Percutaneous transhepatic endoscopic electrohydraulic lithotripsy of biliary tract calculi after orthotopic liver transplantation

The development of biliary tract calculi after orthotopic liver transplantation presents a unique clinical problem. Previously described techniques for removing biliary stones by shock wave lithotripsy, litholytic therapy with oral bile acids, and endoscopic mechanical extraction may be ineffective or contraindicated in liver transplant patients. For this reason, percutaneous transhepatic electrohydraulic lithotripsy (EHL) was performed using an 11 French flexible ureteroscope in two pediatric patients who developed biliary tract calculi following orthotopic liver transplant. There were no complications and postoperative follow-up over 4 years has been uneventful. To our knowledge, these represent the first reported cases of percutaneous transhepatic endoscopic EHL to fragment biliary tract stones in a transplanted liver, which for us has been a safe and effective therapeutic option.     

Disease recurrence after orthotopic liver transplantation

With the advent of cyclosporine immunosuppression in the late 1970s, liver transplantation became a widespread modality for the treatment of end-stage liver disease. Several metabolic disorders that produce liver injury, such as Wilson's disease and alpha-1-antitrypsin deficiency, are cured by liver transplantation. However, many other diseases for which transplantation is undertaken may recur in the allograft. As follow-up increases and newer diagnostic modalities become available, those diseases that recur, and their natural histories, are becoming better understood. This new information may lead to a reevaluation of the suitability of some conditions for transplantation. This article briefly reviews disease recurrence in orthotopic liver transplants.     

Infant survival after orthotopic liver transplantation

Of all head and neck neoplasms, 3% are malignant salivary neoplasms. Only 20% of them affect submandibular glands. These tumours vary histologically, which results from the complex embryogenesis of the glands. Malignant submandibular gland tumours are twice as frequent as parotid gland tumours. Simultaneous occurrence of quite different malignant tumours in the same salivary gland is extremely rare. The age range of patients affected with salivary gland neoplasms is wide. However, the occurrence of these neoplasms in children is exceptionally rare. The authors describe a case of a 13-year-old girl with acinose adenoid carcinoma and cystiscarcinoma coexisting in one submandibular salivary gland.     

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

K02 (morpholine-urea-Phe-Hphe-vinylsulfone), a newly developed peptidomimetic, acts as a potent cysteine protease inhibitor, especially of cathepsins B and L (which are associated with cancer progression) and cruzain (a cysteine protease of Trypanosoma cruzi, which is responsible for Chagas' disease). Here we investigated features of the disposition of K02 using in vitro systems, characterizing the interaction of the drug with human cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp), a mediator of multidrug resistance (MDR) to cancer chemotherapy and a countertransporter in the intestine that limits oral drug bioavailability. P-gp functions as an ATP-dependent drug efflux pump to reduce intracellular cytotoxic concentrations. An HPLC assay was developed to analyze K02 and its metabolites formed in human liver microsomes. Three major primary metabolites were determined by LC/MS/MS to be hydroxylated products of the parent compound. A rabbit anti-CYP3A polyclonal antibody (200 microl antibody/mg microsomal protein) produced 75-94% inhibition of the formation of these three hydroxylated metabolites. Ketoconazole (5 microM), a selective CYP3A inhibitor, produced up to 75% inhibition, whereas other CYP-specific inhibitors, i.e. quinidine (CYP2D6), 7,8-benzoflavone (CYP1A2), and sulfaphenazole (CYP2C9), showed no significant effects. An identical metabolite formation profile for K02 was observed with cDNA-expressed human CYP3A4 (Gentest). These data demonstrate that K02 is a substrate for CYP3A. Formation of 1'-hydroxymidazolam, the primary human midazolam metabolite, was markedly inhibited by K02 via competitive processes, which suggests the potential for drug-drug interactions of K02 with other CYP3A substrates. K02 significantly inhibited the photoaffinity labeling of P-gp with azidopine and LU-49888, a photoaffinity analogue of verapamil. Transport studies with [14C]K02, using MDR1-transfected Madin-Darby canine kidney cell monolayers in the Transwell system, demonstrated that the basolateral-to-apical flux of K02 across MDR1-transfected Madin-Darby canine kidney cells was markedly greater than the apical-to-basolateral flux (ratio of 63 with 10 microM [14C]K02). This suggests that K02 is also a P-gp substrate. These studies are important for formulating strategies to increase the absorption and/or decrease the elimination of K02 and to optimize its delivery to malignant cells and parasite-infected host cells.     

