Sex-determining region Y gene promotes liver fibrosis and accounts for sexual dimorphism in its pathophysiology.

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.

Quality of Life and Real-time Patient Experience During Neoadjuvant Therapy: A Prospective Cohort Study.

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.

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.

A Prognostic Model To Predict Survival After Recurrence Among Patients With Recurrent Hepatocellular Carcinoma.

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.

Perioperative Changes in Serum Transaminase Levels: Impact on Postoperative Morbidity Following Liver Resection of Hepatocellular Carcinoma.

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.

Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients.

BACKGROUND: The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection. METHODS: A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20 ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS). RESULTS: Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001). CONCLUSION: The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.

Association of ICD-10 Clinical Modification Codes for Social Determinants of Health with Surgical Outcomes and Hospital Charges Among Cancer Patients.

INTRODUCTION: We sought to characterize the impact of social determinants of health (SDOH)-related codes on outcomes among patients with a cancer diagnosis. METHODS: Patients diagnosed with lung, pancreas, colon, or rectal cancer between 2017 and 2020 were identified in the California Department of Healthcare Access and Information Patient Discharge Database. Data on concomitant SDOH-related codes (International Classification of Diseases, Tenth Revision [ICD-10] Z55-Z65) designating health hazards related to socioeconomic and psychosocial circumstances were obtained. The association of these SDOH codes with postoperative outcomes was evaluated. RESULTS: Among 10,421 patients who underwent an operation from 2017 to 2020, median age was 66 years (interquartile range [IQR] 56-75) and nearly half of the cohort was male (n = 551,252.9%). In total, 102 (1%) patients had a concurrent ICD-10 SDOH diagnosis. After controlling for competing risk factors, the risk-adjusted probability of in-hospital death was 4.1% (95% confidence interval [CI] 1.0-7.2) among patients with an SDOH diagnosis compared with 2.9% (95% CI 2.5-3.2) among patients without an SDOH diagnosis (odds ratio [OR] 1.52, 95% CI 0.63-3.66; p = 0.258); postoperative complications were 27.0% (95% CI 20.0-34.1) compared with 24.9% (95% CI 24.1-25.6) among patients without an SDOH diagnosis (OR 1.15, 95% CI 0.73-1.82; p = 0.141), and length of stay was 10.6 days (95% CI 10.0-11.2) compared with 9.4 days (95% CI 9.3-9.5) among patients without an SDOH diagnosis. Patients with an SDOH diagnosis had a 5.19 (95% CI 3.23-8.34; p < 0.005) higher odds of being discharged to a skilled nursing facility versus patients without an SDOH diagnosis. CONCLUSION: Uptake and utilization of ICD-10 SDOH was 1% among California patients with lung, pancreas, colon, or rectal cancer. Patients with a concomitant ICD-10 SDOH code had longer length of stay and had higher odds of being discharged to a skilled nursing facility.

Top Hepatobiliary Articles from 2022 to Inform Your Cancer Practice.

Until recently, there have been only modest therapeutic advances in the treatment of hepatobiliary malignancies. However, the introduction of immune checkpoint inhibitors in combination with targeted therapy or chemotherapy has changed the therapeutic landscape of hepatocellular carcinoma and biliary tract cancers. As such, revisions have been made to guidelines reflecting therapeutic advances for patients who can be considered for surgical options including resection and liver transplantation. This article highlights recently published studies that have impacted both the oncological and surgical approach to the treatment of patients with hepatobiliary malignancies.

Association of Hospital Market Competition with Outcomes of Complex Cancer Surgery.

