Rubber transcystic drainage reduces the post-removal biliary complications in liver transplantation: a matched case-control study.

PURPOSE: Bile duct (BD) complications continue to be the "Achilles' heel" of liver transplantation, and the utilization of bile duct drainage is still on debate. We describe the results of a less invasive rubber trancystic biliary drainage (TBD) compared to a standard silicone T-tube (TT). METHODS: The transplanted patients (n = 248), over a period of 5 years with a TBD (n = 20), were matched 1:2 with control patients with a TT (n = 40). Primary end points were the overall incidence of BD complications and graft and patient survival. Secondary end points included the complications after the drainage removal. RESULTS: Although the bile duct leakage rates were not significantly different between both groups, the TT group had a significantly higher rate of overall 1-year BD stenosis (40 versus 10 %) (p = 0.036). Three-year patient/graft survival rates were 83.2/80.1 and 84.4/84.4 % for the TT and TBD groups, respectively. The postoperative BD complications, after drainage removal (peritonitis and stenosis), were significantly reduced (p = 0.011) with the use of a TBD. CONCLUSION: The use of rubber TBD in liver transplant recipients does not increase the number of BD complications compared to the T-tube. Furthermore, less BD anastomotic stenosis and post-removal complications were observed in the TBD group compared to the TT group.

Combined pancreatojejunal and hepatojejunal anastomotic stent placement in total laparoscopic pancreaticoduodenectomy.

INTRODUCTION: Laparoscopic pancreaticoduodenectomy (LPD) is a technically demanding procedure that is considered safe and feasible if performed in a high-volume institution, where surgeons and medical staff is appropriately trained. For this advanced abdominal procedure only few studies described a reproducible stepwise technique and a standard approach is still lacking. METHODS: The attached video reports all steps of our standardized LPD with pancreatojejunal and hepatojejunal anastomotic stent placement performed with a double approach. The laparoscopic demolitive phase, exactly as the laparotomic one, begins with the surgeon placed on the patient's right side, while for the reconstructive one he moves between the patient's legs. The main characteristic of this technique is an easy realization of the end-to-side biliary anastomosis with a Kehr's "T" tube segment placement as internal biliary stent. This easy technical tip can facilitate the anastomosis realization that remains the most challenging step of this laparoscopic technique, especially in case of small common bile duct. RESULTS: We consider that our standardized technique can be safely performed and it can facilitate the anastomosis execution, especially the hepatic-jejunal. DISCUSSION: Despite our reproducible stepwise technique could help to minimize the learning curve for LPD, further randomized controlled trials are needed to validate the superiority of minimally invasive approach.

Incidence and clinical significance of bacterial and fungal contamination of the preservation solution in liver transplantation.

A perfusion fluid used in the preservation of the grafted liver represents a medium suitable for microorganism growth. In this observational study, a sample of 232 transplanted livers was collected. Perfusion fluid samples were stored for microbiological analysis from harvested donors. Bacteria were isolated in 91 out of 232 samples, post-operative infections related to contaminated perfusion solution occurred in 13 cases. The contamination rate of the preservation medium appears to be high, but postoperative infections occurs rarely. We suggest periodic detection and a protocol in place designed for antibiotic use for transplanted patients exposed to contaminated perfusion solution.

Liver transplantation in recipients over 65 yr old: a single center experience.

