Controlled donation after circulatory death up to 80 years for liver transplantation: Pushing the limit again.

Our main objective was to compare liver transplant (LT) results between donation after circulatory death (DCD) and donation after brainstem death (DBD) in our hospital and to analyze, within the DCD group, the influence of age on the results obtained with DCD donors aged >70 years and up to 80 years. All DCD-LTs performed were analyzed prospectively. The results of the DCD group were compared with those of a control group who received a DBD-LT immediately after each DCD-LT. Later, the results obtained within the DCD group were analyzed according to the age of the donors, considering 2 subgroups with a cut-off point at 70 years. Survival results for LT with DCD and super rapid recovery were not inferior to those obtained in a similar group of patients transplanted with DBD livers. However, the cost of DCD was a higher rate of biliary complications, including ischemic cholangiopathy. Donor age was not a negative factor.

The distance from the peroneal tendons sheath to the sural nerve at the posterior tip of the fibula decreases from proximal to distal.

PURPOSE: The aim of this study is to compare the distance from the peroneal tendons sheath to the sural nerve in different points proximally and distally to the tip of the fibula. METHODS: Ten fresh-frozen lower extremities were dissected to expose the nerves and tendons. Having the posterior tip of the fibula as a reference, the distance between the tendons sheath and the sural nerve was measured in each point with a tachometer with three independent different observers. Two measures were taken distally at 1.5 and 2 cm from fibula tip and 3 measures were performed proximally at 2, 3, and 5 cm from fibula tip. Data were described using means, standard deviations, medians, and minimum and maximum values. RESULTS: The average distance between distance between the fibula tip and sural nerve is 16.6 ± 4.4 mm. The average distance between peroneal tendons sheath and the sural nerve at 5 cm, 3 cm, and 2 cm from the proximal fibular tip was 29.6 ± 3.2 mm, 24.2 ± 3.6 mm, and 19.7 ± 2.7 mm, respectively. The average distance between the peroneal tendons sheath and the sural nerve at 2 cm and 1.5 cm distal to fibular tip was 9.1 ± 3.5 mm and 7.8 ± 3.3 mm, respectively. CONCLUSION: The distance from the peroneal tendons sheath to the sural nerve decreases from proximal to distal. As the distance between the peroneal tendons sheath and the sural nerve decreases from proximal to distal, performing the tendoscopy portal more distally would increase the risk of nerve iatrogenic injury.

Outcome of strict patient selection for surgical treatment of hepatic and pulmonary metastases from colorectal cancer.

BACKGROUND: Surgery is currently the only potentially curative treatment for hepatic or pulmonary metastases from colorectal cancer. However, the benefit of surgery and the criteria for the inclusion of patients developing hepatic and pulmonary metastases are not well defined. OBJECTIVE: The aim of this study was to describe the outcome for patients who undergo surgery for both hepatic and pulmonary metastases from colorectal cancer, to present a set of preoperative criteria for use in patient selection, and to analyze potential prognostic factors related to survival. DESIGN: This was an observational study with retrospective analysis of data collected with a prospective protocol. SETTINGS: This investigation was conducted at a tertiary centre. PATIENTS: Between January 1996 and January 2010, of 319 patients who underwent surgery for hepatic metastases from colorectal cancer, 44 also had resection of pulmonary metastases. A set of strict selection criteria established by a panel of liver surgeons, chest surgeons, oncologists, and radiologists was used. MAIN OUTCOME MEASURES: Survival was estimated with the Kaplan-Meier method, and univariate analyses were performed to evaluate potential prognostic factors for survival, including variables related to patient, primary tumour, hepatic, and pulmonary metastases and chemotherapy. RESULTS: The 44 patients received a total of 53 pulmonary resections: 36 patients had 1, 7 patients had 2, and 1 patient had 3 resections. There was no postoperative mortality and the morbidity rate after pulmonary resection was 1.8%. No patient was lost to follow-up. Overall survival was 93% at 1 year, 81% at 3 years, and 64% at 5 years. Factors related to poor prognosis in the univariate analysis were presence of more than 1 pulmonary metastasis (p = 0.04), invasion of the surgical margin (p = 0.006), and administration of neoadjuvant chemotherapy (p = 0.01 for hepatic metastases and p = 0.02 for pulmonary metastases). LIMITATIONS: The study was limited by its observational nature and the relatively small number of patients. CONCLUSION: In patients with hepatic and pulmonary metastases from colorectal cancer selected according to strict inclusion criteria, surgical treatment performed in a specialized center is a safe option that offers prolonged survival.

Successful embolization of a cytomegalovirus-related duodenal ulcer in a kidney-pancreas transplant recipient.

One of the complications that can occur in pancreas transplant is a massive intestinal hemorrhage, although such a hemorrhage is very rarely caused by ulcers due to cytomegalovirus infection. Treatment is fundamentally based on relaparatomy, although in some cases interventional radiology can be an efficient alternative because it allows the exact bleeding point to be located and therapeutic embolization to be performed. In this case, a man with diabetes type 1 who was given a simultaneous kidney-pancreas transplant had an ulcer due to cytomegalovirus infection develop in the duodenal graft (in the early postoperative period), causing a severe hemorrhage in the lower part of the gastrointestinal tract that was controlled via selective embolization of a branch of the pancreaticoduodenal artery.

A high concentration of TGF-ß correlates with opportunistic infection in liver and kidney transplantation.

Transforming growth factor-ß (TGF-ß) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-ß following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients. Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-ß concentration in the supernatant from the activated WPB. Recipients showed higher TGF-ß concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-ß than those without OI. A concentration of TGF-ß > 363.25 pg/ml in liver and TGF-ß > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations. TGF-ß could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection.

[Azoles of then and now: a review]. / Azoles de antes y ahora: una revisión.

The azoles are drugs that inhibit the 14α-sterol-demethylase enzyme preventing the binding of ergosterol, altering the functionality and structure of the fungal cell wall. Especially the group of triazoles: fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole, are a pharmacological alternative for the treatment of the invasive fungal disease, caused by Aspergillus spp, Candida spp, Cryptococcus spp, by emerging pathogens for example, the Mucoral and finally of endemic mycosis as those caused by Histoplasma spp. and Coccidioides spp. The adverse effects of the triazoles are less frequent compared to those caused by amphotericin B, the main ones being hepatics, gastrointestinals and cardiovasculars, such as the prolongation of the QT interval. The pharmacological interactions are common and occur with molecules that use the substrates of the CYP3A4 cytochrome, for example: antiretroviral, anti-tuberculous and immunomodulators. The history, pharmacological characteristics and clinical trials are reviewed.

Severe COVID-19 after liver transplantation, surviving the pitfalls of learning on-the-go: Three case reports.

BACKGROUND: The novel coronavirus 2019 (COVID-19) pandemic has dramatically transformed the care of the liver transplant patient. In patients who are immunosuppressed and with multiple comorbidities, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased severity and mortality. The main objective of this report is to communicate our experience in the therapeutic management of SARS-CoV-2 infection in 3 liver transplant patients. Secondly, we stress the management and investigation of the contagious spreading into a liver transplant ward. CASE SUMMARY: The patients were two women (aged 61 years and 62 years) and one man (aged 68 years), all of them having recently received a liver transplant. All three patients required intensive care unit admission and invasive mechanical ventilation. Two of them progressed severely until death. The other one, who received tocilizumab, had a good recovery. In the outbreak, the wife of one of the patients and four healthcare professionals involved in their care were also infected. CONCLUSION: We illustrate in detail the evolution of a nosocomial COVID-19 outbreak in a liver transplant ward. We believe that these findings will contribute to a better understanding of the natural history of the disease and will improve the treatment of the liver transplant patient with COVID-19.

Immunosuppression withdrawal improves long-term metabolic parameters, cardiovascular risk factors and renal function in liver transplant patients.

After liver transplantation, long-term immunosuppression (IS) administration is commonly complicated by renal dysfunction and cardiovascular complications. Twenty liver transplant patients on cyclosporine (CyA)-based IS were followed up prospectively after IS withdrawal. They consisted of 10 electively weaned patients and 10 either forcibly or incidentally weaned patients. Liver biochemical tests, blood pressure, serum creatinine, serum urea, serum uric acid, triglycerides, cholesterol and glucose were monitored after the start of weaning. Eight of the 20 patients (40%) were IS therapy free for a mean period of 61 +/- 39 months (range: 10-132 months). Of the remaining 12 patients, mild or moderate acute rejection occurred in six patients (30%), and mixed inflammatory portal tract infiltrate was seen in another six patients (30%). At the end of the study, mean (SD) serum creatinine had fallen by 0.28 (0.10) mg/dL (p < 0.001) in operationally tolerant (T) patients whereas the serum creatinine level increased in IS-dependent patients [+0.35 (0.35) mg/dL] (p = 0.005). In T patients, serum cholesterol, serum uric acid, fasting glucose and diastolic arterial pressure values significantly decreased. IS withdrawal can be achieved in selected liver transplant patients, and can improve not only kidney function, but also other CyA-associated side effects, such as hypercholesterolemia, hyperuricemia, hypertension and diabetes.

A new approach to hand-assisted laparoscopic liver surgery.

