Prophylactic defunctioning stomas improve clinical outcomes of anastomotic leak following rectal cancer resections: An analysis of the US Rectal Cancer Consortium.

PURPOSE: Anastomotic leak (AL) is a complication of low anterior resection (LAR) that results in substantial morbidity. There is immense interest in evaluating immediate postoperative and long-term oncologic outcomes in patients who undergo diverting loop ileostomies (DLI). The purpose of this study is to understand the relationship between fecal diversion, AL, and oncologic outcomes. METHODS: This is a retrospective multicenter cohort study using patient data obtained from the US Rectal Cancer Consortium database compiled from six academic institutions. The study population included patients with rectal adenocarcinoma undergoing LAR. The primary outcome was the incidence of AL among patients who did or did not receive DLI during LAR. Secondary outcomes included risk factors for AL, receipt of adjuvant therapy, 3-year overall survival, and 3-year recurrence. RESULTS: Of 815 patients, 38 (4.7%) suffered AL after LAR. Patients with AL were more likely to be male, have unintentional preoperative weight loss, and are less likely to undergo DLI. On multivariable analysis, DLI remained protective against AL (p < 0.001). Diverted patients were less likely to undergo future surgical procedures including additional ostomy creation, completion proctectomy, or pelvic washout for AL. Subgroup analysis of 456 patients with locally advanced disease showed that DLI was correlated with increased receipt of adjuvant therapy for patients with and without AL on univariate analysis (SHR:1.59; [95% CI 1.19-2.14]; p = 0.002), but significance was not met in multivariate models. CONCLUSION: Lack of DLI and preoperative weight loss was associated with anastomotic leak. Fecal diversion may improve the timely initiation of adjuvant oncologic therapy. The long-term outcomes following routine diverting stomas warrant further study.

Association of omental pedicled flap with anastomotic leak following low anterior resection for rectal cancer.

BACKGROUND AND OBJECTIVES: Anastomotic leak following colorectal anastomosis adversely impacts short-term, oncologic, and quality-of-life outcomes. This study aimed to assess the impact of omental pedicled flap (OPF) on anastomotic leak among patients undergoing low anastomotic resection (LAR) for rectal cancer using a multi-institutional database. METHODS: Adult rectal cancer patients in the US Rectal Cancer Consortium, who underwent a LAR for stage I-III rectal cancer with or without an OPF were included. Patients with missing data for surgery type and OPF use were excluded from the analysis. The primary outcome was the development of anastomotic leaks. Multivariable logistic regression was used to determine the association. RESULTS: A total of 853 patients met the inclusion criteria and OPF was used in 106 (12.4%) patients. There was no difference in age, sex, or tumor stage of patients who underwent OPF versus those who did not. OPF use was not associated with an anastomotic leak (p = 0.82), or operative blood loss (p = 0.54) but was associated with an increase in the operative duration [ß = 21.42 (95% confidence interval = 1.16, 41.67) p = 0.04]. CONCLUSIONS: Among patients undergoing LAR for rectal cancer, OPF use was associated with an increase in operative duration without any impact on the rate of anastomotic leak.

Immune checkpoint inhibitors in hepatocellular carcinoma: A review of current clinical trials.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis due to advanced disease presentation or recurrence despite curative-intent resection. Since the approval of sorafenib in 2007, few systemic therapies offered a significant improvement in treatment outcomes. Over the last 3 years, however, rapid advancements in the field of immunotherapy have led to approval of checkpoint inhibitors in 2020 for use in advanced HCC. Since then, a few other clinical trials have shown promising results in the adjuvant and neoadjuvant setting. The objective of this review is to summarize data from existing clinical trials evaluating the use of systemic immune checkpoint inhibitors in HCC and to follow the natural evolution of this development across the metastatic, adjuvant, and neoadjuvant landscapes.

Short-course radiation with consolidation chemotherapy does not increase operative morbidity compared to long-course chemoradiation: A retrospective study of the US rectal cancer consortium.

