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.

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.

Liver Transplantation in Sexagenarian Patients Using Grafts From Uncontrolled Circulatory Death Versus Grafts From Brain Death Donation.

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.

Safe use of livers from deceased donors older than 70 years in recipients with HCV cirrhosis treated with direct-action antivirals. Retrospective cohort study.

INTRODUCTION: There is controversy regarding the use of older grafts for liver transplantation (LT) in HCV-infected patients, but the introduction of direct-acting antivirals (DAA) can radically change that debate. METHODS: The aim of this retrospective cohort study was to evaluate outcomes of the use of liver grafts from donors older than 70 years in recipients with HCV infection who underwent pre- or post-LT treatment with DAA. We compared two groups of patients who underwent LT using livers >70 years; the groups were defined according to antiviral therapy: non-DAA therapy group (n = 62; LT between May 1996 and December 2013), and DAA therapy group (n = 31; LT between January 2014 and December 2019). RESULTS: Thirty (96.8%) patients of DAA therapy and nine (14.5%) of non-DAA therapy (21 patients underwent complete therapy with interferon-ribavirin) achieved sustained viral response (SVR). One, 3-, and 5-year patient survival were 83.9%, 67.7%, and 56.5% in the non-DAA group vs 93.5%, 88.4%, and 88.4% in the DAA group (P = 0.04); the 1-, 3-, and 5-year graft survival were 77.4%, 62.9%, and 51.6% in the non-DAA group vs. 88.6%, 83.7%, and 83.7% in the DAA group (P = 0.03). Multivariate analysis demonstrated donor female sex and DAA therapy as protective factors of graft survival. CONCLUSIONS: Pre- or post-LT therapy with DAA in HCV-infected patients has achieved an almost overall SVR. The use of liver grafts >70 years in these patients treated with DAA was associated with significantly higher 5-year patient and graft survival in DAA group compared to non-DAA group. Thus, the introduction of DAA therapy has allowed the safe use of livers >70 years in HCV-positive recipients.

Liver transplantation for hepatocellular carcinoma using grafts from uncontrolled circulatory death donation.

Controversy exists regarding whether the rate of hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) differs when using livers from donation after controlled circulatory death (DCD) versus livers from donation after brain death (DBD). The aim of this cohort study was to analyze rates of HCC recurrence, patient survival, and graft survival after OLT for HCC, comparing recipients of DBD livers (n = 103) with recipients of uncontrolled DCD livers (uDCD; n = 41). No significant differences in tumor size, tumor number, serum alpha-fetoprotein, proportion of patients within Milan criteria, or pre-OLT bridging therapies were identified between groups, although the waitlist period was significantly shorter in the uDCD group (p = 0.040). HCC recurrence was similar between groups. Patient survival was similar between groups, but graft survival was lower in the uDCD group. Multivariate analysis identified recipient age (p = 0.031), pre-OLT bridging therapy (p = 0.024), and HCC recurrence (p = 0.048) as independent risk factors for patient survival and pre-OLT transarterial chemoembolization (p = 0.045) as the single risk factor for HCC recurrence. In conclusion, similar patient survival and lower graft survival were observed in the uDCD group. However, the use of uDCD livers appears to be justified due to a shorter waitlist time, and lower waitlist dropout and HCC recurrence rates.

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.

Abdominal wall transplantation in organ transplantation: Our experience. / Utilidad del trasplante de la pared abdominal en el trasplante de órganos. Nuestra experiencia inicial.

Abdominal wall transplantation has been consolidated as an alternative to primary abdominal wall closure in intestinal and multiple organ transplant recipients. Given that it is feasible to obtain the visceral graft and the abdominal wall graft from the same donor, abdominal wall transplantation could offer satisfactory outcomes and be easily coordinated. Non-vascularized fascia is one of the alternatives for abdominal wall closure in transplantation. We report two cases of non-vascularized fascia transplantation in intestinal and multivisceral transplants, respectively. Both donors were young (23 and 18 years old). Both recipients had endured multiple previous surgeries, and no surgical alternatives for primary wall repair could be offered. In both cases, a complete abdominal wall flap was retrieved from the donor, however, due to the characteristics of the recipient's abdominal wall defect, only non-vascularized fascia was used after removing skin and subcutaneous cellular tissue from the graft. Abdominal wall transplantation is an option to consider for abdominal wall closure in patients with multiple previous surgeries and no alternatives for primary wall repair.

