Disparities in Presentation at Time of Hepatocellular Carcinoma Diagnosis: A United States Safety-Net Collaborative Study.

BACKGROUND: While hepatocellular carcinoma (HCC) is ideally diagnosed outpatient by screening at-risk patients, many are diagnosed in Emergency Departments (ED) due to undiagnosed liver disease and/or limited access-to-healthcare. This study aims to identify sociodemographic/clinical factors associated with being diagnosed with HCC in the ED to identify patients who may benefit from improved access-to-care. METHODS: HCC patients diagnosed between 2012 and 2014 in the ED or an outpatient setting [Primary Care Physician (PCP) or hepatologist] were identified from the US Safety-Net Collaborative database and underwent retrospective chart-review. Multivariable regression identified predictors for an ED diagnosis. RESULTS: Among 1620 patients, median age was 60, 68% were diagnosed outpatient, and 32% were diagnosed in the ED. ED patients were more likely male, Black/Hispanic, uninsured, and presented with more decompensated liver disease, aggressive features, and advanced clinical stage. On multivariable regression, controlling for age, gender, race/ethnicity, poverty, insurance, and PCP/navigator access, predictors for ED diagnosis were male (odds ratio [OR] 1.6, 95% confidence interval [CI]: 1.1-2.2, p = 0.010), black (OR 1.7, 95% CI: 1.2-2.3, p = 0.002), Hispanic (OR 1.6, 95% CI: 1.1-2.6, p = 0.029), > 25% below poverty line (OR 1.4, 95% CI: 1.1-1.9, p = 0.019), uninsured (OR 3.9, 95% CI: 2.4-6.1, p < 0.001), and lack of PCP (OR 2.3, 95% CI: 1.5-3.6, p < 0.001) or navigator (OR 1.8, 95% CI: 1.3-2.5, p = 0.001). CONCLUSIONS: The sociodemographic/clinical profile of patients diagnosed with HCC in EDs differs significantly from those diagnosed outpatient. ED patients were more likely racial/ethnic minorities, uninsured, and had limited access to healthcare. This study highlights the importance of improved access-to-care in already vulnerable populations.

Surgical management of hepatocellular carcinoma patients with portal vein thrombosis: The United States Safety Net and Academic Center Collaborative Analysis.

BACKGROUND: Although consensus guidelines generally discourage any surgical management (ASM; i.e., resection and/or transplantation) in patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT), recent series from Asia have challenged this paradigm. METHODS: Patients from the US Safety Net Collaborative database (2012-2014) with localized HCC and radiographically confirmed PVT were propensity-score matched based on demographic and clinicopathologic factors associated with receipt of ASM and overall survival (OS). OS was compared between patients undergoing ASM and those not selected for surgery. RESULTS: Of 1910 HCC patients, 207 (14.5%) had localized disease and PVT. The majority received either liver-directed therapies (LDTs; 34%) and/or targeted systemic therapies (36%). Twenty-one patients (10.1%) underwent ASM (resection [n = 11], transplantation [n = 10]); a third experienced any complication with no 30-day mortalities. Independent predictors of undergoing ASM were younger age, recent hepatology consultation, and lower model of end-stage liver disease (MELD) score. After matching for age, comorbidities, MELD, tumor size, receipt of LDT, or systemic therapy, OS was significantly longer for patients selected for ASM versus non-ASM patients (median not reached vs. 5.8 months, p < .001). CONCLUSION: In a large North American multi-institutional cohort, a minority of HCC patients with PVT were selected for ASM. Resection or transplantation was associated with improved survival and may have a role in the multimodality management in selected patients.

Surgical resection of early stage hepatocellular carcinoma improves patient survival at safety net hospitals.

