Pyogenic liver abscesses in liver transplant recipients versus non-transplant population. Outcome and risk factors of patient survival.

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.

Risk factors indicating the need for surgical therapy in patients with pyogenic liver abscesses.

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.

Expanding donor age in liver transplantation using liver grafts from nonagenarian donors.

INTRODUCTION: Satisfactory outcomes in a series of liver transplantations (LT) with octogenarian liver grafts have been reported, as well as several cases of LT using nonagenarian liver grafts with short follow-up. METHODS: From October 2013 to December 2019, we performed 426 LT. Six LTs used nonagenarian livers (case group) and 49 used octogenarian livers (control group). A comparative analysis was performed between groups. Median donor age was significantly higher in the nonagenarian group than in the octogenarian group (90.6 years versus 83.4 years; (P < .001). There was a significant difference in LT indications (P = .026) between the groups, but not in perioperative recipient variables, morbidity, or mortality. The 1-, 3-, and 5-year patient survival rates were 67.7% in the recipients of nonagenarian livers and 85.7%, 78.0%, and 74.4%, respectively, in the recipients of octogenarian livers (P = .631). The 1-, 3-, and 5-year graft survival rates were 66.7% in the recipients of nonagenarian livers and 81.3%, 73.8%, and 70.3%, respectively, in the recipients of octogenarian livers (P = .745). CONCLUSIONS: The results of LT with nonagenarian liver grafts are not significantly different from those obtained with octogenarian donors, taking into consideration the small sample size and careful selection of donors and adequate donor-recipient matching.

Short series regarding uncontrolled donor after cardiac death: A call for caution.

The authors did not receive any funding for this work.

New technique for abdominal wall procurement. Initial experience.

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.

T cell-mediated response to SARS-CoV-2 in liver transplant recipients with prior COVID-19.

Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-γ FluoroSpot assay after a median of 103 days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-γ-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-γ-producing SFUs and time from diagnosis (Spearman's rho: -0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell-mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable-but declining over time-SARS-CoV-2-CMI after a median of 3 months from COVID-19, with no meaningful differences with immunocompetent patients.

Incidence and risk factors of primary non-function after liver transplantation using grafts from uncontrolled donors after circulatory death.

BACKGROUND: Graft primary non-function (PNF) is the most severe complication after orthotopic liver transplantation (OLT) and is frequently associated with livers from uncontrolled circulatory death (uDCD). METHODS: We reviewed retrospectively the incidence, risk factors, and outcome of patients showing PNF after receiving uDCD liver grafts. The series comprises 75 OLT performed during 11 years. RESULTS: The incidence of PNF using uDCD livers was 8%. We compared patients who developed PNF (n = 6) vs. patients without PNF (n = 69). Mean pump flow of donors during normothermic regional perfusion (NRP) was significantly lower in PNF (p = .032). Day 1 post-OLT levels of transaminases and the incidence of renal complications and postoperative mortality were also significantly higher in the PNF group, but 5-year patient survival was similar in both groups (66.7% in PNF and 68.5% in non-PNF). All PNF patients underwent re-OLT, and 2 died. PNF incidence has decreased in the last 5-years. Binary logistic regression analysis confirmed final ALT value >4 times the normal value as risk factor for PNF, and median donor pump flow >3700 ml/min as protective effect. CONCLUSIONS: Adequate donor pump flow during NRP was a protective.

Biliary Complications After Liver Transplantation From Uncontrolled Donors After Circulatory Death: Incidence, Management, and Outcome.