INTRODUCTION: The advanced age of the recipient is considered a "relative contraindication" to liver transplantation (LT). However, recently some studies reported a morbidity rate and an overall survival comparable with those of younger patients. Here, we reported the outcome after LT in recipients aged >65 yr. METHODS: Between January 2000 and December 2006, 565 LT was performed in 502 recipients in our institution. Of these, 34 were recipients of >65 yr old (aged group). We focused our study comparing: donor age, co-morbidities, model for end-stage liver disease (MELD) and American Society of Anesthesiologists (ASA) score, duration of operation, transfusions and outcome between the two groups (young/aged). RESULTS: For the group aged >65: the mean donor age was 52.5 (range 16-75) yr and the graft weight 1339 g (890-1880 g). Co-morbidity was recorded in 25 (73.5%), coronary artery disease (CAD) in 17 (50%), diabetes mellitus (DM) and chronic renal insufficiency in four (11.7%) and chronic obstructive pulmonary disease (COPD) in three patients (8.8%). Mean MELD score was 14.9 (range 12-29) and ASA score was two in 15 (44.1%); and three in 19 (55.8%) recipients. Mean operation time was four h 45 min, three patients also received combined kidney transplantation. Twenty-five (73.5%) recipients received blood transfusions (mean 3.2). Morbidity was observed in 20 patients (58.8%); of these two had hepatic artery thrombosis requiring re-LT. Overall survival was 80% (40 months of follow-up), in particularly, at 30-d, one yr, three yr was 91%, 84%, 80%, respectively. The only two statistical differences reported (p = 0.02) are: the lower rate of CAD in the younger group of recipients (12%), compared with the aged group (50%) and the subsequently lower mortality rate secondary to cardiac causes in the younger group (1.4%) compared with aged group (8.8%). CONCLUSION: Our results suggest that the recipient age should not be considered an absolute contraindication for LT when the graft/recipient matching is optimal and when an adequate cardiac assessment is performed.

Liver transplantation exceeding UCSF criteria: case report of a late recurrence treated by surgery and review of the literature.

INTRODUCTION: Treatment of a recurrence of hepatocellular carcinoma (HCC) after liver transplantation. Surgery has seldom been considered in such a situation because HCC recurrences are generally considered as a systemic disease. PATIENT AND METHODS: We describe a 47-year-old male patient who underwent liver transplantation in October 1999 for HCC exceeding the Milan and University of California, San Francisco (UCSF), criteria. RESULTS: In 2007 (8 years after liver transplantation), the patient developed a cervical bone metastasis treated by surgery. In April 2008, HCC had disseminated to hepatic pedicle lymph nodes. An extended hepatic pedicle lymphadenectomy was then performed. Today, our patient is doing well, without signs of recurrence. DISCUSSION: The risk of developing a tumor recurrence is the main argument against expanding the UCSF criteria. In case of an HCC recurrence, various treatments ranging from a change in the immunosuppression regimen to chemotherapy have been proposed. Surgical treatment has rarely been envisaged in the treatment of HCC recurrences because of the technical difficulties and the frequent dissemination of cancer.

Identification of ubiquitin ligases required for skeletal muscle atrophy.

Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of muscle atrophy, we performed transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 (MuRF1), and a gene we designate Muscle Atrophy F-box (MAFbx), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.

Twenty seven years of experience in pediatric liver transplantation in Strasbourg: focus on the ex situ split techniques.

INTRODUCTION: Despite the well-known controversies about split-liver procedures, since 1979 we have utilized an ex situ instead of an in situ technique because of its feasibility. However, we sought to prove the equality of the results of these two procedures. Herein, we have presented our experience after 27 years' follow-up. MATERIALS AND METHODS: Between March 1979 and June 2006, we transplanted 84 livers in 67 pediatric recipients including 37 ex situ split livers implanted into 28 patients. RESULTS: We recorded demographic characteristics, transplantation, and retransplantation indications, age difference between donors and recipients, comorbidities, cold ischemia times, surgical times and complications, graft/recipient body weight ratios, organ recovery times, and overall survivals after 1, 5, and 15 years follow-up. We have herein reported 1, 5, and 15 years of patient versus organ survivals of 88.9.1%, 84.5%, 62.1% versus 78.6%, 74.2%, 57.4%, respectively. CONCLUSION: We have concluded that an ex situ split liver may be a valid alternative to in situ techniques to achieve good grafts for pediatric transplantation.

Split liver transplantation for acute Wilson's disease: new option for urgent recipient?