BACKGROUND AND OBJECTIVES: Surgical resection is indicated for hepatocellular carcinoma (HCC) patients with Child A cirrhosis. We hypothesize that surgical intervention and survival are limited by advanced HCC presentation at safety net hospitals (SNHs) versus academic medical centers (AMCs). METHODS: Patients with HCC and Child A cirrhosis in the US Safety Net Collaborative (2012-2014) were evaluated. Demographics, clinicopathologic features, operative characteristics, and outcomes were compared between SNHs and AMCs. Liver transplantation was excluded. Kaplan-Meier and Cox proportional-hazards models were used to identify the effect of surgery on overall (OS). RESULTS: A total of 689 Child A patients with HCC were identified. SNH patients frequently presented with T3/T4 stage (35% vs. 24%) and metastases (17% vs. 8%; p < .05). SNH patients were as likely to undergo surgery as AMC patients (17% vs. 18%); however, SNH patients were younger (56 vs. 64 years), underwent minor hepatectomy (65% vs. 38%), and frequently harbored well-differentiated tumors (23% vs. 2%; p < .05). On multivariate analysis, surgical resection and stage, but not hospital type, were associated with improved OS. CONCLUSIONS: Although SNH patients present with advanced HCC, survival outcomes for early stage HCC are similar at SNHs and AMCs. Identifying barriers to early diagnosis at SNH may increase surgical candidacy and improve outcomes.

Survival inequity in vulnerable populations with early-stage hepatocellular carcinoma: a United States safety-net collaborative analysis.

BACKGROUND: Access to health insurance and curative interventions [surgery/liver-directed-therapy (LDT)] affects survival for early-stage hepatocellular carcinoma (HCC). The aim of this multi-institutional study of high-volume safety-net hospitals (SNHs) and their tertiary-academic-centers (AC) was to identify the impact of type/lack of insurance on survival disparities across hospitals, particularly SNHs whose mission is to minimize insurance related access-to-care barriers for vulnerable populations. METHODS: Early-stage HCC patients (2012-2014) from the US Safety-Net Collaborative were propensity-score matched by treatment at SNH/AC. Overall survival (OS) was the primary outcome. Multivariable Cox proportional-hazard analysis was performed accounting for sociodemographic/clinical parameters. RESULTS: Among 925 patients, those with no insurance (NI) had decreased curative surgery, compared to those with government insurance (GI) and private insurance [PI, (PI-SNH:60.5% vs. GI-SNH:33.1% vs. NI-SNH:13.6%, p < 0.001)], and decreased median OS (PI-SNH:32.1 vs. GI-SNH:22.8 vs. NI-SNH:9.4 months, p = 0.002). On multivariable regression controlling for sociodemographic/clinical parameters, NI-SNH (HR:2.5, 95% CI:1.3-4.9, p = 0.007) was the only insurance type/hospital system combination with significantly worse OS. CONCLUSION: NI-SNH patients received less curative treatment than other insurance/hospitals types suggesting that treatment barriers, beyond access-to-care, need to be identified and addressed to achieve survival equity in early-stage HCC for vulnerable populations (NI-SNH).

Impact of hepatitis C treatment on long-term outcomes for patients with hepatocellular carcinoma: a United States Safety Net Collaborative Study.

BACKGROUND: Widespread HCV treatment for hepatocellular carcinoma (HCC) patients remains limited. Our aim was to evaluate the association of HCV treatment with survival and assess barriers to treatment. METHODS: Patients in the U.S. Safety Net Collaborative with HCV and HCC were included. Primary outcome was overall survival (OS). Secondary outcomes were recurrence-free survival (RFS) and barriers to receiving HCV treatment. RESULTS: Of 941 patients, 57% received care at tertiary referral centers (n=533), 74% did not receive HCV treatment (n=696), 6% underwent resection (n=54), 17% liver transplant (n=163), 50% liver-directed therapy (n=473), and 7% chemotherapy (n=60). HCV treatment was associated with improved OS compared to no HCV treatment (70 vs 21 months, p<0.01), persisting across clinical stages, HCC treatment modalities, and treatment facilities (all p<0.01). Surgical patients who received HCV treatment had improved RFS compared to those who did not (91 vs 80 months, p=0.03). On MVA, HCV treated patients had improved OS and RFS. On MVA, factors associated with failure to receive HCV treatment included Black race, higher MELD, and advanced clinical stage (all p<0.05). CONCLUSION: HCV treatment for HCC patients portends improved survival, regardless of clinical stage, HCC treatment, or facility type. Efforts must address barriers to HCV treatment.

