ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity.

Group 2 innate lymphoid cells (ILC2s) regulate inflammation and immunity in mammalian tissues1,2. Although ILC2s are found in cancers of these tissues3, their roles in cancer immunity and immunotherapy are unclear. Here we show that ILC2s infiltrate pancreatic ductal adenocarcinomas (PDACs) to activate tissue-specific tumour immunity. Interleukin-33 (IL33) activates tumour ILC2s (TILC2s) and CD8+ T cells in orthotopic pancreatic tumours but not heterotopic skin tumours in mice to restrict pancreas-specific tumour growth. Resting and activated TILC2s express the inhibitory checkpoint receptor PD-1. Antibody-mediated PD-1 blockade relieves ILC2 cell-intrinsic PD-1 inhibition to expand TILC2s, augment anti-tumour immunity, and enhance tumour control, identifying activated TILC2s as targets of anti-PD-1 immunotherapy. Finally, both PD-1+ TILC2s and PD-1+ T cells are present in most human PDACs. Our results identify ILC2s as anti-cancer immune cells for PDAC immunotherapy. More broadly, ILC2s emerge as tissue-specific enhancers of cancer immunity that amplify the efficacy of anti-PD-1 immunotherapy. As ILC2s and T cells co-exist in human cancers and share stimulatory and inhibitory pathways, immunotherapeutic strategies to collectively target anti-cancer ILC2s and T cells may be broadly applicable.

Outcomes from 871,441 Consecutive Surgical Procedures without Overlap or with Maximally Permissible Non-Concurrent Overlap.

OBJECTIVE: To isolate the impact of subsumed surgery (a shorter procedure completed entirely during overlapping non-critical portions of a longer antecedent procedure) on patient outcomes. SUMMARY BACKGROUND DATA: The American College of Surgeons recently recommended the elimination of "concurrent surgery" with overlap during a procedure's critical portions. Guidelines for non-concurrent overlap have been established, but the safety of subsumed surgery remains to be examined. METHODS: All consecutive procedures from 2013 to 2021 within a multihospital academic medical center were included (n=871,441). Simple logistic regression was performed to compare postoperative events between patients undergoing non-overlap surgery (n=533,032) and completely subsumed surgery (n=11,319). Thereafter, coarsened exact matching was used to match patients with non-overlap and subsumed surgery 1:1 on CPT code, 18 demographic features, baseline health characteristics, and procedural variables (n=7,146). Exact-matched cases were subsequently limited to pairs performed by the same surgeon (n=5,028). Primary outcomes included 30-day readmission, ED visits, and reoperations. RESULTS: Univariate analysis suggested that subsumed surgery had a higher 30-day risk of readmission (OR 1.55, P<0.0001), ED evaluation (OR 1.19, P<0.0001), and reoperation (OR 1.98, P<0.0001). When comparison was limited to the exact same procedure and patients were matched on demographics and health characteristics, there were no outcome differences between patients with subsumed surgery and non-overlapping surgery, even when limiting analyses to the same surgeon. CONCLUSIONS: Similar surgeries for similar patients result in similar outcomes whether there is completely subsumed or no overlap. Individual surgeons performing a specific procedure have no outcome differences with subsumed and non-overlapping cases.

Randomized Prospective Trial of Epidural Analgesia after Open Hepatectomy.

OBJECTIVE: To evaluate whether patient-controlled epidural analgesia (PCEA) improves postoperative pain during ambulation following elective open hepatectomy. BACKGROUND: Strategies to alleviate postoperative pain are a critical element of recovery after surgery. However, the optimal postoperative pain management strategy following open hepatectomy remains unclear. METHODS: We conducted a prospective, nonblinded, randomized comparison of PCEA (intervention) versus intravenous patient-controlled analgesia (IV PCA; control) for postoperative pain following elective open hepatectomy. The primary end point was pain during ambulation on postoperative day (POD) 2. The study was powered to detect a clinically significant 2-point difference on the pain numeric rating scale (NRS). Secondary end points included pain at rest, morbidity, time to return of bowel function, and length of stay. RESULTS: From 2015 to 2020, 231 patients were randomized (116 patients in the PCEA arm and 115 in the IV PCA arm). The incidence of epidural failure was 3% (n=4/116), with no epidural-related complications. Patients in the PCEA arm had a <2-point difference in NRS pain scores during ambulation on POD 2 vs. IV PCA (median 4.0 vs. 5.0, P <0.001). There was no difference in overall complications between the PCEA and IV PCA arms (33% vs. 40%, P =0.276). Secondary outcomes, including pain scores at rest, were similar between the study arms. CONCLUSIONS: PCEA was safe following open hepatectomy and was associated with a small difference in pain with activity on POD 2 that did not reach our pre-specified definition of clinical significance.

Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

A Randomized Controlled Trial to Assess the Impact of Enhanced Recovery After Surgery on Patients Undergoing Elective Spine Surgery.

OBJECTIVE: To conduct a prospective, randomized controlled trial (RCT) of an enhanced recovery after surgery (ERAS) protocol in an elective spine surgery population. BACKGROUND: Surgical outcomes such as length of stay (LOS), discharge disposition, and opioid utilization greatly contribute to patient satisfaction and societal healthcare costs. ERAS protocols are multimodal, patient-centered care pathways shown to reduce postoperative opioid use, reduced LOS, and improved ambulation; however, prospective ERAS data are limited in spine surgery. METHODS: This single-center, institutional review board-approved, prospective RCT-enrolled adult patients undergoing elective spine surgery between March 2019 and October 2020. Primary outcomes were perioperative and 1-month postoperative opioid use. Patients were randomized to ERAS (n=142) or standard-of-care (SOC; n=142) based on power analyses to detect a difference in postoperative opioid use. RESULTS: Opioid use during hospitalization and the first postoperative month was not significantly different between groups (ERAS 112.2 vs SOC 117.6 morphine milligram equivalent, P =0.76; ERAS 38.7% vs SOC 39.4%, P =1.00, respectively). However, patients randomized to ERAS were less likely to use opioids at 6 months postoperatively (ERAS 11.4% vs SOC 20.6%, P =0.046) and more likely to be discharged to home after surgery (ERAS 91.5% vs SOC 81.0%, P =0.015). CONCLUSION: Here, we present a novel ERAS prospective RCT in the elective spine surgery population. Although we do not detect a difference in the primary outcome of short-term opioid use, we observe significantly reduced opioid use at 6-month follow-up as well as an increased likelihood of home disposition after surgery in the ERAS group.

Surgical Management of Germline Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and usually results from a sporadic mutation in KIT or, less frequently, platelet-derived growth factor alpha (PDGFRA). Rarely, a germline mutation in the KIT, PDGFRA, succinate dehydrogenase (SDH), or neurofibromatosis 1 (NF1) gene is responsible for GIST. These tumors are found in the stomach (PDGFRA and SDH), small bowel (NF1), or a combination of both (KIT). There is a need to improve care for these patients regarding genetic testing, screening, and surveillance. Since most GISTs due to a germline mutation do not respond to tyrosine kinase inhibitors, the role of surgery is critical, especially when considering germline gastric GIST. However, in contrast to the established recommendation for prophylactic total gastrectomy in cadherin 1 (CDH1) mutation carriers once they reach adulthood, there are no formal guidelines as to the timing or extent of surgical resection for patients who are either carriers of a germline GIST mutation causing gastric GIST or have already developed gastric GIST(s). Surgeons must balance treating what is often multicentric, yet initially indolent disease with the chance of cure and the complications associated with total gastrectomy. Here, we consider the major issues in performing surgery in patients with germline GIST and illustrate the principles with a previously unreported patient harboring a germline KIT 579 deletion.

Immunotherapy for GI Malignancies, Ready for Prime Time?

Gastrointestinal (GI) cancers include esophageal, gastric, pancreatic, hepatobiliary, and colorectal malignancies. Immunotherapy has proved to be an important treatment method for cancer, and its use for a wide range of GI malignancies has been evaluated recently. This article discusses the type and mechanism of various immunotherapies under investigation in GI cancer. The study also reviews recent clinical trials, with a particular focus on overall survival, and discusses their achievements and limitations. Immunotherapy has shown efficacy for microsatellite instability high colorectal cancer and some promise in some gastroesophageal junction and gastric cancers. Meanwhile, it has not been effective for pancreatic or neuroendocrine tumors. The identification of novel biomarkers likely will guide selection of therapy for individual patients. Nevertheless, immunotherapy for GI cancers is in its infancy, and many other classes of immune therapies are being developed besides anti-PD1 and anti-PDL1. Thus, although immunotherapy has not seen a dramatic advance to date, it still has great potential.

