical steps for an oncologic resection of the rectum were achieved using a combination of TEM and laparoscopic instrumentation transanally. The rectum and mesorectum were mobilized. The left ureter was identified and preserved, the inferior mesenteric artery (IMA) ligated at its origin, the inferior mesenteric vein ligated near the ligament of Treitz, the proximal colon mobilized for transanal extraction, the specimen resected proximal to the ligated IMA, and a hand-sewn coloanal anastomosis performed. Postresection examination showed preservation of the hypogastric nerves and an intact mesorectum. Challenges included maneuverability around the sacral promontory and length of the instruments. However, this was easily overcome by the use of long reticulating instruments and a flexible-tipped laparoscope.Conclusions: Transanal single-port low anterior resection using TEM and laparoscopic techniques is feasible and can maintain the principles of an oncologic resection. [ABSTRACT FROM AUTHOR]

Background & Aims: Perianal fistulizing Crohn's disease (PCD) is a common and debilitating complication with elusive pathophysiology. We examined mucosal cells from patients with PCD and related conditions using a multi-omics approach., Methods: We recruited patients with PCD (n = 24), CD without perianal disease (NPCD, n = 10), and idiopathic perianal fistulas (IPF, n = 29). Biopsies were taken from fistula tracts, fistula opening, and rectal mucosa. Single-cell RNA-sequencing (scRNA-seq), mass cytometry (CyTOF), spatial transcriptomics (ST), immunohistochemistry, and integrated analysis were performed., Results: ScRNA-seq, CyTOF, and ST unraveled immune and non-immune cell compartments in PCD and IPF fistula tracts. PCD fistulas showed hyperactivated pathogenic pathways including interferon (IFN)G response and TNF signaling in myeloid and stromal cells. Intestinal cells from PCD patients also expressed greater levels of IFNG-responsive and EMT genes compared to NPCD patients. Furthermore, both fistula tracts and ileal mucosa from PCD patients harbored expanded IFNG+ pathogenic Th17 cells, which expressed elevated inflammatory mediators. CyTOF also identified skewed immune cell phenotypes in the fistula tracts, fistula opening, and rectum in PCD patients including expanded Th17 cells, increased pathogenic myeloid cells, and altered T cell exhaustion markers. Further analysis also revealed cellular modules associated with anti-TNF therapy in PCD patients., Conclusion: Multi-omics analysis revealed immune, stromal, and epithelial cell landscapes of PCD, which highlight the pathogenic role of hyperactivated IFNG signaling in both fistula tracts and luminal mucosa. This study identified IFNG as a potential therapeutic target for PCD.

Background and Objectives: The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both., Methods: The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response., Results: Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS., Conclusions: SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone., (© 2024 Wiley Periodicals LLC.)

Photoacoustic microscopy offers functional information regarding tissue vasculature while ultrasound characterizes tissue structure. Combining these two modalities provides novel clinical applications including response assessment among rectal cancer patients undergoing therapy. We have previously demonstrated the capabilities of a co-registered photoacoustic and ultrasound device in vivo , but multiple challenges limited broad adoption. In this paper, we report significant improvements in an acoustic resolution photoacoustic microscopy and ultrasound (ARPAM/US) system characterized by simulation and phantom study, focusing on resolution, optical coupling, and signal characteristics. In turn, higher in-probe optical coupling efficiency, higher signal-to-noise ratio, higher data throughput, and better stability with minimal maintenance requirements were all accomplished. We applied the system to 19 ex vivo resected colorectal cancer samples and found significantly different signals between normal, cancer, and post-treatment tumor tissues. Finally, we report initial results of the first in vivo imaging study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier GmbH.)

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., (© 2023 Wiley Periodicals LLC.)

Importance: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment., Objective: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade., Design, Setting, and Participants: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023., Intervention: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP., Main Outcomes and Measures: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test., Results: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT., Trial Registration: ClinicalTrials.gov Identifier: NCT02008656.

