Close distal margin is associated with locoregional rectal cancer recurrence: A multicenter study.

BACKGROUND AND OBJECTIVES: The importance of the radial margin for rectal cancer resection is well understood. However, surgeons have deemphasized the distal margin, accepting very close distal margins to perform sphincter-preserving surgery. We hypothesized that distal margins < 1 cm would be an independent risk factor for locoregional recurrence. The objective was to determine whether close distal margins are associated with increased locoregional recurrence risk. METHODS: This was a multi-institutional retrospective cohort study conducted at six academic medical centers including patients who received low anterior resection surgery for primary rectal cancer between 2007 and 2018. RESULTS: Of 556 low anterior resection patients, the rate of close distal margin was 12.8% (n = 71), and the locoregional recurrence rate was 5.0% (n = 28). The locoregional recurrence rate for close distal margin cases was 9.9% (n = 7) compared to 4.3% (n = 21) for distal margins ≥1.0 cm. In multivariable analysis, the only factor significantly associated with locoregional recurrence was close distal margin (adjusted odds ratio: 2.80, confidence interval: 1.08-7.25, p = 0.035). CONCLUSIONS: Rectal cancer patients with close distal margins (<1 cm) following low anterior resection had a significantly higher risk for locoregional recurrence. Therefore, the decision to perform low anterior resection with margins < 1 cm should be taken with caution.

Cardiac Surgery Exposure in General Surgery Residency-A Survey of General Surgery Residency Program Directors.

BACKGROUND: Little is known regarding how much exposure general surgery residents have to cardiac surgery, despite cardiothoracic (CT) surgery being an offered postresidency fellowship and career. Exposure to a subspecialty is important in shaping residents' interests and career decisions. METHODS: A survey was sent to all general surgery program directors via the Association of Program Directors in Surgery examining cardiac surgery exposure during training. The survey examined the presence of operative rotations in cardiac surgery and cardiac critical care, portions of cases residents were permitted to perform, cardiac surgery mentorship and education, and perceived biases in applying to cardiac surgery. Differences between programs with and without cardiothoracic training programs were analyzed. RESULTS: In total, 44% (102/230) of program directors responded to the survey. Residents were involved in operative cardiac and cardiac ICU rotations in 61 programs (69.8%) and 39 programs (38.2%), respectively. Twenty programs (19.6%) had a dedicated cardiothoracic surgery training program and these programs had significantly more graduates who aspired to be cardiac surgeons (M = 2.75, SD = 2.47) compared to hospitals with no CT programs (M = 1.43, SD = 1.41; p = 0.031). 35.3% of program directors reported resident concern over family life. CONCLUSIONS: There is a notable heterogeneity in general surgery resident exposure to cardiac surgery, cardiac ICU, and cardiac surgery mentorship. Increased exposure, mentorship and mitigating resident concern over the impact of social factors on cardiac surgical careers should be key areas of focus to ensure continued encouragement of future trainees and surgeons.

Conditional Survival Following Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: The long-term prognosis of patients who undergo cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies (PSM) varies considerably on the basis of histological and operative factors. While overall survival (OS) estimates are used to inform adjuvant therapy and surveillance strategies, conditional survival may provide more clinically relevant estimates of prognosis by accounting for disease-free time elapsed. PATIENTS AND METHODS: All patients from 12 academic institutions who underwent CRS ± HIPEC for PSM from 2000 to 2017 were retrospectively analyzed. OS and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method while conditional overall (COS) and conditional disease-free survival (CDFS) rates were calculated at 1, 2, or 3 years from surgery for different tumor histologies. RESULTS: Overall, 1610 patients underwent CRS ± HIPEC. Among patients with benign appendiceal mucinous tumors (N = 460), 5-year OS and COS at 3 years were 92.1% and 96.3% (Δ4.2%), respectively. For patients with well-differentiated appendiceal cancers (N = 400), 5-year OS and COS at 3 years were 76.3% and 88.3% (Δ12.0%), respectively. For patients with high-grade appendiceal cancers (N = 258), 5-year OS and COS at 3 years were 43.8% and 75.4% (Δ31.6%), respectively. For patients with colorectal cancers (N = 362), 5-year OS and COS at 3 years were 31.8% and 67.3% (Δ35.5%), respectively. For patients with peritoneal mesothelioma (N = 130), 5-year OS and COS at 3 years were 67.6% and 89.7% (Δ22.1%), respectively. Similar trends were observed for DFS/CDFS. CONCLUSION: The conditional survival of patients undergoing CRS ± HIPEC for PSM is associated with tumor histology. COS and CDFS provide a more accurate, dynamic estimate of survival than OS and DFS, especially for patients with more aggressive histologies.