Wilson's disease is a rare metabolic disorder that may lead to fulminant hepatitis and subsequent liver failure. Herein, we present a case of split liver transplantation performed on a patient with acute Wilson's disease. A 27-year-old female with acute presentation of Wilson's disease and advanced neurological impairment, received a Right Split liver Graft (Segments: IV, V, VI, VII and VIII) transplant. The graft was obtained by an in situ splitting technique. The graft implantation was performed in a standard fashion. No acute rejection episodes of the organ occurred. The postoperative course was uneventful. The graft function, ceruloplasmine level and copper levels progressively normalized. The patient totally recovered from neurological symptoms and the Kayser-Fleischer rings disappeared within one month. At 13 months of follow-up, the patient presented with no symptoms and in good condition. The current literature reports high preoperative mortality rate in patients that underwent partial liver graft for acute hepatic failure. However, our experience indicates that in situ split technique of liver may be a feasible and effective alternative to whole graft transplantation in urgent cases. Moreover, to our knowledge, this is the first successfully case of in situ split liver transplantation for acute Wilson's disease described in literature.

An overview of EU and USA intestinal transplant current activity.

AIM OF THE STUDY: To report the current activity of intestinal transplantation in Europe (EU) and Unites States of America (USA), underlining outcomes in the last 5 years and discussing possible trends. PATIENTS AND METHODS: Data review of results was performed through analysis of ITR and UNOS registries, Eurotransplant and newsletter transplant reports, congress abstracts, international published literature, personal communications and hospital web sites. RESULTS: The absence in Europe of a sole organization collecting donors and the presence of many low-volume centers (less than 5 cases/year) makes the difference with USA: in the last 5 years (2010-2014), 222 intestinal/multivisceral transplants have been performed in EU countries (most of them in the UK), while in USA, the number of transplants achieved 634 procedures in the same period of time. Waiting list mortality remains unacceptable in both continents. Improved short-term results, with over 80% survival at 1 year, have been achieved in the busiest transplant centers likely due to immune-induction agents, more recently to innovative cross match strategies and optimizing organ allocation, but long term outcomes are still inferior to other organ transplants. Most long-term survivors were reintegrated to society with self-sustained socioeconomic status. The economic burden for the society is high and related costs are different between USA and EU (and inside Europe between member state's health-care systems), but cost-effectiveness for intestinal transplantation still needs to be proved. CONCLUSION: Overall intestinal transplantation continues to develop in EU and USA together with surgical and medical rehabilitation of patients affected by short gut syndrome.

Different reconstitution of peripheral blood lymphocytes and dendritic cells in liver and kidney transplant patients.

T cells and dendritic cells are responsible for immune alloreactivity or tolerance after transplantation. In this study, we compared the levels of circulating T, B, and NK lymphocytes, as well as monocytes, plasmacytoid dendritic cells, and myeloid dendritic cells, in adult patients undergoing a liver transplant or kidney transplant. Our findings show that candidates for liver transplant had significantly lower levels of circulating T, B, and dendritic cells than candidates for kidney transplant. Nevertheless, liver transplant patients showed a greater T-cell recovery, despite the use of thymoglobulin, as compared with kidney transplant patients who were induced with Daclizumab. In four kidney transplant patients with allograft rejection we observed a dramatic drop of circulating T and dendritic cells at the time of rejection, and while myeloid dendritic cells and CD4(+) and CD8(+) cells rapidly recovered after 1 month, plasmacytoid dendritic cells and CD4(+)CD25(+) T-cell numbers remained significantly lower than in patients without rejection. Future studies will evaluate the monitoring of circulating CD4(+)CD25(+) T cells and myeloid dendritic cell:plasmacytoid dendritic cell ratio as potential biomarkers for rejection or, alternatively, for withdrawal of immune suppression.

Laparoscopic physiological hiatoplasty for hiatal hernia: new composite "A"-shaped mesh. Physical and geometrical analysis and preliminary clinical results.

