Pediatric liver transplantation: preliminary results at Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione.

Between July 2003 and November 2004 14 pediatric liver transplantations (LTx) have been performed in 12 children using cadaveric donors. The primary diseases were as follows biliary atresia in 9 cases, whereas the other 3 children were affected by cystic fibrosis, Langherans cells histiocytosis, and hepatoblastoma, respectively. Median patient waiting time was 103 days (range, 2-158); no patient died while on the waiting list. Patients who underwent transplantation included 7 boys and 5 girls, ranging in age from 6 months to 14 years (median age, 5 years). Recipient median weight was 16 kg (range, 6-38). Donor median age was 19 years (range, 3-47), whereas donor median weight was 74 kg (range, 15-90). All children who underwent primary LTx were United Network for Organ Sharing (UNOS) status 2B. Of the 12 transplanted patients, 9 received a left lateral segment (LLS) from an in situ split liver, whereas 3 received a whole graft. Two children developed an episode of acute cellular rejection on the seventh postoperative day, which was treated successfully with a course of intravenous steroids for 3 days. After a median follow-up of 245 days, 10 children are alive but 2 children died due to primary nonfunction (PNF) on the second postoperative day and septic shock on the fifth postoperative day after retransplantation for acute hepatic artery thrombosis, respectively. One child who underwent retransplantation for hepatic artery thrombosis on the 31st postoperative day after primary LTx is currently alive. Evaluation of our initial data suggests that the split liver technique has the potential to meet the needs of pediatric LTx allowing grafting early in the course of the original disease and reducing waiting time.

Changes in serum electrolytes during treatment of patients in liver failure with molecular adsorbent recirculating system.

PURPOSE: To study the effect of MARS on serum electrolytes during liver failure. DESIGN: Twenty-three patients admitted to a quaternary health care facility from September 2000 to May 2002, 22 adults and 1 child, 11 males (48%) and 12 females (52%), age 15-70 (median 53), treated with MARS for: 12 acute-on-chronic liver failure (52%); 4 fulminant hepatic failure (17%); 3 intractable pruritus (13%); 2 primary-non-function (9%); 2 following major liver resection (9%). PROCEDURES: Sodium, potassium, chloride, phosphorus, calcium, and magnesium were measured in the serum, ultrafiltrate and albumin circuit before and after MARS. STATISTICAL METHODS: A comparison of electrolyte concentrations, before and after MARS, was performed using a paired t test. MAIN FINDINGS: Serum electrolyte concentrations before and after MARS, while statistically significant in some cases, were very small, and of no clinical relevance. CONCLUSION: MARS exchanges potassium, chloride, calcium, and magnesium by ultrafiltration; sodium by the albumin dialysis.

[Short bowel syndrome: etiologic, pathogenetic aspects and principles of treatment]. / La sindrome da intestino corto: considerazioni etio-patogenetiche e principi di trattamento.

A significant problem in surgery following massive intestinal resection is the short bowel syndrome characterized by severe fluid and electrolyte loss, watery diarrhoea and malnutrition. Total parenteral nutrition and enteral nutrition are essential in the clinical course of the syndrome; their use for prolonged periods results in the gradual intestinal adaptation and greater absorptive and reservoir capacities of the intestinal remnant. Adjunctive surgery can slow rapid intestinal transit and induce growth of neo-small-bowel mucosa but is not recommended for routine use. The early results of intestinal transplantation in the treatment of short bowel syndrome are encouraging. Furthermore chronic rejection and systemic sepsis with failure of the graft must be considered and indicate that at present this procedure cannot be offered to every patient but will be a potential form of therapy in future.

Rejection of human intestinal allografts: alone or in combination with the liver.

The current results of the present series demonstrate that intestinal allografts are more vulnerable to rejection and continue to be at a significantly higher risk long after transplantation compared with isolated liver allograft recipients. Unexpectedly, a combined liver allograft does not protect small bowel from rejection. The necessarily continuous heavy immunosuppression for these unique recipients is potentially self-defeating. This is clearly demonstrated by their high susceptibility to early and late infectious complications after transplantation as reported in this issue. With the minimal graft-versus-host disease threat in this clinical trial, our revised protocol for future intestinal transplantation is to maximize the passenger leukocyte traffic with supplementary bone marrow from the same intestinal donor in an attempt to augment the development of systemic chimerism and the gradual induction of donor-specific nonreactivity.