Demographic and Clinicopathologic Factors of Patients With Hepatocellular Carcinoma in a Safety Net Hospital.

BACKGROUND: Safety net hospitals have historically cared for a disproportionate number of patients of low socioeconomic status, racial and ethnic minorities, and patients with cancer. These innate challenges make safety net hospitals important in understanding how to improve access to cancer care in order to fit the needs of vulnerable patients and ultimately improve their outcomes. The purpose of this study is to characterize the current state and treatment of hepatocellular carcinoma (HCC) at Ben Taub Hospital, a safety net hospital in Houston, Texas. MATERIALS AND METHODS: A retrospective chart review was performed to review the demographic characteristics, clinicopathologic data, treatment strategies, and outcomes of HCC patients at Ben Taub Hospital between January 2012 and December 2014. RESULTS: Two-hundred twenty-six men and 78 women with a mean age of 58 y underwent evaluation. Most (87%) were either uninsured or covered by Medicaid. The majority (69%) of patients presented with advanced (stage 2 or more) disease, with 58% of patients presenting with multiple lesions. Of the 40% that presented with a solitary lesion, the average size was 4.97 cm. Transarterial chemoembolization was used in 37% of patients and sorafenib was given to 26% of patients. Five patients underwent successful transplant. One hundred seventeen (38%) patients died of their disease, 25 patients are alive with no evidence of disease, and 159 patients have been lost to follow-up. CONCLUSIONS: Most patients with HCC presented to this safety net hospital with advanced disease; however, multiple local and systemic treatments were offered. Screening programs to detect HCC at an earlier stage are essential for successful long-term outcomes in a resource-strapped hospital with limited access to liver transplantation.

Long-Term Assessment of Pancreatic Function After Pancreatectomy for Cystic Neoplasms.

BACKGROUND: With advances in cross-sectional imaging, pancreatic cysts are more frequently diagnosed and have become a common indication for pancreatectomy. The impact of pancreatectomy in these patients is important. The purpose of this study was to assess short-term outcomes, long-term nutritional status, quality of life (QOL), and pancreas function after pancreatectomy for cystic neoplasms. MATERIALS AND METHODS: At a single institution, patients at least 3 y post-pancreatectomy for benign cystic neoplasms were identified. Using a validated questionnaire, short-term outcomes, long-term outcomes including endocrine and exocrine insufficiency, long-term nutritional status, and preoperative and postoperative QOL were compared based on operation and indication for resection. RESULTS: Among 102 eligible patients, 70 had valid contact information and 51 (72.9%) agreed to participate. Median follow-up was 6 (4-8) y. Patients undergoing pancreatoduodenectomy for benign cysts had higher morbidity than a similar cohort resected for pancreatic adenocarcinoma (patients with at least 1 ≥ grade 2 complication [49.0% versus 31.6%, P = 0.038]). After long-term follow-up, pancreatectomy did not significantly affect perceived QOL. Half of patients had mild-moderate or severe malnourishment, but pancreatic enzyme replacement was reported by only 4 (7.8%) patients. New-onset diabetes was present in 15 (29.4%) patients with median time-to-diagnosis of 6 (1-12) mo after resection. CONCLUSIONS: Pancreatectomy for benign cysts did not negatively impact patients' perceived QOL. However, after long-term follow-up, malnutrition and pancreatic insufficiency occurred in a significant percentage and may be greater than previously estimated. Consideration of short- and long-term outcomes should factor into preoperative counseling, especially in cysts with minimal risk of progression to malignancy.

