Reviewing Patient-Reported Outcomes 1 Year after Orthotopic Liver Transplantation.

BACKGROUND: With improved survivorship in liver transplantation (LT), there is an emerging focus on functional recovery and health-related quality of life (HRQoL) after surgery. The present study aimed to assess HRQoL after LT using the Patient-Reported Outcomes Measurement Information System (PROMIS). STUDY DESIGN: This was a prospective analysis of LT recipients between 2020 and 2021. A total of 238 patients were contacted by phone at 3, 6, and 12 months postoperatively using the PROMIS 29-Profile. Scores were recorded and computed using the HealthMeasures Scoring Service. RESULTS: PROMIS was available for 174 patients at 3 (n = 58), 6 (n = 57), and 12 months (n = 59). Overall, mean PROMIS scores were 47.6 ± 3, 47.6 ± 3, and 47.6 ± 3 at 3, 6, and 12 months, respectively. Most domains improved postoperatively by 12 months except for anxiety and sleep disturbance measures. The lowest domain in the immediate postoperative period was physical functioning, but this had the closest return to normative population values. Pain interference was above the population reference during the initial postoperative period, improving by 12 months where they were below mean population values. Depression and fatigue scores improved by 6 months and appeared to stabilize by 12 months post-LT. Patients demonstrated increased social participation, and scores were remarkably higher than general population means at each timepoint. CONCLUSION: LT can impact physical, mental, and social health which, in this setting, remains largely unexplored using PROMIS instruments. We report that although overall patient well being can improve, some mental health domains require further consideration during the postoperative period.

Are Current National Review Board Downstaging Protocols for Hepatocellular Carcinoma Too Restrictive?

BACKGROUND: Liver transplantation (LT) is an effective strategy for patients with unresectable hepatocellular carcinoma (HCC). To qualify for standardized LT model for end-stage liver disease exception points, the United Network for Organ Sharing National Liver Review Board (NLRB) requires that the presenting and final HCC tumor burden be within the University of California San Francisco criteria, which were recently expanded (within expanded UCSF [W-eUCSF]). Current NLRB criteria may be too restrictive because it has been shown previously that the initial burden does not predict LT failure when tumors downstage to UCSF. This study aims to assess LT outcomes for HCC initially presenting beyond expanded UCSF (B-eUCSF) criteria in a large multicenter collaboration. STUDY DESIGN: Comparisons of B-eUCSF and W-eUCSF candidates undergoing LT at seven academic institutions between 2001 and 2017 were made from a multi-institutional database. Survival outcomes were compared by Kaplan-Meier and Cox regression analyses. RESULTS: Of 1,846 LT recipients with HCC, 86 (5%) met B-eUCSF criteria at initial presentation, with the remainder meeting W-eUCSF criteria. Despite differences in tumor burden, B-eUCSF candidates achieved comparable 1-, 5- and 10-year overall (89%, 70%, and 55% vs 91%, 74%, and 60%, respectively; p = 0.2) and disease-free (82%, 60%, and 53% vs 89%, 71%, and 59%, respectively; p = 0.07) survival to patients meeting W-eUCSF criteria after LT. Despite increased tumor recurrence in B-eUCSF vs W-eUCSF patients (24% vs 10%, p = 0.0002), post-recurrence survival was similar in both groups (p = 0.69). CONCLUSION: Transplantation for patients initially presenting with HCC B-eUSCF criteria offers a survival advantage similar to those with tumors meeting W-eUCSF criteria at presentation. The current NLRB policy is too stringent, and considerations to expand criteria should be discussed.

Neoadjuvant Locoregional Therapy and Recurrent Hepatocellular Carcinoma after Liver Transplantation.

