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Hepatic metastatic disease affects more than half of the patients with colorectal cancer and neuroendocrine cancer. Hepatic resection remains the gold standard for liver metastasis from colorectal and neuroendocrine primaries. Thermal ablative technologies, however, are increasingly being used either alone or in combination with resection to treat this group of patients. Radiofrequency ablation is the most common modality used in the United States, whereas microwave ablation has been more widely used in the East. In addition to being adjuncts to hepatic resection, ablation has gained an increased popularity in the management of patients who are not operative candidates or have unresectable colorectal or neuroendocrine hepatic metastasis. Although radiofrequency ablation seems to have a higher local recurrence than resection, ablation remains an important therapeutic option for many patients with hepatic metastasis. [ABSTRACT FROM AUTHOR]

Background: We sought to define the survival benefit of kidney transplantation versus long-term dialysis relative to waitlist time on dialysis, social vulnerability, and age among end-stage renal transplant candidates., Methods: End-stage renal disease patients who were candidates for their first deceased donor kidney transplantation between 2008 and 2020 were identified using the US Renal Data System. Survival probabilities for patient survival were compared using the restricted mean survival times (RMSTs) across different age and social vulnerability index (SVI) ranges., Results: Among 149 923 patients, 68 795 (45.9%) patients underwent a kidney transplant and 81 128 (54.1%) remained on dialysis. After propensity-score matching (n = 58 035 in each cohort), the 5-y RMST difference between kidney transplant and dialysis demonstrated an increasing trend in mean life-years gained within 5 y of follow-up relative to advancing age (<30 y: 0.40 y, 95% confidence interval, 0.36-0.44 y versus >70 y: 0.75 y, 95% confidence interval, 0.70-0.80 y). Conversely, disparities in 5-y RMSTs remained consistent relative to social vulnerability (median 5-y RMST difference: 0.62 y comparing low versus high SVI). When considering waitlist duration, stratified analyses demonstrated increasing trends across different age groups with the largest RMST differences observed among older patients aged ≥70 y. Notably, longer waitlist durations (>3 y) yielded more pronounced RMST differences compared with shorter durations (<1 y)., Conclusions: These data underscore the survival benefit associated with kidney transplantation over long-term dialysis across various age and SVI ranges. Transplantation demonstrated a greater advantage among older patients who had a longer waitlist duration., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To characterize the association between type of fellowship training and patient outcomes following hepatopancreatic (HP) surgery across different surgeon career stages using a national representative cohort of Medicare beneficiaries., Background: The current state of training in HPB surgery in North America is defined through three main pathways: the Complex General Surgical Oncology (CGSO), the Americas HPB Association fellowship, and the American Society of Transplant surgeons fellowship. Each pathway offers a unique perspective on HPB surgery with different number of training years, yet outcomes of graduates performing HP surgery relative to type of fellowship training have not been defined., Methods: Medicare claims were used to identify patients who underwent HP surgery for cancer between 2016-2021. The association of textbook outcomes (TO), defined as no postoperative complications, no prolonged LOS, no 90-day mortality and no 90-day readmission, relative to different fellowship pathways was examined., Results: Overall, 15,411 cancer operations (pancreatectomy: 11,003, 71.4%; hepatectomy: 4,408, 28.6%) were performed by 1,030 HPB surgeons. A total of 9,390 patients (60.9%) were operated on by a CGSO/SONC graduate, 2,315 patients (15.0%) by an HPB fellowship graduate and 3,706 (24.1%) by a transplant fellowship graduate. Patients who were operated on by an HPB fellowship graduate more frequently had a higher Charlson score (>5: 44.8% vs. 38.1%) and more frequently were operated on an urgent basis (7.7% vs. 6.1%) compared with individuals treated by CGSO/SONC graduates. After adjusting for patient, procedural, hospital, and surgeon related factors, the likelihood of TO following an HP operation by an HPB fellowship graduate was 47.7% versus 45.2% among CGSO (% difference 2.7%) and 42.8% among transplant fellowship graduates (% difference 4.9%, P=0.01). While the probability of TO was higher among surgeons having completed a dedicated HPB fellowship during early (1-7th year of independent practice, P=0.032) and middle (8-14th year, P<0.001) career stages, the probability of TO did not differ based on fellowship type among late career surgeons (>15th year, P=0.257)., Conclusions: Achievement of TO following an HP procedure was higher among surgeons who had completed a dedicated HPB fellowship, especially during early and middle career stages. Further efforts should be made to enhance HP surgery exposure and training for CGSO fellows interested in a career in HPB surgery., Competing Interests: Conflict of interest: none, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We sought to characterize postoperative outcomes among patients who underwent an oncologic operation relative to whether the treating surgeon was an international medical graduate (IMG) versus a United States medical graduate (USMG)., Background: IMGs comprise approximately one quarter of the physician workforce in the United States., Methods: The 100% Medicare Standard Analytic Files were utilized to extract data on patients with breast, lung, hepato-pancreato-biliary (HPB), and colorectal cancer who underwent surgical resection between 2014 and 2020. Entropy balancing and multivariable regression analysis were performed to evaluate the association between postoperative outcomes among USMG and IMG surgeons., Results: Among 285,930 beneficiaries, 242,914 (85.0%) and 43,016 (15.0%) underwent surgery by a USMG or IMG surgeon, respectively. Overall, 129,576 (45.3%) individuals were male, and 168,848 (59.1%) patients had a Charlson Comorbidity Index score >2. Notably, IMG surgeons were more likely to care for racial/ethnic minority patients (14.7% vs 12.5%) and individuals with a high social vulnerability index (33.3% vs 32.1%) (all P <0.001). On multivariable analysis after entropy balancing, patients treated by an IMG surgeon were less likely to experience adverse postoperative outcomes, including 90-day readmission [odds ratio (OR) 0.89, 95% CI: 0.80-0.99] and index complications (OR: 0.84, 95% CI: 0.74-0.95) versus USMG surgeons (all P <0.05). Patients treated by IMG versus USMG surgeons had no difference in likelihood to achieve a textbook outcome (OR: 1.10, 95% CI: 0.99-1.21; P =0.077)., Conclusions: Postoperative outcomes among patients treated by IMG surgeons were roughly equivalent to those of USMG surgeons. In addition, IMG surgeons were more likely to care for patients with multiple comorbidities and individuals from vulnerable communities., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We sought to define the association of privilege on rates of unplanned surgery and perioperative outcomes for access-sensitive surgical conditions., Background: Social determinants of health (SDOH) are critical in influencing timely access to healthcare. Privilege represents a right, benefit, advantage, or opportunity that positively influences all SDOH., Methods: The California Department of Health Care Access and Information (HCAI) database identified patients who underwent abdominal aortic aneurysm repair, ventral hernia repair, or colectomy for colon cancer between 2017 and 2020 