Evidence Versus Practice in Early Drain Removal After Pancreatectomy.

BACKGROUND: Early drain removal when postoperative day (POD) one drain fluid amylase (DFA) was ≤5000 U/L reduced complications in a previous randomized controlled trial. We hypothesized that most surgeons continue to remove drains late and this is associated with inferior outcomes. METHODS: We assessed the practice of surgeons in a prospectively maintained pancreas surgery registry to determine the association between timing of drain removal with demographics, comorbidities, and complications. We selected patients with POD1 DFA ≤5000 U/L and excluded those without drains, and subjects without data on POD1 DFA or timing of drain removal. Early drain removal was defined as ≤ POD5. RESULTS: Two hundred and forty four patients met inclusion criteria. Only 90 (37%) had drains removed early. Estimated blood loss was greater in the late removal group (190 mL versus 100 mL, P = 0.005) and pathological findings associated with soft gland texture were more frequent (97 [63%] versus 35 [39%], P < 0.0001). Patients in the late drain removal group had more complications (84 [55%] versus 30 [33%], P = 0.001) including pancreatic fistula (55 [36%] versus 4 [4%], P < 0.0001), delayed gastric emptying (27 [18%] versus 3 [3%], P = 0.002), and longer length of stay (7 d versus 5 d, P < 0.0001). In subset analysis for procedure type, complications and pancreatic fistula remained significant for both pancreatoduodenectomy and distal pancreatectomy. CONCLUSIONS: Despite level one data suggesting improved outcomes with early removal when POD1 DFA is ≤ 5000 U/L, experienced pancreas surgeons more frequently removed drains late. This practice was associated with known risk factors (estimated blood loss, soft pancreas) and may be associated with inferior outcomes suggesting potential for improvement.

PIAS1 SUMO ligase regulates the self-renewal and differentiation of hematopoietic stem cells.

The selective and temporal DNA methylation plays an important role in the self-renewal and differentiation of hematopoietic stem cells (HSCs), but the molecular mechanism that controls the dynamics of DNA methylation is not understood. Here, we report that the PIAS1 epigenetic pathway plays an important role in regulating HSC self-renewal and differentiation. PIAS1 is required for maintaining the quiescence of dormant HSCs and the long-term repopulating capacity of HSC. Pias1 disruption caused the abnormal expression of lineage-associated genes. Bisulfite sequencing analysis revealed the premature promoter demethylation of Gata1, a key myeloerythroid transcription factor and a PIAS1-target gene, in Pias1(-/-) HSCs. As a result, Pias1 disruption caused the inappropriate induction of Gata1 in HSCs and common lymphoid progenitors (CLPs). The expression of other myeloerythroid genes was also enhanced in CLPs and lineage-negative progenitors, with a concurrent repression of B cell-specific genes. Consistently, Pias1 disruption caused enhanced myeloerythroid, but reduced B lymphoid lineage differentiation. These results identify a novel role of PIAS1 in maintaining the quiescence of dormant HSCs and in the epigenetic repression of the myeloerythroid program.

Sequential drain amylase to guide drain removal following pancreatectomy.

BACKGROUND: Although used as criterion for early drain removal, postoperative day (POD) 1 drain fluid amylase (DFA) ≤ 5000 U/L has low negative predictive value for clinically relevant postoperative pancreatic fistula (CR-POPF). It was hypothesized that POD3 DFA ≤ 350 could provide further information to guide early drain removal. METHODS: Data from a pancreas surgery consortium database for pancreatoduodenectomy and distal pancreatectomy patients were analyzed retrospectively. Those patients without drains or POD 1 and 3 DFA data were excluded. Patients with POD1 DFA ≤ 5000 were divided into groups based on POD3 DFA: Group A (≤350) and Group B (>350). Operative characteristics and 60-day outcomes were compared using chi-square test. RESULTS: Among 687 patients in the database, all data were available for 380. Fifty-five (14.5%) had a POD1 DFA > 5000. Among 325 with POD1 DFA ≤ 5000, 254 (78.2%) were in Group A and 71 (21.8%) in Group B. Complications (35 (49.3%) vs 87 (34.4%); p = 0.021) and CR-POPF (13 (18.3%) vs 10 (3.9%); p < 0.001) were more frequent in Group B. CONCLUSIONS: In patients with POD1 DFA ≤ 5000, POD3 DFA ≤ 350 may be a practical test to guide safe early drain removal. Further prospective testing may be useful.

