Search

We report herein on two male liver transplant (LT) recipients who presented with cyclosporine (CsA)-related gynecomastia 6 and 10 months after transplantation. The clinical workup showed increased luteinizing hormone (LH), associated with a slight reduction in testosterone blood levels in one patient and increased prolactin levels in the other. After excluding concomitant primary endocrine and/or malignant disease, conversion to tacrolimus (TAC) was performed resulting in clinical improvement of gynecomastia and return of hormone blood levels to normal range within 3 months. Our report confirms a putative role of CsA in post-LT gynecomastia, reversible however upon conversion to TAC.

The aim of this study was to compare a number of potentially stress-generating factors related to an intensive care unit (ICU) stay from the points of view of patients undergoing liver transplantation or elective major abdominal surgery and their caregivers in order to identify differences and similarities that may help to optimize patient care. The ICU Environmental Stressor Scale questionnaire was administered to 104 liver transplant recipients, 103 major abdominal surgery patients, 35 nurses and 21 physicians. The ICU staff were asked to complete the questionnaire on the basis of their perception of patient stressors. Both patient groups identified Being unable to sleep, Being in pain, Having tubes in nose/mouth, Missing husband/wife, and Seeing family and friends only a few minutes a day as the major stressors; the healthcare providers correctly identified the most stressing factors for the patients, but gave them higher scores. The mean scores were 71.9 +/- 18.7 for the transplant recipients, 66.3 +/- 20.9 for the patients undergoing elective major abdominal surgery, 99.7 +/- 19.2 for the nurses, and 92.7 +/- 16.1 for the physicians (P < 0.001). The qualitative evaluations of potentially stress-inducing ICU situations were substantially the same in the 2 patient groups, but the transplant recipients seemed to feel them more acutely. Although the caregivers identified the most discomforting situations, they overestimated the degree of stress they cause. The staff of each ICU should therefore seek to understand and reduce (even by means of simple interventions) the particular causes of psychophysical stress felt by their patients.

We assessed the diagnostic value of magnetic resonance cholangiography (MRC) when evaluating ischemic-type biliary lesions in the follow-up of liver transplant patients. We retrospectively reviewed magnetic resonance imaging and MRC of 28 liver transplant recipients with ischemic changes of the biliary tree. The MR examinations were performed at 1.5 T. After the acquisition of axial T1w and T2w sequences, MRC involved a coronal respiratory-triggered, fat-suppressed, two-dimensional, thin-slab, heavily T2w fast spin-echo sequence, and/or a coronal breath-hold, thin- and thick-slab, single-shot T2w sequence. Eleven patients underwent either surgical reconstruction of the biliary system (n = 4) or liver retransplantation (n = 7); the pathologic specimens were employed as standard of reference. The final diagnosis was obtained through direct cholangiography in the remaining cases. Without knowledge of the surgical, pathologic, and cholangiographic findings, two experienced investigators evaluated in conference the MR images to determine the presence of biliary tract abnormalities. MRC demonstrated strictures involving the hepatic bifurcation and the extrahepatic bile duct of the graft in 26 patients; a concomitant thickening of the biliary wall was described in 18 out of these 26 subjects. MRC also showed sludge or stones formation in the donor common bile duct in 16 out of these patients. In conclusion, MRC allows noninvasive, reliable, assessment of ischemic-type biliary lesions in liver transplant recipients.

Background The purpose of this study was to analyze the role of interventional ultrasound in the treatment of nonvascular complications in liver transplant recipients. Methods Between August 1996 and May 2003, we performed 426 OLTs in 394 patients, 287 men (73%) and 107 women (27%), mean age of 50 ± 9.5 years (range 17 to 68.2). A total of 2556 diagnostic ultrasound examinations were performed, resulting in a mean of 5.9 per patient (range 2 to 21). The interventional maneuvers included: echo-guided biopsies; drainage of abdominal or thoracic effusions; drainage of abdominal, intrahepatic, or splenic collections; positioning of biliary drains; and use of the “rendezvous” technique. Results Six hundred seventy-seven echo-guided interventional maneuvers were performed in 394 OTL patients, comprising 417 (61.6%) biopsies and 260 (38.4%) therapeutic maneuvers. Eighty-one ascite drains were positioned (31.1%); in 73 cases, pleural effusions were drained (28.1%). Sixty-seven abdominal or intrahepatic collections were drained (25.8%), of which 36 (53.7%) were due to bilomas or biliary peritonitis, 15 (22.4%) hematomas, 4 (5.9%) hepatic abscesses, 11 (16.4%) infected abdominal collections, and 1 (1.5%) splenic abscess. Thirty-nine cases (15%) of biliary drainage were performed. In 33 cases (7.9%), the parenchymal biopsies were not diagnostic because of an inadequate specimen. The treatment success rate was 96.1%. No complications related to the therapeutic maneuvers were recorded, but there were 5 biopsy-related complications (1.2%). Conclusions Echo-guided interventional maneuvers are safe, produce a high success rate, and represent an important option in the management of OLT patients.

