Uncovering Biological Factors That Regulate Hepatocellular Carcinoma Growth Using Patient‐Derived Xenograft Assays

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162740/3/hep31096.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162740/2/hep31096-sup-0001-Suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162740/1/hep31096_am.pd

Current Pattern of Use and Impact of Pringle Maneuver in Liver Resections in the United States

Pringle maneuver (PM) is used for inflow vascular control during hepatectomy, but its use remains controversial. We aimed to report its pattern of use and association with postoperative outcomes. We identified hepatectomy patients using the liver-targeted National Surgical Quality Improvement Program database (2014-2016). Associations between PM and posthepatectomy liver failure (PHLF), receipt of blood transfusion, and total hospital length of stay (LOS) were evaluated. We identified 7870 patients (74.9%) with no Pringle maneuver and 2632 (25.1%) with PM. PM patients were older (median age 61 versus 60 y, P = 0.002) and had higher ASA scores (76.1% versus 71.4% were ASA 3-4, P < 0.001). PM had more malignancy (83.0% versus 73.0%, P < 0.001), neoadjuvant therapy (37.7% versus 28.8%, P < 0.001), total lobectomy (30.6% versus 23.2%, P < 0.001), open resection (90.8% versus 74.9%, P < 0.001), and longer operations (246 min versus 212 min, P < 0.001). PM was associated with longer LOS (0.36 d, 95% confidence interval [CI] 0.11-0.60) and increased risk of PHLF (odds ratio [OR] 1.36, 95% CI 1.11-1.66), although not clinically significant grade B/C PHLF (OR 0.82, 95% CI 0.57-1.19), but was not associated with receipt of perioperative blood transfusions (OR 1.00, 95% CI 0.69-1.64). PM is associated with similar clinically significant PHLF and transfusion requirements but longer LOS compared with no Pringle maneuver

Comparative Outcomes of Adenosquamous Carcinoma of the Gallbladder: an Analysis of the National Cancer Database

Background A paucity of data exists regarding adenosquamous carcinoma of the gallbladder, a histology comprising under 10% of gallbladder cancer diagnoses. The aim of this study is to characterize the clinicopathological features of these tumors utilizing a population-based dataset compared with gallbladder adenocarcinoma. Methods We identified patients with gallbladder adenosquamous and adenocarcinoma from the National Cancer Database from 2004 to 2015. Patient demographics, tumor characteristics, treatment regimens, and overall survival were analyzed between the groups. Results We identified 13,158 patients: 12,455 (95%) with a diagnosis of gallbladder adenocarcinoma and 703 (5%) with adenosquamous carcinoma. Adenosquamous tumors were larger, poorly differentiated, and presented with Stage III/IV disease (75% vs 69%,p < 0.001). Overall 1-, 3-, and 5-year survival for adenosquamous and adenocarcinoma were 24%, 11%, and 9% vs 37%, 16%, and 11%, respectively (p < 0.001). Following surgical resection, adenosquamous carcinoma had more positive margins (31% vs 25%,p < 0.001), and median overall survival was 10.3 months vs 20.5 months for adenocarcinoma (p < 0.001). Overall survival at 1-, 3-, and 5-years for surgically resected adenosquamous and adenocarcinoma were 43%, 23%, and 18% versus 63%, 35%, and 25%, respectively (p < 0.001). In resected adenosquamous carcinoma, positive lymph nodes and margins were associated with worse survival, while adjuvant chemoradiation (HR 0.457, 95% CI 0.31-0.69,p < 0.001) was associated with improved survival. Conclusion Adenosquamous gallbladder cancer presented with larger tumors at advanced clinical stages when compared with adenocarcinoma. Overall survival was worse for adenosquamous tumors both overall, and following curative intent resection. Adjuvant chemoradiation was associated with improved survival in adenosquamous tumors

Adjuvant Therapy is Associated with Improved Survival in pT1N1 Gastric Cancer in a Heterogeneous Western Patient Population