and was merged using ZIP codes with the Index of Concentration of Extremes, a validated measure of racial and economic privilege obtained from the American Community Survey. Clustered multivariable regression was performed to assess the association between privilege and outcomes., Results: Among 185,316 patients who underwent a surgical procedure for one of three access-sensitive surgical conditions, roughly 1 in 5 individuals resided in areas with the highest (Q5; n=37,308; 20.1%) or lowest (Q1; n=36,352, 19.6%) privilege. Nearly one-half of the surgeries were unplanned (n=88,814, 46.9%), and colectomy for colon cancer was the most performed emergent procedure. Patients residing in the lowest privileged areas had higher rates of unplanned surgery compared with those residing in the highest privilege (Q1; 55.4% vs. 39.4%; referent: Q5; adjusted odds ratio [OR], 1.23, 95%CI 1.16-1.31; P<0.001). For each access-sensitive surgical condition, patients in the least privileged areas were more likely to experience higher rates of inpatient mortality (Q1; 3.1% vs. 2.1%; referent: Q5; adjusted OR, 1.41, 95%CI 1.24-1.60; P<0.001), perioperative complications (Q1; 30.4% vs. Q5; 23.8%; referent: Q5; adjusted OR, 1.24, 95%CI 1.18-1.31; P<0.001) and extended hospital stays (Q1; 26.3% vs. 20.1%; referent: Q5; adjusted OR, 1.16, 95%CI 1.09-1.22; P<0.001)., Conclusions and Relevance: Privilege was associated with rates of unplanned surgery and adverse clinical outcomes. This indicates the role privilege as a key SDOH that influences patient access to and quality of surgical care., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Objective: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT)., Background: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers., Methods: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT., Results: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers., Conclusions: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We sought to develop and validate a preoperative model to predict survival after recurrence (SAR) in hepatocellular carcinoma (HCC)., Background: Although HCC is characterized by recurrence as high as 60%, models to predict outcomes after recurrence remain relatively unexplored., Methods: Patients who developed recurrent HCC between 2000 and 2020 were identified from an international multi-institutional database. Clinicopathologic data on primary disease and laboratory and radiologic imaging data on recurrent disease were collected. Multivariable Cox regression analysis and internal bootstrap validation (5000 repetitions) were used to develop and validate the SARScore. Optimal Survival Tree analysis was used to characterize SAR among patients treated with various treatment modalities., Results: Among 497 patients who developed recurrent HCC, median SAR was 41.2 months (95% CI 38.1-52.0). The presence of cirrhosis, number of primary tumors, primary macrovascular invasion, primary R1 resection margin, AFP>400 ng/mL on the diagnosis of recurrent disease, radiologic extrahepatic recurrence, radiologic size and number of recurrent lesions, radiologic recurrent bilobar disease, and early recurrence (≤24 months) were included in the model. The SARScore successfully stratified 1-, 3- and 5-year SAR and demonstrated strong discriminatory ability (3-year AUC: 0.75, 95% CI 0.70-0.79). While a subset of patients benefitted from resection/ablation, Optimal Survival Tree analysis revealed that patients with high SARScore disease had the worst outcomes (5-year AUC; training: 0.79 vs. testing: 0.71). The SARScore model was made available online for ease of use and clinical applicability ( https://yutaka-endo.shinyapps.io/SARScore/ )., Conclusion: The SARScore demonstrated strong discriminatory ability and may be a clinically useful tool to help stratify risk and guide treatment for patients with recurrent HCC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To define how dynamic changes in pre- versus post-operative serum aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels may impact postoperative morbidity after curative-intent resection of hepatocellular carcinoma (HCC)., Background: Hepatic ischemia/reperfusion can occur at the time of liver resection and may be associated with adverse outcomes following liver resection., Methods: Patients who underwent curative resection for HCC between 2010-2020 were identified from an international multi-institutional database. Changes in AST and ALT (CAA) on postoperative day (POD) 3 versus preoperative values () were calculated using the formula: based on a fusion index via Euclidean norm, which was examined relative to the comprehensive complication index (CCI). The impact of CAA on CCI was assessed by the restricted cubic spline regression and Random Forest analyses., Results: A total of 759 patients were included in the analytic cohort. Median CAA was 1.7 (range, 0.9 to 3.25); 431 (56.8%) patients had a CAA<2, 215 (28.3%) patients with CAA 2-5, and 113 (14.9%) patients had CAA ≥5. The incidence of post-operative complications was 65.0% (n=493) with a median CCI of 20.9 (IQR, 20.9-33.5). Spline regression analysis demonstrated a non-linear incremental association between CAA and CCI. The optimal cutoff value of CAA=5 was identified by the recursive partitioning technique. After adjusting for other competing risk factors, CAA≥5 remained strongly associated with risk of post-operative complications (Ref. CAA<5, OR 1.63, 95%CI 1.05-2.55, P=0.03). In fact, the use of CAA to predict post-operative complications was very good in both the derivative (AUC 0.88) and external (ACU 0.86) cohorts (n=1137)., Conclusions: CAA was an independent predictor of CCI after liver resection for HCC. Use of routine labs such as AST and ALT can help identify patients at highest risk of post-operative complications following HCC resection., Competing Interests: Conflicts of interest: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We sought to define the impact of community privilege on variations in travel patterns and access to care at high-volume hospitals for complex surgical procedures., Background: With increased emphasis on centralization of high-risk surgery, social determinants of health play a critical role in preventing equitable access to care. Privilege is a right, benefit, advantage, or opportunity that positively impacts all social determinants of health., Methods: The California Office of State-wide Health Planning Database identified patients who underwent esophagectomy (ES), pneumonectomy (PN), pancreatectomy (PA), or proctectomy (PR) for a malignant diagnosis between 2012 and 2016 and was merged using ZIP codes with the Index of Concentration of Extremes, a validated metric of both spatial polarization and privilege obtained from the American Community Survey. Clustered multivariable regression was performed to assess the probability of undergoing care at a high-volume center, bypassing the nearest and high-volume center, and total real driving time and travel distance., Results: Among 25,070 patients who underwent a complex oncologic operation (ES: n=1216, 4.9%; PN: n=13,247, 52.8%; PD: n=3559, 14.2%; PR: n=7048, 28.1%), 5019 (20.0%) individuals resided in areas with the highest privilege (i.e., White, high-income homogeneity), whereas 4994 (19.9%) individuals resided in areas of the lowest privilege (i.e., Black, low-income homogeneity). Median travel distance was 33.1 miles (interquartile range 14.4-72.2). Roughly, three-quarters of patients (overall: 74.8%, ES: 35.0%; PN: 74.3%; PD: 75.2%; PR: 82.2%) sought surgical care at a high-volume center. On multivariable regression, patients residing in the least advantaged communities were less likely to undergo surgery at a high-volume hospital (overall: odds ratio 0.65, 95% CI 0.52-0.81). Of note, individuals in the least privileged areas had longer travel distances (28.5 miles, 95% CI 21.2-35.8) to reach the destination