Utilization of Immunotherapy as a Neoadjuvant Therapy for Liver Transplant Recipients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.

Combined liver transplantation and sleeve gastrectomy: Report of a brief-interval staged approach.

Pretransplantation bariatric surgery in patients with high Model for End-Stage Liver Disease (MELD) score is fraught with risks. Bariatric surgery after liver transplantation (LT) may be complicated by surgical adhesions but could have advantages if performed at the time of transplantation. We investigated a method of brief-interval staging combining LT and sleeve gastrectomy (SG). LT recipients with a body mass index (BMI) > 40 kg/m 2 received an SG during the same hospitalization as the LT (LT/SG), at the same time as a planned brief-interval return to the operating room for biliary anastomosis. Differences in intraoperative attributes of the LT (Stage 1) versus SG (Stage 2) procedures were analyzed using Wilcoxon signed-rank test with significance p < 0.05 and compared with patients with obesity having a two-stage LT without SG. A total of 14 cases {median MELD score 33 (interquartile range [IQR], 18-40)} were compared with 28 controls; 60% were critically ill prior to surgery with mechanical ventilation, vasopressors, or continuous renal replacement therapy. Median interval between procedures was 16.1 (IQR, 12.5-22.7) hours for cases and 12.2 (IQR, 11.1-16.6) hours for controls, p  = 0.27. Median BMI at LT/SG was 47.0 (IQR, 41.7-51.3) kg/m 2 versus 38.1 (IQR, 35.7-39.8) kg/m 2 for controls, p < 0.001. At 1 year, median excess body weight loss was 74.0% (IQR, 46.2%-78.7%) in cases and 15.8% (IQR, -5.4% to 62.6%) in controls, p  = 0.13; total weight loss was 38.1% (IQR, 23.9-42.9) in cases versus 7.7% (IQR, -2.4% to 27.6%) for controls, p  = 0.03. Graft survival at 1 year was 92.9% for cases and 89.3% for controls with similar early postoperative outcomes. This proof-of-concept study revealed that a brief-interval SG during LT is feasible in patients with high MELD and resulted in sustained weight loss at 1 year with similar graft survival. Further studies are needed to determine an optimal strategy.

Is Surgery-first Still a Reasonable Option in the Era of Neoadjuvant Chemotherapy for Resectable Pancreatic Cancer?

The incidence of pancreatic ductal adenocarcinoma has risen rapidly. By 2030, it is likely to be the second most prevalent cause of death by cancer, following cancer of the lung. Unfortunately, most patients present with advanced disease. In fact, only 20% of patients are candidates for surgery. More research is needed to find dependable treatment options for this disease. Although we wait for more effective treatments to be developed, we continue using chemotherapy, radiation, and surgery-all with less than optimal outcomes. There is a debate about using chemotherapy in the neoadjuvant setting and counter-debate about better outcomes in the adjuvant settings. In the neoadjuvant setting, not everyone is able to make it to surgery; conversely, in the adjuvant setting, not everyone is able to make it to chemotherapy. Drop-out data after surgery are widely available, but similar drop-out rates after neoadjuvant treatment are not widely published. Here, we will analyze the literature to better understand the treatment strategies and outcomes of pancreatic ductal adenocarcinoma. We argue in favor of an upfront surgery and adjuvant therapy strategy for better outcomes and patient quality of life.

Promising new treatments for pancreatic cancer in the era of targeted and immune therapies.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality among men and women in the United States. Its incidence has been on the rise, with a projected two-fold increase by 2030. PDAC carries a poor prognosis due to a lack of effective screening tools, limited understanding of pathophysiology, and ineffective treatment modalities. Recently, there has been a revolution in the world of oncology with the advent of novel treatments to combat this disease. However, the 5-year survival of PDAC remains unchanged at a dismal 8%. The aim of this review is to bring together several studies and identify various recent modalities that have been promising in treating PDAC.