Postoperative Outcomes Among Patients Undergoing Cancer Surgery: United States versus International Medical Graduates.

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). SUMMARY BACKGROUND DATA: 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 (EB) 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 and 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 those with a high social vulnerability index (33.3% vs. 32.1%) (all P<0.001). On multivariable analysis after EB, patients treated by an IMG surgeon were less likely to experience adverse postoperative outcomes including 90-day readmission (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.

Practice Patterns and Outcomes Among Surgical Oncology Fellowship Graduates Performing Complex Cancer Surgery in the United States Across Different Career Stages.

BACKGROUND: Practice patterns and potential quality differences among surgical oncology fellowship graduates relative to years of independent practice have not been defined. METHODS: Medicare claims were used to identify patients who underwent esophagectomy, pancreatectomy, hepatectomy, or rectal resection for cancer between 2016 and 2021. Surgical oncology fellowship graduates were identified, and the association between years of independent practice, serious complications, and 90-day mortality was examined. RESULTS: Overall, 11,746 cancer operations (pancreatectomy [61.2%], hepatectomy [19.5%], rectal resection [13.7%], esophagectomy [5.6%]) were performed by 676 surgical oncology fellowship graduates (females: 17.7%). The operations were performed for 4147 patients (35.3%) by early-career surgeons (1-7 years), for 4104 patients (34.9%) by mid-career surgeons (8-14 years), and for 3495 patients (29.8%) by late-career surgeons (>15 years). The patients who had surgery by early-career surgeons were treated more frequently at a Midwestern (24.9% vs. 14.2%) than at a Northeastern institution (20.6% vs. 26.9%) compared with individuals treated by late-career surgeons (p < 0.05). Surgical oncologists had comparable risk-adjusted serious complications and 90-day mortality rates irrespective of career stage (early career [13.0% and 7.2%], mid-career [12.6% and 6.3%], late career [12.8% and 6.5%], respectively; all p > 0.05). Surgeon case-specific volume independently predicted serious complications across all career stages (high vs. low volume: early career [odds ratio {OR}, 0.80; 95% confidence interval {CI}, 0.65-0.98]; mid-career [OR, 0.81; 95% CI, 0.66-0.99]; late career [OR, 0.78; 95% CI, 0.62-0.97]). CONCLUSION: Among surgical oncology fellowship graduates performing complex cancer surgery, rates of serious complications and 90-day mortality were comparable between the early-career and mid/late-career stages. Individual surgeon case-specific volume was strongly associated with postoperative outcomes irrespective of years of independent practice or career stage.

Neoadjuvant Chemotherapy Improves Oncological Outcomes and Long-Term Survival Among Elderly Patients with Locally Advanced Gastric Cancer: A Propensity Score Matched Analysis.

INTRODUCTION: In the USA, approximately half of newly diagnosed patients with GC are 75 years or older. The objective of the current population-based study was to investigate the impact of neoadjuvant chemotherapy (NAC) on the outcomes of elderly patients with locally advanced GC. PATIENTS AND METHODS: Patients aged > 75 years were identified from the National Cancer Database (NCDB). The primary outcome of the study was overall survival (OS). Secondary outcomes included lymph node (LN) harvest, surgical margin status, and 30-day mortality. To minimize the effect of selection bias on the assessed outcome between the two study groups (NAC versus no NAC), propensity score matching (PSM) was performed. RESULTS: After PSM, a total of 1958 patients were included in both groups. NAC utilization increased from 2013 to 2019 (21% versus 42.7%, ptrend < 0.001). On pathologic analysis, patients who received NAC were more likely to have ≥ 16 LNs evaluated (NAC 60.1% versus no NAC 55.5%, p = 0.044) and negative resection margins (NAC 88.6% versus no NAC 83%, p = 0.001). Patients who received NAC were also less likely to experience 30-day mortality following resection (NAC 4.1% versus no NAC 7.1%). Receipt of NAC was associated with improved 1-year (73.9% versus 68.3%), 3-year (48.2% versus 43.5%), and 5-year OS (36.9% versus 30.5%) compared with patients who underwent upfront surgery (p = 0.01). CONCLUSIONS: Receipt of NAC was associated with improved oncological outcomes among elderly patients undergoing resection for locally advanced GC.