A Multicenter Phase 1 Trial Evaluating Nanoliposomal Irinotecan for Heated Intraperitoneal Chemotherapy Combined with Cytoreductive Surgery for Patients with Peritoneal Surface Disease.

BACKGROUND: Nanoliposomal irinotecan (nal-IRI) is a promising novel hyperthermic intraperitoneal chemotherapy (HIPEC) agent given its enhanced efficacy against gastrointestinal tumors, safety profile, thermo-synergy, and heat stability. This report describes the first in-human phase 1 clinical trial of nal-IRI during cytoreductive surgery (CRS) and HIPEC. METHODS: Patients with peritoneal surface disease (PSD) from appendiceal and colorectal neoplasms were enrolled in a 3 + 3 dose-escalation trial using nal-IRI (70-280 mg/m2) during HIPEC for 30 min at 41 ± 1 °C. The primary outcome was safety. The secondary outcomes were pharmacokinetics (PK) and disease-free survival. Adverse events (AEs) categorized as grade 2 or higher were recorded. The serious AEs (SAEs) were mortality, grade ≥ 3 AEs, and dose-limiting toxicity (DLT). Irinotecan and active metabolite SN38 were measured in plasma and peritoneal washings. RESULTS: The study enrolled 18 patients, who received nal-IRI during HIPEC at 70 mg/m2 (n = 3), 140 mg/m2 (n = 6), 210 mg/m2 (n = 3), and 280 mg/m2 (n = 6). No DLT or mortality occurred. The overall morbidity for CRS/HIPEC was 39% (n = 7). Although one patient experienced neutropenia, no AE (n = 131) or SAE (n = 3) was definitively attributable to nal-IRI. At 280 mg/m2, plasma irinotecan and SN38 measurements showed maximum concentrations of 0.4 ± 0.6 µg/mL and 3.0 ± 2.4 ng/mL, a median time to maximum concentration of 24.5 and 26 h, and areas under the curve of 22.6 h*µg/mL and 168 h*ng/mL, respectively. At the 6-month follow-up visit, 83% (n = 15) of the patients remained disease-free. CONCLUSIONS: In this phase 1 HIPEC trial (NCT04088786), nal-IRI was observed to be safe, and PK profiling showed low systemic absorption overall. These data support future studies testing the efficacy of nal-IRI in CRS/HIPEC.

Management and Outcomes of Pathologic Upstaging of Clinical Stage I Rectal Cancers: An Exploratory Analysis.