facility, as well as over 70% greater odds of bypassing a high-volume hospital to undergo surgical care at a low-volume center (odds ratio 1.74, 95% CI 1.29-2.34) versus individuals living in the highest privileged areas., Conclusions and Relevance: Privilege had a marked effect on access to complex oncologic surgical care at high-volume centers. These data highlight the need to focus on privilege as a key social determinant of health that influences patient access to and utilization of health care resources., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: This forum summarizes the proceedings of the joint European Surgical Association (ESA)/American Surgical Association (ASA) symposium on Quality and Outcome Assessment for Surgery that took place in Bordeaux, France, as part of the celebrations of the 30th anniversary of the ESA. Three presentations focused on a) the main messages from the Outcome4Medicine Consensus Conference, which took place in Zurich, Switzerland, in June 2022, b) the patient perspective, and c) benchmarking were hold by ESA members and discussed by ASA members in a symposium attended by members of both associations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs)., Background: The clinical implications of mut BRAF status in CRLMs are largely unknown., Methods: Patients undergoing resection for mut BRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management., Results: A total of 240 patients harboring BRAF -mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P =0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P =0.01) and similar OS (30 vs 40 mo, P =0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis., Conclusions: Although surgery may be futile in patients with BRAF -mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We sought to characterize the association between prolonged county-level poverty with postoperative outcomes., Background: The impact of long-standing poverty on surgical outcomes remains ill-defined., Methods: Patients who underwent lung resection, colectomy, coronary artery bypass graft, or lower extremity joint replacement were identified from Medicare Standard Analytical Files Database (2015-2017) and merged with data from the American Community Survey and the United States Department of Agriculture. Patients were categorized according to the duration of high poverty status from 1980 to 2015 [ie, never high poverty (NHP), persistent poverty (PP)]. Logistic regression was used to characterize the association between the duration of poverty and postoperative outcomes. Principal component and generalized structural equation modeling were used to assess the effect of mediators in the achievement of Textbook Outcomes (TO)., Results: Overall, 335,595 patients underwent lung resection (10.1%), colectomy (29.4%), coronary artery bypass graft (36.4%), or lower extremity joint replacement (24.2%). While 80.3% of patients lived in NHP, 4.4% resided in PP counties. Compared with NHP, patients residing in PP were at increased risk of serious postoperative complications [odds ratio (OR)=1.10, 95% CI: 1.05-1.15], 30-day readmission (OR=1.09, 95% CI: 1.01-1.16), 30-day mortality (OR=1.08, 95% CI: 1.00-1.17), and higher expenditures (mean difference, $1010.0, 95% CI: 643.7-1376.4) (all P <0.05). Notably, PP was associated with lower odds of achieving TO (OR=0.93, 95% CI: 0.90-0.97, P <0.001); 65% of this effect was mediated by other social determinant factors. Minority patients were less likely to achieve TO (OR=0.81, 95% CI: 0.79-0.84, P <0.001), and the disparity persisted across all poverty categories., Conclusions: County-level poverty duration was associated with adverse postoperative outcomes and higher expenditures. These effects were mediated by various socioeconomic factors and were most pronounced among minority patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We sought to evaluate the impact of liver transplantation (LT) programs on the prognosis of hepatocellular carcinoma (HCC) patients who underwent liver resection (LR) and noncurative intent treatment., Background: LT programs have an array of resources and services that would positively affect the prognosis of patients with HCC., Methods: Patients who underwent LT, LR, radiotherapy (RT), or chemotherapy (CTx) for HCC between 2004 and 2018 were included in the National Cancer Database. Institutions with LT programs were defined as those that performed 1 or more LT for at least 5 years. Centers were stratified by hospital volume. The impact of LT programs was assessed after propensity score matching to achieve covariate balance., Results: A total of 71,735 patients were identified, of which 7997 received LT (11.1%), 12,683 LR (17.7%), 15,675 RT (21.9%), and 35,380 CTx (49.3%). Among a total of 1267 distinct institutions, 94 (7.4%) were categorized as LT programs. Designation as an LT program was also associated with a high volume of LR and noncurative intent treatment (both P <0.001). After propensity score matching, LT programs were associated with better survival among LR and noncurative intent treatment patients. Although hospital volume was also associated with improved prognosis, LT programs were associated with additional survival benefits in noncurative intent treatment. On the other hand, no such benefit was noted in patients who underwent LR., Conclusions: The presence of an LT program was associated with a higher volume of LR and noncurative intent treatment. Furthermore, designation as an LT program had a "halo effect" on the prognosis of patients undergoing RT/CTx that went beyond the procedure-volume effect., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method., Background: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking., Methods: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS., Results: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin., Conclusions: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Determining the impact of county-level upward economic mobility on stage at diagnosis and receipt of treatment among Medicare beneficiaries with pancreatic adenocarcinoma., Summary Background Data: The extent to which economic mobility contributes to socioeconomic disparities in health outcomes remains largely unknown., Methods: Pancreatic adenocarcinoma patients diagnosed in 2004-2015 were identified from the SEER-Medicare linked database. Information on countylevel upward economic mobility was obtained from the Opportunity Atlas. Its impact on early-stage diagnosis (stage I or II), as well as receipt of chemotherapy or surgery was analyzed, stratified by patient race/ethnicity., Results: Among 25,233 patients with pancreatic adenocarcinoma, 37.1% (n = 9349) were diagnosed at an early stage; only 16.7% (n = 4218) underwent resection, whereas 31.7% (n = 7996) received chemotherapy. In turn, 10,073 (39.9%) patients received any treatment. Individuals from counties with high upward economic mobility were more likely to be diagnosed at an earlier stage (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07-1.25), as well as to receive surgery (OR 1.58, 95% CI 1.41-1.77) or chemotherapy (OR 1.51, 95% CI 1.39-1.63). White patients and patients who identified as neither White or Black had increased odds of being diagnosed at an early stage (OR 1.12, 95% CI 1.02-1.22 and OR 1.35, 95% CI 1.02-1.80, respectively) and of receiving treatment (OR 1.73, 95% CI 1.59-1.88 and OR 1.49, 95% CI 1.13-1.98, respectively) when they resided in a county of high vs low upward economic mobility. The impact of economic mobility on stage at diagnosis and receipt of treatment was much less pronounced among Black patients (high vs low, OR 1.28, 95% CI 0.96-1.71 and OR 1.30, 95% CI 0.99-1.72, respectively)., Conclusions: Pancreatic adenocarcinoma patients from higher upward mobility areas were more likely to be diagnosed at an earlier stage, as well as to receive surgery or chemotherapy. The impact