The Role of Delirium on Short- and Long-Term Postoperative Outcomes Following Major Gastrointestinal Surgery for Cancer.

INTRODUCTION: The growing burden of an aging population has raised concerns about demands on healthcare systems and resources, particularly in the context of surgical and cancer care. Delirium can affect treatment outcomes and patient recovery. We sought to determine the prevalence of postoperative delirium among patients undergoing digestive tract surgery for malignant indications and to analyze the role of delirium on surgical outcomes. METHODS: Medicare claims data were queried to identify patients diagnosed with esophageal, gastric, hepatobiliary, pancreatic, and colorectal cancers between 2018 and 2021. Postoperative delirium, occurring within 30 days of operation, was identified via International Classification of Diseases, 10th edition codes. Clinical outcomes of interested included "ideal" textbook outcome (TO), characterized as the absence of complications, an extended hospital stay, readmission within 90 days, or mortality within 90 days. Discharge disposition, intensive care unit (ICU) utilization, and expenditures also were examined. RESULTS: Among 115,654 cancer patients (esophageal: n = 1854, 1.6%; gastric: n = 4690, 4.1%; hepatobiliary: n = 6873, 5.9%; pancreatic: n = 8912, 7.7%; colorectal: n = 93,325, 90.7%), 2831 (2.4%) were diagnosed with delirium within 30 days after surgery. On multivariable analysis, patients with delirium were less likely to achieve TO (OR 0.27 [95% CI 0.25-0.30]). In particular, patients who experienced delirium had higher odds of complications (OR 3.00 [2.76-3.25]), prolonged length of stay (OR 3.46 [3.18-3.76]), 90-day readmission (OR 1.96 [1.81-2.12]), and 90-day mortality (OR 2.78 [2.51-3.08]). Furthermore, patients with delirium had higher ICU utilization (OR 2.85 [2.62-3.11]). Upon discharge, patients with delirium had a decreased likelihood of being sent home (OR 0.40 [0.36-0.46]) and instead were more likely to be transferred to a skilled nursing facility (OR 2.17 [1.94-2.44]). Due to increased utilization of hospital resources, patients with delirium incurred in-hospital expenditures that were 55.4% higher (no delirium: $16,284 vs. delirium: $28,742) and 90-day expenditures that were 100.7% higher (no delirium: $2564 vs. delirium: $8226) (both p < 0.001). Notably, 3-year postoperative survival was adversely affected by delirium (no delirium: 55.5% vs. delirium: 37.3%), even after adjusting risk for confounding factors (HR 1.79 [1.70-1.90]; p < 0.001). CONCLUSIONS: Postoperative delirium occurred in one in 50 patients undergoing surgical resection of a digestive tract cancer. Delirium was linked to a reduced likelihood of achieving an optimal postoperative outcome, increased ICU utilization, higher expenditures, and a worse long-term prognosis. Initiatives to prevent delirium are vital to improve postoperative outcomes among cancer surgery patients.

Association of COVID-19 Pandemic with Colorectal Cancer Screening: Impact of Race/Ethnicity and Social Vulnerability.

BACKGROUND: The COVID-19 pandemic disrupted health care delivery, including cancer screening practices. This study sought to determine the impact of the COVID-19 pandemic lockdown on colorectal cancer (CRC) screening relative to social vulnerability. METHODS: Using the Medicare Standard Analytic File, individuals 65 years old or older who were eligible for guideline-concordant CRC screening between 2019 and 2021 were identified. These data were merged with the Center for Disease Control Social Vulnerability Index (SVI) dataset. Changes in county-level monthly screening volumes relative to the start of the COVID-19 pandemic (March 2020) and easing of restrictions (March 2021) were assessed relative to SVI. RESULTS: Among 10,503,180 individuals continuously enrolled in Medicare with no prior diagnosis of CRC, 1,362,457 (12.97%) underwent CRC screening between 2019 and 2021. With the COVID-19 pandemic, CRC screening decreased markedly across the United States (median monthly screening: pre-pandemic [n = 76,444] vs pandemic era [n = 60,826]; median Δn = 15,618; p < 0.001). The 1-year post-pandemic overall CRC screening utilization generally rebounded to pre-COVID-19 levels (monthly median screening volumes: pandemic era [n = 60,826] vs post-pandemic [n = 74,170]; median Δn = 13,344; p < 0.001). Individuals residing in counties with the highest SVI experienced a larger decline in CRC screening odds than individuals residing in low-SVI counties (reference, low SVI: pre-pandemic high SVI [OR, 0.85] vs pandemic high SVI [OR, 0.81] vs post-pandemic high SVI [OR, 0.85]; all p < 0.001). CONCLUSIONS: The COVID-19 pandemic was associated with a decrease in CRC screening volumes. Patients who resided in high social vulnerability areas experienced the greatest pandemic-related decline.

