Roberto Merenda

A comparative prospective study of two available solutions for kidney and liver preservation

Background. Viaspan (University of Wisconsin [UW]) solution is the gold standard for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low-potassium, low-viscosity solution, initially used for heart and lung preservation. We have performed a prospective multicenter study to compare the role of these cold-storage solutions on kidney and liver recovery after transplantation. Patients and Methods. From March 15, 2000 to December 31, 2001, 441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver transplants (LT) were included in the study. Results. Perfusate volume used was significantly lower in the UW group, being 4,732±796 mL versus 5,826±834 mL in the CEL group (P <0.001). In LT, median total bilirubin serum levels were significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and 92.3 μmol/L, respectively) as compared with CEL (51.3 and 63.4 μmol/L, respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups were 3.8% and 4.2% (P =NS) respectively, with 1-year graft and patient survival being 83.3% versus 85.4% (P =NS) and 89.9% versus 90.6% (P =NS). After RT, delayed graft function (DGF) rates were 23.2% and 22.7% (P =NS), respectively; PNF rates were 1.9% and 1.7% (P =NS) respectively, with 1-year graft and patient survival being 92.3% versus 94.2% (P =NS) and 99.4% versus 97.7% (P =NS). Conclusions. CEL solution was shown to be as effective as UW in both liver and kidney preservation. In LT patients, biliary function recovery is significantly better in the CEL group. CEL solution represents an efficacious option in multiorgan harvesting.

Epstein-Barr virus-associated post-transplant lympho-proliferative disease of donor origin in liver transplant recipients

BACKGROUND/AIMS Post-transplant lymphoproliferative disease, a potential complication of solid organ transplantation, occurs in about 3% of orthotopic liver transplant recipients. We report the genetic and virological characterization of two cases of post-transplant lymphoproliferative disease that occurred early (4 and 6 months) after orthotopic liver transplant as large-cell non-Hodgkins lymphomas located at the hepatic hilum. METHODS Lymphomatous tissues were analyzed for clonality and presence of Epstein-Barr virus (EBV) sequences by Southern blot, polymerase chain reaction, and in situ hybridization techniques. RESULTS The tumors in both cases were sustained by a clonal proliferation of B lymphocytes containing type A EBV DNA. Moreover, in situ hybridization with a digoxigenin-labeled EBV-specific probe evidenced a strong nuclear signal in most of the neoplastic cells. DNA microsatellite analysis at three different loci detected alleles of donor origin in both tumor samples, suggesting that the neoplastic B cells were of donor origin. CONCLUSIONS EBV-infected donor B lymphocytes might be responsible for intragraft post-transplant lymphoproliferative disease in orthotopic liver transplant recipients. As 20 to 30% of post-transplant lymphomas involve the graft itself, donor-derived post-transplant lymphoproliferative disease might be more frequent than presently appreciated. Prospective studies are needed to assess its real incidence and identify possible risk factors.

Different hemodynamic patterns of alcoholic and viral endstage cirrhosis: analysis of explanted liver weight, degree of fibrosis and splanchnic Doppler parameters.

