Lucio Mandalà

Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system

Abstract:  Coagulopathy is a life‐threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell‐free dialysis technique, on the blood coagulation of cirrhotic patients.

Successful treatment of small‐for‐size syndrome in adult‐to‐adult living‐related liver transplantation: single center series

Abstract:  The portal hyperperfusion, or small‐for‐size syndrome (SFSS), is a widely recognized clinical complication that may occur after segmental liver transplantation. Several surgical strategies have been proposed to reduce portal blood inflow and portal pressure after partial liver transplantation. In particular, splenic artery ligation and splenectomy have been used without a firm hemodynamic basis for these procedures. Our group recently demonstrated that, in patients with cirrhosis and portal hypertension, the occlusion of the splenic artery causes a significant reduction in the portal pressure gradient, which is directly related to the spleen volume and indirectly related to the liver volume. This concept is at the center of our strategy for performing early splenic artery embolization (SAE) for the treatment of SFSS after living‐related liver transplantation (LRLT). Six patients developed small‐for‐size syndrome, defined as: onset within the first week after LRLT of progressive hyperbilirubinemia without mechanical cause; marked cholestasis; centrilobular sinusoidal dilatation and hepatocyte atrophy at liver biopsy; and refractory ascites in the absence of vascular complications. All six patients who underwent SAE rapidly improved their clinical condition, with an evident decrease in the value of bilirubin in the serum, in the production of ascites, and improvement in condition of pancytopenia. Coagulopathy expressed by the international normalized ratio value (INR) was not a reliable early marker of SFSS in this series; in fact a slight improvement in the result of this test was already present immediately after LRLT and before SAE. Because splenic flow clearly contributes to portal hyperperfsion, an early SAE can relieve the partial graft from the deleterious effect of this portal overflow.

Critical use of extended criteria donor liver grafts in adult-to-adult whole liver transplantation: A single-center experience

This study presents our experience with the use of extended criteria donor (ECD) liver grafts. One hundred fifteen liver transplants were divided into 2 groups: standard (S) and nonstandard (NS). Fifty‐eight patients in group S received a liver procured from an ideal donor, whereas 57 patients in group NS received an organ from an ECD. On the basis of the number of risk factors, patients were divided into 3 subgroups: the S group with 58 receiving a standard graft, the NS1 group with 44 receiving a graft with 1 or 2 risk factors, and the NS2 group with 13 receiving a graft with 3 to 4 risk factors. Patient survival was not different at 6, 12, and 24 months (P > 0.05), whereas graft survival was different (P = 0.0079). Both patient survival and graft survival were influenced by the cumulative number of risk factors. The univariate analysis of the donor risk factors detected hemodynamic factors as predictive of graft failure (P = 0.024) and death (P = 0.018). In the multivariate analysis, which was adjusted for recipient age and donor and recipient gender, hemodynamic risk factors and Model for End‐Stage Liver. Disease score in the recipient were the only variables independently associated with graft failure (P = 0.006, P = 0.012, negatively). Finally, we observed a reduction of dropout from the list to 9% from 14.1% (P = 0.04) and of mortality on the list to 32.55% from 41.01% (P = 0.11). Critical use of ECD liver grafts allowed recipients in the waiting list to have a greater chance of being transplanted. Liver Transpl 14:220–227, 2008.

Sequential Preoperative Ipsilateral Portal and Arterial Embolization in Patients with Colorectal Liver Metastases

BackgroundPreoperative portal vein embolization (PVE) induces ipsilateral atrophy of the hepatic parenchyma to be resected, as well as contralateral compensatory hypertrophy of the residual liver. However, there are two potential problems with this technique: inadequate contralateral hypertrophy and tumor progression while waiting for the non-embolized liver to hypertrophy. We devised a strategy to deal with these two problems by performing an ipsilateral hepatic artery embolization 6 weeks after an unsatisfactory PVE in an effort to accelerate the hypertrophy of the remnant liver.Materials and MethodsTwo patients with colorectal liver metastases underwent to this sequential preoperative treatment in order to achieve resectability of their metastatic disease.ResultsBoth patients successfully underwent major hepatic resection.ConclusionsIn our experience sequential ipsilateral portal vein and hepatic artery embolization extended the indications for liver resection for metastatic colorectal cancer.

Fulminant hepatic failure bridged to liver transplantation with a molecular adsorbent recirculating system: a single-center experience.

