The Prognostic Significance of Nativity, Enclave Residence, and Socioeconomic Status Among Hispanic Patients with Hepatocellular Carcinoma.

BACKGROUND: Residence in ethnic enclaves and nativity are both associated with survival in Hispanic patients with cancer, although their prognostic significance in patients with hepatocellular carcinoma (HCC) is unknown. We aimed to determine the association between nativity, neighborhood socioeconomic status (nSES), and ethnic enclave residency with overall survival in Hispanic patients with HCC. METHODS: Hispanic patients diagnosed with HCC from 2004 to 2017 were identified in the Texas Cancer Registry. Existing indices were applied to tract-level 2000 US Census data to measure enclave residence and nSES. Enclaves were defined by seven measures. Multivariable Cox proportional hazard models were used to evaluate the association between nativity, enclave residency, and nSES with survival. RESULTS: Among 9496 Hispanic patients with HCC, 2283 (24%) were foreign-born. Compared with US-born Hispanic patients, foreign-born Hispanic patients were less likely to present with localized HCC (45.3% vs. 48.8%, p = 0.03) and less likely to receive HCC treatment (53.9% vs. 47.6%, p < 0.001); however, foreign-born Hispanic patients had lower mortality in adjusted models (adjusted hazard ratio [aHR] 0.86, 95% confidence interval [CI] 0.79-0.93). Neighborhood SES, but not enclave residence, was also associated with overall survival. Compared with those in low nSES non-enclaves, Hispanic patients in high nSES neighborhoods, with either enclave (aHR 0.80, 95% CI 0.72-0.88) or non-enclave (aHR 0.89, 95% CI 0.80-0.98) residence status and low nSES enclaves (aHR 0.93, 95% CI 0.86-0.98) had improved survival. CONCLUSION: In Hispanic patients with HCC, foreign birthplace and higher nSES, but not enclave residence, are associated with improved survival. Additional research on intersectionality between ethnicity, nativity, and neighborhood context is warranted.

Enhancing Readability of Online Patient-Facing Content: The Role of AI Chatbots in Improving Cancer Information Accessibility.

BACKGROUND: Internet-based health education is increasingly vital in patient care. However, the readability of online information often exceeds the average reading level of the US population, limiting accessibility and comprehension. This study investigates the use of chatbot artificial intelligence to improve the readability of cancer-related patient-facing content. METHODS: We used ChatGPT 4.0 to rewrite content about breast, colon, lung, prostate, and pancreas cancer across 34 websites associated with NCCN Member Institutions. Readability was analyzed using Fry Readability Score, Flesch-Kincaid Grade Level, Gunning Fog Index, and Simple Measure of Gobbledygook. The primary outcome was the mean readability score for the original and artificial intelligence (AI)-generated content. As secondary outcomes, we assessed the accuracy, similarity, and quality using F1 scores, cosine similarity scores, and section 2 of the DISCERN instrument, respectively. RESULTS: The mean readability level across the 34 websites was equivalent to a university freshman level (grade 13±1.5). However, after ChatGPT's intervention, the AI-generated outputs had a mean readability score equivalent to a high school freshman education level (grade 9±0.8). The overall F1 score for the rewritten content was 0.87, the precision score was 0.934, and the recall score was 0.814. Compared with their original counterparts, the AI-rewritten content had a cosine similarity score of 0.915 (95% CI, 0.908-0.922). The improved readability was attributed to simpler words and shorter sentences. The mean DISCERN score of the random sample of AI-generated content was equivalent to "good" (28.5±5), with no significant differences compared with their original counterparts. CONCLUSIONS: Our study demonstrates the potential of AI chatbots to improve the readability of patient-facing content while maintaining content quality. The decrease in requisite literacy after AI revision emphasizes the potential of this technology to reduce health care disparities caused by a mismatch between educational resources available to a patient and their health literacy.

Presence of underlying cirrhosis is associated with increased in-hospital mortality and length of stay following pancreatoduodenectomy.