Though resection has been the mainstay of treatment for nonmetastatic rectal cancer over the past century, radiation has become an increasingly integral component of care for locally advanced disease. Today, two predominant radiotherapy approaches-hyperfractionated chemoradiotherapy and "short-course" radiation-are widely utilized to reduce local recurrence and, in some cases, cure disease. Both have been incorporated into total neoadjuvant therapy (TNT) regimens and achieved excellent local control and superior complete response rates compared to chemoradiation alone. Additionally, initial results of "watch and wait" protocols utilizing either radiation modality have been promising. Yet, differences do exist; though short course is cheaper and more convenient for patients, recently published data may show superior complete response and local recurrence rates with chemoradiation. Ultimately, direct comparisons of short-course radiotherapy against chemoradiation within the TNT framework are needed to identify optimal radiation regimens in the treatment of locally advanced rectal cancer., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: Short-course radiation therapy and consolidation chemotherapy with nonoperative intent has emerged as a novel treatment paradigm for patients with rectal cancer, but there are no data on the predictors of clinical complete response., Objective: Evaluate the predictors of clinical complete response and survival., Design: Retrospective cohort., Settings: National Cancer Institute-designated cancer center., Patients: Patients with stage I to III rectal adenocarcinoma treated between January 2018 and May 2019 (n = 86)., Interventions: Short-course radiation therapy followed by consolidation chemotherapy., Main Outcome Measures: Logistic regression was performed to assess for predictors of clinical complete response. The end points included local regrowth-free survival, regional control, distant metastasis-free survival, and overall survival., Results: A positive (+) circumferential resection margin by MRI at diagnosis was a significant predictor of nonclinical complete response (OR: 4.1, p = 0.009) when adjusting for CEA level and primary tumor size. Compared to patients with a negative (-) pathologic circumferential resection margin, patients with a positive (+) pathologic circumferential resection margin had inferior local regrowth-free survival (29% vs 87%, p < 0.001), regional control (57% vs 94%, p < 0.001), distant metastasis-free survival (43% vs 95%, p < 0.001), and overall survival (86% vs 95%, p < 0.001) at 2 years. However, the (+) and (-) circumferential resection margin by MRI subgroups in patients who had a clinical complete response both had similar regional control, distant metastasis-free survival, and overall survival of more than 90% at 2 years., Limitations: Retrospective design, modest sample size, short follow-up, and the heterogeneity of treatments., Conclusions: Circumferential resection margin involvement by MRI at diagnosis is a strong predictor of nonclinical complete response. However, patients who achieve a clinical complete response after short-course radiation therapy and consolidation chemotherapy with nonoperative intent have excellent clinical outcomes regardless of the initial circumferential resection margin status. See Video Abstract at http://links.lww.com/DCR/C190 ., El Margen De Reseccin Circunferencial Como Predictor No Clnico De Respuesta Completa En El Manejo Conservador Del Cncer De Recto: ANTECEDENTES:La radioterapia de corta duración y la quimioterapia de consolidación en el manejo conservador, han surgido como un nuevo paradigma de tratamiento, para los pacientes con cáncer de recto, lastimosamente no hay datos definitivos sobre los predictores de una respuesta clínica completa.OBJETIVO:Evaluar los predictores de respuesta clínica completa y de la sobrevida.DISEÑO:Estudio retrospectivo de cohortes.AJUSTES:Centro oncológico designado por el NCI.PACIENTES:Adenocarcinomas de recto estadio I-III tratados entre 01/2018 y 05/2019 (n = 86).INTERVENCIONES:Radioterapia de corta duración seguida de quimioterapia de consolidación.PRINCIPALES MEDIDAS DE RESULTADO:Se realizó una regresión logística para evaluar los predictores de respuesta clínica completa. Los criterios de valoración incluyeron la sobrevida libre de recidiva local, el control regional, la sobrevida libre de metástasis a distancia y la sobrevida general.RESULTADOS:Un margen de resección circunferencial positivo (+) evaluado por imagenes de resonancia magnética nuclear en el momento del diagnóstico fue un predictor no clínico muy significativo de respuesta completa (razón de probabilidades/ OR: 4,1, p = 0,009) al ajustar el nivel de antígeno carcinoembrionario y el tamaño del tumor primario. Comparando con los pacientes que presetaban un margen de resección circunferencial patológico negativo (-), los pacientes con un margen de resección circunferencial patológico positivo (+) tuvieron una sobrevida libre de recidiva local (29% frente a 87%, p < 0,001), un control regional (57% frente a 94%, p < 0,001), una sobrevida libre de metástasis a distancia (43% frente a 95%, p < 0,001) y una sobrevida global (86% frente a 95%, p < 0,001) inferior en 2 años de seguimiento. Sin embargo, los subgrupos de margen de resección circunferencial (+) y (-) evaluados por imágenes de resonancia magnética nuclear en pacientes que tuvieron una respuesta clínica completa tuvieron un control regional similar, una sobrevida libre de metástasis a distancia y una sobrevida general >90% en 2 años de seguimiento.LIMITACIONES:Diseño retrospectivo, tamaño modesto de la muestra, seguimiento corto y heterogeneidad de tratamientos.CONCLUSIONES:La afectación del margen de resección circunferencial evaluado por resonancia magnética nuclear al momento del diagnóstico es un fuerte factor predictivo no clínico de respuesta completa. Sin embargo, los pacientes que logran una respuesta clínica completa después de un curso corto de radioterapia y quimioterapia de consolidación como manejo conservador tienen excelentes resultados clínicos independientemente del estado del margen de resección circunferencial inicial. Consulte Video Resumen en http://links.lww.com/DCR/C190 . (Traducción-Dr. Xavier Delgadillo )., (Copyright © The ASCRS 2023.)

Background: Up to 10% of patients develop new, persistent opioid use after surgery. We aimed to assess our prescribing practices and patient utilization of opioids after colorectal surgery., Objective: This study aimed to implement an opioid-prescribing protocol that will minimize the number of postoperative opioids to decrease community circulation and persistent use by patients., Design: This was a single-institution, prospective study based on questionnaires of postoperative patients in 2019 and 2020 to determine opioid prescribing and usage patterns. Based on these preliminary results, a protocol was implemented in which patients were discharged with 5 or 15 oxycodone 5 mg equivalents based on opioid usage in the 24 hours before discharge. Patients were surveyed after protocol implementation., Settings: Our institution is a large referral center for surgical treatment of colorectal disease., Patients: Adults who underwent inpatient abdominal colorectal procedures., Main Outcome Measures: End points included the number of opioids prescribed, number of prescribed opioids taken, and refill rate. Nonparametric testing was used., Results: Of 77 eligible patients, 61 were opioid naive. Preprotocol, opioid-naive patients (n = 29) were prescribed a median of 30 (interquartile range [IQR], 30-45) tablets but took only 10 (IQR, 0-10; p < 0.0001). Eighty-three percent took 20 or fewer tablets. After protocol implementation, opioid-naive patients (n = 32) were prescribed fewer tablets (median 15; IQR, 7-15; p < 0.0001) but took a similar number of tablets as the preprotocol group (median 10; IQR, 0-10; p = 0.21). The refill rate remained similar (13.8% vs 18.8%; p = 0.60). Protocol adherence was 90.6%., Limitations: This study is limited by sample size, cohort heterogeneity, and generalizability., Conclusions: Patients took significantly fewer opioids than were prescribed. Our protocol limited overprescribing and resulted in fewer opioids in the community without opportunity costs such as increased refills. Long-term studies are needed to assess the effects of persistent opioid use after surgery. See Video Abstract at http://links.lww.com/DCR/C93 ., (Copyright © The ASCRS 2022.)

