G. F. Rondinara

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization

Abstract Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22–89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3‐ and 5‐year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient‐related characteristics examined (sex, age) are not significantly related to patient survival. Tumor‐related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

The role of spontaneous portosystemic shunts in the course of orthotopic liver transplantation

Abstract. Spontaneous portosystemic shunts are commonly found in cirrhotic patients. Not yet established is their role after orthotopic liver transplantation (OLTx), especially when an increase in portal pressure develops, as during early acute rejection. In this study, 34 cirrhotic patients in a series of 70 OLTx are considered. Each patient had preoperative angiographic assessment, and, in 21 (62 %), large spontaneous portosystemic shunts were evident. In 12 cases the shunts were not affected by the surgical procedure and were present during the postoperative period; in 9 the hepatectomy itself involved interruption of the shunts. The patient population was divided into two groups: patients with postoperative shunts (n = 12) and those without (n= 22). The two groups were similar in age, sex. Childs stage, transplantation variables, and number and grade of rejection episodes. However, mean transaminases (AST) values in the first 2 weeks were significantly higher levels in shunt versus nonshunt patients (421 ± 335 vs 183 ± 126; P < 0.025), and this was even more evident when rejection occurred (626 + 375 vs 195 ±129; P < 0.001). Furthermore, during an acute rejection reaction, three cases showed a true “steal phenomenon” through the large reopened shunts with ischemic damage to the grafts. The data indicate a possible detrimental effect of the spontaneous shunts on graft perfusion and suggest the prophylactic surgical interruption of the residual shunts during the transplantation.

Is the use of marginal donors justified in liver transplantation? Analysis of results and proposal of modern criteria

Abstract  A discrepancy exists worldwide between the number of suitable liver donors and the in creasing demand for transplantation. Thus many centers have considered widening their liver donor acceptance criteria and this may in crease the incidence of primary dysfunction (PD) with negative effect on the results of transplantation. In order to reduce the incidence of PD and improve patient and graft survival it becomes important to identify those risk factors associated with its occurrence. In a retrospective univariate and multivariate analysis we evaluated several donor, preservation and recipient parameters and their correlation with PD. In our Department 282 orthotopic liver transplantations (OLT) were per formed on 256 adult patients over a 10–year period. Excluded were 15 cases with early vascular problems and 4 intraoperative deaths. A complete series of donor, recipient and procedure‐related data were ana lyzed. About 30 % of donors showed abnormal values. In 70 cases of PD (26 %) there was a 61.4 % graft failure rate compared with 15 % in the group with immediate function (P < 0.05). Univariate analysis showed donor age, steatosis, is chemia time, amines, oliguria, hy potension and ICU stay to be signif icantly associated with PD. Multi variate analysis showed steatosis, is chemia time and amine dosage to be independent risk factors for the de velopment of primary non function. In conclusion, the acceptance of marginal donors worsened the results of transplantation, but the rejection of these donors would reduce by about 30 % our transplant activity resulting in increased mortality in the waiting list. Combinations of risk factors when possible should be avoided, and ischemia time, as the only variable that can be controlled, should be kept as short as possible.

Dysarthria and cerebellar ataxia: late occurrence of severe neurotoxicity in a liver transplant recipient

Abstract Neurological complications of cyclosporin (CyA) therapy are frequent, usually occurring within the f st month after transplantation. Though leukoencephalo‐pathy is one of them, it is rarely documented. Here we report the case of an anti‐HCV‐positive patient with cirrhosis who underwent liver transplantation and developed cyclosporin‐induced leukoencephalopathy. The presenting symptoms were dysarthria, difficulty walking, and dysphagia. They were first noted 6 months after transplantation in association with an episode of recurrent HCV acute hepatitis. White matter abnormalities were evident on computed tomography (CT) scanning and magnetic resonance (MR) imaging. This condition improved to some degree after cyclosporin withdrawal. To our knowledge this is the second reported case of CyA neurotoxicity occurring late after liver transplantation. Moreover, the association with acute hepatitis suggests the possibility of graft dysfunction as a contributing and triggering factor.

Reappraisal of surgical treatment of small hepatocellular carcinomas in cirrhosis: clinicopathological study of resection or transplantation.