BACKGROUND: Neoadjuvant locoregional therapies (LRTs) have been widely used to reduce tumor burden or to downstage hepatocellular carcinoma (HCC) before orthotopic liver transplantation (OLT). We examined the impact of LRT response on HCC recurrence after OLT. STUDY DESIGN: We performed a retrospective study of 384 patients with HCC treated by OLT. Tumor necrosis was determined by pathologic evaluation. The vascular and lymphatic vessels were localized by immunofluorescence staining in formalin-fixed, paraffin-embedded tissue; expressions of vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 were analyzed by Western blot. Plasma vascular endothelial growth factor (VEGF)-A and VEGF-C levels of a consecutive cohort of 171 HCC patients were detected by ELISA. RESULTS: Of the 384 patients with HCC, 268 had undergone pretransplantation neoadjuvant LRTs. Patients with no tumor necrosis (n = 58; 5.2% recurrence) or complete tumor necrosis (n = 70; 6.1% recurrence) had significantly lower 5-year recurrence rates than those with partial tumor necrosis (n = 140; 22.6% recurrence; p < 0.001). Lymphatic metastases were significantly more numerous in patients with partial tumor necrosis than in those without tumor necrosis after OLT (p < 0.001). With immunofluorescence staining of peritumor zone, lymphatics were visualized around partially necrotic tumors, but not around tumors without necrosis. Plasma levels of VEGF-A and VEGF-C were elevated significantly in patients with evidence of tumor necrosis (n = 102) compared with those without necrosis (n = 69; p < 0.001). By Western blot, VEGFR-2 and VEGFR-3 expression in the peritumoral tissue associated with partially necrotic tumors was significantly higher than in peritumoral tissue of non-necrosis tumors (n = 3/group, p < 0.020 and p < 0.006, respectively). CONCLUSIONS: Locoregional therapy-induced or spontaneous partially necrotic HCC was associated with increased risk of lymphatic metastases compared with tumors with no or complete tumor necrosis. Anti-lymphangiogenic agents with neoadjuvant LRTs can decrease the pattern of lymphatic metastasis after OLT.

Liver Transplantation for Malignant Primary Pediatric Hepatic Tumors.

BACKGROUND: Malignant primary pediatric hepatic tumors (MPPHTs) are rare and account for approximately 1% of all childhood malignancies. In recent years, liver transplantation has emerged as a viable treatment options for select patients with MPPHTs. STUDY DESIGN: We performed a single-center retrospective study using a prospective database to compare outcomes of pediatric liver transplant recipients, with and without cancer, between January 2000 and December 2014. RESULTS: One hundred fifty-three children underwent 173 liver transplantations during the study period. Of these, 21 (12%) children received 23 (13.3%) transplants for unresectable MPPHTs: 16 hepatoblastomas (HBs), 3 embryonal cell sarcomas (ECS), and 2 hepatocellular carcinomas (HCCs). There was no significant difference in 1-, 3-, and 10-year patient and graft survival rates between MPPHT and non-MPPHT patients (95.2%, 81.2%, 81.2%, and 95.2%, 72,2%, 72.2% for MPPHT vs 92.7%, 89.8%, 87.6% and 85.4%, 81.1%, 75% for the non-MPPHT group, respectively) (p > 0.05). Rates of 1-, 5-, and 10-year disease-free survival for MPPHT patients were 76%, 76%, and 76%, respectively. Median age at transplantation for MPPHT patients was 3.1 years (range 58 days to 17 years), median listing time was 81 days, and median wait list time was 15 days. Eight (38%) children had 2 tumors or more and 4 of 16 (25%) HB patients had metastatic disease at presentation. All children received neoadjuvant treatment, with radiographic response in 19 of 21 patients. Presence of metastatic HB at presentation, International Society of Pediatric Oncology Epithelial Liver (SIOPEL) high risk status, and persistently elevated alpha fetoprotein levels after neoadjuvant chemotherapy might be risk factors for tumor recurrence and decreased survival. CONCLUSIONS: Liver transplantation is an excellent option for select patients with unresectable MPPHTs, with outcomes comparable to those after transplantation for nonmalignant causes.