Background The published experiences of combined liver–kidney transplantation (LKT) are favorable, but there is still no uniformity concerning the impact on hepatorenal syndrome, or in cases of symptomatic hepatorenal polycystic disease. Herein we describe our experience with two LKTs, with particular reference to the selection and preparation of the candidates, and the surgical approach. Methods Between 1996 and June 2003, we performed 430 liver transplants in 398 recipients, including two LKTs: one in a patient with hepatorenal polycystic disease (case 1) and the other in a patient with HBV + cirrhosis undergoing dialysis after a previous isolated kidney transplant (case 2). Results In case 1, LKT and right nephrectomy were performed 2 months after a left lumbar nephrectomy. In case 2, LKT was performed 10 months after an isolated kidney transplant, without removing the first graft, which recovered function after 3 months. Both patients are now in good health with functioning grafts. Conclusions LKT requires careful selection and preparation of candidates to optimize the probability of success. In well-compensated dialyzed patients with cirrhosis due to viral hepatitis, we believe that a combined approach is indicated after antiviral therapy. In cases of hepatorenal cystic disease, a two-stage surgical approach makes it possible to eliminate the risk of infection and intracyst hemorrhage in nonfunctioning polycystic kidneys.

Background. The incidence and clinical relevance of increased intraabdominal pressure after orthotopic liver transplantation (OLT) has not yet been evaluated despite the finding that occurrence of this condition in postsurgical critically ill patients may impair various organ functions. The aim of this study was to assess whether the occurrence of abdominal hypertension among a population of OLT recipients was an important cofactor producing early postoperative complications. Method. This prospective clinical study measured abdominal pressure every 6 hours during the intensive care unit (ICU) stay using the urinary bladder method. A value of ≥25 mm Hg was considered high. Hemodynamic status was simultaneously evaluated and renal function assessed based on the hourly urinary output, and by calculating serum creatinine on postoperative days 2 and 4. Renal failure was defined as a serum creatinine level of >1.5 mg/dL, or an increase in peak of >1 mg/L within 72 hours of surgery. The filtration gradient and patient outcomes were also considered. Results. Intraabdominal hypertension was observed in 32% of cases. The subjects displaying high IAP showed significantly lower artery pressure values (P

The purpose of this study is to review the role of the percutaneous interventional procedures in the treatment of vascular complications after orthotopic liver transplantations (OLT). Vascular complications, such as arterial stenosis and venous thrombosis, which occur in approximately 1% to 10% of liver transplant patients, are associated with a higher risk of graft dysfunction. Percutaneous interventional procedures, including angioplasty, local thrombolysis, and embolization, are useful to manage these complications. A reduced blood loss and a low incidence of procedural complications allow for rapid recovery. Hepatic arterial and portal vein anastomotic stenosis can be treated effectively by means of balloon dilation; stenting has also been proposed, particularly for venous complications. Infusional local thrombolysis may be useful in venous thrombosis. Arteriovenous fistulas, occurring at the level of the anastomosis or after liver biopsy, require intraarterial embolization using microcoils or gelfoam. Timing of the intervention for the treatment of ischemic complications is of outmost importance to guarantee liver functional recovery and avoid irreversible parenchymal injuries. Other interventional procedures may be extremely useful to manage portal hypertension after OLT; for example, by creation of transjugular portosystemic shunts, or, in the case of associated hypersplenism, transarterial embolization of the splenic artery. Finally, in patients with recurrent hepatitis, the transjugular approach has been shown to be safe and effective for liver biopsy, whereas transarterial chemoembolization may be extremely useful to treat recurrent hepatocarcinoma.

