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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: Chronic idiopathic constipation (CIC) is a substantial problem in pediatric and adult patients with similar symptoms and workup; however, surgical management of these populations differs. We systematically reviewed the trends and outcomes in the surgical management of CIC in pediatric and adult populations., Methods: A literature search was performed using Ovid MEDLINE, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov between January 1, 1995 and June 26, 2020. Clinical trials and retrospective and prospective studies of patients of any age with a diagnosis of CIC with data of at least 1 outcome of interest were selected. The interventions included surgical resection for constipation or antegrade continence enema (ACE) procedures. The outcome measures included bowel movement frequency, abdominal pain, laxative use, satisfaction, complications, and reinterventions., Results: Adult patients were most likely to undergo resection (94%), whereas pediatric patients were more likely to undergo ACE procedures (96%) as their primary surgery. Both ACE procedures and resections were noted to improve symptoms of CIC; however, ACE procedures were associated with higher complication and reintervention rates., Conclusion: Surgical management of CIC in pediatric and adult patients differs with pediatric patients receiving ACE procedures and adults undergoing resections. The evaluation of resections and long-term ACE data in pediatric patients should be performed to inform patients and physicians whether an ACE is an appropriate procedure despite high complication and reintervention rates or whether resections should be considered as an initial approach for CIC., (Copyright © 2023 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

As treatment options for patients with rectal cancer evolve, patients with early-stage rectal cancer may have a treatment choice between surgery and a trial of nonoperative management. Patients must consider the treatments' clinical tradeoffs alongside their personal goals and preferences. Shared decision-making (SDM) between patients and clinicians can improve decision quality when patients are faced with preference-sensitive care options. We interviewed 28 stakeholders (13 clinicians and 15 patients) to understand their perspectives on early-stage rectal cancer treatment decision-making. Clinicians included surgeons, medical oncologists, and radiation oncologists who treat rectal cancer. Adult patients included those diagnosed with early-stage rectal cancer in the past 5 years, recruited from an institutional database. A semi-structured interview guide was developed based on a well-established decision support framework and reviewed by the research team and stakeholders. Interviews were conducted between January 2022 and January 2023. Transcripts were coded by 2 raters and analyzed using thematic analysis. Both clinicians and patients recognized the importance of SDM to support high-quality decisions about the treatment of early-stage rectal cancer. Barriers to SDM included variable clinician motivation due to lack of training or perception of patients' desires or abilities to engage, as well as time-constrained encounters. A decision aid could help facilitate SDM for early-stage rectal cancer by providing standardized, evidence-based information about treatment options that align with clinicians' and patients' decision needs., Competing Interests: M.C.P. was a consultant for UCB Biopharma in 2022 on a topic unrelated to this manuscript. The remaining authors declare that they have nothing to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Objective: Socially assistive robots (SARs) are a promising tool to manage children's pain and distress related to medical procedures, but current options lack autonomous adaptability. The aim of this study was to understand children's and caregivers' perceptions surrounding the use of an artificial intelligence (AI)-enhanced SAR to provide personalized procedural support to children during intravenous insertion (IVI) to inform the design of such a system following a user-centric approach., Methods: This study presents a descriptive qualitative needs assessment of children and caregivers. Data were collected via semi-structured individual interviews and focus groups. Participants were recruited from two Canadian pediatric emergency departments (EDs) between April 2021 and January 2022., Results: Eleven caregivers and 19 children completed 27 individual interviews and one focus group. Three main themes were identified: A. Experience in the clinical setting, B. Acceptance of and concerns surrounding SARs, and C. Features that support child engagement with SARs. Most participants expressed comfort with robot technology, however, concerns were raised about sharing personal information, photographing/videotaping, and the possibility of technical failure. Suggestions for feature enhancements included increasing movement to engage a child's attention and tailoring language to developmental age. To enhance the overall ED experience, participants also identified a role for the SAR in the waiting room., Conclusion: Artificial intelligence-enhanced SARs were perceived by children and caregivers as a promising tool for distraction during IVIs and to enhance the overall ED experience. Insights collected will be used to inform the design of an AI-enhanced SAR., Competing Interests: None., (© The Author(s) 2023.)

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.)

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.)

