The role of cytoreductive surgery and HIPEC for the treatment of primary and secondary peritoneal malignancies-experience from a tertiary care center in Germany.

PURPOSE: Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. METHODS: A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. RESULTS: Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years. CONCLUSION: Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.

Immunomonitoring via ELISPOT Assay Reveals Attenuated T-Cell Immunity to CMV in Immunocompromised Liver-Transplant Patients.

Assessing immune responses to cytomegalovirus (CMV) after liver transplant in patients on immunosuppressive therapy remains challenging. In this study, employing ELISPOT assays, 52 liver-transplant recipients were evaluated for antiviral T-cell activity in peripheral blood mononuclear cells (PBMCs), measuring interferon-γ (IFN-γ) secretion upon stimulation with CMV-specific peptides (CMV peptide pool, CMV IE-1, and pp65 antigens). Parameters such as stimulation index, mean spot size, and mean spot count were measured. The study found that heightened immunosuppression, especially with prednisolone in triple therapy, significantly dampened CMV-specific immune responses. This was demonstrated by decreased IFN-γ production by CMV-specific T-cells (CMV peptide pool: p = 0.036; OR = 0.065 [95% CI: 0.005-0.840], pp65 antigen: p = 0.026; OR = 0.048 [95% CI: 0.003-0.699]). Increased immunosuppression correlated with reduced IFN-γ secretion per cell, reflected in smaller mean spot sizes for the CMV peptide pool (p = 0.019). Notably, shorter post-transplant intervals correlated with diminished antiviral T-cell IFN-γ release at two years (CMV peptide pool: p = 0.019; IE antigen: p = 0.010) and five years (CMV peptide pool: p = 0.0001; IE antigen: p = 0.002; pp65 antigen: p = 0.047), as did advancing age (pp65 antigen: p = 0.016, OR = 0.932, 95% CI: 0.881-0.987). Patients with undetectable CMV antigens had a notably higher risk of CMV reactivation within six months from blood collection, closely linked with triple immunosuppression and prednisolone use. These findings highlight the intricate interplay between immunosuppression, immune response dynamics, and CMV reactivation risk, emphasizing the necessity for tailored immunosuppressive strategies to mitigate CMV reactivation in liver-transplant recipients. It can be concluded that, particularly in the early months post-transplantation, the use of prednisolone as a third immunosuppressant should be critically reconsidered. Additionally, the use of prophylactic antiviral therapy effective against CMV in this context holds significant importance.