Stromal-derived NRG1 enables oncogenic KRAS bypass in pancreas cancer.

Activating KRAS mutations (KRAS*) in pancreatic ductal adenocarcinoma (PDAC) drive anabolic metabolism and support tumor maintenance. KRAS* inhibitors show initial antitumor activity followed by recurrence due to cancer cell-intrinsic and immune-mediated paracrine mechanisms. Here, we explored the potential role of cancer-associated fibroblasts (CAFs) in enabling KRAS* bypass and identified CAF-derived NRG1 activation of cancer cell ERBB2 and ERBB3 receptor tyrosine kinases as a mechanism by which KRAS*-independent growth is supported. Genetic extinction or pharmacological inhibition of KRAS* resulted in up-regulation of ERBB2 and ERBB3 expression in human and murine models, which prompted cancer cell utilization of CAF-derived NRG1 as a survival factor. Genetic depletion or pharmacological inhibition of ERBB2/3 or NRG1 abolished KRAS* bypass and synergized with KRASG12D inhibitors in combination treatments in mouse and human PDAC models. Thus, we found that CAFs can contribute to KRAS* inhibitor therapy resistance via paracrine mechanisms, providing an actionable therapeutic strategy to improve the effectiveness of KRAS* inhibitors in PDAC patients.

Minorities Face Delays to Pancreatic Cancer Treatment Regardless of Diagnosis Setting.

INTRODUCTION: Our analysis was designed to characterize the demographics and disparities between the diagnosis of pancreas cancer during emergency presentation (EP) and the outpatient setting (OP) and to see the impact of our institutions pancreatic multidisciplinary clinic (PMDC) on these disparities. METHODS: Institutional review board-approved retrospective review of our institutional cancer registry and PMDC databases identified patients diagnosed/treated for pancreatic ductal adenocarcinoma between 2014 and 2022. Chi-square tests were used for categorical variables, and one-way ANOVA with a Bonferroni correction was used for continuous variables. Statistical significance was set at p < 0.05. RESULTS: A total of 286 patients met inclusion criteria. Eighty-nine patients (31.1%) were underrepresented minorities (URM). Fifty-seven (64.0%) URMs presented during an EP versus 100 (50.8%) non-URMs (p = 0.037). Forty-one (46.1%) URMs were reviewed at PMDC versus 71 (36.0%) non-URMs (p = 0.10). No differences in clinical and pathologic stage between the cohorts (p = 0.28) were present. URMs took 22 days longer on average to receive treatment (66.5 days vs. 44.8 days, p = 0.003) in the EP cohort and 18 days longer in OP cohort (58.0 days vs. 40.5 days, p < 0.001) compared with non-URMs. Pancreatic Multidisciplinary Clinic enrollment in EP cohort eliminated the difference in time to treatment between cohorts (48.3 days vs. 37.0 days; p = 0.151). RESULTS: Underrepresented minorities were more likely to be diagnosed via EP and showed delayed times to treatment compared with non-URM counterparts. Our PMDC alleviated some of these observed disparities. Future studies are required to elucidate the specific factors that resulted in these findings and to identify solutions.

Payer-Negotiated Price Variation and Relationship to Surgical Outcomes for the Most Common Cancers at NCI-Designated Cancer Centers.

BACKGROUND: Federal rules mandate that hospitals publish payer-specific negotiated prices for all services. Little is known about variation in payer-negotiated prices for surgical oncology services or their relationship to clinical outcomes. We assessed variation in payer-negotiated prices associated with surgical care for common cancers at National Cancer Institute (NCI)-designated cancer centers and determined the effect of increasing payer-negotiated prices on the odds of morbidity and mortality. MATERIALS AND METHODS: A cross-sectional analysis of 63 NCI-designated cancer center websites was employed to assess variation in payer-negotiated prices. A retrospective cohort study of 15,013 Medicare beneficiaries undergoing surgery for colon, pancreas, or lung cancers at an NCI-designated cancer center between 2014 and 2018 was conducted to determine the relationship between payer-negotiated prices and clinical outcomes. The primary outcome was the effect of median payer-negotiated price on odds of a composite outcome of 30 days mortality and serious postoperative complications for each cancer cohort. RESULTS: Within-center prices differed by up to 48.8-fold, and between-center prices differed by up to 675-fold after accounting for geographic variation in costs of providing care. Among the 15,013 patients discharged from 20 different NCI-designated cancer centers, the effect of normalized median payer-negotiated price on the composite outcome was clinically negligible, but statistically significantly positive for colon [aOR 1.0094 (95% CI 1.0051-1.0138)], lung [aOR 1.0145 (1.0083-1.0206)], and pancreas [aOR 1.0080 (1.0040-1.0120)] cancer cohorts. CONCLUSIONS: Payer-negotiated prices are statistically significantly but not clinically meaningfully related to morbidity and mortality for the surgical treatment of common cancers. Higher payer-negotiated prices are likely due to factors other than clinical quality.