BACKGROUND: Preoperative staging of clinical stage I rectal cancer can fail to diagnose T3 or nodal disease. Adjuvant treatment of these upstaged patients remains controversial. OBJECTIVE: The objective was to identify predictors of clinical stage I rectal cancer upstaging and quantify rates of local and systemic recurrence. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted using data from the United States Rectal Cancer Consortium, a registry of 1881 rectal cancer resections performed at 6 academic medical centers. PATIENTS: There were a total of 94 clinical stage I rectal cancer patients who underwent proctectomy without preoperative therapy. MAIN OUTCOME MEASURES: The primary measures were incidence of pathologic upstaging, recurrence (local and systemic), and overall survival. RESULTS: Among 94 clinical stage I patients who underwent proctectomy without preoperative therapy, 23 (24.5%) were upstaged by surgical pathology. There were 6 pT3N0 patients, 8 pT1-2N+ patients, and 9 pT3N+ patients. There were no significant differences in demographic or clinical characteristics between upstaged and nonupstaged patients. Of the 6 patients who were upstaged to T3N0 disease, none received adjuvant therapy and none developed recurrence. Of the 17 patients who were upstaged to N+ disease, 14 (82%) received adjuvant chemotherapy and 6 (35%) received adjuvant chemoradiation. None developed a local recurrence, but 4 (24%) developed systemic recurrence, and 2 (12%) died of disease over a mean of 36 months of follow-up. Among the 9 pT3N+ patients, the systemic recurrence rate was 33%, despite 8 of 9 patients receiving adjuvant fluorouracil, leucovorin, and oxaliplatin. LIMITATIONS: Small sample size hinders the ability to draw significant conclusions. CONCLUSIONS: One in 4 patients with stage I rectal cancer had unrecognized T3 or nodal disease found on operative pathology. Occult nodal disease was associated with worse outcomes, despite receiving adjuvant therapy. Systemic recurrence was more common than local recurrence. See Video Abstract at http://links.lww.com/DCR/B885 . MANEJO Y RESULTADOS DEL AUMENTO DEL ESTADIO PATOLGICO DE LOS CNCERES DE RECTO EN ESTADIO CLNICO I UN ANLISIS EXPLORATORIO: ANTECEDENTES:El estadiaje pre-operatorio del cáncer de recto en fase clínica I puede ser erróneo en el diagnóstico T3 o en la diseminación ganglionar. El tratamiento adyuvante de estos pacientes sobre-estadificados ​​sigue siendo controvertido.OBJETIVO:El identificar los factores predictivos en fase clínica I del cáncer de recto y cuantificar las tasas de recurrencia local y sistémica.DISEÑO:Estudio de cohortes retrospectivo.AJUSTE:El estudio se realizó utilizando los datos del Consorcio del Cáncer de Recto de los Estados Unidos, con un registro de 1.881 resecciones oncológicas rectales realizadas en seis centros médicos académicos.PACIENTES:Un total de 94 pacientes con cáncer de recto en fase clínica I fueron sometidos a proctectomía sin terapia preoperatoria.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron la incidencia del sobre-estadiaje histopatológico, la recurrencia (local y sistémica) y la sobrevida general.RESULTADOS:De 94 pacientes en fase clínica I que se sometieron a una proctectomía sin terapia preoperatoria, 23 (24,5%) fueron sobre-estadiados ​​por la histopatología quirúrgica. Hubieron 6 pacientes pT3N0, 8 pT1-2N + y 9 pT3N +. No hubo diferencias significativas en las características demográficas o clínicas entre los pacientes sobre-estadiados ​​y los no sobre-estadiados. De los 6 pacientes que fueron sobre-estadiados en la enfermedad T3N0, ninguno de ellos recibió terapia adyuvante y ninguno recidivó. De los 17 pacientes que fueron sobre-estadiados a la enfermedad N +, 14 (82%) recibieron quimioterapia adyuvante y 6 (35%) recibieron quimio-radioterapia adyuvante. Ninguno desarrolló recidiva local, pero 4 (24%) desarrollaron recidiva sistémica y 2 (12%) murieron a causa de la enfermedad durante el seguimiento medio de 36 meses. Entre los 9 pacientes con pT3N +, la tasa de recidiva sistémica fue del 33%, a pesar de que 8 de 9 pacientes recibieron fluorouracilo, leucovorina y oxaliplatino como quimio-adyuvantes.LIMITACIONES:El tamaño pequeño de la muestra dificulta la capacidad de obtener conclusiones significativas.CONCLUSIONES:Uno de cada cuatro pacientes con cáncer de recto en estadío I presentaba enfermedad ganglionar o T3 no descrita en la histopatología operatoria. La enfermedad ganglionar oculta se asoció con peores resultados, a pesar de recibir terapia adyuvante. La recidiva sistémica fue más común que la recidiva local. Consulte Video Resumen en http://links.lww.com/DCR/B885 . (Traducción-Dr. Xavier Delgadillo ).

Development and Validation of an Explainable Machine Learning Model for Major Complications After Cytoreductive Surgery.

Importance: Cytoreductive surgery (CRS) is one of the most complex operations in surgical oncology with significant morbidity, and improved risk prediction tools are critically needed. Machine learning models can potentially overcome the limitations of traditional multiple logistic regression (MLR) models and provide accurate risk estimates. Objective: To develop and validate an explainable machine learning model for predicting major postoperative complications in patients undergoing CRS. Design, Setting, and Participants: This prognostic study used patient data from tertiary care hospitals with expertise in CRS included in the US Hyperthermic Intraperitoneal Chemotherapy Collaborative Database between 1998 and 2018. Information from 147 variables was extracted to predict the risk of a major complication. An ensemble-based machine learning (gradient-boosting) model was optimized on 80% of the sample with subsequent validation on a 20% holdout data set. The machine learning model was compared with traditional MLR models. The artificial intelligence SHAP (Shapley additive explanations) method was used for interpretation of patient- and cohort-level risk estimates and interactions to define novel surgical risk phenotypes. Data were analyzed between November 2019 and August 2021. Exposures: Cytoreductive surgery. Main Outcomes and Measures: Area under the receiver operating characteristics (AUROC); area under the precision recall curve (AUPRC). Results: Data from a total 2372 patients were included in model development (mean age, 55 years [range, 11-95 years]; 1366 [57.6%] women). The optimized machine learning model achieved high discrimination (AUROC: mean cross-validation, 0.75 [range, 0.73-0.81]; test, 0.74) and precision (AUPRC: mean cross-validation, 0.50 [range, 0.46-0.58]; test, 0.42). Compared with the optimized machine learning model, the published MLR model performed worse (test AUROC and AUPRC: 0.54 and 0.18, respectively). Higher volume of estimated blood loss, having pelvic peritonectomy, and longer operative time were the top 3 contributors to the high likelihood of major complications. SHAP dependence plots demonstrated insightful nonlinear interactive associations between predictors and major complications. For instance, high estimated blood loss (ie, above 500 mL) was only detrimental when operative time exceeded 9 hours. Unsupervised clustering of patients based on similarity of sources of risk allowed identification of 6 distinct surgical risk phenotypes. Conclusions and Relevance: In this prognostic study using data from patients undergoing CRS, an optimized machine learning model demonstrated a superior ability to predict individual- and cohort-level risk of major complications vs traditional methods. Using the SHAP method, 6 distinct surgical phenotypes were identified based on sources of risk of major complications.