PERIOD (PER) and Casein Kinase 1δ regulate circadian rhythms through a phosphoswitch that controls PER stability and repressive activity in the molecular clock. CK1δ phosphorylation of the familial advanced sleep phase (FASP) serine cluster embedded within the Casein Kinase 1 binding domain (CK1BD) of mammalian PER1/2 inhibits its activity on phosphodegrons to stabilize PER and extend circadian period. Here, we show that the phosphorylated FASP region (pFASP) of PER2 directly interacts with and inhibits CK1δ. Co-crystal structures in conjunction with molecular dynamics simulations reveal how pFASP phosphoserines dock into conserved anion binding sites near the active site of CK1δ. Limiting phosphorylation of the FASP serine cluster reduces product inhibition, decreasing PER2 stability and shortening circadian period in human cells. We found that Drosophila PER also regulates CK1δ via feedback inhibition through the phosphorylated PER-Short domain, revealing a conserved mechanism by which PER phosphorylation near the CK1BD regulates CK1 kinase activity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Nonoperative management (NOM) is increasingly utilized for rectal cancer patients with a clinical complete response (cCR) following total neoadjuvant therapy (TNT). The objective of this pilot study was to determine whether FDG-PET/MRI alters clinical response assessments among stage I-III rectal cancer patients undergoing TNT followed by NOM, relative to MRI alone. This prospective study included 14 subjects with new rectal cancer diagnoses. Imaging consisted of FDG-PET/MRI for initial staging, post-TNT restaging, and surveillance during NOM. Two independent readers assessed treatment response on MRI followed by FDG-PET/MRI. Inter-reader differences were resolved by consensus review. The reference standard for post-TNT restaging consisted of surgical pathology or clinical follow-up. 7/14 subjects completed post-TNT restaging FDG-PET/MRIs. 5/7 subjects had evidence of residual disease and underwent total mesorectal excision; 2/7 subjects had initial cCR with no evidence of disease after 12 months of NOM. FDG-PET/MRI assessments of cCR status at post-TNT restaging had an accuracy of 100%, compared with 71% for MRI alone, as FDG-PET detected residual tumor in 2 more subjects. Inter-reader agreement for cCR status on FDG-PET/MRI was moderate (kappa, 0.56). FDG-PET provided added value in 82% (9/11) of restaging/surveillance scans. Our preliminary data indicate that FDG-PET/MRI can detect more residual disease after TNT than MRI alone, with the FDG-PET component providing added value in most restaging/surveillance scans.

