Rare primary liver cancers: An EASL position paper.

In recent years, owing to advances in our understanding of hepatocarcinogenesis, rare primary liver cancers (PLCs), including combined hepatocellular-cholangiocarcinoma, fibrolamellar carcinoma, and hepatic epithelioid hemangioendothelioma have garnered increased attention. In this position paper, an international panel of experts representing oncology, hepatology, pathology, radiology, surgery, and molecular biology has summarised the available information and evidence on the pathogenesis, diagnosis, and treatment of rare PLCs. While clinical trials of systemic treatments are underway for some rare PLCs, it is evident that more research, involving national and international collaboration, is required.

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.

Community Privilege and Unplanned Surgery for Access-Sensitive Surgical Conditions.

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.

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). 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.

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.

Racial and Sex Differences in Genomic Profiling of Intrahepatic Cholangiocarcinoma.

BACKGROUND: Racial and sex disparities in the incidence and outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) exist, yet potential genomic variations of iCCA based on race and sex that might be contributing to disparate outcomes have not been well studied. METHODS: Data from the American Association for Cancer Research Project GENIE registry (version 15.0) were analyzed to assess genetic variations in iCCA. Adult patients (age >18 years) with histologically confirmed iCCA who underwent next-generation sequencing were included in the analytic cohort. Racial and sex variations in genomic profiling of iCCA were examined. RESULTS: The study enrolled 1068 patients from 19 centers (White, 71.9%; Black, 5.1%; Asian, 8.4%, other, 14.6%). The male-to-female ratio was 1:1. The majority of the patients had primary tumors (73.7%), whereas 23.0% had metastatic disease sequenced. While IDH1 mutations occurred more frequently in White versus Black patients (20.8% vs. 5.6%; p = 0.021), FGFR2 mutations tended to be more common among Black versus White populations (27.8% vs. 16.1%; p = 0.08). Males were more likely to have TP53 mutations than females (24.3% vs. 18.2%, p = 0.016), whereas females more frequently had IDH1 (23.3% vs 16.0 %), FGFR2 (21.0% vs. 11.3%), and BAP1 (23.4% vs. 14.5%) mutations than males (all p < 0.05). Marked variations in the prevalence of other common genomic alterations in iCCA were noted across different races and sexes. CONCLUSION: Distinct genomic variations exist in iCCA across race and sex. Differences in mutational profiles of iCCA patients highlight the importance of including a diverse patient population in iCCA clinical trials as well as the importance of recognizing different genetic drivers that may be targetable to treat distinct patient cohorts.

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.

The Association of Established Primary Care with Postoperative Outcomes Among Medicare Patients with Digestive Tract Cancer.

BACKGROUND: Primary care (PC) is essential to overall wellness and management of comorbidities. In turn, patients without adequate access to PC may face healthcare disparities. We sought to characterize the impact of established PC on postoperative outcomes among patients undergoing a surgical procedure for a digestive tract cancer. METHODS: Medicare beneficiaries with a diagnosis of hepatobiliary, pancreas, and colorectal cancer between 2005 and 2019 were identified within the Surveillance, Epidemiology, and End Results program and Medicare-linked database. Individuals who did versus did not have PC encounters within 1-year before surgery were identified. A postoperative textbook outcome (TO) was defined as the absence of complications, no prolonged hospital stay, no readmission within 90 days, and no mortality. RESULTS: Among 63,177 patients, 50,974 (80.7%) had at least one established PC visit before surgery. Patients with established PC were more likely to achieve TO (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.09-1.19) with lower odds for complications (OR, 0.85; 95% CI, 0.72-0.89), extended hospital stay (OR, 0.86; 95% CI, 0.81-0.94), 90-day readmission (OR, 0.94; 95% CI, 0.90-0.99), and 90-day mortality (OR, 0.87; 95% CI, 0.79-0.96). In addition, patients with established PC had a 4.1% decrease in index costs and a 5.2% decrease in 1-year costs. Notably, patients who had one to five visits with their PC in the year before surgery had improved odds of TO (OR, 1.21; 95% CI, 1.16-1.27), whereas individuals with more than 10 visits had lower odds of a postoperative TO (OR, 0.91; 95% CI, 0.84-0.98). CONCLUSION: Most Medicare beneficiaries with digestive tract cancer had established PC within the year before their surgery. Established PC was associated with a higher probability of achieving ideal outcomes and lower costs. In contrast, patients with more than 10 PC appointments, which was likely a surrogate of overall comorbidity burden, experienced no improvement in postoperative outcomes.