Older donors are a growing part of the total donor pool but no definite consensus exists on the limit of age for their acceptance. From November 1998 to January 2003, in a retrospective case-control multicenter study, we compared the outcome of 30 orthotopic liver transplantations (OLTs) with octogenarian donors and of 60 chronologically correlated OLTs performed with donors

Purpose The purpose of this study was to evaluate the accuracy of Multidetector Computed Tomographic Angiography (MDCTA) to detect hepatic artery (HA) stenosis after orthotopic liver transplantation (OLT) and the efficacy of treatment using percutaneous transluminal angioplasty (PTA). Materials and methods Twenty-two consecutive patients with OLT underwent MDCTA for evaluation of HA, followed by digital subtraction angiography (DSA) (gold standard). Source images (Ax) were processed, obtaining multiplanar reformations (MPRs), maximum intensity projections (MIPs), and volume renderings (VRs). Images were evaluated to identify the following: (1) arterial depiction (celiac axis, anastomosis, and left [LHA] and right [RHA] HA), (2) detection of stenoses, and (3) grading of stenoses. Indications for PTA were set at MDCTA and DSA, and PTA was performed when appropriate. Results MDCTA depicted the celiac axis and anastomoses in all patients; LHA and RHA were visualized in 21 of 22 patients with Ax, MPRs, and MIPs, and in 17 of 22 with VRs. All reconstruction modalities enabled correct diagnosis of celiac (n = 3) and anastomotic stenoses (n = 14). Of 6 LHA and RHA stenoses, 4 (66.7%) were visualized with Ax, MPRs, and VRs, and 5 (83.3%) were visualized with MIPs. Stenosis was overestimated in 9 (39.1%) cases with VRs and in 3 (13%) with the other modalities. PTA was performed in 8 cases, with 1 case of arterial dissection requiring re-OLT. At a median follow-up of 28 months, the primary and secondary patency rates were 71.4% (5 of 7) and 85.7% (6 of 7), respectively. Conclusions MDCTA and accurate postprocessing enable confident depiction of the arterial anatomy and detection of stenosis after OLT. PTA is safe and allows allograft saving, at least until another suitable donor becomes available.

Mycophenolate mofetil (MMF) is an immunosuppressant used for the prophylaxis of rejection in renal, pancreas, and liver transplantation. It inhibits the inducible isoform of the enzyme inosine-monophosphate dehydrogenase (IMPDH II) via its active metabolite mycophenolic acid (MPA). IMPDH II is necessary for de novo purine synthesis in activated lymphocytes. The aims of the present study were to evaluate the feasibility of a real-time polymerase chain reaction (PCR) quantitative assessment of IMPDH II gene expression in liver transplant recipients as well as to provide a preliminary evaluation of possible correlations with drug tolerability. RNA was extracted from peripheral blood mononuclear cells of liver recipients after at least 6 months of MMF administration. IMPDH II gene expression was assessed using quantitative, real-time PCR and normalized using glyceraldheyde-3-phosphate dehydrogenase (GAPDH). Finally, adverse events associated with MMF administration were recorded. Real-time PCR quantitation of IMPDH II gene expression was reliable, sensitive, and specific. The intrapatient variability for both IMPDH II and GAPDH assays was lower than 0.6% in all patients. The results demonstrated a wide interpatient variability, with the mean value +/- standard deviation of 0.949 +/- 0.525 (95% confidence interval, 0.669-1.229) and a median value of 0.797. Patients with treatment-related toxicities displayed a trend to a higher level of IMPDH II expression than those without toxicity (mean, 1.126 vs 0.771). In conclusion, pharmacogenetic analysis of IMPDH II may represent a novel approach to MMF therapeutic monitoring.

