Outcome of cirrhotic patients with incidental hepatocellular carcinoma undergoing liver transplantation.
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Biomedical subjects
Publications and source records attributed to E Hidalgo.
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BACKGROUND: Only two previous cases of villoglandular adenocarcinoma of the vulva, an entity morphologically similar to tumors found in the uterine cervix and colorectum, have been reported. This paper communicates the first complete immunohistochemical study in villoglandular adenocarcinoma in order to determine its phenotype and histogenesis. CASE: A 69-year-old woman had a 1.5-cm nodule in the right labium majus. Histologically, it corresponded to a minimally atypical, villoglandular adenocarcinoma with a small microinvasion. Immunohistochemically, it was positive to OC125, CEA, and OC19.9 and coexpressed cytokeratins 7 and 20. Chromogranin, nuclear estrogen, and progesterone receptors were negative. CONCLUSION: Phenotypic expression was more consistent with a papillary mucinous ovarian or cervical neoplasm than of a colonic one. Its behavior was similar to that of its morphologic counterpart in the cervix, since the patient had no recurrence 3 years after a wide local excision.
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AIM: To present the results of hepatectomies performed for hepatocellular carcinoma in a specialist unit and to compare the results of an initial period (1987-1993) with those obtained in a second period (1995-2000) in which the indications were limited to Child class A patients without portal hypertension. During the second period technical improvements such as intermittent selective hilar clamping and greater hiliar restrictions on transfusions were introduced. PATIENTS AND METHODS: One hundred and ten hepatectomies were performed in 105 patients with hepatocellular carcinoma in our unit over a 12-year period. Eighty percent of the tumors occurred in cirrhotic livers, mainly caused by hepatitis C virus. In the second period, upper gastrointestinal endoscopy was systematically performed to study the presence of varices. Hemodynamics studies were optionally performed to rule out portal hypertension. RESULTS: In the second period larger tumors were resected, a greater number of major hepatectomies were performed due to the increased frequency of hepatocellular carcinoma in non-cirrhotic liver, and fewer patients underwent transfusion. Early mortality was reduced from 21% to 1.8% and mean survival significantly increased from 37 to 52 months. Actuarial survival increased from 64% to 91% at 1 year and from 23% to 52% at 5 years in the first and second periods, respectively. Disease-free survival also increased significantly from 53% and 84% at 1 year and 27% and 40% at 5 years in the first and second periods, respectively. Analysis of the results in cirrhotic patients also showed a statistically significant improvement in early mortality and survival. Multivariate analysis of prognostic factors for survival demonstrated that the absence of blood transfusion, patients who underwent resection in the second period and the presence of pseudocapsules were independent factors for increased survival. CONCLUSIONS: The results of liver resection for hepatocellular carcinoma improved significantly due to the reduction in early mortality produced by more rigorous patient selection and the introduction of technical improvements.
UNLABELLED: Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported. AIM: To evaluate the effect of portal vein arterialization on hepatic hemodynamics and long-term clinical outcome in three patients undergoing liver transplantation. METHODS: Two patients with extensive splanchnic venous thrombosis received an orthotopic liver transplant and one with fulminant hepatic failure received an auxiliary heterotopic graft. Portal vein arterialization was performed in all cases. RESULTS: One patient died 4 months after transplant and two are still alive. Auxiliary liver graft was removed 3 months post-transplant when complete native liver regeneration was achieved. Immediate post-transplant liver function was excellent in all cases. Only one patient developed encephalopathy and variceal bleeding owing to prehepatic portal hypertension secondary to arterioportal fistula 14 months after transplant. He was successfully treated by embolization of the hepatic artery. Hepatic hemodynamic measurements demonstrated a normal pressure gradient between wedged and free hepatic venous pressures in all cases. Liver biopsy showed acceptable graft architecture in two cases and microsteatosis in one. CONCLUSIONS: Liver transplantation with portal vein arterialization is an acceptable salvage alternative when insufficient portal venous flow to the graft is present. The double arterial supply does not imply changes in hepatic hemodynamics, at least in the early months post-transplant.
Sodium hypochlorite, the most widely used antimicrobial active chlorine compound in chemical disinfection, is little used as an antiseptic in clinical practice. This study aimed to assess the capacity of hypochlorite to alter human dermal fibroblast growth in vitro in relation to the concentration and exposure time. Effects of decreasing concentrations of hypochlorite (0.5%-0.00025%) on fibroblast adherence capacity and proliferation, according to varying exposure times and fetal calf serum (FCS) concentrations were investigated combining XTT assay, which provides cytochemical quantification of metabolically-active cell number, and total cell protein content, an indirect method for assessing substrate-adhered cell number. Initial cytotoxicity was produced at 0.0075% hypochlorite within contact time of two hours, provoking concentration-dependent cell detachment. From 0.1% upwards, NaOCl exerted a profound cytotoxic effect on fibroblasts. At later stages (4 h) and concentrations > or = 0.01% hypochlorite produced dose-dependent mitochondrial dysfunction: cell survival progressively diminished from 71% to 10%. Cytotoxic effects were not significantly affected by exposure-time periods, probably because maximum chlorine is released within the first four hours. Hypochlorite concentrations from 0.005% to 0.00025% were found to have no inhibitory effects on cell growth; in fact, they appear to exhibit the opposite effect. Increments in protein content found after 24 h exposure ranged from 30% to 120% above control values. Hypochlorite is highly cytotoxic for fibroblasts at concentrations > or = 0.01% provoking concentration-dependent loss of cell adherence capacity and mitochondrial dysfunction. In contrast, a mitogenic effect was observed with concentrations < or = 0.005% which supports NaOCl as a source growth-promoting activity in cultured human fibroblasts. Hypochlorite proved to be a highly reactive molecule which inhibits or stimulates cell division according to the concentration.