Purpose: This study aimed to determine the clinical efficacy and safety of nonoperative management (NOM) for patients with rectal cancer with a clinical complete response (cCR) after short-course radiation therapy and consolidation chemotherapy., Methods and Materials: Patients with stage I-III rectal adenocarcinoma underwent short-course radiation therapy followed by consolidation chemotherapy between January 2018 and May 2019 (n = 90). Clinical response was assessed by digital rectal examination, pelvic magnetic resonance imaging, and endoscopy. Of the patients with an evaluable initial response, those with a cCR (n = 43) underwent NOM, and those with a non-cCR (n = 43) underwent surgery. The clinical endpoints included local regrowth-free survival, regional control, distant metastasis-free survival, disease-free survival, and overall survival., Results: Compared with patients with an initial cCR, patients with initial non-cCR had more advanced T and N stage (P = .05), larger primary tumors (P = .002), and more circumferential resection margin involvement on diagnostic magnetic resonance imaging (P < .001). With a median follow-up of 30.1 months, the persistent cCR rate was 79% (30 of 38 patients) in the NOM cohort. The 2-year local regrowth-free survival was 81% (95% confidence interval [CI], 70%-94%) in the initial cCR group, and all patients with local regrowth were successfully salvaged. Compared with those with a non-cCR, patients with a cCR had improved 2-year regional control (98% [95% CI, 93%-100%] vs 85% [95% CI, 74%-97%], P = .02), distant metastasis-free survival (100% [95% CI, 100%-100%] vs 80% [95% CI, 69%-94%], P < .01), disease-free survival (98% [95% CI, 93%-100%] vs 71% [95% CI, 59%-87%], P < .01), and overall survival (100% [95% CI, 100%-100%] vs 88% [95% CI, 79%-98%], P = .02). No late grade 3+ gastrointestinal or genitourinary toxicities were observed in the patients who underwent continued NOM., Conclusions: Short-course radiation therapy followed by consolidation chemotherapy may be a feasible organ preservation strategy in rectal cancer. Additional prospective studies are necessary to evaluate the safety and efficacy of this approach., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Short-course radiation followed by chemotherapy as total neoadjuvant therapy has been investigated primarily in Europe and Australia with increasing global acceptance. There are limited data on this regimen's use in the United States, however, potentially delaying implementation., Objective: This study aimed to compare clinical performance and oncologic outcomes of 2 rectal cancer neoadjuvant treatment modalities: short-course total neoadjuvant therapy versus standard chemoradiation., Design: This is a retrospective cohort study., Setting: This study was performed at a National Cancer Institute-designated cancer center., Patients: A total of 413 patients had locally advanced rectal cancers diagnosed from June 2009 to May 2018 and received either short-course total neoadjuvant therapy or standard chemoradiation., Interventions: There were 187 patients treated with short-course total neoadjuvant therapy (5 × 5 Gy radiation followed by consolidation oxaliplatin-based chemotherapy) compared with 226 chemoradiation recipients (approximately 50.4 Gy radiation in 28 fractions with concurrent fluorouracil equivalent)., Main Outcome Measures: Primary end points were tumor downstaging, measured by complete response and "low" neoadjuvant rectal score rates, and progression-free survival. Secondary analyses included treatment characteristics and completion, sphincter preservation, and recurrence rates., Results: Short-course total neoadjuvant therapy was associated with higher rates of complete response (26.2% vs 17.3%; p = 0.03) and "low" neoadjuvant rectal scores (40.1% vs 25.7%; p < 0.01) despite a higher burden of node-positive disease (78.6% vs 68.9%; p = 0.03). Short-course recipients also completed trimodal treatment more frequently (88.4% vs 50.4%; p < 0.01) and had fewer months with temporary stomas (4.8 vs 7.0; p < 0.01). Both regimens achieved comparable local control (local recurrence: 2.7% short-course total neoadjuvant therapy vs 2.2% chemoradiation, p = 0.76) and 2-year progression-free survival (88.2% short-course total neoadjuvant therapy (95% CI, 82.9-93.5) vs 85.6% chemoradiation (95% CI, 80.5-90.7))., Limitations: Retrospective design, unbalanced disease severity, and variable dosing of neoadjuvant consolidation chemotherapy were limitations of this study., Conclusions: Short-course total neoadjuvant therapy was associated with improved downstaging and similar progression-free survival compared with chemoradiation. These results were achieved with shortened radiation courses, improved treatment completion, and less time with diverting ostomies. Short-course total neoadjuvant therapy is an optimal regimen for locally advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B724.TERAPIA NEOADYUVANTE TOTAL CON RADIACIÓN DE CORTA DURACIÓN: EXPERIENCIA ESTADOUNIDENSE DE UNA TERAPIA NEOADYUVANTE CONTRA EL CÁNCER DE RECTO., Antecedentes: La radiación de corta duración seguida de quimioterapia como terapia neoadyuvante total se ha investigado principalmente en Europa y Australia con una aceptación mundial cada vez mayor. Sin embargo, datos limitados sobre el uso de este régimen en los Estados Unidos, han potencialmente retrasando su implementación., Objetivo: Comparar el desempeño clínico y los resultados oncológicos de dos modalidades de tratamiento neoadyuvante del cáncer de recto: terapia neoadyuvante total de corta duración versus quimioradiación. estándar., Diseo: Cohorte retrospectivo., Ajuste: Centro oncológico designado por el NCI., Pacientes: Un total de 413 cánceres rectales localmente avanzados diagnosticados entre junio de 2009 y mayo de 2018 que recibieron cualquiera de los regímenes neoadyuvantes., Intervenciones: Hubo 187 pacientes tratados con terapia neoadyuvante total de ciclo corto (radiación 5 × 5 Gy seguida de quimioterapia de consolidación basada en oxaliplatino) en comparación con 226 pacientes de quimiorradiación (aproximadamente 50,4 Gy de radiación en 28 fracciones con equivalente de fluorouracilo concurrente)., Principales Medidas De Resultado: Los criterios primarios de valoración fueron la disminución del estadio del tumor, medido por la respuesta completa y las tasas de puntuación rectal neoadyuvante "baja", y la supervivencia libre de progresión. Los análisis secundarios incluyeron las características del tratamiento y las tasas de finalización, conservación del esfínter y recurrencia., Resultados: La terapia neoadyuvante total de corta duración, se asoció con tasas más altas de respuesta completa (26,2% versus 17,3%, p = 0,03) y puntuaciones rectales neoadyuvantes "bajas" (40,1% versus 25,7%, p < 0,01) a pesar de una mayor carga de enfermedad con ganglios positivos (78,6% versus 68,9%, p = 0,03). Los pacientes de ciclo corto también completaron el tratamiento trimodal con mayor frecuencia (88,4% versus 50,4%, p < 0,01) y tuvieron menos meses con estomas temporales (4,8 versus 7,0, p < 0,01). Ambos regímenes lograron un control local comparable (recidiva local: 2,7% de SC-TNT versus 2,2% de TRC, p = 0,76) y supervivencia libre de progresión a 2 años (88,2% de SC-TNT [IC: 82,9 - 93,5] versus 85,6% CRT [CI: 80,5 - 90,7])., Limitaciones: Diseño retrospectivo, gravedad de la enfermedad desequilibrada y dosificación variable de quimioterapia neoadyuvante de consolidación., Conclusiones: La terapia neoadyuvante total de ciclo corto se asoció con una mejora en la reducción del estadio y una supervivencia libre de progresión similar en comparación con la quimioradiación. Estos resultados se lograron con ciclos de radiación más cortos, tratamientos mejor finalizados y menos tiempo en ostomías de derivación. La terapia neoadyuvante total de corta duración es un régimen óptimo para el cáncer de recto localmente avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B724. (Traducción- Dr. Fidel Ruiz Healy)., (Copyright © The ASCRS 2021.)