Thirty-two patients with hepatocellular carcinoma (HCC) occurring in individuals with cirrhosis had a potentially curative surgical procedure. Twenty-two had segmental hepatic resections (HR), and 10 underwent orthotopic liver transplantation (OLTx). The diagnosis of hepatic malignancy was established in each case preoperatively, and each case was studied intraoperatively by means of sonography. Postoperatively each surgical specimen was examined pathologically with attention to the possibility of intrahepatic tumor spread. Twenty-three of the 32 patients had single small HCC lesion (<5 cm diameter) identified preoperatively. Sixteen of these underwent HR and seven underwent OLTx. Multiple additional neoplastic lesions were found in 19% of the 16 HR cases and in 14% of those undergoing OLTx when the resection specimens were examined pathologically. Vascular invasion was present in 43% of the OLTx patients and in 25% of the HR patients. Subtotal hepatic resection for small HCC occurring in cirrhosis has produced few long-term survivals. Both pre- and intraoperative sonography have been shown to underestimate the extent and distribution of these tumors. Based upon this experience that (1) vascular spread occurs often in HCC and (2) a high risk of postoperative hepatic failure can be expected after HR in cirrhotic individuals, OLTx is the most rational surgical procedure for such cases as it has the potential to cure.

Long-term efficacy of endoscopic stenting in patients with stricture of the biliary anastomosis after orthotopic liver transplantation

BACKGROUND AND STUDY AIMS The choledocho-choledochostomy (CCS) stricture is one of the most frequent complications occurring after liver transplantation. Endoscopic retrograde cholangiography (ERCP) is the most sensitive method used to define the presence and narrowness of the stricture. Endoscopic stenting of the strictured anastomosis could provide an effective alternative to the surgical intervention. PATIENTS AND METHOD ERCP was performed in 36 of 210 patients with liver transplantation and acute cholestasis or jaundice: in 15 cases biliary anastomotic stricture was found. These patients were endoscopically treated by long-term stenting of the common bile duct (CBD) (1 year) and followed up for more than 12 months after stent removal. RESULTS In all cases the stenting procedure resolved the biliary obstruction syndrome within 7 days. At the end of the stenting period the CCS was dilated enough to allow adequate bile flow and absence of cholestasis. Moreover, in most patients (10) the anastomosis was kept patient for more than 1 year after stent removal, whereas only two patients had stricture recurrence and needed endoscopic restenting. Four patients dropped out of the study, respectively because of liver rejection (two), acute liver failure (one) and myocardial infarction (one). One patient who developed a stone of the transplanted CBD underwent surgical intervention. CONCLUSIONS According to our data, the endoscopic stenting of the CBD might be considered as the first choice procedure in the setting of the biliary anastomotic strictures occurring after liver transplantation. It has proved to be safe and effective, avoiding the need for more invasive surgery, which in any case should be considered for nonresponsive patients.

Biliary complications in orthotopic liver transplantation: experience with a modified technique of duct-to-duct reconstruction

Abstract. Biliary complications are described as frequent causes of morbidity during the postoperative course of orthotopic liver transplantation (OLTx), even in recent papers. The authors report here on their experience with duct‐to‐duct anastomosis as their method of choice for biliary reconstruction in a consecutive series of 100 OLTx in adult patients. The original technique, as described by Starzl, was modified by the authors by performing a wide, longitudinal plasty of both the donor and recipient bile ducts, joined together with two polidioxanone running sutures, producing the effect of a side‐to‐side anastomosis. This technique was used in all procedures, even when a significant discrepancy was evident between the ducts (n= 10). Follow‐up was completed in 100% of the patients for a period of 2–40 months (mean 13.1 months). Four major complications (4%) occurred including hepatic abscesses due to ascending cholangitis, T‐tube dislocation, partial occlusion by a branch of the T‐tube at the anastomotic site, and disruption of the bile duct after T‐tube removal. In four other patients, transient abdominal pain followed removal of the stent. Neither strictures nor fistulas were observed. Choledochocholedochostomy on a T‐tube stent represents, in our experience, the technique of choice for biliary reconstruction in OLTx. The procedure, as described in the present study, proved to be safe in preventing strictures and leakages and appears to be feasible in nearly 100% of all adult patients undergoing OLTx.

