The Helsinki approach to face transplantation

Aim

We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases.

Cyclosporine in Severe Interstitial Cystitis

Purpose

Cyclosporine is a widely used immunosuppressive drug in organ transplantation and recently it has been used in several autoimmune disorders with good results. Because interstitial cystitis may have an autoimmune etiology, we wished to determine whether cyclosporine has any effect on symptoms in patients with severe interstitial cystitis.

Materials and Methods

A total of 11 patients, who fulfilled the criteria for interstitial cystitis according to an international accrual form, received cyclosporine for 3 to 6 months at an initial dose of 2.5 to 5 mg./kg. daily and a maintenance dose of 1.5 to 3 mg./kg. daily. Blood pressure, serum creatinine and cyclosporine concentrations were monitored regularly. The patients completed frequency-volume charts at 2-week intervals.

Results

The frequency-volume charts showed favorable effects. Micturition frequency decreased (p less than 0.01), and mean and maximum voided volumes increased significantly (p less than 0.001 and p less than 0.01, respectively). Bladder pain decreased or disappeared in 10 patients, allowing for storage of larger urine volumes. Serum creatinine did not change with the dosages used. Mild hypertension occurred in 2 patients and resolved after the cyclosporine dose was lowered. After cessation of treatment symptoms recurred in the majority of patients.

Conclusions

The findings revive the concept of interstitial cystitis as an autoimmune disease.     

Impaired intention‐to‐treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years’ experience from the Nordic countries

Biliary atresia (BA) is the most common indication for LT in children. We investigated whether this diagnosis per se, compared to other chronic liver diseases (OCLD), had an influence on patient survival. Data from 421 Scandinavian children, 194 with BA and 227 with OCLD, listed for LT between 1990 and 2010 were analyzed. The intention‐to‐treat survival and influencing risk factors were studied. Patients with BA had higher risk of death after listing than patients with OCLD. The youngest (<1 year) and smallest (<10 kg) children with the highest bilirubin (>510 μmol/L), highest INR (>1.6), and highest PELD score (>20) listed during 1990s had the worst outcome. Given the same PELD score, patients with BA had higher risk of death than patients with OCLD. For adolescents, low weight/BMI was the only prognostic marker. Impaired intention‐to‐treat survival in patients with BA was mainly explained by more advanced liver disease in younger ages and higher proportion of young children in the BA group rather than diagnosis per se. PELD score predicted death, but seemed to underestimate the severity of liver disease in patients with BA. Poor nutritional status and severe cholestasis had negative impact on survival, supporting the “sickest children first” allocation policy and correction of malnutrition before surgery.     

Renal allograft immunosuppression

A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidnery allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n=12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81%, 88%, 88%, and 88%, respecively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 mol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3.5–4.2 mg/kg per day and CyA concentrations were equal.     

Long-term results of 1047 cadaveric kidney transplantations with special emphasis on initial graft function and rejection

We studied the effect of initial graft function and acute rejection on graft survival in 1047 cadaveric renal transplantations during 1991–1997 with a constant policy of donor selection, graft allocation, and immunosuppression. The overall 1- and 5-year patient survival rates were 96 % and 88 %, and the 1- and 5-year graft survival (GS) rates were 92 % and 78 %. Delayed graft function (DGF) occurred in 31 % and there were 1.2 % never-functioning grafts. One-year GS in transplantations with early graft function (EGF) was 95 % compared to 87 % in DGF (P < 0.001). Donor age and cause of death, type of graft perfusion and cold ischemia time, and type and length of dialysis treatment were significant factors in determining the onset of graft function. These factors did not have a significant direct effect on GS. Early ( < 100 days) acute rejection occurred in 25 %. In transplantations without rejection, the 1 and 5-year GS was 93.3 % and 80.8 %. In acute rejection responding to steroids, the GS was equal to that up to 3 years, but after that a significantly worse survival rate was observed (1- and 5-year GS: 93.6 % and 73.4 %). DGF was detrimental to GS both in transplantations without rejection and in all rejection types. Received: 4 May 1999/Revised: 9 December 1999/Accepted: 15 December 1999     

Albumin dialysis has a favorable effect on amino acid profile in hepatic encephalopathy