Neoadjuvant Chemotherapy in Retroperitoneal Sarcoma: A National Cohort Study.

INTRODUCTION: Management of retroperitoneal sarcoma (RPS) remains controversial, with the mainstay of treatment being surgery. While neoadjuvant radiation demonstrated no improvement in recurrence-free survival in a prospective randomized trial (STRASS), the role of neoadjuvant chemotherapy (NCT) remains unknown and is the subject of ongoing study (STRASS2). METHODS: Patients who underwent surgical resection of high-grade RP leiomyosarcoma (LMS) or dedifferentiated liposarcoma (DDLS) were identified from the National Cancer Database (2006-2019). Predictors of NCT were analyzed using univariate and multivariate logistic regression analyses. Differences in 5-year survival were examined using the Kaplan-Meier (KM) method and by Cox proportional hazard modeling. RESULTS: A total of 2656 patients met inclusion criteria. Fifty-seven percent of patients had DDLS and 43.5% had LMS. Six percent of patients underwent NCT. Patients who received NCT were younger (median age 60 vs 64 years, p < 0.001) and more likely to have LMS (OR 1.4, p = 0.04). In comparing NCT with no-NCT patients, there was no difference in 5-year overall survival (OS) on KM analysis (57.3% vs 52.8%, p = 0.38), nor was any difference seen after propensity matching (54.9% vs 49.1%, p = 0.48, N = 144 per group). When stratified by histology, there was no difference in OS based on receipt of NCT (LMS: 59.8% for NCT group, 56.6% for no-NCT, p = 0.34; DDLS: 54.2% for NCT group, 50.1% for no-NCT, p = 0.99). CONCLUSION: In patients undergoing surgical resection of RP LMS or DDLS, NCT does not appear to confer an OS advantage. Prospective randomized data from STRASS2 will confirm or refute these retrospective data.

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer.

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.

Are Volume Pledge Standards Worth the Travel Burden for Major Abdominal Cancer Operations?

OBJECTIVE: The study objective is to determine the association between travel distance and surgical volume on outcomes after esophageal, pancreatic, and rectal cancer resections. SUMMARY OF BACKGROUND DATA: "Take the Volume Pledge" aims to centralize esophagectomies, pancreatectomies, and proctectomies to hospitals meeting minimum volume standards. The impact of travel, and possible care fragmentation, on potential benefits of centralized surgery is not well understood. METHODS: Using the National Cancer Database (2004-2016), patients who underwent esophageal, pancreatic, or rectal resections at far HVH meeting volume standards versus local intermediate (IVH) and low-volume (LVH) hospitals were identified. Perioperative outcomes and 5-year OS were compared. RESULTS: Of 49,454 patients, 17,544 (34.5%) underwent surgery at far HVH, 11,739 (23.7%) at local IVH, and 20,171 (40.8%) at local LVH. The median (interquartilerange) travel distances were 77.1 (51.1-125.4), 13.2 (5.8-27.3), and 7.8 (3.1-15.5) miles to HVH, IVH, and LVH, respectively. By multivariable analysis, LVH was associated with increased 30-day mortality for all resections compared to HVH, but IVH was associated with mortality only for proctectomies [odds ratio 1.90, 95% confidence interval (CI) 1.31-2.75]. Compared to HVH, both IVH (hazard ratio 1.25, 95% CI 1.19-1.31) and LVH (hazard ratio 1.35, 95% CI 1.29-1.42) were associated with decreased 5-year OS. CONCLUSIONS: Compared to far HVH, 30-day mortality was higher for all resections at LVH, but only for proctectomies at IVH. Five-year OS was consistently worse at local LVH and IVH. Improving long-term outcomes at IVH may provide opportunities for greater access to quality cancer care.

Genetic Determinants of Outcome in Intrahepatic Cholangiocarcinoma.