What's the magic number? Impact of time to initiation of treatment for rectal cancer.

BACKGROUND: National guidelines, including the National Accreditation Program for Rectal Cancer, recommend initiation of rectal cancer treatment within 60 days of diagnosis; however, the effect of timely treatment initiation on oncologic outcomes is unclear. The purpose of this study was to evaluate the impact on oncologic outcomes of initiation of rectal cancer treatment within 60 days of diagnosis. METHODS: This was a retrospective review of stage II/III rectal cancer patients performed using the United States Rectal Cancer Consortium, a collaboration of 6 academic medical centers. Patients with clinical stage II/III rectal cancer who underwent radical resection between January 1, 2010 and December 31, 2018 were included. The primary exposure was treatment initiation, defined as either resection or initiation of chemotherapy or chemoradiotherapy, within 60 days of diagnosis. The primary outcome was disease recurrence, and the secondary outcome was all-cause mortality. RESULTS: A total of 1,031 patients meeting inclusion criteria were included in the analysis. Treatment was initiated within 60 days of diagnosis in 830 patients (80.5%) and after 60 days in 201 patients (20.3%). In multivariable logistic regression, older age, non-White race, and residence greater than 100 miles from the treatment center were significantly associated with delay in treatment beyond 60 days. In survival analysis, 167 patients (16.2%) experienced recurrent disease, and 127 patients (12.3%) died of any cause. In an adjusted model accounting for pathologic staging, treatment sequence, distance to care, age, comorbidities, treatment center, and receipt of adjuvant chemotherapy, neither progression-free survival nor all-cause mortality was significantly associated with timely initiation of therapy with hazard ratios of 1.09 (0.70, 1.69) and 1.03 (0.63, 1.66), respectively. CONCLUSION: This study found no difference in oncologic outcomes with initiation of treatment beyond 60 days.

Radiological assessment of persistent retroperitoneal and lateral pelvic lymph nodes after neoadjuvant therapy for rectal cancer: An analysis of the United States Rectal Cancer Consortium.

INTRODUCTION: Management of retroperitoneal and lateral pelvic lymph nodes (RLPN) in rectal cancer remains unclear. With total neoadjuvant therapy (TNT), more patients have radiologic complete clinical response (rCR). We sought to evaluate the impact of radiographic persistent RLPN after neoadjuvant therapy on survival. MATERIALS AND METHODS: Patients with rectal adenocarcinoma with isolated RLPN metastasis, who received neoadjuvant therapy before surgery were included from the United States Rectal Cancer Consortium database. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 77 patients, all received neoadjuvant therapy, with 35 (46%) receiving TNT. Posttreatment, 33 (43%) had rCR while 44 (57%) had radiographic persistent RLPN. Median number of radiographic positive RLPN was 1 (IQR 1-2). Receipt of TNT was associated with radiographic RLPN rCR (OR 4.77, 95% CI 1.81-12.60, p < .01). However, there was no difference in RFS and OS between patients who achieved rCR or with persistent RLPN (all p > .05). CONCLUSIONS: Radiographic persistence of RLPN was not associated with worse survival in well-selected patients and may not be a reliable indicator of pathological response. TNT may be the preferred management strategy to select patients given its association with rCR. Radiographic persistence of RLPN after preoperative therapy should not necessarily preclude surgery.

Perioperative Blood Transfusions Are Associated With Worse Overall Survival But Not Disease-Free Survival After Curative Rectal Cancer Resection: A Propensity Score-Matched Analysis.

