Impact of Biopsy Attempts, Race, and Access on Time to Initiation of Treatment for Pancreatic Cancer.

BACKGROUND: Biopsy of suspected pancreatic cancer (PDAC) in surgical candidates is informative however not always necessary. Biopsies impact treatment options as histological diagnosis are presently required for neo-adjuvant therapy, but not surgical resection. We explored the impact of pursuing tissue diagnosis by endoscopic ultrasound (EUS) biopsy on time to treatment in patients with resectable and borderline resectable PDAC. METHODS: A retrospective review of surgical patients with ultimately proven PDAC was performed (2011-2021). Milestone dates (cancer suspected, biopsy(ies), surgical or neo-adjuvant treatment) were collected. Mann-Whitney-Wilcoxon tests, Pearson's chi-squared tests, Fisher's exact tests, linear regressions, and Cox proportional hazard models were used for data analysis. RESULTS: Among 131 resectable and 58 borderline resectable patients, the borderline resectable group underwent more biopsies (1.2 vs 0.7, p < 0.0001), were more likely to undergo biopsy at tertiary care centers (67.2% vs 30.5%, p < 0.0001), and trended toward longer time to treatment (49 vs 44 days, p = 0.070). Significant increases in days to treatment were seen in patients with Black race (29 days, p = 0.0002) and Medicare insurance (22 days, p = 0.038) and no biopsies at a tertiary care center (10 days, p = 0.039). After adjusting for covariates, additional biopsies significantly delayed treatment (1 biopsy: 21 days, p = 0.0001; 2 biopsies: 44 days, p < 0.0001; 3 biopsies: 68 days, p < 0.0001). CONCLUSIONS: EUS biopsy significantly impacts time between suspicion and treatment of PDAC. This may be exacerbated by clinical practices increasingly favoring neo-adjuvant therapy that necessitates biopsy-proven disease. Time to treatment may also be impacted by access to tertiary centers and racial disparities.

Ethical Considerations of Biopsies in Early-Stage Pancreatic Cancer.

PURPOSE: The standard of care in resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC) has evolved to include neoadjuvant treatment before surgical resection. Current guidelines call for obtaining histologic tissue diagnosis via endoscopic ultrasound fine-needle aspiration before administration of neoadjuvant therapy, which differ from guidelines discouraging delay in surgical resection for a biopsy. MATERIALS AND METHODS: Whether to proceed with treatment before a biopsy confirms that malignancy is a nuanced decision and includes considerations of physical and psychological risks entailed in both pursuing and forgoing a biopsy. RESULTS: Accuracy of imaging and biopsy results, the presence of contributing clinical signs/symptoms, and the existing precedents of considering biopsies as waivable such as in scenarios with high clinical suspicion and primary surgical resection. CONCLUSION: When considering the aspects of ethical medical practice including beneficence (doing good), nonmaleficence (avoiding harm), autonomy (allowing patients to make decisions about their care), and utilitarianism (doing the most good for the most people), analysis of whether guidelines guiding biopsies should continue to differ between resection and neoadjuvant treatments in PDAC is prudent.

Epidural pain management in advanced gastric cancer with inoperable malignant bowel obstruction.

Presented is a case of a man in his 20s with gastric cancer with metastasis to a perineal nodule and the splenic flexure (previously resected due to acute bowel obstruction) who presented with prolonged, intermittent, inoperable bowel obstruction likely due to adhesions, exacerbated by functional ileus due to substantial opioid requirement. In an episode of obstruction during the described admission, the patient remained obstructed after more than 10 days of medical management. The patient suffered from intense abdominal distention and pain, necessitating hundreds of oral morphine equivalents daily. A ropivacaine thoracic epidural infusion was initiated, allowing decreased opioid use and relief of opioid-induced ileus contributing to his bowel obstruction. He subsequently had multiple formed bowel movements, which quickly decreased the patient's abdominal distention and immediate risk of perforation. This case explores epidurals as an underutilised approach to pain management in metastatic gastric malignancy and inoperable malignant bowel obstructions.

The interleukin-1 axis and the tumor immune microenvironment in pancreatic ductal adenocarcinoma.

Interleukin-1 (IL-1) plays a key role in carcinogenesis and several IL-1-targeted therapeutics are under investigation for the treatment of pancreatic ductal adenocarcinoma (PDAC). We sought to broaden our understanding of how the family of IL-1 ligands and receptors impact the tumor immune landscape and patient survival in PDAC. Gene expression data and DNA methylation data for IL1A, IL1B, IL1RN, IL1R1, IL1R2, and IL1RAP was attained from The Cancer Genome Atlas (TCGA) database and cross validated using the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Immune cell-type abundance was estimated using CIBERSORTx. Further confirmatory soluble protein analysis and peripheral blood immunophenotyping were performed on available tissue samples from our institution. 169 PDAC patients and 50 benign pancreatic TCGA-based samples were analyzed. IL1A (p < 0.001), IL1RN (p < 0.001), IL1R2 (p < 0.001), and IL1RAP (p = 0.006) were markedly increased in PDAC tumor tissue compared to benign pancreatic tissue. Furthermore, expression of IL1A, IL1B and IL1R1 were positively correlated with gene expression of immune checkpoints PVR, CD274, CD47, CD80, and HLA-A/B/C (p < 0.001). IL1B and IL1R1 were correlated to expression of PDCD1, CD86, CTLA4 and IDO1 (<0.001). Low expression of IL1RN (p = 0.020), IL1R2 (p = 0.015), and IL1RAP (p = 0.003) and high expression of IL1B (p = 0.031) were correlated with increased patient survival. At the protein level, IL-1ß was correlated with increased peripheral central memory CD4+ and CD8+ T-cells as well as decreased Th2 cells. These findings suggest that the IL-1 axis plays a complex and pivotal role in the host immune response to PDAC.

Impact of polysubstance use on social and non-affective cognitive performance among treatment-seeking individuals with alcohol use disorders.

BACKGROUND: Individuals with alcohol use disorder (AUD) display deficits across a range of cognitive processes. Decrements in social cognition may be particularly important for interpersonal functioning and post-treatment adaptation. Although social cognitive deficits are associated with chronic use of numerous substances, the role of polysubstance use in AUD-associated deficits remains largely unaddressed. METHODS: Community volunteers (n = 49; 22 men) and inpatient treatment-seekers with AUD were administered neurocognitive tasks indexing emotion processing and non-affective cognitive functioning. Tasks included an emotion discrimination task, a working memory task with affective stimuli, a general face processing (control) task, two measures of executive function, and two measures of visual spatial function. AUD subgroups included individuals with no recent (6-month) polysubstance use (AUD-Only; n = 22; 15 men), and those with at least weekly use (Poly-SU; n = 22; 18 men). RESULTS: Poly-SU individuals evinced disadvantaged performance relative to other groups on the emotion discrimination task [ps ≤ 0.001], affective working memory task [ps ≤ 0.050], and two executive function measures [ps ≤ 0.051]. No differences were observed for visual spatial functioning [ps ≥ 0.498] or general face processing [ps ≥ 0.190]. No performance differences between AUD-Only and community volunteers were noted. CONCLUSIONS: Results extend the emerging literature exploring emotion processing in AUD and add to the established literature regarding cognitive deficits in this population. The data suggest that among individuals with AUD, those with polysubstance use may be particularly vulnerable to deficits in decoding emotional face content. The current work highlights the need to incorporate more nuanced and careful considerations of polysubstance use in the design and analysis for future investigations of alcohol-associated deficits in emotion processing.