BACKGROUND AND OBJECTIVES: Neoadjuvant short-course radiation and consolidation chemotherapy (SC TNT) remains less widely used for rectal cancer in the United States than long-course chemoradiation (LCRT). SC TNT may improve compliance and downstaging; however, a longer radiation-to-surgery interval may worsen pelvic fibrosis and morbidity with total mesorectal excision (TME). A single, US-center retrospective analysis has shown comparable risk of morbidity after neoadjuvant short-course radiation with consolidation chemotherapy (SC TNT) and long-course chemoradiation (LCRT). Validation by a multi-institutional study is needed. METHODS: The US Rectal Cancer Consortium database (2010-2018) was retrospectively reviewed for patients with nonmetastatic, rectal adenocarcinoma treated with neoadjuvant LCRT or SC TNT before TME. The primary endpoint was severe postoperative morbidity. Cohorts were compared by univariate analysis. Multivariable logistic regression modeled the odds of severe complication. RESULTS: Of 788 included patients, 151 (19%) received SC TNT and 637 (81%) LCRT. The SC TNT group had fewer distal tumors (33.8% vs. 50.2%, p < 0.0001) and more clinical node-positive disease (74.2% vs. 47.6%, p < 0.0001). The intraoperative complication rate was similar (SC TNT 5.3% vs. 4.4%, p = 0.65). There was no difference in overall postoperative morbidity (38.4% vs. 46.3%, p = 0.08). Severe morbidity was similar with low anterior resection (9.1% vs. 15.3%, p = 0.10) and abdominoperineal resection (24.4% vs. 29.7%, p = 0.49). SC TNT did not increase the odds of severe morbidity relative to LCRT on multivariable analysis (OR 0.64, 95% CI 0.37-1.10). CONCLUSIONS: SC TNT does not increase morbidity after TME for rectal cancer relative to LCRT. Concern for surgical complications should not discourage the use of SC TNT when aiming to increase the likelihood of complete clinical response.

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.

Is There a Role for Adjuvant Chemotherapy in Pathologic Node-Negative Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiation Therapy?

BACKGROUND: Neoadjuvant chemoradiation therapy (NCRT, 5-fluorouracil and radiation) followed by resection and adjuvant chemotherapy (AC) is one of the standard treatment paradigms for locally advanced rectal adenocarcinoma. However, the utility of AC in patients with pathologic lymph node (pLN)-negative disease is unclear. Our aim is to assess the value of AC stratified by pLN status. METHODS: The US Rectal Cancer Consortium database (2007-2017) was retrospectively reviewed for patients with clinical stage II and III rectal adenocarcinoma who received neoadjuvant chemoradiation (NACR) and curative-intent resection. Those who received neoadjuvant systemic chemotherapy or underwent local resection were excluded. Patients were categorized by pLN status. Primary outcome was overall survival (OS). RESULTS: Of 213 patients, 70% had pLN-negative disease and 30% pLN-positive disease. Median age was 57 years, 65% were male, and median follow-up was 31 months. Among patients with pLN-negative disease, 74% received AC. Receipt of AC was not associated with improved 5-year OS (82% versus 74%, respectively; p = 0.16). This finding persisted on multivariable analysis. Of patients with pLN-positive disease, 83% received AC. Patients with pLN-positive disease demonstrated improved 5-year OS with receipt of AC (72% compared with 0% with no adjuvant chemotherapy, p = 0.04). CONCLUSION: After receiving neoadjuvant chemoradiation, adjuvant chemotherapy for patients with pLN-negative disease does not appear to be associated with improved survival. Further validation and prospective studies are needed to evaluate the utility of adjuvant chemotherapy in this setting.

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.

A novel preoperative risk score to guide patient selection for resection of soft tissue sarcoma lung metastases: An analysis from the United States Sarcoma Collaborative.

BACKGROUND: Surgical resection for sarcoma lung metastases has been associated with improved overall survival (OS). METHODS: Patients who underwent curative-intent resection of sarcoma lung metastases (2000-2016) were identified from the US Sarcoma Collaborative. Patients with extrapulmonary metastatic disease or R2 resections of primary tumor or metastases were excluded. Primary endpoint was OS. RESULTS: Three hundred and fifty-two patients met inclusion criteria. Location of primary tumor was truncal/extremity in 85% (n = 270) and retroperitoneal in 15% (n = 49). Forty-nine percent (n = 171) of patients had solitary and 51% (n = 180) had multiple lung metastasis. Median OS was 49 months; 5-year OS 42%. Age ≥55 (HR 1.77), retroperitoneal primary (HR 1.67), R1 resection of primary (HR 1.72), and multiple (≥2) lung metastases (HR 1.77) were associated with decreased OS(all p < 0.05). Assigning one point for each factor, we developed a risk score from 0 to 4. Patients were then divided into two risk groups: low (0-1 factor) and high (2-4 factors). The low-risk group (n = 159) had significantly better 5-year OS compared to the high-risk group (n = 108) (51% vs. 16%, p < 0.001). CONCLUSION: We identified four characteristics that in aggregate portend a worse OS and created a novel prognostic risk score for patients with sarcoma lung metastases. Given that patients in the high-risk group have a projected OS of <20% at 5 years, this risk score, after external validation, will be an important tool to aid in preoperative counseling and consideration for multimodal therapy.

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.

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

Impact of Postoperative Complications on Oncologic Outcomes After Rectal Cancer Surgery: An Analysis of the US Rectal Cancer Consortium.