BACKGROUND AND AIM: Genetic alterations in intrahepatic cholangiocarcinoma (iCCA) are increasingly well characterized, but their impact on outcome and prognosis remains unknown. APPROACH AND RESULTS: This bi-institutional study of patients with confirmed iCCA (n = 412) used targeted next-generation sequencing of primary tumors to define associations among genetic alterations, clinicopathological variables, and outcome. The most common oncogenic alterations were isocitrate dehydrogenase 1 (IDH1; 20%), AT-rich interactive domain-containing protein 1A (20%), tumor protein P53 (TP53; 17%), cyclin-dependent kinase inhibitor 2A (CDKN2A; 15%), breast cancer 1-associated protein 1 (15%), FGFR2 (15%), polybromo 1 (12%), and KRAS (10%). IDH1/2 mutations (mut) were mutually exclusive with FGFR2 fusions, but neither was associated with outcome. For all patients, TP53 (P < 0.0001), KRAS (P = 0.0001), and CDKN2A (P < 0.0001) alterations predicted worse overall survival (OS). These high-risk alterations were enriched in advanced disease but adversely impacted survival across all stages, even when controlling for known correlates of outcome (multifocal disease, lymph node involvement, bile duct type, periductal infiltration). In resected patients (n = 209), TP53mut (HR, 1.82; 95% CI, 1.08-3.06; P = 0.03) and CDKN2A deletions (del; HR, 3.40; 95% CI, 1.95-5.94; P < 0.001) independently predicted shorter OS, as did high-risk clinical variables (multifocal liver disease [P < 0.001]; regional lymph node metastases [P < 0.001]), whereas KRASmut (HR, 1.69; 95% CI, 0.97-2.93; P = 0.06) trended toward statistical significance. The presence of both or neither high-risk clinical or genetic factors represented outcome extremes (median OS, 18.3 vs. 74.2 months; P < 0.001), with high-risk genetic alterations alone (median OS, 38.6 months; 95% CI, 28.8-73.5) or high-risk clinical variables alone (median OS, 37.0 months; 95% CI, 27.6-not available) associated with intermediate outcome. TP53mut, KRASmut, and CDKN2Adel similarly predicted worse outcome in patients with unresectable iCCA. CDKN2Adel tumors with high-risk clinical features were notable for limited survival and no benefit of resection over chemotherapy. CONCLUSIONS: TP53, KRAS, and CDKN2A alterations were independent prognostic factors in iCCA when controlling for clinical and pathologic variables, disease stage, and treatment. Because genetic profiling can be integrated into pretreatment therapeutic decision-making, combining clinical variables with targeted tumor sequencing may identify patient subgroups with poor outcome irrespective of treatment strategy.

Opioid Use Disorder is Associated With Complications and Increased Length of Stay After Major Abdominal Surgery.

OBJECTIVE: The objective of this study was to determine the impact of opioid use disorder (OUD) on perioperative outcomes after major upper abdominal surgeries. SUMMARY OF BACKGROUND DATA: OUD, defined as dependence/abuse, is a national health epidemic. Its impact on outcomes after major abdominal surgery has not been well characterized. METHODS: Patients who underwent elective esophagectomy, total/partial gastrectomy, major hepatectomy, and pancreatectomy were identified using the National Inpatient Sample (2003-2015). Propensity score matching by baseline characteristics was performed for patients with and without OUD. Outcomes measured were in-hospital complications, mortality, length of stay (LOS), and discharge disposition. RESULTS: Of 376,467 patients, 1096 (0.3%) had OUD. Patients with OUD were younger (mean 53 vs 61 years, P < 0.001) and more often male (55.1% vs 53.2%, P < 0.001), black (15.0% vs 7.6%, P < 0.001), Medicaid beneficiaries (22.0% vs 6.4%, P < 0.001), and in the lowest income quartile (32.6% vs 21.3%, P < 0.001). They also had a higher rate of alcohol (17.2% vs 2.8%, P < 0.001) and nonopioid drug (2.2% vs 0.2%, P = 0.023) dependence/abuse. After matching (N = 1077 OUD, N = 2164 no OUD), OUD was associated with a higher complication rate (52.9% vs 37.3%, P < 0.001), including increased pain [odds ratio (OR) 3.5, P < 0.001], delirium (OR 3.0, P = 0.004), and pulmonary complications (OR 2.0, P = 0.006). Additionally, OUD was associated with increased LOS (mean 12.4 vs 10.6 days, P = 0.015) and nonroutine discharge (OR 1.6, P < 0.001). In-hospital mortality did not differ (OR 2.4, P = 0.10). CONCLUSION: Patients with OUD more frequently experienced complications and increased LOS. Close postoperative monitoring may mitigate adverse outcomes.