BACKGROUND: The association of hospital market competition, financial costs, and quality of oncologic care has not been well-defined. This study sought to evaluate variations in patient outcomes and financial expenditures after complex cancer surgery across high- and low-competition markets. METHODS: Medicare 100% Standard Analytic Files were used to identify patients with lung, esophageal, gastric, hepatopancreaticobiliary, or colorectal cancer who underwent surgical resection between 2018 and 2021. Data were merged with the annual hospital survey database, and the hospital market Herfindahl-Hirschman index was used to categorize hospitals into low- and high-concentration markets. Multi-level, multivariable regression models adjusting for patient characteristics (i.e., age, sex, comorbidities, and social vulnerability), year of procedure, and hospital factors (i.e., case volume, nurse-bed ratio, and teaching status) were used to assess the association between hospital market competition and outcomes. RESULTS: Among 117,641 beneficiaries who underwent complex oncologic surgery, the mean age was 73.8 ± 6.1 years, and approximately one-half of the cohort was male (n = 56,243, 47.8%). Overall, 63.8% (n = 75,041) of the patients underwent care within a high-competition market. Notably, there was marked geographic variation relative to market competition. High versus low market-competition hospitals were more likely to be in high social vulnerability areas (35.1 vs 27.5%; p < 0.001), as well as care for racial/ethnic minority individuals (13.8 vs 7.7%; p < 0.001), and patients with more comorbidities (≥ 2 Elixhauser comorbidities: 63.1 vs 61.1%; p < 0.001). In the multivariable analysis, treatment at hospitals in high- versus low-competition markets was associated with lower odds of achieving a textbook outcome (odds ratio, 0.95; 95% confidence interval, 0.91-0.99; p = 0.009). Patients at high-competition hospitals had greater mean index hospitalization costs ($19,462.2 [16211.9] vs $18,844.7 [14994.7]) and 90-day post-discharge costs ($7807.8 [15431.3] vs $7332.8 [14038.2]) (both p < 0.001) than individuals at low-competition hospitals. CONCLUSIONS: Hospital market competition was associated with poor achievement of an optimal postoperative outcome and greater hospitalization costs.

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.

Variation in Hospital Mortality After Complex Cancer Surgery: Patient, Volume, Hospital or Social Determinants?

INTRODUCTION: We sought to define the individual contributions of patient characteristics (PCs), hospital characteristics (HCs), case volume (CV), and social determinants of health (SDoH) on in-hospital mortality (IHM) after complex cancer surgery. METHODS: The California Department of Health Care Access and Information database identified patients who underwent esophagectomy (ES), pneumonectomy (PN), pancreatectomy (PD), or proctectomy (PR) for a malignant diagnosis between 2010 and 2020. Multi-level multivariable regression was performed to assess the proportion of variance explained by PCs, HCs, CV and SDoH on IHM. RESULTS: A total of 52,838 patients underwent cancer surgery (ES: n = 2,700, 5.1%; PN: n = 30,822, 58.3%; PD: n = 7530, 14.3%; PR: n = 11,786, 22.3%) across 294 hospitals. The IHM for the overall cohort was 1.7% and varied from 4.4% for ES to 0.8% for PR. On multivariable regression, PCs contributed the most to the variance in IHM (overall: 32.0%; ES: 21.6%; PN: 28.0%; PD: 20.3%; PR: 39.9%). Among the overall cohort, CV contributed 2.4%, HCs contributed 1.3%, and SDoH contributed 1.2% to the variation in IHM. CV was the second highest contributor to IHM among ES (5.3%), PN (5.3%), and PD (5.9%); however, HCs were a more important contributor among patients who underwent PR (8.0%). The unexplained variance in IHM was highest among ES (72.4%), followed by the PD (67.5%) and PN (64.6%) patient groups. CONCLUSIONS: PCs are the greatest underlying contributor to variations in IHM following cancer surgery. These data highlight the need to focus on optimizing patients and exploring unexplained sources of IHM to improve quality of surgical care.

Association Between Historical Redlining and Access to High-Volume Hospitals Among Patients Undergoing Complex Cancer Surgery in California.