The utilization of livers from donation after uncontrolled circulatory death (uDCD) increases the availability of liver grafts, but it is associated with a higher incidence of biliary complications (BCs) and lower graft survival than those organs donated after brain death. From January 2006 to December 2016, we performed 75 orthotopic liver transplantations (OLTs) using uDCD livers. To investigate the relationship of BCs with the use of uDCD OLT, we compared patients who developed BCs (23 patients) with those who did not (non-BC group, 43 patients) after excluding cases of hepatic artery thrombosis (a known cause of BC) and primary nonfunction. The groups had similar uDCD donor maintenance, donor and recipient characteristics, and perioperative morbidity/mortality rates, but we observed a higher rate of hepatocellular carcinoma and hepatitis C virus in the non-BC group. Percutaneous transhepatic biliary dilation, endoscopic retrograde cholangiopancreatography dilation, Roux-en-Y hepaticojejunostomy (HJ), a T-tube, and retransplantation were used for BC management. In the BC group, 1-, 3-, and 5-year patient survival rates were 91.3%, 69.6%, and 65.2%, respectively, versus 77.8%, 72.9%, and 72.9%, respectively, in the non-BC group (P = 0.89). However, 1-, 3-, and 5-year graft survival rates were 78.3%, 60.9%, and 56.5%, respectively, in the BC group versus 77.8%, 72.9%, and 72.9%, respectively, in the non-BC group (P = 0.38). Multivariate analysis did not indicate independent risk factors for BC development. In conclusion, patient and graft survival rates were generally lower in patients who developed BCs but not significantly so. These complications were managed in the majority of patients through radiological dilation, endoscopic dilation, or Roux-en-Y HJ. Retransplantation is necessary in rare cases after the failure of biliary dilation or surgical procedures.

Varied clinical presentation and outcome of SARS-CoV-2 infection in liver transplant recipients: Initial experience at a single center in Madrid, Spain.

BACKGROUND: Which are the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant (LT) recipients? METHODS: We attempted to address this question by reviewing our single-center experience during the first 2 months of the pandemics at a high incidence area. RESULTS: Nineteen adult patients (5 females) were diagnosed by May 5, 2020. Median age was 58 (range 55-72), and median follow-up since transplantation was 83 (range 20-183) months. Cough (84.2%), fever (57.9%), and dyspnea (47.4%) were the most common symptoms. Thirteen patients (68.4%) had pneumonia in x-ray/CT scan. Hydroxychloroquine was administered in 11 patients, associated with lopinavir/ritonavir and interferon ß in 2 cases each. Immunomodulatory therapy with tocilizumab was used in 2 patients. Immunosuppression (IS) was halted in one patient and modified in only other two due to potential drug interactions. Five (26.3%) patients were managed as outpatient. Two patients (10.5%) died, 10 (52.6%) were discharged home, and 2 (10.5%) were still hospitalized after a median follow-up of 41 days from the onset of symptoms. Baseline IS regimen remained unchanged in all surviving recipients, with good liver function. CONCLUSIONS: Our preliminary experience shows a broad spectrum of disease severity in LT patients with COVID-19, with a favorable outcome in most of them without needing to modify baseline IS.

Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation.

BACKGROUND & AIMS: Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transplants performed with postmortem NRP vs. super-rapid recovery (SRR), the current standard for cDCD. METHODS: This was an observational cohort study including all cDCD liver transplants performed in Spain between June 2012 and December 2016, with follow-up ending in December 2017. Each donor hospital determined whether organ recovery was performed using NRP or SRR. The propensity scores technique based on the inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups; logistic and Cox regression models were used for binary and time-to-event outcomes. RESULTS: During the study period, there were 95 cDCD liver transplants performed with postmortem NRP and 117 with SRR. The median donor age was 56 years (interquartile range 45-65 years). After IPTW analysis, baseline covariates were balanced, with all absolute standardised differences <0.15. IPTW-adjusted risks were significantly improved among NRP livers for overall biliary complications (odds ratio 0.14; 95% CI 0.06-0.35, p <0.001), ischaemic type biliary lesions (odds ratio 0.11; 95% CI 0.02-0.57; p = 0.008), and graft loss (hazard ratio 0.39; 95% CI 0.20-0.78; p = 0.008). CONCLUSIONS: The use of postmortem NRP in cDCD liver transplantation appears to reduce postoperative biliary complications, ischaemic type biliary lesions and graft loss, and allows for the transplantation of livers even from cDCD donors of advanced age. LAY SUMMARY: This is a propensity-matched nationwide observational cohort study performed using livers recovered from donors undergoing cardiac arrest provoked by the intentional withdrawal of life support (controlled donation after circulatory death, cDCD). Approximately half of the livers were recovered after a period of postmortem in situ normothermic regional perfusion, which restored warm oxygenated blood to the abdominal organs, whereas the remainder were recovered after rapid preservation with a cold solution. The study results suggest that the use of postmortem normothermic regional perfusion helps reduce rates of post-transplant biliary complications and graft loss and allows for the successful transplantation of livers from older cDCD donors.