BACKGROUND: The effects of blood transfusions on oncologic outcomes after surgery remain inconclusive. Thus, we examined the association between receiving a perioperative blood transfusion and oncologic outcomes in patients undergoing curative rectal cancer resection. OBJECTIVE: The purpose of this study was to assess the association between receiving a perioperative blood transfusion with disease-free and overall survival in patients undergoing curative resection of clinical stage I to III rectal cancer. We hypothesized that blood transfusion is associated with worse disease-free and overall survival in this patient cohort. DESIGN: This was a retrospective cohort study using a propensity score-matched analysis. SETTINGS: The study involved 6 tertiary academic medical centers in the United States contributing to the United States Rectal Cancer Consortium. PATIENTS: Patients who underwent curative resection for rectal cancer from 2010 to 2018 were included. MAIN OUTCOME MEASURES: The primary outcome was disease-free survival. The secondary outcomes were overall survival, intensive care unit length of stay, hospital length of stay, surgical site infection, and readmission. RESULTS: Of the 924 patients eligible for matching, 312 patients were matched, including 100 patients who received a transfusion and 212 who did not. In a propensity score-matched analysis, receiving a perioperative blood transfusion was not associated with worse 5-year disease-free survival (transfused, 78%; not transfused, 83%; p = 0.32) but was associated with worse 5-year overall survival (transfused 65% vs not transfused 86%; p < 0.001) and increased hospital length of stay (transfused, 9.9 d; not transfused, 7.6 d; p = 0.001). LIMITATIONS: Despite propensity matching, confounding may remain. Propensity matching may limit the power to detect a difference in disease-free survival. CONCLUSIONS: Receiving a perioperative blood transfusion is not associated with worse disease-free survival but is associated with worse overall survival. Such findings are important for clinicians and patients to understand when considering perioperative blood transfusions. See Video Abstract at http://links.lww.com/DCR/B531. LAS TRANSFUSIONES DE SANGRE PERIOPERATORIAS SE ASOCIAN CON UNA PEOR SOBREVIDA GLOBAL, PERO NO CON LA SOBREVIDA LIBRE DE ENFERMEDAD POSTERIOR A LA RESECCIN CURATIVA DEL CNCER DE RECTO UN PUNTAJE DE PROPENSIN POR ANLISIS DE CONCORDANCIA: ANTECEDENTES:El impacto de las transfusiones de sangre en los resultados oncológicos posteriores a la cirugía no son concluyentes. Por lo anterior, estudiamos la asociación entre recibir una transfusión de sangre perioperatoria y los resultados oncológicos en pacientes llevados a resección curativa de cáncer de recto.OBJETIVO:El propósito de este estudio fue evaluar la asociación entre recibir una transfusión de sangre perioperatoria con la sobrevida libre de enfermedad y la sobrevida general en pacientes llevados a resección curativa de cáncer de recto en estadio clínico I-III. Nuestra hipótesis es que la transfusión de sangre se asocia con una peor sobrevida global y libre de enfermedad en esta cohorte de pacientes.DISEÑO:Es un estudio de cohorte retrospectivo que utilizó un puntaje de propensión por análisis de concordancia.AMBITO:El estudio se realizó en seis centros médicos académicos de tercer nivel en los Estados Unidos que contribuían al Consorcio de Cáncer de Recto de los Estados Unidos.PACIENTES:Se incluyeron pacientes que fueron llevados a resección curativa por cáncer de recto entre 2010 y 2018.PRINCIPALES VARIABLES EVALUADAS:El objeitvo principal fue la sobrevida libre de enfermedad. Los objetivos secundarios fueron la sobrevida global, el tiempo de estancia en la unidad de cuidados intensivos, el tiempo de la estancia hospitalaria, la infección del sitio quirúrgico y el reingreso.RESULTADOS:De los 924 pacientes elegibles para el emparejamiento, se emparejaron 312 pacientes, incluidos 100 pacientes que recibieron una transfusión y 212 que no. En el puntaje de propensión por análisis de concordancia, recibir una transfusión de sangre perioperatoria no se asoció con una peor sobrevida libre de enfermedad a 5 años (TRANSFUSIÓN 78%; NO TRANSFUSIÓN 83%; p = 0,32), pero se asoció con una peor sobrevida global a 5 años (TRANSFUSION 65% vs NO TRANSFUSION 86%; p <0,001) y aumento de la estancia hospitalaria (TRANSFUSIÓN 9,9 días; NO TRANSFUSION 7,6 días; p = 0,001).LIMITACIONES:A pesar de la concordancia de propensión, pueden existir desviaciones. El emparejamiento de propensión puede limitar el poder para detectar una diferencia en la sobrevida libre de enfermedad.CONCLUSIONES:Recibir una transfusión de sangre perioperatoria no se asocia con una peor sobrevida libre de enfermedad, pero sí con una peor sobrevida global. Es importante que los médicos y los pacientes comprendan estos hallazgos al considerar las transfusiones de sangre perioperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B531. (Traducción-Dr Lisbeth Alarcon-Bernes).

