Selective Indication of T-Tube in Liver Transplantation: Prospective Validation of the Results of a Randomized Controlled Trial.

BACKGROUND AND AIMS: T-tube placement during choledochocholedochostomy (CCS) associated with liver transplantation (LT) remains controversial. This study was designed to validate the results of an earlier prospective randomized controlled trial (RCT) on use versus nonuse of the T-tube during CCS associated with LT. METHODS: Prospective cohort study. The primary outcome was the overall incidence of biliary complications (BCs). RESULTS: In total, 405 patients were included, and the median overall monitoring period was 29 months (interquartile range: 13-47 months). Selective use of the T-tube reduced BCs (23% vs 13%; P = .003), of which 75% were type IIIa or less in the Clavien-Dindo classification. The overall BC rate did not differ between patients with versus without T-tube placement. CONCLUSIONS: We confirmed that selective use of a rubber T-tube during CCS associated with LT, following the principles established in our prospective RCT, reduced the rate of BC by 10% without detriment, even after enrolling patients at an a priori greater risk of BCs than were the RCT patients.

Does Surgeon Fatigue Influence the Results of Liver Transplantation?

BACKGROUND: Recently, there has been an attempt to relate fatigue of the surgical team according to the start time of the transplant surgery and the surgeon's activity during the week, with the morbidity and mortality of liver transplant recipients. If this relationship could be demonstrated, it would be desirable to reconsider organization of transplant surgical teams. METHODS: We carried out a retrospective study of 439 successive cases of adult hepatic transplant from 2012 to 2016. We divided the patients into 2 groups, bearing in mind the interval between transplant procedures. Solitary liver transplantation was defined when >12 hours had elapsed since the last transplant, and consecutive liver transplant was defined when <12 hours had passed since the previous transplant. We analyzed the morbidity and mortality of the recipient (survival, vascular and biliary complications, early bleeding, and duration of surgery). Fatigue was measured as it related to the start time of the transplant, day of the week, and accumulation of daily and weekly activity of the surgical teams. RESULTS: No significant differences were found between the 2 groups with regard to donor or recipient characteristics. No variable related to the fatigue of the surgeons had an effect on the survival, biliary and vascular complications, early bleeding, or duration of the surgical intervention. CONCLUSION: We were unable to show that fatigue level of the surgical team influences the results of transplant procedures. Morbidity and mortality are likely related to other factors.

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

Prognostic Value of Pre-transplantation Serum Alpha-Fetoprotein Levels in Hepatocellular Carcinoma Recurrence.

Serum alpha-fetoprotein (AFP) value is still not included in the consensus guidelines to make decisions referring to liver transplantation (LT) for hepatocellular carcinoma (HCC). Many studies demonstrated the influence of high AFP level in poor prognosis after LT for HCC. We studied 301 consecutive recipients transplanted for HCC from January 2002 to December 2011. The median follow-up was 64.3 months (interquartile range, 41.6-90.8). HCC recurrence was 31.6% when AFP was >400 ng/mL and 50% when AFP was >1,000 ng/mL. Specificity to predict HCC recurrence was 95.1% (95% confidence interval [CI], 91.9-97.1) when AFP was >400 ng/mL and 98.9% (95% CI, 96.8-99.6) when AFP was >1,000 ng/mL. The overall survival (P = .008) and disease-free survival (P = .004) differed between patients groups when an AFP cutoff level of 1,000 ng/mL was used. The predictive accuracy of high pre-transplantation serum AFP level for HCC post-transplantation recurrence should be used in decision algorithms for LT.

Update on the diagnosis and treatment of mirizzi syndrome in laparoscopic era: our experience in 7 years.