Objective. In cirrhosis, portal hemodynamics is usually considered independently of the disease etiology. The objective of this study was to investigate the role of the etiology of liver disease on the relationship between liver blood flow and liver pathology in endstage cirrhosis. Material and methods. Portal blood velocity and volume, congestion index of the portal vein, and hepatic and splenic pulsatility indices were evaluated with echo-Doppler in cirrhotic patients immediately before liver transplantation. When a patent paraumbilical vein was present, its blood flow was measured and effective portal liver perfusion was calculated as portal blood flow minus paraumbilical blood flow. The hemodynamic parameters were correlated with liver weight and the pattern of the liver fibrosis morphometrically assessed in explanted livers. A total of 131 patients with alcoholic or viral cirrhosis were included in the study. Results. In alcoholic cirrhosis, liver weight was higher than that in viral disease (1246±295 g versus 1070±254 g, p=0.001), portal liver perfusion per gram of liver tissue was lower (0.49±0.36 ml g−1 min−1 versus 0.85±0.56 ml g−1 min−1, p=0.004) and hepatic pulsatility indices were higher (1.45±0.31 versus 1.26±0.30, p=0.018). The degree of liver fibrosis was similar in alcoholic and viral cirrhosis (11.7±5.5% versus 11.0±4.4%, p=NS). An inverse relationship between liver weight and Child-Pugh score was disclosed in viral (p<0.001) but not in alcoholic disease. Conclusions. A different hemodynamic pattern characterizes the advanced stage of cirrhosis of alcoholic and viral origin. A more severe alteration of intrahepatic portal perfusion, probably coexisting with a more severe hepatocyte dysfunction, and a higher liver weight can be detected in alcoholic cirrhosis.

Infrahepatic Terminolateral Cavo–Cavostomy as a Rescue Technique in Complicated “Modified” Piggyback Liver Transplantation

Orthotopic liver transplantation is a well-known and widely applied codified procedure. Milestones of the standard technique are the use of the veno– venous bypass (1, 2), and the resection, en bloc with the liver, of the retrohepatic vena cava (3–5). Since its original description by Starzl (3–4), many modifications of the original technique have been suggested to reduce risks and time and to make the technique more flexible. Also, the graft caval implant has undergone gradual evolution through the introduction of variants that render the surgical procedure more adaptable toward problems. These techniques apply the dissection of the recipient liver from the vena cava during hepatectomy (6); then the graft implant may be performed preserving the recipient vena cava, according to the piggyback procedure (7, 8), anastomosing the donor’s suprahepatic vena cava and a “cuff” made out of the recipient’s suprahepatic veins, or, as described by some authors (9), using a side-to-side cavo–caval anastomosis after stitching the donor’s suprahepatic caval stumps. In both cases, the remnant of the donor’s infrahepatic vena cava must be ligated. Since 1992 we have used a modified piggyback technique, by performing an end-to-side cavo– caval anastomosis between the suprahepatic donor’s vena cava and the recipient’s vena cava, using the caudally enlarged hole of the common left and middle suprahepatic veins stump, after stitching the recipient’s right suprahepatic vein (10). Also by this technique, the remnant of the donor’s infrahepatic vena cava must be ligated. A drawback of these techniques may be either hepatic venous outflow obstruction because of stenosis or kinking of the caval anastomosis, or obstruction of the recipient’s inferior vena cava (11). We report a case of hepatic venous outflow obstruction at liver reperfusion because of kinking of the caval anastomosis. The stenosis was overcome performing an end-to-side cavo–caval anastomosis using the infrahepatic stump of the donor’s vena cava.

Selective variceal decompression and its role relative to other therapies

Seventy patients, selected from 265 patients with proved variceal bleeding, underwent a distal splenorenal shunt (DSRS) procedure with or without splenopancreatic disconnection (SPD). Alcoholic cirrhosis was the cause of portal hypertension in 57% of the patients. The operative mortality was 13% (Childs classes A and B 2%, class C 66%). Despite fewer varices in all of the patients, variceal rebleeding and death occurred in one patient (2%). Late portal perfusion was observed in 91% of the patients, with worsening in 23%, compared with the preoperative study. Persistent hepatocyte necrosis and incomplete SPD were the most significant prognostic factors for decreased perfusion (presence and absence of necrosis, 38% and 12%, respectively; DSRS and DSRS with SPD, 43% and 12%, respectively). SPD also decreased ongoing hepatocyte damage. Post-shunt encephalopathy was clinically evident in 7% of the patients, but after electroencephalographic evaluation, it increased to 24.6%. Significant factors in its development included decreased portal perfusion (62% versus 14%), active hepatitis (48% versus 17%), and incomplete SPD (43% versus 14%). The higher late liver-related mortality was associated with a lack of or decreased portal perfusion and the absence of SPD.