BACKGROUND: We sought to determine the impact of historical redlining on travel patterns and utilization of high-volume hospitals (HVHs) among patients undergoing complex cancer operations. METHODS: The California Department of Health Care Access and Information database was utilized to identify patients who underwent esophagectomy (ES), pneumonectomy (PN), pancreatectomy (PA), or proctectomy (PR) for cancer between 2010 and 2020. Patient ZIP codes were assigned Home Owners' Loan Corporation grades (A: 'Best'; B: 'Still Desirable'; C: 'Definitely Declining'; and D: 'Hazardous/Redlined'). A clustered multivariable regression was used to assess the likelihood of patients undergoing surgery at an HVH, bypassing the nearest HVH, and total real driving time and travel distance. RESULTS: Among 14,944 patients undergoing high-risk cancer surgery (ES: 4.7%, n = 1216; PN: 57.8%, n = 8643; PD: 14.4%, n = 2154; PR: 23.1%, n = 3452), 782 (5.2%) individuals resided in the 'Best', whereas 3393 (22.7%) individuals resided in redlined areas. Median travel distance was 7.8 miles (interquartile range [IQR] 4.1-14.4) and travel time was 16.1 min (IQR 10.7-25.8). Overall, 10,763 (ES: 17.4%; PN: 76.0%; PA: 63.5%; PR: 78.4%) patients underwent surgery at an HVH. On multivariable regression, patients residing in redlined areas were less likely to undergo surgery at an HVH (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.54-0.82) and were more likely to bypass the nearest hospital (OR 1.80, 95% CI 1.44-2.46). Notably, Medicaid insurance, minority status, limited English-language proficiency, and educational level mediated the disparities in access to HVH. CONCLUSION: Surgical disparities in access to HVH among patients from historically redlined areas are largely mediated by social determinants such as insurance and minority status.

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.

Poor Access to Mental Healthcare is Associated with Worse Postoperative Outcomes Among Patients with Gastrointestinal Cancer.

BACKGROUND: Mental health has an important role in the care of cancer patients, and access to mental health services may be associated with improved outcomes. Thus, poor access to psychiatric services may contribute to suboptimal cancer treatment. We conducted a geospatial analysis to characterize psychiatrist distribution and assess the impact of mental healthcare shortages with surgical outcomes among patients with gastrointestinal cancer. METHODS: Medicare beneficiaries with mental illness diagnosed with complex gastrointestinal cancers between 2004 and 2016 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry. National Provider Identifier-registered psychiatrist locations were mapped and linked to SEER-Medicare records. Regional access to psychiatric services was assessed relative to textbook outcome, a composite assessment of postoperative complications, prolonged length of stay, 90-day readmission and mortality. RESULTS: Among 15,714 patients with mental illness and gastrointestinal cancer, 3937 were classified as having high access to psychiatric services while 3910 had low access. On multivariable logistic regression, areas with low access had higher risk of worse postoperative outcomes. Specifically, individuals residing in areas with low access had increased odds of prolonged length of stay (OR 1.11, 95%CI 1.01-1.22; p = 0.028) and 90-day readmission (OR 1.19, 95%CI 1.08-1.31; p < 0.001), as well as decreased odds of textbook outcome (OR 0.85, 95%CI 0.77-0.93; p < 0.001) and discharge to home (OR 0.89, 95%CI 0.80-0.99; p = 0.028). CONCLUSION: Patients with mental illness and lower access to psychiatric services had worse postoperative outcomes. Policymakers and providers should prioritize incorporating mental health screening and access to psychiatric services to address disparities among patients undergoing gastrointestinal surgery.

Disparities in Breast Cancer Screening Rates Among Adults With and Without Intellectual and Developmental Disabilities.

BACKGROUND: Individuals with intellectual and developmental disabilities may face barriers in accessing healthcare, including cancer screening and detection services. We sought to assess the association of intellectual and developmental disabilities (IDD) with breast cancer screening rates. METHODS: Data from 2018 to 2020 was used to identify screening-eligible individuals from Medicare Standard Analytic Files. Adults aged 65-79 years who did not have a previous diagnosis of breast cancer were included. Multivariable regression was used to analyze the differences in breast cancer screening rates among individuals with and without IDD. RESULTS: Among 9,383,349 Medicare beneficiaries, 11,265 (0.1%) individuals met the criteria for IDD. Of note, individuals with IDD were more likely to be non-Hispanic White (90.5% vs. 87.3%), have a Charlson Comorbidity Index score ≤ 2 (66.2% vs. 85.5%), and reside in a low social vulnerability index neighborhood (35.7% vs. 34.4%). IDD was associated with reduced odds of undergoing breast cancer screening (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.74-0.80; p < 0.001). Breast cancer screening rates in individuals with IDD were further influenced by social vulnerability and belonging to a racial/ethnic minority. CONCLUSIONS: Individuals with IDD may face additional barriers to breast cancer screening. The combination of IDD and social vulnerability placed patients at particularly high risk of not being screened for breast cancer.