According to one popular theory, hepatic encephalopathy (HE) is partly caused by an imbalance in plasma amino acid levels. The Fischer's ratio between branched chain amino acids (BCAAs) and aromatic amino acids (AAAs) correlates with the degree of HE; the lower Fischer's ratio, the higher the grade of HE. Extra-corporeal liver support systems, like MARS(R)-albumin dialysis (Molecular Adsorbents Recirculating System), can improve HE. The MARS(R) system uses a hyperosmolar albumin circuit to remove both water-soluble and albumin-bound substances. Plasma levels of neuroactive amino acids were analyzed in 82 consecutive patients with life-threatening liver failure admitted to our ICU. All patients fulfilled our indications for MARS treatment and most also fulfilled the criteria for liver transplantation (LTx). In patients with acute liver failure (ALF), as compared to those with acute decompensation of chronic liver failure (AcOChr), levels of leucine and isoleucine were significantly higher before MARS(R) treatment. In all patients, before MARS(R) treatment the higher the grade of HE grade the lower was the Fischer's ratio and higher were the levels of inhibitory neuroactive amino acids. During MARS(R) treatments the Fischer's ratio increased, and the grade of HE decreased. The increase in Fischer's ratio was mainly due to the decrease in AAAs. The plasma levels of neuroactive amino acids, methionine, glutamine, glutamate, histidine and taurine decreased during MARS(R)-treatment. In this study MARS(R)-albumin dialysis had a favorable effect on the plasma amino acid profile of patients with HE.     

Histopathological findings in well-functioning, long-term renal allografts.

One hundred and twenty-eight patients with a first cadaveric kidney allograft participated in a prospective, randomized, clinical trial comparing triple treatment, consisting of initial low-dose cyclosporine (CsA), azathioprine (Aza) and methylprednisolone (MP), with all possible combinations of two immunosuppressive drugs. A protocol core biopsy was performed on all patients with a functioning graft two years after transplantation. The histological findings were evaluated blindly and correlated to possible risk factors for renal allograft damage. The most common histological features were diffuse fibrosis in 62% of biopsies, tubular atrophy in 64% and diffuse inflammation in 30%. Two other important findings were glomerulosclerosis (43%) and vascular intimal proliferation (36%). The histological findings were scored mostly mild. A total of 77% (69 of 89) of patients had normal or only slightly increased serum creatinine. Decreased graft function was related to increased interstitial fibrosis, inflammation, glomerulosclerosis, mesangial matrix increase of glomeruli, intimal proliferation of vessels and tubular atrophy. These findings are characteristic, but not pathognomonic, of chronic renal allograft rejection both in experimental models and in humans. Possible risk factors were correlated to graft histology. Donor age correlated strongly with mesangial matrix increase, intimal proliferation, and tubular atrophy; there was no correlation with interstitial changes. The number of acute rejections and cold ischaemia time did not correlate with any one of the histological findings at two years following transplantation. Cyclosporine dose and concentration had a negative correlation to interstitial inflammation. A "chronic allograft damage index" was eventually created for the comparison of the four different treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Health-related quality of life before and after liver transplantation in patients with primary sclerosing cholangitis

Abstract

Background and aims: Liver transplantation (LTx) remains the only curative treatment in patients with primary sclerosing cholangitis (PSC) and liver failure. In Helsinki we have also performed pre-emptive LTx in PSC patients without liver insufficiency but considered to have a high risk for cholangiocarcinoma. The present study evaluates the possible differences in health-related quality of life (HRQoL) in these two PSC groups before and after LTx.

Methods: The total study population was 48 patients, 16 were transplanted due to increased risk of cholangiocarcinoma without liver insufficiency (the premalignant group) and 32 patients with end-stage liver disease (the symptomatic group).

Results: HRQoL remained good after LTx in the premalignant group, and this difference was also clinically important compared with the symptomatic group, although not statistically significant. Both groups had slightly lower mean HRQoL scores after LTx than the age- and gender-standardized general population, and this difference was not clinically important in either group and statistically significant only in the symptomatic group.

Conclusions: HRQoL does not decrease markedly after LTx in the premalignant PSC group, and this group does cope better than the symptomatic PSC group. After LTx, mean HRQoL of the premalignant group stays close to that of the age- and gender-standardized general population.