Venous thromboembolism in patients with pancreatic adenocarcinoma: Disease burden and initiation of ambulatory thromboprophylaxis.

BACKGROUND/OBJECTIVES: Ambulatory thromboprophylaxis (AT) in patients with pancreatic adenocarcinoma (PAC) reduces venous thromboembolism (VTE) risk and is recommended for patients receiving systemic chemotherapy. We evaluated VTE rates, severity, timing, and risk factors in PAC patients as well as AT rates and initiation times. METHODS: Patients diagnosed with PAC were included. Data collected included patient demographics, medical history, PAC diagnosis, development of VTE, AT, and bleeding episodes. VTE was defined as a DVT or a PE. Patients were classified as receiving AT for VTE prevention if they received a prescription for outpatient anticoagulation. RESULTS: The cohort included 243 PAC patients. VTE occurred in 24 %. Overall, 52 % developing VTE were hospitalized and 5 % died as a result of the VTE. Of those who developed VTE 50 % were diagnosed within the first 2 months of PAC diagnosis. Univariate predictors of elevated VTE risk included an elevated Onkotev score, metastasis at diagnosis, male gender and not receiving AT. Multivariate predictors of elevated VTE risk included male gender (P = 0.014) and not receiving AT (P = 0.001). Overall, 30 % of patients received AT. The median time from diagnosis to initiation of AT was 43 days. Major bleeding occurred in 5.8 %. Patients receiving AT were not at a significantly increased risk of major bleeding (p = 0.5). Patients with intestinal tumor invasion were at significantly increased risk of major bleeding (P = 0.021). CONCLUSION: VTE risk is significant and morbid in PAC patients. AT rates are low, and initiation is often delayed. Therapeutic endoscopists diagnosing PAC may be helpful in AT initiation.

Changes in characteristics of gastroenterology center inpatients in Japan because of rapidly aging society.

BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.

Evaluation of the availability of single-position treatment with a rotating gantry and the validity of deformable image registration dose assessment for pancreatic cancer carbon-ion radiotherapy.

BACKGROUND: This study aimed to evaluate the clinical acceptability of rotational gantry-based single-position carbon-ion radiotherapy (CIRT) to reduce the gastrointestinal (GI) dose in pancreatic cancer. We also evaluated the usefulness of the deformable image registration (DIR)-based dosimetry method for CIRT. MATERIAL AND METHODS: Fifteen patients with pancreatic cancer were analyzed. The treatment plans were developed for four beam angles in the supine (SP plan) and prone (PR plan) positions. In the case of using multiple positions, the treatment plan was created with two angles for each of the supine and prone position (SP + PR plan). Dose evaluation for multiple positions was performed in two ways: by directly adding the values of the DVH parameters for each position treatment plan (DVH sum), and by calculating the DVH parameters from the accumulative dose distribution created using DIR (DIR sum). The D2cc and D6cc of the stomach and duodenum were recorded for each treatment plan and dosimetry method and compared. RESULTS: There were no significant differences among any of the treatment planning and dosimetry methods (p > 0.05). The DVH parameters for the stomach and duodenum were higher in the PR plan and SP plan, respectively, and DVH sum tended to be between the SP and PR plans. DVH sum and DIR sum, DVH sum tended to be higher for D2cc and DIR sum tended to be higher for D6cc. CONCLUSION: There were no significant differences in the GI dose, which suggests that treatment with a simple workflow performed in one position should be clinically acceptable. In CIRT, DIR-based dosimetry should be carefully considered because of the potential for increased uncertainty due to the steep dose distributions.

Current landscape of gastrointestinal radiation oncology in Spain: a multicenter real-life survey and comparison with key clinical guidelines.

