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.

Decreasing utilization of surgical interventions amongst patients with pancreatic neuroendocrine tumor with liver metastases.

BACKGROUND: Since 2013, North American Neuroendocrine Tumor Society (NANETS) consensus-guidelines have endorsed consideration of surgical intervention for pancreatic- neuroendocrine tumors (PNET) with liver metastases. METHODS: Patients with non-functional PNET with liver only metastases from 2010 to 2019 were identified from the National Cancer Database. RESULTS: 34.7% underwent surgical intervention (13% PNET resection, 2.1% surgical management of liver metastases (SMLM), 19.5% PNET resection â€‹+ â€‹SMLM). In multivariable analysis, government insurance, year of diagnosis>2013, increasing primary tumor size were associated with lower rate of surgical intervention. Receiving treatment at an academic center (OR 3.59, 95%CI 1.81-7.11; P â€‹< â€‹0.001) or integrated cancer network (OR 3.21, 95%CI 1.57-6.54; P â€‹= â€‹0.001) was associated with a higher rate of surgical intervention. The overall rate of surgical intervention decreased from 45.7% in 2010 to 23.0% in 2019. CONCLUSION: Despite guideline recommendations and the suggested survival benefits, only one-third of patients underwent surgical intervention, potentially influenced by the rising utilization of systemic therapy in the past decade.

Adjuvant hepatic artery infusion pump chemotherapy for resected colorectal cancer liver metastases.

First introduced in the late 1980s in the setting of unresectable liver metastasis, the use of the hepatic artery infusion pump was expanded to deliver chemotherapy in the adjuvant setting after hepatic resection about 1 decade later. Though the initial randomized clinical trial comparing the hepatic artery infusion pump to resection alone failed to show an improvement in overall survival, 2 large randomized clinical trials, namely the Memorial Sloan Kettering Cancer Center (1999) and European Cooperative Group (2002) trials, did report improved hepatic disease-free survival with the use of a hepatic artery infusion pump. There remained limited evidence of a replicable improvement in overall survival, and the expansion of hepatic artery infusion pump into the adjuvant space was cautioned by a Cochrane review in 2006, highlighting the need for further studies to establish a consistent benefit. Those data were forthcoming over the 2000s and 2010s in large-scale retrospective analyses for the most part, but the recommendations from international guidelines remain equivocal to this day. With widespread retrospective data and high-quality randomized clinical trial evidence that a hepatic artery infusion pump in the setting of resected hepatic metastasis from colorectal liver metastasis decreases hepatic recurrence and indications that it may improve overall survival, it is clear that there is a subset of patients that greatly benefit from this treatment modality. New randomized clinical trials, specifically in the adjuvant setting, are currently enrolling and should continue to elucidate the benefit that hepatic artery infusion pumps may confer. That being said, it remains a challenge to reliably identify these patients, and the procedure is limited by complexity and resources to high-volume academic centers, leaving accessibility as a further potential barrier for patients. It remains to be seen what volume of literature may shift the hepatic artery infusion pump into the standard of care, but adjuvant hepatic artery infusion pump in the setting of colorectal liver metastasis should certainly be explored further as a validated treatment for patients.

Potential Role for Observation in Small Solid Pseudopapillary Neoplasm (SPN).

BACKGROUND: Solid pseudopapillary neoplasms (SPN) are rare tumors of the pancreas, typically affecting young women. Resection is the mainstay of treatment but is associated with significant morbidity and potential mortality. We explore the idea that small, localized SPN could be safely observed. METHODS: This retrospective review of the Pancreas National Cancer Database from 2004 to 2018 identified SPN via histology code 8452. RESULTS: A total of 994 SPNs were identified. Mean age was 36.8 ± 0.5 years, 84.9% (n = 844) were female, and most had a Charlson-Deyo Comorbidity Coefficient (CDCC) of 0-1 (96.6%, n = 960). Patients were most often staged clinically as cT2 (69.5%, n = 457) followed by cT3 (17.6%, n = 116), cT1 (11.2%, n = 74), and cT4 (1.7%, n = 11). Clinical lymph node and distant metastasis rates were 3.0 and 4.0%, respectively. Surgical resection was performed in 96.6% of patients (n = 960), most commonly partial pancreatectomy (44.3%) followed by pancreatoduodenectomy (31.3%) and total pancreatectomy (8.1%). In patients clinically staged as node (N0) and distant metastasis (M0) negative, occult pathologic lymph node involvement was found in 0% (n = 28) of patients with stage cT1 and 0.5% (n = 185) of patients with cT2 disease. The risk of occult nodal metastasis significantly increased to 8.9% (n = 61) for patients with cT3 disease. The risk further increased to 50% (n = 2) in patients with cT4 disease. CONCLUSIONS: Herein, the specificity of excluding nodal involvement clinically is 99.5% in tumors ≤ 4 cm and 100% in tumors ≤ 2 cm. Therefore, there may be a role for close observation in patients with cT1N0 lesions to mitigate morbidity from major pancreatic resection.

Pancreatic Cancer Patient-derived Organoids Can Predict Response to Neoadjuvant Chemotherapy.

OBJECTIVE: To evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma. BACKGROUND: PDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer. METHODS: During 2017-2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing. RESULTS: One hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection. CONCLUSION: Herein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.

Ampullary Neuroendocrine Tumors: Insight into a Rare Histology.

