G.P. Guerrini

Effects of Everolimus Monotherapy on Hematological Parameters and Iron Homeostasis in De Novo Liver Transplant Recipients: Preliminary Results

INTRODUCTION Anemia after orthotopic liver transplantation (OLT) is a common complication due to several reasons. Immunosuppressive drugs play an important role in anemia occurring at 1 month or more after OLT. Several studies describe myelosuppression immunosuppressants such as the mammalian target of rapamycin inhibitors. METHODS We performed a single-center, prospective trial consisting of a short 30-day course of cyclosporine (CsA) associated with everolimus (EVL) from postoperative day 10 (Group EVL) versus a CsA immunosuppressive regimen (Group CsA) in de novo OLT patients. We explored the influence of immunosuppressive drugs on hematological parameters comparing EVL versus CsA. RESULTS Twenty-eight patients were enrolled in the EVL and 12 in the CsA Groups. After OLT, hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC), platelets (PLT), transferrin saturation (TSAT), iron, ferritin, and transferrin did not differ significantly between the 2 groups at any time point. Among the patients who reached 6-months of follow-up, 5 (41.7%) EVL and 4 (80%) CsA subjects were anemic (P=not significant [NS]). Only anemia in patients enrolled in Group EVL showed a trend toward the features of microcytic, hypochromic anemia. DISCUSSION Our results demonstrated that de novo anemia in OLT patients treated with EVL monotherapy showed the same incidence as in patients treated with CsA. Hb values remained similar during the entire follow-up. Moreover, overall myelosuppression in the EVL Group was not significantly different from patients in the CsA Group.

University of Modena Experience in HIV-Positive Patients Undergoing Liver Transplantation

INTRODUCTION Highly effective antiretroviral therapy in the last decade has increased the survival rates of HIV-positive patients, yielding a greater number of HIV patients suffering from liver-related disease. Liver transplantation (LT) is the only curative treatment for end-stage liver disease (ESLD) associated or not with hepatocellular carcinoma (HCC). PATIENTS AND METHODS From June 2003 to September 2010, 23 patients underwent cadaveric donor LT for ESLD at our institution. Inclusion criteria followed the Italian Protocol for LT in HIV-positive patients. Immunosuppressive regimens were based on cyclosporine or tacrolimus, eventually switched to Rapamycin. RESULTS The median CD4 T-cell count was 275/mmc (range=119-924). All patients were affected by ESLD, which was associated with HCC in 14 cases. Ten patients were within the Milan criteria and four patients exceeded them but were within the San Francisco criteria. Conversion from calcineurin inhibitors (CNI) to rapamycin occurred in ten cases. Hepatitis C virus (HCV) recurrence occurred in 13/21 HCV-positive patients. Acute cellular rejection occurred in eight patients with one developing chronic cellular rejection. Overall patient and graft survivals at 80 months were 50% and 45% respectively. DISCUSSION LT in HIV-positive patients is a feasible procedure, even if in our experience was burdened by a greater incidence of complications including HCV recurrence and infection compared with HIV-negative patients.

Cystic Pancreatic Neuroendocrine Neoplasms with Uncertain Malignant Potential : Report of Two Cases

Neuroendocrine tumors of the pancreas (NETP) represent only 1%–2% of all pancreatic neoplasms. They can be classified as functioning or non-functioning, respectively, according to the presence or absence of paraneoplastic syndrome. Case 1 concerned a 70-year-old woman with a cystic lesion of the pancreatic head and body. All tumor markers were negative. The patient underwent a distal pancreatectomy. The histology revealed a well-differentiated endocrine tumor with uncertain malignant potential. Case 2 was a 61-year-old man with chronic polyserositis. The serum tumor markers were negative, while he was strongly positive for intracystic tumor markers carcinoembryonic antigen, carbohydrate antigen (CA) 19–9, and CA 125. The patient underwent a cephalo-pancreatic duodenectomy. The preoperative differential diagnosis of cystic NETP is still a challenge due to the high rate of the nonfunctional variant. Although cystic NETPs are well differentiated, they are still tumors with a malignant potential, and therefore an early diagnosis and radical surgical resection could be associated with a better long-term survival.