Successful steroid treatment of idiopathic thrombocytopenic purpura after orthotopic liver transplantation for primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver frequently associated with extrahepatic autoimmune phenomena. Specific antibodies against platelet glycoproteins may play an important role in the pathogenesis of thrombocytopenia associated with PBC. This is the first report of life-threatening idiopathic thrombocytopenic purpura successfully treated with steroids in a 62-yr-old woman 2 yr after liver transplantation for PBC.     

Overview: biliary reconstruction after liver transplantation

Changes of intracellular calcium homeostasis in epithelial cell damage of renal tubules caused by cadmium and its relationship with the damage were studied in isolated tubular cells of rabbits. Results showed levels of free calcium (Ca++) in tubular cytoplasm increased significantly with the treatment of cadmium, and a series of cellular ultrastructure were damaged. A calcium channel blocker, phenothiazine, showed blocking and protecting effects on it. This suggested calcium overload played a very important role in kidney damage caused by cadmium.     

Partial orthotopic liver transplantation

From October 1990 to May 1992, nine of 38 patients with liver transplants (24%) had partial orthotopic liver transplantation on account of lack of size-matching donor livers. The preliminary results have presented very few problems; there was no per- or postoperative mortality and no surgical complications. Four patients had episodes of acute rejection which responded to anti-rejection therapy, and two patients were treated for CMV infection. All patients are discharged with normal liver function 4-9 weeks after transplantation (median 5 weeks). The method seems to be safe and can be used in centers with limited activity, where there is a problem of having the correct liver at the correct time.     

Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis

Primary biliary cirrhosis is an autoimmune disease characterized by high titer autoantibodies predominantly against mitochondrial antigens PDC-E2, BCOADC-E2 and OGDC-E2. Currently orthotopic liver transplant (OLT) is the major form of treatment for end-stage primary biliary cirrhosis (PBC), but it is still unclear whether the autoimmune response continues post-transplantation. In this study we took advantage of a well-defined collection of sera collected serially before and after liver transplantation. We assayed these sera for quantitative and isotype-specific titers of antibodies against a set of recombinant mitochondrial autoantigens. We also studied reactivity to gp210. Serum samples were taken before transplantation and at intervals of 6 months, 1, 2, and 3 years after OLT. Before OLT 24/35 patients were AMA-positive, including seven out of the 35 to PDC-E2 alone, eight to both PDC-E2 and OGDC-E2, six to both PDC-E2 and BCOADC-E2, two to BCOADC-E2 alone and one to OGDC-E2. Following OLT, the frequency of sera that responded to PDC-E2 alone increased from seven to 12/35. Similarly, reactivity to BCOADC-E2 slightly increased from two to four out of 35. However, there was an overall decrease in sera that responded to more than one antigen. Neither Ig isotype nor subclass of the autoimmune response changed following OLT. Findings with gp210 were similar, in that reactivity to gp210 was found in nine out of 35 patients pre-OLT; following OLT the frequency decreased to seven out of 35 patients. Overall, the titers of AMAs decline slightly during the first year post-OLT, but are equivalent to pre-OLT values by 6 months. Moreover, the antibody subclass/ isotype remained unchanged. These data suggest that the removal of a diseased PBC liver has little, if any, impact on the serological characteristics of PBC. Moreover, it provides information regarding the natural history of PBC, particularly on the long latency time for disease development.     

