Primary nonfunction: timing retransplantation versus hemodynamic parameters and kidney function.

BACKGROUND: Patients with acute liver failure (ALF) show an aggravated hyperdynamic circulation. We evaluated potential changes in systemic hemodynamics and improved kidney function induced by the molecular adsorbent recirculating system (MARS) in a group of patients with primary nonfunction (PNF). PATIENTS AND METHODS: In the intensive care unit we treated 18 patients with PNF (6 females and 12 males) after orthotopic liver transplantation (OLT) of overall mean age 47.8 years (range, 28-60 years). Continuous MARS treatment was performed on all patients with a kit change every 8 hours during a mean of 10 days (range, 1-20 days). Double-lumen catheter type veno-venous access was used for the blood supply. The blood flow rate was 150 to 250 mL/min, depending on the hemodynamic situation of the patient. Blood passed through an albumin nonpermeable, high flux dialysis membrane. During MARS treatment we monitored the hemodynamic condition, using a series of parameters: heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) before (baseline value) as well as after 1 hour (T1), 3 hours (T2), and the end of treatment (T3). RESULTS: There was a progressive decrease in positive inotropic support (dobutamine, norepinephrine) and significant improvement in hemodynamic parameters, such as MAP (P< .01), PVRI/SVRI/V(mean) (P< .002), and KARI (P< .01). The improved kidney functions were shown by significant improvements in serum creatinine (P< .03), urea (P< .02), and urine volume (P< .005). Eleven patients were alive: 6 with OLT and 5 without OLT. Seven patients died: 4 after OLT and 3 before OLT due to multiorgan failure. CONCLUSIONS: The MARS device significantly improved the hemodynamic parameters and kidney function that also determine patient survival in ALF (61.1%) with PNF while awaiting retransplantation presumably by removal of certain vasoactive substances.

Combined liver-kidney transplantation in polycystic disease: case reports.

Polycystic disease causes a progressive decrease in renal function and liver degeneration. The progression of the disease evolves separately between organs and transplantation options vary: simultaneous or sequential liver-kidney transplantation or single-organ transplantation. From September 2006 to June 2007 3 combined liver kidney transplantations (CLKT) were performed for polycystic disease with end-stage renal disease: 2 with polycystic liver disease, and 1 with hepatic failure due to congenital hepatic fibrosis. The widest dimensions of the polycystic liver of 50 and 60 cm diameter were due to extensive cystic degeneration. We performed 1 simultaneous CLKT and 2 sequential transplantations: 1 liver after kidney, and 1 kidney after liver. At present all patients are alive with 100% graft function. Median creatinine level at discharge was 0.9 mg/dL (ranges, +/-0.2). Good liver graft function was reported in all 3 cases. Transplant benefit in polycystic liver-kidney disease has been already demonstrated; conservative surgical options may result in a high incidence of complications in highly involved polycystic livers. Delaying transplantation results in a more difficult surgical technique, a higher rate of postoperative complications, and a disturbance of optimal graft retrieval because of the worse preoperative condition of the patients.

Is legalizing the organ market possible?

INTRODUCTION: Two opposing views of the human body have existed since time began. Can it be traded or does its value go beyond a monetary one? Today it is illegal to sell organs but the success of organ transplantation has give rise to an enormous controversy. The continued increase in the need for organs has lead to a major use of live donors. Consequently, clandestine selling of organs is becoming more widespread for two main reasons: scientific progress and market demand. Our aim was to consider the protection of ethical principles through legislation. MATERIALS AND METHODS: Based on the principle that it is morally unacceptable for people to die on a waiting list, we analysed various ways in which the National Health Service could give incentives to live donors, including reimbursement of health expenses, tax relief, pension or early retirement benefits, or education grants for the children. Possible incentives for cadaveric organ donation included reimbursal of health and funeral costs, or increase in widow/er's pension. CONCLUSION: The tendency may be toward reimbursement of costs rather than actual payments. A legal, ethical organ market could save thousands of human lives, but it must be correctly regulated.

Outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered an optimal indication for liver transplantation (LT) because it may eliminate both the tumor and the underlying liver disease. The present study sought to compare cumulative survival, rate of HCC recurrence, and causes of death among patients with cirrhosis and HCC before and after the adoption of more restrictive criteria (Milan selection criteria) at the time of patient listing. Among 226 adult patients who received an elective liver transplantation between 1999 and 2005, 58 (27%) had a diagnosis of HCC at the time. The 38 patients who underwent transplantation for HCC in the period 1989 to 1998 were considered the "historical group." After LT (mean follow-up, 34 + 28 months), the cumulative survival rate was better among HCC versus non-HCC recipients (93% vs 71% at 1 year and 81% vs 67% at 3 years, respectively; P < .046), although the difference tended to attenuate after 5 years (66% vs 67%, respectively). Tumor recurrence (evaluated in patients surviving at least 3 months after LT) was observed in 10/31 in the historical group versus 4/53 among those who underwent transplantation after 1999. Among the causes of death, recurrence represented 50% in the old series and 23% in patients who underwent transplantation after 1999. Cumulative survival significantly improved among HCC patients who underwent transplantation after 1999 (93% vs 66% at 1 year and 81% vs 50% at 3 years; P < .00001). The 58 patients who underwent transplantation with a diagnosis of cirrhosis and concomitant HCC after 1999 showed even better survival than patients who underwent transplantation for end-stage liver disease without malignancy.

One hundred sixteen cases of acute liver failure treated with MARS.

The various definitions of acute liver failure do not accurately reflect the differences in clinical signs and prognosis. Liver support devices to improve the clinical condition before liver transplantation (LT) were used in 13 patients with primary nonfunction, 24 with fulminant hepatitis, 17 were affected by delayed nonfunction, and 56 of acute on chronic hepatic failure. The average age of these patients was 41.8 years. The average number of applications of molecular absorbing recirculating system (MARS) was about 6 (range: 1-24). The mean length of application was about 9 hours (range: 8-20). MARS treatment was carried out in HLF patients with continuous acute-on-chronic hepatic failure dialisate flow similar to continuous veno venus hemofiltration (CVVH), albumin flow < 20% of hematic flow, heparin 5/10 UI/kg. In acute on chronic hepatic failure (AoCHF) patients, 6- to 11-hour (average 8.5) treatments were performed for a minimum of three treatments. The majority of patients were treated in the intensive care unit (ICU). Laboratory results were also monitored and showed progressive modification: bilirubin (before treatment 22.37 +/- 11.6 mg/dL, after treatment 11.36 +/- 7.5 mg/dL) and ammonium (before treatment 238.2 +/- 19 microg/dL, after treatment 115.4 +/- 12 microg/dL) showed significant change (P < .01). Lactates (before treatment 3.48 +/- 1.3 mmol/L, after treatment 1.76 +/- 1.1 mmol/L) and creatinine (before treatment 2.36 +/- 0.18 mg/dL, after treatment 1.26 +/- 0.67 mg/dL) also showed significant changes (P < .02 and P < .04). Glasgow Coma Score (GCS) went from 8.6 +/- 1.4 to 11.9 +/- 3.9 (P < .05). The mean middle cerebral artery flow (V media) went from 46 cm/s/26-59) to 73 cm/s (52-106) representing decreased cerebral edema, a difference that was not significant. INR scores (before treatment 2.4 after treatment 1.8) also showed no significant change. The MARS can be applied with tolerability for long periods for patients with PDF and FH as a bridge to transplant. In patients with PDF, it is used for a waiting recovery of the transplanted organ. Therefore MARS can also limit the necessity to perform further transplants.

Molecular adsorbent recirculating system treatment for acute hepatic failure in patients with hepatitis B undergoing chemotherapy for non-Hodgkin's lymphoma.

Hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface (HBsAg) antigen-positive patients treated with chemotherapy. Because the hepatitis is related to HBV virological reactivation, application of effective antiviral therapy, such as Lamivudine, has been attempted. Despite the use of these antiviral agents at the time of clinical hepatitis, some HBsAg-positive patients still develop hepatic failure and die. We used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock, Germany) to treat 5 HBsAg-positive lymphoma patients with acute hepatic failure due to chemotherapy despite lamivudine treatment. Before and after each treatment we monitored the parameters of neurological status (EEG, cerebral CT and Glasgow coma score), hemodynamic parameters, acid-base equilibrium and blood gases as well as hepatic and renal function. The inclusion criteria were these of the King's College Hospital. Statistical analysis by Student t method showed significant results (P < .01). Three of 5 patients are alive without signs of reactivation of viral or hematological diseases at 1 year follow-up. The 2 patients died because MARS treatment was started too late, with Glascow coma score grade IV, hemodynamic instability, and mechanical ventilator assistance. Despite the limited number of cases, we believe that MARS can be applied to patients with a high tolerance and yield good results, but the treatment has to start at the first signs of hepatic failure.

Aortic connective tissue in atherosclerotic aorta--a biochemical study.

Biochemical analysis of the extracellular matrix of human aortas was performed on samples of ascending and descending aortas affected by atherosclerosis in comparison with a control group of nonatherosclerotic aortas. Ulcerated or heavily calcified atheromas were excised and excluded from the analysis in order to differentiate biochemical alterations leading to the formation of atheromas from those due to complications of already formed atheromas. Our results show that the development of atheromas brings about an extensive destruction of elastic fibers and muscular cells, and their place is occupied by other components of the extracellular matrix, most notably, collagen, non-uronic sugars, water, and lipids, which were found significantly increased.

Aortic connective tissue in ageing--a biochemical study.

The biochemical analysis of samples of aortic connective tissue was carried out in 22 subjects from 9 to 84 years old. Aortic samples were taken at necropsy performed after sudden or, more often, traumatic death. The results suggest that aging of the aorta is accompanied by an increase both in collagen content and in total sugar content when expressed as mg/cm2 while the elastin content, when expressed in the same way, does not undergo any variation.

Biochemical analysis of dermal connective tissue in subjects affected by primary uncomplicated varicose veins.

Biochemical analysis of dermal connective tissue was carried out in 14 subjects affected by primary uncomplicated varicose veins and 14 controls. Skin samples were taken, according to fixed criteria, from operation pieces of total mastectomy for breast cancer. The results suggest that the dermal tissue in these subjects is just thinner than that of controls, confirming previous similar clinical findings. The elective reduction of the collagen content observed, unassociated with changes of other components of the dermal connective tissue, brings evidence for a systemic biochemical defect of the extracellular matrix i.e. a collagen defect affecting the entire body structure and not only the varicose or pre-varicose veins of the lower limbs.

[Incidence of the manifestations of the so-called status varicosus of Curtius in subjects with idiopathic varices of the lower extremities]. / Incidenza delle manifestazioni del cosidetto status varicosus di Curtius nei soggetti portatori di varici idiopatiche degli arti inferiori.

Two groups of subjects have been studied: the first one affected by varicose veins in lower legs, the second one as control (both groups include 138 subjects, mostly corresponding about age, sex and general health conditions). Acrocyanosis, blue sclerae, juvenile spontaneous epistaxis, hand's primary osteoarthrosis, articular hypermobility, thin skin and hernia were present more frequently in the group affected by varicose veins, the difference being statistically very significant. We suggest that mechanical revealing factors lead to the development of varicose veins in subjects who have a constitutional and probably hereditary systemic weakness of connective tissue network.

Connective tissue in aging lung.

Collagen, elastin and structural glycoproteins were measured in 21 intact lungs taken at postmortem examination after sudden death from subjects aged from 15 to 83. The data were expressed as milligrams per cubic centimeter of lung peripheral parenchyma inflated and fixed at the standard pressure of 25 cm H2O to exclude the pitfall of referring to dried tissue weight. The volume/weight ratio of inflated dried lung parenchyma increased significantly with aging; likewise the collagen content decreased and so did the collagen/elastin ratio, while the elastin content did not show any significant correlation with age. The present findings indicate that biochemical, morphological and functional data on the senile lung agree well.