Comparing Multivisceral Resection with Tumor-only Resection of Liposarcoma Using the Win Ratio.

BACKGROUND: Multivisceral resection of retroperitoneal liposarcoma (LPS) is associated with increased morbidity and may not confer a survival benefit compared with tumor-only (TO) resection. We compared both approaches using a novel statistical method called the "win ratio" (WR). METHODS: Patients who underwent resection of LPS from 2004 to 2015 were identified from the National Cancer Database. Multivisceral resection was defined as removal of the primary site in addition to other organs. The WR was calculated based on a hierarchy of postoperative outcomes: 30-day and 90-day mortality, long-term survival, and severe complication. RESULTS: Among 958 patients (multivisceral 634, TO 324) who underwent resection, the median age was 63 years (interquartile range [IQR] 54-71) with a median follow-up of 51 months (IQR 30-86). There was no difference in the WR among patients who underwent TO versus multivisceral resection in the matched cohort (WR 0.82, 95% confidence interval [CI] 0.61-1.10). In patients aged 72-90 years, those who underwent multivisceral resection had 36% lower odds of winning compared with patients undergoing TO resection (WR 0.64, 95% CI 0.40-0.98). A subgroup analysis of patients classified as not having adjacent tumor involvement at the time of surgery revealed that those patients who underwent multivisceral resection had 33% lower odds of winning compared to TO resection (WR 0.67, 95% CI 0.45-0.99). CONCLUSIONS: Based on win-ratio assessments of a hierarchical composite endpoint, multivisceral resection in patients without adjacent tumor involvement may not confer improved outcomes. This method supports the rationale for less invasive resection of LPS in select patients, especially older patients.

Recurrent Intrahepatic Cholangiocarcinoma: A 10-Point Score to Predict Post-Recurrence Survival and Guide Treatment of Recurrence.

INTRODUCTION: Although up to 50-70% of patients with intrahepatic cholangiocarcinoma (ICC) recur following resection, data to predict post-recurrence survival (PRS) and guide treatment of recurrence are limited. METHODS: Patients who underwent resection of ICC between 2000 and 2020 were identified from an international, multi-institutional database. Data on primary disease as well as laboratory and radiologic data on recurrent disease were collected. Factors associated with PRS were examined and a novel scoring system to predict PRS (PRS score) was developed and internally validated. RESULTS: Among 986 individuals who underwent resection for ICC, 588 (59.6%) patients developed recurrence at a median follow up of 20.3 months. Among patients who experienced a recurrence, 97 (16.5%) underwent re-resection/ablation for recurrent ICC; 88 (15.0%) and 403 (68.5%) patients received intra-arterial treatment or systemic chemotherapy/supportive therapy, respectively. Patient American Society of Anesthesiologists (ASA) class > 2 (1 point), primary tumor N1/Nx status (1 point), primary R1 resection margin (1 point), primary tumor G3/G4 grade (1 point), carbohydrate antigen (CA) 19-9 > 37 UI/mL (2 points) at recurrence and carcinoembryonic antigen (CEA) > 5 ng/mL (2 points) at recurrence, as well as recurrent bilateral disease (1 point) and early recurrence (1 point) were included in the PRS score. The PRS score successfully stratified patients relative to PRS and demonstrated strong discriminatory ability (C-index 0.70, 95% confidence interval 0.68-0.72). While a PRS score of 0-3 was associated with a 3-year PRS of 62.5% following resection/ablation for recurrent ICC, a PRS score > 3 was associated with a low 3-year PRS of 35.5% (p = 0.03). CONCLUSIONS: The PRS score demonstrated strong discriminatory ability to predict PRS among patients who had developed recurrence following initial resection of ICC. The PRS score may be a useful tool to guide treatment among patients with recurrent ICC.

