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Biomedical subjects

A D Pinna

Publications and source records attributed to A D Pinna.

At least 73 records · Page 4Linked to original sources

Treatment of fibrolamellar hepatoma with subtotal hepatectomy or transplantation.

Fibrolamellar hepatoma (FL-HCC) is an uncommon variant of hepatocellular carcinoma (HCC), distinguished by histopathological features suggesting greater differentiation than conventional HCC. However, the optimal treatment and the prognosis of FL-HCC have been controversial. Follow-up studies are available from 1 year to 27 years, after 41 patients with FL-HCC were treated with partial hepatectomy (PHx) (28 patients) or liver transplantation (13 patients). In this retrospective study, the effect on outcome was determined for the pTNM stage and other prognostic factors routinely recorded at the time of surgery. Cumulative survival at 1, 3, 5, and 10 years was 97.6%, 72.3%, 66.2%, and 47.4%. Tumor-free survival at these times was 80.3%, 49.4%, 33%, and 29.3%. The TNM stage was significantly associated with tumor-free survival. Patients with positive nodes had a shorter tumor-free survival than those with negative nodes (P < .015). Patient survival was most adversely affected by the presence of vascular invasion (P < .05). FL-HCC is an indolently growing tumor of the liver, which usually was diagnosed in our patients at a stage too advanced for effective surgical treatment of most conventional HCC. Nevertheless, long-term survival frequently was achieved with aggressive surgical treatment. When a subtotal hepatectomy could not be performed, total hepatectomy (THx) with liver transplantation was a valuable option.

Adolescent↗

Urgent revascularization of liver allografts after early hepatic artery thrombosis.

Between April 1993 and May 1995, 17 adult orthotopic liver transplant recipients were found to have early hepatic artery thrombosis (HAT) after a median of 7 postoperative days (mean, 11). The HAT was diagnosed in all cases by duplex ultrasound. Thrombectomy was performed with urgent revascularization (UR), using an interposition arterial graft procured from the cadaveric liver donor, and arterial patency was verified with intraoperative angiography. In seven cases, intra-arterial urokinase was administered after the thrombectomy. Fifteen (88%) of the livers remained arterialized throughout the follow-up period (median, 15 months); the remaining two patients developed recurrent HAT after 6 and 8 months. Although there was a high rate of subsequent complications, 11 (65%) of the patients are alive without retransplantation, with a mean follow-up of 17 months. Despite having a patent hepatic artery, the remaining six patients (35%) died from infectious complications that usually were present before the UR. Thus, UR effectively restored arterial inflow in 88% of the patients with early HAT. The ultimate outcome was determined mainly by the presence of intra-abdominal complications at the time of UR. In conclusion, UR, rather than retransplantation, should be considered the prime treatment option for patients who develop early posttransplant HAT.

Adult↗

Dynamic behavior of hepatitis C virus in chronically infected patients receiving liver graft from infected donors.

We studied the outcome of hepatitis C virus (HCV) infection in 14 patients with end-stage HCV-related liver disease who received HCV-positive liver allografts. Viral sequences specific for donor and recipient were established by direct sequencing of PCR products from the NS5 region and by single-strand conformation polymorphism. Within a few months after transplantation the donor strain took over the recipient strain in 8 patients while in 6 patients it was the recipient strain which ultimately prevailed. Donor and recipient were infected by identical genotypes in 6 donor/recipient pairs and by different genotypes in the remaining 8 pairs. Subtype 1b and type 1 (1a + 1b) became the predominant strains in all recipient/donor pairs in which they were present. Patients retaining their own strain were found to have significantly more active liver disease than those infected by the donor strain. We show that HCV superinfection and overtake phenomena occur in humans and suggest that genotypes 1b and 1 (1a + 1b) may possess replicative advantages over other genotypes. Furthermore, we provide evidence of the existence of interference preventing simultaneous continuous infection even by the same genotype strains. The development of active liver disease associated with recipient strain infection and mild or no disease associated with infection from the donor suggests various pathogenic abilities of different HCV strains.

Adult↗

Differences in outcomes for patients with bacteremia due to vancomycin-resistant Enterococcus faecium or vancomycin-susceptible E. faecium.

To determine the differences in outcome in cases of enterococcal bacteremia due to vancomycin-resistant organisms, we compared consecutive patients on a liver transplant service who had clinically significant bacteremia due to vancomycin-resistant Enterococcus faecium (VREF) (n = 54) with a contemporaneous cohort of patients who had vancomycin-susceptible E. faecium (VSEF) bacteremia (n = 48). VREF bacteremia occurred significantly later in the hospitalization than did VSEF bacteremia (43 days vs. 24 days, respectively; P < .01); in addition, VREF was more frequently the sole blood pathogen isolated (91% of patients) than was VSEF (56% of patients) (P = .0002). Invasive interventions for intraabdominal and intrathoracic infection were required more often in the VREF cohort than in the VSEF cohort (34 of 45 patients vs. 20 of 41 patients, respectively; P = .01). Vancomycin resistance more frequently resulted in recurrent bacteremia (22 of 54 patients infected with VREF vs. 7 of 48 patients infected with VSEF; P = .006), persistent isolation of Enterococcus species at the primary site (27 of 33 patients infected with VREF vs. 7 of 18 patients infected with VSEF; P = .005), and endovascular infection (4 patients infected with VREF vs. none infected with VSEF). The decrement in patient survival, as measured from the last bacteremic episode, was greater in the VREF cohort (P = .02). Vancomycin resistance, shock, and liver failure were independent risk factors for Enterococcus-associated mortality. Higher rates of refractory infection, serious morbidity, and attributable death occurred in the VREF cohort and were partially mediated by the lack of effective antimicrobial therapy.