BACKGROUND: Postoperative complications (POCs) are associated with worse oncologic outcomes in several cancer types. The implications of complications after rectal cancer surgery are not well studied. METHODS: The United States Rectal Cancer Consortium (2007-2017) was reviewed for primary rectal adenocarcinoma patients who underwent R0/R1 resection. Ninety-day POCs were categorized as major or minor and were grouped into infectious, cardiopulmonary, thromboembolic, renal, or intestinal dysmotility. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS: Among 1136 patients, the POC rate was 46% (n = 527), with 63% classified as minor and 32% classified as major. Of all POCs, infectious complications comprised 20%, cardiopulmonary 3%, thromboembolic 5%, renal 9%, and intestinal dysmotility 19%. Compared with minor or no POCs, major POCs were associated with both worse RFS and worse OS (both p < 0.01). Compared with no POCs, a single POC was associated with worse RFS (p < 0.01), while multiple POCs were associated with worse OS (p = 0.02). Regardless of complication grade, infectious POCs were associated with worse RFS (p < 0.01), while cardiopulmonary and thromboembolic POCs were associated with worse OS (both p < 0.01). Renal POCs were associated with both worse RFS (p < 0.001) and worse OS (p = 0.01). After accounting for pathologic stage, neoadjuvant therapy, and final margin status, Multivariable analysis (MVA) demonstrated worse outcomes with cardiopulmonary, thromboembolic, and renal POCs for OS (cardiopulmonary: hazard ratio [HR] 3.6, p = 0.01; thromboembolic: HR 19.4, p < 0.01; renal: HR 2.4, p = 0.01), and renal and infectious POCs for RFS (infectious: HR 2.1, p < 0.01; renal: HR 3.2, p < 0.01). CONCLUSIONS: Major complications after proctectomy for cancer are associated with decreased RFS and OS. Given the association of infectious complications and postoperative renal dysfunction with earlier recurrence of disease, efforts must be directed towards defining best practices and standardizing care.

Relationship between Cancer Diagnosis and Complications Following Pancreatoduodenectomy for Duodenal Adenoma.

BACKGROUND: Pancreatoduodenectomy (PD) for duodenal adenoma (DA) resection may be associated with excessive surgical risk for patients with potentially benign lesions, given the absence of pancreatic duct obstruction. We examined factors associated with final malignant pathology and evaluated the postoperative course of patients with DA versus pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively analyzed patients with DA who underwent PD from 2008 to 2018 and assessed the accuracy rate of preoperative biopsy and factors associated with final malignant pathology. Complications for DA patients were compared with those of matched PDAC patients. RESULTS: Forty-five consecutive patients who underwent PD for DA were identified, and the preoperative biopsy false negative rate was 29. Factors associated with final malignant pathology included age over 70 years, preoperative biliary obstruction, and common bile duct diameter > 8 mm (p < 0.05). Compared with patients with PDAC (n = 302), DA patients experienced more major complications (31% vs. 15%, p < 0.01), more grade C postoperative pancreatic fistulas (9% vs. 1%, p < 0.01), and greater mortality (7% vs. 2%, p < 0.05). Propensity score matched patients with DA had more major complications following PD (32% vs. 12%, p < 0.05). CONCLUSIONS: Preoperative biopsy of duodenal adenomas is associated with a high false-negative rate for malignancy, and PD for DA is associated with higher complication rates than PD for PDAC. These results aid discussion among patients and surgeons who are considering observation versus PD for DA, especially in younger patients without biliary obstruction, who are less likely to harbor malignancy.

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.

A novel preoperative risk score to optimize patient selection for performing concomitant liver resection with cytoreductive surgery/HIPEC.

BACKGROUND: While parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC. METHODS: Patients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS). RESULTS: A total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p < .001) per patient and required more reoperations (22% vs. 11%; p = .007) and readmissions (39% vs. 25%; p = .014) than non-LR patients. LR patients had decreased OS (2-year OS 62% vs. 79%, p < .001), even when accounting for peritoneal carcinomatosis index and histology type. Preoperative factors associated with decreased OS on multivariable analysis in LR patients included age < 60 years (HR, 3.61; 95% CI, 1.10-11.81), colorectal histology (HR, 3.84; 95% CI, 1.69-12.65), and multiple liver tumors (HR, 3.45; 95% CI, 1.21-9.85) (all p < .05). When assigning one point for each factor, there was an incremental decrease in 2-year survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%). CONCLUSIONS: As CRS/HIPEC + LR has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC + LR. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in OS.

Impact of hepatitis C treatment on long-term outcomes for patients with hepatocellular carcinoma: a United States Safety Net Collaborative Study.