of county-level upward mobility was less pronounced among Black patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Objectives: To identify the role and mechanism of a male specific gene, SRY, in I/R-induced hepatic injury., Background: Males are more vulnerable to I/R injury than females. However, the mechanism of these sex-based differences remains poorly defined., Methods: Clinicopathologic data of patients who underwent hepatic resection were identified from an international multi-institutional database. Liver specific SRY TG mice were generated, and subjected to I/R insult with their littermate WT controls in vivo. In vitro experiments were performed by treating primary hepatocytes from TG and WT mice with hypoxia/reoxygen-ation stimulation., Results: Clinical data showed that postoperative aminotransferase level, incidence of overall morbidity and liver failure were markedly higher among 1267 male versus 508 female patients who underwent hepatic resection. SRY was dramatically upregulated during hepatic I/R injury. Overexpression of SRY in male TG mice and ectopic expression of SRY in female TG mice exacerbated liver I/R injury compared with WTs as manifested by increased inflammatory reaction, oxidative stress and cell death in vivo and in vitro. Mechanistically, SRY interacts with Glycogen synthase kinase-3β (GSK-3β) and β-catenin, and promotes phosphorylation and degradation of β-catenin, leading to suppression of the downstream FOXOs, and activation of NF-κBand TLR4 signaling. Furthermore, activation of β-catenin almost completely reversed the SRYoverexpression-mediated exacerbation of hepatic I/R damage., Conclusions: SRY is a novel hepatic I/R mediator that promotes hepatic inflammatory reaction, oxidative stress and cell necrosis via inhibiting Wnt/β-catenin signaling, which accounts for the sex-based disparity in hepatic I/R injuries., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To define the association between hospital occupancy rate and postoperative outcomes among patients undergoing hepatopancreatic (HP) resection., Summary Background Data: Previous studies have sought to identify hospital-level characteristics associated with optimal surgical outcomes and decreased expenditures. The present study utilized a novel hospital quality metric coined "occupancy rate" based on publicly available data to assess differences in postoperative outcomes among Medicare beneficiaries undergoing HP procedures., Methods: Medicare beneficiaries who underwent an elective HP surgery between 2013 and 2017 were identified. Occupancy rate was calculated and hospitals were categorized into quartiles. Multivariable logistic regression was utilized to assess the association between occupancy rate and clinical outcomes., Results: Among 33,866 patients, the majority underwent a pancreatic resection (58.5%; n = 19,827), were male (88.4%; n = 7,488), or white (88.4%; n = 29,950); median age was 72 years [interquartile range (IQR): 68-77] and median Charleston Comorbidity Index was 3 (IQR 2-8). Hospitals were categorized into quartiles based on hospital occupancy rate (cutoffs: 48.1%, 59.4%, 68.2%). Most patients underwent an HP operation at a hospital with an above average occupancy rate (n = 20,865, 61.6%), whereas only a small subset of patients had an HP procedure at a low occupancy rate hospital (n = 1,218, 3.6%). On multivariable analysis, low hospital occupancy rate was associated with increased odds of a complication [(OR) 1.35, 95% confidence interval (CI) 1.18-1.55) and 30-day mortality (OR 1.58, 95% CI 1.27-1.97). Even among only high-volume HP hospitals, patients operated on at hospitals that had a low occupancy rate were at markedly higher risk of complications (OR 1.42, 95% CI 1.03-1.97), as well as 30 day morality (OR 2.20, 95% CI 1.27-3.83)., Conclusions: Among Medicare beneficiaries undergoing an elective HP resection, more than 1 in 4 hospitals performing HP surgeries utilized less than half of their beds on average. There was a monotonic relationship between hospital occupancy rate and the odds ofexperiencing a complication, as well as 30-day mortality, independent of other hospital level characteristics including procedural volume., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Physicians are increasingly recommending neoadjuvant therapy (NT) before surgery for pancreatic ductal adenocarcinoma (PDAC). However, patient preferences for and opinions regarding NT are poorly understood., Methods: Survivors and caregivers from a national PDAC patient advocacy organization completed an online survey assessing preferences for NT versus surgery first (SF) and factors influencing their decision making., Results: Among 54 participants, 74.1% had a personal history of PDAC. While most patients preferred SF for resectable disease, NT was the preferred treatment approach for borderline resectable, locally advanced, and resectable cancers with high carbohydrate antigen 19-9. The most important factor influencing patient decision making regarding NT was its impact on overall survival while the least important was published national guidelines. The most preferred rationale for NT was ability to downstage to surgical resection and early treatment of micrometastatic disease., Conclusions: Among a national cohort of PDAC survivors and caregivers, the majority preferred SF for resectable PDAC, whereas NT was preferred when the resectability of a tumor was in question. The impact of NT on quantity and quality of life, as well as the likelihood of achieving surgical resection, was most highly valued by participants., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system., Background: Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial., Methods: Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification., Results: The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts., Conclusion: A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: There is a paucity of literature evaluating new-onset diabetes mellitus (NODM) after resection of pancreatic cystic lesions (PCLs). We sought to characterize the incidence and risk factors associated with NODM after partial pancreatectomy for PCLs., Methods: We utilized the IBM MarketScan Database (2012-2018) to identify all nondiabetic adults who underwent partial pancreatectomy for PCLs. Patients with any other pancreatic disease were excluded. We performed Kaplan-Meier analysis and multivariable Cox proportional hazards regression to define the incidence and risk factors of postoperative NODM., Results: Among 311 patients, the overall risk (95% confidence interval) of NODM was 9.1% (6.3-12.9%), 15.1% (11.3-20.2%), and 20.2% (15.3-26.4%) at 6, 12 and 24 months, respectively. Multivariable analysis (adjusted hazard ratio; 95% confidence interval) revealed that older age (1.97; 1.04-3.72; 55-64 vs 18-54 years), obesity (2.63; 1.35-5.12), hypertension (1.79; 1.01-3.17), and cardiovascular disease (2.54; 1.02-6.28) were independent predictors of NODM. Rates of NODM were similar after distal pancreatectomy versus pancreaticoduodenectomy., Conclusions: Within 2 years, 1 in 5 patients without any other pancreatic disease will develop NODM after partial pancreatectomy for PCLs. Those with advanced age, metabolic syndrome features, and/or cardiovascular disease may benefit from preoperative counseling and intensive postoperative monitoring, education, and treatment for diabetes mellitus., Competing Interests: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. No other potential conflicts of interest exist for any author in relationship to this publication., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We sought to characterize the association between patient county-level vulnerability with postoperative outcomes., Summary Background Data: Although the impact of demographic-, clinical- and hospital-level factors on outcomes following surgery have been examined, little is known about the