Background Two recent South Korean studies showed adjuvant therapy (AT) was not associated with improved survival in pT1N1 gastric adenocarcinoma (GAC). We established the prognostic utility of lymph node status, determined the pattern of use of AT, and compared survival stratified by type of AT in pT1N1 GAC in a Western patient population. Methods We identified patients with pT1N0 and pT1N1 GAC using the National Cancer Database from 2004 to 2012. Clinicopathologic variables, treatment regimens, and overall survival (OS) were compared. Results We compared 4516 (86.6%) pT1N0 to 696 (13.4%) pT1N1 patients. pT1N1 tumors were larger (median size 2.5 vs. 1.8 cm, p  < 0.001), more often poorly differentiated (56.2% vs. 39.6%, p  < 0.001), and had higher median retrieved lymph nodes (RLN) (14 vs. 12, p  < 0.001) compared with pT1N0. pT1N1 was associated with worse median overall survival (OS) (6.9 vs. 9.9 years for pT1N0, p  < 0.001). pN1 was independently associated with worse OS (hazard ratio [HR] 2.17, 95% confidence interval [CI] 1.84–2.56). Increased RLN was associated with improved OS (HR 0.73, 95% CI 0.65–0.83). Among pT1N1 patients, 330 (47.4%) had observation (OBS), 77 (11.1%) received adjuvant chemotherapy (ACT), 68 (9.8%) received adjuvant radiation therapy (ART), and 221 (31.8%) received adjuvant chemoradiation therapy (ACRT). ACT and ACRT were independently associated with improved OS (HR 0.37, 95% CI 0.22–0.65 and HR 0.40, 95% CI 0.28–0.57). Conclusions pN1 was associated with worse survival and RLN ≥ 15 was associated with improved survival in pT1 GAC. ACT and ACRT were independently associated with improved survival in pT1N1 gastric cancer suggesting a valuable role in Western patients

Treatment and Survival Disparities of Colon Cancer in the Texas-Mexico Border Population: Cancer Disparities in Border Population

Previous studies have reported healthcare disparities in the Texas-Mexico border population. Our aim was to evaluate treatment utilization and oncologic outcomes of colon cancer patients in this vulnerable population. Patients with localized and regional colon cancer (CC) were identified in the Texas Cancer Registry (1995-2016). Clinicopathological data, hospital factors, receipt of optimal treatment, and overall survival (OS) were compared between Texas-Mexico Border (TMB) and the Non-Texas-Mexico Border (NTMB) cohorts. Multivariable analysis was performed to identify risk factors associated with decreased survival. We identified 43,557 patients with localized/regional CC (9% TMB and 91% NTMB). TMB patients were more likely to be Hispanic (73% versus 13%), less likely to have private insurance (13% versus 21%), were more often treated at safety net hospitals (82% versus 22%) and less likely at ACS-CoC accredited hospitals (32% versus 57%). TMB patients were more likely to receive suboptimal treatment (21% versus 16%) and had a lower median OS for localized (8.58 versus 9.58 y) and regional colon cancer (5.75 versus 6.18 y, all P < 0.001). In multivariable analysis, TMB status was not associated with worse OS. Factors associated with worse survival included receipt of suboptimal treatment, Medicare/insured status, and treatment in safety net and non-accredited ACS-CoC hospitals (all P < 0.001) CONCLUSIONS: While TMB CC patients had worse OS, TMB status itself was not found to be a risk factor for decreased survival. This survival disparity is likely associated with higher rate of suboptimal treatment, Medicare/Uninsured status, and decreased access to ACS-CoC accredited hospitals

Incidence and comparative outcomes of periampullary cancer: A population-based analysis demonstrating improved outcomes and increased use of adjuvant therapy from 2004 to 2012

Background and Objectives Periampullary adenocarcinoma (PAC) is stratified anatomically: ampullary adenocarcinoma (AA), distal cholangiocarcinoma (DCC), duodenal adenocarcinoma (DA), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine differences in incidence, prognosis, and treatment in stage-matched PAC patients in a longitudinal study. Methods PAC patients were identified in The National Cancer Database from 2004 to 2012. Clinicopathological variables were compared between subtypes. Covariate-adjusted treatment use and OS were compared. Results The 116 705 patients with PAC were identified: 1320 (9%) AA, 3732 (3%) DCC, 7142 (6%) DA, and 95 511 (82%) PDAC. DA, DCC, and PDAC were associated with worse survival compared with AA (hazard ratio [HR], 1.10; 95% CI, 1.1-1.1; HR, 1.50; 95% CI, 1.4-1.6, and HR, 1.90; 95% CI, 1.8-1.9). Among resected patients, DA was associated with improved survival compared with AA (HR, 0.70; 95% CI, 0.67-0.75); DCC and PDAC were associated with worse survival (HR, 1.41; 95% CI, 1.31-1.53 and HR, 2.041; 95% CI, 1.07-2.12). Resected AA, PDAC, and DA, but not DCC, demonstrated significantly improved survival over the studied period. While all patients had increased adjuvant therapy (AT) receipt over time (P < 0.001), only patients with PDAC had increased neoadjuvant therapy (NAT) receipt (P < 0.001). Conclusion Resected PDAC, AA, and DA were associated with clinically significant improved survival over time, mirroring a concurrent associated increased receipt of AT