Complications of transarterial chemoembolization (TACE) in the treatment of liver tumors. / Complicaciones de la quimioembolización transarterial (QETA) en el tratamiento de los tumores hepáticos.

INTRODUCTION: Transarterial chemoembolization (TACE) is considered a therapeutic option. It is mostly used in hepatocellular carcinoma or liver colorectal, neuroendocrine or melanoma metastases. Although it is considered a safe procedure, TACE presents complications, such as acute cholecystitis, which is the most common. Other procedure-related complications include pulmonary embolism, hepatic abscess, bile duct injury, gastric mucosa injury and, less frequently, acute pancreatitis. The aim of this study is to review the complications following TACE for liver tumors. METHODS: We performed a retrospective study including all the TACE procedures performed in a single center during the period between January 2013 and December 2016. RESULTS: Out of the 196 patients with liver tumors who had undergone 322 TACE, 258 (80%) were male and 64 (20%) were female. Mean patient age was 66.5years. Major complications after chemoembolization included: decompensation with edema/ascites (6patients), acute cholecystitis (4), acute pancreatitis (3), liver rupture (1), liver abscess (1) and renal failure (1). Postembolization syndrome appeared in 71 (20%) patients. On multivariate analysis, it was observed that concomitant cardiovascular disease (OR: 4.5; 95%CI: 1.2-17; P=.025) is a risk factor for the development of complications. CONCLUSIONS: TACE is a safe and effective procedure for liver tumor treatment. The majority of the complications are rare and present a low incidence of mortality.

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.

Incidence, risk factors and outcome of de novo tumors in liver transplant recipients focusing on alcoholic cirrhosis.

Orthotopic liver transplantation (OLT) is an established life-saving procedure for alcoholic cirrhotic (AC) patients, but the incidence of de novo tumors ranges between 2.6% and 15.7% and is significantly increased in comparison with patients who undergo OLT for other etiologies. Tobacco, a known carcinogen, has been reported to be between 52% and 83.3% in AC patients before OLT. Other risk factors that contribute to the development of malignancies are dose-dependent immunosuppression, advanced age, viral infections, sun exposure, and premalignant lesions (inflammatory bowel disease, Barrett's esophagus). A significantly more frequent incidence of upper aerodigestive (UAD) tract, lung, skin, and kidney-bladder tumors has been found in OLT recipients for AC in comparison with other etiologies. Liver transplant recipients who develop de novo non-skin tumors have a decreased long-term survival rate compared with controls. This significantly lower survival rate is more evident in AC recipients who develop UAD tract or lung tumors after OLT mainly because the diagnosis is usually performed at an advanced stage. All transplant candidates, especially AC patients, should be encouraged to cease smoking and alcohol consumption in the pre- and post-OLT periods, use skin protection, avoid sun exposure and over-immunosuppression, and have a yearly otopharyngolaryngeal exploration and chest computed tomography scan in order to prevent or reduce the incidence of de novo malignancies. Although still under investigation, substitution of calcineurin inhibitors for sirolimus or everolimus may reduce the incidence of de novo tumors after OLT.

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.

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.

The real value of lower esophageal sphincter measurement for predicting acid gastroesophageal reflux or Barrett's esophagus.

The study goal was to ascertain the true value of lower esophageal sphincter measurement in order to establish the risk of presenting gastroesophageal reflux or Barrett's esophagus. Of 671 patients assessed for symptoms of gastroesophageal reflux, 459 were included in a prospective study, practicing esophagogastroscopy, esophageal manometry, and 24-hour pH-metry. The risks of presenting a pathologic DeMeester score or Barrett's esophagus were estimated according to different values for the lower esophageal sphincter parameters. The risk of a pathologic DeMeester score only increased when pressure was less than 6 mm Hg, total length was less than 2 cm, or abdominal length was less than 1 cm; regardless of which parameter was affected, the risk being greater when the three parameters were altered (odds ratio=2.4, 3.1, and 4 for one, two, and three altered parameters). Male sex, sphincter pressure, and DeMeester score were associated with Barrett's esophagus (P<0.05) but not total or abdominal length. Pressure and total and abdominal lengths have a similar influence over establishing the risk of pathologic acid reflux, but only pressure may indicate the risk of Barrett's esophagus.