With the aim of assessing whether fenoldopam can help to preserve renal function after liver transplantation, we randomized 140 consecutive recipients with comparable preoperative renal function to receive fenoldopam 0.1 microg/kg/minute (group F, 46 patients), dopamine 3 microg/kg/minute (group D, 48 patients), or placebo (group P, 46 patients) from the time of anesthesia induction to 96 hours postoperatively. There were no differences between the groups in intraoperative urinary output or furosemide administration (both P =.1). Daily recordings made during the first 4 postoperative days revealed no significant differences in urinary output (P =.1), serum creatinine (P =.5), the incidence of renal insufficiency (P =.7), the need for loop diuretics (P =.9) or vasoactive drugs (P =.8). In comparison with preoperative levels, creatinine clearance at the end of the study in the patients receiving fenoldopam remained substantially unchanged, whereas it decreased by 39 and 12.3%, respectively, in the subjects receiving placebo or dopamine (P

Advanced donor age has been considered a risk factor for the use of organs for transplantation. We report the case of an orthotopic liver transplant performed using a 93-year-old donor. The donor had been admitted to the intensive care unit 3 days before due to cerebral hemorrhage. History, viral serology, liver function tests and hemodynamics were normal. At laparotomy, the liver appeared macroscopically normal; histology showed mild parenchymal congestion and focal signs of steatosis (less than 10%). The liver was therefore procured and transplanted into a 52-year-old recipient with alcoholic, post-hepatitis C. cirrhosis. Cold and warm ischemia times were 8 hours 20 min and 67 min, respectively. Production of bile was observed after reperfusion. Six months post-transplantation there is clinical and histological evidence of hepatitis C virus recurrence. Nevertheless, the patient enjoys an acceptable quality of life. Even very old donor livers can be used for transplantation, although it is still debatable whether hepatitis C virus-positive patients are good recipients of such livers.

Purpose To describe the results of the treatment of eight liver transplantation (LT) patients subsequently developing large volumes of long-lasting ascites. Patients and methods Between August 1996 and February 2003, 405 LTs were performed in 375 patients, eight (1.97%) of whom (six men and two women of mean age of 55.4 ± 5.2 years) subsequently developed massive (> 500 mL/d) and persistent ascites and/or hydrothorax. All patients were HCV positive. The mean age of the liver donors was 66.8 ± 21.9 years. All LTs were performed by replacement of the recipient retrohepatic vena cava. Results The eight patients displayed sinusoidal portal hypertension related to biopsy-proven recurrence of HCV infection. Mean wedged hepatic venous pressure was 14.9 ± 5.1 mm Hg and mean portal vein/right atrial pressure gradient (PAPG) was 17.3 ± 4.8 mm Hg. In two patients, the ascites appeared the day after LT; in the remaining six, ascites and/or hydrothorax appeared after 342.3 ± 167.7 days. Seven patients with a mean PAPG of 18.4 ± 3.9 mm Hg and a mean plasma/ascites albumin concentration gradient of 2.8 ± 0.3 g/L were treated by means of a trans-jugular intrahepatic portosystemic shunt TIPS, and one (with a PAPG of 9 mm Hg and a plasma/ascites albumin concentration gradient of 1.38 g/L) by means of spleen arterial embolisation. After a mean follow-up of 558 ± 147.2 days, the ascites and/or hydrothorax have resolved in five patients (62.5%), one (12.5%) has stable ascites not requiring paracentesis, and two (25%) have died of multiorgan failure. Conclusion These data suggest the efficacy of the aggressive treatment of massive and persistent ascites and/or hydrothorax.

A SUCCESSFUL liver transplantation needs an adequate portal inflow. In cases of grade 4 portal vein (PV) thrombosis, ie, complete thrombosis of the PV, and the proximal and distal superior mesenteric veins, salvage procedures have been described to restore portal inflow: anastomosis of the donor PV with a suitable recipient PV tributary, arterialization of the donor PV to increase flow through the portal system, and multivisceral transplantation. Since the report of Tzakis et al, proposing cavoportal hemitransposition (CPHT) as a possible means of overcoming the problem of extensive PV thrombosis, individual case studies of CPHT have been published. The common complications after CPHT are severe ascites, renal insufficiency, and variceal bleeding. We here report the patient selection criteria and outcomes of the first eight transplantations performed using this technique at our Centre between July 2000 and February 2002.

We present a case of non-anastomotic biliary strictures, mainly and initially localized in the right hemiliver and subsequently extending to the IV segment, in a 65-year-old male who had undergone liver transplantation because of hepatitis B virus-related cirrhosis. After the failure of endoscopic and percutaneous interventions, the patient was successfully treated by means of extended right hepatectomy up to 70% of graft volume. The surgical technique of liver graft resection is discussed. The authors recommend hepatic resection as a graft-saving option in selected patients affected by non-anastomotic biliary strictures in order to rescue the graft and avoid retransplantation.