Background: The GI Tumors Workgroup, a division of the Spanish Society of Radiation Therapy, conducted a survey in December 2020 to assess the adherence of radiation oncologists in Spain to international guidelines for gastrointestinal tumors. Materials and methods: Using Google Forms, we designed a survey covering treatments for esophageal, gastric, pancreatic, and rectal cancers. Results: In esophageal cancer treatment, neoadjuvant chemoradiation was the standard in 76.7% of institutions. Radiation doses range from 41.1 to 50.4 Gy in conventional fractionation. Planning positron emission tomography-computed tomography (PET-CT) was performed in 83.3% of centers, and intensity-modulated radiation therapy/volumetric-arc radiation therapy (IMRT/VMAT) was the preferred technique in 86.7% of institutions. For gastric cancer, 71.4% followed perioperative chemotherapy guidelines. In the case of adjuvant radiotherapy, the majority prescribed 45-50.4 Gy, and 82.1% used IMRT/VMAT for treatment. For pancreas cancer, neoadjuvant chemotherapy followed by surgery in borderline resectable tumors and induction chemotherapy followed by radical radiotherapy for non-resectable tumors were the most frequent approaches. IMRT/VMAT was the primary technique. Locally advanced rectal cancer treatment is mainly based on neoadjuvant radiotherapy in all institutions. The preferred radiation doses typically range from 45 to 50 Gy in conventional fractionation. IMRT/VMAT was standard in most Institutions. Conclusions: Spain's radiotherapy practices among respondents generally align with international guidelines for GI tumors highlighting Spain's commitment to evidence-based medical practice.

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden.

BACKGROUND: Pembrolizumab confers minimal benefit to most patients with pancreas cancer. We explored survival and patient treatment burden (for example, death within 14 days of therapy) in a subgroup who had early access to pembrolizumab . METHODS: This multisite study examined consecutive pancreas cancer patients, who received pembrolizumab from 2004 through 2022. Median overall survival of > 4 months was to be deemed favorable. Patient treatment burden and medical record quotations are presented descriptively. RESULTS: Forty-one patients (median age 66 years; range 36, 84) are included. Fifteen (37%) had dMMR, MSI-H, TMB-H, or Lynch syndrome; and 23 (56%) received concurrent therapy. The median overall survival was 7.2 months (95% confidence interval (CI): 5.2, 12.7 months); 29 were deceased at the time of reporting. Patients with dMMR, MSI-H, TMB-H, or Lynch syndrome had a lower risk of death: hazard ratio (HR): 0.29 (95% CI: 0.12, 0.72); p = 0.008. Medical record phrases ("brilliant response") aligned with the above. One patient died within 14 days of therapy, and one was in an intensive care unit within 30 days of death. Fifteen patients enrolled in hospice; four of these died < 3 days later. CONCLUSIONS: These unexpectedly favorable findings underscore the need for healthcare providers-including palliative care providers-to knowledgeably guide patients about cancer therapy even near the end of life.

Effective anticancer agents based-on two Pillar[5]arene derivatives for pancreas cancer cell lines: synthesis, apoptotic effect, caspase pathway.

This study aimed to evaluate the possible anticancer effects of two different pillar[5]arene derivatives (5Q-[P5] and 10Q-P[5]) on two different pancreatic cancer cell lines in vitro. For this purpose, changes in the expression of major genes that play a role in apoptosis and caspase pathways were investigated. Panc-1 and BxPC-3 cell lines were used in the study and the cytotoxic dose of pillar[5]arenes was determined by the MTT method. Changes in gene expression after pillar[5]arenes treatment were evaluated by real-time polymerase chain reaction (qPCR). Apoptosis was studied by flow cytometry. As a result of analysis, it was determined that proapoptotic genes and genes involved in major caspase activation were upregulated and antiapoptotic genes were down-regulated in Panc-1 cell line treated with pillar[5]arenes. Flow cytometric apoptosis analysis also showed an increased apoptosis rate in this cell line. On the contrary, although MTT analysis showed cytotoxic effect in BxPC-3 cell line treated with two pillar[5]arene derivatives, the apoptosis pathway was not active. This suggested that it may activate different death pathways for BxPC-3 cell line. Thus, it was first determined that the pillar[5]arene derivatives reduced cancer cell proliferation on pancreatic cancer cells.

Identifying patient profiles of disparate care in resectable pancreas cancer using latent class analysis.

