ATM phosphorylates the FATC domain of DNA-PKcs at threonine 4102 to promote non-homologous end joining.

Ataxia-telangiectasia mutated (ATM) drives the DNA damage response via modulation of multiple signal transduction and DNA repair pathways. Previously, ATM activity was implicated in promoting the non-homologous end joining (NHEJ) pathway to repair a subset of DNA double-stranded breaks (DSBs), but how ATM performs this function is still unclear. In this study, we identified that ATM phosphorylates the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a core NHEJ factor, at its extreme C-terminus at threonine 4102 (T4102) in response to DSBs. Ablating phosphorylation at T4102 attenuates DNA-PKcs kinase activity and this destabilizes the interaction between DNA-PKcs and the Ku-DNA complex, resulting in decreased assembly and stabilization of the NHEJ machinery at DSBs. Phosphorylation at T4102 promotes NHEJ, radioresistance, and increases genomic stability following DSB induction. Collectively, these findings establish a key role for ATM in NHEJ-dependent repair of DSBs through positive regulation of DNA-PKcs.

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.

Machine Learning Improves Prediction Over Logistic Regression on Resected Colon Cancer Patients.

INTRODUCTION: Despite advances, readmission and mortality rates for surgical patients with colon cancer remain high. Prediction models using regression techniques allows for risk stratification to aid periprocedural care. Technological advances have enabled large data to be analyzed using machine learning (ML) algorithms. A national database of colon cancer patients was selected to determine whether ML methods better predict outcomes following surgery compared to conventional methods. METHODS: Surgical colon cancer patients were identified using the 2013 National Cancer Database (NCDB). The negative outcome was defined as a composite of 30-d unplanned readmission and 30- and 90-d mortality. ML models, including Random Forest and XGBoost, were built and compared with conventional logistic regression. For the accounting of unbalanced outcomes, a synthetic minority oversampling technique (SMOTE) was implemented and applied using XGBoost. RESULTS: Analysis included 528,060 patients. The negative outcome occurred in 11.6% of patients. Model building utilized 30 variables. The primary metric for model comparison was area under the curve (AUC). In comparison to logistic regression (AUC 0.730, 95% CI: 0.725-0.735), AUC's for ML algorithms ranged between 0.748 and 0.757, with the Random Forest model (AUC 0.757, 95% CI: 0.752-0.762) outperforming XGBoost (AUC 0.756, 95% CI: 0.751-0.761) and XGBoost using SMOTE data (AUC 0.748, 95% CI: 0.743-0.753). CONCLUSIONS: We show that a large registry of surgical colon cancer patients can be utilized to build ML models to improve outcome prediction with differential discriminative ability. These results reveal the potential of these methods to enhance risk prediction, leading to improved strategies to mitigate those risks.

Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome as Risk Factors for Acute Coronary Syndrome in Young Patients: Analysis of the National Inpatient Sample.

OBJECTIVE: This study aimed to compare the odds of acute coronary syndrome (ACS) in patients aged 18 to 40 years to patients older than 40 years with and without secondary diagnoses of systemic lupus erythematosus (SLE) or antiphospholipid antibody syndrome (APLS) while controlling for traditional cardiovascular (CV) risk factors. METHODS: Data were extracted from the National Inpatient Sample database from 2016 to 2018. The National Inpatient Sample was searched for hospitalizations of adult patients with ACS as the principal diagnosis, with and without SLE or APLS as secondary diagnoses. Age was divided categorically into 2 groups: adults aged 18 to 40 years and those older than 40 years. The primary outcome was the development of ACS. Multivariate logistic regression analyses were used to adjust for confounders. RESULTS: There were 90,879,561 hospital discharges in the 2016 to 2018 database. Of those, 55,050 between the ages of 18 to 40 years and 1,966,234 aged older than 40 years were hospitalized with a principal diagnosis of ACS. Traditional CV risk factors were associated with ACS hospitalizations in both age groups. In multivariate analysis of the 18 to 40 years age group, both SLE (odds ratio, 2.18; 95% confidence interval, 1.814-2.625) and APLS (odds ratio, 2.18; 95% confidence interval, 1.546-3.087) were strongly associated with ACS hospitalizations. After the age of 40 years, there were no increased odds of ACS hospitalizations for SLE or APLS. CONCLUSIONS: In the younger population, SLE and APLS were strongly associated with ACS hospitalizations in addition to the traditional CV risk factors. In the older age group, traditional CV risk factors dominated and diluted the effect of SLE and APLS.