We herein describe the clinical course of a consecutive series of fulminant hepatic failure patients treated with a molecular adsorbent recirculating system (MARS), a cell-free albumin dialysis technique. From November 2000 to September 2002, seven adult patients ages 22–61 (median, 41), one male (14.2%) and six females (85.7%), affected by fulminant hepatic failure underwent seven courses (one to five sessions each, 6 hr in duration) of extracorporeal support using the MARS technique. Pre- and posttreatment blood glucose, liver function tests, ammonia, arterial lactate, electrolytes, hemodynamic parameters, arterial blood gases, liver histology, Glasgow Coma Scale, and coagulation studies were reviewed. No adverse side effects such as generalized bleeding on noncardiogenic pulmonary edema, often seen during MARS treatment, occurred in the patients included in this study. Six patients (85.7%) are currently alive and well, and one (14.2%) died. Four patients (57%) were successfully bridged (two patients in 1 day and two other patients in 4 days) to liver transplantation, while two (5%) recovered fully without transplantation. All the measured variables stabilized after commencement of the MARS. No differences were noted between the pre- and the post-MARS histology. We conclude that the MARS is a safe, temporary life support mechanism for patients awaiting liver transplantation or recovering from fulminant hepatic failure.

Fulminant hepatic failure and autoimmune disorders in patient with multiple sclerosis on interferon beta 1a: A fatal combination?

We report the case of a 46-year-old woman admitted to our liver transplant unit for sudden onset of jaundice, elevated transaminases and coma. She had been diagnosed, ten years before, with progressive relapsing multiple sclerosis (MS) involving predominantly the left side of her body, and treated with steroids for 8 years. She was then switched to interferon (IFN)-beta 1a 30 lg/0.5 ml i.m. once weekly. She had never taken anti-inflammatory drugs or alcohol. Six months later IFN was initiated; a diagnosis of chronic thyroiditis was made on the basis of positive antiperoxidase antibodies (160 IU/l, normal value 0–35) and nodular goiter. The thyroid hormones and liver function were found within normal ranges a few months before liver decompensation. One year ago, after a two-and-a-half-year course of IFN-beta treatment, the patient had a relapse of MS requiring steroid treatment with clinical improvement. One-and-half months later, after receiving her weekly injection of IFN-beta, she became jaundiced and confused reaching comatose stage in 48 h requiring intubation. She was then transferred to our liver transplant unit and was treated with steroids, antibiotic prophylaxis and fluids. Upon admission, no signs of portal hypertension were present. The laboratory tests showed aspartate transaminase 505 (normal value = 10–42 IU/l), alanine transaminase 1232 (10–40 IU/l), gamma glutamyl transpeptidase 73 (2–30 IU/l), alkaline phosphatase 221 (39–92 IU/l), total bilirubin 15.2 (0.2–1.2 mg/dl), direct bilirubin 9.1 (0.0–0.3 mg/dl), prothrombin activity 28.6 (70–120%), prothrombine time (PT) 24.9 s, international normalized ratio (INR) 1.97, total protein 5.4 g/dl (6–8 g/dl), gammaglobulins 23.1 (12–22.5%), free tri-iodothyronine <1 (1.5–4.1 pg/ml), and free thyroxine 0.64 (0.80–1.9 ng/ml). Anti-smooth muscle antibodies (SMA) were positive 1:80 and antiperoxidase antibodies were 112 (normal value: 0–35 IU/ml). All other autoantibodies and serology screening were negative. The abdominal computerised tomography scan showed a normal liver with a patent enlarged portal vein and mild ascites. We then performed a transjugular liver biopsy, which showed severe acute hepatitis with sub-massive hepatic necrosis involving 80% of liver parenchyma. The inflammatory infiltrate was a mix consisting of lymphocyte and small clusters of plasma cells seen predominantly in centrilobular areas (Fig. 1). Trichrome stain highlighted the presence of mild portal fibrosis. The patient’s score for autoimmune hepatitis was 10. Three days after admission, the patient developed fulminant hepatic failure and, according to King’s College criteria, underwent uneventful cadaveric liver transplantation. She had a regular postoperative course on single immunosuppressant drug (tacrolimus) but has developed hypothyroidism. The autoantibodies repeated were negative except for antiperoxidase antibodies (73.8 IU/ ml). Multiple sclerosis is an organ-specific autoimmune disease thought to be mediated by type 1 helper T cells (Th1) that produce IFN-gamma that has been thought to induce the autoimmune process observed in Hashimoto’s disease. Moreover, the IFNs can contribute to the development of chronic inflammation by preventing activated T-cell apoptosis [1]. MS has also been found to be associ-

New technique in hepatic parenchymal transection for living related liver donor and liver neoplasms

BACKGROUND Many different surgical techniques have been described for hepatic parenchymal transection. A retrospective analysis of perioperative mortality, length of hospitalization and blood transfused during operation in two patient groups undergoing liver resection was carried out. In group A, we developed a new technique to resect hepatic parenchyma, using an ultrasonic surgical aspirator with monopolar floating ball cautery, while in group B the crushing clamp technique was used. METHODS In all, 42 patients with liver resection were enrolled in group A and 107 resections in group B. All patients had hepatic neoplasms except for seven living transplant donors. In group A 43% of resections involved >or=3 segments and 57% involved <or=2 segments; in group B 36.4% involved >or=3 segments and 63.6% consisted of <or=2 segments. Statistical analysis utilised independent T square (Pearson Q square) and Mann-Whitney U test. RESULTS In group A 2.4% of patients died perioperatively, while 3.7% died in group B; mean length of stay (LOS) was 10.9 days in group B and 8.0 days in group A. The length of procedure was 7.5 h in group B and 6.7 h in group A. In group A, 79% did not undergo blood transfusion intraoperatively as opposed to 61% in group B. A mean of 0.5 U of blood was utilized in group A and 1.60 U in group B. DISCUSSION The new method of parenchymal transection seems to reduce the LOS, length of procedure and need for intraoperative blood transfusion.