INTRODUCTION: Mirizzi syndrome (MS) is a rare complication of cholelithiasis. The objective of this study was to assess the current incidence of MS in our area and present our experience in the clinical, diagnostic, and therapeutic management, focussing in laparoscopic approach. MATERIALS AND METHODS: We prospectively analyzed 35 cases of MS between January 2006 and November 2012, collecting information regarding demographics, clinical management, diagnostic methods, surgical procedure, postoperative morbidity, and follow-up. All patients underwent abdominal ultrasonography. In patients with suspected obstructive jaundice, magnetic cholangiography resonance and endoscopic retrograde cholangiopancreatogram were performed preoperatively, detecting MS in 68.5% of patients. RESULTS: The incidence of MS was 2.8% in 1168 cholecystectomies for cholelithiasis. There were 13 men and 22 women, with a mean age of 70.1 years. Nineteen patients had MS type I (54.2%). Fourteen were treated with laparoscopic cholecystectomy (LC) successfully, whereas 3 conversions were performed because of difficult surgical dissection. In the remaining 2, subtotal cholecystectomy was performed. Seven patients had type II MS (20%). In 5 cases cholecystectomy and bile duct repair were performed with T-tube placement (in 4 by laparoscopic approach), in another one subtotal cholecystectomy with primary biliary choledochorrhaphy was performed, because of dilated bile duct. Finally, the remaining patients with type III and IV SM (14.2% and 11.4%, respectively) were treated with Roux-en-Y hepaticojejunostomy.We observed 14.5% morbidity, highlighting 2 cases of postoperative collection and 1 case of biliary fistula. There was no postoperative mortality. The mean follow-up of patients was 13.4±4 months. CONCLUSIONS: Preoperative diagnosis of MS is difficult, but it is essential in the proper management of the disease. Investigations as magnetic cholangiography resonance and endoscopic retrograde cholangiopancreatogram contribute to the success of preoperative identification. LC should be reserved to MS type I and type II highly selected cases. This pathology should be treated by experienced surgeons to decrease the risk of iatrogenia.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

A surgical model for isolating the pig liver in vivo for gene therapy.

Several studies report results that suggest the need of vascularization blocking for efficient gene transfer to the liver, especially in nonviral gene therapy. In this study, we describe a surgical strategy for in vivo isolation of the pig liver, resulting in a vascular watertight organ that allows the evaluation of several gene injection conditions. The hepatic artery and portal, suprahepatic and infrahepatic cava veins were dissected. Then, liver vascularization was excluded for 5-7 min. In that time, we first injected 200 ml saline solution containing the p3c-eGFP plasmid (20 µg/ml) simultaneously through two different catheters placed in the portal and cava veins, respectively. Vital constants were monitored during the surgery to assess the safety of the procedure. Basal systolic/diastolic blood pressures were 92.8/63.2 mm Hg and dropped to 40.7/31.3 mm Hg at the end of vascular exclusion; the mean basal heart rate was 58 bpm, reaching 95 bpm when the blood pressure was low. Oxygen saturation was maintained above 98% during the intervention, and no relevant changes were observed in the ECG tracing. Peak plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels were observed after 24 h (151 and 57 IU, respectively). These values were higher, but not relevant, in 60 ml/s injection than in 20 ml/s injection. Efficiency of gene transfer was studied with simultaneous (cava and portal veins) injection of eGFP gene at flow rates of 20 and 60 ml/s. Liver tissue samples were collected 24 h after injection and qPCR was carried out on each lobe sample. The results confirmed the efficiency of the procedure. Gene delivery differed between 20 ml/s (9.9-31.0 eGFP DNA copies/100 pg of total DNA) and 60 ml/s injections (0.6-1.1 eGFP DNA copies/100 pg of total DNA). Gene transcription showed no significant differences between 20 ml/s (15,701.8-21,475.8 eGFP RNA copies/100 ng of total RNA) and 60 ml/s (12,014-36,371 eGFP RNA copies/100 ng of total RNA). The procedure is not harmful for animals and it offers a wide range of gene delivery options because it allows different perfusion ways (anterograde and retrograde) and different flow rates to determine the optimal conditions of gene transfer. This strategy permits the use of cell therapy and viral or non-viral liver gene therapy, especially appropriated to a wide variety of inherited or acquired diseases because of the liver's ability to produce and deliver proteins to the bloodstream.

Estimation of the elastic parameters of human liver biomechanical models by means of medical images and evolutionary computation.

This paper presents a method to computationally estimate the elastic parameters of two biomechanical models proposed for the human liver. The method is aimed at avoiding the invasive measurement of its mechanical response. The chosen models are a second order Mooney-Rivlin model and an Ogden model. A novel error function, the geometric similarity function (GSF), is formulated using similarity coefficients widely applied in the field of medical imaging (Jaccard coefficient and Hausdorff coefficient). This function is used to compare two 3D images. One of them corresponds to a reference deformation carried out over a finite element (FE) mesh of a human liver from a computer tomography image, whilst the other one corresponds to the FE simulation of that deformation in which variations in the values of the model parameters are introduced. Several search strategies, based on GSF as cost function, are developed to accurately find the elastics parameters of the models, namely: two evolutionary algorithms (scatter search and genetic algorithm) and an iterative local optimization. The results show that GSF is a very appropriate function to estimate the elastic parameters of the biomechanical models since the mean of the relative mean absolute errors committed by the three algorithms is lower than 4%.

