Alighieri Mazziotti

Improved Results of Liver Resection for Hepatocellular Carcinoma on Cirrhosis Give the Procedure Added Value

ObjectiveTo review a single-center experience to update the performance indexes of liver resection (LR). Summary Background DataSeveral therapies have been proposed in the treatment of hepatocellular carcinoma (HCC) on cirrhosis, although LR was the first to be widely applied. MethodsOf 408 patients with cirrhosis admitted for HCC in the period 1983 to 1998, 264 had a LR. Patient selection, surgical technique, 30-day deaths, long-term survival, recurrence rate, and recurrence treatment were reviewed after stratifying patients according to the year of surgery. Mean follow-up was 34.5 ± 29.1 months. ResultsThe number of Child A patients who underwent surgery after the discovery of the tumor at routine evaluation increased significantly from 64.5% to 87.9% during the study period. Procedures carried out without blood transfusions increased from 31.4% to 76.9%. The overall operative death rate was 4.9%. Actuarial survival rates were 63.1% and 41.1% after 3 and 5 years, respectively; actuarial tumor-free survival rates were 49.3% and 27.9% at the same intervals. After 1992, surgical deaths decreased from 9.3% to 1.3%. Actuarial survival rates increased from 52.9% and 32.3% to 71.7% and 49.4% after 3 and 5 years, respectively. There was no difference in the actuarial recurrence rate between the two periods, but the chance to treat recurrence increased over time from 22.4% to 53.7% with a concomitant, significant improvement in survival. ConclusionsLR represents a well-established therapy for HCC on cirrhosis. It remains one of the fundamentals in the multidisciplinary approach to this tumor and should be considered as the first option for patients with preserved hepatic function and limited disease. Today, LR should offer a surgical death rate of less than 1.5%, a 5-year survival rate of approximately 50%, and a 5-year tumor-free survival rate of 28% when performed in specialized centers.

No treatment, resection and ethanol injection in hepatocellular carcinoma: a retrospective analysis of survival in 391 patients with cirrhosis

BACKGROUND/AIMS This retrospective study was undertaken to obtain information relevant to the therapeutic strategy in single hepatocellular carcinoma associated with Childs A and B cirrhosis. METHODS From a total of 1108 consecutive patients with hepatocellular carcinoma, 391 patients with single, small (< or = 5 cm) hepatocellular carcinoma (260 in Child A class and 131 in Child B class) were observed: 120 were treated by surgical resection, 155 by percutaneous ethanol injection and 116 were untreated. The end point of the study was 3-year survival. The log rank test was used to compare survival among the different groups. RESULTS In the Child A group the cumulative 3-year survival was 79% for surgery, 71% for percutaneous ethanol injection and 26% for no treatment (p < 0.001 for surgery versus no treatment, p < 0.001 for percutaneous ethanol injection vs no treatment). In patients comparable to the surgical group, i.e. potentially operable, survival was 80% for percutaneous ethanol injection and 30% for no treatment. In the Child B group the 3-year survival was 40% for surgery, 41% for percutaneous ethanol injection and 13% for no treatment (p < 0.01 for surgery vs no treatment and p < 0.001 for percutaneous ethanol injection vs no treatment). CONCLUSIONS Surgery and percutaneous ethanol injection improve survival in single hepatocellular carcinoma associated with Child A and B cirrhosis compared to untreated patients in the same Child class. A controlled study to identify factors affecting the choice of treatment is justified.

Piggy‐back versus conventional technique in liver transplantation: report of a randomized trial

Abstract Liver transplantation with preservation of the recipient vena cava (the “piggy-back” technique) has been proposed as an alternative to the traditional method. We performed a randomized study on 39 cirrhotic patients, 20 who underwent the piggy-back technique (group 1) and 19 the traditional method using venovenous bypass (group 2) to evaluate the feasibility and true advantages of the piggy-back technique compared to the traditional method. Two patients were switched to the conventional technique due to the presence of a caudate lobe embracing the vena cava in one patient and a caval lesion in the other. Statistically significant differences between the two groups were only found for the warm ischemia time (48.5 ± 13 min for piggy-back vs 60 ± 12 min for the conventional method) and for renal failure (zero cases in group 1 vs four cases in group 2). We therefore believe that liver transplantation with the piggy-back technique can easily be performed in almost all cases, and that only a few, specific situations, such as a very enlarged caudate lobe, do not justify its routine use.

Gross pathologic types of hepatocellular carcinoma in Italian patients. Relationship with demographic, environmental, and clinical factors.