Q-T interval prolongation in liver cirrhosis. Reversibility after orthotopic liver transplantation

Squamous carcinoma of the bladder is a rare tumour, little known in Western countries in contrast with the high incidence in the Middle East and East Africa. It has a sex-ratio of 1 and black populations appear to be preferentially affected. Several recent theories of carcinogenesis elucidate the pathophysiology of this tumour. Its risk factors essentially consist of urinary schistosomiasis and mechanical and chemical vesical irritant factors. The diagnosis of this cancer is often delayed, but can be facilitated by strict follow-up of high-risk patients. Prevention appears possible in these patients. Its prognosis, traditionally poor, essentially depends on tumour stage and grade. Treatment is surgical, essentially radical cystectomy, which has a real therapeutic efficacy. The respective roles of chemotherapy and radiotherapy are currently under evaluation.     

Pathogenesis of early operative site infections after orthotopic liver transplantation

BACKGROUND: We hypothesized that operative site infections after orthotopic liver transplantation arise from bacteria in bile or jejunum. METHODS: To ascertain the validity of this hypothesis and to assess the effect of systemic antibiotic prophylaxis, we obtained intraoperative cultures of peritoneum, fascia, explant and donor liver bile, and jejunal lumen in 77 liver transplantations, and we monitored outcome. RESULTS: Pathogens were recovered from peritoneum, fascia, or bile in 11 cases. By univariate analysis, a positive culture was significantly associated with choledochojejunostomy (P=0.0002), previous liver transplantation (P=0.0002), and previous hepatobiliary surgery (P=0.002). Operative site infections during the first 2 weeks after transplantation occurred only in cases with positive intraoperative cultures, and three of the four infections were caused by the same bacteria detected intraoperatively. Antibiotic susceptibility of intraoperative isolates was tested in nine cases; infection occurred in two of three cases in which the isolates were resistant to the systemic antibiotic prophylaxis and in none of six cases with susceptible isolates. CONCLUSIONS: Our findings suggest that systemic antibiotic prophylaxis for more than 2 days may be beneficial in cases with bacterial contamination of the operative site but may not be necessary in other cases.     

Rehabilitation of patients with alcoholic liver cirrhosis after orthotopic liver transplantation: a 7-year follow-up

Endemic infectious diseases still constitute a threat to Latin American countries. In view of this, research on tropical medicine should be encouraged, particularly in countries like Brazil where this kind of scientific investigation was historically highly early in this century. It is suggested that more resources should be made available to stimulate such studies and the publication in English, Portuguese and Spanish.     

Impact of N-acetylcysteine on the hepatic microcirculation after orthotopic liver transplantation

Recent observations showed an improvement of hepatic macro- and microhemodynamics as well as survival rates after warm ischemia of the liver following treatment with N-acetylcysteine (NAC). In this study we assessed the influence of NAC on the hepatic microcirculation after orthotopic liver transplantation (OLT) using intravital fluorescence microscopy. OLT with simultaneous arterialization was performed in 16 male Lewis rats following cold storage in University of Wisconsin solution for 24 hr. Within the experimental group (n = 8) donors received NAC (400 mg/kg) 25 min before hepatectomy. In addition, high-dose treatment of recipients with NAC (400 mg/kg) was started with reperfusion. Control animals (n = 8) received an equivalent amount of Ringer's solution. Intravital fluorescence microscopy was performed 30-90 min after reperfusion assessing acinar and sinusoidal perfusion, leukocyte-endothelium interaction, and phagocytic activity. Treatment with NAC reduced the number of nonperfused sinusoid from 52.4 +/- 0.8% to 15.7 +/- 0.5% (p = 0.0001) (mean +/- SEM). Furthermore, we achieved a significant reduction of leukocytes adhering to sinusoidal endothelium (per mm2 liver surface) from 351.9 +/- 13.0 in controls to 83.6 +/- 4.2 in the experimental group (P = 0.0001). In postsinusoidal venules, treatment with NAC decreased the number of sticking leukocytes (per mm2 endothelium) from 1098.5 +/- 59.6 to 425.9 +/- 37.7 (P = 0.0001). Moreover, bile flow was significantly increased after therapy with NAC (4.3 +/- 1.2 vs. 2.2 +/- 0.7 ml/90 min x 100g liver) (P < 0.05). Phagocytic activity was not influenced by application of NAC. We conclude that high-dose therapy with NAC in OLT attenuates manifestations of microvascular perfusion failure early after reperfusion and should be considered as a means to reduce reperfusion injury.