BACKGROUND: Patient- and hospital-level factors associated with outcomes following pancreatoduodenectomy (PD) are well established. However, despite theoretical disruption in hepatopetal flow, the impact of cirrhosis on in-hospital mortality following PD is not well-studied. The objective of this study was to evaluate in-hospital mortality, length of stay (LOS), and post-discharge disposition in patients with cirrhosis undergoing PD. METHODS: A retrospective analysis of the National Inpatient Sample (January 2002-August 2015) was conducted identifying patients undergoing PD. Using previously validated ICD-9-CM codes, patients were stratified into presence and absence of cirrhosis. Factors associated with in-hospital mortality following PD were analyzed adjusting for patient- and hospital-level factors. Following PD were analyzed after adjusting for patient- and hospital-level factors. RESULTS: In 16,344 patients that underwent PD, 203 (1.2 %) patients had underlying cirrhosis prior to resection. Overall in-hospital mortality following PD was significantly worse in the cirrhosis cohort (11.3 % vs. 3.6 %, p < 0.001). Patients with underlying cirrhosis were less likely to be discharged home (73.9 % vs. 83.2 %, p < 0.001) and had a longer median LOS (12.0 vs. 10.0 days, p = 0.001). CONCLUSION: The presence of underlying cirrhosis is associated with increased in-hospital mortality, longer LOS, and decreased likelihood of home discharge following PD. Given the prohibitive risks, PD should not be performed in patients with underlying cirrhosis.

Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites.

BACKGROUND: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. METHODS: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era. RESULTS: Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04). CONCLUSIONS: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

Association of race, demographic and socioeconomic factors with failure to rescue after hepato-pancreato-biliary surgery in the United States.

BACKGROUND: We aimed to describe the association of patient-related factors such as race, socioeconomic status, and insurance on failure to rescue (FTR) after hepato-pancreato-biliary (HPB) surgeries. METHODS: Using the National Inpatient Sample, we analyzed 98,788 elective HPB surgeries between 2004 and 2017. Major and minor complications were identified using ICD9/10 codes. We evaluated mortality rates and FTR (inpatient mortality after major complications). We used multivariate logistic regression analysis to assess racial, socioeconomic, and demographic factors on FTR, adjusting for covariates. RESULTS: Overall, 43 % of patients (n = 42,256) had pancreatic operations, 36% (n = 35,526) had liver surgery, and 21% (n = 21,006) had biliary interventions. The overall major complication rate was 21% (n = 20,640), of which 8% (n = 1655) suffered FTR. Factors independently associated with increased risk for FTR were male sex, older age, higher Charlson Comorbidity Index, Hispanic ethnicity, Asian or other race, lower income quartile, Medicare insurance, and southern region hospitals. CONCLUSIONS: Medicare insurance, male gender, Hispanic ethnicity, and lower income quartile were associated with increased risk for FTR. Efforts should be made to improve the identification and subsequent treatment of complications for those at high risk of FTR.

Defining Volume Targets for Regionalization of Pancreaticoduodenectomy, Esophagectomy, and Major Lung Resection Centers to Improve Oncologic and Surgical Outcomes.

BACKGROUND: Performance of complex cancer surgeries at high-volume (HV) centers has been shown to reduce operative mortality. However, the case volume threshold that should be used to define HV centers is unknown. In this study, we determined thresholds to define HV pancreaticoduodenectomy, esophagectomy, and major lung resection centers based on clinical parameters. Then, we assessed the association of hospital volume with oncologic outcomes and overall survival. METHODS: We identified adult NCDB patients undergoing pancreaticoduodenectomy, esophagectomy, and major lung resections between 2004 and 2015. Multivariable models with restricted cubic splines were built to predict 5-year overall survival for each surgery group according to average yearly case volume, adjusting for demographic and clinicopathologic factors. The change point procedure was then used to identify volume cut-points for each surgery type. RESULTS: We identified the following thresholds to define HV status: 25 cases/year for pancreaticoduodenectomy; 18 cases/year for esophagectomy; and 54 cases/year for major lung resections. For all surgery types, treatment at a HV center was associated with an increased likelihood of R0 resection and adequate lymph node evaluation. HV centers had significantly decreased 30- and 90-day, postoperative mortality after adjusting for age, sex, race, comorbidities, histology, and stage. An overall survival benefit also was observed for patients undergoing resections at HV centers. CONCLUSIONS: Using novel methodology, our study identified volume thresholds for HV pancreaticoduodenectomy, esophagectomy, and major lung resection centers that were associated with improved oncologic outcomes and overall survival. These definitions of HV centers should be considered when evaluating regionalization of complex cancer care.

