Andries E. Braat

The Eurotransplant Donor Risk Index in Liver Transplantation: ET-DRI

Recently we validated the donor risk index (DRI) as conducted by Feng et al. for the Eurotransplant region. Although this scoring system is a valid tool for scoring donor liver quality, for allocation purposes a scoring system tailored for the Eurotransplant region may be more appropriate. Objective of our study was to investigate various donor and transplant risk factors and design a risk model for the Eurotransplant region. This study is a database analysis of all 5939 liver transplantations from deceased donors into adult recipients from the 1st of January 2003 until the 31st of December 2007 in Eurotransplant. Data were analyzed with Kaplan–Meier and Cox regression models. From 5723 patients follow‐up data were available with a mean of 2.5 years. After multivariate analysis the DRI (p < 0.0001), latest lab GGT (p = 0.005) and rescue allocation (p = 0.007) remained significant. These factors were used to create the Eurotransplant Donor Risk Index (ET‐DRI). Concordance‐index calculation shows this ET‐DRI to have high predictive value for outcome after liver transplantation. Therefore, we advise the use of this ET‐DRI for risk indication and possibly for allocation purposes within the Eurotrans‐plant region.

Validation of the donor risk index in orthotopic liver transplantation within the Eurotransplant region

In Eurotransplant, more than 50% of liver allografts come from extended criteria donors (ECDs). However, not every ECD is the same. The limits of their use are being explored. A continuous scoring system for analyzing donor risk has been developed within the Organ Procurement and Transplantation Network (OPTN), the Donor Risk Index (DRI). The objective of this study was the validation of this donor risk index (DRI) in Eurotransplant. The study was a database analysis of all 5939 liver transplants involving deceased donors and adult recipients from January 1, 2003 to December 31, 2007 in Eurotransplant. Data were analyzed with Kaplan‐Meier and Cox regression models. Follow‐up data were available for 5723 patients with a median follow up of 2.5 years. The mean DRI was remarkably higher in the Eurotransplant region versus OPTN (1.71 versus 1.45), and this indicated different donor populations. Nevertheless, we were able to validate the DRI for the Eurotransplant region. Kaplan‐Meier curves per DRI category showed a significant correlation between the DRI and outcomes (P < 0.001). A multivariate analysis demonstrated that the DRI was the most significant factor influencing outcomes (P < 0.001). Among all donor, transplant, and recipient variables, the DRI was the strongest predictor of outcomes. Liver Transpl 18:113–120, 2012.

The sentinel node procedure in colon carcinoma: a multi-centre study in The Netherlands.

BackgroundLymph node status is the most important predictive factor in colorectal carcinoma. Recurrences occur in 20% of the patients without lymph node metastases. The sentinel lymph node (SLN) biopsy is a tool to facilitate identification of micrometastatic disease and aberrant lymphatic drainage. We studied the feasibility of in vivo SLN detection in a multi-centre setting and evaluated nodal micro-staging using immunohistochemistry (IHC).Materials and methodsSub-serosal injection with Patent Blue dye was used in the SLN procedure in 69 patients operated for localized colon cancer in six Dutch hospitals. Each SLN was examined with routine haematoxylin–eosin staining. In tumour-negative SLNs, we performed CK7/8 or 18 IHC.ResultsThe procedure was successful in 67 of 69 patients (97%). The SLN was negative in 43 patients. In three cases, it was false negative, resulting in a negative predictive value of 93% and an accuracy of 96%. In 24 of 27 patients with lymph node metastases in a successful SLN procedure, the SLN was positive (sensitivity 89%). In 15 patients, the SLN was the only positive node (21%). In nine patients, we only found micrometastases or isolated tumour cells, resulting in 18% upstaging. Aberrant lymphatic drainage was seen in three patients (4%).ConclusionThe SLN procedure in localized colon carcinoma is reliable in a multi-centre setting. It is helpful to identify patients who would be classified as stage II with conventional staging (18%) and who might benefit from adjuvant treatment.