An effective recruitment plan and the use of donors with risk factors are essential means of compensating for the lack of organs, but mean a significant change in the type of donor. This study defines the characteristics of the donors currently used, evaluates their impact on short-term outcome and underlines the need for a different approach to organ selection.Data concerning 244 patients were collected for the study of donor characteristics by age groups, and the multivariate analysis of the associated risk factors.There were no significant differences other than the cause of donor death and the appearance of the organ. The annual percentage of donors aged more than 60 years has increased from 5.2% to 47.6%; the percentage of organs from over-60-year-old donors discarded after bioptic sampling was 25.6% (10.4% for donors aged60 years). Perioperative mortality did not significantly differ on the basis of donor age (p = 0.186).Today's liver donors are mainly subjects who have died of cerebrovascular disease, often at an age of60 years, and are also affected by other diseases or metabolic alterations. They require a different method of evaluation and, in those aged more than 60 years, the routine use of histological examinations in organ selection. Furthermore, the judicious extension of the inclusion criteria and the characteristics of the currently available donors do not seem to affect short-term, post-transplant outcome.

This article discusses a new simple, fast, and easily performed technique that allows reduction of morbidity and hospital stay after T-tube removal. A retrospective analysis was conducted of 145 recipients who underwent T-tube removal 3 months after orthotopic liver transplantation. Patients were divided in two groups: group 1 (n=93) underwent T-tube removal and contemporary placement under fluoroscopic guidance of a counter-drain. Group 2 (n=52) T-tubes were removed from the bile duct under fluoroscopy but were left in place as a counter-drain. Overall, there were 33 (22.7%) complications related to T-tube removal. Treatment was always conservative and no deaths were related to T-tube. In group 1, 29 (31.2%) complications occurred; and the mean hospital stay was 9.4+/-9.3 days. In group 2, four complications (7.7%) occurred (P=0.002); and the mean hospital stay was 5.8+/-5.5 days (P=0.012). The adoption of this new technique-under fluoroscopic guidance, using the T-tube itself as a counter-drain-for T-tube removal allowed us to significantly reduce biliary complications and hospital stay.

There is growing interest in measuring intra-abdominal pressure (IAP) in postsurgical and critically ill patients because increased pressure can impair various organs and functions. The aim of this study was to evaluate the effect of different IAP levels on the postoperative renal function of subjects undergoing orthotopic liver transplantation. IAP was measured every 8 hours with the urinary bladder pressure method for at least 72 hours after surgery. At the end of the study, the patients were classified on the basis of their IAP values:or = 18 mm Hg (group A), 19 to 24 mm Hg (group B),or = 25 mm Hg (group C). The three groups were compared in terms of the incidence of acute renal failure (defined as blood creatinine1.5 mg/dL or an increase in the same of1.1 mg/dL within 72 hours of surgery), hourly diuresis, blood creatinine, the filtration gradient, hemodynamic variations, and outcome. The incidence of renal failure was higher among the subjects in group C (P.05 versus group A and.01 versus group B), who also had higher creatinine levels (P.01), a greater need for diuretics (P.01) and a worse outcome (P.05). Receiver Operator Characteristic curve analysis showed that an abdominal pressure of 25 mm Hg had the best sensitivity/specificity ratio for renal failure. An intra-abdominal pressure ofor = 25 mm Hg is an important risk factor for renal failure in subjects undergoing liver transplant.