Cerebral aspergillosis in a liver transplant recipient: a case report of long-term survival after combined treatment with liposomal amphotericin B and surgery

Cerebral aspergillosis is a life-threatening complication in liver transplant recipients, with mortality rates approaching 100%; treatment with amphotericin B is of limited efficacy because of its poor distribution in the cerebrospinal fluid and its systemic side effects. We report the case of a liver transplant recipient who developed recurrent cerebral Aspergillus fumigatus infection, and was successfully treated by combined surgical excision of the lesion and administration of liposomal amphotericin B. This first report of long-term complication-free survival in a liver transplant recipient suggests that therapy with liposomal amphotericin B may reduce the risk of recurrence of cerebral aspergillosis in these immunocompromised patients.

A rare surgical case of metachronous double carcinoma of the biliary tract

We report on a rare case of metachronous double carcinoma of the biliary tract, occurring in a 65-year-old male. The patient was admitted to the hospital with jaundice in March 2004. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) scans of the abdomen showed a minimally dilated intrahepatic biliary tree with normal-appearing choledocus. Obstruction of the common hepatic duct was revealed by endoscopic retrograde cholangiopancreatography (ERCP). The patient underwent a resection of the middle third of the extrahepatic duct and cholecystectomy (cholangiocarcinoma, pT1N0M0), with the surgical margins of resection showing as negative. After 2 years, during follow-up, the findings of a positron emission tomography (PET)-CT scan suggested a possible cholangiocarcinoma of the distal part of the biliary tract; CT and MRI scanning of the abdomen showed mild dilatation of the distal common hepatic duct; an ERCP showed mild dilatation of the retropancreatic remnant of the biliary tree with endoluminal defects. Eventually the patient underwent pancreaticoduodenectomy. The histopathological diagnosis of the resected specimen confirmed a cholangiocarcinoma; 10 lymph nodes were negative (pT1N0M0). At 6 months post-op after the second operation the patient is progressing well with no signs of recurrence. Patients with cholangiocarcinoma – in whom survival is prolonged with surgical resection – should undergo careful follow-up for both recurrence and second primary cancer. PET scanning seems to play the most important diagnostic role.

Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma

Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis.

The role of the leukocyte adherence inhibition (LAI), CA 19-9, and tissue polypeptide antigen (TPA) tests in the diagnosis of pancreatic cancer

The leukocyte adherence inhibition (LAI) assay measures host cell‐mediated tumor immunity. The original test used by Halliday and Miller was modified by substituting tissue extracts with purified tumor antigens (gastrointestinal cancer antigen [GICA]) with the aim of reducing false‐positive results in the diagnosis of patients with early pancreatic cancer. By our modified technique, the LAI assay identified four of five pancreatic cancers at an early stage and gave only one false‐positive result in 16, showing a sensitivity of 80% and a specificity of 94%. Later stages of the disease responded poorly on the test. These results were significantly better than those by the CA 19‐9 and tissue polypeptide antigen (TPA) tests. Should our findings be confirmed in larger material over a longer follow‐up period, the LAI test could be proposed as a useful tool in the early diagnosis of pancreatic cancer.

Pancreaticoduodenectomy for dysplastic duodenal adenoma in a patient with familial adenomatous polyposis

Colorectal polyposis is the main feature of familial adenomatous polyposis (FAP), but benign and malignant lesions have also been described in the stomach, duodenum, small bowel, biliary tract and pancreas. There are few reports on FAP patients with duodenal polyps that developed at a younger age and even fewer on cases with dysplastic degeneration. The progression to carcinoma usually presents quite late in the clinical history of FAP patients, typically at least 20 to 25 years after proctocolectomy. This report described the rare case of a patient presenting with duodenal adenomas with dysplastic changes and tumor infiltration as the first sign of FAP, who was treated by pancreaticoduodenectomy followed by proctocolectomy for subsequent dysplastic changes in colonic polyps.