effect of a patient's community of residence on surgical outcomes., Methods: Individuals who underwent colon resection, coronary artery bypass graft (CABG), lung resection, or lower extremity joint replacement (LEJR) were identified in the 2016 to 2017 Medicare database, which was merged with Center for Disease Control social vulnerability index (SVI) dataset at the beneficiary level of residence. Logistic regression models were utilized to estimate the probability of postoperative complications, mortality, readmission, and expenditures., Results: Among 299,583 Medicare beneficiary beneficiaries who underwent a colectomy (n = 88,778, 29.6%), CABG (n = 109,564, 36.6%), lung resection (n = 30,401, 10.1%), or LEJR (n = 70,840, 23.6%).Mean SVI score was 50.2 (standard deviation: (25.2); minority patients were more likely to reside in highly vulnerable communities (low SVI: n = 3531, 5.8% vs high SVI: n = 7895, 13.3%; P < 0.001). After controlling for competing risk factors, the risk-adjusted probability of a serious complication among patients from a high versus low SVI county was 10% to 20% higher following colectomy [odds ratio (OR) 1.1 95% confidence intervals (CI) 1.1-1.2] or CABG (OR 1.2 95%CI 1.1-1.3), yet there no association of SVI with risk of serious complications following lung resection (OR 1.2 95%CI 1.0-1.3) or LEJR (OR 1.0 95%CI 0.93-1.2). The risk-adjusted probability of 30-day mortality was incrementally higher among patients from high SVI counties following colectomy (OR 1.1 95%CI 1.1-1.3), CABG (OR 1.4, 95%CI 1.2-1.5), and lung resection (OR 1.4 (95%CI 1.1-1.8), yet not LEJR (OR 0.95 95%CI 0.72-1.2). Black/minority patients undergoing a colectomy, CABG, or lung resection who lived in highly socially vulnerable counties had an estimate 28% to 68% increased odds of a serious complication and a 58% to 60% increased odds of 30-day mortality compared with a Black/minority patient from a low socially vulnerable county, as well as a markedly higher risk than White patients (all P > 0.05)., Conclusions: Patients residing in vulnerable communities characterized by a high SVI generally had worse postoperative outcomes. The impact of social vulnerability was most pronounced among Black/minority patients, rather than White individuals. Efforts to ensure equitable surgical outcomes need to focus on both patient-level, as well as community-specific factors., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To determine the prognostic implication of the number and station of LNM, and the minimal number of LNs needed for evaluation to accurately stage patients with intrahepatic cholangiocarcinoma (ICC)., Background: Impact of the number and station of LNM on long-term survival, and the minimal number of LNs needed for accurate staging of ICC patients remain poorly defined., Methods: Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide. External validation was performed using the SEER registry. Primary outcomes included overall (OS), disease-specific, and recurrence-free survival., Results: Among 603 patients who underwent curative-intent resection, median and 5-year OS were 30.6 months and 30.4%. Patients with 1 or 2 LNM had comparable worse OS versus patients with no nodal disease (median OS, 1 LNM 18.0, 2 LNM 20.0 vs no LNM 45.0 months, both P < 0.001), yet better OS versus patients with 3 or more LNM (median OS, 1-2 LNM 19.8 vs ≥3 LNM 16.0 months, P < 0.01). On multivariable analysis, a proposed new nodal staging with N1 (1-2 LNM) (Ref. N0, HR 2.40, P < 0.001) and N2 (≥3 LNM) [Ref. N0, hazard ratio (HR) 3.85, P < 0.001] categories were independently associated with incrementally worse OS. Patients with no nodal metastasis, 1-2 LNM and ≥3 LNM also had an increasingly worse disease-specific survival, and recurrence-free survival (both P < 0.05). Total number of LNs examined ≥6 had the greatest discriminatory power relative to OS among patients with 1-2 LNM, and patients with ≥3 LNM in both the multi-institutional (area under the curve 0.780) and SEER database (area under the curve 0.820) (n = 1036). Among patients who underwent an adequate regional lymphadenectomy (total number of LNs examined ≥6), LNM beyond the HDL was associated with worse OS versus LNM within the HDL only (median OS, 14.0 vs 24.0 months, HR 2.41, P = 0.003)., Conclusion: Standard lymphadenectomy of at least 6 LNs is strongly recommended and should include examination beyond station 12 to have the greatest chance of accurate staging. The proposed new nodal staging of N0, N1, and N2 should be considered to stratify outcomes among patients after curative-intent resection of ICC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The objective of the current study was to characterize the role of patient social vulnerability relative to hospital racial/ethnic integration on postoperative outcomes among patients undergoing pancreatectomy., Background: The interplay between patient- and community-level factors on outcomes after complex surgery has not been well-examined., Methods: Medicare beneficiaries who underwent a pancreatectomy between 2013 and 2017 were identified utilizing 100% Medicare inpatient files. P-SVI was determined using the Centers for Disease Control and Prevention criteria, whereas H-REI was estimated using Shannon Diversity Index. Impact of P-SVI and H-REI on "TO" [ie, no surgical complication/extended length-of-stay (LOS)/90-day mortality/90-day readmission] was assessed., Results: Among 24,500 beneficiaries who underwent pancreatectomy, 12,890 (52.6%) were male and median age was 72 years (Interquartile range: 68-77); 10,619 (43.3%) patients achieved a TO. The most common adverse postoperative outcome was 90-day readmission (n = 8,066, 32.9%), whereas the least common was 90-day mortality (n = 2282, 9.3%). Complications and extended LOS occurred in 30.4% (n = 7450) and 23.3% (n = 5699) of the cohort, respectively. Patients from an above average SVI county who underwent surgery at a below average REI hospital had 18% lower odds [95% confidence interval (CI): 0.74-0.95] of achieving a TO compared with patients from a below average SVI county who underwent surgery at a hospital with above average REI. Of note, patients from the highest SVI areas who underwent pancreatectomy at hospitals with the lowest REI had 30% lower odds (95% CI: 0.54-0.91) of achieving a TO compared with patients from very low SVI areas who underwent surgery at a hospital with high REI. Further comparisons of these 2 patient groups indicated 76% increased odds of 90-day mortality (95% CI: 1.10-2.82) and 50% increased odds of an extended LOS (95% CI: 1.07-2.11)., Conclusion: Patients with high social vulnerability who underwent pancreatectomy in hospitals located in communities with low racial/ethnic integration had the lowest chance to achieve an "optimal" TO. A focus on both patient- and community-level factors is needed to ensure optimal and equitable patient outcomes., Competing Interests: The authors report no conflict of interests., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine whether there are racial and ethnic differences in postoperative complications after nonobstetric surgery during pregnancy in the United States., Methods: We conducted a secondary analysis of the prospective ACS NSQIP (American College of Surgeons National Surgical Quality Improvement) program from 2005 to 2012. We assessed pregnant women 18-50 years without prior surgery in the preceding 30 days who underwent a nonobstetric surgery. Race and ethnicity were categorized as non-Hispanic Black, Hispanic, and non-Hispanic White (reference). The primary outcome was a composite of 30-day major postoperative complications inclusive of cardiovascular, pulmonary, and infectious complications, reoperation, unplanned readmission, blood transfusion, and death. We used modified Poisson regression to estimate the relative risk of complications., Results: Among 3,093 pregnant women, 18% were non-Hispanic