The Cost of Quarantine: Projecting the Financial Impact of Canceled Elective Surgery on the Nation's Hospitals.

OBJECTIVE: We sought to quantify the financial impact of elective surgery cancellations in the US during COVID-19 and simulate hospitals' recovery times from a single period of surgery cessation. BACKGROUND: COVID-19 in the US resulted in cessation of elective surgery-a substantial driver of hospital revenue-and placed patients at risk and hospitals under financial stress. We sought to quantify the financial impact of elective surgery cancellations during the pandemic and simulate hospitals' recovery times. METHODS: Elective surgical cases were abstracted from the Nationwide Inpatient Sample (2016-2017). Time series were utilized to forecast March-May 2020 revenues and demand. Sensitivity analyses were conducted to calculate the time to clear backlog cases and match expected ongoing demand in the post-COVID period. Subset analyses were performed by hospital region and teaching status. RESULTS: National revenue loss due to major elective surgery cessation was estimated to be $22.3 billion (B). Recovery to market equilibrium was conserved across strata and influenced by pre- and post-COVID capacity utilization. Median recovery time was 12-22 months across all strata. Lower pre-COVID utilization was associated with fewer months to recovery. CONCLUSIONS: Strategies to mitigate the predicted revenue loss of $22.3B due to major elective surgery cessation will vary with hospital-specific supply-demand equilibrium. If patient demand is slow to return, hospitals should focus on marketing of services; if hospital capacity is constrained, efficient capacity expansion may be beneficial. Finally, rural and urban nonteaching hospitals may face increased financial risk which may exacerbate care disparities.

Outcome of 1000 Patients With Gastrointestinal Stromal Tumor (GIST) Treated by Surgery in the Pre- and Post-imatinib Eras.

OBJECTIVE: To characterize the results of surgery for gastrointestinal stromal tumor (GIST) in the pre and post-imatinib eras at a single institution and to identify current prognostic clinicopathologic factors. BACKGROUND: Imatinib has radically changed the management of GIST, yet the magnitude of impact on outcome across the spectrum of GIST presentation and relevance of historical prognostic factors are not well defined. METHODS: We retrospectively analyzed 1000 patients who underwent surgery for GIST at our institution from 1982 to 2016. Patients were stratified by presentation status as primary tumor only (PRIM), primary with synchronous metastasis (PRIM + MET), or metachronous recurrence/metastases (MET), and also imatinib era (before and after it became available). Cox proportional-hazard models and Kaplan-Meier methods were used to model and estimate overall survival (OS) and recurrence-free survival (RFS). RESULTS: OS was longer in the imatinib era compared with the pre-imatinib era in each presentation group, including in Miettinen high-risk primary tumors. Among PRIM patients from the pre-imatinib era, tumor site, size, and mitotic rate were independently associated with OS and RFS on multivariate analysis. PRIM patients in the imatinib era who received imatinib (neoadjuvant and/or adjuvant) had higher risk tumors, but after adjusting for treatment, only size >10 cm remained independently prognostic of RFS [hazard ratio (HR) 3.85, 95% confidence interval (CI) 2.00-7.40, P < 0.0001) and OS (HR 3.37, 95% CI 1.60-7.13, P = 0.001)]. CONCLUSIONS: Patients treated in the imatinib era had prolonged OS across all presentations. In the imatinib era, among site, size, and mitotic rate, high-risk features were associated with treatment with the drug, but only size >10 cm correlated with outcome. Imatinib should still be prescribed for patients with high-risk features.

Gastric Neuroendocrine Tumors: Reappraisal of Type in Predicting Outcome.