Nucleoside plus nucleotide analogs and cessation of hepatitis B immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective

BACKGROUND After orthotopic liver transplantation (OLT) in chronic hepatitis B (HBV), adequate prophylaxis for recurrence of HBV in the graft is mandatory. OBJECTIVES Evaluate safety of HBV prophylaxis with tenofovir and emtricitabine (TDF/FTC) after cessation of hepatitis B immunoglobulin (HBIG) after OLT in chronic HBV. STUDY DESIGN In 17 consecutive patients after OLT in chronic HBV we started TDF/FTC after cessation of HBIG. All had received HBIG >6 months. 15/17 were HBsAg negative and 16/17 had undetectable HBV-DNA. RESULTS After mean follow-up of 2 years 16/17 patients were alive, one died due to urosepsis. All 16 with undetectable HBV-DNA remained HBV-DNA negative. From 15 HBsAg negative patients at start, in one seroconversion to positive HBsAg occurred, without detectable HBV-DNA. Liver biochemistry remained within the normal ranges. There were no cases of drug discontinuation. No major side effects were reported. TDF/FTC use saves €16,262/year over standard-of-care (HBIG+LAM). This prospective follow-up study shows that in liver transplantation for chronic hepatitis B, after initial treatment including HBIG for at least 6 months combined with or followed by (dual) nucleos(t)ide analog therapy, TDF/FTC provides adequate prophylaxis against recurrent HBV infection without major side effects and leads to substantial cost savings over a regimen with HBIG. CONCLUSION Combined prophylaxis with TDF/ETV nucleoside plus nucleotide analogs and cessation of immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective.

Sentinel node detection after preoperative short‐course radiotherapy in rectal carcinoma is not reliable

Seninel node (SN) detection may be used in patients with colonic carcinoma. However, its use in patients with rectal carcinoma may be unreliable. To address this, SN detection was evaluated in patients with rectal carcinoma after short‐course preoperative radiotherapy.

Longterm results of liver transplantation from donation after circulatory death

Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by posttransplantation complications such as primary nonfunction or ischemic‐type biliary lesions. However, similar survival rates for DCD and donation after brain death (DBD) LT have been reported. The objective of this study is to determine the longterm outcome of DCD LT in the Eurotransplant region corrected for the Eurotransplant donor risk index (ET‐DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003 to December 31, 2007) in adult recipients were included. Graft failure was defined as either the date of recipient death or retransplantation whichever occurred first (death‐uncensored graft survival). Mean follow‐up was 7.2 years. In total, 126 DCD and 1264 DBD LTs were performed. Kaplan‐Meier survival analyses showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%, respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02), and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log‐rank P = 0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, which is most likely caused by other risk factors being less in DCD livers. Patient survival was not significantly different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio of 1.7 (P < 0.001) for DCD (corrected for ET‐DRI and recipient factors). First warm ischemia time (WIT), which is the time from the end of circulation until aortic cold perfusion, over 25 minutes was associated with a lower graft survival in univariate analysis of all DCD transplants (P = 0.002). In conclusion, DCD LT has an increased risk for diminished graft survival compared to DBD. There was no significant difference in patient survival. DCD allografts with a first WIT > 25 minutes have an increased risk for a decrease in graft survival. Liver Transplantation 22 1107–1114 2016 AASLD

High peak alanine aminotransferase determines extra risk for nonanastomotic biliary strictures after liver transplantation with donation after circulatory death

Orthotopic liver transplantation (OLT) with donation after circulatory death (DCD) often leads to a higher first week peak alanine aminotransferase (ALT) and a higher rate of biliary nonanastomotic strictures (NAS) as compared to donation after brain death (DBD). This retrospective study was to evaluate whether an association exists between peak ALT and the development of NAS in OLT with livers from DBD (n = 399) or DCD (n = 97) from two transplantation centers. Optimal cutoff value of peak ALT for risk of development of NAS post‐DCD‐OLT was 1300 IU/l. The 4‐year cumulative incidence of NAS after DCD‐OLT was 49.5% in patients with a high ALT peak post‐OLT, compared with 11.3% in patients with a low ALT peak. (P < 0.001). No relation between peak ALT and NAS was observed after DBD‐OLT. Multivariate analysis revealed peak ALT ≥1300 IU/l [adjusted hazard ratio (aHR) = 3.71, confidence interval (CI) (1.26–10.91)] and donor age [aHR = 1.04, CI 1.00–1.07] to be independently associated with development of NAS post‐DCD‐OLT. A peak ALT of <1300 IU/l carries a risk for NAS similar to DBD‐OLT. Thus, in DCD‐OLT, but not in DBD‐OLT, peak ALT discriminates patients at high or low risk for NAS.

First experience on laparoscopic near-infrared fluorescence imaging of hepatic uveal melanoma metastases using indocyanine green.

