Program Evaluation: exploring health disparities that impact chronic pain referrals within a VA Health Care System.

Introduction: The present Program Evaluation study examines sociodemographic characteristics of Veterans in the Phoenix VA Health Care System who have back pain, and specifically the likelihood of those characteristics being associated with a referral to the Chronic Pain Wellness Center (CPWC) in the year 2021. We examined the following characteristics: Race/ethnicity, gender, age, mental health diagnosis, substance use disorder diagnosis, and service-connected diagnosis. Methods: Our study used cross sectional data from the Corporate Data Warehouse for 2021. 13624 records had complete data for the variables of interest. Univariate and multivariate logistic regression was used to determine the likelihood of patients' being referred to the Chronic Pain Wellness Center. Results: The multivariate model found under-referral to be significant for younger adults and for patients who identified as Hispanic/Latinx, Black/African American, or Native American/Alaskan. Those with depressive disorders and opioid use disorders, on the other hand, were found to be more likely to be referred to the pain clinic. Other sociodemographic characteristics were not found to be significant. Discussion: Study limitations include the use of cross-sectional data, which cannot determine causality, and the inclusion of patients only if the ICD-10 codes of interest were recorded for an encounter in 2021 (i.e., a prior history of a particular diagnosis was not captured). In future efforts, we plan to examine, implement, and track the impact of interventions designed to mitigate these identified disparities in access to chronic pain specialty care.

Assessment of proliferating cell nuclear antigen activity using digital image analysis in breast carcinoma following magnetic resonance-guided interstitial laser photocoagulation.

This study examines proliferative activity in tumor cells of patients with histologically documented invasive breast carcinoma treated with magnetic resonance-guided interstitial laser photocoagulation (MR-GILP). Immunohistochemical marker for proliferating cell nuclear antigen (PCNA), a nuclear protein abundant in actively proliferating cells, is used. The study demonstrates the effectiveness of MR-GILP in ablating tumor cells of infiltrating breast cancer. The diagnosis of infiltrating breast carcinoma was confirmed by core needle biopsies. Using a specially designed magnetic resonance imaging (MRI) device, rotating delivery of excitation off-resonance (RODEO), tumors were measured ranging from 1.8 to 4.0 cm in greatest dimension. Seven formalin-fixed, paraffin-embedded archival tissues from seven patients with infiltrating carcinoma, status post-MR-GILP, were analyzed. Using PCNA immunoperoxidase (Biomeda Corp.), the proliferative capability of the remaining tumor cells around the focus of laser photocoagulation was determined. The lesions were digitally acquired using a Nikon Eclipse E800 microscope with an automated stage. Images were analyzed using Cool SNAP image editing software (version 1.0). Appropriate thresholds were set for positive staining and limited concentric radial measurements of equal area between all samples were compared at radial millimeter intervals from the center of laser ablation. The integrated area occupied by PCNA-positive cells per radial millimeter from the charcoal site (the center of the laser) increased as the distance from this site increased (a mean average at each radial measurement revealed: at the 1 mm radius the positive integrated area was 0.0024 mm2; at 2 mm, 0.0145 mm2; at 3 mm, 0.0351 mm2; at 4 mm, 0.0696 mm2; at 5 mm, 0.1025 mm2; and at 6 mm, 0.1263 mm2). MR-GILP is an effective mean of ablating breast carcinoma. This treatment option may represent an alternative to lumpectomy for a single lesion < or =1 cm, or make patients with two separate lesions eligible for lumpectomy.

Restoration of tumor-specific HLA class I restricted cytotoxicity in tumor infiltrating lymphocytes of advanced breast cancer patients by in vitro stimulation with tumor antigen-pulsed autologous dendritic cells.

Breast tumor infiltrating lymphocytes (TIL) are enriched in tumor-specific cytotoxic T lymphocytes (CTL), and may represent a superior source of CTL compare to peripheral blood lymphocytes (PBL), for adoptive T cell immunotherapy of breast cancer. However, the immunocompetence of TIL and the possibility to consistently restore their tumor-specific lytic activity in vitro remains an open issue. In this study we evaluated the potential of tumor antigen-pulsed fully mature dendritic cell (DC) stimulation in restoring tumor-specific cytotoxicity in anergic TIL populations from advanced breast cancer patients. In addition we have compared tumor-specific T cell responses induced by tumor antigen-loaded DC stimulation of TIL to responses induced from PBL. Although TIL were consistently non-cytotoxic after isolation or culture in the presence of interleukin-2 (IL-2), in matched experiments from three consecutive patients, tumor-lysate-pulsed DC-stimulated CD8+ T cell derived from TIL were found to be significantly more cytotoxic than PBL (p < 0.05). In addition, cytotoxicity against autologous tumor cells was more significantly inhibited by an anti-HLA class I (W6/32) MAb in TIL compared to PBL (p < 0.05). CTL populations derived from TIL and PBL did not lyse autologous EBV-transformed lymphoblastoid cell lines, and showed negligible cytotoxicity against the NK-sensitive cell line K562. Furthermore, in both CD8+ T cell populations the majority of the tumor-specific CTL exhibited a Th1 cytokine bias (IFN-gamma(high)/IL-4(low)). Taken together, these data show that tumor lysate-pulsed mature DC can consistently restore tumor-specific lytic activity in non-cytotoxic breast cancer TIL. These results may have important implications for the treatment of chemotherapy resistant breast cancer with active or adoptive immunotherapy.

In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells.

BACKGROUND: Early dissemination of treatment-resistant tumor cells remains the major cause of metastatic recurrence and death in breast cancer patients. Dendritic cells (DCs) are the most powerful antigen-presenting cells, and recently DC-based vaccination has shown great promise for the treatment of human malignancies by immunological intervention. MATERIALS AND METHODS: CD8+ T lymphocytes derived from peripheral blood mononuclear cells stimulated in vitro with autologous breast tumor antigen-pulsed DCs were tested for their ability to induce a HLA class I restricted cytotoxic T lymphocyte (CTL) response against autologous tumor cells. To correlate cytotoxic activity by CTL with T cell phenotype, two-color flow cytometric analysis of surface markers and intracellular cytokine expression was performed. RESULTS: DC pulsed with breast tumor extracts consistently elicited a tumor-specific HLA class I restricted CTL response in vitro in three consecutive patients harboring locally advanced breast cancer. CTL expressed strong cytolytic activity against autologous tumor cells but did not lyse autologous Epstein Barr virus-transformed lymphoblastoid cell lines and showed variable cytotoxicity against the natural killer-sensitive cell line K-562. In all patients, two color flow cytometric analysis of surface markers and intracellular cytokine expression demonstrated that tumor-specific CTL exhibited an heterogeneous CD8+/CD56+ expression and a striking Th1 cytokine bias (IFNgamma(high)/IL-4 (low)). CONCLUSIONS: Tumor lysate-pulsed DCs can consistently stimulate specific CD8+ CTLs able to kill autologous tumor cells in patients with locally advanced breast cancer in vitro. Tumor antigen-pulsed DC-based vaccinations may be appropriate for the treatment of residual and/or chemotherapy-resistant breast cancer refractory to standard salvage treatment modalities.