BACKGROUND: Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs. METHODS: The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression. RESULTS: Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n = 149, 17%) than patients with duodenal (n = 197, 2%) or pancreatic head (n = 740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n = 297, 34%) than patients with duodenal (n = 950, 10%) or pancreatic head (n = 1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p < 0.0001), Charlson-Deyo score of 2 (HR 2.3, p = 0.001) or ≥3 (HR 2.9, p = 0.013), grade 2 (HR 1.9, p = 0.007) or grade 3 tumors (HR 4.0, p < 0.0001), and metastatic disease (HR 2.0, p = 0.001) were associated with decreased survival. At 5 years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p < 0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p < 0.0001). CONCLUSIONS: Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.

Core Competency Self-Assessment Enhances Critical Review of Complications and Entrustable Activities.

BACKGROUND: The Accreditation Council for Graduate Medical Education has defined six core competencies (CCs) that every successful physician should possess. However, the assessment of CC achievement among trainees is difficult. This project was designed to prospectively evaluate the impact of resident identification of CC as a component of morbidity review on error identification and standard of care (SOC) assessments. The platform was assessed for its reliability as a measure of resident critical analysis of complication causality across postgraduate year (PGY). MATERIALS AND METHODS: A total of 1945 general surgery cases with complications were assessed for error identification and SOC management between January 1, 2016, and December 31, 2018. CC identification was additionally assessed between January 1, 2019, and December 31, 2019, and included 708 general surgery cases. Data were evaluated for error assessments and overall SOC management. PGY4 and 5 residents were compared for number of cases and complications reviewed, severity, error causation, and CC relevance. RESULTS: Study groups were equivalent by Clavien-Dindo scores. Error identification significantly increased in all categories: diagnostic (P < 0.001), technical (P < 0.05), judgment (P < 0.001), system (P < 0.001), and communication (P < 0.001). Overall SOC assessments validated by a supervising surgical quality officer were unchanged. An increased exposure to cases with severe complications, error causation, and CC relevance was noted across PGY. CONCLUSIONS: The addition of CC assessment into morbidity review appears to improve the critical thinking of evaluating residents by increasing the identification of management errors. Used as an element of prospective self-assessment, teaching residents to identify CC principles in cases with complications may assist in learner progression toward clinical competence and critical thinking.

Associations between brain inflammatory profiles and human neuropathology are altered based on apolipoprotein E ε4 genotype.

Alzheimer disease (AD) is a chronic neurodegenerative disease with a multitude of contributing genetic factors, many of which are related to inflammation. The apolipoprotein E (APOE) ε4 allele is the most common genetic risk factor for AD and is related to a pro-inflammatory state. To test the hypothesis that microglia and AD-implicated cytokines were differentially associated with AD pathology based on the presence of APOE ε4, we examined the dorsolateral frontal cortex from deceased participants within a community-based aging cohort (n = 154). Cellular density of Iba1, a marker of microglia, was positively associated with tau pathology only in APOE ε4 positive participants (p = 0.001). The cytokines IL-10, IL-13, IL-4, and IL-1α were negatively associated with tau pathology, independent of Aß1-42 levels, only in APOE ε4 negative participants. Overall, the association of mostly anti-inflammatory cytokines with less tau pathology suggests a protective effect in APOE ε4 negative participants. These associations are largely absent in the presence of APOE ε4 where tau pathology was significantly associated with increased microglial cell density. Taken together, these results suggest that APOE ε4 mediates an altered inflammatory response and increased tau pathology independent of Aß1-42 pathology.

Contact sport participation and chronic traumatic encephalopathy are associated with altered severity and distribution of cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) consists of beta-amyloid deposition in the walls of the cerebrovasculature and is commonly associated with Alzheimer's disease (AD). However, the association of CAA with repetitive head impacts (RHI) and with chronic traumatic encephalopathy (CTE) is unknown. We evaluated the relationship between RHI from contact sport participation, CTE, and CAA within a group of deceased contact sport athletes (n = 357), a community-based cohort (n = 209), and an AD cohort from Boston University AD Center (n = 241). Unsupervised hierarchal cluster analysis demonstrated a unique cluster (n = 11) with increased CAA in the leptomeningeal vessels compared to the intracortical vessels (p < 0.001) comprised of participants with significantly greater frequencies of CTE (7/11) and history of RHI. Overall, participants with CTE (n = 251) had more prevalent (p < 0.001) and severe (p = 0.010) CAA within the frontal leptomeningeal vessels compared to intracortical vessels. Compared to those with AD, participants with CTE had more severe CAA in frontal than parietal lobes (p < 0.001) and more severe CAA in leptomeningeal than intracortical vessels (p = 0.002). The overall frequency of CAA in participants with CTE was low, and there was no significant association between contact sport participation and the presence of CAA. However, in those with CAA, a history of contact sports was associated with increased CAA severity in the frontal leptomeningeal vessels (OR = 4.01, 95% CI 2.52-6.38, p < 0.001) adjusting for AD, APOE ε4 status, and age. Participants with CAA had increased levels of sulcal tau pathology and decreased levels of the synaptic marker PSD-95 (p's < 0.05), and CAA was a predictor of dementia (OR = 1.75, 95% CI 1.02-2.99, p = 0.043) adjusting for age, sex, and comorbid pathology. Overall, contact sport participation and CTE were associated with more severe frontal and leptomeningeal CAA, and CAA was independently associated with worse pathological and clinical outcomes.