Inaccurate Clinical Stage Is Common for Gastric Adenocarcinoma and Is Associated with Undertreatment and Worse Outcomes.

BACKGROUND: Accurate clinical staging (CS) of gastric cancer is critical for appropriate treatment selection and prognostication, but CS remains highly imprecise. Our study evaluates factors associated with inaccurate CS, the impact of inaccurate CS on outcomes, and utilization of adjuvant therapy in patients who are understaged. METHODS: We conducted a retrospective review of NCDB patients diagnosed with clinical early stage gastric adenocarcinoma (cT1-2N0M0) between 2004 and 2016. Patients not undergoing upfront gastrectomy or with missing pathologic staging were excluded. Patients were classified as accurately staged, inaccurately staged with receipt of adjuvant therapy (IS+), and inaccurately staged with no receipt of adjuvant therapy (IS-). Logistic regression was utilized to assess the impact of factors on CS accuracy and receipt of adjuvant therapies. Kaplan-Meier and Cox proportional hazard methods were used for survival analysis. RESULTS: Approximately 40% of patients were inaccurately staged (IS). cT2, moderately/poorly differentiated, and site-overlapping tumors were associated with increased likelihood of being IS. Treatment at an academic facility was associated with decreased likelihood of understaging. Only 54% of patients who were IS received adjuvant therapy. CONCLUSION: Accurate CS of gastric cancer remains inadequate. Understaging is associated with detrimental effects on receiving guideline-concordant care and, possibly, patient outcomes. Targeted interventions reducing the proportion of understaged patients and ensuring receipt of appropriate therapy is needed to optimize outcomes. Patients with high-risk disease that are frequently understaged may benefit from selective neoadjuvant therapy. Centralization of gastric cancer care may also be a key strategy in improving receipt of guideline-concordant therapies.

Tumor Biology Impacts Survival in Surgically Managed Primary Hepatic Vascular Malignancies.

BACKGROUND: Hepatic angiosarcoma (AS) and hepatic epithelioid hemangioendothelioma (HEHE) are rare primary hepatic vascular malignancies (PHVM) that remain poorly understood. To guide management, we sought to identify factors and trends predicting survival after surgical intervention using a national database. MATERIALS AND METHODS: In a retrospective analysis of the National Cancer Database patients with a diagnosis of PHVM were identified. Clinicopathologic factors were extracted and compared. Overall survival (OS) was estimated and predictors of survival were identified. RESULTS: Three hundred ninty patients with AS and 216 with HEHE were identified. Only 16% of AS and 36% of HEHE patients underwent surgery. The median OS for patients who underwent surgical intervention was 97 months, with 5-year OS of 30% for AS versus 69% for HEHE patients (P< 0.001). Tumor biology strongly impacted OS, with AS histology (Hazard Ratio [HR] of 3.61 [1.55-8.42]), moderate/poor tumor differentiation (HR = 3.86 [1.03-14.46]) and tumor size (HR = 1.01 [1.00-1.01]) conferring worse prognosis. The presence of metastatic disease in the surgically managed cohort (HR = 5.22 [2.01-13.57]) and involved surgical margins (HR = 3.87 [1.59-9.42]), were independently associated with worse survival. CONCLUSIONS: In this national cohort of PHVM, tumor biology, in the form of angiosarcoma histology, tumor differentiation and tumor size, was strongly associated with worse survival after surgery. Additionally, residual tumor burden after resection, in the form of positive surgical margins or the presence of metastasis, was also negatively associated with survival. Long-term clinical outcomes remain poor for patients with the above high-risk features, emphasizing the need to develop effective forms of adjuvant systemic therapies for this group of malignancies.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

B7-h2 is a costimulatory ligand for CD28 in human.

CD28 and CTLA-4 are cell surface cosignaling molecules essential for the control of T cell activation upon the engagement of their ligands B7-1 and B7-2 from antigen-presenting cells. By employing a receptor array assay, we have demonstrated that B7-H2, best known as the ligand of inducible costimulator, was a ligand for CD28 and CTLA-4 in human, whereas these interactions were not conserved in mouse. B7-H2 and B7-1 or B7-2 interacted with CD28 through distinctive domains. B7-H2-CD28 interaction was essential for the costimulation of human T cells' primary responses to allogeneic antigens and memory recall responses. Similar to B7-1 and B7-2, B7-H2 costimulation via CD28 induced survival factor Bcl-xL, downregulated cell cycle inhibitor p27(kip1), and triggered signaling cascade of ERK and AKT kinase-dependent pathways. Our findings warrant re-evaluation of CD28 and CTLA-4's functions previously attributed exclusively to B7-1 and B7-2 and have important implications in therapeutic interventions against human diseases.

Predictors and outcomes of converted minimally invasive pancreaticoduodenectomy: a propensity score matched analysis.

BACKGROUND: Data-driven patient selection guidelines are not available to optimize outcomes in minimally invasive pancreaticoduodenectomy (MIPD). We aimed to define risk factors associated with conversion from MIPD to open PD and to determine the impact of conversion on post-operative outcomes. METHODS: We conducted a retrospective review of MIPD using NSQIP from 2014 to 2015. Propensity score was used to match patients who underwent completed MIPD to converted MIPD. RESULTS: 467 patients were included: 375 (80.3%) MIPD and 92 (19.7%) converted. Converted patients were more often male (64% vs. 52%, p = 0.030), had higher rates of dyspnea (10% vs. 3%, p = 0.009), underwent more vascular (44% vs. 14%, p < 0.001) or multivisceral resection (19% vs. 6%, p = 0.0005), and were more likely attempted laparoscopically compared to robotically (76% vs. 51%, p < 0.001). Robotic approach was independently associated with reduced risk of conversion (OR 0.40, 95% CI 0.23-0.69), while male gender (OR 1.70, 95% CI 1.02-2.84), history of dyspnea (OR 3.85, 95% CI 1.49-9.96), vascular resection (OR 4.32, 95% CI 2.53-7.37), and multivisceral resection (OR 2.18, 95% CI 1.05-4.52) were associated with increased risk. Major complications were more common in converted patients (68% vs. 37%, p < 0.001). Converted patients had increased odds of non-home discharge (OR 3.25, 95% CI 1.06-9.97) and an associated increased length of stay of 3 days (95% CI 0.1-6.7). CONCLUSION: Patients with a history of dyspnea or tumors requiring vascular or multivisceral resection were at increased risk of conversion, and the robotic platform was associated with a lower rate of conversion. Conversion was independently associated with increased overall complications, increased length of stay, and non-home discharge.

Effect of fragmentation of cancer care on treatment use and survival in hepatocellular carcinoma.

BACKGROUND: Fragmented cancer care (FC), or care received from multiple institutions, increases systemic health care costs and potentiates cancer care disparities. There is a paucity of data on mechanisms contributing to FC and the resulting effect on patient outcomes. This study characterized patient- and hospital-level factors associated with FC, time to treatment (TTT), and overall survival (OS) in patients with hepatocellular carcinoma (HCC). METHODS: Patients newly diagnosed with HCC from 2004 to 2015 and receiving treatment were identified in the Texas Cancer Registry. Patient- and hospital-level factors were compared across 2 cohorts: an FC treatment group and a nonfragmented cancer care (NFC) treatment group. Covariate-adjusted treatment use and OS were compared between the 2 treatment groups. RESULTS: Among 4329 patients with HCC, 1185 (27.4%) received FC, and 3144 (72.6%) received NFC. Compared with NFC patients, FC patients had larger tumors (median size ≥4 cm, 52.6% vs 35.2%; P < .001), and a higher proportion had a regional/metastatic stage (35.9% vs 26.7%; P < .001). Among patients with localized disease, FC was associated with decreased odds of curative therapy (odds ratio, 0.83; 95% confidence interval [CI], 0.7-0.9). FC was associated with worse OS (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24) and increased TTT (HR, 0.76; 95% CI, 0.7-0.8). In the subset of patients with localized-stage HCC who received curative therapy, FC was associated with worse OS (median survival, 67 vs 43 months; HR, 1.2; 95% CI, 1.0-1.4) and increased TTT (HR, 0.74; 95% CI, 0.7-0.8). CONCLUSIONS: FC patients were less likely to undergo curative therapy when they were diagnosed at an early stage. After covariate adjustment, newly diagnosed patients with HCC receiving FC had worse OS and increased TTT.