BACKGROUND AND OBJECTIVES: Disparities in pancreas cancer care are multifactorial, but factors are often examined in isolation. Research that integrates these factors in a single conceptual framework is lacking. We use latent class analysis (LCA) to evaluate the association between intersectionality and patterns of care and survival in patients with resectable pancreas cancer. METHODS: LCA was used to identify demographic profiles in resectable pancreas cancer (n = 140 344) diagnosed from 2004 to 2019 in the National Cancer Database (NCDB). LCA-derived patient profiles were used to identify differences in receipt of minimum expected treatment (definitive surgery), optimal treatment (definitive surgery and chemotherapy), time to treatment, and overall survival. RESULTS: Minimum expected treatment (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.65, 0.75) and optimal treatment (HR 0.58, 95% CI: 0.55, 0.62) were associated with improved overall survival. Seven latent classes were identified based on age, race/ethnicity, and socioeconomic status (SES) attributes (zip code-linked education and income, insurance, geography). Compared to the referent group (≥65 years + White + med/high SES), the ≥65 years + Black profile had the longest time-to-treatment (24 days vs. 28 days) and lowest odds of receiving minimum (odds ratio [OR] 0.67, 95% CI: 0.64, 0.71) or optimal treatment (OR 0.76, 95% CI: 0.72, 0.81). The Hispanic patient profile had the lowest median overall survival-55.3 months versus 67.5 months. CONCLUSIONS: Accounting for intersectionality in the NCDB resectable pancreatic cancer patient cohort identifies subgroups at higher risk for inequities in care. LCA demonstrates that older Black patients and Hispanic patients are at particular risk for being underserved and should be prioritiz for directed interventions.

Robotic pancreatoduodenectomy: trends in technique and training challenges.

BACKGROUND: More complex cases are being performed robotically. This study aims to characterize trends in robotic pancreatoduodenectomy (RPD) over time and assess opportunities for advanced trainees. METHODS: Using the ACS-NSQIP database from 2014 to 2019, PD cases were characterized by operative approach (open-OPN, laparoscopic-LAP, robotic-ROB). Proficiency and postoperative outcomes were described by approach over time. RESULTS: 24,268 PDs were identified, with the ROB approach increasing from 2.8% to 7.5%. Unplanned conversion increased over time for LAP (27.7-39.0%, p = 0.003) but was unchanged for ROB cases (14.8-14.7%, p = 0.257). Morbidity increased for OPN PD (35.5-36.8%, p = 0.041) and decreased for ROB PD (38.7-30.3%, p = 0.010). Mean LOS was lower in ROB than LAP/OPN (9.5 vs. 10.9 vs. 10.9 days, p < 0.00001). Approximately, 100 AHPBA, SSO, and ASTS fellows are being trained each year in North America; however, only about 5 RPDs are available per trainee per year which is far below that recommended to achieve proficiency. CONCLUSION: Over a 6-year period, a significant increase was observed in the use of RPD without a concomitant increase in conversion rates. RPD was associated with decreased morbidity and length of stay. Despite this shift, the number of cases being performed is not adequate for all fellows to achieve proficiency before graduation.

Lovastatin Treatment Inducing Apoptosis in Human Pancreatic Cancer Cells by Inhibiting Cholesterol Rafts in Plasma Membrane and Mitochondria.

Resistance to anticancer drugs is a problem in the treatment of pancreatic ductal carcinoma (PDAC) and overcoming it is an important issue. Recently, it has been reported that statins induce apoptosis in cancer cells but the mechanism has not been completely elucidated. We investigated the antitumor mechanisms of statins against PDAC and their impact on resistance to gemcitabine (GEM). Lovastatin (LOVA) increased mitochondrial oxidative stress in PDAC cells, leading to apoptosis. LOVA reduced lipid rafts in the plasma membrane and mitochondria, suppressed the activation of epithelial growth factor receptor (EGFR) and AKT in plasma membrane rafts, and reduced B-cell lymphoma 2 (BCL2)-Bcl-2-associated X protein (BAX) binding and the translocation of F1F0 ATPase in mitochondrial rafts. In the three GEM-resistant cell lines derived from MIA and PANC1, the lipid rafts in the cell membrane and the mitochondria were increased to activate EGFR and AKT and to increase BCL2-BAX binding, which suppressed apoptosis. LOVA abrogated these anti-apoptotic effects by reducing the rafts in the resistant cells. By treating the resistant cells with LOVA, GEM sensitivity improved to the level of the parental cells. Therefore, cholesterol rafts contribute to drug resistance in PDAC. Further clinical research is warranted on overcoming anticancer drug resistance by statin-mediated intracellular cholesterol regulation.