The latest advances in liver transplantation at the pittsburgh transplantation institute: evolution of FK506, liver-intestinal transplantation, clinical xenotransplantation, and the induction of graft acceptance.

During the past 30 years orthotopic liver transplantation (OLTx) has become a highly successful form of therapy, and as of this writing it is being performed at more than 100 institutions in the U.S., and a similar number in Europe. This is testimony to the great advances achieved in this field since the 1960s and 1970s, when there were essentially only two places actively engaged in liver transplantation. Essential to its success have been the technical refinements introduced during the last three decades, which have allowed many surgeons around the world to be able to do the procedure safely. Liver transplantation is still considered as one of the most complex operations, and therefore the margin of error is small and attention to technical detail is crucial to a satisfactory outcome. This is magnified in importance since OLTx, unlike kidney, heart, pancreas and intestinal transplantation, lacks a back-up system, such as dialysis, ventricular assist device, insulin or total parenteral nutrition. Thus, the smallest mistake in the surgical management of the patient may prove fatal.

Effect on the canine Eck fistula liver of intraportal TGF-beta alone or with hepatic growth factors.

Transforming growth factor-beta canceled the hepatocyte proliferation caused by transforming growth factor-alpha when the two substances were mixed and administered through a disconnected central portal vein branch after creation of an Eck fistula. In contrast, transforming growth factor-beta had no antidotal action on the stimulatory effects of insulin or full test doses of insulinlike factor-2, hepatocyte growth factor, epidermal growth factor or triiodothymanine. A minor antidotal effect on hepatic stimulatory substance activity could be detected, but only with hepatic stimulatory substance was given in doses smaller than those known to cause maximum stimulatory response. These results suggest a highly specific pharmacological and physiological interaction between transforming growth factor-alpha and transforming growth factor-beta in the modulation of liver growth control.

Outcome of hepatic amebic abscesses managed with three different therapeutic strategies.

Three different approaches to hepatic abscesses due to Entamoeba histolytica were compared in 51 patients. The three modes of therapy utilized were: medical therapy with nitroimidazoles (N = 11 patients), open surgical drainage (N = 9 patients), and percutaneous drainage using ultrasound guidance followed by intralesional nitroimidazole administration (N = 31 patients). The results with each form of therapy were assessed clinically and by abdominal ultrasound. Patients receiving combined US-guided drainage and intralesional chemotherapy experienced a faster and overall better clinical response, which was confirmed also by sonographic follow-up of the hepatic lesions. This better response was associated with faster resolution, fewer relapses, and less residual hepatic scarring than either with medical therapy alone or open surgical drainage combined with medical therapy.

Cyclosporine and liver regeneration studied by in vivo 31P nuclear magnetic resonance spectroscopy.

The changes in fructose-1-phosphate (F-1-P), intracellular pH, and ATP content of the liver after a fructose challenge were investigated noninvasively in vivo using phosphorus-31 nuclear magnetic resonance spectroscopy of dog liver four days after a portacaval shunt (PCS) with or without portal venous infusion of cyclosporin (CsA). The F-1-P metabolism was slower in PCS dogs (N = 2) as compared to either the normal (N = 2) or PCS + CsA-treated dogs (N = 3) (P less than 0.05). The intracellular pH temporarily decreased from 7.3 +/- 0.05 to 7.0 +/- 0.05 during the fructose challenge. The regenerative indexes were increased in the PCS + CsA group (P less than 0.01). These data obtained in vivo using 31P-NMR spectroscopy in the liver following a portacaval shunt, suggest that: (1) the energy status of the liver and the metabolic response to fructose are reduced in PCS compared to normal animals and (2) CsA treatment enhances the regenerative response of the liver and prevents the reduction in hepatic function associated with portacaval shunting.