Importance: Short-course radiotherapy and total neoadjuvant therapy (SCRT-TNT) followed by total mesorectal excision (TME) has emerged as a new treatment paradigm for patients with locally advanced rectal adenocarcinoma. However, the economic implication of this treatment strategy has not been compared with that of conventional long-course chemoradiotherapy (LCCRT) followed by TME with adjuvant chemotherapy., Objective: To perform a cost-effectiveness analysis of SCRT-TNT vs LCCRT in conjunction with TME for patients with locally advanced rectal cancer., Design, Setting, and Participants: A decision analytical model with a 5-year time horizon was constructed for patients with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma treated with SCRT-TNT or LCCRT. Markov modeling was used to model disease progression and patient survival after treatment in 3-month cycles. Data on probabilities and utilities were extracted from the literature. Costs were evaluated from the Medicare payer's perspective in 2020 US dollars. Sensitivity analyses were performed for key variables. Data were collected from October 3, 2020, to January 20, 2021, and analyzed from November 15, 2020, to April 25, 2021., Exposures: Two treatment strategies, SCRT-TNT vs LCCRT with adjuvant chemotherapy, were compared., Main Outcomes and Measures: Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio and net monetary benefits. Effectiveness was defined as quality-adjusted life-years (QALYs). Both costs and QALYs were discounted at 3% annually. Willingness-to-pay threshold was set at $50 000/QALY., Results: During the 5-year horizon, the total cost was $41 355 and QALYs were 2.21 for SCRT-TNT; for LCCRT, the total cost was $54 827 and QALYs were 2.12, resulting in a negative incremental cost-effectiveness ratio (-$141 256.77). The net monetary benefit was $69 300 for SCRT-TNT and $51 060 for LCCRT. Sensitivity analyses using willingness to pay at $100 000/QALY and $150 000/QALY demonstrated the same conclusion., Conclusions and Relevance: These findings suggest that SCRT-TNT followed by TME incurs lower cost and improved QALYs compared with conventional LCCRT followed by TME and adjuvant chemotherapy. These data offer further rationale to support SCRT-TNT as a novel cost-saving treatment paradigm in the management of locally advanced rectal cancer.

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.)

Carotenoid excited singlet states, in particular, are typically very short lived. Therefore, time-resolved absorption spectroscopy in the time regime from femtoseconds to sub-milliseconds are required to unravel and understand the complicated relaxation and excitation energy-transfer pathways of carotenoids in solution and in photosynthetic pigment-protein complexes. The focus of this chapter is to explain how to use ultrafast time-resolved absorption spectroscopy in carotenoid research. The importance of a systematic approach to understanding the various carotenoid excited states by using a series of carotenoids with different conjugation lengths and the isomers of carotenoids is also emphasized., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Protein kinases catalyze the transfer of a phosphate group thereby activating proteins and initiating signaling cascades. Their cousins, the pseudokinases, are enzymatically nonactive counterparts of protein kinases that can be considered zombie enzymes. Interestingly, pseudokinases, which constitute about 10% of the human kinome, have been implicated in many cancers, despite their sequences predicting a lack of catalytic activity. Owing to recent research, it has been demonstrated that dysregulation of many pseudokinases triggers changes in cell signaling, proliferation, and drug resistance. This review is aimed at describing methods that can be used for detection of Tribbles family of pseudokinases, specifically TRIB2. We describe intracellular staining by flow cytometry and Western blotting techniques for the detection of endogenous TRIB2 protein., (Copyright © 2022 Elsevier 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: Risk-prediction indices are one category of the many tools implemented to guide efforts to decrease readmissions. However, using fied models to predict a complex process can prove challenging. In addition, no risk-prediction index has been developed for patients undergoing colorectal surgery. Therefore, we evaluated the performance of a widely utilized simplified index developed at the hospital level - LACE (length of stay, acute admission, Charlson comorbidity index score, and emergency department visits) and developed and evaluated a novel index in predicting readmissions in this patient population., Methods: Using a retrospective split-sample cohort, patients discharged after colorectal surgery were identified within the inpatient databases of the Healthcare Cost and Utilization Project for the states of New York, California, and Florida (2006-2014). The primary outcome was death or readmission within 30 days after discharge. Multivariable logistic regression models incorporated patient comorbidities, postoperative complications, and hospitalization details, and were evaluated using the C statistic., Results: A total of 440,742 patients met eligibility criteria. The rate of death or readmission within 30 days after discharge was 14.0% (n = 61,757). When applied to surgical patients, the LACE index demonstrated a poor model fit (C = 0.631). The model fit improved significantly-but remained poor (C = 0.654; P < .001)-with the addition of the following variables, which are known to be associated with readmission after colorectal surgery: age, indication for surgery, and creation of a new ostomy. A novel, simplified model also yielded a poor model fit (C = 0.660)., Conclusion: Postdischarge death or readmission after colorectal surgery is not accurately modeled using existing, modified, or novel simplified risk prediction models. Payers and providers must ensure that quality improvement efforts applying simplified models to complex processes, such as readmissions following colorectal surgery, may not be appropriate, and that models reflect the relevant patient population., (Published by Elsevier Inc.)