BACKGROUND: Type I gastric neuroendocrine tumors (GNETs) are typically managed either expectantly or endoscopically. In contrast, locoregional surgery has been recommended for patients with type III GNETs because of the risk of metastasis. This study aimed to identify predictors of outcome independent of type in a contemporary cohort of GNET patients. METHODS: A single-institution retrospective cohort study of 121 patients with a pathologic diagnosis of primary GNET between January 2009 and June 2019 was performed. GNETs were designated as type 1 (n = 74) if atrophic gastritis was present, or as type III (n = 47) in the absence of atrophic gastritis. Demographic, clinical, and histopathologic factors were examined using Kaplan-Meier and multivariable Cox regression to assess the impact of various factors on recurrence and overall survival. RESULTS: Median follow-up for the entire cohort was 62.7 months. While there was no difference in OS in patients with different GNET types (p = 0.10), higher tumor grade (p = 0.02) and presence of nodal or distant metastases (p = 0.02) predicted worse survival on multivariable analysis. Among type III GNET patients, those with small (< 0.5 cm), grade 1 lesions ("low-risk") were less likely to develop metastases (0% versus 33%, p < 0.01) and more likely to survive (100% versus 67%, p < 0.01) at 5 years. CONCLUSIONS: Size and tumor grade predict recurrence and survival in patients with GNETs irrespective of type. Small, low-grade type III GNETs are associated with minimal risk of progression and may be managed accordingly.

Long-term Outcomes After Surgical Resection of Pancreatic Metastases from Renal Clear-Cell Carcinoma.

BACKGROUND: Pancreatic metastases (PM) from renal cell carcinoma (RCC) are uncommon. We herein describe the long-term outcomes associated with pancreatectomy at two academic institutions, with a specific focus on 10-year survival. METHODS: This investigation was limited to patients undergoing pancreatectomy for PM between 2000 and 2008 at the University of Verona and Memorial Sloan Kettering Cancer Center, allowing a potential for 10 years of surveillance. The probabilities of further RCC recurrence and RCC-related death were estimated using a competing risk analysis (method of Fine and Gray) to account for patients who died of other causes during follow-up. RESULTS: The study population consisted of 69 patients, mostly with isolated metachronous PM (77%). The median interval from nephrectomy to pancreatic metastasectomy was 109 months, whereas the median post-pancreatectomy follow-up was 141 months. The 10-year cumulative incidence of new RCC recurrence was 62.7%. In the adjusted analysis, the relative risk of repeated recurrence was significantly higher in PM synchronous to the primary RCC (sHR = 1.27) and in patients receiving extended pancreatectomy (sHR = 3.05). The 10-year cumulative incidence of disease-specific death was 25.5%. The only variable with an influence on disease-specific death was the recurrence-free interval following metastasectomy (sHR = 0.98). In patients with repeated recurrence, the 10-year cumulative incidence of RCC-related death was 35.4%. CONCLUSION: In a selected group of patients followed for a median of 141 months and mostly with isolated metachronous PM, resection was associated with a high possibility of long-term disease control in surgically fit patients with metastases confined to the pancreas.

Impact of Primary Tumor Laterality on Adjuvant Hepatic Artery Infusion Pump Chemotherapy in Resected Colon Cancer Liver Metastases: Analysis of 487 Patients.

BACKGROUND: Hepatic artery infusion (HAI) chemotherapy is associated with overall survival (OS) in patients with resected colon cancer liver metastases (CLM). The prognostic impact of primary tumor location in CLM following hepatic resection in patients receiving regional HAI is unknown. This study seeks to investigate the prognostic impact of HAI in relation to laterality in this patient population. METHODS: Consecutive patients with resected CLM, with known primary tumor site treated with and without HAI, were reviewed from a prospective institutional database. Correlations between HAI, laterality, other clinicopathological factors, and survival were analyzed, and Cox proportional hazard regression was used to determine whether laterality was an independent prognostic factor. RESULTS: From 1993 to 2012, 487 patients [182 with right colon cancer (RCC), 305 with left colon cancer (LCC)] were evaluated with a median follow-up of 6.5 years. Fifty-seven percent (n = 275) received adjuvant HAI. Patients with RCC had inferior 5-year OS compared with LCC (56% vs. 67%, P = 0.01). HAI was associated with improved 5-year OS in both RCC (68% vs. 45%; P < 0.01) and LCC (73% vs. 55%; P < 0.01). On multivariable analysis, HAI remained associated with improved OS (HR 0.52; 95% CI 0.39-0.70; P < 0.01) but primary tumor site did not (HR 0.83; 95% CI 0.63-1.11; P = 0.21). Additional significant prognostic factors on multivariable analysis included age, number of tumors, node-positive primary, positive margins, RAS mutation, two-stage hepatectomy, and extrahepatic disease. Cox proportional hazard regression determined no significant interaction between HAI and laterality on OS [parameter estimate (SEM), 0.12 (0.28); P = 0.67]. CONCLUSIONS: Our data show an association of adjuvant HAI and increased OS in patients who underwent curative hepatectomy, irrespective of primary tumor location. Laterality should therefore not impact decision-making when offering adjuvant HAI.

