Improved results of liver resection for hepatocellular carcinoma on cirrhosis give the procedure added value.

OBJECTIVE: To review a single-center experience to update the performance indexes of liver resection (LR). SUMMARY BACKGROUND DATA: Several therapies have been proposed in the treatment of hepatocellular carcinoma (HCC) on cirrhosis, although LR was the first to be widely applied. METHODS: Of 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. RESULTS: The 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. CONCLUSIONS: LR 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.

Splenoadrenal shunt. An original portosystemic decompressive technique.

Management of gastrointestinal hemorrhage from rupture of esophageal and gastric varices due to portal hypertension remains a debated question. In patients with sclerotherapy-resistant esophagogastric varices, and preserved hepatic function, a surgical shunt is considered the treatment of choice. A 63-year-old male was admitted in our Department with a diagnosis of idiopathic fibrosis of the liver, portal hypertension, esophageal and gastric varices and previous history of variceal bleeding. A distal splenorenal shunt was planned. During the isolation, a large diameter left adrenal vein was identified. An end-to-end anastomosis utilizing the distal splenic vein and the proximal adrenal stump was performed. The procedure was uneventful. An ultrasound color-Doppler on the 3rd postoperative day, showed normal intrasplenic resistance index, demonstrating the efficacy of the shunt. A splenic angiography carried out on the 8th postoperative day showed the complete patency of the splenoadrenal shunt. At the 15th postoperative day, the patient was discharged. In patients with portal hypertension, sclerotherapy-resistant esophagogastric varices and preserved hepatic function, a surgical portosystemic shunt is mandatory. Splenoadrenal shunt, utilizing a left adrenal vein represent an excellent option in selected cases.

Treatment of vascular complications following liver transplantation: multidisciplinary approach.

BACKGROUND/AIMS: Complications affecting the vascularization of the graft following orthotopic liver transplantation still represent a significant cause of graft loss and patient mortality. Strategies have recently been developed for the early detection and treatment of these complications before irreversible graft failure takes place. METHODOLOGY: A series of 429 consecutive liver transplants performed on 384 patients between April 1986 and December 1998 was retrospectively reviewed to assess the incidence of all the vascular complications and the results of their treatment with either surgery or interventional radiology. RESULTS: The incidence of vascular complications was 6.06% for the hepatic artery, 2.56% for the inferior vena cava and 1.16% for the portal vein. As regards anastomotic stenosis and thrombosis, the requirement of retransplantation decreased progressively with the advent of systematic postoperative screening with duplex Doppler ultrasonography and the introduction of graft-salvage procedures, falling from 50% for those cases diagnosed before 1996 to 19% for those diagnosed from 1996 on. Mortality following 18 graft-salvage procedures was 11.1% versus 41.6% following retransplantation. Graft-salvage procedures were successful in 14 out of 18 cases. CONCLUSIONS: Close surveillance of the vascular anastomoses and multidisciplinary approach to the treatment of vascular complication after liver transplantation considerably reduces graft loss and patient mortality.

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 patient's 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.

Interferon-alpha plus ribavirin and amantadine in patients with post-transplant hepatitis C: results of a pilot study.

BACKGROUND: Recurrence of hepatitis C after liver transplantation is almost constant and may lead to graft loss. The results of treatment with interferon and/or other agents have been controversial. AIMS: To evaluate the efficacy and safety of combination therapy with interferon-alpha2b (3 MU, 3 times weekly), ribavirin (600 mg daily) and amantadine (100 mg daily) in post-transplant hepatitis C. PATIENTS AND METHODS: Enrolled in the study were 9 liver transplant recipients with histologically proven recurrent hepatitis C. Patients were treated for 12 months and followed up for 6 months after treatment. RESULTS: Treatment was not tolerated: only one patient completed the planned course, two stopped therapy within the first 3 months and 6 needed a change. However, mean alanine aminotransferase levels significantly decreased during treatment and were significantly lower than baseline at the end of follow-up. One patient out of 9 (11%) achieved a biochemical and virological sustained response. Control liver biopsy showed improvement in 2/7 patients, no change in 3 and worsening in 2. CONCLUSIONS: In recurrent post-transplant hepatitis C, antiviral treatment with interferon, ribavirin and amantadine seems to be poorly tolerated. However further studies are needed before expressing any conclusion on this potentially important option.

Isolated resection of segment 8 for liver tumors: a new approach for anatomical segmentectomy.