Background: Although diverting stomas have reduced anastomotic leak rates after sphincter-preserving proctectomy in some series, the effectiveness of routine diversion among a broad population of rectal cancer patients remains controversial. We hypothesized that routine temporary diversion is not associated with decreased rates of leak or reintervention in cancer patients at large undergoing sphincter-sparing procedures., Study Design: The Florida State Inpatient Database (AHRQ, Healthcare Cost and Utilization Project) was queried for patients undergoing sphincter-preserving proctectomy for cancer (2005 to 2014). Matched cohorts defined by diversion status were created using propensity scores based on patient and hospital characteristics. Incidence of anastomotic leak, nonelective reintervention, and readmission were compared, and cumulative 90-day inpatient costs were calculated., Results: Of 8,620 eligible sphincter-sparing proctectomy patients, 1,992 matched pairs were analyzed. Leak rates did not significantly vary between groups (4.5% vs 4.3%; p = 0.76), but diversion was associated with significantly higher odds of nonelective reintervention (2.37; 95% CI 1.90 to 2.96) and readmission (1.55; 95% CI 1.33 to 1.81) compared with undiverted patients. Median costs were higher among those diverted (US$21,325 vs US$15,050; p < 0.01)., Conclusions: No association between diversion and anastomotic leak was found. However, temporary diversion was associated with increased incidence of nonelective reinterventions, readmissions, and higher costs. We therefore challenge the paradigm of routine diversion in rectal cancer operations. Additional study is needed to identify which patients would benefit most from diversion., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Resection of T4 colon cancer remains challenging compared to lower T stages. Data on the effect of neoadjuvant radiation to improve resectability and survival are lacking. The purpose of this study is to describe the use and outcomes of neoadjuvant radiation therapy in clinical T4 colon cancer., Methods: Adults with clinical evidence of T4 locally advanced colon cancer were included from the National Cancer Database (2004-2014). Bivariate and multivariable analyses were used to examine the association between neoadjuvant radiation therapy and R 0 resection rate, multivisceral resection, and overall survival., Results: Fifteen thousand two hundred and seven patients with clinical T4 disease who underwent resection were identified over the study period. One hundred ninety-five (1.3%) underwent neoadjuvant radiation therapy. Factors associated with the use of neoadjuvant radiation therapy included younger age, male sex, private insurance, lower Charlson Comorbidity Index score, and treatment at an academic research program. Neoadjuvant radiation therapy was associated with superior R 0 resection rates (87.2% neoadjuvant radiation therapy vs 79.8% no neoadjuvant radiation therapy; P = .009). Five-year overall survival was increased in the neoadjuvant radiation therapy group (62.0% neoadjuvant radiation therapy vs 45.7% no neoadjuvant radiation therapy; P < .001). The benefit of neoadjuvant radiation therapy persisted in a Cox proportional hazards multivariable model containing a number of confounding variables, including comorbidity and postoperative chemotherapy (odds ratio 1.37; 95% confidence interval 1.05-1.77; P = .01). In a subgroup analysis of T4b patients, there was an even greater size effect in adjusted overall survival (odds ratio 1.71; 95% confidence interval 1.07-2.72; P = .02)., Conclusion: Although radiation is rarely used in locally advanced colon cancer, this National Cancer Database analysis suggests that the use of neoadjuvant radiation for clinical T4 disease may be associated with superior R 0 resection rates and improved overall survival. Patients with clinical T4b disease may benefit the most from treatment. Neoadjuvant radiation therapy should be considered on a case-by-case basis in locally advanced colon cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Human papillomavirus (HPV) infection is responsible for 4.3% of the global cancer burden. Since 2006, current HPV vaccines have reduced the prevalence of the virus in adolescent girls, reduced the prevalence of genital warts, and been proven to reduce the progression of anal intraepithelial neoplasia in men. Herein, we review the epidemiology, virology, and immunology behind the prophylactic HPV vaccines and current recommendations for its use. We also review future immune therapies being trialed for use against HPV-related cancers including anal cancer.