Background. The prevalence of the different hepatocellular carcinoma (HCC) macroscopic types, and the association between these types and age, gender, blood group, alcohol and coffee intake, smoking habit, hepatitis virus markers, underlying cirrhosis, and cancer histologic type were retrospectively assessed in 416 unselected patients (321 with cirrhosis).

Pulmonary complications of liver transplantation: radiological appearance and statistical evaluation of risk factors in 300 cases.

Abstract. The aim of this study was to evaluate the incidence, radiographic appearance, time of onset, outcome and risk factors of non-infectious and infectious pulmonary complications following liver transplantation. Chest X-ray features of 300 consecutive patients who had undergone 333 liver transplants over an 11-year period were analysed: the type of pulmonary complication, the infecting pathogens and the mean time of their occurrence are described. The main risk factors for lung infections were quantified through univariate and multivariate statistical analysis. Non-infectious pulmonary abnormalities (atelectasis and/or pleural effusion: 86.7 %) and pulmonary oedema (44.7 %) appeared during the first postoperative week. Infectious pneumonia was observed in 13.7 %, with a mortality of 36.6 %. Bacterial and viral pneumonia made up the bulk of infections (63.4 and 29.3 %, respectively) followed by fungal infiltrates (24.4 %). A fairly good correlation between radiological chest X-ray pattern, time of onset and the cultured microorganisms has been observed in all cases. In multivariate analysis, persistent non-infectious abnormalities and pulmonary oedema were identified as the major independent predictors of posttransplant pneumonia, followed by prolonged assisted mechanical ventilation and traditional caval anastomosis. A “pneumonia-risk score” was calculated: low-risk score ( < 2.25) predicts 2.7 % of probability of the onset of infections compared with 28.7 % of high-risk ( > 3.30) population. The “pneumonia-risk score” identifies a specific group of patients in whom closer radiographic monitoring is recommended. In addition, a highly significant correlation (p < 0.001) was observed between pneumonia-risk score and the expected survival, thus confirming pulmonary infections as a major cause of death in OLT recipients.

A Revised Consideration on the Use of Very Aged Donors for Liver Transplantation

The upper age limit for organ donation for liver transplantation has increased over the past few years. A retrospective case control study was carried out to evaluate the outcome of 36 liver transplants (group A) performed with grafts procured from donors over 70 years old in the period 1996 to April 2000, matched with 36 transplants (group B) chronologically performed thereafter with organs procured from donors below the age of 40 yr. The groups were comparable as regards main clinical characteristics. Mean follow‐up was 14.5 months. Clinical and laboratory parameters of the donors, cold ischemia period, intraoperative blood transfusions, 30‐d mortality, incidence of primary graft nonfunction, acute rejection episodes, arterial complications and long‐term survival of recipients were considered. The main postoperative biochemical parameters were also collected and compared. A liver biopsy was obtained in 20/36 old donors, revealing less than 25% of steatosis in all but one, which showed steatosis involving 70% of the hepatocytes. There were two postoperative deaths (5.6%) in group A and one (2.8%) in group B (p = NS). Seven postoperative arterial complications (19.4%) occurred in group A, leading to the patients death because of rupture of the hepatic artery in one case, to successful surgical revascularization in three cases and to retransplantation in three cases. Only one patient in group B (2.8%) experienced hepatic artery thrombosis (p = 0.055). One‐year patient survival rates were 77.4% for group A and 88.8% for group B (p = NS); 1‐yr graft survival rates were 73.3% for group A and 85.7% for group B (p = NS). In conclusion, donors over 70 should not be excluded a priori for liver transplantation in elective settings. Great attention should be paid to the pathological conditions of arterial vessels caused by atherosclerosis, i.e. the presence of calcified plaques on the hepatic artery, which might represent the source of severe complications.

Lamivudine treatment for acute hepatitis B after liver transplantation

BACKGROUND/AIMS Acute hepatitis caused by recurrent or de novo hepatitis B virus (HBV) infection after liver transplantation frequently induces aggressive disease leading to liver failure. The aim of this study was to determine the efficacy and safety of lamivudine treatment in post-transplant acute hepatitis B. METHOD Twelve patients with acute hepatitis B were started on lamivudine 100 mg p.o. daily within 8 weeks of the appearance of HBsAg. One patient was excluded after 1 month because of hepatocellular carcinoma recurrence. Patients were followed for an average of 68.6 weeks (range 32-108), and were clinically and biochemically evaluated on a monthly basis. They had a histological assessment at baseline, after at least 6 months, and whenever clinically indicated. RESULTS Basal HBV-DNA ranged between 13 and 1288 pg/ml and serum alanine aminotransferase between 97 and 1036 U/l. HBV-DNA became undetectable within 8 weeks and transaminases normalized within 24 weeks in all cases. At the last visit, eight patients (73%) remained HBV-DNA negative by liquid hybridization and had normal or close to normal alanine aminotransferase. Five patients (45%) were also HBsAg negative and HBV-DNA negative by polymerase chain reaction. HBV-DNA and transaminase breakthrough occurred in three patients (27%). Histology after 6-9 months showed chronic hepatitis in seven patients. Lamivudine was well tolerated without serious adverse reactions. CONCLUSIONS These results indicate that lamivudine treatment induces sustained inhibition of viral replication and normalization of transaminases in the majority of post-transplant patients with acute hepatitis B. HBsAg loss may be achieved in a considerable number of cases. Although viral resistance is relatively frequent, early initiation of lamivudine appears to be effective and safe.