BACKGROUND: We analyzed, using a theoretical model, the modality of recurrence after a simple cruroplasty for large hiatal hernias, and on the basis of physical and geometrical principles, we conceived a new shaped mesh for a "tension-free" repair. METHODS: We performed a physical and geometrical analysis of the hiatal region on a theoretical model. We also performed an anatomic study on 20 fresh cadavers to verify the reproducibility of the theoretical model and to study the most suitable shape for mesh and its adaptability to the hiatal region. Between September 2000 and October 2001, eight patients received laparoscopic reparation of large (type II or III) hiatal hernias by means of a composite "A"-shaped polytetrafluoroethylene (PTFE)-polypropylene mesh. There were two men and six women; mean age was 65 years (range, 35-78 years). Concomitant esophagitis was found in five patients and impaired esophageal peristalsis in two patients. A total or a partial fundoplication was associated in these cases. RESULTS: The physical and geometrical analysis of the hiatal region explained the reasons for the recurrence after hiatoplasty. The anatomical study on fresh cadavers resulted in a mesh tailored in an "A" shape and permitted to verify the adaptability of such a shaped mesh composed of two layers, polypropylene and PTFE. In the clinical series no conversions occurred; the mortality rate was null. Persistent dysphagia was present in two patients and disappeared after 3 months of treatment. No recurrence was observed at an 8-month average follow-up. CONCLUSION: The preliminary clinical study confirms the feasibility of this tension-free repair and the effectiveness of this composite A-shaped mesh.

Laparoscopic splenectomy for hematological diseases.

BACKGROUND: We reviewed retrospectively the records of all patients who underwent laparoscopic splenectomy (LS) at our institution for a wide range of hematological disorders. We compared our experience to those reported in the literature and analyzed various aspects of the treatment that are still under discussion and in need of confirmation, such as the treatment of malignant blood diseases, the indication in case of splenomegaly, and the adequacy of the detection of accessory spleens. METHODS: Between June 1997 and June 2001, we performed 43 LS. The patients were classified into three groups according to clinical diagnosis: idiopathic thrombocytopenic purpura (ITP) (n = 23), hemolytic anemia (HA) (n = 5), and hematological malignancy (HM) (n = 15). Statistical analyses were done to compare the three groups. RESULTS: LS was completed in 41 patients, with a conversion rate of 5%. Splenomegaly was present in 37% of all patients (73% of HM). Mean operative time was 128 min. The incidence of accessory spleens was 20%. A concomitant laparoscopic procedure was done in three cases (cholecystectomy). Postoperative complications occurred in eight patients (18%). Duration of surgery, length of hospital stay, transfusions rate, and some demographics features, such as age and spleen weight and length, were significantly different in each group. No deaths were attributed to the procedure. CONCLUSIONS: The statistical analysis of our series shows that, the laparoscopic approach reliable even in the management of malignant and nonmalignant blood diseases.

Potential predictive value of the MELD score for short-term mortality after liver transplantation.

In the last years, a model for end-stage liver disease (MELD) was suggested as a disease severity score for patients with end-stage liver disease awaiting liver transplantation. In the early 2002, United Network for Organ Sharing (UNOS) has proposed to replace the current status 2A, 2B, and 3 by a modified version of the original MELD score based upon patient risk for 3-month mortality on the waiting list. In this study UNOS status and MELD score were evaluated retrospectively for postoperative 3-month mortality in patients who underwent liver transplantation from 2000 to 2001. Liver recipients were stratified for UNOS status 2A, 2B, and 3, and the corresponding MELD score was calculated for each patient. A receiver operating characteristic (ROC) analysis was performed for both conventional UNOS status and MELD score by fitting patient deaths within 3 months after liver transplantation. The MELD score revealed a better prediction rate for 3-month mortality after the first LT than conventional UNOS status, although no statistical significance was evident by ROC curve comparison. This preliminary study seems to suggest a potentially better predictive rate for the MELD score than conventional UNOS status concerning short-term mortality after liver transplantation.