A US Rectal Cancer Consortium Study of Inferior Mesenteric Artery Versus Superior Rectal Artery Ligation: How High Do We Need to Go?

BACKGROUND: The optimal level of pedicle ligation during proctectomy for rectal cancer, either at the origin of the inferior mesenteric artery or the superior rectal artery, is still debated. OBJECTIVE: The objective was to determine whether superior rectal artery ligation portends equivalent technical or oncologic outcomes. DESIGN: This was a retrospective analysis of a rectal cancer database (2007-2017). SETTINGS: The study was conducted at 6 tertiary referral centers in the United States (Emory University, University of Michigan, University of Pittsburgh Medical Center, The Ohio State University Wexner Medical Center, Vanderbilt University Medical Center, and Washington University School of Medicine in St. Louis). PATIENTS: Patients with primary, nonmetastatic rectal cancer who underwent low anterior resection or abdominoperineal resection were included. MAIN OUTCOME MEASURES: Anastomotic leak, lymph node harvest, locoregional recurrence-free survival, recurrence-free survival, and overall survival were measured. RESULTS: Of 877 patients, 86% (n = 755) received an inferior mesenteric artery ligation, whereas 14% (n = 122) received a superior rectal artery ligation. A total of 12%, 33%, 24%, and 31% were pathologic stage 0, I, II, and III. Median follow-up was 31 months. Superior rectal artery ligation was associated with a similar anastomotic leak rate compared with inferior mesenteric artery ligation (9% vs 8%; p = 1.0). The median number of lymph nodes removed was identical (15 vs 15; p = 0.38). On multivariable analysis accounting for relevant clinicopathologic factors, superior rectal artery ligation was not associated with increased anastomotic leak rate, worse lymph node harvest, or worse locoregional recurrence-free survival, recurrence-free survival, or overall survival (all p values >0.1). LIMITATIONS: This was a retrospective design. CONCLUSIONS: Compared with inferior mesenteric artery ligation, superior rectal artery ligation is not associated with either worse technical or oncologic outcomes. Given the potential risks of inadequate blood flow to the proximal limb of the anastomosis and autonomic nerve injury, we advocate for increased use of superior rectal artery ligation. See Video Abstract at http://links.lww.com/DCR/B646. ESTUDIO DEL CONSORCIO DE CNCER DE RECTO DE ESTADOS UNIDOS DE LIGADURA BAJA DE LA ARTERIA MESENTRICA INFERIOR CONTRA LIGADURA ALTA DE LA ARTERIA MESENTRICA INFERIOR QU TAN ALTO DEBEMOS EXTENDERNOS: ANTECEDENTES:el nivel óptimo de la ligadura del pedículo en la proctectomía para el cáncer de recto, ya sea en el origen de la arteria mesentérica inferior o en la arteria rectal superior aún no esta definido.OBJETIVO:El objetivo era determinar si la ligadura de la arteria rectal superior pronostica resultados técnicos u oncológicos similares.DISEÑO:Análisis retrospectivo de una base de datos de cáncer de recto (2007-2017).ESCENARIO:el estudio se realizó en seis centros de referencia de tercer nivel en los Estados Unidos (Universidad de Emory, Universidad de Michigan, Centro médico de la Universidad de Pittsburgh, Centro médico Wexner de la Universidad Estatal de Ohio, Centro médico de la Universidad de Vanderbilt y Escuela de Medicina de la Universidad de Washington en St. Louis).PACIENTES:Se incluyeron pacientes con cáncer de recto primario no metastásico que se sometieron a resección anterior baja o resección abdominoperineal.PRINCIPALES VARIABLES ANALIZADAS:Se midió la fuga anastomótica, los ganglios linfáticos recuperados, la sobrevida sin recidiva locorregional, la sobrevida sin recidiva y la sobrevida global.RESULTADOS:De 877 pacientes, en el 86% (n = 755) se realizó una ligadura de la arteria mesentérica inferior, y en el 14% (n = 122) se realizó una ligadura de la arteria rectal superior. El 12%, 33%, 24% y 31% estaban en estadio patológico 0, I, II y III respectivamente. La mediana de seguimiento fue de 31 meses. La ligadura de la arteria rectal superior se asoció con una tasa de fuga anastomótica similar a la ligadura de la arteria mesentérica inferior (9 vs 8%, p = 1,0). La mediana del número de ganglios linfáticos extirpados fue idéntica (15 contra 15, p = 0,38). En el análisis multivariado que tiene en cuenta los factores clínico-patológicos relevantes, la ligadura de la arteria rectal superior no se asoció con una mayor tasa de fuga anastomótica, una peor cosecha de ganglios linfáticos o una peor sobrevida libre de recurrencia locorregional, sobrevida libre de recurrencia o sobrevida global (todos p> 0,1).LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:En comparación con la ligadura de la arteria mesentérica inferior, la ligadura de la arteria rectal superior no se asocia a peores resultados técnicos ni oncológicos. Debido a los riesgos potenciales de un flujo sanguíneo inadecuado del muñon proximal de la anastomosis y la lesión de los nervios autonómicos, proponemos una mayor realización de la ligadura de la arteria rectal superior. Consulte Video Resumen en http://links.lww.com/DCR/B646.