Importance of technical aspects in the beginnings of a pancreas transplantation program.

Pancreas and kidney transplantation is the treatment of choice for patients with type 1 diabetes mellitus and terminal renal insufficiency. Herein we have presented a series of 35 patients transplanted between 2002 and 2009 including periods before and after 2007 divided based on introduction of some technical aspects. In the first phase (learning period) we have noted complications related to pancreatic surgery with a morbidity among 12 of 18 patients (66.6%). In the second period (stabilization period), complications appeared in 6 out of 17 patients (35.2%; P < .028). The reoperation rate was 83.3% in the learning period and 23.5% in the stabilization period (P < .03). Seven transplantectomies were performed in the first period (P < .004). Five patients died, all of them in the learning group (P < .019). Changes in the technical aspects of the procedure were responsible for improved outcomes obtained among pancreas and kidney transplantations.

Indications for and results of liver retransplantation.

Liver retransplantation (LReTx) is the therapeutic option for the irreversible failure of a hepatic graft. Our aim was to evaluate the rate of and indications for LReTx and actuarial patient survivals. Among 1260 LTx were 79 LReTx (6.3%). During the first LTx, there were no apparent differences between patients who did or did not required LReTx. The most frequent reasons were hepatic artery thrombosis (31.6%), recurrence of the VHC cirrhosis (30.4%), and primary graft failure (21.5%). The actuarial survivals at 1 and 5 years were 83% and 69% among those without LReTx versus 71% and 61% among early LReTx, and 64% and 34% among late LReTx (P < .001). Although there exists high morbidity and mortality with LReTx, it seems that this therapeutic alternative continues to be valid for patients with early hepatic loss, but not when the graft loss was late. It becomes necessary to define the minimal acceptable results that patient can benefit from LReTx.

Indications for and results of liver retransplantation.

Liver retransplantation (LRT) is the only therapeutic option for the irreversible failure of a hepatic graft. The aim of this study was to evaluate our rate, indications, postoperative morbidity and mortality and patient survival at one and 5 years after LRT. 1,260 liver transplants (LT) were performed between 1991 and 2006, 79 were LRT (6.3%). During the first LT, there were no apparent differences between patients who did or did not require LRT. The most common reasons for LRT were hepatic artery thrombosis (31.6%), recurrence of hepatitis C virus cirrhosis (30.4%) and primary graft non function (21.5%). The actuarial survival rates at one and 5 years were 83% and 69% among those without LRT versus 71% and 61% among those with early LRT, and 64% and 34% among those with late LRT (p < 0.001). Although high morbidity and mortality were associated with LRT, it seems that this therapeutic option is valid for patients with early hepatic loss, although not when the graft loss is late. It becomes necessary to define the minimal acceptable results so that patients can benefit from LRT.

[A new case of hepatic adenomatosis treated with orthotopic liver transplantation]. / Un nouveau cas d'adénomatose hépatique traité par transplantation hépatique orthotopique.

Hepatic adenomatosis is a rare disease with multiple hepatic adenomas (10 or more), not associated with an history of oral contraceptive use or anabolic steroids use or with glycogen storage disease. A new case is reported in a 23 year-old woman who consulted for an abdominal mass and who had more than 50 adenomas of the liver. The suspicion of malignant transformation by the elevation of the alpha-foetoprotein, and the diffuse affectation of the liver, with minimum free parenchyma, suggested to carry out an orthotopic liver transplantation. The definitive histological examination of the surgical specimen confirmed the existence of local areas of hepatocellular carcinoma.

Are posttransplantation protocol liver biopsies useful in the long term?