Portal vein pressure and graft oxygen consumption monitoring during liver transplantation.

UNLABELLED: Abnormal splanchnic circulation (ASC) is often detected too late, when hepatic circulation is already irreversibly compromised. If we could detect surgical or metabolic problems early after graft reperfusion, we might be able to correct them immediately before the damage becomes irreversible. The aim of this study was to determine if ASC can be predicted early after liver transplantation (LT) using portal vein pressure measurements and graft oxygen consumption monitoring. PATIENTS AND METHODS: Twenty-patients (13 men, 7 women of mean age 46 years) undergoing LT with the piggyback technique for hepatitis C virus (HCV)/hepatitis B virus (HBV)-related cirrhosis were retrospectively divided in two groups. Group A (16 patients), in which LT was successful, and group B (4 patients) in which LT was unsuccessful because of primary nonfunction (2 patients), infrahepatic portal vein thrombosis (1 patient), or hepatic vein kinking (1 patient). We then compared the portal blood pressure values and the prehepatic and posthepatic oxygen content difference (p-pDO(2)) before portal clamping; at the end of anhepatic phase; 5, 15, and 25 minutes after portal vein (PV) reperfusion; and 5, 20, 40, and 100 minutes after hepatic artery anastomosis. RESULTS: Early after graft reperfusion; portal pressure decreased to levels lower than that at baseline in group A, but remained high until the end of surgery in group B. At the end of surgery, p-pDO(2) increased more among group B than group A. CONCLUSION: ASC, specifically an increased PV resistance, can be predicted early after LT by portal vein pressure measurements and graft oxygen consumption monitoring.

Modifications of cerebral vascular resistance and autoregulation after graft reperfusion during human orthotopic liver transplantation.

We have studied cerebral blood flow velocity (CBFV) and cerebral autoregulation (CA) in 23 orthotopic liver transplantation (OLT) patients using transcranial doppler. CBFV was continuously recorded using a fixed (helmet) 2-Mz probe through the trans-temporal window. CA changes were studied using a linear regression analysis of percentile changes in CBFV and mean arterial blood pressure (MABP) after phenylephrine infusion compared with baseline. Pearson's "r" coefficient was considered an index of CA. In case of autoregulation is lost "r" tends to 1, thus representing complete dependence of CBFV on MABP. We regarded the slope coefficient parameter "S" as an index of cerebral vascular resistance (CVR), namely, the ratio of the corresponding variations of CBFV to MABP. Wilcoxon test showed a significant increase in both "r" and "S" between the anhepatic versus postreperfusion phases (within the first hour) and versus recovery in the neohepatic phase (end of surgery). A decreased CVR was observed within the first hour after graft reperfusion producing a loss of CA. These phenomena lead to an increase of CBFV and exposed the brain to hyperperfusion.

Impact of ischemia/reperfusion on transplanted livers procured from elderly cadaveric donors.

The increasing number of clinical indications for liver transplantation has forced physicians to use livers procured from elderly cadaveric donors to expand the graft pool. However, the degree of ischemia/reperfusion damage in elderly livers remains poorly investigated. In this study, the outcomes of livers procured from a group (I) of young donors (n=12; 38 +/- 12 years; range: 21-58) were compared with a group (II) from elderly donors (n=7; 68 +/- 7 years; range: 62-84) for changes in reduced glutathione, the main hepatic free radical scavenger. Reduced and oxidized glutathione were assayed by high performance liquid chromatography in liver biopsies performed just before cold ischemia and during early reperfusion. A significant decrease in reduced glutathione was observed at the time of reperfusion in both groups I (P=.0195) and II (P=.002). Before cold ischemia and during early reperfusion, no differences between young versus elderly donors were noted in the oxidized/reduced glutathione ratio, in conventional graft function markers or in liver-related hemostatic parameters. Comparable glutathione contents were measured at the time of early reperfusion in livers obtained from young and elderly cadaveric donors, suggesting that livers procured from elderly donors might be adequately protected against ischemia/reperfusion damage.