Several previous reports have suggested that autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in a single gene (the PKDH1 gene). Linkage analysis showed a positive linkage for polymorphic markers at the short arm of chromosome 6 (6p) in all families. PKHD1 has not been cloned. Recombinants in the critical region would permit the narrowing of the 6p interval containing the PKHD1 gene, thus facilitating the final identification (cloning) of this gene. Our study included 30 Spanish families. Each family consisted of both parents and at least two children, with at least one diagnosed with ARPKD by clinical and pathological parameters. DNA was obtained and 6p microsatellite markers were used to establish haplotypes for each family. A positive linkage to chromosome 6p was found for all families. In 2 cases, recombinants in the region containing the PKHD1 gene were found. These families will help narrow the size of the 6p region, facilitating the efforts to position and clone the PKHD1 gene. In conclusion, our analysis of Spanish ARPKD families confirms the lack of linkage heterogeneity. This suggests that mutations at a single locus on chromosome 6p21.1-p12 are responsible for the broad clinical spectrum of variable phenotypes.
Auxiliary liver transplantation for patients with fulminant hepatic failure supports the patient's failing liver for a period of time until the native liver (NL) has recovered and immunosuppression can be withdrawn. Auxiliary heterotopic liver transplantation (AHLT) with portal vein arterialization (PVA) has several advantages over auxiliary orthotopic liver transplantation: NL resection is not required, and the hepatic hilum is left untouched; thus, the chances of liver regeneration are optimal. The successful application of emergency AHLT with PVA in a young patient who developed toxic fulminant hepatic failure caused by tuberculostatic drugs is described. Two and one-half months after the procedure, the NL had completely regenerated; the graft was removed, and immunosuppression was suspended.
Two patients with previous distal splenorenal shunts (DSRSs) performed 6 years earlier underwent liver transplantation (LT). A preoperative selective mesenteric artery angiogram showed collateral veins draining mesenteric venous flow into the shunt. Intraoperative flow measurements were performed to assess the steal of portal venous flow by the shunt and determine the need for shunt occlusion. Portal vein, hepatic artery, and shunt flows were measured by ultrasound transit-time flow probes in the native liver and after graft implantation with and without temporary shunt occlusion. Hemodynamic studies showed that long-standing DSRSs are high-flow shunts that steal portal flow. After graft implantation, DSRS flows remained high. Occlusion of the shunts produced an increase in portal vein flow at an amount similar to those of splenorenal shunt. Thus, the flow measurements showed persistent steal by the shunts after graft implantation and, therefore, the DSRSs were occluded but splenectomy was not performed. We conclude that the decision to occlude a DSRS should be based on the demonstration of steal of portal flow by the shunt and reversibility once the shunt is occluded. Splenectomy is not required when the DSRS is occluded.
The aim of this study was to compare the long-term effect of tacrolimus and cyclosporine therapies on serum cholesterol levels in liver transplant recipients. We retrospectively studied 127 consecutive adult liver transplant recipients who survived for at least 1 year after transplantation. Basal immunosuppression consisted of cyclosporine plus prednisone in 100 patients and tacrolimus plus prednisone in 27 patients. Hypercholesterolemia was defined as a fasting serum cholesterol level greater than 220 mg/dL. Mean follow-up was 39 months. No statistical significance was found between cyclosporine- and tacrolimus-treated patients regarding age, sex, diagnosis, and previous cholesterol levels; both groups were similar. Significantly more tacrolimus-treated patients were steroid free in the first and second year of follow-up (tacrolimus, 37% and 63%; cyclosporine, 13% and 32%, respectively; P <.01). In the third year of follow-up, this difference was not significant (77% v 56%). The overall incidence of hypercholesterolemia was 34.6% (44 patients). At the end of the study, hypercholesterolemia was found in 24 of 51 and 14 of 70 patients with and without steroids, respectively (P <.002). Also, mean cholesterol levels were 224 +/- 70 and 191 +/- 48 mg/dL before and after steroid withdrawal, respectively, P <.001. Hypercholesterolemia was found in 43.7% of the patients during cyclosporine plus prednisone therapy compared with 46.1% of the patients during tacrolimus plus prednisone therapy (P <.9). Greater mean cholesterol levels were found in the cyclosporine group, particularly in the second and third years of follow-up (P <.01). Hypercholesterolemia was found in 22% of the patients during cyclosporine monotherapy compared with 15% during tacrolimus monotherapy (P <.5). No differences were found in mean cholesterol levels during follow-up when both monotherapy groups were compared. In conclusion, a lower incidence of hypercholesterolemia was achieved in tacrolimus-treated patients, mainly when steroids were still part of the immunosuppressive treatment.