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.

Non-home Discharge and Prolonged Length of Stay After Cytoreductive Surgery and HIPEC.

BACKGROUND: Predictive models for nonhome discharge (NHD) have been proposed in major surgical specialties. The rates and risk factors associated with NHD and prolonged length of stay (PLOS) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) have not been evaluated. The aim of this study is to identify risk factors for NHD and PLOS after CRS/HIPEC in a national cohort of patients. MATERIALS AND METHODS: CRS/HIPEC cases were identified from the National Surgical Quality Improvement Program 2011-2012 data set. Patients with an NHD or PLOS (>30 d) were compared with a group of patients discharged to home within 30 d. Univariate analysis was used to compare patient characteristics, operative variables, and postoperative complications among both groups. Multivariate regression analysis was used to identify independent predictors of NHD and PLOS. RESULTS: Five hundred fifty-six patients undergoing CRS/HIPEC were identified, of which 44 (7.9%) were not discharged to home within 30 d. The rate of NHD and PLOS in this cohort was 4.1% and 3.7%, respectively. Multivariate analysis identified age ≥65 y, pre-op albumin <3.0 g/dL, and having a multivisceral resection as independent predictors of NHD/PLOS. If all three predictors are met preoperatively, the probability of NHD/PLOS was calculated to be 30.2%. CONCLUSIONS: The main risk factors for NHD/PLOS after CRS/HIPEC were advanced age, hypoalbuminemia, and multivisceral resection. Adequate identification of these risk factors may facilitate preoperative discussion with patients, and improve discharge planning and resource utilization.

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.

Minimally Invasive Versus Open Pancreaticoduodenectomy: A Propensity-matched Study From a National Cohort of Patients.

OBJECTIVE: To compare the perioperative outcomes of minimally invasive pancreaticoduodenectomy (MIPD) in comparison with open pancreaticoduodenectomy (OPD) in a national cohort of patients. BACKGROUND: Limited well-controlled studies exist comparing perioperative outcomes between MIPD and OPD. METHODS: Patients who underwent MIPD and OPD were abstracted from the 2014 to 2015 pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program. OPD and MIPD patients were matched 3:1 using propensity score, and perioperative outcomes were compared. RESULTS: A total of 4484 patients were identified with 334 (7.4%) undergoing MIPD. MIPD patients were younger, more likely to be White, and had a lower rate of weight loss. They were more likely to undergo classic Whipple and to have a drain placed. After 3:1 matching, 1002 OPD patients were compared with 334 MIPD patients. MIPD was associated with longer mean operative time (426.6 vs 359.6 minutes; P < 0.01), higher readmission rate (19.2% vs 14.3%; P = 0.04) and lower rate of prolonged length of stay >14 days (16.5% vs 21.6%; P = 0.047). The 2 groups had a similar rate of 30-day mortality (MIPD 1.8% vs OPD 1.3%; P = 0.51), overall complications, postoperative pancreatic fistula, and delayed gastric emptying. A secondary analysis comparing MIPD without conversion or open assist with OPD showed that MIPD patients had lower rates of overall surgical site infection (13.4% vs 19.6%; P = 0.04) and transfusion (7.9% vs 14.4%; P = 0.02). CONCLUSIONS: MIPD had an equivalent morbidity and mortality rate to OPD, with the benefit of a decreased rate of prolonged length of stay, though this is partially offset by an increased readmission rate.