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy With and Without Routine Intraperitoneal Drainage.

OBJECTIVE: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. BACKGROUND: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. METHODS: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. RESULTS: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. CONCLUSIONS: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

Characterization of human T lymphocytes engineered to express interleukin-15 and herpes simplex virus-thymidine kinase.

INTRODUCTION: Preclinical studies have demonstrated that tumor-reactive T cells expressing the interleukin (IL)-15 transgene had enhanced activity. Gene therapy strategies using IL-15 should include a safety mechanism in anticipation of possible adverse effects because IL-15 overexpression has been implicated in autoimmune disorders and may be involved in the pathogenesis of some leukemias. We developed a retroviral vector carrying both IL-15 and the herpes simplex virus-thymidine kinase (HSV-TK) suicide gene and characterized its application in the transduction of human T lymphocytes. METHODS: A retroviral vector carrying IL-15 and HSV-TK genes was optimized for the transduction of human T lymphocytes. IL-15 production was measured by enzyme-linked immunosorbent assay. Thymidine incorporation and cell viability assays were used to assess the efficacy of the HSV-TK suicide gene. Genetically modified tumor-infiltrating lymphocytes (TILs) were assayed for survival after withdrawal from exogenous IL-2. The activity and specificity of retrovirally transduced TILs were assessed using tumor coculture assays. RESULTS: Human T cells transduced with the IL-15 HSV-TK vector exhibited thymidine uptake in the absence of exogenous cytokine support and survived in culture for up to 80 d without IL-2. IL-15 HSV-TK-transduced T cells were efficiently killed by ganciclovir at concentrations as low as 0.1 µM. TILs transduced with the IL-15 HSV-TK vector retained specific recognition of HLA-A2+, MART1+ melanomas, even after withdrawal of IL-2. CONCLUSIONS: Human T lymphocytes genetically modified with the IL-15 HSV-TK retroviral vector retained the ability to recognize tumor antigen while gaining the ability to secrete IL-15 and prolong their own survival. IL-15 HSV-TK-transduced T cells expressed HSV-TK and could be efficiently eliminated by ganciclovir.

Varying malignant potential of appendiceal neuroendocrine tumors: importance of histologic subtype.

BACKGROUND: Neuroendocrine tumors (NETs) of the appendix include malignant carcinoid tumor (MCT), goblet cell carcinoid (GCT), and composite goblet cell carcinoid-adenocarcinoma (CGCC-A). METHODS: We compared characteristics and outcomes of these histologic subtypes. Patients with appendiceal NETs were identified from the National Cancer Database (1998-2007). Descriptive statistics were used to compare cohorts and associations between clinicopathologic factors and overall survival (OS) were examined using Cox proportional hazards models. RESULTS: A total of 2,812 patients with appendiceal NETs were identified. The most common histologic subtype was GCT (59.6%), followed by MCT (32.1%), CGCC-A (6.9%), and others (1.4%). CGCC-A had a significantly higher incidence of lymph node metastases (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.1-4.8) and distant metastases (OR, 6.0; 95% CI = 3.8-9.3) than GCT. The 5-year OS was 86.3% (95% CI, 81.4-89.9) for MCT, 77.6% (95% CI, 74.0-80.8) for GCT, and 56.3% (95% CI, 42.1-68.4) for CGCC-A (P < 0.0001). CONCLUSION: Appendiceal NETs represent a spectrum of disease with varying malignant potential: MCT (low), GCT (intermediate), and CGCC-A (high). GCTs represent the most common subtype, whereas CGCC-As place the patient at highest risk for regional and distant metastases and have the worst prognosis.