Impact of COVID-19 Restrictions on Demographics and Outcomes of Patients Undergoing Medically Necessary Non-Emergent Surgeries During the Pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in large-scale healthcare restrictions to control viral spread, reducing operating room censuses to include only medically necessary surgeries. The impact of restrictions on which patients undergo surgical procedures and their perioperative outcomes is less understood. METHODS: Adult patients who underwent medically necessary surgical procedures at our institution during a restricted operative period due to the COVID-19 pandemic (March 23-April 24, 2020) were compared to patients undergoing procedures during a similar time period in the pre-COVID-19 era (March 25-April 26, 2019). Cardinal matching and differences in means were utilized to analyze perioperative outcomes. RESULTS: 857 patients had surgery in 2019 (pre-COVID-19) and 212 patients had surgery in 2020 (COVID-19). The COVID-19 era cohort had a higher proportion of patients who were male (61.3% vs. 44.5%, P < 0.0001), were White (83.5% vs. 68.7%, P < 0.001), had private insurance (62.7% vs. 54.3%, p 0.05), were ASA classification 4 (10.9% vs. 3%, P < 0.0001), and underwent oncologic procedures (69.3% vs. 42.7%, P < 0.0001). Following 1:1 cardinal matching, COVID-19 era patients (N = 157) had a decreased likelihood of discharge to a nursing facility (risk difference-8.3, P < 0.0001) and shorter median length of stay (risk difference-0.6, p 0.04) compared to pre-COVID-19 era patients. There was no difference between the two patient cohorts in overall morbidity and 30-day readmission. CONCLUSIONS: COVID-19 restrictions on surgical operations were associated with a change in the racial and insurance demographics in patients undergoing medically necessary surgical procedures but were not associated with worse postoperative morbidity. Further study is necessary to better identify the causes for patient demographic differences.

Adjuvant Hepatic Artery Infusion Chemotherapy is Associated With Improved Survival Regardless of KRAS Mutation Status in Patients With Resected Colorectal Liver Metastases: A Retrospective Analysis of 674 Patients.

OBJECTIVE: To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM). BACKGROUND: Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection. METHODS: Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders. RESULTS: Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors. CONCLUSION: Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.

Benchmarking Accomplishments of Leaders in American Surgery and Justification for Enhancing Diversity and Inclusion.

OBJECTIVE: To comprehensively assess the level of achievement and demographics of national surgical society presidents. BACKGROUND: Data on the accomplishments needed to rise to positions of national surgical leadership is scarce and merit alone does not always yield such opportunities. Recognizing the shortcomings of sex and ethnic diversity within academic surgical leadership, the American College of Surgeon (ACS), American Surgical Association (ASA), Association of Women Surgeons (AWS), and the Society of Black Academic Surgeons (SBAS) partnered to address these challenges by performing a comprehensive assessment of their presidents over the last 16 years. METHODS: ACS, ASA, AWS, and SBAS presidents' CVs, at the time of their presidential term, were assessed for demographics and scholastic achievements. Regression analyses controlling for age were performed to determine relative differences across societies. RESULTS: A total of 62 of the 64 presidents' CVs were received and assessed (97% response rate). There was a large discrepancy in the average age in years of ACS (70) and ASA (66) presidents compared to the AWS (51) and SBAS (53) presidents. For the ACS and ASA cohort, 87% were male and 83% were White, collectively. After controlling for age (52), the AWS and SBAS presidents' scholastic achievements were comparable to the ACS (and ASA) cohort in 9 and 12 of the 15 accessed metrics, respectively. CONCLUSION: The ACS and ASA presidents' CVs displayed unsurpassed scholastic achievement, and although not equivalent, both the AWS and the SBAS presidents had comparable attainment. These findings further substantiate that women and ethnic minority surgeons are deserving of additional national leadership consideration as organized medicine pursues a more diverse and reflective physician workforce.