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: 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.)

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.

Background: Adjuvant chemotherapy for T3N0 colon cancer is controversial. National guidelines recommend its use in patients with stage II with high-risk features, including lymph node harvest of less than 12, yet this treatment is underused., Objective: The purpose of this study was to demonstrate that the use of adjuvant chemotherapy in patients with T3N0 adenocarcinoma with inadequate lymph node harvest is beneficial., Design: This was a retrospective population-based study of patients with resected T3N0 adenocarcinoma of the colon., Settings: The National Cancer Database was queried from 2003 to 2012., Patients: A total of 134,567 patients with T3N0 colon cancer were included in this analysis., Main Outcome Measures: The use of chemotherapy, short-term outcomes, and overall survival was evaluated. Clinicopathologic factors associated with omission of chemotherapy were also analyzed., Results: Inadequate lymph node harvest was observed in 23.3% of patients, and this rate decreased over the study period from 46.8% in 2003 to 12.5% in 2012 (p < 0.0001). Overall 5-year survival for patients with T3N0 cancer was 66.8%. Inadequate lymph node harvest among these patients was associated with lower overall 5-year survival (58.7% vs 69.8%; p < 0.001). The use of adjuvant chemotherapy among patients with T3N0 cancer after inadequate lymph node harvest was only 16.7%. In a multivariable analysis, factors associated with failure to receive chemotherapy included advanced age (OR = 0.44 (95% CI, 0.43-0.45)), increased comorbidities (OR = 0.7 (95% CI, 0.66-0.76)), and postoperative readmission (OR = 0.78 (95% CI, 0.67-0.91)). Patients with inadequate lymph node harvest who received adjuvant chemotherapy had improved 5-year survival (chemotherapy, 78.4% vs no chemotherapy, 54.7%; p < 0.001). Even when controlling for all of the significant variables, the administration of chemotherapy remained a predictor of decreased mortality (HR = 0.57 (95% CI, 0.54-0.60); p < 0.001)., Limitations: This study was limited by its retrospective, population-based design., Conclusions: Patients with T3N0 colon cancer with inadequate lymph node harvest who receive adjuvant chemotherapy have increased overall survival. Despite this survival benefit, a fraction of these patients receive adjuvant chemotherapy. Barriers to chemotherapy are multifactorial.

Objective: Assess the impact of ostomy formation on quality of life for U.S. Service Members., Methods: U.S. personnel sustaining colorectal trauma from 2003 to 2011 were identified using the Department of Defense Trauma Registry. A cross-sectional observational study was conducted utilizing prospective interviews with standard survey instruments. Primary outcome measures were the Stoma Quality of Life Scale and Veterans RAND 36 scores and subjective responses. Patients with colorectal trauma not requiring ostomy served as controls., Results: Of 177 available patients, 90 (50.8%) male veterans consented to participate (55 ostomy, 35 control). No significant differences were observed between ostomy and control groups for Injury Severity Score (25.6 ± 9.9 vs. 22.9 ± 11.8, p = 0.26) or mechanism of injury (blast: 55 vs. 52%, p = 0.75); nonostomates had fewer anorectal injuries (3.2 vs. 47.9%, p < 0.01). Median follow-up was 6.7 years. Veterans RAND-36 Physical and Mental Component Scores were similar between groups. About 45.8% of ostomates were willing-to-trade a median of 10 years (interquartile range = 5-15) of their remaining life for gastrointestinal continuity. At last follow-up, 95.9% of respondents' combat-related ostomies were reversed with a median duration of 6 (range = 3-19) months diverted., Conclusions: Ostomy creation in a combat environment remains safe and does not have a quantifiable impact on long-term quality of life., (Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.)