Outcome of patients with hemodialysis or peritoneal dialysis undergoing simultaneous pancreas-kidney transplantation. Comparative study.

BACKGROUND: Controversy remains with regard to the higher risk of intra-abdominal infections and lower patient and graft survival when peritoneal dialysis (PD) rather than hemodialysis (HD) is used in simultaneous pancreas-kidney transplantation (SPKT). METHODS: From March 1995 to December 2015, we performed 165 SPKTs. Prior to transplant, patients received hemodialysis (group HD; n = 98) or peritoneal dialysis (group PD; n = 67). A comparison was made to analyze post-transplant complications and patient, pancreas, and kidney graft survivals. RESULTS: Donor, pretransplant, and perioperative recipient variables were similar in both groups. Overall rates of infections (69.4% in HD vs 73.1% in PD; P = .50) and intra-abdominal infections (31.6% in HD vs 35.8 in PD; P = .57) were similar in both groups. The rates of pancreatitis, hemorrhage or thrombosis of the graft, duodenal graft leak, relaparotomy, transplantectomy, pancreas rejection, and retransplantation were similar in both groups. Patient survival at 1, 3, and 5 years (95.9%, 93.9%, and 93.9% in HD vs 95.5%, 92.2%, and 90.4% in PD; P = .54) and pancreas graft survival (83.6%, 78.0%, and 71.8% in HD vs 79.2%, 77.4%, and 71.0% in PD; P = .8) were similar in both groups. Kidney graft survival was similar in both groups. Pancreas graft thrombosis, rejection, and relaparotomy for intra-abdominal complications were independent predictors of lower pancreas graft survival, but dialysis modality did not influence patient or graft survival. CONCLUSIONS: Pre-SPKT modality of dialysis does not significantly influence overall or intra-abdominal infection and patient, pancreas, or kidney graft survivals.

A retrospective analysis of patients with gallbladder cancer: surgical treatment and survival according to tumor stage.

INTRODUCTION: gallbladder cancer is the most common biliary neoplasm and the sixth most common tumor of the digestive system. The disease has an ominous prognosis, with a 5-year survival rate of approximately 5%. It is usually diagnosed late and surgical resection is the only potential cure. METHODS: a retrospective study was carried out in 92 patients with a pathological diagnosis of gallbladder cancer from January 2000 to January 2016. RESULTS: the mean age of cases was 72 ± 11 years; 64 subjects were females and 28 were males. Symptoms at admission included abdominal pain (78%), anorexia (77%), nausea (76%) and jaundice (45%). Surgery was indicated in 92 (100%) patients and 59 (64%) underwent a curative/intent resection. The initial surgical procedures included simple cholecystectomy in 69 (75%) cases and extended cholecystectomy in eleven (11%) subjects. Rescue surgery was performed in 15 patients with tumor tissue in the cholecystectomy specimen; ten individuals underwent an R0 curative resection. Adjuvant therapy was administered in 30 (33%) patients. The median survival in our series was 12.5 months, with survival rates of 57%, 30% and 20% at one, three and five years, respectively. CONCLUSION: to conclude, surgical treatment with a complete tumor resection should be considered for all patients, provided that their clinical status allows it.

Long-term results using old liver grafts for transplantation: sexagenerian versus liver donors older than 70 years.