Cerebral hemodynamic and metabolic changes in patients with fulminant hepatic failure during liver transplantation.

BACKGROUND: Cerebral autoregulation and metabolism may be seriously compromised in patients with fulminant hepatic failure (FHF). The mechanism responsible for the alteration in cerebral blood flow (CBF) has not been yet clearly defined; however, it is known that it does correlate with liver function. Orthotopic liver transplant (OLT) rapidly restores normal liver function, but little is known about the restoration of cerebral metabolism and hemodynamics. To investigate the relationship between liver function and CBF, we evaluated autoregulation and metabolic changes during OLT in six patients comatose due to FHF. METHODS: We evaluated autoregulation based on a linear regression analysis between mean arterial blood pressure and parallel CBF velocity (CBFV) changes using transcranial Doppler ultrasound. Cerebral metabolism rate was estimated by the arterial-jugular venous oxygen content difference (a-jDO2), while the percentile variation in cerebral metabolic rate for oxygen (CMRO2) was estimated using CBFV percentile variation rather than CBF percentile variation (eCMRO2). RESULTS: Prior to transplant autoregulation was impaired in all patients. However it markedly improved at the end of surgery (P <.05). The eCMRO2 improved as well, particularly among subjects who displayed prompt neurological recovery. In all patients the a-jDO2 was low before transplantation increasing to normal values at the end of surgery. CONCLUSIONS: A hallmark of FHF seems to be failure of autoregulation, which is linked to uncoupling between CBF and CMRO2 as attested by an a-jDO2 lower than normal in all patients (luxury perfusion). The recovery of liver function rapidly improves cerebral hemodynamics and metabolic stability. The study of autoregulation and eCMRO2 recovery using Doppler monitoring proffers the possibility to predict early graft function after liver reperfusion. In our patients eCMRO2 seemed to be associated with improved neurological outcomes.

Simultaneous liver-kidney transplantation for glycogen storage disease type IA (von Gierke's disease).

INTRODUCTION: Glycogen storage disease type Ia (GSDIa) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney, and intestine. Although significant progress has been achieved in the management of patients with GSDIa, complications still emerge. The potential for development of liver adenomatosis and kidney failure makes these patients candidates for simultaneous liver-kidney transplantation (SLKT). Herein, we describe such a transplantation in a patient affected by this rare storage disease. METHODS: A 25-year-old female patient with GSDIa developed hepatic adenoma and kidney failure despite dietary therapy. The patient underwent an SLKT from a cadaveric donor. RESULTS: The operative time was 8 hours without hemotransfusion. Only a transitory lactic acidosis was observed. Laboratory results normalized on postoperative day 7. The patient was discharged on postoperative day 9. After 4 months, the patient is in good condition with well-functioning kidney and liver allografts. CONCLUSION: Patients with end-stage renal disease secondary to GSDIa should be considered for SLKT, especially when the disease is in an early stage.

[Cystic lymphangioma of the adult: our experience and review of literature]. / Linfangioma cistico dell'adulto: nostra esperienza e revisione della letteratura.

Cystic lymphangioma is an uncommon benign pathology, usually reported in children, rarely in adult. Its embryopathogenesis is still controversial: it seems to arise from the lymphatic vessels, mainly in the cervico-cranial district. It is macroscopically characterised by multiple cystic non-communicating concamerations. Definitive diagnosis used to be intraoperative and was usually an unexpected finding. Nowadays, with modern imaging technologies, CT and MRI, diagnosis can be assumed before intervention even though certain diagnosis can still be reached only with histological examination. Imaging techniques can help for a precise mapping of the lesion and definition of its limits with the other structures, improving therapeutic success. Various therapeutical options are reported in literature, but complete surgical excision is still considered the best approach and the most successful. The Authors report their experience and review the literature on cystic lymphangioma in adult.