BACKGROUND: The best type of laparoscopic approach in solid liver tumours (SLTs), whether total laparoscopic surgery or hand-assisted laparoscopic surgery (HALS), has not yet been established. Our objective is to present our experience with laparoscopic liver resections in SLTs performed by HALS using a new approach. METHODS: We performed 35 laparoscopic resections in SLTs, of which 26 were carried out using HALS (in 25 patients) and 21 patients had liver metastases of a colorectal origin (LMCRC) (1 patient had 2 resections), 1 metastasis from a neuroendocrine tumour of the pancreas, 1 hepatocarcinoma on a healthy liver, 1 primary hepatic leiomyosarcoma and 1 giant haemangioma. Mean follow-up was 22 months. OPERATION: One right hemihepatectomy, one left hemihepatectomy, five bisegmentectomies II-III, three bisegmentectomies VI-VII and 16 segmentectomies (five of S. VI, three of S. VIII; three of S. V; two of S. IVb; one of S. II; one of S. IV; and in the remaining case resection of S. III and VI plus resection of a metastasis in S. VIII). MAIN OUTCOME MEASURES: Morbidity and mortality, conversion to open procedure, intraoperative blood loss, intra- and postoperative transfusion, length of stay and survival. RESULTS: There were no intra- or postoperative deaths, nor were there any conversions. One patient presented with morbidity (3.8%) (liver abscess). Mean blood loss was 200 ml (range 0-600 ml). One patient required transfusion (3.8%). Mean operative time was 180 min (range 120-360 min). Mean length of hospital stay was 4 days (range 2-5 days). The actuarial survival rate of the patients at 36 months with liver metastases from colorectal carcinoma (LMCRC) was 80%. CONCLUSIONS: Liver resection with HALS reproduces the low morbidity and mortality rates and effectiveness (3-year survival) of open surgery in SLTs when indicated selectively.

Role of 18F-FDG PET/CT vs CT-scan in patients with pulmonary metastases previously operated on for colorectal liver metastases.

OBJECTIVE: There is currently no conclusive scientific evidence available regarding the role of the 18F-FDG PET/CT for detecting pulmonary metastases from colorectal cancer (PMCRC) in patients operated on for colorectal liver metastases (CRLM). In the follow up of patients who underwent surgery for CRLM, we compare CT-scan and 18F-FDG PET/CT in patients with PMCRC. METHODS: We designed the study prospectively performing an 18F-FDG PET/CT on all patients operated on for CRLM where the CT-scan detected PMCRC during the follow up. We included patients who were operated on for PMCRC because the histological findings were taken as a control rather than biopsies. RESULTS: Of the 101 pulmonary nodules removed from 57 patients, the CT-scan identified a greater number (89 nodules) than the 18F-FDG PET/CT (75 nodules) (p < 0.001). Sensitivity was greater with the CT-scan (90 vs 76%, respectively) with a lower specificity (50 vs 75%, respectively) than with the 18F-FDG PET/CT. There were no differences between positive-predictive value and negative-predictive value. The 18F-FDG PET/CT detected more pulmonary nodules in four patients (one PMCRC in each of these patients) and more extrapulmonary disease in six patients (four mediastinal lymph nodes, one retroperitoneal lymph node and one liver metastases) that the CT-scan had not detected. CONCLUSION: Although CT-scans have a greater capacity to detect PMCRC, the 18F-FDG PET/CT could be useful in the detection of more pulmonary and extrapulmonary disease not identified by the CT-scan. Advances in knowledge: We tried to clarify the utility of 18F-FDG PET/CT in the management of this subpopulation of patients.

Prognostic factors for hepatitis C recurrence in patients undergoing orthotopic liver transplantation.

End-stage liver disease caused by the hepatitis C virus (HCV) is a major indication for liver transplantation. HCV re-infection after LT is constant, and it significantly impairs patient and graft survival. Factors that may influence histological recurrence in the graft remain unclear. The aim of our study is to analyse the factors that influence the histological recurrence of HCV in a series of 142 patients undergoing orthotopic liver transplantation. In this series, donors age until 1995 were mostly younger than 30 years, however, from 2000 onwards most of the cases had graft implants from elderly donors. Histological recurrence was 92% after a mean follow-up of 60 months (12-120 months), 17% of which had poor-prognostic recurrence. Half of the patients presenting with recurrence did so in the first six months and more than two thirds developing hepatitis in the graft did so in the first year. The accumulated probability of histological recurrence is 40.1%, 51.5%, 70.3%, 83.5% and 92% at 6, 12, 24, 36 and 60 months respectively. In our experience, the variables associated with the development of histological recurrence in the graft, in the multivariate analysis, are donors age > or =31 years and immunosuppressive treatment without mycophenolate mophetil (MMF). Treatment with MMF still acts as a protection factor and is associated with histological non-recurrence.

Liver recipients harbouring anti-donor preformed lymphocytotoxic antibodies exhibit a poor allograft survival at the first year after transplantation: experience of one centre.