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Linguatula serrata is a pentastomid, a cosmopolitan parasite belonging to the Phylum Pentastomida. Humans may act as an intermediate or accidental definitive host of this parasite, manifesting the nasopharyngeal or visceral form, with the latter having been described more frequently. The occurrence of ocular linguatuliasis is extremely rare, but it has been reported in the United States and Israel. The objective of the present paper was to report the first case of ocular linguatuliasis in Ecuador and to extend the morphologic study of L. serrata by morphometric analysis. The patient studied was a 34-year old woman from Guayaquil, Ecuador who complained of ocular pain with conjunctivitis and visual difficulties of two-months duration. Biomicroscopic examination revealed a mobile body in the anterior chamber of the eye. The mobile body was surgically removed. The specimen was fixed in alcohol, cleared using the technique of Loos, stained with acetic carmine, and mounted on balsam between a slide and a coverslip. It was observed with stereoscopic and common light microscopes in combination with an automatic system for image analysis and processing. The morphologic and morphometric characteristics corresponded to the third-instar larval form of L. serrata. To our knowledge, ocular linguatuliasis has not been previously described in South America, with this being the first report for Ecuador and South America. The present study shows that computer morphometry can adequately contribute both to the morphologic study and to the systematic classification of Pentastomids, and L. serrata in particular.
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Genetic responses to oxidative stress are triggered by excessive levels of agents such as superoxide. The soxRS regulon of Escherichia coli includes at least a dozen oxidative-stress and antibiotic-resistance genes that are activated by the SoxS protein, the synthesis of which is controlled by the redox-sensing SoxR protein. SoxR is a homodimer of 17 kDa subunits, each of which contains a [2Fe-2S] cluster. Transcriptional activation by SoxR is controlled by the oxidation state of these metal centres. In the absence of oxidative stress, the [2Fe-2S] centres are in the reduced form and the protein is inactive, although it still binds the soxS promoter. Agents that generate superoxide in the cell (e.g. paraquat) cause rapid oxidation of the metal centres, which triggers the transcriptional activity of SoxR; removal of the oxidative stress is followed by rapid re-reduction of the [2Fe-2S] centres. This facile mechanism links oxidation state to control of protein activity and may be used widely to allow cells to respond to oxidative stress.
Certain concentrations of the antiseptic AgNO3, a potent broad-spectrum antimicrobial agent, exert cytotoxic effects on fibroblasts and endothelial cells which are directly related to the wound-healing process. In vitro assessment of human fibroblast cytotoxicity has proved to be a useful method for characterizing cell toxicity mechanisms of topically-applied antiseptics. In the present study human dermal fibroblasts were exposed to AgNO3 at concentrations of 4.12-82.4 microM for 8 and 24 h. Silver ions greatly inhibited fibroblast proliferation and prolonged AgNO3 exposure produced Ag-dependent cell loss. In the sequence of events occurring during our in vitro experimental model, the inhibitory action on DNA synthesis was the primary event in AgNO3 cytotoxicity, associated with significant loss of cell protein. Both parameters decreased as the content of fetal calf serum (FCS) in the exposure medium was gradually reduced from 10 to 2%. The parallel study of DNA synthesis and cell protein content suggests that the toxic damage produced by silver in different phases of the cell cycle may lead to destruction of the entire cell population and therefore hinder the tissue regeneration process. A concentration- and time-dependent depletion of intracellular ATP content is also caused by ionic silver, thereby compromising the cell energy charge which precedes human dermal fibroblast death. Concomitant incorporation of FCS to the medium always attenuated Ag+ cytotoxicity curves in a concentration-dependent fashion and maximum protection was observed at 10% in situations closely resembling physiological conditions.
The SoxR protein of Escherichia coli responds to redox signals by activating the transcription of soxS, which encodes another transcription activator that directly stimulates oxidative stress genes. We show here that transcription of the soxR gene, which is positioned head-to-head with soxS in the chromosome, initiates in the intergenic region and is itself repressed by SoxR protein in in vitro transcription experiments. Analysis of single-copy operon fusions to soxR, combined with the results of Northern blotting experiments, verified this regulation and the transcription start site in vivo. The structure of the overlapping promoters is such that the single SoxR-binding site is located in the -10/-35 spacer of the soxS promoter, but just downstream of the -10 element of the soxR promoter. Activated and non-activated SoxR bind this site equally well, exerting nearly constant repression of soxR; activated SoxR simultaneously stimulates the soxS promoter >/=30-fold. The functional soxR promoter depresses soxS transcription when SoxR is not activated and enhances soxS transcription when SoxR is activated, as shown by comparing the expression of soxS'::lacZ fusions with and without the soxR -35 element (induction ratio only approximately 7-fold). SoxR thus represents a highly polar, redox-regulated transcriptional switch that maximizes the change in expression of soxS.