Effect of cold ischemia time on the early outcome of human hepatic allografts preserved with UW solution.

Five hundred ninety-three cadaveric livers were used for primary liver transplantation between October 24, 1987, and May 19, 1989. The grafts were procured with a combined method, using in situ cooling with cold electrolyte solution and backtable flushing with UW solution. The mean cold-ischemia time was 12.8 (range 2.4-34.7) hr. The cases were divided into 5 groups according to the cold-ischemia time: group 1: less than 10 hr (n = 223); group 2: 10-14 hr (n = 188); group 3: 15-19 hr (n = 101); group 4: 20-24 hr (n = 52); and group 5: greater than or equal to 25 hr (n = 29). There was no difference between the 5 groups in 1-year patient survival, highest SGOT in first week after operation, and SGOT and total bilirubin during the first month after operation. However, with a logistic regression model, the retransplantation rate (P = 0.001) and primary nonfunction rate (P = 0.006) significantly rose as cold-ischemia time increased, meaning that the equivalency of patient survival was increasingly dependent on aggressive retransplantation.

Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo.

The effect of cyclosporin A on the hepatic energy status and intracellular pH of the liver and its response to a fructose challenge has been investigated using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy in dogs. Three experimental groups were studied: (a) control dogs (n = 5), (b) dogs 4 days after the creation of an end-to-side portacaval shunt (n = 5), and (c) dogs 4 days after portacaval shunt and continuous infusion of cyclosporin A (4 mg/kg/day) by way of the left portal vein (portacaval shunt plus cyclosporin A, n = 5). The phosphorus-31 nuclear magnetic resonance spectra were obtained at 81 MHz using a Bruker BIOSPEC II 4.7-tesla nuclear magnetic resonance system equipped with a 40-cm horizontal bore superconducting solenoid. The phosphomonoesters (p less than 0.01), inorganic phosphate and ATP levels (p less than 0.05) were decreased significantly in portacaval shunt-treated and in portacaval shunt-plus-cyclosporin A-treated dogs compared with unshunted control dogs. After a fructose challenge (750 mg/kg body wt, intravenously), fructose-1-phosphate metabolism was reduced in portacaval shunt-treated dogs compared with either the normal or portacaval shunt-plus-cyclosporin A-treated dogs (p less than 0.05). Both portacaval shunt- and portacaval shunt-plus-cyclosporin A-treated dogs demonstrated a reduced decline in ATP levels after fructose infusion when compared with the controls (p less than 0.05). Immediately after the fructose challenge, the intracellular pH decreased from 7.30 +/- 0.03 to 7.00 +/- 0.05 in all animals (p less than 0.01) and then gradually returned to normal over 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The hepatotropic influence of cyclosporine.

The effect of cyclosporine on liver regeneration has been investigated in 25 dogs that underwent an end-to-side portacaval shunt (Eck fistula) followed by 4 days continuous infusion of the drug into the left branch of the portal vein. Three different cyclosporine infusion rates were used: 0.06, 0.6, and 4.0 mg/kg/day. Control animals received the intravenous vehicle of cyclosporine at the same rate as the treated animals; a second control group received insulin, 0.42 units/kg/day. Hepatocyte 3H-thymidine-labeled mitoses (index of hyperplasia) and hepatocyte volume (index of hypertrophy) were studied in the left (infused) and right (control) lobes in each animal. Cyclosporine vehicle had no measurable effect on hepatocytes that suffered typical atrophy and moderate increase in mitotic index after the Eck fistula. Cyclosporine infusion stimulated cell renewal significantly and restored hepatocyte size in the infused lobes with a dose-response relation. Similar positive effects were observed in the right (nonperfused) lobes, although they were less than those in the left (infused) lobes. This was because of an unmistakable spillover of cyclosporine from the infused lobes, especially in the large-dose group. No sign of hepatotoxicity was detected at any cyclosporine infusion rate. Cyclosporine has a remarkable hepatotropic effect that may be helpful in the context of liver transplantation.