Perioperative Comfort and Discomfort: Transitioning From Epidural to Oral Pain Treatment After Pancreas Surgery: A Qualitative Study.

PURPOSE: To explore patients' experiences of pain treatment in the perioperative period after surgery for pancreatic cancer. DESIGN: A qualitative descriptive design using semi-structured interviews. METHODS: This study was a qualitative study based on 12 interviews. Participants were patients that had undergone surgery for pancreatic cancer. The interviews were conducted 1 to 2 days after the epidural was turned off, in a surgical department in Sweden. The interviews were analysed with qualitative content analysis. The Standard for Reporting Qualitative Research checklist was used for reporting the qualitative research study. FINDINGS: The analysis of the transcribed interviews, generated one theme: Maintaining a sense of control in the perioperative phase, and two subthemes: (i) Sense of vulnerability and safety, and (ii) Sense of comfort and discomfort, were found. CONCLUSIONS: The participants experienced comfort after pancreas surgery if they maintained a sense of control in the perioperative phase and when the epidural pain treatment provided pain relief without any side effects. The transition from epidural pain treatment to oral pain treatment with opioid tablets was experienced individually, from an almost unnoticed transition to the experience of severe pain, nausea, and fatigue. The sense of vulnerability and safety among the participants were affected by nursing care relationship and the environment on the ward.

Long noncoding RNAs in pancreas cancer: from biomarkers to therapeutic targets.

Long noncoding RNAs (lncRNAs) are noncoding RNA molecules with a heterogeneous structure consisting of 200 or more nucleotides. Because these noncoding RNAs are transcribed by RNA polymerase II, they have properties similar to messenger RNA (mRNA). Contrary to popular belief, the term "ncRNA" originated before the discovery of microRNAs. LncRNA genes are more numerous than protein-coding genes. They are the focus of current molecular research because of their pivotal roles in cancer-related processes such as cell proliferation, differentiation, and migration. The incidence of pancreatic cancer (PC) is increasing around the world and research on the molecular aspects of PC are growing. In this review, it is aimed to provide critical information about lncRNAs in PC, including the biological and oncological behaviors of lncRNAs in PC and their potential application in therapeutic strategies and as diagnostic tumor markers.

[The first experience of small intestinal autotransplantation for advanced digestive cancer]. / Pervyi opyt autotransplantatsii tonkoi kishki pri mestno-rasprostranennykh opukholyakh zheludochno-kishechnogo trakta.

Usually, gastrointestinal tumors (GIT) invading great vessels are acknowledged to be irresectable. Along with that, we can expect positive oncological results only when there is combination treatment with radical surgery (R0 resection). In this article we share the first experience of small intestinal autotransplantation as a method of radical surgery in locally advanced GIT. We conducted the analysis of outcomes of three patients (with pancreas cancer (n=2) and neuroendocrine tumor of caecum (n=1), with neoplastic process involving to superior mesenteric artery and vein. We analyzed intraoperative aspects and algorithm of small intestinal autotransplantation. Long-term outcomes with 1.5-13 months of observing time are presented. On the basis of conducted analysis the authors suggest the possibility of small intestinal autotransplantation in referral centers with strict personalized approach and multidisciplinary surgical team.

Pancreatic cancer pathology viewed in the light of evolution.

One way to understand ductal adenocarcinoma of the pancreas (pancreatic cancer) is to view it as unimaginably large numbers of evolving living organisms interacting with their environment. This "evolutionary view" creates both expected and surprising perspectives in all stages of neoplastic progression. Advances in the field will require greater attention to this critical evolutionary prospective.

Associations of gender, race, and ethnicity with disparities in short-term adverse outcomes after pancreatic resection for cancer.