Cost Analysis and Financial Implications of a Peritoneal Surface Malignancy Program in the USA.

BACKGROUND: We aimed to describe the financial implications of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in the USA. MATERIALS AND METHODS: We conducted a retrospective cost analysis of 100 CRS/HIPEC procedures to examine the impact of patient and procedural factors on hospital costs and reimbursement. A comparison of surgeons' work relative value units (wRVUs) between CRS/HIPEC and a representative sample of complex surgical oncology procedures was made to assess the physicians' compensation rate. Univariable and multivariable backward logistic regression was used to analyze the association between perioperative variables and high direct cost (HDCs). RESULTS: The median direct cost per CRS/HIPEC procedure was US $44,770. The median hospital reimbursement was US $43,066, while professional reimbursement was US $8608, resulting in a positive contribution margin of US $7493/procedure. However, the contribution margin significantly varied with the payer mix. Privately insured patients had a positive median contribution margin of US $23,033, whereas Medicare-insured patients had a negative contribution margin of US $13,034. Length of stay (LOS) had the most significant association with HDC, and major complications had the most significant association with LOS. Finally, CRS/HIPEC procedures generated a median of 13 wRVU/h, which is significantly lower than the wRVU/h generated by open pancreatoduodenectomies, open gastrectomies, and hepatectomies. However, higher operation complexity and multiple visceral resections help compensate for the relatively low wRVU/h. CONCLUSIONS: CRS/HIPEC is an expensive operation, and prolonged LOS has the most significant impact on the total cost of the procedure. High-quality care is essential to improve patient outcomes and maintain the economic sustainability of the procedure.

Impact of Neoadjuvant Treatment and Minimally Invasive Surgery on Perioperative Outcomes of Pancreatoduodenectomy: an ACS NSQIP Analysis.

BACKGROUND: There is an increasing use of neoadjuvant treatment (NAT) for pancreatic cancer (PC) followed by minimally invasive pancreatoduodenectomy (MIPD). We evaluate the impact of the surgical approach on 30-day outcomes in PC patients who underwent NAT. METHODS: Patients with PC who had NAT followed by MIPD or open pancreatoduodenectomy (OPD) were identified from a pancreatectomy-targeted dataset (2014-2020) of the National Surgical Quality Improvement Program. Comparisons were made between MIPD and OPD within NAT groups. RESULTS: A total of 5588 patients were analyzed. Of those, 4907 underwent OPD and 476 underwent MIPD. In addition, 3559 patients received neoadjuvant chemotherapy alone and 1830 received neoadjuvant chemoradiation. In the chemotherapy-alone group, the MIPD subgroup had lower rates of any complication (38.2% vs. 45.8%, P = 0.005), but there were no differences in mortality (2.1% for MIPD vs 1.9% for OPD, P=0.8) or serious complication (11.8% for MIPD vs 15% for OPD, P=0.1). On multivariable analysis, MIPD was independently predictive of lower rates of any complication (OR: 0.74, 95% CI 0.6-0.93, P = 0.0009), CR-POPF (OR: 0.58, 95% CI 0.35-0.96, P = 0.04), and shorter LOS (estimate: -1.03, 95% CI -1.73 to -0.32, P = 0.004). In the chemoradiation group, patients undergoing MIPD had higher rates of preoperative diabetes (P < 0.05), but there were no significant differences in any outcomes between the two approaches in this group. CONCLUSION: MIPD is safe and feasible after NAT. Patients having neoadjuvant chemotherapy alone followed by MIPD had lower rates of complications, shorter LOS, and fewer CR-POPFs compared to OPD.

Serum Interleukin 6 Level is Associated With Overall Survival and Treatment Response in Gastric and Gastroesophageal Junction Cancer.

OBJECTIVE: To identify novel prognostic and predictive biomarkers for gastric and gastroesophageal junction (G+GEJ) adenocarcinoma. BACKGROUND: There are few biomarkers to guide treatment for G+GEJ. The systemic inflammatory response of G+GEJ patients is associated with survival. In this study, we evaluated the relationship of circulating serum cytokine levels with overall survival (OS) and pathologic tumor regression grade (TRG) in G+GEJ patients. PATIENTS AND METHODS: We queried the UT Southwestern gastric cancer biobank to identify consecutive patients diagnosed with G+GEJ from 2016 to 2022; these patients had pretreatment serum collected at diagnosis. For patients who received neoadjuvant therapy, an additional serum sample was collected immediately before surgical resection. An unbiased screen of 17 cytokines was measured in a discovery cohort. A multivariable Cox proportional hazards model was used to assess the association of cytokine concentration with OS. Findings were validated in additional patients. In patients who received neoadjuvant therapy, we assessed whether the change in interleukin 6 (IL-6) after therapy was associated with TRG. RESULTS: Sixty-seven patients were included in the discovery cohort, and IL-6 was the only pretreatment cytokine associated with OS; this was validated in 134 other patients (hazard ratio: 1.012 per 1 pg/mL increase, 95% CI: 1.006-1.019, P = 0.0002). Patients in the top tercile of IL-6 level had worse median OS (10.6 months) compared with patients in the intermediate (17.4 months) and bottom tercile (35.8 months, P < 0.0001). Among patients who underwent neoadjuvant therapy (n = 50), an unchanged or decrease in IL-6 level from pretreatment to posttreatment, had a sensitivity and specificity of 80% for predicting complete or near-complete pathologic tumor regression (TRG 0-1). CONCLUSIONS: Pretreatment serum level of IL-6 is a promising prognostic biomarker for G+GEJ patients. Comparing pre and post-neoadjuvant IL-6 levels may predict pathologic response to neoadjuvant therapy.

Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer. Do They Matter?

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) requires complex multidisciplinary care. European evidence suggests potential benefit from regionalization, however, data characterizing the ideal setting in the United States are sparse. Our study compares the significance of four hospital designations on guideline-concordant care (GCC) and overall survival (OS). PATIENTS AND METHODS: The Texas Cancer Registry was queried for 17,071 patients with PDAC treated between 2004 and 2015. Clinical data were correlated with hospital designations: NCI designated (NCI), high volume (HV), safety net (SNH), and American College of Surgeons Commission on Cancer accredited (ACS). Univariable (UVA) and multivariable (MVA) logistic regression were used to assess associations with GCC [on the basis of National Comprehensive Cancer Network (NCCN) recommendations]. Cox regression analysis assessed survival. RESULTS: Only 43% of patients received GCC. NCI had the largest associated risk reduction (HR 0.61, CI 0.58-0.65), followed by HV (HR 0.87, CI 0.83-0.90) and ACS (HR 0.91, CI 0.87-0.95). GCC was associated with a survival benefit in the full (HR 0.75, CI 0.69-0.81) and resected cohort (HR 0.74, CI 0.68-0.80). NCI (OR 1.52, CI 1.37-1.70), HV (OR 1.14, CI 1.05-1.23), and SNH (OR 0.78, CI 0.68-0.91) all correlated with receipt of GCC. For resected patients, ACS (OR 0.63, CI 0.50-0.79) and SNH (OR 0.50, CI 0.33-0.75) correlate with GCC. CONCLUSIONS: A total of 43% of patients received GCC. Treatment at NCI and HV correlated with improved GCC and survival. Including GCC as a metric in accreditation standards could impact survival for patients with PDAC.

ACTA2 Expression Predicts Survival and Is Associated with Response to Immune Checkpoint Inhibitors in Gastric Cancer.

PURPOSE: We sought to identify biomarkers that predict overall survival (OS) and response to immune checkpoint inhibitors (ICI) for patients with gastric cancer. EXPERIMENTAL DESIGN: This was a retrospective study of multiple independent cohorts of patients with gastric cancer. The association between tumor ACTA2 expression and OS and ICI response were determined in patients whose tumors were analyzed with bulk mRNA sequencing. Single-cell RNA sequencing (scRNA-seq) and digital spatial profiling data were used to compare tumors from patients with gastric cancer who did and did not respond to ICI. RESULTS: Increasing tumor ACTA2 expression was independently associated with worse OS in a 567-patient discovery cohort [HR, 1.28 per unit increase; 95% confidence interval (CI), 1.02-1.62]. This finding was validated in three independent cohorts (n = 974; HR, 1.52 per unit increase; 95% CI, 1.34-1.73). Of the 108 patients treated with ICI, 56% of patients with low ACTA2 expression responded to ICI versus 25% of patients with high ACTA2 expression (P = 0.004). In an analysis of a publicly available scRNA-seq dataset of 5 microsatellite instability-high patients treated with ICI, the patient who responded to ICI had lower tumor stromal ACTA2 expression than the 4 nonresponders. Digital spatial profiling of tumor samples from 4 ICI responders and 5 ICI nonresponders revealed that responders may have lower ACTA2 expression in α-SMA-positive cancer-associated fibroblasts (CAF) than nonresponders (median: 5.00 vs. 5.50). CONCLUSIONS: ACTA2 expression is associated with survival and ICI response in patients with gastric cancer. ACTA2 expression in CAFs, but not in other cellular compartments, appears to be associated with ICI response.

Arid1a loss potentiates pancreatic ß-cell regeneration through activation of EGF signaling.

The dynamic regulation of ß-cell abundance is poorly understood. Since chromatin remodeling plays critical roles in liver regeneration, these mechanisms could be generally important for regeneration in other tissues. Here, we show that the ARID1A mammalian SWI/SNF complex subunit is a critical regulator of ß-cell regeneration. Arid1a is highly expressed in quiescent ß-cells but is physiologically suppressed when ß-cells proliferate during pregnancy or after pancreas resection. Whole-body Arid1a knockout mice are protected against streptozotocin-induced diabetes. Cell-type and temporally specific genetic dissection show that ß-cell-specific Arid1a deletion can potentiate ß-cell regeneration in multiple contexts. Transcriptomic and epigenomic profiling of mutant islets reveal increased neuregulin-ERBB-NR4A signaling. Chemical inhibition of ERBB or NR4A1 blocks increased regeneration associated with Arid1a loss. Mammalian SWI/SNF (mSWI/SNF) complex activity is a barrier to ß-cell regeneration in physiologic and disease states.

Variation of Hepatocellular Carcinoma Treatment Patterns and Survival Across Geographic Regions in a Veteran Population.

BACKGROUND: Veteran populations have five times the incidence of hepatocellular carcinoma (HCC) compared with the general population. The incidence of HCC has increased in the Veteran's Affairs Health System (VAHS), primarily due to the increased prevalence of cirrhosis. This study aimed to characterize differences in treatment patterns and overall survival rates across the five VAHS geographic regions. METHODS: Using the VA Corporate Data Warehouse, the authors built a comprehensive national dataset of Veteran patients with HCC diagnosed between 2001 and 2015 to compare patients across VAHS regions. A multivariable Cox proportional hazards model was used to identify factors associated with 5-year all-cause mortality. Kaplan-Meier curves were used to visualize the patient survival function, and the log-rank test was applied to test statistical significance. RESULTS: This retrospective study analyzed 13,434 patients. The West region had the highest rate of overall treatment receipt (63.6%), and the Southwest had the lowest rate (52.9%). After adjustment for demographic, clinicopathologic, treatment, and hospital factors, treatment in a non-West region continued to be significantly associated with a 10% to 13% increased risk of 5-year mortality (Midwest: hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.03-1.17; Northeast: HR, 1.10; 95% CI, 1.03-1.17; Southeast: HR, 1.13; 95% CI, 1.06-1.21; Southwest: HR, 1.11; 95% CI, 1.03-1.19) (p < 0.01). CONCLUSIONS: Treatment patterns and overall survival rates of HCC patients differ significantly across VAHS geographic regions. Targeted interventions to increase the rate of treatment in the non-West regions are needed to improve survival of HCC Veterans and provide uniformly high-quality care across VAHS facilities.