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.

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.

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 ).

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.

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.

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).

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.

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.

Predictors of Anastomotic Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Technique Matter?

BACKGROUND: Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood. METHODS: Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula). RESULTS: Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p < 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p > 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p < 0.01), higher complication rate (90% vs 59%; p < 0.01), higher reoperation rate (41% vs 9%; p < 0.01), more 30-day readmissions (59% vs 22%; p < 0.01), greater 30-day mortality (9% vs 1%; p < 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p < 0.01). CONCLUSIONS: Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

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.

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 Readmission After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Risk factors for hospital readmission after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are poorly understood. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program databases from 2011 to 2016 were used to identify all patients who underwent CRS-HIPEC. Demographic, clinical, and perioperative variables were examined using logistic regression to identify factors associated with 30-d postoperative readmission. RESULTS: Among 618 patients who underwent CRS-HIPEC, 96 (15.5%) required hospital readmission within 30 d of surgery. The incidence of readmission decreased over the study period (18.3% in 2011 to 4.8% in 2016). Among the 59 patients who were readmitted and had complete data available, readmission occurred on mean postoperative day 18.5 ± 5.5; the most common reasons for readmission were digestive complications (39.0%), postoperative infections (25.4%), uncontrolled pain (8.5%), and venous thromboembolism (5.1%). On multivariate logistic regression analysis, increasing age (OR 1.02, 95% CI 1.00-1.05), number of operative procedures (OR 1.12, 95% CI 1.00-1.25), perioperative complication (OR 7.06, 95% CI 3.96-12.59), need for reoperation (OR 10.21, 95% CI 3.50-29.83), and length of stay (OR 0.93, 0.90-0.97) were associated with hospital readmission. CONCLUSIONS: In this population-based analysis of patients undergoing CRS-HIPEC, older age, perioperative complications, need for reoperation, and extent of cytoreduction were associated with hospital readmission. The American College of Surgeons-National Surgical Quality Improvement Program database is a powerful research tool that can be used to identify opportunities to improve the perioperative care of surgical patients.

Perioperative Morbidity of Gastrectomy During CRS-HIPEC: An ACS-NSQIP Analysis.

BACKGROUND: Formal gastrectomy is occasionally required to achieve complete cytoreduction for patients with peritoneal surface malignancies. In addition, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer is increasingly being explored. Nevertheless, data on the safety of gastrectomy at the time of CRS-HIPEC are limited. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program databases from 2005 to 2016 were used to identify patients who underwent CRS-HIPEC. Demographic, clinical, and perioperative outcomes were compared between patients who underwent CRS-HIPEC with and without gastrectomy. RESULTS: Among 1168 patients who underwent CRS-HIPEC, 43 (4%) underwent partial (n = 20) or total (n = 23) gastrectomy. Patients who underwent gastrectomy at the time of CRS-HIPEC had a longer operative time (529.3 versus 457.6 min, P = 0.004), were more likely to need an intraoperative transfusion (32.6% versus 14.3%, P = 0.001), experienced a longer length of stay (19.0 versus 11.3 d, P < 0.001), and had a significantly greater complication rate (60.5% versus 27.9%, P < 0.001), whereas postoperative mortality was not statistically significantly different (4.7% versus 1.4%, P = 0.09). On multivariate logistic regression, gastrectomy (odds ratio [OR] 3.52, P < 0.001) was the strongest predictor of postoperative morbidity, in addition to American Society of Anesthesiologists class 4 (OR 2.82, P = 0.001), malnutrition (OR 1.63, P = 0.01), liver resection (OR 1.88, P = 0.01), and colectomy (OR 2.04, P < 0.001). CONCLUSIONS: Patients undergoing gastrectomy at the time of CRS-HIPEC experience a substantial postoperative complication rate (60%) and extended length of stay (mean 19 d). These findings highlight the need for cautious patient selection and preoperative counseling before performing concomitant gastrectomy and CRS-HIPEC.

Impact of concomitant ablation on the perioperative outcomes of patients with colorectal liver metastases undergoing hepatectomy: a propensity score matched nationwide analysis.

BACKGROUND: Intraoperative ablation (IA) is often performed at the time of liver resection (LR) for colorectal liver metastases (CRLMs) but its impact on postoperative outcomes remains poorly understood. METHODS: The ACS-NSQIP targeted hepatectomy database was used to identify patients who underwent LR vs LR + IA for CRLMs during 2014-2016. Perioperative outcomes were compared following propensity score match based on age, receipt of neoadjuvant therapy, operative approach, liver resection type, tumor diameter and number of metastases. RESULTS: Among 1,384 patients, 692 (50%) underwent LR alone and 692 (50%) underwent LR + IA. After propensity score matching, overall morbidity (22% vs 13%, P < 0.0001) was increased among patients undergoing LR alone compared to LR + IA, whereas mortality did not differ (1.1% vs 0.8%, P=0.5911). On multivariable analysis, ASA class ≥3 (OR: 1.5, 95% CI: 1.06-2.3), preoperative biliary stent (OR: 3.5, 95% CI: 0.9-13.01), biliary reconstruction (OR: 5.02, 95% CI: 1.3-18.6), operative time > 245 minutes (OR: 1.8, 95% CI:1.3-2.4) and IA (OR:0.5, 95% CI:0.3-0.7) were associated with overall morbidity. CONCLUSIONS: In this propensity matched nationwide analysis of patients undergoing LR for CRLM, the use of concomitant IA was associated with decreased postoperative morbidity compared to LR alone. These findings suggest that IA combined with LR is a safe approach that may expand the number of patients who are candidates for curative-intent surgical strategies.