Perioperative Lymphopenia is Associated with Increased Risk of Recurrence and Worse Survival Following Hepatectomy for Hepatocellular Carcinoma.

INTRODUCTION: Immune dysregulation may be associated with cancer progression. We sought to investigate the prognostic value of perioperative lymphopenia on short- and long-term outcomes among patients undergoing resection of hepatocellular carcinoma (HCC). METHODS: Patients undergoing resection of HCC between 2000 and 2020 were identified using an international database. The incidence and impact of perioperative lymphopenia [preoperative, postoperative day (POD) 1/3/5], defined as absolute lymphocyte count (ALC) <1000/µL, on short- and long-term outcomes was assessed. RESULTS: Among 1448 patients, median preoperative ALC was 1593/µL [interquartile range (IQR) 1208-2006]. The incidence of preoperative lymphopenia was 14.0%, and 50.2%, 45.1% and 35.6% on POD1, POD3 and POD5, respectively. Preoperative lymphopenia predicted 5-year overall survival (OS) [lymphopenia vs. no lymphopenia: 49.1% vs. 66.1%] and 5-year disease-free survival (DFS) [25.0% vs. 41.5%] (both p < 0.05). Lymphopenia on POD1 (5-year OS: 57.1% vs. 71.2%; 5-year DFS: 30.0% vs. 41.1%), POD3 (5-year OS: 57.3% vs. 68.9%; 5-year DFS: 35.4% vs. 42.7%), and POD5 (5-year OS: 53.1% vs. 66.1%; 5-year DFS: 32.8% vs. 42.3%) was associated with worse long-term outcomes (all p < 0.05). Patients with severe lymphopenia (ALC <500/µL) on POD5 had worse 5-year OS and DFS (5-year OS: 44.7% vs. 54.3% vs. 66.1%; 5-year DFS: 27.8% vs. 33.3% vs. 42.3%) [both p < 0.05], as well as higher incidence of overall (45.5% vs. 25.3% vs. 30.9%; p = 0.013) and major complications (18.2% vs. 3.4% vs. 4.5%; p < 0.001) versus individuals with moderate (ALC 500-1000/µL) or no lymphopenia following hepatectomy for HCC. After adjusting for competing risk factors, prolonged lymphopenia was independently associated with higher hazards of death [hazard ratio (HR) 1.38, 95% CI 1.11-1.72] and recurrence (HR 1.22, 95% CI 1.02-1.45). CONCLUSION: Perioperative lymphopenia had short- and long-term prognostic implications among individuals undergoing hepatectomy for HCC.

Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features.

INTRODUCTION: Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited. METHODS: Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (>50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases. RESULTS: Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p < 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients. CONCLUSIONS: Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.

Effect of the opioid crisis on the liver transplantation donor pool: A national analysis.

BACKGROUND: Over the last decade there has been a surge in overdose deaths due to the opioid crisis. We sought to characterize the temporal change in overdose donor (OD) use in liver transplantation (LT), as well as associated post-LT outcomes, relative to the COVID-19 era. METHODS: LT candidates and donors listed between January 2016 and September 2022 were identified from the Scientific Registry of Transplant Recipients database. Trends in LT donors and changes related to OD were assessed pre- versus post-COVID-19 (February 2020). RESULTS: Between 2016 and 2022, most counties in the United States experienced an increase in overdose-related deaths (n = 1284, 92.3%) with many counties (n = 458, 32.9%) having more than a doubling in drug overdose deaths. Concurrently, there was an 11.2% increase in overall donors, including a 41.7% increase in the number of donors who died from drug overdose. In pre-COVID-19 overdose was the 4th top mechanism of donor death, while in the post-COVID-19 era, overdose was the 2nd most common cause of donor death. OD was younger (OD: 35 yrs, IQR 29-43 vs. non-OD: 43 yrs, IQR 31-56), had lower body mass index (≥35 kg/cm2, OD: 31.2% vs. non-OD: 33.5%), and was more likely to be HCV+ (OD: 28.9% vs. non-OD: 5.4%) with lower total bilirubin (≥1.1 mg/dL, OD: 12.9% vs. non-OD: 20.1%) (all p < .001). Receipt of an OD was not associated with worse graft survival (HR .94, 95% CI .88-1.01, p = .09). CONCLUSIONS: Opioid deaths markedly increased following the COVID-19 pandemic, substantially altering the LT donor pool in the United States.