Pretreatment Health-Related Quality-of-Life Status and Survival in Pancreatobiliary Surgical Patients.

BACKGROUND: Pancreatobiliary (PB) disorders, especially cancer, negatively affect patients' health-related quality of life (HRQoL). However, the influence of baseline, preintervention HRQoL on perioperative and oncologic outcomes has not been well defined. We hypothesized that low baseline HRQoL is associated with worse perioperative and long-term survival outcomes for PB surgical patients. STUDY DESIGN: Pretreatment Functional Assessment of Cancer Therapy - Hepatobiliary Survey results and clinical data from PB patients (2008 to 2016) from a single center's prospective database were analyzed. Survey responses were aggregated into composite scores and divided into quintiles. Patients in the highest quintile of HRQoL were compared to patients in the bottom four quintiles combined. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Logistic and Cox regressions were used to determine associations between quintiles of HRQoL scores and 30-day complications and long-term survival, respectively. RESULTS: Of 162 patients evaluated, 99 had malignancy, and 63 had benign disease. Median follow-up was 31 months. Baseline HRQoL scores were similar for benign and malignant disease (p = 0.42) and were not associated with the development of any (p = 0.08) or major complications (p = 0.64). Patients with highest quintile HRQoL scores had improved 3-year OS (84.6 vs 61.7%, p = 0.03) compared to patients in the lowest four quintiles of HRQoL. Among cancer patients only, those with the highest quintile scores had improved 3-year OS (81.6 vs 47.4%, p = 0.02). On multivariable analysis, highest quintile HRQoL scores were associated with longer OS and DFS for patients with malignancy. CONCLUSIONS: Pretreatment HRQoL was associated with both OS and DFS among PB patients and might have prognostic utility. Future studies are necessary to determine whether patients with poorer HRQoL may benefit from targeted psychosocial interventions.

Factors associated with inability to return to intended oncologic treatment in pancreatic cancer.

BACKGROUND: Return to Intended Oncologic Treatment (RIOT) has been proposed as a quality metric in the care of cancer patients. We sought to define factors associated with inability to RIOT in Pancreatic Ductal Adenocarcinoma (PDAC) patients. METHODS: The NCDB was queried for patients who underwent pancreaticoduodenectomy for pathologic stage IB, IIA, or IIB PDAC from 2010 to 2016. Multivariable binary logistic regression models identified factors associated with failure to RIOT, and Kaplan-Meier survival analysis and Cox multivariable regression models demonstrated the impact of failure to RIOT on survival. RESULTS: Increasing age (p < .001), Hispanic race (p = .002), pathological stage IB (p = .004) and IIA (p = .001) as compared to IIB, increasing hospital stay (p < .001), and open surgical approach (p = .024) were associated with increased risk of inability to RIOT. Male sex (p < .001), Charlson-Deyo scores of 0 (p < .001) and 1 (p = .001) as compared to >2, negative surgical margins (p = .048), receiving care at academic institutions (p = .001), and increasing institutional case volume (p = .001) were associated with improved odds of RIOT. CONCLUSIONS: Patient features can impact RIOT and should be considered when designing multi-modality treatment strategies.

Long-Term Survival and Curative-Intent Treatment in Hepatitis B or C Virus-Associated Hepatocellular Carcinoma Patients Diagnosed during Screening.