Practices and Perceptions Among Surgical Oncologists in the Perioperative Care of Obese Cancer Patients.

BACKGROUND: Obesity and cancer are two common diseases in the United States. Although there is an interaction of obesity and cancer, little is known about surgeon perceptions and practices in the care of obese cancer patients. We sought to characterize perceptions and practices of surgical oncologists regarding the perioperative care of obese patients being treated for cancer. METHODS: A cross-sectional survey was designed, pilot tested, and utilized to assess perceptions and practices of surgeons treating cancer patients. Surgical oncologists were identified using a commercially available database, and Qualtrics® was used to distribute and manage the survey. Statistical analyses were completed by using SPSS. RESULTS: Of the 1731 electronic invitations, 172 recipients initiated the survey, and 157 submitted responses (91.2%). Many surgeons (65.7%) believed that obese patients are more likely to present with more advanced cancers and were more likely than system factors to explain this delayed treatment [t(87) = 4.84; p < 0.001]. Nearly two-thirds of providers (64.5%) reported that obesity had no impact on the timing of surgery; however, one-third of respondents (34.2%) were more likely to recommend preoperative nonsurgical therapy rather than upfront surgery among obese patients. For operations of the chest/abdomen and breast/soft tissue, surgeons perceived obesity to be more related to risk of postoperative than intraoperative complications (chest/abdomen mean 4.13 vs. 3.26; breast/soft tissue 4.11 vs. 2.60; p < 0.001). CONCLUSIONS: One in three surgeons reported that patient obesity would change the timing/sequence of when resection would be offered. Many surgeons perceived that obesity was related to a wide array of intra- and postoperative adverse outcomes.

Targeting BRAF Mutations in High-Grade Neuroendocrine Carcinoma of the Colon.

Mutations in the RAS/RAF/MEK/ERK pathway leading to constitutive activation and uncontrolled cellular growth have been identified in various human malignancies, making this pathway a target for potential therapeutics. The activating BRAFV600E mutation is one well-characterized oncogenic mutation that has been described and targeted with clinical success in various malignancies, including melanoma and hairy cell leukemia. Although BRAF-directed treatments have yielded clinical benefit in a subset of tumor types, such as melanoma, thyroid cancer, and lung cancer, BRAF inhibition fails to confer a clinical benefit in colon cancer. Identification of patients for whom BRAF inhibition may produce clinically meaningful outcomes is imperative. The incidence of BRAF mutations in neuroendocrine carcinoma (NEC) is estimated to be 5% to 10%. A recent case series demonstrated benefit in targeting the BRAFV600E mutation in metastatic high-grade rectal NECs. Combination BRAF and MEK inhibition is known to yield improved outcomes compared with BRAF inhibition alone in melanoma. This report presents 2 patients with high-grade colorectal NECs who had different responses to treatment with combined BRAF/MEK inhibition after experiencing disease progression through first-line platinum-based chemotherapy. One patient experienced an excellent initial response to therapy before ultimately experiencing progression, and in the other patient initially had stable disease before eventually experiencing progression. These cases highlight the complicated role BRAF mutations play in gastrointestinal NECs, and the need for further research to identify not only patients who may benefit from BRAF-directed therapies but also strategies to avoid development of resistance.

Implementation and early outcomes for a surgeon-directed hepatic arterial infusion pump program for colorectal liver metastases.

INTRODUCTION: Hepatic arterial infusion pump (HAIP) therapy for colorectal liver metastases (CRLM) is beneficial in selected patients yet wide acceptance in the oncology community is lacking. METHODS: A surgeon-led team implemented a HAIP program in 2012. Pumps were placed by laparotomy for CRLM and fluorodeoxyuridine was infused via HAIP every 28 days without systemic chemotherapy supervised by the operating surgeon. RESULTS: Sixty patients were treated with HAIP, either in the adjuvant setting after liver resection or ablation of CRLM in 26 (43%) patients or with the unresectable disease in 34 (57%). Perioperative complications occurred in 19 (32%) and pump-specific complications in 14 (23%) that included intrahepatic biliary stricture in one (2%). Time to liver progression was a median 9.2 months (95% CI, 3.1-15.3 months) in unresectable patients and liver recurrence was a median 24.7 months (2.5-46.9 months) in the adjuvant group. Estimated 3-year overall survival from the time of HAIP placement was 64% in the adjuvant group and 37% in the unresectable group. Sarcopenia was prevalent (48%) and was associated with a worse survival (HR 2.4, 95% CI, 1.1-5.0). CONCLUSION: A surgeon-led HAIP program may achieve outcomes on par with those of experienced centers and foster strong relationships between surgical and medical oncologists.