Cryopreserved nanostructured fibrin-agarose hydrogels are efficient and safe hemostatic agents.

Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.

Women Are Also Disadvantaged in Accessing Transplant Outside the United States: Analysis of the Spanish Liver Transplantation Registry.

Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID).

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.

Evaluation of the validated intraoperative bleeding scale in liver surgery: study protocol for a multicenter prospective study.

Background: Surgical hemostasis has become one of the key principles in the advancement of surgery. Hemostatic agents are commonly administered in many surgical specialties, although the lack of consensus on the definition of intraoperative bleeding or of a standardized system for its classification means that often the most suitable agent is not selected. The recommendations of international organizations highlight the need for a bleeding severity scale, validated in clinical studies, that would allow the selection of the best hemostatic agent in each case. The primary objective of this study is to evaluate the VIBe scale (Validated Intraoperative Bleeding Scale) in humans. Secondary objectives are to evaluate the scale's usefulness in liver surgery; to determine the relationship between the extent of bleeding and the hemostatic agent used; and to assess the relationship between the grade of bleeding and postoperative complications. Methods: Prospective multicenter observational study including 259 liver resections that meet the inclusion criteria: patients scheduled for liver surgery at one of 10 medium-high volume Spanish HPB centers using an open or minimally invasive approach (robotic/laparoscopic/hybrid), regardless of diagnosis, ASA score <4, age ≥18, and who provide signed informed consent during the study period (September 2023 until the required sample size has been recruited). The participating researchers will be responsible for collecting the data and for reporting them to the study coordinators. Discussion: This study will allow us to evaluate the VIBe scale for intraoperative bleeding in humans, with a view to its subsequent incorporation in daily clinical practice. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05369988?term = serradilla&draw = 2&rank = 3, [NCT0536998].

Effectiveness and safety of once-daily tacrolimus formulations in de novo liver transplant recipients: The PRETHI study.

Data comparing long-term effectiveness and safety of once-daily tacrolimus formulations in de novo liver transplantation are scarce. We compared the effectiveness, pharmacokinetic profile, and safety of LCPT (Envarsus) and PR-Tac (Advagraf) for up to 12 months post-transplant. Adult de novo liver transplant recipients who started IR-Tac (Prograf) and were converted to LCPT or PR-Tac 3-5 days post-transplant were included. Data from 163 patients were analyzed, 87 treated with LCPT and 76 with PR-Tac. The incidence of treatment failure was 30.5% in the LCPT group versus 23.0% in the PR-Tac group (p = .291). Biopsy-proven acute rejection (BPAR) was reported in 26.8% of patients in the LCPT group and 17.6% in the PR-Tac group (p = .166). Graft loss was experienced in one patient (1.2%) in the LCPT group and three patients (4.1%) in the PR-Tac group (p = .346). Death was registered in three patients (3.7%) in the LCPT group and three patients (4.1%) in the PR-Tac group (p > .999). Patients in the LCPT group showed 45.7% higher relative bioavailability (Cmin /total daily dose [TDD]; p < .01) with similar Cmin and 33.3% lower TDD versus PR-Tac (p < .01). The evolution of renal function, safety profile, and the incidence of post-transplant renal failure, dyslipidemia, obesity, hypertension, and diabetes mellitus were similar in patients treated with LCPT and PR-Tac. In de novo liver transplant patients, LCPT and PR-Tac showed comparable effectiveness with higher relative bioavailability, similar Cmin and lower TDD in the LCPT group. Renal function, safety, and post-transplant complications were comparable in LCPT and PR-Tac groups.

Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis.

BACKGROUND & AIMS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. METHODS: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. RESULTS: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001). CONCLUSIONS: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. IMPACT AND IMPLICATIONS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

Liver Resuscitation With Hypothermic Oxygenated Perfusion After Donation in Asystolic Type Iii With Regional Perfusion in Normothermia: A Case Report About First Experience in Spain.