Black, 20% Hispanic, and 62% non-Hispanic White. The most common surgeries were appendectomy (36%) and cholecystectomy (19%). Black women (18%) were more likely to be assigned American Society of Anesthesiologists (ASA) physical status class III or higher than their White (12%) or Hispanic (9%) peers. Non-Hispanic Black pregnant women had a higher risk of 30-day major postoperative complications compared with their White peers (9% vs 6%; adjusted relative risk [aRR] 1.41, 95% CI 1.11-1.99). This difference persisted when limiting the analysis to apparently healthy women (ASA class I or II) (7% vs 4%; aRR 1.64, 95% CI 1.08-2.50), those who underwent appendectomy (10% vs 3%; aRR 2.36, 95% CI 1.13-4.96), and when appendectomy and cholecystectomy were performed by laparoscopy (7% vs 3%; aRR 2.62, 95% CI 1.22-5.58). Hispanic pregnant women were not at an increased risk of complications compared with non-Hispanic pregnant White women., Conclusions: Pregnant non-Hispanic Black women were at higher risk of major postoperative complications after nonobstetric surgery compared with their White counterparts., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities., Background: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled. The Coronavirus Global Surgical Collaborative sought to formulate, through rigorous scientific methodology, consensus-based recommendations in collaboration with a multidisciplinary group of international experts and policymakers., Methods: Recommendations were developed following a Delphi process. Domain topics were formulated and subsequently subdivided into questions pertinent to different aspects of surgical care in the COVID-19 crisis. Forty-four experts from 15 countries across 4 continents drafted statements based on the specific questions. Anonymous Delphi voting on the statements was performed in 2 rounds, as well as in a telepresence meeting., Results: One hundred statements were formulated across 10 domains. The statements addressed terminology, impact on procedural services, patient/staff safety, managing a backlog of surgeries, methods to restart and sustain surgical services, education, and research. Eighty-three of the statements were approved during the first round of Delphi voting, and 11 during the second round. A final telepresence meeting and discussion yielded acceptance of 5 other statements., Conclusions: The Delphi process resulted in 99 recommendations. These consensus statements provide expert guidance, based on scientific methodology, for the safe resumption of surgical activities during the COVID-19 pandemic., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the prognostic role of metastatic lymph node (LN) number and the minimal number of LNs for optimal staging of patients with pancreatic neuroendocrine tumors (pNETs)., Background: Prognosis relative to number of LN metastasis (LNM), and minimal number of LNs needed to evaluate for accurate staging, have been poorly defined for pNETs., Methods: Number of LNM and total number of LN evaluated (TNLE) were assessed relative to recurrence-free survival (RFS) and overall survival (OS) in a multi-institutional database. External validation was performed using Surveillance, Epidemiology and End Results (SEER) registry., Results: Among 854 patients who underwent resection, 233 (27.3%) had at least 1 LNM. Patients with 1, 2, or 3 LNM had a comparable worse RFS versus patients with no nodal metastasis (5-year RFS, 1 LNM 65.6%, 2 LNM 68.2%, 3 LNM 63.2% vs 0 LNM 82.6%; all P < 0.001). In contrast, patients with ≥4 LNM (proposed N2) had a worse RFS versus patients who either had 1 to 3 LNM (proposed N1) or node-negative disease (5-year RFS, ≥4 LNM 43.5% vs 1-3 LNM 66.3%, 0 LNM 82.6%; all P < 0.05) [C-statistics area under the curve (AUC) 0.650]. TNLE ≥8 had the highest discriminatory power relative to RFS (AUC 0.713) and OS (AUC 0.726) among patients who had 1 to 3 LNM, and patients who had ≥4 LNM in the multi-institutional and SEER database (n = 2764)., Conclusions: Regional lymphadenectomy of at least 8 lymph nodes was necessary to stage patients accurately. The proposed nodal staging of N0, N1, and N2 optimally staged patients., Competing Interests: The authors report no conflicts of interest, (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status., Background: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors., Methods: Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status., Results: 277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38)., Conclusions: This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this study was to characterize the tumor microenvironment of patients with gastroenteropancreatic neuroendocrine tumors relative to progression-free survival (PFS)., Methods: Immune profiling for CD3, CD8, programmed death-1/programmed death-ligand 1, and indoleamine 2,3-dioxygenase expression in 2 cohorts of gastroenteropancreatic neuroendocrine tumors: patients with short PFS (<4 years, n = 12) versus long PFS (≥4 years, n = 14) after surgery. Immune infiltrates in the tumor and interface were quantified. Programmed death-ligand 1 expression was determined within the tumor, stroma, and interface., Results: Patients with shorter PFS had larger tumors (P = 0.02), mostly in the pancreas (P = 0.04). We observed a higher mean expression of CD3+, CD8+, programmed death-1+ cells, and indoleamine 2,3-dioxygenase at the interface compared with the tumor: log 10 mean differences 0.56 (95% confidence interval [CI], 0.43-0.68; P < 0.0001), 0.45 (95% CI, 0.32-0.59; P = 0.0002), 0.50 (95% CI, 0.40-0.61; P < 0.0001), and 0.24 (95% CI, 0.03-0.46; P = 0.046), respectively. Patients with longer PFS had higher intratumoral CD3+ T cells, log 10 mean difference 0.38 (95% CI, 0.19-0.57; P = 0.004). Programmed death-ligand 1 expression tended to be higher among patients with shortened PFS (odds ratio, 2.00; 95% CI, 0.68-5.91)., Conclusions: Higher intratumoral CD3+ T-cell infiltrate was associated with longer PFS after resection., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to define trends in the geographic distribution of surgical services in the United States to assess possible geographic barriers and disparities in access to surgical care., Summary Background Data: Despite the increased need and utilization of surgical procedures, Americans often face challenges in gaining access to health care that may be exacerbated by the closure and consolidation of hospitals. Although access to surgical care has been evaluated relative to the role of insurance, race, and health literacy/education, the relationship of geography and travel distance to access has not been well studied., Methods: The 2005 and 2015 American Hospital Association annual survey was used to identify hospitals with surgical capacity; the data were merged with 2010 Census Bureau data to identify the distribution of the US population relative to hospital location, and geospatial analysis tools were used to examine a service area of real driving time surrounding each hospital., Results: Although the number of hospitals that provided surgical services slightly decreased over the time periods examined (2005, n = 3791; 2015, n = 3391; P<0.001), the number of major surgery hospitals increased from 2005 (n = 539) to 2015 (n = 749) (P<0.001). The geographic location of hospitals that provided surgical services changed over time. Specifically, although in 2005 852 hospitals were located in a rural area, that number had decreased to 679 by 2015 (P<0.001). Of particular note, from 2005 to 2015 there was an 82% increase in the number of people who lived further than 60 minutes from any hospital (P<0.001). However, the number of people who lived further than 60 minutes from a major surgery hospital decreased (P<0.001)., Conclusions: Although the number of rural hospitals decreased over the last decade, the number of large, academic medical centers has increased; in turn, there has