Immunosuppressive Switch to Sirolimus in Renal Dysfunction After Liver Transplantation

OBJECTIVE Nephrotoxicity is a serious adverse effect after liver transplantation often related to calcineurin inhibitors (CNI) with a incidence of 18.1% at 5 years. Sirolimus (SRL) is a new immunosuppressive drug that was introduced into solid organ transplant management in 1999. Herein we have performed a retrospective review of patients who developed renal insufficiency owing to CNI therapy after orthotopic liver transplantation (OLT). MATERIALS AND METHODS Thirty-one patients were switched to SRL monotherapy because of nephrotoxicity as evidenced by serum creatinine levels (SCr) > 1.8 mg/dL and estimated glomerular filtration rates (eGFR) < 45 mL/min/1.73 m(2). The dosage was adjusted to achieve trough levels between 8 and 10 ng/mL. RESULTS The patients were followed for a mean of 52 months (range 2-88 months) after OLT. Mean follow-up after the switch was 27.5 months (range, 2-71.2 months). Immunosuppression was switched after a mean of 35.2 months (range, 0.2-43.4 months). Renal function was significantly improved, as shown by the improved SCr, urea, and eGFR after the switch. CONCLUSIONS CNIs may be associated with significant nephrotoxicity and chronic kidney damage. Patients who develop renal dysfunction after OLT may be successfully treated by an early switch from CNIs to SRL, stopping the progression toward chronic renal damage and preserving allograft survival.

Temporary Porto-Caval Shunt Utility During Orthotopic Liver Transplantation

INTRODUCTION In liver transplantation (OLT) a porto-caval shunt is a well-defined technique practiced by many surgeons in several centers. METHODS We considered 186 cadaveric OLT patients who underwent a cavo-cavostomy-type reconstruction; they were divided into two groups: those in whom we performed a porto-caval shunt (group A) and those in whose we did not (group B). We evaluated several variables: warm and total ischemia time, intraoperative blood and fresh frozen plasma transfusions, crystalloid and colloid requirements, blood loss, operative duration, hemodynamic intraoperative changes and diuresis, length of hospital stay, and creatinine values at days 1 and 2, and at discharge day. RESULTS Total and warm ischemic time differed significantly between the two groups. Infusion of blood, fresh frozen plasma, colloid, and crystalloid did not significantly differ. Blood loss was lower, and intraoperative diuresis was not significantly increased in group A subjects. Postoperative hospitalizations were 16.5 and 17.8 days and operative times, 504 and 611 minutes in the two groups. Both cardiac index and ejection fraction values during the anhepatic phase were significantly greater among group A than group B patients. PAD at the two phases was greater in group B. The PAS was significantly different only at reperfusion time. Creatinine values were significantly different at discharge. Better survival was shown for group A patients over group B subjects. CONCLUSION The results presented herein confirmed that a porto-caval shunt during OLT was a safe, useful expedient contributing to an improved hemodynamic status and a better time distribution in the various phases of liver transplantation.

Primary Squamous Cell Carcinoma of the Liver Associated with Caroli’s Disease: A Case Report

RUQ pain and acholic stool with dark urine that spontaneously resolved. A diagnosis of cholelithiasis and hepatolithiasis/Caroli’s disease was made by abdominal ultrasonography (US). The patient was a non-drinker, and the entire hepatitis serology was negative. At the time of evaluation, the patient was not jaundiced, with a total bilirubin level of 1.5 mg/dl (normal value: 0.2–1.2 mg/dl), a normal transaminase value, and a slightly increased Ca 19.9 value (87.7 U/ml, normal value: 0–37 U/ml). A computed tomography (CT) scan of the abdomen and pelvis with contrast showed a non-homogeneous voluminous liver mass with mild contrast enhancement, located between S5 and S6, and associated with ectasic and spindle aspect of the hepatic biliary ducts. Magnetic resonance imaging (MRI) of the upper abdomen showed a 9-cm mass with a low-intensity signal in the T2-weighted image, and high and irregular enhancement after the injection of paramagnetic contrast (fig. 1). The diagnosis of Caroli’s disease was confirmed by the detection at MRI of dilated main and secondary biliary ducts with intraductal lithiasis (fig. 1). A fine-needle aspiration biopsy of the mass was positive for SCC and the immunochemistry stain was strongly positive for cytokeratin (CK) 903, specific for SCC, and CK 7, a marker of bile duct epithelium (fig. 2). A thorough search for a primary tumor was undertaken, with negative findings, including a total body CT, upper gastrointestinal endoscopy, and colonscopy, and a final diagnosis of primary SCC of the liver was made. At the end of March 2003, we performed a right hepatectomy. The pathologic findings showed a whitish liver mass, measuring 10 cm in the largest diameter, 1 cm distant from the surgical margin, and associated with several biliary stones in the rest of the liver. Histologically, the tumor was a moderately differentiated SCC with large areas of necrosis and areas of keratinous debris. Perineural and vessel invasion was identified. The neighboring hepatic tissue presented cholangitis and biliary stones (fig. 2). The post-operative course was uneventful and the patient was discharged home on the 7th post-operative day. Routine observation was continued in the oncology clinic with periodic CT scans of the abdomen and pelvis. No further evidence of the disease was noted over a 7-year period.