Background: Anastomotic leak is one of the most feared complications of gastrointestinal surgery. Surgeons routinely perform a diverting loop ileostomy (DLI) to protect high-risk colo-rectal anastomoses., Study Design: The NSQIP database was queried from 2012 to 2013 for patients undergoing open ileo-colic resection with and without a DLI. The primary outcome was the development of any anastomotic leak-including those managed operatively and non-operatively. Secondary outcomes included overall complication rate, return to the OR, readmission, and 30-day mortality., Results: Four thousand one hundred fifty-nine patients underwent open ileo-colic resection during the study period. One hundred eighty-six (4.5 %) underwent a DLI. Factors associated with the addition of a DLI included emergency surgery, pre-operative sepsis, and IBD. There were 197 anastomotic leaks (4.7 %) with 100 patients requiring reoperation (2.4 %). DLI was associated with a decrease in anastomotic leaks requiring reoperation (DLI vs no DLI: 0 (0 %) vs 100 (2.5 %); p = 0.02) and with increased readmission (OR 1.93; 95 % CI 1.30-2.85; p = 0.001)., Conclusion: DLI is rarely used for open ileo-colic resection. There were no serious leaks requiring reoperation in the DLI group. A DLI was associated with an almost two-fold increase in the odds of readmission. Surgeons must weigh the reduction in serious leak rate with postoperative morbidity when considering a DLI for open ileo-colic resection.

Despite medical and surgical advances leading to increased ability to restore or preserve gastrointestinal continuity, creation of stomas remains a common surgical procedure. Every ostomy results in a risk for subsequent parastomal herniation, which in turn may reduce quality of life and increase health care expenditures. Recent evidence-supported practices such as utilization of prophylactic reinforcement, attention to stoma placement, and laparoscopic-based stoma repairs with mesh provide opportunities to both prevent and successfully treat parastomal hernias.

Background: There is excellent evidence that surgical safety checklists contribute to decreased morbidity and mortality., Objective: The purpose of this study was to develop a surgical checklist composed of the key phases of care for patients with rectal cancer., Design: A consensus-oriented decision-making model involving iterative input from subject matter experts under the auspices of The American Society of Colon and Rectal Surgeons was designed., Settings: The study was conducted through meetings and discussion to consensus., Patients: Patient data were extracted from an initial literature review., Main Outcome Measures: The checklist was measured by its ability to improve care in complex rectal surgery cases by reducing the possibility of omission through the division of treatment into 3 distinct phases., Results: The process generated a 25-item checklist covering the spectrum of care for patients with rectal cancer who were undergoing surgery., Limitations: The study was limited by its lack of prospective validation., Conclusions: The American Society of Colon and Rectal Surgeons rectal cancer surgery checklist is composed of the essential elements of preoperative, intraoperative, and postoperative care that must be addressed during the surgical treatment of patients with rectal cancer.

Inflammatory bowel disease patients will likely come to the surgeon's attention at some point in their course of disease, and they present several unique anatomic, metabolic, and physiologic challenges. Specific and well-recognized complications of chronic Crohn disease and ulcerative colitis are presented as well as an organized and evidence-based approach to the medical and surgical management of such disease sequelae. Topics addressed in this article include intestinal fistula and short bowel syndrome, pouch complications, and deep venous thrombosis with emphasis placed on optimization of the patient's physiologic state for best outcomes., (Published by Elsevier Inc.)

OBJECTIVE. The purpose of this article is to highlight the most salient imaging features of retrorectal masses with regard to surgical planning, preoperative biopsy, and identification of nonneoplastic mimickers of malignancy. CONCLUSION. Retrorectal tumors are associated with high morbidity. CT and MRI aid in preoperative planning because surgical resection is the treatment of choice for both benign and malignant entities. Radiologists need to understand the operative techniques currently used for retrorectal tumors because the first attempt at excision is the best chance for complete resection and optimal outcome.

