Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination platforms have been tested in the clinical setting, from off-the-shelf peptide-based vaccines (e.g., AMPLFIFY-201 study, where over 80% of participants exhibited T-cell and biomarker responses) to personalized neoantigen mRNA vaccine approaches (e.g., autogene cevumeran, with significant responders experiencing longer median recurrence-free survival (RFS)). The key considerations for enhancing the efficacy of vaccination include combinations with chemotherapy, radiotherapy, and/or ICBs, as well as selecting appropriate immunomodulators or adjuvants. Recent results suggest that with continued mechanistic advancement and novel therapeutic development, cancer vaccines may finally be poised for clinical success in PDAC.

Background: Hepatocellular carcinoma (HCC) is a major cause of mortality in the United States, but it can be cured with orthotopic liver transplant (OLT) in selected patients. Despite curative intent, post-OLT recurrence can occur in up to 15% of patients. The need for a program of post-OLT surveillance is widely accepted but the specifics of an optimal program have not been established. There is interest in identifying lower-risk cohorts of patients in whom an abbreviated strategy of surveillance may prove adequate, utilizing tools such as the RETREAT score. Unique challenges are posed in the post-transplant population regarding safety and tolerability of systemic therapy for HCC recurrence, suggesting early detection is beneficial. Methods: This was a single-center retrospective analysis of characteristics and outcomes for all patients undergoing transplant at our center between 1 January 2012 and 31 December 2024. Diagnosis of HCC was determined by histological confirmation or Liver Imaging and Reporting Data System (LI-RADS) 5 findings on contrast-enhanced cross-sectional imaging. RETREAT scores were calculated for all patients. Results: During the study period, 923 transplants were performed, of which 329 (35.6%) were for HCC. Post-OLT recurrence occurred in 36 (10.9%) of these. Recurrence was associated with the presence of any viable tumor on explant surgical pathology, the presence of a viable tumor beyond Milan Criteria, the presence of microvascular invasion, a larger diameter of viable tumor on explant, and a higher RETREAT score. Although higher RETREAT scores were associated with post-OLT recurrence, one-third of patients who experienced post-OLT recurrence had RETREAT scores of 0 or 1. RETREAT scores did not correlate with the time interval between transplant and HCC recurrence. Systemic therapy proved challenging, with 10/25 patients receiving systemic therapy for post-OLT recurrence having to stop or alter regimens due to the severity of adverse effects. Conclusions: The rates of post-transplant recurrence and the experience of patients managed with systemic therapy for post-OLT recurrence in our experience were in line with previously published data. Due to the overall low RETREAT scores, the sensitivity of the RETREAT score in identifying patients at risk for post-OLT recurrence was limited, and the low RETREAT score had very limited incremental negative predictive value for identifying a low-risk population. This suggested that a broad screening strategy for post-OLT recurrence may be better than a personalized strategy in which patients with low RETREAT scores receive abbreviated surveillance.

Toxic epidermal necrolysis (TEN) is a dermatological emergency that is often associated with high mortality. It is differentiated from Stevens-Johnson syndrome (SJS) based on the percentage of the total body surface area affected. There has been an established correlation with certain medications that could trigger the development of such a devastating disease. Despite numerous research studies conducted on aspects of this disease entity, TEN remains foreign to many general Internists situated in a community setting due to the extremely low disease prevalence that leads to a lack of overall experience and medical resources in dealing with this medical condition. Thus, we outlined several important management aspects of TEN/SJS that an Internist should be aware of in order to assist in prompt clinical decision making and prognosis forecasting as well as deliver effective family communication.