In this retrospective study, we analyzed the effect of the presence of anti-donor preformed alloantibodies in 268 liver allograft transplants. Crossmatches were performed by complement-dependent cytotoxicity (CDC) assay and HLA antibody screening by flow cytometry (FlowPRA). Positive anti-donor crossmatch was detected in 5.2% of transplants. Acute rejection frequency in +CDC crossmatch patients was not different from that observed in -CDC crossmatch patients. None of the patients transplanted with +CDC crossmatch developed chronic rejection, but they showed a significantly lower allograft survival rate, and the majority of them had allograft failures before the end of the first post-transplant year, mainly within the 3 first months. Indeed, positive FlowPRA determination was concordant with data from the CDC assay. In conclusion, these findings show a direct correlation between the presence of anti-donor preformed antibodies and a poor allograft survival in liver transplant.

Azoles de antes y ahora: una revisión / Azoles of then and now: a review

Resumen Los azoles son fármacos que inhiben la enzima 14α-esteroldemetilasa, impidiendo la unión de ergosterol; esto altera la estructura y función de la pared celular fúngica. Especialmente el grupo de los triazoles: fluconazol, itraconazol, voriconazol, posaconazol e isavuconazol, son una alternativa farmacológica para el tratamiento de la enfermedad fúngica invasora causada por Aspergillus spp, Candida spp, Cryptococcus spp, patógenos emergentes como los Mucorales, y de micosis endémicas como las ocasionadas por Histoplasma spp y Coccidioides spp. Los efectos adversos de los triazoles son menos frecuentes comparados con los ocasionados por anfotericina B, un antifúngico de uso común para estas micosis. Los principales efectos adversos de los triazoles son hepáticos, gastrointestinales y cardiovasculares como la prolongación del intervalo QT. Las interacciones farmacológicas son usuales y se presentan con moléculas que usan sustratos del citocromo CYP3A4, lo que incluye anti-retrovirales, anti-tuberculosos e inmunomoduladores. En este trabajo se revisan la historia, características farmacológicas y los ensayos clínicos que evidencian su eficacia clínica en los diferentes escenarios clínicos.

Abstract The azoles are drugs that inhibit the 14α-sterol-demethylase enzyme preventing the binding of ergosterol, altering the functionality and structure of the fungal cell wall. Especially the group of triazoles: fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole, are a pharmacological alternative for the treatment of the invasive fungal disease, caused by Aspergillus spp, Candida spp, Cryptococcus spp, by emerging pathogens for example, the Mucoral and finally of endemic mycosis as those caused by Histoplasma spp. and Coccidioides spp. The adverse effects of the triazoles are less frequent compared to those caused by amphotericin B, the main ones being hepatics, gastrointestinals and cardiovasculars, such as the prolongation of the QT interval. The pharmacological interactions are common and occur with molecules that use the substrates of the CYP3A4 cytochrome, for example: antiretroviral, anti-tuberculous and immunomodulators. The history, pharmacological characteristics and clinical trials are reviewed.

Endothelial cell chimerism does not influence allograft tolerance in liver transplant patients after withdrawal of immunosuppression.

BACKGROUND: Human liver allografts sometimes show self-induced permanent tolerance without immunosuppression. It has recently been proposed that the replacement of liver donor endothelial cells by recipient cells could confer a survival advantage. The aim of this study was to analyze liver endothelial cell replacement in relation to the response (tolerance or rejection) after withdrawal of immunosuppression in liver transplant patients. METHODS: Nine liver recipient patients were entered into a program of immunosuppressive drug withdrawal. The authors studied liver endothelial cell chimerism in five of these patients who received a liver from a donor of the opposite sex by in situ hybridization for X and Y chromosomes. RESULTS: Three patients (33%) achieved complete withdrawal of immunosuppression. The authors' data show similar endothelial cell chimerism in both the tolerant and nontolerant patients analyzed. CONCLUSIONS: Endothelial cell chimerism has nothing to do with the induction of clinical tolerance in liver transplant patients after withdrawal of immunosuppression.

Liver transplantation for hilar cholangiocarcinoma.

The most appropriate treatment for Klatskin tumor (KT) with a curative intention is multimodal therapy based on achieving resection with tumour-free margins (R0 resections) combined with other types of neoadjuvant or adjuvant treatment (the most important factor affecting KT survival is the possibility of R0 resections, achieving 5-year survival rate of 40%-50%). Thirty to forty percent of patients with KT are inoperable and present a 5-year survival rate of 0%. In irresectable non-disseminated KT patients, using liver transplantation without neoadjuvant treatment, the 5-year survival rate increase to 38%, reaching 50% survival in early stage. In selected cases, with liver transplantation and neoadjuvant treatment (chemotherapy and radiotherapy), the actuarial survival rate is 65% at 5 years and 59% at 10 years. In conclusion, correct staging, neoadjuvant treatment, living donor and priority on the liver transplant waiting list may lead to improved results.