Objective: Investigate the association between neoadjuvant treatment strategy and perioperative complications in patients undergoing proctectomy for nonmetastatic rectal cancer., Summary of Background Data: Neoadjuvant SC-TNT is an alternative to neoadjuvant CRT for rectal cancer. Some have argued that short-course radiation and extended radiation-to-surgery intervals increase operative difficulty and complication risk. However, the association between SC-TNT and surgical complications has not been previously investigated., Methods: This single-center retrospective cohort study included patients undergoing total mesorectal excision for nonmetastatic rectal cancer after SC-TNT or CRT between 2010 and 2018. Univariate analysis of severe POM and multiple secondary outcomes, including overall POM, intraoperative complications, and resection margins, was performed. Logistic regression of severe POM was also performed., Results: Of 415 included patients, 156 (38%) received SC-TNT and 259 (62%) received CRT. The cohorts were largely similar, though patients with higher tumors (69.9% vs 47.5%, P < 0.0001) or node-positive disease (76.9% vs 62.6%, P = 0.004) were more likely to receive SC-TNT. We found no difference in incidence of severe POM (9.6% SC-TNT vs 12.0% CRT, P = 0.46) or overall POM (39.7% SC-TNT vs 37.5% CRT, P = 0.64) between cohorts. Neoadjuvant regimen was also not associated with a difference in severe POM (odds ratio 0.42, 95% confidence interval 0.04-4.70, P = 0.48) in multivariate analysis. There was no significant association between neoadjuvant regimen and any secondary outcome., Conclusion: In rectal cancer patients treated with SC-TNT and proctectomy, we found no significant association with POM compared to patients undergoing CRT. SC-TNT does not significantly increase the risk of POM compared to CRT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Short-course radiation therapy (SCRT) and nonoperative management are emerging paradigms for rectal cancer treatment. This clinical trial is the first to evaluate SCRT followed by chemotherapy as a nonoperative treatment modality., Methods: Patients with nonmetastatic rectal adenocarcinoma were treated on the single-arm, Nonoperative Radiation Management of Adenocarcinoma of the Lower Rectum study of SCRT followed by chemotherapy. Patients received 25 Gy in 5 fractions to the pelvis followed by FOLFOX ×8 or CAPOX ×5 cycles. Patients with clinical complete response (cCR) underwent nonoperative surveillance. The primary end point was cCR at 1 year. Secondary end points included safety profile and anorectal function., Results: From June 2016 to March 2019, 19 patients were treated (21% stage I, 32% stage II, and 47% stage III disease). At a median follow-up of 27.7 months for living patients, the 1-year cCR rate was 68%. Eighteen of 19 patients are alive without evidence of disease. Patients with cCR versus without had improved 2-year disease-free survival (93% vs 67%; P = .006), distant metastasis-free survival (100% vs 67%; P = .03), and overall survival (100% vs 67%; P = .03). Involved versus uninvolved circumferential resection margin on magnetic resonance imaging was associated with less initial cCR (40% vs 93%; P = .04). Anorectal function by Functional Assessment of Cancer Therapy-Colorectal cancer score at 1 year was not different than baseline. There were no severe late effects., Conclusions: Treatment with SCRT and chemotherapy resulted in high cCR rate, intact anorectal function, and no severe late effects. NCT02641691., (Copyright © 2021. Published by Elsevier Inc.)

Background: The objective of this study was to determine if there is an impact of surgical delay on 5-year overall survival (OS) from early stage colon cancer, and if so, to define how long surgery can safely be postponed., Methods: Using the NCDB, we compared early (14-30 days) and delayed surgery (31-90 days) in patients with Stage I/II colon cancer. Outcomes included OS at five years and odds of death., Results: Delayed resection conferred a decreased 5-year OS of 73.0% (95% CI, 72.6-73.4), compared to early resection 78.3% (95% CI, 77.9-78.8). When time to surgery was divided into one-week intervals, there was no difference in the odds of death with delay up to 35-41 days (6 weeks), but odds of death increased by 9% per week thereafter., Conclusions: These data support that definitive resection for early stage colon cancer may be safely delayed up to 6 weeks., (Copyright © 2020. Published by Elsevier Inc.)