HYPOTHESIS: Isolated resection of segment 8 (the right anterosuperior liver segment) is one of the most difficult hepatectomies to perform because of the location of segment 8, the relation between section 8 and the main intrahepatic vessels, and the absence of any anatomical landmarks. The few reports that deal with isolated resection of section 8 generally describe the use of a deep wedge transparenchymal transection. DESIGN: Original surgical technique. PATIENTS AND METHODS: The proposed technique is based on the extraparenchymal isolation and temporary clamping of the right anterior artery and portal branches, causing ischemic demarcation on the liver surface, which corresponds to the anatomical borders of the right paramedian segments (5 and 8). The liver is widely transected along the main hepatic fissure; then the pedicles of segment 8 are selectively ligated inside the parenchyma, and the resection is accomplished. This technique was used in 10 patients: 5 with hepatocellular carcinoma on cirrhosis and 5 with liver metastases. RESULTS: The mean operation time was 253 minutes. Intraoperative blood loss was minimal in all cases, and 7 patients did not require blood transfusion. Slight complications developed in 3 patients, and there was no operative death. The mean hospital stay was 9.3 days. CONCLUSIONS: This operative procedure is safe and ensures a complete anatomical resection of segment 8. The wide opening of the liver parenchyma facilitates hemostasis and makes it possible to obtain a correct resection margin. This technique is recommended for limited metastatic lesions located in segment 8 or for hepatocellular carcinoma arising in a cirrhotic liver.

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

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.

Highly aggressive policy of hepatic resections for neuroendocrine liver metastases.

BACKGROUND/AIMS: Neuroendocrine tumors are usually slow growing and carry a prolonged prognosis. The presence of liver metastases significantly impairs long-term survival. The clinical experience with 28 patients admitted since 1981 for liver metastases from neuroendocrine tumors was retrospectively reviewed to analyze the clinical and surgical management and to evaluate their outcome. METHODOLOGY: Surgery was indicated in 25 (89.2%) patients. Three had metachronous metastases. A correct diagnosis of these liver metastases was achieved before laparotomy in 15 (68.1%) of the remaining 22. The primary tumor site, unknown in 14/22 patients, was located during surgery only in 8 (57.1%). RESULTS: Due to tumoral spread, surgery was limited to exploration in 3 cases. Liver resections were performed in 19/22 patients (3 for palliation): 11/19 (57.9%) were major hepatectomies and in 8/19 (42.1%) cases they were accomplished by procedures for removing the primary tumor. Overall, curative procedures were carried out in 16/28 (57.1%). Resections were performed in 6 cases without the knowledge of the primary site. There was no operative mortality. Overall recurrence rate was 50.0%. Four-year actuarial survival was 92.6% after resection and 18.5% for patients that did not receive surgery (P < 0.001). CONCLUSIONS: Our experience confirms that the small number of patients makes the management of liver metastases from neuroendocrine tumors difficult to plan. In consideration of the satisfactory results achieved with an aggressive policy of resection, we advise referral of these patients to specialized liver units where major hepatic procedures, even if extended, can be safely performed.

The lidocaine (MEGX) test as an index of hepatic function: its clinical usefulness in liver surgery.

BACKGROUND: The purpose of this study was to evaluate the clinical usefulness of the lidocaine test, as an index of hepatic function, in the different fields of liver surgery. METHODS: The lidocaine (MEGX [monoethylglycinexylidide]) test, which was performed in 200 patients with different liver diseases and in 23 organ donors, was compared with common laboratory tests. The MEGX value was related to postoperative complications in patients who undergo liver resection and to the survival of patients with cirrhosis who are awaiting transplantation. In organ donors, the test was related to the outcome of patients who underwent transplantation. RESULTS: The MEGX value was significantly higher in patients without cirrhosis compared to patients with cirrhosis (77.8 +/- 25 ng/mL vs 35.6 +/- 30 ng/mL; P < .05); among patients with cirrhosis, there was a significant difference between those patients classified Child A and those classified Child B and C (43.3 +/- 25 ng/mL vs 11.5 +/- 7.1 ng/mL; P < .05). The patients classified Child A who underwent liver resection with MEGX value less than 25 ng/mL had a significantly higher rate of postoperative complications compared with other patients (P < .001). Patients with cirrhosis who were awaiting liver transplantation and who had a MEGX value of less than 10 ng/mL had a life expectancy of no longer than 1 year. CONCLUSIONS: The MEGX test is a reliable index of hepatic function. Patients carrying hepatocellular carcinoma with MEGX value of less than 25 ng/mL have a high risk of liver insufficiency after hepatic resection. Patients with decompensated cirrhosis who have an MEGX value of less than 10 ng/mL should undergo transplantation as soon as possible.

Allelic imbalance on 16q in small, unifocal hepatocellular carcinoma: correlation with HBV and HCV infections and cellular proliferation rate.

