Controversy Over Liver Transplantation or Resection for Neuroendocrine Liver Metastasis: Tumor Biology Cuts the Deal

Background: In patients with neuroendocrine liver metastasis (NELM), liver transplantation (LT) is an alternative to liver resection (LR), although the choice of therapy remains controversial. In this multicenter study, we aim to provide novel insight in this dispute. Methods: Following a systematic literature search, 15 large international centers were contacted to provide comprehensive data on their patients after LR or LT for NELM. Survival analyses were performed with the Kaplan-Meier method, while multivariable Cox regression served to identify factors influencing survival after either transplantation or resection. Inverse probability weighting and propensity score matching was used for analyses with balanced and equalized baseline characteristics. Results: Overall, 455 patients were analyzed, including 230 after LR and 225 after LT, with a median follow-up of 97 months [95% confidence interval (CI): 85-110 months]. Multivariable analysis revealed G3 grading as a negative prognostic factor for LR [hazard ratio (HR)=2.22, 95% CI: 1.04-4.77, P=0.040], while G2 grading (HR=2.52, 95% CI: 1.15-5.52, P=0.021) and LT outside Milan criteria (HR=2.40, 95% CI: 1.16-4.92, P=0.018) were negative prognostic factors in transplanted patients. Inverse probability-weighted multivariate analyses revealed a distinct survival benefit after LT. Matched patients presented a median overall survival (OS) of 197 months (95% CI: 143-not reached) and a 73% 5-year OS after LT, and 119 months (95% CI: 74-133 months) and a 52.8% 5-year OS after LR (HR=0.59, 95% CI: 0.3-0.9, P=0.022). However, the survival benefit after LT was lost if patients were transplanted outside Milan criteria. Conclusions: This multicentric study in patients with NELM demonstrates a survival benefit of LT over LR. This benefit depends on adherence to selection criteria, in particular low-grade tumor biology and Milan criteria, and must be balanced against potential risks of LT

The role of resection in hepatocellular carcinoma BCLC stage B: A multi-institutional patient-level meta-analysis and systematic review

Purpose: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. Methods: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. Results: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03–0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce. Conclusion: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies

(18)FDG-PET-CT improves specificity of preoperative lymph-node staging in patients with intestinal but not diffuse-type esophagogastric adenocarcinoma

INTRODUCTION The accuracy of preoperative lymph-node staging in patients with adenocarcinoma of the esophagogastric junction (AEG) or gastric cancer (GC) is low. The aim of this study was to assess the accuracy of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) for lymph-node staging in patients with AEG or GC, with or without neoadjuvant treatment. PATIENTS AND METHODS 221 consecutive patients with GC (n = 88) or AEG (n = 133) were evaluated. Initial staging included endoscopic ultrasound (EUS), multidetector spiral CT (MDCT) and PET-CT. PET-CT was performed for restaging in patients after neoadjuvant treatment (n = 94). Systematic lymphadenectomy was routinely performed with histopathological assessment of individual mediastinal and abdominal lymph-node stations. Preoperative staging from EUS, MDCT, and PET-CT was correlated with histopathological results. RESULTS PET-CT showed a high specificity (91%) and positive predictive value (89%) for the preoperative detection of lymph-node metastases. In comparison, EUS was more sensitive (73% versus 50%, P < 0.01) but less specific (60%, P < 0.01). In patients with intestinal/mixed-type tumors, PET-CT improved the detection of extra-regional lymph-node metastases (P = 0.01) and distant metastases (P = 0.01) compared to CT alone. In contrast, lymph-node assessment by PET/CT after neoadjuvant treatment (32%, P < 0.01) and in diffuse-type cancers (24%, P < 0.01) is futile because of low sensitivities. CONCLUSION PET-CT does not improve the overall accuracy of N staging, but does improve specificity compared to EUS and MDCT in AEG and GC. We do not recommend routine PET-CT for the initial staging in patients with diffuse-type cancer or for restaging of lymph nodes after neoadjuvant treatment

Meta-analysis of associating liver partition with portal vein ligation and portal vein occlusion for two-stage hepatectomy