Impact of Medicaid expansion on the multimodal treatment of biliary tract cancer.

INTRODUCTION: The impact of Medicaid expansion (ME) on the treatment of patients with cancer remains controversial, especially individuals requiring complex multidisciplinary care. We sought to evaluate the impact of Medicaid expansion (ME) on receipt of multimodal care, including surgical resection, for Stage I-III biliary tract cancer (BTC). METHODS: Patients diagnosed with BTC between 40 and 65 years of age were identified from the National Cancer Database and divided into pre- (2008-2012) and post- (2015-2018) ME cohorts. Difference-in-difference (DID) analysis was used to determine the impact of ME on the utilization of surgery and multimodal chemotherapy and/or radiotherapy treatment for BTC. RESULTS: Among 12,415 patients with BTC (extrahepatic, n = 5622, 45.3%; intrahepatic, n = 4352, 35.1%; gallbladder, n = 1944, 15.7%; overlapping, n = 497, 4.0%), 5835 (47.0%) and 6580 (53.0%) patients were diagnosed before versus after ME, respectively. Overall utilization of surgery (OR 1.13, 95% CI 1.02-1.26) and multimodality therapy (OR 1.13, 95% CI 1.01-1.27) increased in states that adopted ME. Utilization of surgery among uninsured/Medicaid patients in ME states increased relative to patients living in non-ME states (∆+10.1%, p = 0.01). Similarly, the use of multimodal treatment increased among uninsured/Medicaid patients living in ME versus non-ME states (∆+6.4%, p = 0.04); in contrast, there were no difference among patients with other insurance statuses (overall: ∆+1.5%, private: ∆-2.0%, other: ∆+3.9%, all p > 0.5). Uninsured/Medicaid patients with BTC who lived in a ME state had a lower risk of long-term death in the post-ME era (HR 0.81, 95% CI 0.67-0.98; p = 0.03). CONCLUSIONS: Implementation of ME positively impacted survival among patients who underwent surgical and multimodal treatment for Stage I-III BTC.

Association between social determinants of health and delayed postoperative adjuvant therapy among patients undergoing resection of pancreatic cancer.

BACKGROUND AND OBJECTIVES: Pancreatic cancer (PDAC) requires a multimodality approach. We sought to define the association between social determinants of health (SDOH) and delayed or nonreceipt of adjuvant chemotherapy (aCT) among patients undergoing PDAC resection. METHODS: Data on patients who underwent PDAC resection between 2014 and 2020 were identified from Medicare Standard Analytic Files and merged with the county-level social vulnerability index (SVI). Mediation analysis defined the association between SVI subthemes and aCT receipt. RESULTS: Among 24 078 patients, 47.7% received timely aCT, 17.7% received delayed aCT, and 34.6% did not receive any aCT. High SVI was associated with delay (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.10-1.34) and nonreceipt of aCT (OR 1.30, 95% CI 1.20-1.41) (both p < 0.05). 73.1% of the variation in timely aCT receipt was directly attributable to SVI, whereas 26.9% of the effect was due to indirect mediators including hospital volume (6.4%), length-of-stay (7.9%) and postoperative complications (12.6%). Socioeconomic status (delayed aCT: OR 1.25, 95% CI 1.13-1.38; nonreceipt aCT: OR 1.25, 95% CI 1.15-1.36) and household composition and disability (delayed aCT: OR 1.30, 95% CI 1.17-1.43; nonreceipt aCT: OR 1.19, 95% CI 1.09-1.29) were associated with receipt of aCT (both p < 0.001). CONCLUSIONS: Most of the disparities in receipt of aCT after PDAC surgery are driven by underlying SDOH such as SVI.

Prognostic significance of postoperative complications for patients with hepatocellular carcinoma relative to alpha-feto protein and tumor burden score.