Background: We initiated a prospective screening trial in patients with hepatitis to diagnose HCC in the early stage and to evaluate the impact on long-term survival. Methods: From 1993−2006, 10,372 patients with chronic hepatitis B (14%), hepatitis C (81%), or both (5%) were enrolled in an HCC screening program. All patients underwent liver biopsy at enrollment. Transabdominal ultrasonography and serum alpha-fetoprotein were evaluated every 6 months. Abnormal screening results led to axial imaging and tumor biopsy. Results: Cirrhosis was confirmed on biopsy in 2074 patients (20%). HCC was diagnosed in 1016 patients (9.8%), all of whom had cirrhosis (49.0% HCC incidence in patients with cirrhosis). HCC was diagnosed at the initial screening in 165 patients (16.2%) and on follow-up in 851 patients (83.8%). The HCC diagnosis median time during follow-up screening was 6 years (range 4−10). Curative-intent treatment (resection, ablation, or transplant) was performed in 713 patients (70.2%). Overall survival at 5 and 10 years in those 713 patients was 30% and 4%, respectively, compared to no 5-year survivors in the 303 patients with advanced-stage disease (p < 0.001). Cause of death at 5 years in the 713 patients treated with curative intent was HCC in 371 patients (52%), progressive cirrhosis in 116 patients (16%), and other causes in 14 patients (2%). At 10 years, 456 patients (64%) had died from HCC, 171 (24%) from progressive cirrhosis, and 57 (8%) from other causes. Conclusions: Our screening program diagnosed early-stage HCC, permitting curative-intent treatment in 70%, but the 10-year survival rate is 4% due to HCC recurrence and progressive cirrhosis.

The Evolving Landscape of Hepatocellular Carcinoma : A US Safety Net Collaborative Analysis of Etiology of Cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) has historically been the most common cause of cirrhosis and hepatocellular carcinoma (HCC) in the United States. With improved HCV treatment, cirrhosis secondary to other etiologies is increasing. Given this changing epidemiology, our aim was to determine the impact of cirrhosis etiology on overall survival (OS) in patients with HCC. METHODS: All patients with cirrhosis and primary HCC from the US Safety Net Collaborative (2012-2014) database were included. Patients were grouped into "safety net" and "academic" based on where they received their care. The primary outcome was the OS. RESULTS: 1479 patients were included. The average age was 60 years and 78% (n = 1156) were male. 56% (n = 649) received care at academic and 44% (n = 649) at safety net hospitals. The median model for end-stage liver disease (MELD) was 10 (IQR 8-16). Median OS was 23 months. Etiology of cirrhosis was viral hepatitis 56% (n = 612), alcohol abuse 14% (n = 152), alcohol and hepatitis 23% (n = 251), and other 7% (n = 85). Patients with alcohol-related cirrhosis (alcohol alone or with hepatitis) were younger (59 vs 62 years), more likely to be male (86% vs 75%), treated at a safety net facility (45% vs 35%), uninsured (17% vs 13%), and had a higher MELD (median 12 vs 10) (all P < .003). They were less likely to have been screened for HCC within 1 year of diagnosis (20% vs 29%) and to receive treatment (69% vs 81%), and more likely to present with stage IV disease (21% vs 15%) (all P < .001). Patients with alcohol-related cirrhosis had decreased OS (5-year OS 24% vs 40%, P < .001), which persisted in a subset analysis of both academic and safety net populations. CONCLUSION: Although not significant on MVA, alcohol-related cirrhosis is associated with all factors that correlate with decreased survival from HCC. Efforts must focus on this vulnerable patient population to optimize screening, treatment, and outcomes.

Dissecting disease, race, ethnicity, and socioeconomic factors for hepatocellular carcinoma: An analysis from the United States Safety Net Collaborative.