Background: Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) is a validated tool for capturing a patient's perception of their physical capacity. The goal of this study was to determine whether preoperative PF correlates with a risk of postoperative complications., Study Design: Patients from a single-institution American College of Surgeons NSQIP database undergoing elective colorectal abdominal operations from January 2018 to June 2019 with a preoperative PROMIS-PF T-score were eligible for this retrospective study. Patients were divided into moderate to severe (score <40) and minimal to mild (score ≥40) physical disability cohorts. Primary outcomes were any complication and any Clavien-Dindo grade III or higher complication. Multivariate logistic regression was performed., Results: In total, 249 patients were included: 78 (31%) with self-scored moderate to severe disability and 171 (69%) with minimal to mild disability. Patients who scored as moderate to severe disability had a higher frequency of comorbidities and an open operative approach compared with patients with minimal to mild disability. These patients then had higher rates of any complication (37.2% vs 19.9%; p = 0.0036) and Clavien-Dindo grade III or higher complications (14.1% vs 7.6%; p = 0.017). After adjusting for patient factors, surgical procedure, and approach, patients scoring as moderate to severe disability were 2.00 times more likely (95% CI, 1.05 to 3.84; p = 0.036) to have any complication and 2.76 times more likely (95% CI, 1.07 to 7.14; p = 0.036) to have a Clavien-Dindo grade III or higher complication., Conclusions: Moderate to severe PF disability score is associated with increased risk of postoperative complications among patients undergoing colorectal operations. PROMIS-PF T-score can be a useful tool to identify patients who would benefit from targeted preoperative interventions, such as patient education, nutritional optimization, and prehabilitation., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Vaccination recommendations for childhood cancer survivors are ambiguous. Limited data exist on vaccination rates and patient/caregiver knowledge of vaccination postchemotherapy., Procedure: A single-institution study of childhood cancer survivors treated from 1996 to 2018. Study included a retrospective chart review assessing patient's vaccination status, survey of patient's/caregiver's knowledge/beliefs regarding vaccination postchemotherapy, and assessment of immunoglobulin titers., Results: A total of 120 patient charts were included. Vaccination records were available for 82% (98/120) of patients, 57% (56/98) were up to date with vaccinations before chemotherapy, and 83% (81/98) received vaccinations after chemotherapy. Children who resumed vaccination postchemotherapy were younger at cancer diagnosis compared to those who did not resume vaccination (2 vs 4 years, P < .02). Median time since chemotherapy was higher in vaccinated versus unvaccinated patients (107 vs 60 months, P < .02). Immunoglobulin titers were assessed in 27 patients, and 74% (20/27) were not immune to one or more infections tested. Lack of immunity to pneumococcal strains was the most common. There was no difference in median age at diagnosis or time since chemotherapy completion in immune versus nonimmune patients. In 33 surveyed patients/caregivers, 33% (11/33) were not advised about resuming vaccinations postchemotherapy. Over one-third (12/33) of respondents were concerned about vaccination safety after chemotherapy, although 88% (29/33) agreed they would vaccinate if recommended by their pediatrician/pediatric oncologist., Conclusions: Most childhood cancer survivors resume vaccinations postchemotherapy. Considerable variability exists in vaccination timing after chemotherapy. Pediatric oncologists play a central role in educating patients/pediatricians about vaccination recommendations postchemotherapy., (© 2020 Wiley Periodicals LLC.)

Post-translational control of PERIOD stability by Casein Kinase 1δ and ε (CK1) plays a key regulatory role in metazoan circadian rhythms. Despite the deep evolutionary conservation of CK1 in eukaryotes, little is known about its regulation and the factors that influence substrate selectivity on functionally antagonistic sites in PERIOD that directly control circadian period. Here we describe a molecular switch involving a highly conserved anion binding site in CK1. This switch controls conformation of the kinase activation loop and determines which sites on mammalian PER2 are preferentially phosphorylated, thereby directly regulating PER2 stability. Integrated experimental and computational studies shed light on the allosteric linkage between two anion binding sites that dynamically regulate kinase activity. We show that period-altering kinase mutations from humans to Drosophila differentially modulate this activation loop switch to elicit predictable changes in PER2 stability, providing a foundation to understand and further manipulate CK1 regulation of circadian rhythms., Competing Interests: JP, RN, CR, AF, SH, LY, RP, ST, DV, CP No competing interests declared, (© 2020, Philpott et al.)

Background: Thoracic epidural analgesia has been shown to be an effective method of pain control. The utility of epidural analgesia as part of an enhanced recovery after surgery protocol is debatable., Objective: This study aimed to determine if the use of thoracic epidural analgesia in an enhanced recovery after surgery protocol decreases hospital length of stay or inpatient opioid consumption after elective colorectal resection., Design: This is a single-institution retrospective cohort study., Settings: The study was performed at a high-volume, tertiary care center in the Midwest. An institutional database was used to identify patients., Patients: All patients undergoing elective transabdominal colon or rectal resection by board-certified colon and rectal surgeons from 2013 to 2017 were included., Main Outcome Measures: The main outcome was length of stay. The secondary outcome was oral morphine milligram equivalents consumed during the first 48 hours., Results: There were 1006 patients (n = 815 epidural, 191 no epidural) included. All patients received multimodal analgesia with opioid-sparing agents. Univariate analysis demonstrated no difference in length of stay between those who received thoracic epidural analgesia and those who did not (median, 4 vs 5 days; p = 0.16), which was substantiated by multivariable linear regression. Subgroup analysis showed that the addition of epidural analgesia resulted in no difference in length of stay regardless of an open (n = 362; p = 0.66) or minimally invasive (n = 644; p = 0.46) approach. Opioid consumption data were available after 2015 (n = 497 patients). Univariate analysis demonstrated no difference in morphine milligram equivalents consumed in the first 48 hours between patients who received epidural analgesia and those who did not (median, 135 vs 110 oral morphine milligram equivalents; p = 0.35). This was also confirmed by multivariable linear regression., Limitations: The retrospective observational design was a limitation of this study., Conclusion: The use of thoracic epidural analgesia within an enhanced recovery after surgery protocol was not found to be associated with a reduction in length of stay or morphine milligram equivalents consumed within the first 48 hours. We cannot recommend routine use of thoracic epidural analgesia within enhanced recovery after surgery protocols. See Video Abstract at http://links.lww.com/DCR/A765.