BACKGROUND: Widespread HCV treatment for hepatocellular carcinoma (HCC) patients remains limited. Our aim was to evaluate the association of HCV treatment with survival and assess barriers to treatment. METHODS: Patients in the U.S. Safety Net Collaborative with HCV and HCC were included. Primary outcome was overall survival (OS). Secondary outcomes were recurrence-free survival (RFS) and barriers to receiving HCV treatment. RESULTS: Of 941 patients, 57% received care at tertiary referral centers (n=533), 74% did not receive HCV treatment (n=696), 6% underwent resection (n=54), 17% liver transplant (n=163), 50% liver-directed therapy (n=473), and 7% chemotherapy (n=60). HCV treatment was associated with improved OS compared to no HCV treatment (70 vs 21 months, p<0.01), persisting across clinical stages, HCC treatment modalities, and treatment facilities (all p<0.01). Surgical patients who received HCV treatment had improved RFS compared to those who did not (91 vs 80 months, p=0.03). On MVA, HCV treated patients had improved OS and RFS. On MVA, factors associated with failure to receive HCV treatment included Black race, higher MELD, and advanced clinical stage (all p<0.05). CONCLUSION: HCV treatment for HCC patients portends improved survival, regardless of clinical stage, HCC treatment, or facility type. Efforts must address barriers to HCV treatment.

Should Signet Ring Cell Histology Alter the Treatment Approach for Clinical Stage I Gastric Cancer?

BACKGROUND: Surgery alone is standard-of-care for stage I gastric adenocarcinoma; however, clinicians can offer preoperative therapy for clinical stage I disease with signet ring cell histology, given its presumed aggressive biology. We aimed to assess the validity of this practice. METHODS: The National Cancer Database (2004-2015) was reviewed for patients with clinical stage I signet ring cell gastric adenocarcinoma who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical/pathologic stage. Primary outcome was overall survival (OS). RESULTS: Of 1018 patients, median age was 60 years (±14); 53% received surgery alone (n = 542), 5% received perioperative chemotherapy (n = 47), 12% received neoadjuvant therapy (n = 125), and 30% received adjuvant therapy (n = 304). For clinical stage I disease, surgery alone was associated with an improved 5-year OS rate (71%) versus perioperative chemotherapy (58%), neoadjuvant therapy (38%), or adjuvant therapy (52%) [overall p < 0.01]. For pathologic stage I, surgery alone had equivalent or improved survival compared with perioperative, neoadjuvant, and adjuvant therapy (5-year OS: 78% vs. 89% [p = 0.77] vs. 64% [p = 0.04] vs. 84% [p = 0.99]). Adjuvant therapy was associated with improved 5-year OS compared with pretreatment for those patients upstaged (37%) to pathologic stage II/III (55% vs. 36% and 34% vs. 7%; all p < 0.01). CONCLUSIONS: This stage-specific study demonstrates improved survival with surgery alone for clinical stage I signet ring cell gastric adenocarcinoma. Despite 37% of clinical stage I patients being upstaged to pathologic stage II/III, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared with those treated preoperatively. Surgery alone also affords similar or improved survival for pathologic stage I disease versus multimodality therapy. This study challenges the bias to overtreat stage I signet ring cell gastric adenocarcinoma.

HSP90 expression and early recurrence in gastroenteropancreatic neuroendocrine tumors: Potential for a novel therapeutic target.

BACKGROUND: Heat shock protein (HSP)-90 promotes tumor growth and is overexpressed in many malignancies. HSP90 expression profile and its potential as a therapeutic target in primary and metastatic neuroendocrine tumors (NETs) are not known. METHODS: HSP90 cytoplasmic expression and Ki-67 index were re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables for patients who underwent resection of primary and metastatic gastroenteropancreatic (GEP) neuroendocrine tumors at a single institution (2000-2013). Primary outcome was recurrence-free survival (RFS). RESULTS: Of 263 tumors reviewed, 73% (n = 191) were primary GEP NETs, and 12% (n = 31) were NET liver metastases. Of the primary GEP-NETs, mean age was 56 years, 42% were male; 53% (n = 103) were pancreatic and 23% (n = 44) were small bowel. HSP90 expression was high in 34% (n = 64) and low in 66% (n = 127). Compared to low expression, high HSP90 was associated with advanced T-stage (T3/T4) (47 vs 27%; p = 0.02). Among patients who underwent curative-intent resections for primary, non-metastatic NETs (n = 145), high HSP90 was independently associated with worse RFS (HR 5.09, 95% CI 1.65-15.74; p = 0.005), after accounting for positive margin, LN involvement, increased tumor size, site of primary tumor, and Ki-67. When assessing NET liver metastases, 13% (n = 4) had high HSP90 expression and 87% (n = 26) had low expression. Patients with liver metastases with high HSP90 tended to have worse 1- and 3-year progression-free survival (25%, 25%) compared to those with low HSP90 (69%, 49%; p = 0.059). CONCLUSION: HSP90 exhibits differential expression in resected GEP-NETs and liver metastases. High cytoplasmic expression is associated with early disease recurrence, even after accounting for other adverse pathologic factors. HSP90 inhibition may be a potential therapeutic target for neuroendocrine tumors.