BACKGROUND: Racial/ethnic and socioeconomic disparities are assumed to negatively affect treatment and outcomes for hepatocellular carcinoma (HCC). Our aim was to investigate the interaction of racial/ethnic and socioeconomic factors with stage of disease and type of treatment facility in receipt of treatment and overall survival (OS) of patients with HCC. METHODS: All patients with primary HCC in the US Safety-Net Collaborative database (2012-2014) were included. Patients were categorized into "safety-net" or "tertiary referral center" based on where they received treatment. Socioeconomic factors were determined at the zip-code level and included median income and percent of adults who graduated from high-school. Primary outcomes were receipt of treatment and OS. RESULTS: On MV Cox regression, neither race/ethnicity, median income, nor care provided at a SNH were associated with decreased OS (all p > 0.05). Independent predictors of decreased OS included lack of insurance (HR 1.34), less educational attainment (HR 1.59) higher MELD score (HR 1.07), higher stage at diagnosis (II:HR 1.34, III:HR 2.87, IV:HR 3.23), and not receiving treatment (HR 3.94) (all p < 0.05). Factors associated with not receiving treatment included history of alcohol abuse (OR 0.682), increasing MELD (OR 0.874), higher stage at diagnosis (III: OR 0.234, IV: OR 0.210) and care at a safety net facility (OR 0.424) There were no racial/ethnic or socioeconomic disparities in receipt of treatment. CONCLUSIONS: There is no intrinsic or direct association of race/ethnicity, socioeconomic status, or being treated at select safety-net hospitals with worse outcomes. Poor liver function, no insurance, and advanced stage of presentation are the main determinants of not receiving treatment and decreased survival.

Understaging of clinical stage I pancreatic cancer and the impact of multimodality therapy.

BACKGROUND: Although current guidelines recommend multimodal therapy for all patients with pancreatic ductal adenocarcinoma, it is unclear the extent to which clinical stage I patients are accurately staged and how this may affect management. METHODS: In this retrospective cohort study of 4,404 patients aged 18-79 years with clinical stage 1 (ie, T1N0 or T2N0) pancreatic ductal adenocarcinoma treated with upfront resection in the National Cancer Database (2004-2014), understaging was ascertained by comparing pretreatment clinical stage with pathologic stage. The association between adjuvant treatment and overall risk of death among true stage I and understaged patients was evaluated using multivariable Cox regression. RESULTS: Upstaging was identified in 72.6% of patients (62.8% T3/4, 53.9% N1) of whom 69.7% received adjuvant therapy compared with 47.0% with true stage I disease. Overall survival at 5 years among those with true stage I disease was significantly higher than those who had been clinically understaged (42.9% vs 16.6%; log-rank, p < 0.001). For true stage I patients, adjuvant therapy was not associated with risk of death (hazard ratio: 1.07, 95% confidence interval: 0.89-1.29). For understaged patients, adjuvant therapy significantly decreased risk of death (hazard ratio: 0.64, 95% confidence interval: 0.55-0.74). CONCLUSION: The majority of clinical stage I pancreatic ductal adenocarcinoma patients actually have higher-stage disease and benefit from multimodal therapy; however, one third of understaged patients do not receive any adjuvant treatment. Clinicians should discuss all potential treatment strategies with patients (in the context of the acknowledged risks and benefits), including the utilization of neoadjuvant approaches in those presenting with potentially resectable disease.

Evidence-Based Management of Drains Following Pancreatic Resection: A Systematic Review.

Many pancreatic surgeons continue to use intraperitoneal drains, but others have limited or avoided their use, believing this improves outcomes. We conducted a systematic review and meta-analysis of the literature assessing outcomes in pancreatectomy without drains, selective drainage, and early drain removal. We searched PubMed, Embase, and the Cochrane Library databases and conducted a systematic review of randomized and nonrandomized studies comparing routine intra-abdominal drainage versus no drainage, selective drain use, and early versus late drain removal after pancreatectomy, with major complications as the primary outcome. A meta-analysis of the literature assessing routine use of drains was conducted using the random-effects model. A total of 461 articles met search criteria from PubMed (168 articles), Embase (263 articles), and the Cochrane Library (30 articles). After case reports and articles without primary data on complications were excluded, 14 studies were identified for systematic review. Definitive evidence-based recommendations cannot be made regarding the management of drains following pancreatectomy because of limitations in the available literature. Based on available evidence, the most conservative approach, pending further data, is routine placement of a drain and early removal unless the patient's clinical course or drain fluid amylase concentration suggests a developing fistula.