Current Surgical Management Strategies for Colorectal Cancer Liver Metastases

Colorectal cancer is the third most common cancer diagnosis in the world, and the second most common cause of cancer-related deaths. Despite significant progress in management strategies for colorectal cancer over the last several decades, metastatic disease remains difficult to treat and is often considered incurable. However, for patients with colorectal liver metastases (CRLM), surgical resection offers the best opportunity for survival, can be curative, and remains the gold standard. Unfortunately, surgical treatment options are underutilized. Misperceptions regarding resectable and unresectable CRLM likely play a role in this. The assessment of factors that impact resectability status like medical fitness, technical considerations, and disease biology can be difficult, necessitating careful multidisciplinary input and discussion. The identification of ideal operative time windows that align with the multimodal management of these patients can also be perplexing. For all patients with CRLM it may therefore be advantageous to obtain surgical evaluation at the time of discovering liver metastases to mitigate these challenges and minimize the risk of undertreatment. In this review we summarize current surgical management strategies for CRLM and discuss factors to be considered when determining resectability

Neoantigen Identification and Response to Adoptive Cell Transfer in anti PD-1 Naïve and Experienced Patients with Metastatic Melanoma

Immune checkpoint blockade (ICB) agents and adoptive cell transfer (ACT) of tumor infiltrating lymphocytes (TIL) are prominent immunotherapies used for the treatment of advanced melanoma. Both therapies rely on activation of lymphocytes that target shared tumor antigens or neoantigens. Recent analysis of patients with metastatic melanoma who underwent treatment with TIL ACT at the National Cancer Institute (NCI) demonstrated decreased responses in patients previously treated with anti PD-1 agents. We aimed to find a basis for the difference in response rates between anti PD-1 naïve and experienced patients. We examined the tumor mutational burden (TMB) of resected tumors and the repertoire of neoantigens targeted by autologous TIL in a cohort of 112 anti PD-1 naïve and 69 anti PD-1 experienced patients. Anti PD-1 naïve patients were found to have higher TMBs (352.0 vs. 213.5, p = 0.005) and more neoantigens (2 vs. 1, p = 0.003) compared to anti PD-1 experienced patients. Among patients treated with TIL ACT, TMB and number of neoantigens identified were higher in ACT responders than ACT non-responders in both anti PD-1naïve and experienced patients. Among patients with comparable TMBs and predicted neoantigen loads, patients naïve to anti PD-1 therapy were more likely to have identifiable neoantigens and tumor specific lymphocytes in their treatment products (2.5 vs. 1, p = 0.02). These results indicate that decreases in TMB and targeted neoantigens only partially account for the difference in response to ACT and that additional factors likely influence responses in these patients

Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers.

Immunotherapies can mediate regression of human tumors with high mutation rates, but responses are rarely observed in patients with common epithelial cancers. This raises the question of whether patients with these common cancers harbor T lymphocytes that recognize mutant proteins expressed by autologous tumors that may represent ideal targets for immunotherapy. Using high-throughput immunologic screening of mutant gene products identified via whole-exome sequencing, we identified neoantigen-reactive tumor-infiltrating lymphocytes (TIL) from 62 of 75 (83%) patients with common gastrointestinal cancers. In total, 124 neoantigen-reactive TIL populations were identified, and all but one of the neoantigenic determinants were unique. The results o

Improvement in lipids after switch to boosted atazanavir or darunavir in children/adolescents with perinatally acquired HIV on older protease inhibitors: results from the Pediatric HIV/AIDS Cohort Study

Objectives Dyslipidaemia is common in perinatally HIV‐infected (PHIV) youth receiving protease inhibitors (PIs). Few studies have evaluated longitudinal lipid changes in PHIV youth after switch to newer PIs. Methods We compared longitudinal changes in fasting lipids [total cholesterol (TC), triglycerides (TG), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and TC:HDL‐C ratio] in PHIV youth enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) study who switched to atazanavir/ritonavir (ATV/r)‐ or darunavir/ritonavir (DRV/r)‐based antiretroviral therapy (ART) from an older PI‐based ART and those remaining on an older PI. Generalized estimating equation models were fitted to assess the association of a switch to ATV/r‐ or DRV/r‐based ART with the rate of change in lipids, adjusted for potential confounders. Results From 2007 to 2014, 47 PHIV children/adolescents switched to ATV/r or DRV/r, while 120 remained on an older PI [primarily lopinavir/r (72%) and nelfinavir (24%)]. Baseline age ranged from 7 to 21 years. After adjustment for age, Tanner stage, race/ethnicity, and HIV RNA level, a switch to ATV/r or DRV/r was associated with a more rapid annual rate of decline in the ratio of TC:HDL‐C. (β = −0.12; P = 0.039) than remaining on an older PI. On average, TC declined by 4.57 mg/dL/year (P = 0.057) more in the switch group. A switch to ATV/r or DRV/r was not associated with the rate of HDL‐C, LDL‐C, or TG change. Conclusions A switch to ATV/r or DRV/r may result in more rapid reduction in TC and the TC:HDL‐C ratio in PHIV youth, potentially impacting long‐term cardiovascular disease risk

Correction: Implementation of Genomic Surveillance of SARS-CoV-2 in the Caribbean: Lessons learned for sustainability in resource-limited settings.

[This corrects the article DOI: 10.1371/journal.pgph.0001455.]