BACKGROUND: Extended criteria donor livers are increasingly being accepted for transplant in an attempt to bridge the gap between the number of patients on the waiting list and the number of available donor livers. Our objective was to describe our first case of hepatic resuscitation by means of an ex situ perfusion machine in hypothermia with oxygen insufflation of a liver graft extracted from a donor in type 3 asystole after regional perfusion in normothermia. METHODS: A 53-year-old woman with disabling polycystic liver disease was included on the liver transplant waiting list. Donation was offered in type 3 asystole with regional perfusion in normothermia. Given that it was an elderly donor with a low-weight graft, hepatic resuscitation was decided by means of an ex situ perfusion machine in hypothermia with oxygen insufflation. RESULTS: After performing the bench work, the injector is selectively cannulated via the portal to connect it to the hypothermic perfusion machine. The average temperature of the perfusate (3 L modified Belzer) was 10°C for 120 minutes at 250 mL/min. The implant was completed without the need for transfusion of blood products, postreperfusion Sd, or vasoactive support. Peak of GOT/GPT was 803/276 at 24 hours posttransplant.

Impact of a Donor Age >75 Years on the Survival of Liver Transplant Recipients.

BACKGROUND: An organ shortage is the reason why it is necessary to expand the pool of donors, which can be achieved by using elderly donors. The main goal of this study is to analyze the outcomes of liver transplant (LT) when it is performed with donors older than 75 years. METHODS: We carried out a retrospective case-control study (N = 212) that included LTs with donors older than 75 years (group A, n = 106 cases) that were performed in our center between the years 2010 and 2020. This cohort has been paired off with a similar control group (group B, n = 106) whose donors were significantly younger. A survival analysis using the Kaplan-Meier model was performed. RESULTS: Average (SD) age of donors in group A was statistically greater than group B (A, 79.1 [3.0] years vs B, 54.4 [15.3], P < .001). There were no differences either in the average age of the recipients or in the Model for End-Stage Liver Disease score of both groups. Indications for LT were distributed equally in both groups: the most common was cellular hepatocarcinoma followed by alcohol-related cirrhosis. Survival rates for group A were 81%, 78%, and 67%, in 1, 3, and 5 years, respectively, while in group B they were 85%, 76%, and 71%, respectively, without differences found between the groups (P = .57). CONCLUSIONS: Using elderly liver donors is safe, achieving good outcomes in terms of short- and midterm rates of survival.

Radiofrequency-assisted transection of the pancreas versus stapler in distal pancreatectomy: study protocol for a multicentric randomised clinical trial (TRANSPAIRE).

INTRODUCTION: To date, no pancreatic stump closure technique has been shown to be superior to any other in distal pancreatectomy. Although several studies have shown a trend towards better results in transection using a radiofrequency device (radiofrequency-assisted transection (RFT)), no randomised trial for this purpose has been performed to date. Therefore, we designed a randomised clinical trial, with the hypothesis that this technique used in distal pancreatectomies is superior in reducing clinically relevant postoperative pancreatic fistula (CR-POPF) than mechanical closures. METHODS AND ANALYSIS: TRANSPAIRE is a multicentre randomised controlled trial conducted in seven Spanish pancreatic centres that includes 112 patients undergoing elective distal pancreatectomy for any indication who will be randomly assigned to RFT or classic stapler transections (control group) in a ratio of 1:1. The primary outcome is the CR-POPF percentage. Sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-ß), expected POPF in control group of 32%, expected POPF in RFT group of 10% and a clinically relevant difference of 22%. Secondary outcomes include postoperative results, complications, radiological evaluation of the pancreatic stump, metabolomic profile of postoperative peritoneal fluid, survival and quality of life. Follow-ups will be carried out in the external consultation at 1, 6 and 12 months postoperatively. ETHICS AND DISSEMINATION: TRANSPAIRE has been approved by the CEIM-PSMAR Ethics Committee. This project is being carried out in accordance with national and international guidelines, the basic principles of protection of human rights and dignity established in the Declaration of Helsinki (64th General Assembly, Fortaleza, Brazil, October 2013), and in accordance with regulations in studies with biological samples, Law 14/2007 on Biomedical Research will be followed. We have defined a dissemination strategy, whose main objective is the participation of stakeholders and the transfer of knowledge to support the exploitation of activities. REGISTRATION DETAILS: ClinicalTrials.gov Registry (NCT04402346).

