ABSTRACT
Background: Liver transplantation is an increasingly frequent surgical procedure, with elevated rates of postoperative incisional hernias ranging from 5% to 46%. There are numerous known risk factors for incisional hernia, including the type of incision, patient sex, and presence of comorbidities such as diabetes, ascites, older age, and the use of steroids. Most studies on the treatment of incisional hernias in patients who have undergone liver transplantation have shown consistently high rates of complications. Consequently, we propose the use of nonvascular fascia for the symptomatic treatment of incisional hernias in patients with concomitant liver transplantation. Methods: We performed our new technique on 8 patients, who had previously undergone liver transplantation, between January 2019 and January 2023. The patients were examined using imaging techniques during the follow-up period. Results: Of the 8 patients, 7 were liver transplant recipients and 1 was a combined liver-kidney transplant patient. The median donor age was 57 y (5-66 y), whereas the mean recipient age was 58 y (31-66 y). The median patient height and weight were 163 cm (117-185 cm) and 76 kg (17-104 kg), respectively. Immunosuppression did not change in fascia recipients. The median time between transplantation and hernia repair surgery was 41 mo (5-116 mo). The sizes of the aponeurotic defects varied from 6â ×â 6 to 25â ×â 20 cm. Two patients experienced complications: one experienced bulging that required reintervention and the other experienced surgical site seroma. There was no mortality related to the use of the technique, and none were reported during follow-up. Conclusions: With its promising results, nonvascularized fascial transplantation can be a successful treatment for incisional hernias in patients who had previously received a liver transplant.
ABSTRACT
BACKGROUND: Massive blood transfusion (MBT) is a common occurrence in liver transplant (LT) patients. Recipient-related risk factors include cirrhosis, history of multiple surgeries and suboptimal donors. Despite advances in surgical techniques, anesthetic management and graft preservation have decreased the need for transfusions, this complication has not been completely eliminated. METHODS: One thousand four hundred and sixty-nine LT were performed at our institution between May 2003 and December 2020, and data was available regarding transfusion for 1198 of them. We divided the patients into two groups, with regards to transfusion of 6 or more units of packed red blood cells in the first 24 h posttransplant, and we analyzed the differences between the groups. RESULTS: Out of the 1198 patients, 607 (50.7%) met criteria for MBT. Survival was statistically lower at 1, 3, and 5 years when comparing the groups that had MBT to those that did not (92.6%, 85.2% and 79.7%, respectively, in the non MBT group, vs. 78.1%, 71.6% y 66.8%, respectively, in the MBT group). MBT was associated with a 1.5 mortality risk as opposed to non-MBT patients. Logistical regression analysis of our variables yielded the following results for a new model, including serum creatinine (OR 1.97), sodium (OR 1.73), hemoglobin (OR 1.99), platelets (OR 1.37), INR (OR 1.4), uDCD (OR 2.13) and split liver donation. CONCLUSION: Massive blood transfusion impacts patient survival in a statistically significant way. The most significant risk factors are preoperative hemoglobin, INR and serum creatinine.
Subject(s)
Liver Transplantation , Humans , Liver Transplantation/adverse effects , Liver Transplantation/methods , Creatinine , Blood Transfusion , Risk Factors , HemoglobinsABSTRACT
Different mutations in the SERPINA1 gene result in alpha-1 antitrypsin (AAT) deficiency and in an increased risk for the development of liver diseases. More than 90% of severe deficiency patients are homozygous for Z (Glu342Lys) mutation. This mutation causes Z-AAT polymerization and intrahepatic accumulation which can result in hepatic alterations leading to steatosis, fibrosis, cirrhosis, and/or hepatocarcinoma. We aimed to investigate lipid status in hepatocytes carrying Z and normal M alleles of the SERPINA1 gene. Hepatic organoids were developed to investigate lipid alterations. Lipid accumulation in HepG2 cells overexpressing Z-AAT, as well as in patient-derived hepatic organoids from Pi*MZ and Pi*ZZ individuals, was evaluated by Oil-Red staining in comparison to HepG2 cells expressing M-AAT and liver organoids from Pi*MM controls. Furthermore, mass spectrometry-based lipidomics analysis and transcriptomic profiling were assessed in Pi*MZ and Pi*ZZ organoids. HepG2 cells expressing Z-AAT and liver organoids from Pi*MZ and Pi*ZZ patients showed intracellular accumulation of AAT and high numbers of lipid droplets. These latter paralleled with augmented intrahepatic lipids, and in particular altered proportion of triglycerides, cholesterol esters, and cardiolipins. According to transcriptomic analysis, Pi*ZZ organoids possess many alterations in genes and cellular processes of lipid metabolism with a specific impact on the endoplasmic reticulum, mitochondria, and peroxisome dysfunction. Our data reveal a relationship between intrahepatic accumulation of Z-AAT and alterations in lipid homeostasis, which implies that liver organoids provide an excellent model to study liver diseases related to the mutation of the SERPINA1 gene.