BACKGROUND: Several studies have identified disparities in pancreatic cancer treatment associated with gender, race, and ethnicity. There are limited data examining disparities in short-term adverse outcomes after pancreatic resection for cancer. The aim of this study is to evaluate associations of gender, race, and ethnicity with morbidity and mortality after pancreatic resection for malignancy. METHODS: The American College of Surgeons National Surgical Quality Improvement database was retrospectively reviewed. The χ2 test and Student's t-test were used for univariable analysis and hierarchical logistic regression for multivariable analysis. RESULTS: Morbidity and major morbidity after pancreaticoduodenectomy are associated with male gender, Asian race, and Hispanic ethnicity, whereas 30-day mortality is associated with the male gender. Morbidity and major morbidity after distal pancreatectomy are associated with the male gender. Morbidity after pancreaticoduodenectomy is independently associated with male gender, Asian race, and Hispanic ethnicity; major morbidity is independently associated with male gender and Asian race, and mortality is independently associated with Hispanic ethnicity. CONCLUSIONS: Gender, race, and ethnicity are independently associated with morbidity after pancreaticoduodenectomy for cancer; gender and race are independently associated with major morbidity; and ethnicity is independently associated with mortality. Further studies are warranted to determine the basis of these associations.

Differences in receipt of multimodality therapy by race, insurance status, and socioeconomic disadvantage in patients with resected pancreatic cancer.

BACKGROUND AND METHODS: Racial and socioeconomic disparities in receipt of adjuvant chemotherapy affect patients with pancreatic cancer. However, differences in receipt of neoadjuvant chemotherapy among patients undergoing resection are not well-understood. A retrospective cross-sectional cohort of patients with resected AJCC Stage I/II pancreatic ductal adenocarcinoma was identified from the National Cancer Database (2014-2017). Outcomes included receipt of neoadjuvant versus adjuvant chemotherapy, or receipt of either, defined as multimodality therapy and were assessed by univariate and multivariate analysis. RESULTS: Of 19 588 patients, 5098 (26%) received neoadjuvant chemotherapy, 9624 (49.1%) received adjuvant chemotherapy only, and 4757 (24.3%) received no chemotherapy. On multivariable analysis, Black patients had lower odds of neoadjuvant chemotherapy compared to White patients (OR: 0.80, 95% CI: 0.67-0.97) but no differences in receipt of multimodality therapy (OR: 0.89, 95% CI: 0.77-1.03). Patients with Medicaid or no insurance, low educational attainment, or low median income had significantly lower odds of receiving neoadjuvant chemotherapy or multimodality therapy. CONCLUSIONS: Racial and socioeconomic disparities persist in receipt of neoadjuvant and multimodality therapy in patients with resected pancreatic adenocarcinoma. DISCUSSION: Policy and interventional implementations are needed to bridge the continued socioeconomic and racial disparity gap in pancreatic cancer care.

Disparity in use of modern combination chemotherapy associated with facility type influences survival of 2655 patients with advanced pancreatic cancer.

AIM: Academic and high volume hospitals have better outcome for pancreatic cancer (PC) surgery, but there are no reports on oncological treatment. We aimed to determine the influence of facility types on overall survival (OS) after treatment with chemotherapy for inoperable PC. MATERIAL AND METHODS: 2,657 patients were treated in Denmark from 2012 to 2018 and registered in the Danish Pancreatic Cancer Database. Facilities were classified as either secondary oncological units or comprehensive, tertiary referral cancer centers. RESULTS: The average yearly number of patients seen at the four tertiary facilities was 71, and 31 at the four secondary facilities. Patients at secondary facilities were older, more frequently had severe comorbidity and lived in non-urban municipalities. As compared to combination chemotherapy, monotherapy with gemcitabine was used more often (59%) in secondary facilities than in tertiary (34%). The unadjusted median OS was 7.7 months at tertiary and 6.1 months at secondary facilities. The adjusted hazard ratio (HR) of 1.16 (confidence interval 1.07-1.27) demonstrated an excess risk of death for patients treated at secondary facilities, which disappeared when taking type of chemotherapy used into account. Hence, more use of combination chemotherapy was associated with the observed improved OS of patients treated at tertiary facilities. Declining HR's per year of first treatment indicated improved outcomes with time, however the difference among facility types remained significant. DISCUSSION: Equal access to modern combination chemotherapy at all facilities on a national level is essential to ensure equality in treatment results.

Pancreas Cancer Incidence and Pancreas Cancer-Associated Mortality Are Low in National Cohort of 7211 Pancreas Cyst Patients.

BACKGROUND AND AIMS: Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period. METHODS: We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999-2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality. RESULTS: Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4 years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths). CONCLUSIONS: Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance.