Impact of Oncoplastic Surgery on Oncologic Outcomes in Patients with Breast Cancer.

Background: For patients with breast cancer, oncoplastic surgery (OPS) serves as a valuable technique that allows for immediate reconstruction at the time of resection. While the aim of OPS is to improve breast cosmesis, it is critical to ensure OPS does not negatively impact appropriate cancer treatment. Methods: Based on current literature, this study provides a broad overview on the potential oncologic advantages of OPS for patients diagnosed with breast cancer. Results: OPS has been shown to be a safe and reliable approach with oncologic advantages. More specifically, OPS broadens the indications for breast conservation therapy (BCT); allows for a more generous margin of resection, thus decreasing rates of re-excision; and provides the opportunity to sample additional breast tissue, which may detect occult disease. Reduction mammaplasty may also decrease the risk for developing breast cancer. Importantly, in the era of multimodality therapy, long-term oncologic outcomes and postoperative surveillance algorithms appear to be similar when comparing patients who undergo OPS and BCT. Conclusions: For patients with breast cancer, oncoplastic surgery has emerged as a valuable technique to improve breast cosmesis while achieving optimal oncologic outcomes. As the landscape of breast oncology continues to evolve, it is critical for a multidisciplinary team to be involved to guide management and reconstructive strategies.

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.

Retroperitoneal Sarcomas: Histology Is Everything.

Retroperitoneal sarcomas (RPS) are a rare subset of soft tissue sarcoma that are composed of only a few histologic subtypes, each with a distinct tumor biology, clinical presentation, preferred treatment strategy, recurrence risk, and surveillance plan. In the modern era of precision medicine, our understanding of the implications of subtype tumor biology and anatomic location has led to a more nuanced, histology-specific approach to therapy, including surgery, neoadjuvant radiation therapy, and/or chemotherapy. This article provides a summary of recent updates to the management of RPS.

Diagnostic laparoscopy is underutilized in the staging of gastric adenocarcinoma regardless of hospital type: An US safety net collaborative analysis.

BACKGROUND: Diagnostic laparoscopy (DL) is a key component of staging for locally advanced gastric adenocarcinoma (GA). We hypothesized that utilization of DL varied between safety net (SNH) and affiliated tertiary referral centers (TRCs). METHODS: Patients diagnosed with primary GA eligible for DL were identified from the US Safety Net Collaborative database (2012-2014). Clinicopathologic factors were analyzed for association with use of DL and findings on DL. Overall survival (OS) was analyzed by Kaplan-Meier method. RESULTS: Among 233 eligible patients, 69 (30%) received DL, of which 24 (35%) were positive for metastatic disease. Forty percent of eligible SNH patients underwent DL compared to 21.5% at TRCs. Lack of insurance was significantly associated with decreased use of DL (OR 0.48, p < 0.01), while African American (OR 6.87, p = 0.02) and Asian race (OR 3.12, p ≤ 0.01), signet ring cells on biopsy (OR 3.14, p < 0.01), and distal tumors (OR 1.62, p < 0.01) were associated with increased use. Median OS of patients with a negative DL was better than those without DL or a positive DL (not reached vs. 32 vs. 12 months, p < 0.005, Figure 1). CONCLUSIONS: Results from DL are a strong predictor of OS in GA; however, the procedure is underutilized. Patients from racial minority groups were more likely to undergo DL, which likely accounts for higher DL rates among SNH patients.

Do Oncologic Outcomes From Head and Neck Versus Truncal and Extremity Melanoma Differ? A Single-Institution Single-Subspecialty Experience.

BACKGROUND: Outcomes are thought to be worse in head and neck (H&N) melanoma patients. However, definitive evidence of inferior outcomes in H&N melanoma in the modern era is lacking. We sought to ascertain whether H&N melanomas carry a worse prognosis than melanomas of other sites. METHODS: All patients who underwent excision for primary melanoma by fellowship-trained surgical oncologists at a single institution from 2014 to 2020 were queried from the electronic medical record. Patients who had AJCC eighth edition stage I-III disease were included. RESULTS: Of 1127 patients, 28.7% had primary H&N melanoma. H&N patients were more likely to be male, older, and present with more advanced AJCC stage. Median follow-up was 20.0 months (IQR 26.4). On multivariable analyses controlling for other variables, H&N melanoma was associated with worse RFS. Notably, H&N melanoma was not associated with worse MSS, DMFS, or OS on univariate or multivariable analyses. Among patients who recurred, H&N patients were significantly more likely to recur locally compared to non-H&N patients. On subgroup analysis, scalp melanoma was also associated with worse RFS compared to patients with melanoma in locations other than the scalp. When patients with scalp melanoma were excluded from analysis, non-scalp H&N RFS was not significantly different from the non-H&N group on univariate or multivariable analyses. DISCUSSION: In this series from a high-volume tertiary referral center, the differences in rates and sites of recurrence between H&N and non-H&N melanoma do not impact melanoma-specific or overall survival, suggesting that H&N melanoma patients should be treated similarly with respect to regional and systemic therapies.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Clinical Presentation Patterns and Survival Outcomes of Hispanic Patients With Gastric Cancer.

BACKGROUND: Hispanic patients have a higher incidence of gastric cancer when compared to non-Hispanics. Outlining clinicodemographic characteristics and assessing the impact of ethnicity on stage-specific survival may identify opportunities to improve gastric cancer care for this population. METHODS: Patients with gastric cancer in the US Safety Net Collaborative (2012-2014) were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative details, and outcomes were compared between Hispanic and non-Hispanic patients. Early onset gastric cancer was defined as age <50 years. Kaplan-Meier and Cox proportional-hazards models were used to identify the impact of ethnicity on disease-specific survival (DSS). RESULTS: Seven hundred and ninety-seven patients were included, of which 219 (28%) were Hispanic. Hispanic patients were more likely to seek care at safety-net hospitals (66 vs 39%) and be uninsured (36 vs 17%), and less likely to have a primary care provider (PCP) (46 vs 75%; all P<0.05). Hispanic patients were twice as likely to present with early onset gastric cancer (28 vs 15%) and were more frequently diagnosed in the emergency room (54 vs 37%) with both abdominal pain and weight loss (44 vs 31%; all P <0.05). Treatment paradigms, operative outcomes, and DSS were similar between Hispanic and non-Hispanic patients when accounting for cancer stage. Cancer stage, pathologically positive nodes, and negative surgical margins were independently associated with DSS. CONCLUSIONS: A diagnosis of gastric cancer must be considered in previously healthy Hispanic patients who present to the emergency room with both abdominal pain and weight loss. Fewer than 50% of Hispanic patients have a PCP, indicating poor outpatient support. Efforts to improve outpatient support and screening may improve gastric cancer outcomes in this vulnerable population.

Attrition during neoadjuvant chemotherapy for gastric adenocarcinoma is associated with decreased survival: A United States Safety-Net Collaborative analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is standard management for localized gastric cancer (GC). Attrition during NAC due to treatment-related toxicity or functional decline is considered a surrogate for worse biologic outcomes; however, data supporting this paradigm are lacking. We investigated factors predicting attrition and its association with overall survival (OS) in GC. METHODS: Patients with nonmetastatic GC initiating NAC were identified from the US Safety-Net Collaborative (2012-2014). Patient/treatment-related characteristics were compared between attrition/nonattrition cohorts. Cox models determined factors associated with OS. RESULTS: Of 116 patients initiating NAC, attrition during prescribed NAC occurred in 24%. No differences were observed in performance status, comorbidities, treatment at safety-net hospital, or clinicopathologic factors between cohorts. Despite absence of distinguishing factors, attrition was associated with worse OS (median: 11 vs. 37 months; p = 0.01) and was an independent predictor of mortality (hazard ratio [HR]: 4.7, 95% confidence interval [CI]: 1.5-15.2; p = 0.02). Fewer patients with attrition underwent curative-intent surgery (39% vs. 89%; p < 0.001). Even in patients undergoing surgical exploration (n = 89), NAC attrition remained an independent predictor of worse OS (HR: 50.8, 95% CI: 3.6-717.8; p = 0.004) despite similar receipt of adjuvant chemotherapy. CONCLUSION: Attrition during NAC for nonmetastatic GC is independently associated with worse OS, even in patients undergoing surgery. Attrition during NAC may reflect unfavorable tumor biology not captured by conventional staging metrics.

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.

Is there a difference in utilization of a perioperative treatment approach for gastric cancer between safety net hospitals and tertiary referral centers?

BACKGROUND AND OBJECTIVES: Perioperative therapy is a favored treatment strategy for gastric cancer. We sought to assess utilization of this approach at safety net hospitals (SNH) and tertiary referral centers (TRC). MATERIALS AND METHODS: Patients in the US Safety Net Collaborative (2012-2014) with resectable gastric cancer across five SNH and their sister TRC were included. Primary outcomes were receipt of neoadjuvant chemotherapy (NAC) and perioperative therapy. RESULTS: Of 284 patients, 36% and 64% received care at SNH and TRC. The distribution of Stage II/III resectable disease was similar across facilities. Receipt of NAC at SNH and TRC was similar (56% vs. 46%, p = 0.27). Compared with overall clinical stage, 38% and 36% were pathologically downstaged at SNH and TRC, respectively. Among patients who received NAC, those who also received adjuvant chemotherapy at SNH and TRC were similar (66% vs. 60%, p = 0.50). Asian race and higher clinical stage were associated with receipt of perioperative therapy (both p < 0.05) while treatment facility type was not. CONCLUSIONS: There was no difference in utilization of a perioperative treatment strategy between facility types for patients with gastric cancer. Pathologic downstaging from NAC was similar across treatment facilities, suggesting similar quality and duration of therapy. Treatment at an SNH is not a barrier to receiving standard-of-care perioperative therapy for gastric cancer.

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.

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.

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.

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 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.

Dissecting disease, race, ethnicity, and socioeconomic factors for hepatocellular carcinoma: An analysis from the United States Safety Net Collaborative.

BACKGROUND: Racial/ethnic and socioeconomic disparities are assumed to negatively affect treatment and outcomes for hepatocellular carcinoma (HCC). Our aim was to investigate the interaction of racial/ethnic and socioeconomic factors with stage of disease and type of treatment facility in receipt of treatment and overall survival (OS) of patients with HCC. METHODS: All patients with primary HCC in the US Safety-Net Collaborative database (2012-2014) were included. Patients were categorized into "safety-net" or "tertiary referral center" based on where they received treatment. Socioeconomic factors were determined at the zip-code level and included median income and percent of adults who graduated from high-school. Primary outcomes were receipt of treatment and OS. RESULTS: On MV Cox regression, neither race/ethnicity, median income, nor care provided at a SNH were associated with decreased OS (all p > 0.05). Independent predictors of decreased OS included lack of insurance (HR 1.34), less educational attainment (HR 1.59) higher MELD score (HR 1.07), higher stage at diagnosis (II:HR 1.34, III:HR 2.87, IV:HR 3.23), and not receiving treatment (HR 3.94) (all p < 0.05). Factors associated with not receiving treatment included history of alcohol abuse (OR 0.682), increasing MELD (OR 0.874), higher stage at diagnosis (III: OR 0.234, IV: OR 0.210) and care at a safety net facility (OR 0.424) There were no racial/ethnic or socioeconomic disparities in receipt of treatment. CONCLUSIONS: There is no intrinsic or direct association of race/ethnicity, socioeconomic status, or being treated at select safety-net hospitals with worse outcomes. Poor liver function, no insurance, and advanced stage of presentation are the main determinants of not receiving treatment and decreased survival.

Suppressive myeloid cells are expanded by biliary tract cancer-derived cytokines in vitro and associate with aggressive disease.

BACKGROUND: BTC is an aggressive disease exacerbated by inflammation and immune suppression. Expansion of immunosuppressive cells occurs in biliary tract cancer (BTC), yet the role of BTC-derived cytokines in this process is unclear. METHODS: Activated signalling pathways and cytokine production were evaluated in a panel of human BTC cell lines. Human peripheral blood mononuclear cells (PBMCs) were cultured with BTC supernatants, with and without cytokine neutralising antibodies, and analysed by flow cytometry or immunoblot. A human BTC tissue microarray (TMA, n = 69) was stained for IL-6, GM-CSF, and CD33+S100a9+ cells and correlated with clinical outcomes. RESULTS: Immunomodulatory factors (IL-6, GM-CSF, MCP-1) were present in BTC supernatants. BTC supernatants expanded CD33dimCD11b+HLA-DRlow/- myeloid-derived suppressor cells (MDSCs) from human PBMCs. Neutralisation of IL-6 and GM-CSF in BTC supernatants inhibited activation of STAT3/5, respectively, in PBMCs, with heterogeneous effects on MDSC expansion in vitro. Staining of a BTC TMA revealed a positive correlation between IL-6 and GM-CSF, with each cytokine and more CD33+S100a9+ cells. Increased CD33+S100a9+ staining positively correlated with higher tumour grade, differentiation and the presence of satellite lesions. CONCLUSION: BTC-derived factors promote suppressive myeloid cell expansion, and higher numbers of CD33+S100a9+ cells in resectable BTC tumours correlates with more aggressive disease.