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.

Surveillance-Associated Anxiety After Curative-Intent Cancer Surgery: A Systematic Review.

BACKGROUND: Regular surveillance imaging is commonly used after curative-intent resection of most solid-organ cancers to enable prompt diagnosis and management of recurrent disease. Given the fear of cancer recurrence, surveillance may lead to distress and anxiety ("scanxiety") but its frequency, severity, and management among cancer survivors are poorly understood. METHODS: A systematic review of the PubMed, Embase, CINAHL, and PsycINFO databases was conducted to evaluate existing literature on anxiety and emotional experiences associated with surveillance after curative-intent cancer surgery as well as interventions aimed at reducing scanxiety. RESULTS: Across the 22 included studies encompassing 8693 patients, reported rates of scanxiety varied significantly, but tended to decrease as time elapsed after surgery. Qualitative studies showed that scanxiety arises from various factors innate to the surveillance experience and is most prevalent in the scan-to-results waiting period. Common risk factors for scanxiety included sociodemographic and cancer-related characteristics, low coping self-efficacy, pre-existing anxiety, and low patient well-being. Conversely, reassurance was a positive aspect of surveillance reported in several studies. Trials evaluating the impact of interventions all focused on modifying the surveillance regimen compared with usual care, but none led to reduced rates of scanxiety. CONCLUSIONS: Although scanxiety is nearly universal across multiple cancer types and patient populations, it is transient and generally limited in severity. Because existing trials evaluating interventions to reduce scanxiety have not identified effective strategies to date, future research is needed to identify interventions aimed at reducing their impact on high-risk individuals.

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.

Clinical Outcomes, Costs, and Value of Surgery Among Older Patients with Colon Cancer at US News and World Report Ranked Versus Unranked Hospitals.

BACKGROUND: US News and World Report (USNWR) hospital rankings influence patient choice of hospital, but their association with surgical outcomes remains ill-defined. We sought to characterize clinical outcomes and costs of surgery for colon cancer among USNWR top ranked and unranked hospitals. METHODS: Using Medicare Standard Analytic Files, patients aged ≥65 years undergoing surgery for colon cancer were identified. Hospitals were categorized as 'ranked' or 'unranked' based on USNWR cancer hospital rankings. One-to-one matching was performed between patients treated at ranked and unranked hospitals, and clinical outcomes and costs of surgery were compared. RESULTS: Among 50 ranked and 2522 unranked hospitals, 13,650 patient pairs were compared. Overall, 30-day mortality was 2.13% in ranked hospitals versus 3.68% in unranked hospitals (p < 0.0001), and the overall paired cost difference was $8159 (p < 0.0001). As patient risk increased, 30-day mortality differences became larger, with the ranked hospitals having 30-day mortality of 7.59% versus 11.84% for unranked hospitals among the highest-risk patients (p < 0.0001). Overall paired cost differences also increased with increasing patient risk, with cost of care being $72,229 for ranked hospitals versus $56,512 for unranked hospitals among the highest-risk patients (difference = $14,394; p = 0.02). The difference in cost per 1% reduction in 30-day mortality was $9009 (95% confidence interval [CI] $6422-$11,597) for lowest-risk patients, which dropped to $3387 (95% CI $2656-$4119) for highest-risk patients (p < 0.0001). CONCLUSION: Treatment at USNWR-ranked hospitals, particularly for higher-risk patients, was associated with better outcomes but higher-cost care. The benefit of being treated at highly ranked USNWR hospitals was most pronounced among high-risk patients.