Comparison of Overall Survival Between Preoperative Chemotherapy and Chemoradiotherapy for Resectable Pancreatic Adenocarcinoma.

Background: Preoperative therapy is being increasingly used in the treatment of resectable pancreatic cancer. Because there are only limited data on the optimal preoperative regimen, we compared overall survival (OS) between preoperative chemotherapy (CT) and preoperative chemoradiotherapy (CRT) in resectable pancreatic adenocarcinoma. Patients and Methods: Patients receiving preoperative therapy and resection for clinical T1-3N0-1M0 adenocarcinoma of the pancreas were identified in the National Cancer Database for 2006 through 2012. We constructed inverse probability of treatment weights to balance baseline group differences, and compared OS between CT and CRT, as well as pathologic and postoperative findings. Results: We identified 1,326 patients (CT: 616; CRT: 710). Differences in OS were not significant between CRT and CT (median survival, 25 vs 26 months; P=.10; weight-adjusted hazard ratio, 0.89; 95% CI, 0.77-1.02). Compared with patients in the CT group, those in the CRT group had lower pathologic T stage (ypT0/T1/T2: 36% vs 21%; P<.01), less lymph node involvement (ypN1: 35% vs 59%; P<.01), and fewer positive resection margins (14% vs 21%; P=.01), but had more postoperative unplanned readmissions (9% vs 6%; P=.01) and increased 90-day mortality (7% vs 4%; P=.03). Those in the CRT group were also less likely to receive postoperative therapy (26% vs 51%; P<.01). Conclusions: Preoperative CT and CRT have similar OS, but CRT is associated with more favorable pathologic features at the cost of higher postoperative morbidity and mortality. Additional trials investigating preoperative therapy are needed for patients with resectable pancreatic cancer.

Racial and ethnic disparities in a national cohort of ampullary cancer patients.

BACKGROUND AND OBJECTIVES: Racial and ethnic variations have been described in the different malignancies, but no such data exists for ampullary cancer. The aim of this study was to present an updated report on the epidemiology, treatment patterns, and survival of a national cohort of ampullary cancer patients. METHODS: Patients diagnosed with ampullary cancer between 2004 and 2014 were identified in the National Cancer Database. Overall survival was estimated and compared between racial/ethnic groups using the log-rank test. RESULTS: A total of 14 879 patients were identified; 78% of the patients were White, 9% Hispanic, 8% Black, and 5% Asian. We noted significant differences in disease presentation, socioeconomic status, and outcomes. Blacks had the lowest median overall survival at 18.9 months followed by Whites at 23.9 months, Hispanics at 32.7 months, and Asians at 37.4 months. On a multivariate Cox proportional-hazards model, being Black was associated with worse survival compared to being White while being Asian and Hispanic were associated with better survival. CONCLUSIONS: Overall survival of ampullary cancer patients was independently associated with race and ethnicity. Further studies are needed to clarify whether these disparities are primarily due to socioeconomic status or biologic factors.

Comparative outcomes of adenosquamous carcinoma of the pancreas: An analysis of the National Cancer Database.

