Four-year data after pediatric renal transplantation: a randomized trial of tacrolimus vs. cyclosporin microemulsion.

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 yr) were randomly assigned (1:1) to receive either Tac (n = 103) or CyA (n = 93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection (intent-to-treat). Baseline characteristics were comparable between treatment groups. Excluding deceased patients (n = 9) and patients lost to follow-up (n = 31, mostly transferred to adult care), 95% of 2-yr data (159 of 167 possible patients), 87% of 3-yr data (142 of 163) and 73% of 4-yr data (114 of 156) were retrieved. At 1 yr Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA (59.1%, p = 0.003). The incidence of corticosteroid-resistant rejection was also significantly lower with Tac (7.8% vs. 25.8%, p = 0.001). At 4 yr, patient survival was similar (94% vs. 92%, p = 0.86) but graft survival significantly favored Tac (86% vs. 69%; p = 0.025, log-rank test), respectively. At 1 yr, the mean glomerular filtration rate (GFR) (Schwartz formula, ml/min/1.73 m(2)) was 64.9 +/- 20.7 (n = 84) vs. 57.8 +/- 21.9 (n = 77, p = 0.0355), at 2 yr 64.9 +/- 19.8 (n = 71) vs. 51.7 +/- 20.3 (n = 66, p = 0.0002), at 3 yr 66.7 +/- 26.4 (n = 81) vs. 53.0 +/- 23.3 (n = 55, p = 0.0022), and at 4 yr 71.5 +/- 22.9 (n = 51) vs. 53.0 +/- 21.6 (n = 44, p = 0.0001) for Tac vs. CyA, respectively. Cholesterol remained significantly higher with CyA throughout follow-up. Three patients in each arm developed post-transplant lymphoproliferative disease. Incidence of insulin-dependent diabetes mellitus was not different. Tac was significantly more effective than CyA in preventing acute rejection in pediatric renal recipients. Renal function and graft survival were also superior with Tac. Glomerular filtration rate appears to be an useful surrogate marker for long-term outcome.

[Surgical treatment of hormone-producing adrenocortical carcinoma with liver metastases]. / Kirurgisk behandling av hormonproduserende binyrebarkkarsinom med levermetastaser.

BACKGROUND: Adrenocortical carcinoma is a highly malignant tumour with a poor prognosis. Surgery is the treatment of choice, with repeated procedures if necessary. MATERIAL AND METHODS: A 39-year-old woman presented with a pronounced Cushing's syndrome with virilizsation. Investigations showed an adrenocortical carcinoma with a diameter of 12 cm and two large metastases in the liver. She was admitted for palliative surgery. The primary tumour and one liver metastasis were resected. Three months later a right hepatectomy was performed, with excision of the remaining liver metastasis. Mitotane tablets were given all the time. RESULTS: After the first operation the patient's clinical condition improved radically. Two years later she was clinically healthy without any tumours and normal hormone levels. After 27 months a relapse in the liver was found by computed tomography, and after 33 months steroid hormone precursors again increased. Radiotherapy to the liver metastasis was given, and at 48 months the patient is still healthy and has no relapse. INTERPRETATION: Patients with adrenocortical carcinoma should be treated with extensive surgery, if necessary with repeated resections. Additional chemotherapy should be considered. This case confirms that surgical therapy has effect on metastasizing and hormone producing adrenal carcinoma and we consider that intensive surgery has improved this patient's prognosis.

Hepatic autotransplantation with ex situ neoplasm extirpation and vena cava replacement.

The treatment of a 64-year-old man with a retrohepatic neoplasm deemed not accessible by conventional in situ surgical techniques is presented to illustrate the potential benefit offered by techniques adapted from liver transplantation and vascular surgery. A computed tomography scan performed for uncharacteristic abdominal discomfort revealed a hepatic or retrohepatic tumor compressing the inferior vena cava. Biopsies were interpreted as probably leiomyoma or malignant schwannoma. The liver with neoplasm and retrohepatic inferior vena cava was removed en bloc and taken to the back table where the neoplasm invading the inferior vena cava wall was removed together with the inferior vena cava. The inferior vena cava was then replaced by a 22-mm polytetrafluoroethylene graft and the 3 hepatic veins were reconstructed with anastomoses to this graft. The liver was then autotransplanted by standard transplantation technique. The postoperative course was uneventful and the patient is in good health more than 2 years after surgery.

Individualized T cell monitored administration of ATG versus OKT3 in steroid-resistant kidney graft rejection.

Acute steroid-resistant rejection episodes are recommended to be treated with set doses of anti-thymocyte globulin (ATG) or anti-CD3 monoclonal antibody (OKT3). Individualized T cell monitoring has been proposed as a tool for dose finding. A randomized study comparing the efficacy and safety of ATG (n = 27) with OKT3 (n = 28) in the treatment of biopsy verified acute steroid-resistant rejection (ASRR) when both drugs were administered on the basis of daily individualized T cell measurements. A drop to below 50 cells/mm3 CD2+ T cells was considered adequate and used to guide the dose of ATG/OKT3. Demographic, clinical and histopathological severities of rejections were equal in the two groups. During the 10 days of T cell monitoring and antibody treatment, 13 patients were in need of dialysis (ATG = 7/OKT3 = 6). Two grafts did not respond to antibody treatment and were lost due to rejection (ATG = 1/OKT3 = 1). There were 26 biopsy verified re-rejections (ATG = 12/OKT3 = 14) within the first 3 months following antibody treatment. Mean serum creatinine (micromol/L) was similar in the two groups (ATG/OKT3: before rejection 157 +/- 72/151 +/- 88, at start of antibody treatment 308 +/- 125/330 +/- 94, end of antibody treatment 254 +/- 122/246 +/- 144 and at follow-up after a mean of 32 months 166 +/- 55 (n = 24)/164 +/- 57(n = 23)). To keep the T cell count below 50 cells/mm3, average dose ATG given was 354 +/- 151 mg (2.3 administrations, range 1-4) and average OKT3 was 32.5 +/- 6.8 mg in 10 doses. In conclusion, individualized T cell monitored administration of ATG and OKT3 is safe and seems as effective as a standard set dose in treatment of ASRR. Tailoring the dose for each individual patient lowers the cost.

[Extracorporeal surgery and liver autotransplantation]. / Ekstrakorporeal kirurgi og autotransplantasjon av lever.

BACKGROUND: Though the great majority of hepatic and perihepatic neoplasms may very well be treated by conventional surgical techniques, a few patients will have lesions seemingly inaccessible by traditional in situ surgical procedures. MATERIAL AND METHOD: We present two patients with retrohepatic sarcoma and liver haemangioma respectively, treated by hepatectomy, ex situ resection and hepatic autotransplantation. RESULTS: The first patient, a 64-year-old man, had a completely uneventful postoperative course and had no indication of recurrent sarcoma two years later. The second patient, a 29-year-old female with a giant hepatic haemangioma developed postoperative hepatic artery thrombosis. Following thrombectomy her further course was satisfactory and the patient was discharged with normal liver function three weeks postoperatively. INTERPRETATION: Ex situ liver surgery (bench surgery) with liver autotransplantation should be considered when traditional in situ surgery on the liver or adjacent structures is not applicable.