The functional properties of myeloid dendritic cells (DCs) differ, depending on microenvironmental factors as well as on their stage of maturation. The main approaches for the selective enhancement of the tolerogenic properties of DCs include the induction of a pharmacological arrest of the DCs maturation and the genetical engineering of DCs expressing immunosuppressive molecules. Several immunosuppressive/anti-inflammatory agents have been discovered that potentially inhibit DC maturation and immunogenicity. Photopheresis (ECP) is an immunomodulatory therapy in which leucocytes are exposed to 8-methoxypsoralen (8-MOP) and ultraviolet (UV) A radiation (PUVA). The combination of ECP with immunosuppressive agents has demonstrated efficacy in the management of transplanted patients by reducing either the incidence of organ rejection or the pharmacological toxicity. In particular, we have observed in hepatitis C virus (HCV)-positive patients that the same combination has reduced the immunosuppressive burden and improved sustainability and efficacy of pre-emptive antiviral therapy after liver transplantation. Therefore, in our work we investigated the in vitro effects of PUVA, combined with immunosuppressive drugs (IDs), on both in vitro human DC generation and maturation, in order to contribute to understanding the immunological mechanisms underlying this pharmacological combination. Monocyte PUVA-treatment was performed by using an in vitro experimental protocol that we previously described. PUVA-treated or -untreated highly purified CD14+ cells were incubated with the association of the immunosuppressive drugs, used in the management of liver transplantation, at two different concentrations, in the presence of IL-4 and GM-CSF. The treatment with IDs at the highest concentration (corresponding to that used in clinical practice), alone or in association with PUVA, induced an immunosuppressive effect, by impairing both DC generation and maturation. Neither immunosuppressive drugs at the lowest concentration nor their combination with PUVA affected myeloid DC generation, but modified DC functions, strengthening the induction of a tolerogenic pattern. As this ID concentration was arbitrarily chosen, further experiments could highlight whether lower concentrations than those used in clinical practice would elicit the same effect on DCs and potentially improve their functional properties. This work describes an original experimental approach exploring the in vitro mechanism of action of the combined procedure of PUVA with immunosuppressive drugs, used in liver transplantation, on DCs generation and function. Our results contribute to the knowledge of the mechanisms of action of this combined procedure on DCs, suggesting useful therapeutic implications for the in vivo therapy.

In randomized studies linezolid, indicated for Gram-positive infections, was as effective as teicoplanin in critical ill patients or was superior to teicoplanin in skin infection, pneumonia and bacteremia. We performed a 2-year comparative, retrospective study of patients treated with linezolid or teicoplanin in a single hospital for the same indications. We collected information about the type of infection, the responsible pathogen, therapy administered before study drugs, antibiotic associated with the study drugs, length of hospital stay (LOS), adverse events and outcome of the infections. The aim of the study was to evaluate the efficacy of linezolid in this retrospective patients series. Overall we identified 169 patients treated with linezolid and 91 with teicoplanin. Response to therapy, (resolution or improvement of infection) was better in patients treated with linezolid compared to teicoplanin (83.9% versus 69.2%, p=0.002). Response to therapy by type of pathogen showed the superior efficacy of linezolid against Staphylococcus aureus (including MRSA) and enterococci; although not statistically significant because of the small number of patients enrolled, they were close to significance (p0.056 for S. aureus, p0.055 for MRSA, p0.061 for enterococci). Overall LOS in linezolid-treated patients was 4.6 days (p0.041) less. Empirical use of linezolid reduced lOS by 6 days (p0.038), especially in VAP and bacteremia patients (p0.05). Mortality due to infection was 9.8% in both groups, and adverse events were most frequently documented in linezolid-treated patients. Linezolid was clinically superior to teicoplanin in the treatment of Gram-positive infections.

The aim of the present work was to assess the incidence of neuro-nephrotoxicity after a single-staggered dose of calcineurin inhibitors (CI) with different immunosuppressive approaches. From January to December 2006, all liver transplantation (LT) recipients at risk of renal or neurological complications treated with extracorporeal photopheresis (ECP) + mycophenolate mofetil + steroids and staggered introduction of CI (ECP group) were compared with a historical control group on standard CI-based immunosuppression. The ECP group included 24 patients with a mean model for end-stage liver disease (MELD) score of 19.9 +/- 11.1. The control group consisted of 18 patients with a mean MELD score of 12.5 +/- 5.2 (p = 0.012). In the ECP group CI were introduced at a mean of 9.2 +/- 6.2 d (4-31 d) after LT. Five patients in the ECP group presented acute neuro-nephrotoxicity after the first CI administration on post-transplant d 4, 5, 6, 6, and 14. Overall patient survival at one, six, and 12 months was 100%, 95.8%, and 95.8% in the ECP group vs. 94.4%, 77.7%, and 72.2% in the control group (p < 0.001). In conclusion, we showed that CI toxicity may occur after a single-staggered dose administration, ECP seems to be a valuable tool for managing CI-related morbidity regardless of the concomitant immunosuppressive regimen, being associated with a lower mortality rate in the early post-transplant course.