Incidence and clinical characteristics of posttransplant lymphoproliferative disorders: report from a single center.

Abstract In the period 1973‐1998, among 2139 allograft recipients treated with standard immunosuppression, posttransplant lymphoproliferative disorders (PTLD) developed in 19 patients (0.9%): one plasmacytic hyperplasia, two polymorphic PTLD, one myeloma, and 15 lymphomas. PTLD developed 1 year after transplantation (tx) in 14 patients. Five patients were diagnosed at autopsy, 2 were lost to follow up, 3 died before therapy could be instituted, and 1 patient has just started chemotherapy. Of the 8 evaluable patients, 2 received acyclovir and are alive in complete remission (CR) and 6 received chemotherapy ± surgery. Of these 6, 4 died of lymphoma and/or infection, 1 died of unrelated causes in CR, and 1 is alive in CR. PTLD is a severe complication of tx, usually running an aggressive course which may preclude prompt diagnosis and treatment. Nevertheless, therapy is feasible and must be tailored on the histologic subtype. Seventy‐four percent of patients were diagnosed with late‐onset PTLD stressing the need for long‐term follow up.

Early pancreas retransplantation for vascular thrombosis in simultaneous pancreas-kidney transplants.

Vascular thrombosis is still the leading cause of nonimmunologic, technical pancreatic transplant graft failures and usually occurs in the early postoperative period. Little data exist regarding the issue of pancreas retransplantation although it has been described for chronic rejection in pancreas transplant alone with poor results. From October 1993 to December 1996, 16 patients with type I diabetes mellitus and end-stage renal disease underwent to SPK at our Dept. of General Surgery and Adominal Organ Transplantation. Twelve were males and 4 females with a mean age of 36.8 (range 25 to 56). Therteen had bladder drainage (BD) and 3 enteric drainage (ED). One patient in the BD group and 1 patient in the ED group had vascular thrombosis of their pancreas graft 7 and 3 days after SPK respectively. Both patients presented hematuria, abdominal tenderness, pain and oedema of the ipsilateral lower limb. At operation, hemorragic necrosis involving the whole pancreas with thrombosis of portal vein extended in the external and common iliac veins was seen. Pancreasectomy and throm-bectomy associated to pancreas retransplantion was performed in 1 patient in the same time while in the other, pancreas retransplant was performed 1 day later. The postoperative course was uneventful and both patients were discharged 16 and 23 days p.o. They are alive and well 6 and 11 months with functioning grafts.

Prospective randomized trial of steroid withdrawal in liver transplant patients: preliminary report

Abstract Although steroid withdrawal has been successfully performed in heart and kidney transplant recipients, no controlled studies of SW have been carried out in liver transplant patients. To evaluate this possibility a prospective controlled study was carried out in 46 liver transplant recipients operated on after may 1991. They all received a sequential quadruple immunosuppression consisting of 3 mg/kg antithymocyte globulins (RATG) for the first 5 postoperative days, cyclosporin A (starting from day 3–5 and maintaining parenteral whole‐blood trough levels at 200–300 ng/ml during the first month and at 150–250 thereafter), azathioprine (1 mg/kg per day for the first month) and steroids. Prednisone was started at a dose of 200 mg per day 1 and then tapered to 20 mg/day over the first posteroperative week; this dose was maintained until day 90 when the patients were randomly allocated either to long‐term steroid therapy (0.1 mg/kg per day) or to steroid withdrawal. Minimum follow‐up after randomization was 6 months (6–27 months). Liver biochemistry was checked at regular intervals throughout the follow‐up period. Liver biopsies were performed whenever clinically indicated and also in the first 19 patients during readmission for annual review. The incidence ot acute and chronic rejection 90 days from liver transplantation was 2.5% in patients maintained on long‐term therapy. No patient in the steroid‐withdrawal group had experienced either an acute or a chronic rejection episode so far. Steroid‐related complications did not differ significantly between the two groups. The most recent interim analysis showed that steroid withdrawal is a safe undertaking in liver transplant recipients arid may be successfully accomplished in almost all patients.