Clinicopathologic Features and Outcomes of Early-Onset Pancreatic Adenocarcinoma in the United States

Limited research has been performed regarding pancreatic ductal adenocarcinoma (PDAC) diagnosed in early-onset patients. This study defined early-onset disease as cancer diagnosed before the age of 50 years and aimed to characterize the clinicopathologic factors associated with early- versus late-onset patients. The National Cancer Database was queried to identify early- and late-onset PDAC patients with cancer diagnosed from 2004 to 2013. Patient demographics, tumor characteristics, treatment regimens, and overall survival (OS) were compared between the groups. The study enrolled 207,062 patients, including 12,137 early-onset patients (5.9%) and 194,925 late-onset patients (94.1%). The early-onset patients (stage 3 or 4 cancer) were more likely to present with a later stage of disease (62.1% vs. 55.2%; p < 0.001) and to be male (57.1% vs. 50.0%; p < 0.001) than those with late-onset PDAC. The early-onset patients also presented with a lower Charlson/Deyo comorbidity score (80.9% vs. 66.6% had a score of 0; p < 0.001) and received higher rates of treatment (22.8% vs. 40.1% received no treatment, p < 0.001) than the late-onset patients. Furthermore, early-onset PDAC was associated with improved OS among all the PDAC patients (9.2 vs. 6.0 months; p < 0.001) and among the surgically resected patients (27.3 vs. 24.3 months; p < 0.001). Early-onset PDAC also was found to be independently associated with improved OS after adjustment for other significant clinicopathologic factors. Despite features suggestive of aggressive tumor biology at presentation, early-onset PDAC was independently associated with better OS than late-onset PDAC among all patients and among curatively resected stage-matched patients

Improved Survival in Surgically Resected Distal Cholangiocarcinoma Treated with Adjuvant Therapy: a Propensity Score Matched Analysis

Background Data on the efficacy of adjuvant therapy (AT) in distal cholangiocarcinoma (dCCA) is limited. This study aimed to determine the role of AT in resected dCCA and identify subgroups that benefit from AT. Methods We conducted a retrospective review of surgically resected dCCA in the NCDB from 2004 to 2013. Patients who received AT or observation (OB) were matched by propensity score. Log-rank test was used to compare OS. Results Of 1782 patients with resected dCCA, 840 (47%) were in the OB group and 942 (53%) in the AT group. AT was younger (64.0 vs. 68.7 years, p < 0.001), had less comorbidities (Charlson Deyo score 0) (74.6 vs. 68.0%, p < 0.001), and more likely to have private insurance (p < 0.001). AT was more likely to present with T3/T4 stage (72 vs. 57%, p < 0.001), N1/N2 disease (58 vs. 37%, p < 0.001), and positive surgical margins (26 vs. 16%, p < 0.001). After 1: 1 propensity score matching, 500 OB and 500 AT patients were compared. AT was associated with better OS (HR 0.79; 95% CI 0.67-0.93). Median OS was 31 and 25 months for the AT and OB (p = 0.006). The 1-, 3-, and 5-year survival rates were 87, 46, and 31% for AT; 79, 39, and 24% for OB. Subgroup analysis revealed an associated survival advantage for AT in T3/T4 tumors (HR = 0.72; 95% CI 0.59-0.89), node positive disease (HR 0.70; 95% CI 0.56-0.87), and positive margins (HR 0.58; 95% CI 0.42-0.81). Conclusion AT is associated with improved OS in resected dCCA, especially in T3/T4 tumors, node positive disease, and positive margins