BACKGROUND: A paucity of data exists regarding the natural history and outcome measures of adenosquamous carcinoma of the pancreas (ASCP), a histology distinct from pancreatic adenocarcinoma (PDAC). The aim of this study is to characterize the clinicopathological features of ASCP in a large cohort of patients comparing outcome measures of surgically resected patients to PDAC. METHODS: We identified patients diagnosed with ASCP or PDAC from the National Cancer Database from 2004 to 2012. Patient demographics, tumor characteristics, treatment regimens, and overall survival were analyzed between the groups. RESULTS: We identified 207 073 patients: 205 328 (99%) in the PDAC group and 1745 (1%) in the ASCP group. ASCP tumors were larger, located more frequently in a body/tail location (36% vs 24%, P < 0.001), undifferentiated/anaplastic histology (41% vs 17%, P < 0.001), and early stage presentation, (39% vs 32%, P < 0.001). There was no significant difference in OS when comparing all patients with PDAC and ASCP (6.2 months and 5.7 months, P = 0.601). In surgical patients ASCP histology was associated with worse OS (14.8 months vs 20.5 months, P < 0.001) but had lower nodal involvement (55% vs 61%, P < 0.001). ASCP histology was independently associated with worse OS, after adjusting for tumor characteristics, treatment, and patient demographics. In patients with only resected ASCP histology, negative lymph node status, R0 surgical resection, and receipt of chemotherapy was independently associated with improved overall survival following surgical resection. CONCLUSION: Although patients with ASCP and PDAC tumors have similar survival when non-surgical and surgical patients are combined, ASCP is associated with worse survival in stage I/II resected patients.

Conversion of Minimally Invasive Distal Pancreatectomy: Predictors and Outcomes.

BACKGROUND: Data on the risk factors for conversion during minimally invasive distal pancreatectomy (MIDP) and its effect on postoperative outcomes are limited. METHODS: This retrospective study used the pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program database to compare MIDP requiring unplanned conversion with completed MIDP and open distal pancreatectomy (ODP). RESULTS: Of the 2926 cases identified in this study, 48.8% had ODP, 42.8% had MIDP, and 7.9% had conversion to MIDP. The conversion rate was 15.3% overall, 17.3% for laparoscopic surgery, and 8.5% for robotic surgery (p < 0.001). The risk factors associated with conversion were higher body mass index (BMI), low preoperative albumin level, a current smoking habit, and malignant T3/T4 disease or chronic pancreatitis compared with benign tumor smaller than 5 cm. A robotic approach was associated with a lower adjusted conversion rate than laparoscopy (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.19-0.52). After adjustment, conversion was associated with a higher overall complication rate than MIDP (OR 1.89; 95% CI 1.35-2.66) or ODP (OR 1.41; 95% CI 1.00-1.98). CONCLUSIONS: Chronic pancreatitis, large malignant tumors, higher BMI, lower serum albumin, and a current smoking habit were shown to be independent risk factors for conversion during MIDP. A robotic approach was associated with a lower conversion rate than laparoscopic MIDP. Conversion of MIDP was associated with a higher overall complication rate than completed MIDP or ODP. Adequate patient selection for MIDP may prevent conversion and associated increased morbidity.

The Yield of Staging Laparoscopy in Gastric Cancer is Affected by Racial and Ethnic Differences in Disease Presentation.

BACKGROUND: Gastric cancer is a heterogeneous disease with variable presentation between racial and ethnic groups. Staging laparoscopy (SL) detects occult metastases not visible on cross-sectional imaging and therefore improves staging. It remains unclear how differences in race and ethnicity affect disease presentation and the yield of SL. METHODS: We performed a retrospective review of a prospectively maintained database to identify patients with gastric cancer treated with curative intent at our institutions from 2008 to 2015. RESULTS: Hispanic patients presented at an earlier mean age (55.5 ± 11.9 years) compared with Asian (59.8 ± 13.9 years), African American (61.0 ± 10.0 years), and white patients (61.7 ± 12.5 years; p = 0.046) and with more locally advanced disease (clinical stage T3/T4 or node positive; Hispanic 87%; African American 79%; white 68%, Asian 55%; p = 0.03). SL identified 42 patients (34%) with occult metastatic disease. Hispanics were more likely to have a positive SL (44%) than white patients (21%; p = 0.04). On univariate analysis, Hispanic ethnicity, clinical T3/T4, positive nodal disease, signet ring cells, and poor differentiation were predictors of a positive SL. On multivariable analysis, clinical T3/T4, signet ring cells, and poor differentiation independently predicted radiographically occult disease. CONCLUSIONS: Hispanic patients presented with more locally advanced disease and were more likely to have occult disease found on SL compared with white patients. Laparoscopy should be used routinely as part of the pretreatment staging evaluation for patients with locally advanced disease as it alters the management in a significant proportion of patients.