In advanced hepatocellular carcinoma (HCC), allelic loss on chromosome 16q may occur. To better define the frequency of this alteration in small HCC and to more closely identify the affected region for further positional cloning of the putative tumor suppressor gene contained in this region, microsatellite polymorphism analysis was conducted on small, unifocal HCC, without signs of intrahepatic or systemic spread. We also tried to assess its possible correlation with hepatitis virus infections (HBV and HCV) and cellular proliferation rate. DNA from 35 small (<4 cm), unifocal HCC and from the corresponding nontumorous surrounding tissue was analyzed by 10 sets of microsatellite polymorphic markers. Serologic markers for hepatitis virus B and C infections were investigated in all cases. AgNOR protein quantity was assessed by image analysis on cryostatic sections stained with silver. The percentage of tumours with allelic imbalance ranged from 11.1 to 37%. The minimal involved region was assessed at 16q24.3, corresponding to the D16S413 marker, which was also the most commonly affected locus (10 of 27 informative cases, 37%). Allelic imbalance on chromosome 16q was significantly associated with HBV infection: 8 of 10 cases showed an actual or previous HBV infection in the group showing allelic imbalance, versus 6 with a previous HBV infection out of 25 in the control group (P < 0.01). No difference was found as far as HCV infection is concerned. The mean (+/-SE) AgNOR protein value in six cases showing allelic imbalance was 8.36 +/- 1.2 microm2, compared to 6.45 +/- 0.68 microm2 in 13 cases retaining both the alleles at 16q but the difference proved not statistically significant. In conclusion, in this series of small, unifocal HCC the minimal region of allelic imbalance on 16q was restricted to 16q24.3. It was found to be associated with HBV infection but not with increased cellular proliferation rate.

[Monoclonal antibody SPan-1 in the diagnosis of exocrine pancreatic adenocarcinoma]. / L'anticorpo monoclonale SPan-1 nella diagnosi di adenocarcinoma pancreatico esocrino.

The great progress made in imaging techniques over the past few years has not resulted in an improvement in terms of earlier diagnosis of exocrine pancreatic cancer. The search for a non-invasive diagnostic tool, capable of yielding an early diagnosis, has led to the development of a series of serum tumour markers. This article discusses the clinical evaluation of SPan-1 and its comparison with established markers such as CA 19.9, CEA, TPA and CA 242. The markers were tested in preoperative serum samples collected from 46 patients operated on for ductal carcinoma of the pancreas, 20 patients with chronic pancreatitis and 23 patients with other digestive neoplasms. Sensitivity, specificity and diagnostic accuracy for pancreatic cancer were as follows: [table: see text] The antigenic determinant recognised by monoclonal antibody SPan-1 is high in sera of patients with exocrine pancreatic cancer. SPan-1 may be another useful, reliable serum marker in detecting this neoplasm, but this study indicates that SPan-1 does not greatly improve the diagnostic accuracy achieved with CA19.9.

Antimicrobial prophylaxis with ceftriaxone for prevention of early postoperative infections after 49 liver transplantations.

Infection remains a major problem for individuals who undergo solid organ transplantation and liver transplant recipients are particularly susceptible to infectious complications with a high morbidity and mortality rate. The risk of these infections is determined by previous or future environmental exposures as well as the patient's immune status. We report here the results of an open prospective study involving 49 consecutive liver transplantations, undertaken to evaluate the efficacy of ceftriaxone in the prevention of early postoperative infectious complications. Antimicrobial prophylaxis was done using a single dose of ceftriaxone (2 g i.v.) given at the induction of anesthesia and then 2 further once-daily doses were administered 2 days postoperatively. Early postoperative bacterial infection rate was 43.5% (20/46); this result is comparable or even lower than those documented in other studies. This study, even though open and non-comparative, showed that a once-daily regimen containing ceftriaxone provides adequate antimicrobial prophylaxis and significant cost-savings in comparison with multiple-dose prophylactic regimens in patients undergoing liver transplantation.

Aberrant fragile histidine triad gene transcripts in primary hepatocellular carcinoma and liver cirrhosis.

To determine whether transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of human hepatocellular carcinoma (HCC) we used reverse transcription-PCR to examine mRNA FHIT expression in 28 paired samples of HCC (24 in cirrhotic and 4 in noncirrhotic livers) and matched noncancerous tissue and in 10 normal livers. We also assessed loss of heterozygosity of the polymorphic D3S1300 microsatellite marker in the intron between exons 5 and 6 of the FHIT gene. Abnormal FHIT transcripts were detected in 13 cases (46.4%): 10 in the cancerous tissue only, 1 with the same pattern in both cancerous and matched noncancerous tissue, and 2 in the noncancerous tissue only. The four HCCs that arose in noncirrhotic liver all showed abnormal FHIT transcripts. No alterations were found in normal livers. Sequence analysis of abnormally sized transcripts revealed that they were generated by the fusion of exons 3 or 4 with exons 8 or 9. Among the cancerous specimens, one case showed only an abnormal sized transcript derived from the fusion of exons 4 and 9 in the absence of any normal-sized transcript, and another case showed deletion of a sequence comprised between nucleotides -35 and 399 resulting in an exon 4-9 fusion not respecting the exons' bounds. Loss of heterozygosity was found in two cases with abnormal FHIT transcripts and in only one case with normal transcript. Patients with aberrant FHIT transcripts showed a significantly higher relapse rate and shorter recurrence time (P = 0.001). This could be related to a primary genomic instability affecting particularly susceptible regions like FRA3B and could be associated with an increasing risk of recurrence without involving a causative role.

Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites.

Patients with advanced cirrhosis frequently show hemodynamic abnormalities. Autonomic dysfunction (AD) is also common and, owing to the importance of autonomic function in cardiovascular homeostasis, it may be involved in the pathogenesis of the hyperdynamic circulation. We, therefore, evaluated the hemodynamic status and autonomic function in 30 patients with cirrhosis, most of them with an advanced stage of the disease. Autonomic function was assessed with 7 cardiovascular tests exploring the vagal or sympathetic function. Each test was scored from 1 to 3 (normal, borderline, altered). Cardiac index (CI) was measured by an echocardiogram. Twenty-four (80%) patients showed an AD, this being definite in 14 (47%) patients. A vagal dysfunction (VD) was found in 19 patients (63%), this being definite in 11 patients (37%), and a sympathetic dysfunction (SD) in 7 patients (definite in 3 [10%] patients). The patients with AD showed a faster heart rate (P =.021), lower indicized peripheral vascular resistance (P =.013), and increased CI (P =.004) than patients without AD whereas mean arterial pressure did not differ. Similar results were seen by grouping patients according to the VD. AD score was directly correlated with heart rate (r = 0.53; P =.002) and CI (r = 0.45; P =. 016), and inversely correlated with peripheral vascular resistance (r = 0.46; P =.013). Even closer correlations were found with vagal score. AD (mainly VD) may be involved in the pathogenesis of the hyperdynamic circulatory syndrome of patients with advanced cirrhosis.

[Liver transplantation from elderly donors]. / Trapianto di fegato da donatori anziani.

This retrospective, case-controlled study compared the outcome of 17 OLTs (group A) using livers donated by subjects over 70 years of age with 17 OLTs (group B) with livers from donors under 40. Clinical data were used form the period 1996-1998. The following variables were considered in the analysis: donor clinical and laboratory parameters, cold ischemic periods, intra-operative blood and plasma replacement, 30-day mortality rate, incidence of primary graft dysfunction, acute rejection and arterial complication and long term survival. The main post-operative parameters were also included. Liver biopsy, performed in 9/17 of group A, revealed minimal steatosis. There were 2 post-operative deaths in group A and 1 in group B (p = NS). Two arterial complications were observed in group A (p = NS) and only one patient required retransplantation (p = NS). The only other difference found among clinical variables was the amount of total bilirubin at post-operative days 8 and 10, aPTT at days 6 and 13 and albumin at days 5 and 6. A two-year follow-up showed survival rates to be 88.2% and 94.1% for groups A and B, respectively (p = NS). Candidates over 70 years of age should be excluded as liver donors. In such cases, greater care needs to be placed on pathological vascular conditions related to advanced stage atherosclerosis such as calcified plaques on the hepatic artery, a possible factor in severe postoperative complications.

Porcine living liver transplantation using a vascular prosthesis to replace the intrahepatic vena cava.

BACKGROUND: This study aimed to determine whether the porcine model could be adapted to accommodate living donor liver transplantation (LLT). Because the pig hepatic anatomy precludes a standard approach, a study was designed to evaluate the results using a segment of vascular prosthesis to replace the intrahepatic portion of the inferior vena cava (IVC) with establishment of hepatic venous drainage into the graft. METHODS: A total of 10 LLT were performed using 20 pigs. After left hepatectomy, the intrahepatic IVC was replaced with a modified aorto-iliac prosthesis, anastomosing the proximal (aortic limb) to the infradiaphragmatic IVC, one distal iliac limb to infrahepatic IVC and the other (after shortening) to establish hepatic venous drainage after transplant. Conventional venous bypass was used, and no immunosuppressives were administered. RESULTS: All donors survived the 10-day posthepatectomy observation period. Eight of the 10 transplanted pigs survived at least 2 days (mean 7.6 days; range 3-13 days). No evidence of caval graft thrombosis was observed. CONCLUSIONS: Replacement of the recipient intrahepatic IVC by a vascular prosthesis allows to overcome the major technical obstacle which has limited the use of pigs in LLT.