BACKGROUND: We sought to elucidate the impact of postoperative complications on patient outcomes relative to differences in alpha-fetoprotein-tumor burden score (ATS) among patients with hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection of HCC between 2000 and 2020 were identified from an international database. Moderate/severe complications were defined using the optimal cut-off value of the comprehensive complication index (CCI) based on the log-rank test. RESULTS: A total of 1124 patients was included. CCI cut-off value of 16.6 was identified as the optimal prognostic threshold. Patients who experienced moderate/severe complications were more likely to have worse recurrence free survival [RFS] versus individuals who had no/mild complications (2-year RFS; no/mild complication: 55.9% vs. moderate/severe complication: 38.1% p < 0.001). Of note, low and medium ATS patients who experienced moderate/severe complications had a higher risk of recurrence (2-year RFS; no/mild complication: postoperative complications 70.0% vs. moderate/severe complication: 51.1%, p = 0.006; medium: no/mild complication: 50.8% vs moderate/severe complication: 56.7%, p = 0.01); however, postoperative complications were not associated with worse outcomes among patients with high ATS (no/mild complication: 39.1% vs. moderate/severe complication: 29.2%, p = 0.20). CONCLUSION: These data serve to emphasize how reduction in postoperative complications may be crucial to improve prognosis, particularly among patients with favorable HCC characteristics.

The aMAP score predicts long-term outcomes after resection of hepatocellular carcinoma: a multi-institutional analysis.

BACKGROUND: The aMAP score is a proposed model to predict the development of hepatocellular carcinoma (HCC) among high-risk patients with chronic hepatitis. The role of the aMAP score to predict long-term survival among patients following resection of HCC has not been determined. METHODS: Patients undergoing resection for HCC between 2000 and 2020 were identified using a multi-institutional database. The impact of the aMAP score on long-term outcomes following HCC resection was assessed. RESULTS: Among 1377 patients undergoing resection for HCC, a total of 972 (70.6 %) patients had a low aMAP score (≤63), whereas 405 (29.4 %) individuals had a high aMAP score (≥64). aMAP score was associated with 5-year OS in the entire cohort (low vs high aMAP score:66.5 % vs. 54.3 %, p < 0.001). aMAP score predicted 5-year OS following resection among patients with HBV-HCC (low vs. high aMAP:68.8 % vs. 55.6 %, p = 0.01) and NASH/other-HCC (64.7 % vs. 53.7, p = 0.04). aMAP score could sub-stratify 5-year OS among patients undergoing HCC resection within (low vs. high aMAP:81.5 % vs. 67.4 %, p < 0.001) and beyond (55.9 % vs. 38.8 %, p < 0.001) Milan criteria. DISCUSSION: The aMAP score predicted postoperative outcomes following resection of HCC within and beyond Milan criteria. Apart from a surveillance tool, the aMAP score can also be used as a prognostic tool among patients undergoing resection of HCC.

Machine-Based Learning Hierarchical Cluster Analysis: Sex-Based Differences in Prognosis Following Resection of Hepatocellular Carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) may have a heterogeneous presentation, as well as different long-term outcomes following surgical resection. We sought to use machine learning to cluster patients into different prognostic groups based on preoperative characteristics. METHODS: Patients who underwent curative-intent liver resection for HCC between 2000 and 2020 were identified from a large international multi-institutional database. A hierarchical cluster analysis was performed based on preoperative factors to characterize patterns of presentation and define disease-free survival (DFS). RESULTS: Among 966 with HCC, 3 distinct clusters were identified: Cluster 1 (n = 160, 16.5%), Cluster 2 (n = 537, 55.6%) and Cluster 3 (n = 269, 27.8%). Cluster 1 (n = 160, 16.5%) consisted of female patients (n = 160, 100%), low inflammation-based scores, intermediate tumor burden score (TBS) (median: 4.71) and high alpha-fetoprotein (AFP) levels (median 41.3 ng/mL); Cluster 2 consisted of male individuals (n = 537, 100%), mainly with a history of HBV infection (n = 429, 79.9%), low inflammation-based scores, intermediate AFP levels (median 26.0 ng/mL) and lower TBS (median 4.49); Cluster 3 was comprised of older patients (median age 68 years) predominantly male (n = 248, 92.2%) who had low incidence of HBV/HCV infection (7.1% and 8.2%, respectively), intermediate AFP levels (median 16.8 ng/mL), high inflammation-based scores and high TBS (median 6.58). Median DFS worsened incrementally among the three different clusters with Cluster 3 having the lowest DFS (Cluster 1: median not reached; Cluster 2: 34 months, 95% CI 23.0-48.0, Cluster 3: 19 months, 95% CI 15.0-29.0, p < 0.05). CONCLUSION: Cluster analysis classified HCC patients into three distinct prognostic groups. Cluster assignment predicted DFS following resection of HCC with the female cluster having the most favorable prognosis following HCC resection.