been an almost doubling in the number of people who live outside a 60-minute driving range to a hospital capable of performing surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe., Summary/background: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients., Methods: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers., Results: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries., Conclusions: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Objective: The objective of the current study was to define surgical outcomes after resection of multinodular hepatocellular carcinoma (HCC) beyond the Milan criteria, and develop a prediction tool to identify which patients likely benefit the most from resection., Background: Liver resection for multinodular HCC, especially beyond the Milan criteria, remains controversial. Rigorous selection of the best candidates for resection is essential to achieve optimal outcomes after liver resection of advanced tumors., Methods: Patients who underwent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Patients were categorized according to Milan criteria status. Pre- and postoperative overall survival (OS) prediction models that included HCC tumor burden score (TBS) among patients with multinodular HCC beyond Milan criteria were developed and validated., Results: Among 1037 patients who underwent resection for HCC, 164 (15.8%) had multinodular HCC beyond the Milan criteria. Among patients with multinodular HCC, 25 (15.2%) patients experienced a serious complication and 90-day mortality was 3.7% (n = 6). Five-year OS after resection of multinodular HCC beyond Milan criteria was 52.8%. A preoperative TBS-based model (5-year OS: low-risk, 73.7% vs intermediate-risk, 45.1% vs high-risk, 13.1%), and postoperative TBS-based model (5-year OS: low-risk, 80.1% vs intermediate-risk, 37.2% vs high-risk, not reached) categorized patients into distinct prognostic groups relative to long-term prognosis (both P < 0.001). Pre- and postoperative models could accurately stratify OS in an external validation cohort (5-year OS; low vs medium vs high risk; pre: 66.3% vs 25.2% vs not reached, P = 0.012; post: 61.4% vs 42.5% vs not reached, P = 0.045) Predictive accuracy of the pre- and postoperative models was good in the training (c-index; pre: 0.68; post: 0.71), internal validation (n = 2000 resamples) (c-index, pre: 0.70; post: 0.72) and external validation (c-index, pre: 0.67; post 0.68) datasets. TBS alone could stratify patients relative to 5-year OS after resection of multinodular HCC beyond Milan criteria (c-index: 0.65; 5-year OS; low TBS: 70.2% vs medium TBS: 54.7% vs high TBS: 16.7%; P < 0.001). The vast majority of patients with low and intermediate TBS were deemed low or medium risk based on both the preoperative (98.4%) and postoperative risk scores (95.3%)., Conclusion: Prognosis of patients with multinodular HCC was largely dependent on overall tumor burden. Liver resection should be considered among patients with multinodular HCC beyond the Milan criteria who have a low- or intermediate-TBS.

Objective: The aim of this study was to define the prevalence of preexisting mental illness, as well as characterize the impact of a preexisting mental illness diagnosis on postoperative outcomes., Summary Background Data: Preoperative surgical evaluation and risk stratification have traditionally centered on optimizing physical health. The influence of mental health on postoperative surgical outcomes has not been investigated., Methods: Medicare beneficiaries who underwent elective colectomy, coronary artery bypass grafting, abdominal aortic aneurysm repair, abdominal aortic aneurysm repair, total hip arthroplasty, total knee arthroplasty, and lung resection were identified. Patients were classified as having mental illness using International Classification of Diseases, 9th and 10th Revisions Procedures codes (ICD9/10CM) codes for anxiety, depression, bipolar disorder, schizophrenia, or other psychotic disorder., Results: Among 1,889,032 Medicare beneficiaries who met inclusion criteria 560,744 (n = 29.7%) individuals had an antecedent diagnosis of mental illness. The majority had anxiety and/or depression (91.8%), whereas a smaller subset (8.2%) had a severe mental illness diagnosis. Patients who did and did not have mental illness were comparable relative to age and comorbidities. Patients with preoperative mental illness had a higher chance of surgical complications [anxiety/depression odds ratio (OR) 1.44, 95% confidence interval (CI) 1.42-1.46, severe mental illness OR 1.71, 95%CI 1.66-1.77] and an extended length of stay (anxiety/depression OR 1.45, 95% CI 1.44-1.46, severe mental illness OR 2.34, 95% CI 2.28-2.39). History of anxiety/depression (OR 1.87, 95% CI 1.85-1.90) or severe mental illness (OR 2.86, 95% CI 2.77-2.94) was also associated with higher odds of 30-day readmission. Additionally, individuals with mental illness had a higher prevalence of suicidal ideation within the first year after surgery (no mental illness: 1.88 per 100,000 individuals; anxiety/depression: 51.3 per 100,000 individuals; severe mental illness: 238.9 per 100,000 individuals)., Conclusions: Three in 10 Medicare beneficiaries had a preexisting mental illness diagnosis, which was strongly associated with worse postoperative outcomes, as well as suicide risk. Surgeons need to optimize mental health assessment and services in the preoperative setting to improve outcomes for this vulnerable population., Competing Interests: The authors report no conflicts of interests., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare there are no conflicts of interest.

Competing Interests: The authors report no conflicts of interest.

Objective: To define and test "Textbook Outcome" (TO)-a composite measure for healthcare quality-among Medicare patients undergoing hepatopancreatic resections. Hospital variation in TO and Medicare payments were analyzed., Background: Composite measures of quality may be superior to individual measures for the analysis of hospital performance., Methods: The Medicare Provider Analysis and Review (MEDPAR) Inpatient Files were reviewed to identify Medicare patients who underwent pancreatic and liver procedures between 2013 and 2015. TO was defined as: no postoperative surgical complications, no prolonged length of hospital stay, no readmission ≤ 90 days after discharge, and no postoperative mortality ≤ 90 days after surgery. Medicare payments were compared among patients who achieved TO versus patients who did not. Multivariable logistic regression was used to investigate patient factors associated with TO. A nomogram to predict probability of TO was developed and validated., Results: TO was achieved in 44% (n = 5919) of 13,467 patients undergoing hepatopancreatic surgery. Adjusted TO rates at the hospital level varied from 11.1% to 69.6% for pancreatic procedures and from 16.6% to 78.7% for liver procedures. Prolonged length of hospital stay represented the major obstacle to achieve TO. Average Medicare payments were substantially higher among patients who did not have a TO. Factors associated with TO on multivariable analysis were age, sex, Charlson comorbidity score, previous hospital admissions, procedure type, and surgical approach (all P > 0.05)., Conclusions: Less than one-half of Medicare patients achieved a TO following hepatopancreatic procedures with a wide variation in the rates of TO among hospitals. There was a discrepancy in Medicare payments for patients who achieved a TO versus patients who did not. TO could be useful for the public reporting of patient level hospital performance and hospital variation.

Objectives: The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established., Methods: The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed., Results: Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%., Conclusions: Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.