Adult↗

Hyaluronate levels in donor organ washout effluents: a simple and predictive parameter of graft viability.

The principal cause of primary non-function in orthotopic liver transplantation is thought to be preservation injury to the microvasculature. We, therefore, evaluated if effluent levels of hyaluronate, whose uptake is an endothelial cell marker, could predict early graft function and ultimate graft outcome in orthotopic liver transplantation. A total of 102 cases were studied in two phases. In the first phase, we attempted to determine if a correlation existed between effluent hyaluronate levels, early graft function and ultimate graft outcome. This phase of the study was also used to determine hypothetical cut-off values for hyaluronate which could discriminate between good and bad livers. Thirty-two livers orthotopically transplanted to randomly selected primary recipients were studied. After varying periods of static cold storage (4 degrees C) in University of Wisconsin solution, the livers were reinfused with cold (4 degrees C) lactated Ringer's solution. The first 50 ml of the reperfusion effluent was collected from the infrahepatic vena cava. Effluent samples were analyzed for hyaluronate. Linear regression analysis demonstrated a significant correlation between effluent hyaluronate levels and post-operative aspartate and alanine aminotransferase levels (p < 0.001 for both). Logistic regression demonstrated a highly significant correlation (p = 0.0056) between effluent hyaluronate levels and ultimate graft outcome. Generation of Receiver Characteristics Curves indicated that a level between 400 and 430 micrograms.l-1 could possibly discriminate between good livers and those at risk of early graft failure. The authenticity of this hyaluronate cut-off level was further confirmed in the second phase of the study where 70 consecutive primary crossmatch-negative transplants were performed. A highly significant difference was observed in peak aspartate and alanine aminotransferase levels in the first week (p < 0.0006 and p < 0.0005, respectively) between livers with effluent hyaluronate levels < or = 400 micrograms.l-1 and livers with hyaluronate levels higher than 400 micrograms.l-1. Logistic regression revealed a highly significant correlation between effluent hyaluronate levels and graft success (p = 0.0001). Since hyaluronate uptake by the microvascular endothelial cell is significantly greater than production, high hyaluronate effluent levels in failed livers would be due to decreased hyaluronate uptake by the injured microvascular endothelial cell. We therefore conclude that effluent hyaluronate levels may prove to be a reliable preoperative test to assess early graft function and outcome in clinical orthotopic liver transplantation.

Adult↗

Peptidergic (VIP) nerves in normal human pancreas and in pancreatitis: an immunohistochemical study.

Vasoactive intestinal polypeptide was demonstrated in the nerves of the human normal pancreas and in pancreatitis by light microscope immunohistochemical technique. In specimens of normal pancreas, vasoactive intestinal polypeptide-immunoreactive neuronal cells were present in the autonomic ganglia. These ganglia were found to receive an abundant supply of vasoactive intestinal polypeptide-positive fibre plexuses. Immunoreactive nerve fibres were seen to run in the stroma, in association with secretory acini, ducts and blood vessels. Vasoactive intestinal polypeptide-positive fibres were also seen close to the Langerhans' islets, but no vasoactive intestinal polypeptide-like immunoreactivity was observed in the endocrine cells. In specimens from patients affected by pancreatitis, even in lesioned regions, immunoreactive elements were extremely scarce.

Connective Tissue↗

Surgical treatment of hydatidosis.

Hydatidosis is particularly widespread in some geographic areas. Among these Sardinia presents one of the highest incidences. The authors examine the results obtained of 382 patients submitted to surgery between 1973 and 1989. The average age was 38.9 years. Liver involvement was observed in 215 cases, lung involvement in 167 cases, while localizations in other organs were rare. Forty liver cysts and 54 lung cysts were complicated preoperatively. The patients were submitted predominantly to total or subtotal cysto-pericystectomy (270 cases), parenchymal resection (75 cases), simple cystectomy (40 cases). Total postoperative mortality was 2.35%. Postoperative time was significantly shorter after cysto-pericystectomy and after parenchymal resection than after simple cystectomy. Patients suffering from multiple or complicated cysts were given supplementary chemotherapy.

Adolescent↗

Thoracic extension of hydatid cysts of the liver.