Controversy exists about the usefulness of yearly protocol liver biopsies after liver transplantation, mainly among patients with normal transaminase levels. The aim of this study is to determine (1) the prevalence and cause of histological liver injury in transplant recipients with a minimum histological follow-up of 1 year (n = 254), and (2) the correlation between histological findings and transaminase values. The main indication for liver transplantation was viral-related cirrhosis (61%; 86% caused by hepatitis C virus [HCV]). Protocol liver biopsies were performed yearly for the first 5 years in HCV-infected transplant recipients and at 1 and 5 years in the remaining patients. Histological liver injury included several categories of liver damage (hepatitis, rejection, steatohepatitis, cholangitis, and Budd-Chiari-like lesions). Among biopsy specimens categorized as hepatitis, severe hepatitis was defined as the presence of stage 3 or greater fibrosis. The prevalence of liver injury increased significantly with time (42% v 56% at 1 and 5 years, respectively; P =.09) and was significantly greater in patients who underwent transplantation for HCV-related cirrhosis than in those who underwent transplantation for other reasons (P =.0001). The most frequent category of liver injury was hepatitis (97% and 96% at 1 and 5 years, respectively). Although a proportion of patients with liver injury (12% to 29%) had normal transaminase values, this percentage was almost null in patients with severe hepatitis. Normal histological characteristics were found in the vast majority of non-HCV-infected transplant recipients with normal transaminase values. Given the high prevalence of abnormal histological findings, particularly the increase over time of those defined as severe, protocol liver biopsies are clearly justified in HCV-infected transplant recipients. Conversely, given the rarity of abnormal histological findings, protocol liver biopsies should be questioned in non-HCV-infected transplant recipients with normal transaminase values.

[Incidence of de novo neoplasms after liver transplantation]. / Incidencia de neoplasias internas después del trasplante hepático.

BACKGROUND: De novo malignancy developing after transplantation constitutes a well-known complication or organ transplantation, mainly described among renal recipients. AIM: To determine the incidence of de novo internal malignancies (excluding therefore skin cancers and recurrent hepatocellular carcinoma) in a cohort of 183 patients undergoing liver transplantation (OLT) between 6/1/1991 and 12/1/1996 with a minimum follow-up of 12 months and under cyclosporine-azathioprine-prednisone. PATIENTS AND METHODS: The study comprised 183 patients (mean age: 53 [8] years, with 70% males) whose charts were reviewed retrospectively. Rejection, steroids treatment, methyl-prednisolone bolus and OKT3 use were compared in the cases and in the matched control group. RESULTS: Seven malignancies were detected: 3 lung carcinomas, 1 larynx, 1 prostate, 1 colon and 1 ovarian. The mean age was 53 (8) years. The diagnosis of cancer was made at an average time of 24 (17) months (range, 10-54) post-OLT. Three patients died with a mean survival of 31 (16) months. OLT indication was mainly for viral liver disease (5/7). Although not statistically significant, immunosuppression data were higher among patients with cancer than in the matched group. Two additional patients developed post-transplantation lymphoproliferative diseases at 2 and 9 months, respectively. CONCLUSION: We observed a wide variety of malignancies after OLT, but no associated factor was found, even though there was a trend to higher doses of immunosuppression in patients with cancers. The institution of preventive measures and surveillance programs may allow for early institution of therapy, improving therefore the survival.

[Malignant tumors of the Vater's ampulla. Presentation of 28 cases and review of the literature]. / Tumores malignos de la ampolla de Vater. Presentación de 28 cases y revisión de la literatura.

We present a study of 28 patients, treated for adenocarcinoma of Vater's ampulla. We emphasize the distinct behavior of each one of the peri-ampullar tumors, those which affect Vater's ampulla yielding the best prognosis. We gathered data regarding gender, age, clinical manifestations, and analytical data. The confirmatory diagnosis gives us 100% of CPRE cases. All of the patients were submitted to surgical treatment with anatomic pathological confirmation of the diagnosis, be it pre or postoperative. We practiced curative surgery in 57.2% of the cases and palliative in 42.8% of the cases. We observed postoperative complications in 17.8% of the patients and peroperative mortality in 3.5%. Actual survival of the series of patients for whom exeretic surgery was performed is significantly superior to that of the other patients.

[Neoplasms of the Meckel diverticulum. Apropos of 2 new cases]. / Neoplasias del divertículo de Meckel. A propósito de dos nuevos casos.

We present two new cases of cancer in a Meckel's diverticulum, representing 3.3% of the complicated Meckel's diverticula encountered in our department. The first case was a carcinoid tumor encountered in a pathology study of an inflamed Meckel's diverticulum, and the second case was a leiomyosarcoma on a Meckel's diverticulum that presented as diverticular perforation. We emphasize the advanced age of the two patients and review the cases reported in Spain and in the Western literature.