Pulmonary Hypertension as a Predictor of Postoperative Complications and Mortality After Liver Transplantation

Most transplant centers consider severe pulmonary hypertension (PHT) to be an absolute contraindication for orthotopic liver transplantation (OLT). We retrospectively examined the outcome of 24 patients with PHT (group 1) who underwent OLT compared with 24 matched patients (group 2) without PHT, who also underwent OLT. Based on right cardiac catheterization measurements made after the induction of anesthesia for OLT, PHT was defined as mild or moderate-to-severe if the mean pulmonary arterial pressure exceeded 25 or 35 mm Hg, respectively. The incidence of PHT was 9.8% (24/244); 21/24 PHT patients showed mild and 3/24 moderate PHT. Kaplan-Meier survival analysis did not show a significant difference between the two groups. The incidence of pulmonary infections was significantly greater in group 1 (P < .05). The duration of ventilation and intensive care unit stay was similar in the two groups. Echocardiography detected only the three moderate cases of PHT and not the twenty-one cases of mild PHT. Our analysis suggested that mild PHT was common and did not affect patient outcomes after OLT; moderate or severe PHT was uncommon. The two patients with moderate PHT survived OLT and did not succum to PHT during long-term follow-up.

Novel genetic mutation in apolipoprotein E2 homozygosis and its implication in organ donation: a case report.

Disorders in lipoprotein metabolism do not contraindicate liver procurement and transplantation (LT). In this circumstance, LT provides an intriguing opportunity to assess the in vivo contribution of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. Apolipoprotein (APO) E exists with several common phenotypic differences due to gene polymorphism. Some authors have shown that the APOE phenotype of the recipient was virtually completely converted to that of the donor, providing evidence that >90% of plasma APOE arises from the liver. Homozygosis for APOE2 (E2-E2) is related to an increased incidence of type III hyperlipoproteinemia (HLP). Recently, some authors have identified 4 new APOE mutations that are strongly linked to a unique entity of renal lipidosis called lipoprotein glomerulopathy (LPG). At present, 65 cases of LPG have been reported worldwide, although most patients have been discovered in Japan and other East Asian countries. We have herein reported a case of LT in a patient with advanced hepatocarcinoma who received a liver from a caucasian donor affected by type III HLP due to homozygous E2-E2. The LPG was due to a novel genetic mutation in APOE. After the LT, the recipient, developed de novo severe lipid abnormalities despite good graft function. To our knowledge this is the first report of an LT using a graft from a non Asian donor with homozygous E2-E2 with the presence of a novel APOE mutation.

Liver transplantation in patients aged 65 and over: a case–control study

Montalti R, Rompianesi G, Di Benedetto F, Ballarin R, Gerring RC, Busani S, De Pietri L, De Ruvo N, Iemmolo RM, Guerrini GP, Smerieri N, Gerunda GE. Liver transplantation in patients aged 65 and over: a case–control study.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2010.01230.x.
© 2010 John Wiley & Sons A/S.

Outcome in right living related liver transplantation with branch-patch arterial reconstruction.

AbstractcRight lobe living liver transplantation is being performed worldwide with increased frequency. Difficult arterial reconstructions are often encountered because of small diameter or discrepancy between arterial stumps. The risk of arterial thrombosis is reported as high as 26%: microsurgical techniques have reduced this rate below 2%, increasing warm ischemia time. We have developed a new branch patch technique in living related liver transplantation using the donor cystic artery to create an enlarged patch anastomosis that enables increase in the vessel’s diameter and therefore greater inflow to the liver. We have followed 8 patients treated with this technique. After more than 1 year (mean follow-up: 636 days) we did not observe any arterial thrombosis by Doppler ultrasound performed every 3 months. The mean resistance index was 0.68 (0.57–0.83–). Three patients died with functional graft without signs of thrombosis. We believe that the cystic artery branch patch technique is feasible in all cases. It is fast (mean time: 6.2 min), it allows a shorter warm ischemia time, and there is no increased risk of thrombosis.