Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors

Recently, there is considerable interest in the field of anti-HIV therapy to identify and develop chromatin-modifying histone deacetylase (HDAC) inhibitors that can effectively reactivate latent HIV in patients. The hope is that this would help eliminate cells harboring latent HIV and achieve an eventual cure of the virus. However, how effectively these drugs can stimulate latent HIVs in quiescent primary CD4 T cells, despite their relevant potencies demonstrated in cell line models of HIV latency, is not clear. Here, we show that the HDAC inhibitors valproic acid (VPA) and trichostatin A (TSA) are unable to reactivate HIV in latently infected primary CD4 T cells generated in the H80 co-culture system. This raises a concern that the drugs inhibiting HDAC function alone might not be sufficient for stimulating latent HIV in resting CD4 T cells in patients and not achieve any anticipated reduction in the pool of latent reservoirs

Management and outcomes among patients with mixed hepatocholangiocellular carcinoma: A population-based analysis

Background: We sought to define the management of mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC) as well as characterize short- and long-term outcomes of patients with mixed HCC-ICC. Methods: Patients diagnosed with HCC-ICC, HCC, or ICC between 2004 and 2015 were identified from the National Cancer Data Base using the International Classification of Diseases for Oncology codes. Short- and long-term outcomes were assessed using univariate and multivariate analyses. Results: Among 174 454 patients, 86.8% had HCC, 12.1% ICC, and 1.1% HCC-ICC. The incidence of lymphadenectomy was 55.6% among ICC patients vs 15.1% and 34.2% for HCC and HCC-ICC patients, respectively (P < 0.001). A 90-day mortality was comparable among patients with HCC (9.1%), ICC (8.8%), and HCC-ICC (10.5%) (all P > 0.2). While 42.0% of ICC patients received adjuvant chemotherapy, adjuvant chemotherapy among HCC and HCC-ICC patients was 13.1% and 27.4%, respectively (P < 0.001). A 5-year survival was 43.5% (95% CI, 42.5-44.5), 33.3% (95% CI, 31.4-35.3), 34.4% (95% CI, 29.1-39.8) for HCC, ICC, and HCC-ICC patients, respectively. Conclusion: Patients who underwent resection of mixed HCC-ICC had a prognosis that was comparable to ICC, yet worse than HCC. Utilization of lymphadenectomy and adjuvant therapy were low. HCC-ICC remains a rare disease with a guarded prognosis that should be treated in a multidisciplinary setting

A Comparison of Open and Minimally Invasive Surgery for Hepatic and Pancreatic Resections Among the Medicare Population

Introduction: Minimally invasive surgery (MIS) has become standard of care for many gastrointestinal surgical procedures. Despite possible clinical benefits, MIS may be underutilized in some populations. The aim of this study was to access the utilization of MIS among Medicare patients undergoing hepatopancreatic procedures and define clinical outcomes, as well as costs, of minimally invasive techniques compared with the conventional open approach. Methods: The Medicare Provider Analysis and Review (MEDPAR) Inpatient Files were reviewed to identify Medicare patients who underwent pancreatic and liver procedures between 2013 and 2015. Primary outcomes of the analysis included perioperative clinical outcomes such as rates of complications, index hospitalization length-of-stay (LOS), failure-to-rescue, rates, and causes of 90-day readmission, as well as 90-day mortality. Secondary outcomes were Medicare payments for index hospitalization and readmission. Multivariable logistic regression was used to investigate the impact of MIS on clinical outcomes and health expenditures. Results: A total of 13,716 (90.6%) patients underwent open resection, while MIS was performed in 1424 (9.4%) patients. LOS was shorter among patients undergoing MIS (mean 7.3 \ub1 SD 7.3) versus open (mean 9.3 \ub1 SD 9.1) surgery (p 0.05). Mean total payments for open pancreatic surgery were on average $1421 higher in the open versus MIS pancreatic group (p = 0.01); in contrast, there was no difference in the overall payment for hepatic resection (p > 0.05). Conclusion: The MIS approach was underutilized among patients undergoing liver and pancreatic procedures. MIS was associated with lower complication and readmission and shorter LOS, as well as comparable/slightly lower Medicare payments, compared with the open approach. The MIS approach should strongly be considered among older patients undergoing liver and pancreatic procedures

Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma

The liver maintains a balance between immune tolerance and activation in its role as a filtration system. Chronic inflammation disrupts this immune microenvironment, thereby allowing for the rise and progression of cancer. Hepatocellular carcinoma (HCC) is a liver tumor generally diagnosed in the setting of chronic liver disease. When diagnosed early, the primary treatment is surgical resection, liver transplantation, or liver directed therapies. Unfortunately, patients with HCC often present at an advanced stage or with poor liver function, thereby limiting options. To further complicate matters, most systemic therapies are relatively limited and ineffective among patients with advanced disease. Recently, the IMbrave150 trial demonstrated that the combination of atezolizumab and bevacizumab was associated with better survival compared to sorafenib among patients with advanced HCC. As such, atezolizumab and bevacizumab is now recommended first-line therapy for these patients. Tumor cells work to create an immunotolerant environment by preventing the activation of stimulatory immunoreceptors and upregulating expression of proteins that bind inhibitory immunoreceptors. ICIs work to block these interactions and bolster the anti-tumor function of the immune system. We herein provide an overview of the use of ICIs in the treatment of HCC

Cardiac metastases and tumor embolization: A rare sequelae of primary undifferentiated liver sarcoma

AbstractINTRODUCTIONPrimary hepatic sarcomas are uncommon malignant neoplasms; prognostic features, natural history, and optimal management of these tumors are not well characterized.PRESENTATION OF CASEThis report describes the management of a 51-year-old patient that underwent a right trisectionectomy for a large hepatic mass found to be a liver sarcoma on pathology. He subsequently developed tumor emboli to his lungs and was discovered to have cardiac intracavitary metastases from his primary tumor. The patient underwent cardiopulmonary bypass and resection of the right-sided heart metastases to prevent further pulmonary sequela of tumor embolization.DISCUSSIONThe lack of distinguishing symptoms or imaging characteristics that clearly define hepatic sarcomas makes it challenging to achieve a diagnosis prior to pathologic examination. Metastatic spread is frequently to the lung or pleura, but very rarely seen within the heart. Failure to recognize cardiac metastatic disease will ultimately lead to progressive tumor embolization and cardiac failure if left untreated.CONCLUSIONThe most effective therapy for primary liver sarcomas is surgery; radical resection should be performed if possible given the aggressive nature of these tumors to progress and metastasize