Dialectical behavior therapy (DBT) can be challenging to implement in community-based settings. Little guidance is available on models to evaluate the effectiveness or sustainability of training and implementation efforts. Residential programs have much to gain from introduction of evidence-based practices, but present their own challenges in implementation. This paper presents a low-cost process evaluation model to assess DBT training piloted in residential programs. The model targets staff and organizational factors associated with successful implementation of evidence-based practices and matches data collection to the four stages of the DBT training model. The strengths and limitations of the evaluation model are discussed.

Purpose: Pelvic floor abnormalities often affect multiple organs. The incidence of concomitant uterine/vaginal prolapse with rectal prolapse is at least 38%. For these patients, addition of sacrocolpopexy to rectopexy may be appropriate. Our aim was to determine if addition of sacrocolpopexy to rectopexy increases the procedural morbidity over rectopexy alone., Methods: We utilized the ACS-NSQIP database to examine female patients who underwent rectopexy from 2005 to 2014. We compared patients who had a combined procedure (sacrocolpopexy and rectopexy) to those who had rectopexy alone. Thirty-day morbidity was compared and a multivariable model constructed to determine predictors of complications., Results: Three thousand six hundred patients underwent rectopexy; 3394 had rectopexy alone while 206 underwent a combined procedure with the addition of sacrocolpopexy. Use of the combined procedure increased significantly from 2.6 to 7.7%. Overall morbidity did not differ between groups (14.8% rectopexy alone vs. 13.6% combined procedure, p = 0.65). Significant predictors of morbidity included addition of resection to a rectopexy procedure, elevated BMI, smoking, wound class, and ASA class. After controlling for these and other patient factors, the addition of sacrocolpopexy to rectopexy did not increase overall morbidity (OR 1.00, p = 0.98)., Conclusions: There is no difference in operative morbidity when adding sacrocolpopexy to a rectopexy procedure. Despite a modest increase in utilization of combined procedures over time, the overall rate remains low. These findings support the practice of multidisciplinary evaluation of patients presenting with rectal prolapse, with the goal of offering concurrent surgical correction for all compartments affected by pelvic organ prolapse disorders.

Background: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response., Objective: The purpose of this study was to analyze disease-free and overall survival., Design: This was a nonrandomized phase II trial., Settings: The study was conducted at multiple institutions., Patients: Four sequential study groups with stage II or III rectal cancer were included., Intervention: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6., Main Outcome Measures: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study., Results: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03)., Limitations: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients., Conclusions: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.

Multisite phosphorylation of the PERIOD 2 (PER2) protein is the key step that determines the period of the mammalian circadian clock. Previous studies concluded that an unidentified kinase is required to prime PER2 for subsequent phosphorylation by casein kinase 1 (CK1), an essential clock component that is conserved from algae to humans. These subsequent phosphorylations stabilize PER2, delay its degradation, and lengthen the period of the circadian clock. Here, we perform a comprehensive biochemical and biophysical analysis of mouse PER2 (mPER2) priming phosphorylation and demonstrate, surprisingly, that CK1δ/ε is indeed the priming kinase. We find that both CK1ε and a recently characterized CK1δ2 splice variant more efficiently prime mPER2 for downstream phosphorylation in cells than the well-studied splice variant CK1δ1. While CK1 phosphorylation of PER2 was previously shown to be robust to changes in the cellular environment, our phosphoswitch mathematical model of circadian rhythms shows that the CK1 carboxyl-terminal tail can allow the period of the clock to be sensitive to cellular signaling. These studies implicate the extreme carboxyl terminus of CK1 as a key regulator of circadian timing., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Background: In 2012, the American Society of Colon and Rectal Surgeons published the Rectal Cancer Surgery Checklist, a consensus document listing 25 essential elements of care for all patients undergoing radical surgery for rectal cancer. The authors herein examine checklist adherence in a mature, multisurgeon specialty academic practice., Materials and Methods: A retrospective medical record review of patients undergoing elective radical resection for rectal adenocarcinoma over a 23-mo period was conducted. Checklists were completed post hoc for each patient, and these results were tabulated to determine levels of compliance. Subgroup analyses by compliance and experience levels of the treating surgeon were performed., Results: A total of 161 patients underwent resection, demonstrating a median completion rate of 84% per patient. Poor compliance was noted consistently in documenting baseline sexual function (0%), multidisciplinary discussion of treatment plans (16.8%), pelvic nerve identification (8.7%) and leak testing (52.9%), and radial margin status reporting (57.5%). Junior surgeons achieved higher rates of compliance and were more likely to restage after neoadjuvant therapy (67.9% versus 29.4%, P < 0.001), discuss patients at tumor board (31.3% versus 13.2%, P = 0.014), and document leak testing (86.7% versus 47.2%, P = 0.005) compared with senior surgeons., Conclusions: Checklist compliance within a high-volume, specialty academic practice remains varied. Only surgeon experience level was significantly associated with high checklist compliance. Junior surgeons achieved greater compliance with certain items, particularly those that reinforce decision-making. Further efforts to standardize rectal cancer care should focus on checklist implementation, targeted surgeon outreach, and assessment of checklist compliance correlation to clinical outcomes., (Published by Elsevier Inc.)