The optimal treatment of early (T1 and T2) rectal adenocarcinomas remains controversial. Local excision and radical resection with total mesorectal excision are the two surgical techniques for excising early rectal cancer. Each has their respective benefits, with local excision allowing for decreased operative morbidity and mortality while radical resection provides an oncologically complete treatment through lymphadenectomy. Local excision can be accomplished via transanal endoscopic microsurgery or transanal excision. There is no significant difference in the recurrence rates (21% vs. 33%) or overall survival (80% vs. 66%) between the two local excision modalities; however, transanal endoscopic microsurgery does allow for a higher rate of R0 resection. Current selection criteria for local excision include well to moderately differentiated tumors without high-risk features such as lymphovascular invasion, perineural invasion, or mucinous components. In addition, tumors should ideally be <3 cm in size, excised with a clear margin, occupy less than 1/3 of the circumference of the bowel and be mobile/nonfixed. Despite these stringent inclusion criteria, local excision continues to be plagued with a high recurrence rate in both T1 and T2 tumors due to a significant rate of occult locoregional metastases (20% to 33%). For both tumor groups, the recurrence rate in the local excision group is more than double compared to radical resection. However, the overall survival is not significantly different between those with and without metastases. With intense postoperative surveillance, these recurrences can be identified early while they are confined to the pelvis allowing for salvage surgical options. Recently, neoadjuvant therapy followed by local excision has shown favorable short and long-term oncological outcomes to radical resection in the treatment of T2 rectal cancer. Ultimately, the management of early rectal cancer must be individualized to each patient's expectations of quality and quantity of life. With informed consent, patients may be willing to accept a higher failure rate and an increased post-operative surveillance regimen to preserve a perceived increased quality of life.

Background: Despite the potential for morbidity and permanent lifestyle alteration, few reports exist examining traumatic injury to the anal canal, particularly among modern-day combatants., Objective: The aim of this study was to document the incidence, initial surgical management, and long-term outcomes of wartime anal trauma., Design: This study is a retrospective review., Data Sources: Data were compiled from multiple electronic medical record systems, including the Department of Defense Trauma Registry, the Patient Administration Systems and Biostatistics Activity, and the Armed Forces Health Longitudinal Tracking Application., Settings: Combatants were treated at military treatment facilities with surgical capability during the wars in Iraq and Afghanistan, 2003 through early 2011., Patients: All US and coalition combatants sustaining trauma to the anal canal or sphincter musculature were included., Main Outcome Measures: The quantification of incidence, the evaluation of initial treatment approach, and the determination of clinical and surgical factors correlating with restoration or preservation of GI tract continuity were the primary outcomes measured., Results: Anal trauma occurred in 46 combatants, predominantly from blast injury (76.1%). Most (36, 78.2%) underwent fecal diversion. Concurrent severe systemic or intra-abdominal injuries correlated with colostomy creation. Acute anoplasty was attempted in 11 patients (23.7%) but did not influence eventual colostomy reversal. Among 33 US personnel, the permanent colostomy rate was 30.3%. Concurrent injury to the abdomen strongly predicted long-term colostomy (p = 0.009), along with hypogastric arterial ligation (p = 0.05) and pelvic fracture (p = 0.06)., Limitations: This study was limited by the potential underdiagnosis of anal injury and the restricted follow-up of non-US personnel., Conclusions: Other injuries besides anal trauma typically have guided the decision for fecal diversion, and acute anal repair has rarely been indicated. The majority of patients with anal trauma regained normal GI continuity, although certain pelvic injuries increased the likelihood of permanent colostomy.