Objective: The aim of this study was to characterize preoperative super-utilizers and examine the effect of surgery on service utilization among patients undergoing major elective surgery., Summary Background Data: Rising healthcare costs are becoming increasingly burdensome for Medicare. Super-utilizers have been increasingly identified and studied as this subset of patients consume a disproportionate amount of healthcare services compared with the majority of the population., Methods: Patients aged 65 or older who underwent any of the following general elective surgeries: abdominal aortic aneurysm repair (AAA), coronary artery bypass graft (CABG), colectomy, or hip replacement were identified using 100% Medicare Inpatient and Outpatient Standard Analytic Files (SAFs) from years 2012 to 2016. Medicare inpatient and outpatient expenditures the year before surgery, around the time of surgery, and the year after surgery were examined., Results: Among 603,105 Medicare beneficiaries, 32,145 patients (5.3%) were categorized as super-utilizers. Compared with low-utilizers, super-utilizers were more likely to be male (low-utilizer vs super-utilizer: 47.9% vs 54.2%) and African American (4.0% vs 7.2%), whereas 58.8% (n = 208,080) of low-utilizers presented without any comorbidity [Charlson Comorbidity Index (CCI) = 0] and 49.8% (n = 16,007) of super-utilizers presented with a CCI score of ≥3. Total preoperative spending among super-utilizers was approximately $1.7 billion with a median of $3,159 [interquartile range (IQR): $554-$15,181] per beneficiary. Spending among super-utilizers accounted for 39.6% of total spending for all Medicare beneficiaries versus only 8.4% among low-utilizers. Although the median spending per Medicare beneficiary in the year after surgery was higher for super-utilizers compared with low-utilizers [$1,837 (IQR: $341-$11,390) vs $18,223 (IQR: $3,466-$43,356)], super-utilizers accounted for 13.5% of total postoperative spending. The reduction in adjusted average annual Medicare expenditure ranged from >$15,000 per year for patients undergoing CABG to approximately $30,000 per year for patients undergoing a hip replacement., Conclusions: Although super-utilizers accounted for only 5.3% of patients, these patients accounted for 39.6% of total Medicare expenditures in the year before surgery. Among a subset of super-utilizers, surgical intervention was associated with a reduction in annual Medicare expenditure in the year after surgery.

Objective: To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis., Background: CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery., Methods: CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences., Results: According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5)., Conclusions: The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.

Background: Patient blood management (PBM) programs represent a perioperative bundle of care that aim to reduce or eliminate unnecessary transfusions., Objective: To evaluate the impact of a PBM program on transfusion practices and clinical outcomes at a single surgical department at a tertiary care hospital in the United States., Methods: This pre-post, cross-sectional study was performed using data from 17,114 patients undergoing gastrointestinal surgery between 2010 and 2013. Multivariable regression analysis was used to evaluate the impact of implementing a PBM program on transfusion practices and perioperative clinical outcomes., Results: Implementation of the PBM program was associated with a reduction in the proportion of patients receiving packed red blood cell (PRBC) using a liberal trigger hemoglobin concentration (pre-PBM vs post-PBM: trigger ≥8.0 g/dL: 20.2% vs 15.3%, P < 0.001), as well as an increase in the proportion of patients receiving PRBC using a restrictive trigger hemoglobin concentration (trigger <7.0 g/dL: 37.1% vs 46.4%, P < 0.001). The proportion of patients overtransfused to a target hemoglobin concentration of 9.0 g/dL (54.8% vs 43.9%, P < 0.001) or 10.0 g/dL (22.3% vs 15.8%, P < 0.001) also decreased following implementation of the PBM program. On multivariable analysis, implementation of the PBM program was associated with 23% lower odds of receiving PRBC transfusion (odds ratio = 0.77, 95% confidence interval 0.657-0.896, P = 0.001); hospital length-of-stay, postoperative morbidity, and postoperative mortality were unchanged (all P > 0.05)., Conclusions: Implementation of a PBM program was associated with fewer patients receiving PRBC transfusion using a liberal trigger hemoglobin concentration and fewer patients being "overtransfused," without any detectable change in length-of-stay, morbidity or mortality. PBM programs can be safely implemented across hospitals and should be used to improve quality and reduce unnecessary transfusions.

Objective: The aim of the study was to estimate the cost of major complications after liver resection and determine whether high-volume (HV) centers are cost-effective., Methods: From 2002 to 2011, 96,107 cases of liver resection performed in the United States were identified using Nationwide Inpatient Sample. Hospitals were categorized as HV (150+ cases/yr), medium-volume (51-149 cases/yr), and low-volume (LV) (1-50 cases/yr) centers. Multivariable regression analysis identified predictors of cost. Propensity score matching comparing cases with versus without complications and costs of specific complications were estimated. Cost-effectiveness of HV centers was determined by calculating the incremental cost-effectiveness ratio., Results: After propensity score matching, the occurrence of a major complication added $33,855 extra cost, increased mean length of stay by 8.7 [95% confidence interval (CI), 8.4-9] days and increased risk of death by 9.3% (all P < 0.001). The cost of most common complications was wound infection (3.8%, $21,995), renal failure (2.8%, $19,201), respiratory failure (2.7%, $25,169), and hemorrhage (3.3%, $9,180), whereas sepsis (0.8%, $33,009), gastrointestinal bleeding (0.5%, $32,835), fistula (0.2%, $27,079), and foreign body removal (0.1%, $29,404) were most costly, but less frequent. Compared with LV centers, liver resection at HV centers was associated with $5109 (95% CI, 4409-5809, P < 0.001) more cost per case, yet on average 0.54 years (95% CI, 0.23-0.86) longer survival for an incremental cost-effectiveness ratio of $9392., Conclusions: HV centers were cost-effective at performing liver resection compared with LV centers. After liver resection, complications such as surgical site infection, respiratory failure, and renal failure contributed the most to annual cost burden.

Objectives: The role of radiation therapy (RT) in resected pancreatic cancer (PC) remains incompletely defined. We sought to determine clinical variables which predict for local-regional recurrence (LRR) to help select patients for adjuvant RT., Materials and Methods: We identified 73 patients with PC who underwent resection and adjuvant gemcitabine-based chemotherapy alone. We performed detailed radiologic analysis of first patterns of failure. LRR was defined as recurrence of PC within standard postoperative radiation volumes. Univariate analyses (UVA) were conducted using the Kaplan-Meier method and multivariate analyses (MVA) utilized the Cox proportional hazard ratio model. Factors significant on UVA were used for MVA., Results: At median follow-up of 20 months, rates of local-regional recurrence only (LRRO) were 24.7%, LRR as a component of any failure 68.5%, metastatic recurrence (MR) as a component of any failure 65.8%, and overall disease recurrence (OR) 90.5%. On UVA, elevated postoperative CA 19-9 (>90 U/mL), pathologic lymph node positive (pLN+) disease, and higher tumor grade were associated with increased LRR, MR, and OR. On MVA, elevated postoperative CA 19-9 and pLN+ were associated with increased MR and OR. In addition, positive resection margin was associated with increased LRRO on both UVA and MVA., Conclusions: About 25% of patients with PC treated without adjuvant RT develop LRRO as initial failure. The only independent predictor of LRRO was positive margin, while elevated postoperative CA 19-9 and pLN+ were associated with predicting MR and overall survival. These data may help determine which patients benefit from intensification of local therapy with radiation.