BACKGROUND: The most practical measure to augment the available number of liver grafts and thus reduce waiting list mortality is to increase the donor age limit. We hypothesized that with careful selection of old liver donors without age limit it should be possible to obtain good patient and graft survival. METHODS: The present study comprises 351 adults who underwent liver transplantation. They were divided into three groups according to the age of the liver donors: group 1: 226 recipients of donors <60 years; group 2: 75 recipients of donors between 60 and 70 years; and group 3: 50 recipients of donors >70 years. A comparative study among the groups was performed. RESULTS: Patient survival rates at 1, 3, and 5 years were, respectively, 81.0, 76.1, and 71.1 % in group 1; 83.8, 74, and 72.2 % in group 2; and 76, 70.0, and 62.9 % in group 3 (P = NS). Graft survival at 1, 3, and 5 years was, respectively, 74.8, 69.0, and 64.1 % in group 1; 82.7, 71.4, and 69.6 % in group 2; and 71.4, 64.8, and 58.3 % in group 3 (P = NS). We analyzed the use of older grafts in recipients with HCV cirrhosis and did not find significant differences in patient and graft survival at 1, 3, and 5 years. In multivariate analysis increased donor body mass index and decreased recipient albumin were associated with lower patient and graft survival. CONCLUSIONS: Because patient and graft survival rates are not affected by donor age, well-selected older donor livers can be safely used if they show good function and preharvesting conditions.

Risk factors of massive blood transfusion in liver transplantation: consequences and a new index for prediction including the donor.

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.

Post-transplant biliary complications using liver grafts from deceased donors older than 70 years: Retrospective case-control study.

BACKGROUND: The shortage of liver grafts and subsequent waitlist mortality led us to expand the donor pool using liver grafts from older donors. AIM: To determine the incidence, outcomes, and risk factors for biliary complications (BC) in liver transplantation (LT) using liver grafts from donors aged > 70 years. METHODS: Between January 1994 and December 31, 2019, 297 LTs were performed using donors older than 70 years. After excluding 47 LT for several reasons, we divided 250 LTs into two groups, namely post-LT BC (n = 21) and without BC (n = 229). This retrospective case-control study compared both groups. RESULTS: Choledocho-choledochostomy without T-tube was the most frequent technique (76.2% in the BC group vs 92.6% in the non-BC group). Twenty-one patients (8.4%) developed BC (13 anastomotic strictures, 7 biliary leakages, and 1 non-anastomotic biliary stricture). Nine patients underwent percutaneous balloon dilation and nine required a Roux-en-Y hepaticojejunostomy because of dilation failure. The incidence of post-LT complications (graft dysfunction, rejection, renal failure, and non-BC reoperations) was similar in both groups. There were no significant differences in the patient and graft survival between the groups. Moreover, only three deaths were attributed to BC. While female donors were protective factors for BC, donor cardiac arrest was a risk factor. CONCLUSION: The incidence of BC was relatively low on using liver grafts > 70 years. It could be managed in most cases by percutaneous dilation or Roux-en-Y hepaticojejunostomy, without significant differences in the patient or graft survival between the groups.

Obesity is an independent risk factor for pre-transplant portal vein thrombosis in liver recipients.

BACKGROUND: Portal vein thrombosis is a frequent complication in end-stage cirrhosis with a considerable peri-operative risk for liver transplant candidates. We aimed to characterize the pre-transplant portal vein thrombosis in a cohort of liver transplant recipients, and to identify independent risk factors for this complication. METHODS: 380 consecutive primary orthotopic liver transplants were performed in the Digestive Surgery Department of "12 de Octubre" Hospital (Madrid, Spain), between January 2001 and December 2006. The main risk factors considered were smoking, obesity, metabolic disorders, previous immobility, surgery or trauma, nephrotic syndrome, associated tumor, inflammatory disease, neoplasm myeloprolipherative. Furthermore we have reported genetic thrombophilia results for 271 recipients. RESULTS: Sixty-two (16.3%) patients developed pre-transplant portal vein thrombosis and its presence had no impact in the overall survival of liver recipients. Obesity was the only independent risk factor for pre-transplant portal vein thrombosis. CONCLUSION: We recommend close control of cardiovascular factors in patients with liver cirrhosis in order to avoid associated thrombosis.

Modifications in Abdominal Wall Graft Retrieval: When the Donor Closure Is Not Guaranteed.

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.