A multi-institutional analysis of Textbook Outcomes among patients undergoing cytoreductive surgery for peritoneal surface malignancies.

BACKGROUND: While recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM). STUDY DESIGN: All patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction >1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay >75th percentile, and non-home discharge. RESULTS: Among 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age <65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time <7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p < 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p < 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p < 0.01). CONCLUSION: Among patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.

The role of surgeons during the COVID-19 pandemic: impact on training and lessons learned from a surgical resident's perspective.

BACKGROUND: Surgeons are trained as "internists that also operate," bringing an important skillset to patient management during the current COVID-19 pandemic. A review was performed to illustrate the response of surgical staff during the pandemic with regard to patient care and residency training. METHODS: The evaluation and assessment of the changes enacted at Stony Brook Medicine's Department of Surgery is illustrated through the unique perspective of surgical residents. No IRB approval or written consent was obtained nor it was necessary for the purposes of this paper. RESULTS: Hospital policy was enacted to hinder transmission of COVID-19 and included limited gatherings of people, restricted travel, quarantined symptomatic staff, and careful surveillance for disease incidence. Surgical residency transformed as residents were diverted from traditional surgical services to staff new COVID-19 ICUs. Education transitioned to an online-based platform for lectures and reviews. New skills sets were acquired such as PICC line placement and complex ventilator management. CONCLUSIONS: The viral surge impacted surgical training while also providing unique lessons regarding preparedness and strategic planning for future pandemic and disaster management.

Revisiting the Value of Drains After Low Anterior Resection for Rectal Cancer: a Multi-institutional Analysis of 996 Patients.

BACKGROUND: Intraoperative pelvic drains are often placed during low anterior resection (LAR) to evacuate postoperative fluid collections and identify/control potential anastomotic leaks. Our aim was to assess the validity of this practice. METHODS: Patients from the US Rectal Cancer Consortium (2007-2017) who underwent curative-intent LAR for a primary rectal cancer were included. Patients were categorized as receiving a closed suction drain intraoperatively or not. Primary outcomes were superficial surgical site infection (SSI), deep SSI, intraabdominal abscess, anastomotic leak, and need for secondary drain placement. Three subgroup analyses were conducted in patients who received neoadjuvant chemoradiation, had a diverting loop ileostomy (DLI), and had low anastomoses < 6 cm from the anal verge. RESULTS: Of 996 patients 67% (n = 551) received a drain. Drain patients were more likely to be male (64 vs 54%), have a smoking history (25 vs 19%), have received neoadjuvant chemoradiation (73 vs 61%), have low tumors (56 vs 36%), and have received a DLI (80 vs 71%) (all p < 0.05). Drains were associated with an increased anastomotic leak rate (14 vs 8%, p = 0.041), although there was no difference in the need for a secondary drainage procedure to control the leak (82 vs 88%, p = 0.924). These findings persisted in all subset analyses. Drains were not associated with increased superficial SSI, deep SSI, or intraabdominal abscess in the entire cohort or each subset analysis. Reoperation (12 vs 10%, p = 0.478) and readmission rates (28 vs 31%, p = 0.511) were similar. CONCLUSIONS: Although not associated with increased infectious complications, intraoperatively placed pelvic drains after low anterior resection for rectal cancer are associated with an increase in anastomotic leak rate and no reduction in the need for secondary drain placement or reoperation. Routine drainage appears to be unnecessary.