Role of Early Extubation in Decreasing Morbidity and Mortality in Liver Transplantation.

BACKGROUND: Early extubation is a fundamental element integrated into enhanced recovery protocols in orthotopic liver transplantation (OLT). The aim is to evaluate whether early extubation influences short- and medium-term postoperative morbidity and mortality. METHODS: A cohort of 209 patients who underwent OLT in a tertiary hospital in a period from January 2016 to December 2018 were retrospectively analyzed. Patients were divided into 2 groups: group 1: early extubation in the intensive care unit and group 2: delayed extubation. Mortality is compared between both groups in the first month and first and third year. Postoperative morbidity was also compared. RESULTS: Patients in group 1 (n = 165, 79.9%) presented, with statistical significance, lower mortality at 1 month, 1 year, and 3 years; shorter duration of admission to the critical care unit and of hospital stay; lower incidence of surgical reoperation and retransplant; lower rate of transfusion of blood products; fewer pulmonary, digestive, neurologic, cardiologic, hemodynamic, kidney, surgical, infectious, metabolic, thrombotic, vascular, and graft complications; less need for kidney replacement therapy; less refractory ascites; and greater infectious risk. However, no statistically significant differences were found in the need for hospital readmission; in biliary, endocrine, nutritional, hematologic, thrombotic, and hematologic complications; or in graft rejection. In group 1, 6.6% of patients required reintubation. In group 2, 97% of patients could be extubated during the first week; 7.8% required noninvasive mechanical ventilation type bilevel positive airway pressure and 8.1% high flow. Only 2.8% of patients required tracheotomy. CONCLUSIONS: The role of early extubation seems key to improve outcomes in OLT because it reduces the incidence of multiple complications and mortality, with low reintubation rates. It is a feasible and safe procedure.

Applicability and reproducibility of the validated intraoperative bleeding severity scale (VIBe scale) in liver surgery: A multicenter study.

BACKGROUND: Bleeding is an intraoperative and postoperative complication of liver surgery of concern, and yet evidence to support utility and reproducibility of bleeding scales for liver surgery is limited. We determined the reproducibility of the clinician-reported validated intraoperative bleeding severity scale and its clinical value of implementation in liver surgery. METHODS: In this descriptive and observational multicenter study, we assessed the performance of liver surgeons instructed on the clinician-reported intraoperative bleeding severity scale using training videos that covered all 5 grades of bleeding severity. Surgeons were stratified according to years of surgical experience and number of surgeries performed per year based on a median split in low and high values. Intraobserver and interobserver agreement was assessed using Kendall's coefficient of concordance (Kendall's W). RESULTS: Forty-seven surgeons from 10 hospitals in Spain participated in the study. The overall intraobserver concordance was 0.985, and the overall interobserver concordance was 0.929. For "high experience" surgeons, the intraobserver and interobserver agreement values were 0.990 and 0.941, respectively. For "low experience" surgeons, the intraobserver and interobserver agreement was 0.981 and 0.922, respectively. Regarding the annual number of surgeries, intraobserver and interobserver agreement values were 0.995 and 0.940, respectively, for surgeons performing >35 surgeries per year, with 0.979 and 0.923, respectively, for surgeons who perform ≤35 surgeries year. CONCLUSION: The clinician-reported intraoperative bleeding severity scale shows high interobserver and intraobserver concordance, suggesting it is a useful tool for assessing severity of bleeding during liver surgery; years of surgical experience and number of annual procedures performed did not affect the applicability of the clinician-reported intraoperative bleeding severity scale.

Long-Term Effectiveness, Safety, and Patient-Reported Outcomes of Self-Administered Subcutaneous Hepatitis B Immunoglobulin in Liver Post-Transplant Hepatitis B Prophylaxis: A Prospective Non-Interventional Study.