Of a total of 77 patients affected by hydatid cysts of the liver observed between 1983 and 1988, we examined a group of 25 patients with cysts that had migrated into the thorax. The main characteristic of these patients was the hydatid hepatic cyst, which was situated in the right hepatic lobe in every patient, involving one or more right hemithoracic structures. In 24 patients, there were different combinations of symptoms, but only ten were thoracic. In those with advanced intrathoracic evolution of the hydatid cyst, we not only found a destruction of the hemidiaphragm, but also the presence of pleural effusion, empyema, atelectasis and multiple pleural hydatidosis caused by the development of a cystic fistula in the pleural cavity. Analysis of these instances allowed us to see that ultrasonograms of the liver and roentgenograms of the thorax are often the most sensitive and reliable diagnostic procedures for showing the intrathoracic evolution of the cyst. We believe that the surgical treatment must be carried out with simultaneous right thoracoabdominal access, which, besides exposing the thoracic lesions, also permits adequate treatment of the hepatic hydatid cyst and the possible associated biliary complications.

Adult↗

Indications and results for splenectomy for beta thalassemia in two hundred and twenty-one pediatric patients.

To determine the advantages and complications of splenectomy in the treatment of beta thalassemia, 221 splenectomies for thalassemia performed upon pediatric patients from 1971 to 1982 are evaluated. There were 125 boys and 96 girls with a mean age of 8.2 +/- 2.5 years at the time of the operation. Sixty-one other patients who underwent splenectomy for other diseases served as the controls. Early and late complications after splenectomy are considered with a follow-up study of ten years. Hemoglobin (Hb) value, transfusional quotients and mean of transfused blood previous to surgical treatment are matched with the same parameters evaluated during the follow-up period. The effect of treatment with salicylates and dipyridamole upon the incidence of early complications after operation is analyzed. The postoperative complications in patients with thalassemia were 43.4 versus 3.2 per cent (p less than 0.01) registered in control patients. Late complications occurred with an incidence of 10.7 per cent and were due principally to sepsis. Six patients died of sepsis during the follow-up period, but the mortality rate for sepsis in the patients we studied was significantly lower than that reported by others in 73 instances of splenectomy for beta thalassemia. Blood consumption dropped from 270 +/- 99 to 155 +/- 31 milliliters per kilogram per year postoperatively (p less than 0.01) and Hb levels rose from 9.7 +/- 1.3 to 11.2 +/- 0.7 grams per milliliter. These results suggest that, even though splenectomy for beta thalassemia causes a relevant incidence of complications and fatalities, surgical treatment permits an improvement in the quality of the lives of patients with beta thalassemia and significantly reduces blood consumption. Prophylactic antibiotic therapy can reduce the incidence of sepsis, as was observed in the patients we studied.

Aspirin↗

Role of therapeutic drug monitoring in a patient with human immunodeficiency virus infection and end-stage liver disease undergoing orthotopic liver transplantation.

Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4(+) count (>500 cells/mm(3)) and HIV-1 RNA (<50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new anti-retroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.

Adult↗

Rituximab as treatment of posttransplant lymphoproliferative disorder in patients who underwent small bowel/multivisceral transplantation: report of three cases.

This report describes three cases of posttransplant lymphoproliferative disorder (PTLD) in multivisceral/small bowel transplant patients treated with rituximab (anti-CD20 monoclonal antibodies). In two cases (one of which was a B-cell lymphoma) a good response to therapy was achieved. A third case (with polymorphic PTLD with low CD20 expression) developed a refractory rejection and PTLD was still documented on graftectomy. Rituximab was well tolerated, and a reduction of Epstein-Barr virus (EBV) viral load was documented by quantitive competitive-EBV polymerase chain reaction. Efficacy of therapy needs to be assessed in controlled studies.

Adolescent↗

Using elderly donors in liver transplantation.

AIM: Elderly donors are half of the grafts available in our center for liver transplantation. We retrospectively investigated their characteristics, outcomes, and variables related to graft failure. MATERIAL AND METHODS: From 1996 to 2003, 540 (46.4%) of 1163 donors were older than 60 years of age and 236 grafts (43.4%) were transplanted, whereas the others were refused. The clinical investigated variables were examined among this cohort. RESULTS: The median age of donors increased from 37 to 62 years. Donors older than 60 years of age were more often refused than younger ones (66% vs 44%); HCV-positive (9.9% vs 5.4%); HbcAb-positive (18.6% vs 12.6%), and steatotic (35.7% vs 13.9%; P < .01). Among donors older than 60 years, the main parameter to refuse the graft was the grade of steatosis. The variables related to the graft loss from donors older than 60 years were as follows: model for end stage liver disease (MELD) recipient >15 (65% vs 39%), cold ischemia time >10 hours (25% vs 13%), high blood losses (3987 +/- 4764 vs 2664 +/- 2043 mL), and year of liver transplantation after 2000 (26% vs 46%; P < .01). The 1-, 3-, and 5-year graft survival rates were significantly lower among donors older than 60 years than other donors: 75%, 65%, and 62% versus 85%, 83%, and 78%, respectively (P < .001). CONCLUSION: Donors older than 60 years of age provided liver transplants to half of our recipients. The graft survival rate of these organs was lower than that of younger donors and to improve it the other risk variables for poor outcome should be reduced, including MELD score of the recipient and prolonged cold ischemia time.

Adult↗