The impact of HIPEC vs. EPIC for the treatment of mucinous appendiceal carcinoma: a study from the US HIPEC collaborative.

INTRODUCTION: Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods. MATERIALS AND METHODS: Patients with mucinous appendiceal carcinoma were identified in the US HIPEC Collaborative database from 12 academic institutions. Patient demographics, clinical characteristics, and survival outcomes were compared among patients who underwent HIPEC vs. EPIC with inverse probability weighting (IPW) used for adjustment. RESULTS: Among 921 patients with mucinous appendiceal carcinoma, 9% underwent EPIC while 91% underwent HIPEC. There was no difference in Grade III-V complications between the two groups (18.5% for HIPEC vs. 15.0% for EPIC, p=.43) though patients who underwent HIPEC had higher rates of readmissions (21.2% vs. 8.8%, p<.01). Additionally, PIC method was not an independent predictor for overall survival (OS) or recurrence-free survival (RFS) after adjustment on multivariable analysis. CONCLUSIONS: Among patients with mucinous appendiceal carcinoma, both EPIC and HIPEC appear to be associated with similar perioperative and long-term outcomes.

Predictors of Non-home Discharge after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients. METHODS: Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD. RESULTS: The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P < 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P < 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P < 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P < 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P < 0.001). CONCLUSIONS: Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

Outcomes of neoadjuvant chemotherapy before CRS-HIPEC for patients with appendiceal cancer.

BACKGROUND: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is indicated for patients with peritoneal dissemination of appendiceal cancer. The role of neoadjuvant chemotherapy (NAC) before CRS-HIPEC remains controversial. METHODS: A retrospective review of adult patients who underwent CRS ± HIPEC for metastatic appendiceal cancer between 2000-2017 was performed. Patients who received NAC followed by surgery were compared with those who underwent surgery first (SF) with and without 1:1 propensity score matching (PSM). RESULTS: Among 803 patients with appendiceal cancer who underwent CRS ± HIPEC, 225 (28%) received NAC, and 578 (72%) underwent SF. After PSM (n = 186), median overall survival (OS) did not differ (NAC: 40 vs SF: 56 months; P = .210) but recurrence-free survival (RFS) was worse among patients who received NAC (14 vs 22 months; P = .007). NAC was independently associated with worse OS (hazards ratio [HR], 1.81; 95% confidence interval [CI], 1.03-3.18) and RFS (HR, 1.93; 95% CI, 1.25-2.99). CONCLUSION: In this multi-institutional retrospective analysis of patients with peritoneal dissemination from appendiceal cancer, the use of NAC before CRS-HIPEC was associated with worse OS and RFS even after PSM and multivariable regression. Immediate surgery should be considered for patients with disease amenable to complete cytoreduction.

Phase I Trial of Trametinib with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer.

PURPOSE: The RAS/RAF/MEK/ERK signaling pathway is critical to the development of colorectal cancers, and KRAS, NRAS, and BRAF mutations foster resistance to radiation. We performed a phase I trial to determine the safety of trametinib, a potent MEK1/2 inhibitor, with 5-fluorouracil (5-FU) chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with stage II/III rectal cancer were enrolled on a phase I study with 3+3 study design, with an expansion cohort of 9 patients at the MTD. Following a 5-day trametinib lead-in, with pre- and posttreatment tumor biopsies, patients received trametinib and CRT, surgery, and adjuvant chemotherapy. Trametinib was given orally daily at 3 dose levels: 0.5 mg, 1 mg, and 2 mg. CRT consisted of infusional 5-FU 225 mg/m2/day and radiation dose of 28 daily fractions of 1.8 Gy (total 50.4 Gy). The primary endpoint was to identify the MTD and recommended phase II dose. IHC staining for phosphorylated ERK (pERK) and genomic profiling was performed on the tumor samples. RESULTS: Patients were enrolled to all dose levels, and 18 patients were evaluable for toxicities and responses. Treatment was well tolerated, and there was one dose-limiting toxicity of diarrhea, which was attributed to CRT rather than trametinib. At the 2 mg dose level, 25% had pathologic complete response. IHC staining confirmed dose-dependent decrease in pERK with increasing trametinib doses. CONCLUSIONS: The combination of trametinib with 5-FU CRT is safe and well tolerated, and may warrant additional study in a phase II trial, perhaps in a RAS/RAF-mutant selected population.

Impact of Neoadjuvant Chemotherapy on the Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Multi-Institutional Retrospective Review.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000-2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.