Background: Limited data exist examining the use of fecal diversion in combatants from modern armed conflicts. Characterization of factors leading to colostomy creation is an initial step toward optimizing and individualizing combat casualty care., Methods: A retrospective review of the US Department of Defense Trauma Registry database was performed for all US and coalition troops with colorectal injuries sustained during combat operations in Iraq and Afghanistan over 8 years. Colostomy rate, anatomic injury location, mechanism of injury, demographic data, and initial physiologic parameters were examined. Univariate and multivariate analyses were conducted., Results: We identified 867 coalition military personnel with colorectal injuries. The overall colostomy rate was 37%. Rectal injuries had the highest diversion rate (56%), followed by left-sided (41%) and right-sided (20%) locations (P < .0001). Those with gunshot wounds (GSW) underwent diversion more often than blast injuries (43% vs 31% respectively, P < .0008). Injury Severity Score ≥16 (41% vs 30%; P = .0018) and damage control surgery (DCS; 48.2% vs 31.4%; P < .0001) were associated with higher diversion rates. On multivariate analysis, significant predictors for colostomy creation were injury location: Rectal versus left colon (odds ratio [OR], 2.2), rectal versus right colon (OR, 7.5), left versus right colon (OR, 3.4), GSW (OR, 2.0), ISS ≥ 16 (OR, 1.7), and DCS (OR, 1.6)., Conclusion: In this exploratory study of 320 combat-related colostomies, distal colon and rectal injuries continue to be diverted at higher rates independent of other comorbidities. Additional outcomes-directed research is needed to determine whether such operative management is beneficial in all patients., (Published by Mosby, Inc.)

Background: Robotic-assisted surgery has become increasingly common; however, it is unclear if its use for colectomy improves in-hospital outcomes compared with the laparoscopic approach., Objective: The aim of the study is to compare in-hospital outcomes and costs between patients undergoing robotic or laparoscopic colectomy., Design: This study is a retrospective review of the 2008 to 2009 Nationwide Inpatient Sample. SETTINGS, PATIENTS, INTERVENTIONS: All adult patients who underwent an elective robotic or laparoscopic colectomy in hospitals performing both procedures (N = 2583 representing an estimated 12,732 procedures) were included., Main Outcome Measures: Outcomes included intraoperative and postoperative complications, length of stay, and direct costs of care. Regression models were used to compare these outcomes between procedural approaches while controlling for baseline differences in patient characteristics., Results: Overall, 6.1% of patients underwent a robotic procedure. Factors associated with robotic-assisted colectomy included younger age, benign diagnoses, and treatment at a lower-volume center. Patients undergoing robotic and laparoscopic procedures experienced similar rates of intraoperative (3.0% vs 3.3%; adjusted OR = 0.88 (0.35-2.22)) and postoperative (21.7% vs 21.6%; adjusted OR = 0.84 (0.54-1.30)) complications, as well as risk-adjusted average lengths of stay (5.4 vs 5.5 days, p = 0.66). However, robotic-assisted colectomy resulted in significantly higher costs of care ($19,231 vs $15,807, p < 0.001). Although the overall postoperative morbidity rate was similar between groups, the individual complications experienced by each group were different., Limitations: A limitation of this study is the potential miscoding of robotic cases in administrative data., Conclusions: Robotic-assisted colectomy significantly increases the costs of care without providing clear reductions in overall morbidity or length of stay. As the use of robotic technology in colon surgery continues to evolve, critical appraisal of the benefits offered in comparison with the resources consumed is required.

