(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

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

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

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

Can hypothermic oxygenated perfusion (HOPE) rescue futile DCD liver grafts?

BACKGROUND The new UK-DCD-Risk-Score has been recently developed to predict graft loss in DCD liver transplantation. Donor-recipient combinations with a cumulative risk of >10 points were classified as futile and achieved an impaired one-year graft survival of <40%. The aim of this study was to show, if hypothermic oxygenated perfusion (HOPE) can rescue such extended DCD livers and improve outcomes. METHODS "Futile"-classified donor-recipient combinations were selected from our HOPE-treated human DCD liver cohort (01/2012-5/2017), with a minimum follow-up of one year. Main risk factors, which contribute to the classification "futile" include: elderly donors>60years, prolonged functional donor warm ischemia time (fDWIT > 30min), long cold ischemia time>6hrs, donor BMI>25 kg/m$^{2}$, advanced recipient age (>60years), MELD-score>25points and retransplantation status. Endpoints included all outcome measures during and after DCD LT. RESULTS Twenty-one donor-recipient combinations were classified futile (median UK-DCD-Risk-Score:11 points). The median donor age and fDWIT were 62 years and 36 min, respectively. After cold storage, livers underwent routine HOPE-treatment for 120 min. All grafts showed immediate function. One-year and 5-year tumor death censored graft survival was 86%. CONCLUSION HOPE-treatment achieved excellent outcomes, despite high-risk donor and recipient combinations. Such easy, endischemic perfusion approach may open the door for an increased utilization of futile DCD livers in other countries

Sources and prevention of graft infection during long‐term ex situ liver perfusion

INTRODUCTION The use of normothermic liver machine perfusion to repair injured grafts ex situ is an emerging topic of clinical importance. However, a major concern is the possibility of microbial contamination in the absence of a fully functional immune system. Here, we report a standardized approach to maintain sterility during normothermic liver machine perfusion of porcine livers for one week. METHODS Porcine livers (n = 42) were procured and perfused with blood at 34°C following aseptic technique and standard operating procedures. The antimicrobial prophylaxis was adapted and improved in a step-wise manner taking into account the pathogens that were detected during the development phase. Piperacillin-Tazobactam was applied as a single dose initially and modified to continuous application in the final protocol. In addition, the perfusion machine was improved to recapitulate partially the host's defense system. The final protocol was tested for infection prevention during one week of perfusion. RESULTS During the development phase, microbial contamination occurred in 27 out of 39 (69%) livers with a mean occurrence of growth on 4 ± 1.6 perfusion days. The recovered microorganisms suggested an exogenous source of microbial contamination. The antimicrobial agents (piperacillin/tazobactam) could be maintained above the targeted minimal inhibitory concentration (8-16 mg/L) only with continuous application. In addition to continuous application of piperacillin/tazobactam, partial recapitulation of the host immune system ex situ accompanied by strict preventive measures for contact and air contamination maintained sterility during one week of perfusion. CONCLUSION The work demonstrates feasibility of sterility maintenance for one week during ex situ normothermic liver perfusion

Sources and prevention of graft infection during long-term ex situ liver perfusion

INTRODUCTION The use of normothermic liver machine perfusion to repair injured grafts ex situ is an emerging topic of clinical importance. However, a major concern is the possibility of microbial contamination in the absence of a fully functional immune system. Here, we report a standardized approach to maintain sterility during normothermic liver machine perfusion of porcine livers for one week. METHODS Porcine livers (n = 42) were procured and perfused with blood at 34°C following aseptic technique and standard operating procedures. The antimicrobial prophylaxis was adapted and improved in a step-wise manner taking into account the pathogens that were detected during the development phase. Piperacillin-Tazobactam was applied as a single dose initially and modified to continuous application in the final protocol. In addition, the perfusion machine was improved to recapitulate partially the host's defense system. The final protocol was tested for infection prevention during one week of perfusion. RESULTS During the development phase, microbial contamination occurred in 27 out of 39 (69%) livers with a mean occurrence of growth on 4 ± 1.6 perfusion days. The recovered microorganisms suggested an exogenous source of microbial contamination. The antimicrobial agents (piperacillin/tazobactam) could be maintained above the targeted minimal inhibitory concentration (8-16 mg/L) only with continuous application. In addition to continuous application of piperacillin/tazobactam, partial recapitulation of the host immune system ex situ accompanied by strict preventive measures for contact and air contamination maintained sterility during one week of perfusion. CONCLUSION The work demonstrates feasibility of sterility maintenance for one week during ex situ normothermic liver perfusion