BACKGROUND Self-administered subcutaneous hepatitis B immunoglobulin (s.c. HBIg) in combination with nucleos(t)ide analogs (NUCs) has proved to be effective and safe in preventing hepatitis B virus (HBV) reinfection after liver transplantation. MATERIAL AND METHODS This non-interventional, prospective, single-arm, multicenter, international study collected data on long-term effectiveness, safety, patient satisfaction (Treatment Satisfaction Questionnaire for Medication, TSQM-11), and quality of life (EQ-5D questionnaire) in routine practice over a 2-year treatment period. Data analysis was based on 195 adults (82.1% male) transplanted for HBV-related liver diseases and treated with s.c. HBIg with/without NUC(s). RESULTS HBV recurrence (seropositivity of HBV surface antigen and/or HBV DNA) was observed in 7/195 (3.6%) patients (annual rate: 2.01%). Hepatocellular carcinoma (HCC) recurred in 4/83 (4.8%) patients transplanted for HBV-HCC (annual rate: 2.88%). Twenty-nine adverse drug reactions occurred in 16/195 (8.2%) patients. Convenience and overall satisfaction scores of the TSQM-11 were significantly (P<0.05) improved under treatment at the 3-month, 2-year, and last follow-up visits. Quality of life remained constant over the entire observation period (EQ-5D index [P≥0.075]). S.c. HBIg was mainly self-administered (6458/9021 administrations, 71.6%) at home (8514/9021 administrations, 94.4%). CONCLUSIONS The results indicate long-term effectiveness and safety of s.c. HBIg in combination with NUC therapy in preventing post-transplant HBV reinfection under real-life conditions. The convenience of the therapy contributed to the high overall treatment satisfaction and acceptance by the patients.

Donor-Specific Cell-Free DNA qPCR Quantification as a Noninvasive Accurate Biomarker for Early Rejection Detection in Liver Transplantation.

(1) Background: Graft-cell-free DNA (cfDNA) in the circulation of liver transplant recipients has been proposed as a noninvasive biomarker of organ rejection. The aim of this study was to detect donor-specific cfDNA (ds-cfDNA) in the recipient's serum after either liver damage or rejection using a qPCR-based method. (2) Methods: We proposed a qPCR method based on the amplification of 10 specific insertion-deletion (InDel) polymorphisms to detect donor-specific circulating DNA diluted in the recipient cfDNA. ds-cfDNA from 67 patients was evaluated during the first month post-transplantation. (3) Results: Graft rejection in the first month post-transplantation was reported in 13 patients. Patients without liver complications showed a transitory increase in ds-cfDNA levels at transplantation. Patients with rejection showed significant differences in ds-cfDNA increase over basal levels at both the rejection time point and several days before rejection. Receiver operator characteristic (ROC) analysis showed that ds-cfDNA levels discriminated rejection, with an AUC of 0.96. Maximizing both sensitivity and specificity, a threshold cutoff of 8.6% provided an estimated positive and negative predictive value of 99% and 60%, respectively. (4) Conclusions: These results suggest that ds-cfDNA may be a useful marker of graft integrity in liver transplant patients to screen for rejection and liver damage.

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID).

BACKGROUND: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. METHODS: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. RESULTS: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). CONCLUSIONS: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

BACKGROUND: Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). METHODS: In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. RESULTS: CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. CONCLUSIONS: CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

Expanding Indications of Liver Transplantation in Spain: Consensus Statement and Recommendations by the Spanish Society of Liver Transplantation.

BACKGROUND: The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain. METHODS: A modified Delphi approach was used to identify areas to expand indications for LT and to build consensus around paramount aspects, such as inclusion criteria and waitlist prioritization within each area. The scientific evidence and strength of recommendations were assessed by the "Grading of Recommendations Assessment, Development, and Evaluation" system. RESULTS: The consensus process resulted in the identification of 7 potential areas to expand criteria in LT: recipient's age, hepatocellular carcinoma, alcoholic hepatitis, acute-on-chronic liver failure, hilar and intrahepatic cholangiocarcinoma, and unresectable liver metastases of colorectal cancer. CONCLUSIONS: We present the main recommendations issued for each topic, together with their core supporting evidence. These recommendations may allow for expanding criteria for LT homogenously in Spain and may provide a guidance to other countries/institutions facing a similar scenario.