Subject(s)
alpha 1-Antitrypsin Deficiency , alpha 1-Antitrypsin , Humans , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin Deficiency/complications , Lipids , Liver Cirrhosis/etiology , Organoids , alpha 1-Antitrypsin/geneticsABSTRACT
Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick disease type A (NPA), type B (NPB) and type A/B (NPA/B), is a rare lysosomal storage disease characterized by progressive accumulation of sphingomyelin (SM) in the liver, lungs, bone marrow and, in severe cases, neurons. A disease model was established by generating liver organoids from a NPB patient carrying the p.Arg610del variant in the SMPD1 gene. Liver organoids were characterized by transcriptomic and lipidomic analysis. We observed altered lipid homeostasis in the patient-derived organoids showing the predictable increase in sphingomyelin (SM), together with cholesterol esters (CE) and triacylglycerides (TAG), and a reduction in phosphatidylcholine (PC) and cardiolipins (CL). Analysis of lysosomal gene expression pointed to 24 downregulated genes, including SMPD1, and 26 upregulated genes that reflect the lysosomal stress typical of the disease. Altered genes revealed reduced expression of enzymes that could be involved in the accumulation in the hepatocytes of sphyngoglycolipids and glycoproteins, as well as upregulated genes coding for different glycosidases and cathepsins. Lipidic and transcriptome changes support the use of hepatic organoids as ideal models for ASMD investigation.
Subject(s)
Niemann-Pick Disease, Type A , Niemann-Pick Diseases , Humans , Niemann-Pick Disease, Type A/genetics , Sphingomyelins , Liver , Gene ExpressionABSTRACT
Pyogenic liver abscess (PLA) is a life-threatening infection in both liver transplant (LT) and non-LT patients. Several risk factors, such as benign and malignant hepatopancreatobiliary diseases and colorectal tumors have been associated with PLA in the non-LT population, and hepatic artery stricture/thrombosis, biliary stricture, and hepaticojejunostomy in the LT patients. The objective of this study is to compare the outcomes of patients with PLA in LT and non-LT patients and to determine the risk factors associated with patient survival. From January 2000 to November 2020, a total of 296 adult patients were diagnosed of PLA in our institution, of whom 26 patients had previously undergone liver transplantation (LTA group), whereas 263 patients corresponded to the non-LTA population. Seven patients with PLA who had undergone previous kidney transplantation were excluded from this retrospective study. Twenty-six patients out of 1503 LT developed PLA (incidence of 1.7%). Median age was significantly higher in non-LTA patients (p = .001). No significant differences were observed in therapy. PLA recurrence was significantly higher in LTA than in non-LTA (34.6% vs. 14.8%; p = .008). In-hospital mortality was greater in the LT group than in the non-LT group (19.2% vs. 9.1% p = .10) and was identified in multivariable analysis as a risk factor for mortality (p = .027). Mortality rate during follow-up did not show significant differences between the groups: 34.6% in LTA patients versus 26.2% in non-LTA patients (p = .10). The most common causes of mortality during follow-up were malignancies, Covid-19 infection, and neurologic disease. 1-, 3-, and 5-year actuarial patient survival rates were 87.0%, 64.1%, and 50.4%, respectively, in patients of LTA group, and 84.5%, 66.5%, and 51.0%, respectively, in patients with liver abscesses in non-LTA population (p = .53). In conclusion, LT was a risk factor for in hospital mortality, but not during long-term follow-up.
Subject(s)
COVID-19 , Liver Abscess, Pyogenic , Liver Transplantation , Adult , Humans , Liver Abscess, Pyogenic/etiology , Liver Abscess, Pyogenic/therapy , Retrospective Studies , Liver Transplantation/adverse effects , Constriction, Pathologic/etiology , COVID-19/etiology , Risk FactorsABSTRACT
BACKGROUND: Percutaneous drainage (PD) and antibiotics are the therapy of choice (non-surgical therapy [non-ST]) for pyogenic liver abscesses (PLA), reserving surgical therapy (ST) for PD failure. The aim of this retrospective study was to identify risk factors that indicate the need for ST. METHODS: We reviewed the medical charts of all of our institution's adult patients with a diagnosis of PLA between January 2000 and November 2020. A series of 296 patients with PLA was divided into two groups according to the therapy used: ST (n = 41 patients) and non-ST (n = 255). A comparison between groups was performed. RESULTS: The overall median age was 68 years. Demographics, clinical history, underlying pathology, and laboratory variables were similar in both groups, except for the duration of PLA symptoms < 10 days and leukocyte count which were significantly higher in the ST group. The in-hospital mortality rate in the ST group was 12.2% vs. 10.2% in the non-ST group (p = 0.783), with biliary sepsis and tumor-related abscesses as the most frequent causes of death. Hospital stay and PLA recurrence were statistically insignificant between groups. One-year actuarial patient survival was 80.2% in the ST group vs. 84.6% in the non-ST (p = 0.625) group. The presence of underlying biliary disease, intra-abdominal tumor, and duration of symptoms for less than 10 days on presentation comprised the risk factors that indicated the need to perform ST. CONCLUSIONS: There is little evidence regarding the decision to perform ST, but according to this study, the presence of underlying biliary disease or an intra-abdominal tumor and the duration of PLA symptoms < 10 days upon presentation are risk factors that should sway the surgeons to perform ST instead of PD.
Subject(s)
Abdominal Neoplasms , Gallbladder Diseases , Liver Abscess, Pyogenic , Aged , Humans , Abdominal Neoplasms/complications , Abdominal Neoplasms/drug therapy , Anti-Bacterial Agents/therapeutic use , Liver Abscess, Pyogenic/diagnosis , Liver Abscess, Pyogenic/etiology , Liver Abscess, Pyogenic/therapy , Polyesters , Retrospective Studies , Risk FactorsSubject(s)
Liver Transplantation , Liver , Humans , Liver/diagnostic imaging , Liver/surgery , AbdomenABSTRACT
BACKGROUND: Twenty percent of intestinal transplant recipients will require a surgical alternative to conventional primary abdominal wall closure. Abdominal wall transplant is a developing technique that is increasingly performed for this purpose in isolated intestinal or multivisceral recipients; however, adequate closure of the donor is paramount while simultaneously obtaining a large enough graft. The aim of this study is to describe alternative surgical techniques for closure of the donor in cases in which abdominal wall graft extraction hinders subsequent donor abdominal closure. METHODS: We describe the cases of 2 young donors in whom intestinal extraction was not carried out and in whom wall closure was not feasible, following standard techniques after abdominal wall graft extraction. We performed 2 different procedures to obtain adequate closure. 1. Hemifascia and hemiabdominal wall graft extraction: It is an option when the recipients require an extension of the abdominal aponeurosis yet have enough skin to guarantee skin closure. The perfusion of both epigastric arteries is needed. The remaining cutaneous half is used for closing the donor's abdomen.2. Hemiabdominal wall graft extraction: Full-thickness abdominal wall is harvested from the donor, selecting the most vascularized half. It is an alternative for recipients who need a skin implant in addition to an aponeurosis extension. This option should be used for recipients who do not require a large fascial graft but do require a significant cutaneous graft. The nontransplanted half of full-thickness abdominal wall is used for donor closure. RESULTS: Abdominal wall transplant allows for expansion of the abdominal cavity in organ recipients and reduces the risk of compartmental syndrome and subsequent ischemia. However, the donor wall defect must be considered. The choice of donation technique was based on the magnitude of the defect in the donor as well as the size of defect to be covered in the recipient while ensuring a tight and complete closure of the donor's abdomen. CONCLUSIONS: Abdominal wall graft extraction can be performed using nonconventional techniques that account for the extension and type of coverage needed by the recipient while guaranteeing proper closure of the donor.
Subject(s)
Abdominal Wall , Humans , Abdominal Wall/surgery , Skin Transplantation , Abdominal Muscles , Tissue Donors , Intestines/transplantationSubject(s)
Hamartoma , Humans , Hamartoma/diagnostic imaging , Hamartoma/surgery , Bile Ducts, IntrahepaticABSTRACT
BACKGROUND: An increased number of older recipients underwent liver transplantation in recent years, and consequently needing to obtain more liver grafts. In order to increase this pool, in 2006, we initiated the use of livers from uncontrolled circulatory death (uDCD). We analyzed the use of uDCD livers in sexagenarian recipients and their effect on overall survival. METHODS: A retrospective and comparative study was performed among 4 groups according to recipient age (less or greater than 60 years) and donor type (donor brain death [DBD] or uDCD): Group A: DBD livers in recipients aged <60 years (n = 169); Group B: uDCD livers in recipients aged <60 years (n = 36); Group C: DBD livers in recipients aged >60 years (n = 96); and Group D: uDCD livers in recipients aged >60 years(n = 39). RESULTS: Intraoperative transfusion, biliary complications, primary non-function, acute rejection, chronic renal dysfunction, retransplantation, and mortality during follow-up (cardiovascular diseases in 3 patients, hepatitis C virus recurrence in 4 patients, and de novo malignancies in 3 patients) were significantly higher, and 5-year patient and graft survival was significantly lower in sexagenarian recipients. Bilirubin and packed red blood cells transfusion were risk factors for patient survival, whereas hepatocelular carcinoma, creatinine, and packed red blood cells transfusion were risk factors for patient survival. Recipient age (<60 years) was confirmed as protective factor for patient and graft survival, whereas the use of uDCD was not a risk factor for patient or graft survival. CONCLUSIONS: Use of a uDCD liver did not demonstrate as a risk factor for patient and graft survival, and recipient age (<60 years) was a protective factor for patient and graft survival.
Subject(s)
Brain Death , Liver Transplantation , Humans , Liver Transplantation/adverse effects , Retrospective Studies , Tissue Donors , Graft Survival , DeathABSTRACT
BACKGROUND: Invasive fungal infection, particularly intraabdominal candidiasis, exerts a negative impact on the outcome of pancreas transplant recipients (PTRs). Optimal antifungal prophylaxis in this context remains unclear. METHODS: We performed a single-centre retrospective study to compare the incidence of invasive candidiasis during the first 6 post-transplant months in a cohort of 218 PTRs over two periods in which different agents for antifungal prophylaxis were used: fluconazole (Fluco-Px) from March 1995 to June 2012, and micafungin followed by fluconazole (Mica-Px) from July 2012 to December 2018. RESULTS: A total of 152 and 66 PTRs received Fluco-Px and Mica-Px. Mean age was 39.7 ± 7.8 years, 56.4% (123/218) were males, and 85.3% (186/218) underwent simultaneous pancreas-kidney transplantation. Invasive candidiasis occurred in 21.7% (33/152) of PTRs under Fluco-Px compared to 24.2% (16/66) of those under Mica-Px (p-value = .681). Median time from transplantation to infection was 8 days (interquartile range [IQR]: 6-16) under Fluco-Px versus 6.5 (IQR: 3.3-15.8) under Mica-Px (p-value = .623). Non-albicans Candida species comprised 27.5% (11/40) and 25.0% (4/16) of episodes under Fluco-Px and Mica-Px respectively (p-value = .849). Surgical site infection was the most common form in both groups (82.5% [33/40] and 87.5% [14/16]; p-value = .954). Multivariable analysis identified cold ischaemia time of the pancreas and kidney grafts, surgical reintervention and insulin requirement after transplantation as risks factor for invasive candidiasis. CONCLUSION: This retrospective study did not reveal a significant benefit from the initial use of micafungin-based antifungal prophylaxis over fluconazole among PTRs in terms of invasive candidiasis.
Subject(s)
Candidiasis, Invasive , Pancreas Transplantation , Adult , Antifungal Agents/therapeutic use , Candida , Candidiasis , Candidiasis, Invasive/drug therapy , Female , Fluconazole/therapeutic use , Humans , Male , Micafungin , Middle Aged , Pancreas , Pancreas Transplantation/adverse effects , Retrospective Studies , Transplant RecipientsABSTRACT
Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.
Subject(s)
Liver Transplantation , Tissue and Organ Procurement , Aged , Death , Graft Survival , Humans , Liver Transplantation/adverse effects , Liver Transplantation/methods , Middle Aged , Organ Preservation/methods , Perfusion/methods , Retrospective Studies , Risk Factors , Tissue DonorsABSTRACT
Difficulty in obtaining adequate abdominal wall closure due to loss of the abdominal domain is a frequent complication of multivisceral, isolated intestinal transplantation and in some cases of liver transplantation. Various methods for primary closure have been proposed, including the use of synthetic and biological meshes, as well as full-thickness abdominal wall and non-vascularized rectus fascia grafts. We describe a novel technique for abdominal wall procurement in which the graft is perfused synchronously with the abdominal organs and can be transplanted as a full-thickness wall or as a non-vascularized rectus fascia graft. We performed six transplants of non-vascularized rectus fascia in three intestinal transplants, one multivisceral transplant, and two liver transplants. The size of the covered abdominal wall defects ranged from 17 cm × 7 cm to 25 cm × 20 cm. Only one patient developed graft infection secondary to enterocutaneous fistula requiring surgical correction and removal of the fascia graft. This patient, as well as two other patients, died due to sepsis. Our procurement technique allows removal of the rectus fascia graft to cover the abdominal wall defect, providing a feasible solution for treatment of abdominal wall defects in recipients after abdominal organ transplantation.
Subject(s)
Abdominal Wall , Liver Transplantation , Organ Transplantation , Abdominal Muscles , Abdominal Wall/surgery , Fascia/transplantation , Humans , Liver Transplantation/methodsABSTRACT
The authors did not receive any funding for this work.
Subject(s)
Tissue and Organ Procurement , Death , Humans , Tissue DonorsABSTRACT
BACKGROUND: The McCluskey index has been used as a tool to predict massive bleeding (>6 red blood cells units) during orthotropic liver transplantation. The objective of this study is to verify its efficacy at our institution. MATERIALS AND METHODS: Between May 1998 and December 2017, we performed 1216 orthotropic liver transplantations, of which 1016 had sufficient data registered with respect to hemoderivative transfusion. We divided these patients into groups based on the original study of McCluskey. This study was approved by the ethical committee of our Institution and was performed in accordance with the Declaration of Helsinki. RESULTS: The mean Model for End-Stage Liver Disease score in the 4 groups was 7.5 (range, 7-8) for low risk; 13 (range, 3-32) for medium risk, 17 (range, 8-41) for high risk, and 25 (range, 11-36) for very high risk (P < .001). No significant differences were observed regarding body mass index or hospital stay. No differences have been found in the number of suboptimal donors among the groups. With respect to hemoderivative transfusions, we observed the following for red blood cells: 7 (range, 6-8) units for low risk; 5.5 (range, 0-74) for medium risk; 7 (range, 0-73) for high risk, and 12 (range, 5-30) for very high risk (P < .001) and transfusion of plasma: 12 (range, 10-15) units for low risk; 11 (range, 0-89) for medium risk; 14 (range, 0-76) for high risk, and 13 (range, 3-30) for very high risk (P = .001). CONCLUSIONS: The McCluskey index is a good indicator of the risk of hemorrhage and hence the necessity of transfusion.