Risk factors and consequences of post-esophagectomy delirium: a systematic review and meta-analysis.

Post-operative delirium (POD) is a state of mental and neurocognitive impairment characterized by disorientation and fluctuating levels of consciousness. POD in the context of esophageal surgery may herald serious and potentially life-threatening post-operative complications, or conversely be a symptom of severe underlying pathophysiologic disturbances. The aim of the present systematic review and meta-analysis is to explore risk factors associated with the development of POD and assess its impact on post-operative outcomes. A systematic literature search of the MedLine, Web of Science, Embase and Cochrane CENTRAL databases and the clinicaltrials.gov registry was undertaken. A random-effects model was used for data synthesis with pooled outcomes expressed as Odds Ratios (OR), or standardized mean differences (WMD) with corresponding 95% Confidence Intervals. Seven studies incorporating 2449 patients (556 with POD and 1893 without POD) were identified. Patients experiencing POD were older (WMD 0.29 ± 0.13 years, P < 0.001), with higher Charlson's Comorbidity Index (CCI; WMD 0.31 ± 0.23, P = 0.007) and were significantly more likely to be smokers (OR 1.38, 95% CI 1.07-1.77, P = 0.01). Additionally, POD was associated with blood transfusions (OR 2.08, 95% CI 1.56-2.77, P < 0.001), and a significantly increased likelihood to develop anastomotic leak (OR 2.03, 95% CI 1.25-3.29, P = 0.004). Finally, POD was associated with increased mortality (OR 2.71, 95% CI 1.24-5.93, P = 0.01) and longer hospital stay (WMD 0.4 ± 0.24, P = 0.001). These findings highlight the clinical relevance and possible economic impact of POD after esophagectomy for malignant disease and emphasize the need of developing effective preventive strategies.

Application of hazard functions to investigate recurrence after curative-intent resection for hepatocellular carcinoma.

BACKGROUND: Defining patterns and risk of recurrence can help inform surveillance strategies and patient counselling. We sought to characterize peak hazard rates (pHR) and peak time of recurrence among patients who underwent resection of hepatocellular carcinoma (HCC). METHODS: 1434 patients who underwent curative-intent resection of HCC were identified from a multi-institutional database. Hazard, patterns, and peak rates of recurrence were characterized. RESULTS: The overall hazard of recurrence peaked at 2.4 months (pHR: 0.0384), yet varied markedly. The incidence of recurrence increased with Barcelona Clinic Liver Cancer (BCLC) stage 0 (29%), A (54%), and B (64%). While the hazard function curve for BCLC 0 patients was relatively flat (pHR: <0.0177), BCLC A patients recurred with a peak at 2.4 months (pHR: 0.0365). Patients with BCLC B had a bimodal recurrence with a peak rate at 4.2 months (pHR: 0.0565) and another at 22.8 months. The incidence of recurrence also varied according to AFP level (≤400 ng/mL: 52.6% vs. >400 ng/mL: 36.3%) and Tumor Burden Score (low: 73.7% vs. medium: 50.6% vs. high: 24.2%) (both p < 0.001). CONCLUSION: Recurrence hazard rates for HCC varied substantially relative to both time and intensity/peak rates. TBS and AFP markedly impacted patterns of hazard risk of recurrence.

Mapping the Endothelial Cell S-Sulfhydrome Highlights the Crucial Role of Integrin Sulfhydration in Vascular Function.