Background. Uveal melanoma is the most common primary intraocular tumor in adults, and up to 50% of patients will develop liver metastases. Complete surgical resection of these metastases can improve 5-year survival, but only a few patients are eligible for radical surgical treatment. The aim of this study was to introduce a near-infrared (NIR) fluorescence laparoscope during minimally invasive surgery for intraoperative identification of uveal melanoma hepatic metastases and to use it to provide guidance during resection. Methods. Three patients diagnosed with one solitary liver metastasis from uveal melanoma are presented. Patients received 10 mg indocyanine green (ICG) intravenously 24 hours before surgery. A NIR fluorescence laparoscope was used to detect malignant liver lesions. Results. In all 3 patients, laparoscopic NIR fluorescence imaging using ICG successfully identified uveal melanoma metastases. In 2 patients, multiple additional lesions were identified by inspection and NIR fluorescence imaging, which were not identified by preoperative conventional imaging. In one patient, one additional lesion, not identified by computed tomography, magnetic resonance imaging, laparoscopic ultrasonography, and inspection, was observed with NIR fluorescence imaging only. Importantly, NIR fluorescence imaging provided guidance during resection of these metastases. Conclusions. We describe the successful use of laparoscopic identification and resection of uveal melanoma liver metastases using NIR fluorescence imaging and ICG. This procedure is minimally invasive and should be used as complementary to conventional techniques for the detection and resection of liver metastases.

Lymphatic Staging in Colorectal Cancer: Pathologic, Molecular, and Sentinel Node Techniques

PURPOSEAccurate staging in colorectal cancer is important to predict prognosis and identify patients who could benefit from adjuvant therapy. Patients with lymphatic metastasis, Stage III/Dukes C, are generally treated with adjuvant chemotherapy. Still, patients without lymphatic metastasis do have relapse as high as 27 percent in five years in Dukes B2. It is hypothesized that these patients have occult (micro)metastasis in their lymph nodes. If these (micro)metastasis can be identified, these patients might benefit from adjuvant therapy. We reviewed the literature on procedures to improve lymph node staging.METHODSAn extensive literature search was performed in PubMed (www.pubmed.com). Using the reference lists, more articles were found.RESULTSWe found 30 articles about sentinel node in colorectal cancer describing original series. Some groups reported several studies including the same patients. We reported their largest studies. For all other techniques, we only included key articles.CONCLUSIONSMany techniques to improve staging have been described. The finding of occult (micro)metastasis is of prognostic significance in most studies. The sentinel node technique has been recently described for use in colorectal cancer. Although it seems clear that this technique has prognostic potential, it is not yet been shown in a follow-up study. Furthermore, the finding of occult (micro)metastasis in any technique used has not been shown to be clinically significant. Whether to treat patients with adjuvant therapy if occult (micro)metastasis are found needs to be proven in future studies.

Combined effect of donor and recipient risk on outcome after liver transplantation: Research of the Eurotransplant database

Recently the Eurotransplant donor risk index (ET‐DRI) was published, a model based on data from the Eurotransplant database that can be used for risk indication of liver donors within the Eurotransplant region. Because outcome after liver transplantation (LT) depends both on donor and recipient risk factors, a combined donor‐recipient model (DRM) would give a more complete picture of the overall risk involved. All liver transplants in adult recipients from January 1, 2008 to December 31, 2010 in the Eurotransplant region were included. Risk factors in donors and recipients for failure‐free (retransplant free) survival were analyzed in univariate and multivariate analyses. A simplified recipient risk index (sRRI) was constructed using all available recipient factors. A total of 4466 liver transplants were analyzed. Median donor risk index and ET‐DRI were 1.78 and 1.91, respectively. The ET‐DRI was validated in this new cohort (P < 0.001; concordance index [c‐index], 0.59). After construction of a simplified recipient risk index of significant recipient factors, Cox regression analysis showed that the combination ET‐DRI and sRRI into a new DRM gave the highest predictive value (P < 0.001; c‐index, 0.62). The combined model of ET‐DRI and sRRI gave a significant prediction of outcome after orthotopic LT in the Eurotransplant region, better than the ET‐DRI alone. This DRM has potential in comparing data in the literature and correcting for sickness/physical condition of transplant recipients. It is a first step toward benchmarking of graft survival in the Eurotransplant region. Liver Transpl 21:1486‐1493, 2015.