Background: A paucity of data exists in the use of neoadjuvant chemoradiation therapy (NRT) for T4, non-metastatic colon cancer. This study was conducted to determine the effect of NRT on outcomes after resection for T4 colon cancer., Methods: All patients with non-metastatic resected clinical T4 colon cancer from 2000 to 2012 at a tertiary care center were included. The cohort was divided into two groups-those that received NRT and those that did not (non-NRT). The primary outcomes were margin-negative resection and overall survival (OS)., Results: One hundred and thirty-one consecutive patients with non-metastatic clinical T4 colon cancer with a mean age of 65 years were included. NRT was used in 23 patients (17.4%). NRT group was noted to have non-statistically significant improvement in R0 resection rate (NRT 95.7% vs non-NRT 88.0%; p = 0.27) and local recurrence (NRT 4.3% vs non-NRT 15.7%; p = 0.15). There was a significant difference in T-stage downstaging between the two groups (NRT 30.4% vs non-NRT 6.5%; p = 0.007). In a bivariate analysis, NRT was associated with improved 5-year OS (NRT 76.4% vs non-NRT 51.5%; p = 0.03). This relationship did not persist in a Cox proportional hazard analysis that included age and comorbidity (HR 2.19; 95% CI 0.87-5.52; p = 0.09)., Conclusions: The use of NRT in locally advanced T4 colon cancer is safe and associated with increased downstaging. While there was a trend toward improvement in local recurrence and the ability to obtain margin-negative resections in the NRT group, this was not significant. Significantly improved overall survival was not observed in a multivariable analysis.

Background: Surgical site infections (SSI) are a common complication after colorectal surgery. An infection prevention bundle (IPB) was implemented to improve outcomes., Study Design: A standardized IPB that included the administration of oral antibiotics with a mechanical bowel preparation, preoperative shower with chlorhexidine, hair removal and skin preparation in holding, antibiotic wound irrigation, and a "clean-closure" protocol was implemented in January 2013. Data from the American College of Surgeons NSQIP were analyzed at a single academic institution to compare pre-IPB and post-IPB SSI rates. In January 2014, a prospective database was implemented to determine compliance with individual IPB elements and their effect on outcomes., Results: For the 24 months pre-IPB, the overall SSI rate was 19.7%. During the 30 months after IPB implementation, the SSI rate decreased to 8.2% (p < 0.0001). A subset of 307 patients was identified in both NSQIP and our prospective compliance databases. Elements of IPB associated with decreased SSI rates included preoperative shower with chlorhexidine (4.6% vs 16.2%; p = 0.005), oral antibiotics (3.4% vs 15.4%; p < 0.001), and mechanical bowel preparation (4.4% vs 14.3%; p = 0.008). Patients who received a full bowel preparation of both oral antibiotics and a mechanical bowel preparation had a 2.7% SSI rate compared with 15.8% for all others (p < 0.001). On multivariate analysis, full bowel preparation was independently associated with significantly fewer SSI (adjusted odds ratio 0.2; 95% CI 0.1 to 0.9; p = 0.006)., Conclusions: Implementation of an IPB was successful in decreasing SSI rates in colorectal surgery patients. The combination of oral antibiotics with a mechanical bowel preparation was the strongest predictor of decreased SSI., (Copyright © 2017 American College of Surgeons. All rights reserved.)

Background: Gynecologic surgeries are performed through abdominal, vaginal, laparoscopic, or robot-assisted laparoscopic routes. However, if the pelvis is not accessible by one of these routes, there are no published reports to guide pelvic surgeons., Case: A 34-year-old conjoined twin status postseparation with uterine didelphys and absence of her left colon and sacrum underwent hemihysterectomy, at which time her müllerian anomaly was unknown. She re-presented with vaginal bleeding and pain eventually attributed to a retained uterine horn. Conservative management failed. Given dense adhesions, traditional approaches to hysterectomy were not successful. She underwent a transperineal hemisupracervical hysterectomy., Conclusion: We propose a novel approach to the pelvis to guide surgeons when traditional approaches are not feasible. We also describe an instance of a retained uterine didelphys horn.

Purpose: Anorectal gastrointestinal stromal tumors (GISTs) are exceedingly rare, and management remains controversial in regard to local resection (LR) and preoperative chemotherapy., Methods: The National Cancer Data Base was queried from 1998 to 2012 for cases of GIST resection in the rectum or anus. Patient demographics, type of surgery (LR vs. radical excision [RE]), short-term outcomes, and overall survival (OS) were analyzed. Preoperative chemotherapy was recorded following the US FDA approval of imatinib in 2002., Results: Overall, 333 patients with resection of anorectal GISTs were included. Mean age at presentation was 62.3 years (range 22-90), and median tumor size was 4.0 cm (interquartile range 2.2-7.0). Five-year OS for all patients was 77.6%. In a multivariable survival analysis, only age and tumor size >5 cm (hazard ratio 2.48, 95% confidence interval 1.50-4.01; p = 0.004) were associated with increased mortality. One hundred and sixty-three (49.0%) patients underwent LR, compared with 158 (47.4%) who underwent RE. For tumors smaller than 5 cm, no difference in 5-year survival by surgical approach was observed (LR 82.3% vs. RE 82.6%; p = 0.71). Fifty-nine patients (17.7%) received preoperative chemotherapy; for patients undergoing RE with tumors >5 cm, there was decreased mortality in the group who received preoperative chemotherapy (5-year OS with chemotherapy 79.2% vs. no chemotherapy 51.2%; p = 0.03)., Conclusions: Size is the most important determinant in survival following resection. Local excision is common, with resection split between LR and RE. For smaller tumors, LR may be adequate therapy. Preoperative chemotherapy may result in improved survival for large tumors treated with radical resection, but the data are imperfect.