BACKGROUND: In vascular endothelial cells, cysteine metabolism by the cystathionine γ lyase (CSE), generates hydrogen sulfide-related sulfane sulfur compounds (H2Sn), that exert their biological actions via cysteine S-sulfhydration of target proteins. This study set out to map the "S-sulfhydrome" (ie, the spectrum of proteins targeted by H2Sn) in human endothelial cells. METHODS: Liquid chromatography with tandem mass spectrometry was used to identify S-sulfhydrated cysteines in endothelial cell proteins and ß3 integrin intraprotein disulfide bond rearrangement. Functional studies included endothelial cell adhesion, shear stress-induced cell alignment, blood pressure measurements, and flow-induced vasodilatation in endothelial cell-specific CSE knockout mice and in a small collective of patients with endothelial dysfunction. RESULTS: Three paired sample sets were compared: (1) native human endothelial cells isolated from plaque-free mesenteric arteries (CSE activity high) and plaque-containing carotid arteries (CSE activity low); (2) cultured human endothelial cells kept under static conditions or exposed to fluid shear stress to decrease CSE expression; and (3) cultured endothelial cells exposed to shear stress to decrease CSE expression and treated with solvent or the slow-releasing H2Sn donor, SG1002. The endothelial cell "S-sulfhydrome" consisted of 3446 individual cysteine residues in 1591 proteins. The most altered family of proteins were the integrins and focusing on ß3 integrin in detail we found that S-sulfhydration affected intraprotein disulfide bond formation and was required for the maintenance of an extended-open conformation of the ß leg. ß3 integrin S-sulfhydration was required for endothelial cell mechanotransduction in vitro as well as flow-induced dilatation in murine mesenteric arteries. In cultured cells, the loss of S-sulfhydration impaired interactions between ß3 integrin and Gα13 (guanine nucleotide-binding protein subunit α 13), resulting in the constitutive activation of RhoA (ras homolog family member A) and impaired flow-induced endothelial cell realignment. In humans with atherosclerosis, endothelial function correlated with low H2Sn generation, impaired flow-induced dilatation, and failure to detect ß3 integrin S-sulfhydration, all of which were rescued after the administration of an H2Sn supplement. CONCLUSIONS: Vascular disease is associated with marked changes in the S-sulfhydration of endothelial cell proteins involved in mediating responses to flow. Short-term H2Sn supplementation improved vascular reactivity in humans highlighting the potential of interfering with this pathway to treat vascular disease.

Is Hospital Occupancy Rate Associated With Postoperative Outcomes Among Patients Undergoing Hepatopancreatic Surgery?

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.

Tumor Necrosis Impacts Prognosis of Patients Undergoing Resection for T1 Intrahepatic Cholangiocarcinoma.

BACKGROUND: The prognostic impact of tumor necrosis among patients undergoing resection for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. METHODS: Patients who underwent curative-intent resection for ICC between 2000 and 2017 were identified using a multi-institutional database. The association of pathologic tumor necrosis with overall survival (OS) and recurrence-free survival (RFS) was examined. RESULTS: Among 757 patients who underwent resection for ICC, tumor necrosis was present in 384 (50.7%) patients (no necrosis: n = 373, 49.3%; <50% necrosis: n = 291, 38.4%; ≥50% necrosis: n = 93, 12.3%). Tumor necrosis was associated with worse OS (5-year OS: no necrosis 39.3% vs. <50% necrosis 34.7% and ≥50% necrosis 24.0%; p = 0.03) and RFS (5-year RFS: no necrosis 25.7% vs. <50% necrosis 13.9% and ≥50% necrosis 18.8%; p < 0.001). After stratifying by T stage, tumor necrosis was able to further stratify prognosis among patients with T1a ICC (5-year RFS: T1a and no necrosis 46.7% vs. T1a and necrosis 36.1%; p = 0.02), and T1b ICC (5-year RFS: T1b and no necrosis 31.1% vs. T1b and necrosis 11.2%; p = 0.006), but was not associated with outcomes among patients with more advanced T2-T3 disease. Patients with T1a ICC and tumor necrosis had similar 5-year RFS as individuals with T1b ICC and no tumor necrosis (36.1% vs. 31.1%; p = 0.66). CONCLUSION: Tumor necrosis was associated with worse prognosis among patients with T1 ICC. Tumor necrosis for T1 ICC should be considered as an important factor to further stratify outcomes of patients with early T-stage ICC.