Background: Steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly, contributing to increased primary graft nonfunction following transplantation. Activation of nuclear factor kappa-B (NFκB) following I/R injury plays a crucial role in activation of pro-inflammatory responses leading to injury., Methods: We evaluated the role of NFκB in steatotic liver injury by using an orthotopic liver transplant (OLT) model in Zucker rats (lean to lean or obese to lean) to define the mechanisms of steatotic liver injury. Obese donors were treated with bortezomib to assess the role of NF-κB in steatotic liver I/R injury. Hepatic levels of NF-κB and pro-inflammatory cytokines were analyzed by ELISA. Serum transaminase levels and histopathological analysis were performed to assess associated graft injury., Results: I/R injury in steatotic liver results in significant increases in activation of NF-κB (40%, p<0.003), specifically the p65 subunit following transplantation. Steatotic donor pretreatment with proteasome inhibitor bortezomib (0.1mg/kg) resulted in significant reduction in levels of activated NF-κB (0.58±0.18 vs. 1.37±0.06O.D./min/10 μg protein, p<0.003). Bortezomib treatment also reduced expression of pro-inflammatory cytokines MIP-2 compared with control treated steatotic and lean liver transplants respectively (106±17.5 vs. 443.3±49.9 vs. 176±10.6 pg/mL, p=0.02), TNF-α (223.8±29.9 vs. 518.5±66.5 vs. 264.5±30.1 pg/2 μg protein, p=0.003) and IL-1β (6.0±0.91 vs. 19.8±5.2 vs. 5±1.7 pg/10 μg protein, p=0.02) along with a significant reduction in ALT levels (715±71 vs. 3712.5±437.5 vs. 606±286 U/L, p=0.01)., Conclusion: These results suggest that I/R injury in steatotic liver transplantation are associated with exaggerated activation of NFκB subunit p65, leading to an inflammatory mechanism of reperfusion injury and necrosis. Proteasome inhibition in steatotic liver donor reduces NFκB p65 activation and inflammatory I/R injury, improving transplant outcomes of steatotic grafts in a rat model., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Treatment decisions for colorectal cancer vary based on lymph node status. While some histopathological features of the primary tumor correlate with lymph node spread, the relative influences of these risk factors are not well quantified., Objective: This study aims to systematically review published studies relating histopathological features of primary colorectal cancer to the presence of lymph node metastases and to determine how reliable certain factors might be at predicting nodal metastasis when only the primary lesion is available for study., Data Sources: Inclusive literature search using EMBASE and Ovid MEDLINE databases plus manual reference checks of all articles correlating lymphatic spread with colorectal cancer (any T stage) from 1984 to mid-2008 was performed., Study Selection: This search generated two levels of screening utilized on 602 citations, yielding 123 articles for full review. Data reported from 76 articles were chosen., Main Outcome Measures: The relative influence of each histopathological feature on the likelihood of lymphatic metastases was determined. Fixed-effects meta-analysis was performed, and results were reported as Mantel-Haenszel odds ratios (OR)., Results: Of 42 histopathological features analyzed, only 40.4% were reported in >2 articles. The positive predictive values for the top quartile of most frequently reported risk factors were 25.5-86.4%. Among the commonly reported histopathological findings, lymphatic invasion (OR, 8.62) significantly outperformed tumor depth (T2 vs. T1; OR, 2.62) and overall differentiation (OR, 2.38) in predicting nodal spread. For the rectal cancer subset, risk factors differed from the overall colorectal group in predictive ability; poor differentiation at the invasive front (OR, 6.08) and tumor budding (OR, 5.82) were the most predictive., Limitations: This literature search is limited by the small number of studies examining only rectal cancers and the potential changes in histological and/or surgical techniques over the study period., Conclusions: No single histopathological feature of colorectal cancer reliably predicted lymph node metastases. Several risk factors that correlate highly with nodal disease are not routine components of standard pathology reports. Until further research establishes histopathological or molecular patterns for predicting lymph node spread, caution should be exercised when basing treatment decisions solely on these factors.

Background: Thorough and objective analysis of long-term results following anal sphincter repair for fecal incontinence will permit the correct application of this operation in the context of newer treatment methods., Objective: This investigation aimed to comprehensively review outcomes beyond 5 years in patients undergoing anal sphincter repair for fecal incontinence., Data Sources: A systematic review of Embase and MEDLINE articles published between January 1991 and December 2010 was conducted; additional studies were identified by hand-searching bibliographies., Study Selection: A 2-step process was used for screening articles examining sphincter repair or sphincteroplasty in adults with fecal incontinence, with a minimum follow-up of 60 months., Main Outcome Measures: Subjective or objective assessment of fecal incontinence in the postoperative period was completed., Results: Data from 16 studies were examined, comprising nearly 900 repairs. There was significant heterogeneity in outcome measures, although most articles utilized at least one established incontinence instrument. In general, most series reported an initial subjectively "good" outcome in the majority of patients, with declines in this proportion over longer follow-up. There was poor correlation between quality of life and the severity of fecal incontinence, with all articles reporting high overall patient satisfaction even if continence declined with time or adaptive measures were needed. No consistent predictive factors for failure were identified., Limitations: This study was limited by the paucity of level I data with an adequate length of follow-up., Conclusion: Despite worsening results over time, most patients remain satisfied with their surgical outcome postsphincteroplasty. Efforts should be directed at identifying patients who may do poorly following sphincter repair, as well as establishing standardized long-term outcome benchmarks for comparing novel techniques for treating fecal incontinence.