Aberrant dipeptidyl peptidase IV (DPP IV/CD26) expression in human hepatocellular carcinoma

BACKGROUND/AIMS Diagnosis of small nodular lesions in the liver is often difficult because polarization of hepatocytes under pathological conditions is not as easily determined as for glandular or squamous epithelia. The aim of the present study was to investigate whether the bile canalicular enzyme dipeptidyl peptidase IV (DPP IV) would be useful to assess the pattern of hepatocellular surface polarity in liver sections. METHODS Expression of DPP IV activity was determined by enzymatic cytochemistry and image cytometry in 25 human hepatocellular carcinomas and five cirrhotic livers removed at transplantation. Samples from the central and/or peripheral portion of neoplastic nodules and from surrounding tissue were analyzed in each case. Control specimens were obtained from normal liver of seven patients who underwent surgery for non-neoplastic conditions. RESULTS In normal liver, DPP IV activity was confined to the bile canalicular plasma membrane with a zone 3 predominance in the hepatic acinus. This was also the case in the majority of pathological non-neoplastic livers, but the cell distribution pattern of DPP IV was altered in all hepatocellular carcinomas: 2/25 cases were completely devoid of DPP IV activity and in the remaining 23 DPP IV expressing hepatocellular carcinomas, three different patterns were observed that deviated distinctly from the typical canalicular pattern: (i) canaliculi were distorted and convoluted and contained an abnormally high DPP IV activity; (ii) canalicular activity was lost and enzymatic activity was restricted to isolated spots; (iii) pseudoacinar structures of hepatocytes with both basolateral and apical DPP IV expression appeared. CONCLUSIONS It is concluded that DPP IV is a useful bile canalicular enzyme to assess the functional polarization of hepatocytes and that aberrant DPP IV expression occurs in human hepatocellular carcinoma.

Physical principles and instrumentation

Sound waves can be defined as mechanical oscillations made to pass through a solid, liquid or gaseous medium. As wave propagation is caused by the movement of particles, it follows that no transmission occurs through a vacuum. The passage of sound waves entails pressure variations in the medium i.e. alternating positive and negative pressures. Wavelength (λ) indicates one complete cycle accomplished by a wave passing through positive and negative positions. Wavelength multiplied by frequency i.e. the number of full cycles per second, gives the velocity (C) of sound: F x λ = C. As velocity is constant in a given medium at a given temperature, frequency and wavelength are inversely proportional.

Protease activities, as well as plasminogen activators, contribute to the "lytic" state during orthotopic liver transplantation.

High levels of tissue plasminogen activator (t-PA) have been reported to be the main component of the high fibrinolytic activity measured in patients during orthotopic liver transplantation. However, a previous study of our group suggested that specific t-PA may not completely account for the massive fibrinolytic activities recorded. In the present study we investigated the fibrinolytic patterns in 10 consecutive liver cirrhosis patients undergoing OLT. Euglobulin fibrinolytic activity, measured either on physiologic (fibrin plates) or amidolytic substrates, increased as expected during anhepatic and reperfusion phases, but largely exceeded the specific activity of t-PA, as proved by quenching procedures using anti-t-PA antibodies. The presence of plasmin- and trypsin-like amidolytic activities was detected in native plasmas at the end of anhepatic and reperfusion phases, together with decreased levels of protease inhibitors, especially α1 Antitrypsin. In conclusion, the hyperfibrinolytic pattern recorded in the central OLT phases is not only attributable to an increased t-PA concentration, and is better described as a complex “lytic” state also including the presence of free proteases (plasmin- and trypsin-like), with limited participation of u-PA. Although t-PA increase is probably the main mechanism of stimulation of the fibrinolytic system during OLT, actual and not just potential proteolytic activities can be found in this condition independent of the occurrence of major hemorrhagic complications.