BACKGROUND: Discussion is ongoing regarding whether associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) or portal vein occlusion is better in staged hepatectomy. The aim of this study was to compare available strategies using a two-stage approach in extended hepatectomy. METHODS: A literature search was performed in MEDLINE, Scopus, the Cochrane Library and Embase, and additional articles were identified by hand searching. Data from the international ALPPS registry were extracted. Clinical studies reporting volumetric changes, mortality, morbidity, feasibility of the second stage and tumour-free resection margins (R0) in two-stage hepatectomy were included. RESULTS: Ninety studies involving 4352 patients, including 320 from the ALPPS registry, met the inclusion criteria. Among these, nine studies (357 patients) reported on comparisons with other strategies. In the comparison of ALPPS versus portal vein embolization (PVE), ALPPS was associated with a greater increase in the future liver remnant (76 versus 37 per cent; P < 0·001) and more frequent completion of stage 2 (100 versus 77 per cent; P < 0·001). Compared with PVE, ALPPS had a trend towards higher morbidity (73 versus 59 per cent; P = 0·16) and mortality (14 versus 7 per cent; P = 0·19) after stage 2. In the non-comparative studies, complication rates were 39 per cent in the PVE group, 47 per cent in the portal vein ligation (PVL) group and 70 per cent in the ALPPS group. After stage 2, mortality rates were 5, 7 and 12 per cent respectively. CONCLUSION: ALPPS is associated with greater future liver remnant hypertrophy and a higher rate of completion of stage 2, but this may be at the price of greater morbidity and mortality

Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors-Need for a Conductor.

Pancreatic neuroendocrine tumors (pNETs) are a vast growing disease. Over 50% of these tumors are recognized at advanced stages with lymph node, liver, or distant metastasis. An ongoing controversy is the role of surgery in the metastatic setting as dedicated systemic treatments have emerged recently and shown benefits in randomized trials. Today, liver surgery is an option for advanced pNETs if the tumor has a favorable prognosis, reflected by a low to moderate proliferation index (G1 and G2). Surgery in this well-selected population may prolong progression-free and overall survival. Optimal selection of a treatment plan for an individual patient should be considered in a multidisciplinary tumor board. However, while current guidelines offer a variety of modalities, there is so far only a limited focus on the right timing. Available data is based on small case series or retrospective analyses. The focus of this review is to highlight the right time-point for surgery in the setting of the multimodal treatment of an advanced pancreatic neuroendocrine tumor

Novel Real-Time Prediction of Liver Graft Function During Hypothermic Oxygenated Machine Perfusion Before Liver Transplantation

OBJECTIVE: The aim of this study was to determine the predictive value of machine perfusate analysis on graft outcome. BACKGROUND: Ex situ machine perfusion (MP) is gaining increasing interest to potentially repair injured organs and to assess organ function. In the field of liver transplantation, however, no studies exist on reliable prediction of graft function during MP. METHODS: We have used hypothermic oxygenated perfusion (HOPE) for donation after circulatory death (DCD) or extended criteria donation after brain death (DBD) human liver grafts during the last 7 years. Our series includes 100 HOPE-treated liver-transplanted patients with an overall tumor-censored 5-year graft survival of 89%. We monitored 54 livers during HOPE in terms of fluorometric analysis of released mitochondrial flavin (flavin mononucleotide, FMN) in the machine perfusate. RESULTS: Real-time optical measurement of mitochondrial FMN release in machine perfusates of livers disclosed a strong correlation with lactate clearance and coagulation factors at day 1 and 2 after transplantation. Receiver-operating characteristic curve analysis revealed an area under the curve (AUROC) of 0.79 [95% confidence interval (CI), 0.62-0.97] for severe allograft dysfunction and for early graft loss (AUROC 0.93, 95% CI, 0.84-1.0). CONCLUSIONS: Assessment of flavin, a marker of mitochondrial complex I injury, in the perfusate provides a fast prediction of liver graft function and loss during ex situ MP before implantation. This finding may have high clinical relevance, as liver grafts from extended DBD or DCD donors carry considerable risks for recipients. On-line estimation of outcome before implantation would therefore substantially increase safe utilization of liver grafts