Noncardiogenic pulmonary edema induced by a molecular adsorbent recirculating system : case report

Noncardiogenic pulmonary edema is a well-recognized manifestation of acute lung injury which has been related, among others, to blood or blood-product transfusion, intravenous contrast injection, air embolism, and drug ingestion. We describe two cases of noncardiogenic pulmonary edema after use of a molecular adsorbent recirculating system, a cell-free dialysis technique. Patients in this series presented at our institution to be evaluated for liver transplantation. Subsequently, they developed an indication for the molecular adsorbent recirculating system. Two patients of 30 (6.6%) treated with the molecular adsorbent recirculating system for acute-on-chronic liver failure and intractable pruritus had normal chest X-rays before treatment and developed severe pulmonary edema, in the absence of cardiogenic causes, following use of the molecular adsorbent recirculating system. For each patient we reviewed the history of blood or blood-product transfusion, echocardiograms if available, daily chest X-rays, and when available pre- and postmolecular adsorbent recirculating systemic blood pressure, central venous pressure, pulmonary arterial pressures, cardiac output, cardiac index, systemic vascular resistance index, and arterial blood gas. Our data suggest that the molecular adsorbent recirculating system may cause noncardiogenic pulmonary edema, possibly by an immune-mediated mechanism.

The role of basiliximab induction therapy in adult-to-adult living-related transplantation and deceased donor liver transplantation: a comparative retrospective analysis of a single-center series.

AIM The aim of this study was to report our single-center experience with the use of basiliximab, in combination with a steroid and tacrolimus-based regimen in adult to adult living-related liver transplantation (ALRLT) and in deceased donor liver transplantation (DDLT). MATERIALS AND METHODS Seventy-seven consecutive ALRLT recipients (group 1) and 244 DDLT recipients (group 2) were analyzed. All patients received 2 20-mg doses of basiliximab (days 0 and 4 after transplantation) followed by tacrolimus (0.15 mg/kg/d; 10-15 ng/mL target trough levels) and a dose regimen of steroids. Follow-up ranged from 4-1972 days after transplantation in group 1 and from 1-2741 days in group. RESULTS In group 1, 89.32% of the patients remained rejection-free during follow-up, with an actuarial rejection-free probability of 93.51% within 3 months. Actuarial patient survival rate at 3 years was 84.49%. In group 2, 86.07% of the patients remained rejection-free during follow-up, with an actuarial rejection-free probability of 93.04% within 3 months. Actuarial patient survival rate at 3 years was 87.69%. We observed 14 cases of hepatitis C virus (HCV) recurrence in group 1 (prevalence of 26.92%) and 80 cases in group 2 (prevalence of 54.05%). CONCLUSION Basiliximab in association with tacrolimus and steroids is effective in reducing episodes of acute cellular rejection (ACR) and increasing ACR-free survival after ALRLT and DDLT. No difference in patient and graft survival was found between group 1 and 2, nor was there any difference in the incidence of ACR between the 2 groups. However, less risk of HCV recurrence was present in the LRLT group.

Successful liver transplant in an HCV‐infected haemophiliac patient with fulminant hepatic failure

L. MANDALÀ,* G. PIETROSI, S. GRUTTADAURIA,* G. VIZZINI, M. SPAMPINATO,* M. SPADA,* G. BURGIO, A. ARCADIPANE, M. IDA MINERVINI,§ G. PAGNUCCO,– U. PALAZZO and B. GRIDELLI* *Istituto Mediterraneo per i Trapianti e le Terapie ad Alta Specializzazione (IsMeTT-UPMC Italy), General Surgery and Organ Transplantation, Palermo, Italy; Istituto Mediterraneo per i Trapianti e le Terapie ad Alta Specializzazione (IsMeTT-UPMC Italy), Hepatology, Palermo, Italy; Istituto Mediterraneo per i Trapianti e le Terapie ad Alta Specializzazione (IsMeTT-UPMC Italy), Anestesiolgy and Critical Care Medicine, Palermo, Italy; §Istituto Mediterraneo per i Trapianti e le Terapie ad Alta Specializzazione (IsMeTT-UPMC Italy), Pathology, Palermo, Italy; and –Civico Hospital, Hematology Unit, Palermo, Italy