Is Precision Surgery Applicable to Colorectal Liver Metastases? A Systematic Review and Meta-analysis of Studies that Investigate the Association of Surgical Technique with Outcomes in the Context of Distinct Tumor Biology.

BACKGROUND: Although some data suggest that patients with mutRAS colorectal liver metastases (CRLM) may benefit from anatomic hepatectomy, this topic remains controversial. We performed a systematic review and meta-analysis to determine whether RAS mutation status was associated with prognosis relative to surgical technique [anatomic resection (AR) vs. nonanatomic resection (NAR)] among patients with CRLM. PATIENTS AND METHODS: A systematic review and meta-analysis of studies were performed to investigate the association of AR versus NAR with overall and liver-specific disease-free survival (DFS and liver-specific DFS, respectively) in the context of RAS mutation status. RESULTS: Overall, 2018 patients (831 mutRAS vs. 1187 wtRAS) were included from five eligible studies. AR was associated with a 40% improvement in liver-specific DFS [hazard ratio (HR) = 0.6, 95% confidence interval (CI) 0.44-0.81, p = 0.01] and a 28% improvement in overall DFS (HR = 0.72, 95% CI 0.54-0.95, p = 0.02) among patients with mutRAS tumors; in contrast, AR was not associated with any improvement in liver-specific DFS or overall DFS among wtRAS patients. These differences may have been mediated by the 40% decreased incidence in R1 resection among patients with mutRAS tumors who underwent AR versus NAR [relative risk (RR): 0.6, 95% CI 0.40-0.91, p = 0.02]. In contrast, the probability of an R1 resection was not decreased among wtRAS patients who underwent AR versus NAR (RR: 0.93, 95% CI 0.69-1.25, p = 0.62). CONCLUSIONS: The data suggest that precision surgery may be relevant to CRLM. Specifically, rather than a parenchymal sparing dogma for all patients, AR may have a role in individuals with mutRAS tumors.

Long-term Health Outcomes of New Persistent Opioid Use After Gastrointestinal Cancer Surgery.

BACKGROUND: New persistent opioid use (NPOU) after surgery has been identified as a common complication. This study sought to assess the long-term health outcomes among patients who experienced NPOU after gastrointestinal (GI) cancer surgery. METHODS: Patients who underwent surgery for hepato-pancreato-biliary and colorectal cancer between 2007 and 2019 were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Mixed-effect multivariable logistic regression and Cox proportional hazard models were used to estimate the risk of mortality and hospital visits related to falls, respiratory events, or pain symptoms. RESULTS: Among 15,456 patients who underwent GI cancer surgery, 967(6.6%) experienced NPOU. Notably, the patients at risk for the development of NPOU were those with a history of substance abuse (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.14-1.84), moderate social vulnerability (OR, 1.26; 95% CI, 1.06-1.50), an advanced disease stage (OR, 4.42; 95% CI, 3.51-5.82), or perioperative opioid use (OR, 3.07; 95% CI, 2.59-3.63. After control for competing risk factors, patients who experienced NPOU were more likely to visit a hospital for falls, respiratory events, or pain symptoms (OR, 1.45, 95% CI 1.18-1.78). Moreover, patients who experienced NPOU had a greater risk of death at 1 year (hazard ratio [HR], 2.15; 95% CI, 1.74-2.66). CONCLUSION: Approximately 1 in 15 patients experienced NPOU after GI cancer surgery. NPOU was associated with an increased risk of subsequent hospital visits and higher mortality. Targeted interventions for individuals at higher risk for NPOU after surgery should be used to help mitigate the harmful effects of NPOU.