Comparison of calcium and alfacalcidol supplement in the prevention of osteopenia after kidney transplantation.

The aim of this observational study was to compare the effect of calcium and alfacalcidol supplementation on the regression of hyperparathyroidism and on prevention of osteopenia in patients up to 3 years after renal transplantation. Two historical cohorts were compared for that purpose. One hundred and fifty-nine patients received calcium carbonate supplement (group 1), while 81 patients were treated with alfacalcidol (group 2). Serum Ca, phosphate (P), Mg, creatinine, alkaline phosphatase (AP) and parathyroid hormone (PTH) levels were determined before and after transplantation in the two groups, for 3 years. Femoral neck and lumbar spine bone mineral density (BMD) was measured only at 3 and 6 months and 1, 2 and 3 years after transplantation. At baseline there was no difference in age or sex ratio, but prevalence in post-menopausal women was higher in group 1 (6.9% versus 1.2%). Duration on dialysis was comparable but prevalence of interstitial and undetermined nephropathies was higher in group 1. Baseline serum concentrations of PTH, Ca and P were comparable in both groups. After transplantation, plasma creatinine decreased to comparable levels in both groups. Immunosuppression by triple therapy was more prevalent in group 2, so that cumulative dose of steroid was higher in group 1, especially at 1 month because of higher incidence of acute rejections (51% versus 13%). Mean intact PTH levels decreased in both groups, from 18 pmol/l to 8.4 and 7.9 at 3 years, but the decrease was significantly greater with alfacalcidol at 6 and 12 months. At 3 months, BMD were comparable at both sites. From 3 months to 3 years after kidney transplantation, mean lumbar spine BMD significantly increased from 0.963 to 1.054 g/cm(2) in group 1, whereas there was no significant decrease (1.048 to 1.006 g/cm(2)) in group 2, the difference in changes being significant ( P<0.05). Femoral neck BMD was not significantly increased in either group (0.932 to 0.993 g/cm(2) in group 1, and 0.850 to 0.907 g/cm(2) in group 2). Expressed as percentages, these changes were +9.4% and -4% for lumbar BMD and +6.5% and +6.7% for femoral neck, for groups 1 and 2, respectively. Prevalence of osteopenia was not significantly lower at 3 years in group 1 (45% and 51%) than in group 2. During the follow-up period, osteonecrosis was diagnosed in six patients (3.8%) in group 1 and in nine (11%) in group 2. In conclusion, alfacalcidol compared to CaCO3 supplement suppressed hyperparathyroidism more rapidly and strongly. In spite of higher osteopenia risk in the CaCO3 group, lumbar BMD increase was greater and incidence of osteonecrosis higher in this group, suggesting better bone protection with CaCO3 than with alfacalcidol.

Flow cytometric DNA analysis of benign hyperfunctioning parathyroid glands: significant difference in the S phase fraction and proliferative index between adenomas and hyperplasias.

AIMS: Flow cytometric DNA analysis was performed to measure the DNA content of benign parathyroid tumours in patients with primary hyperparathyroidism. METHODS: DNA analysis of paraffin-embedded parathyroid samples was performed on 51 parathyroid glands from 29 patients after parathyroidectomy. Histopathology showed parathyroid adenoma in 25 cases and hyperplasia in four patients. DNA ploidy status, DNA index (DI), percentage of cells in S phase and proliferative index (PI) were determined. RESULTS: Normal cells from normal glands were all diploid. DNA cytometry showed 12 aneuploid and 13 diploid adenomas. There were 12 diploid and four aneuploid hyperplastic glands. Incidence of aneuploid DNA histograms did not show a statistically significant difference between adenomas and hyperplasias (P=0.216). Mean S phase fraction was 3.45% in adenomas and 1.53% in hyperplasias (P= 0.015). Mean PI was 6.48% in adenomas and 2.78% in hyperplastic parathyroid glands. This difference was statistically significant (P=0.006). Diploid cases had a mean PI of 4.78% and aneuploid glands a mean PI of 7.7% (P=0.08). Aneuploid DNA content did not reveal statistically significant correlation with age, gender, pre-operative Ca, alkaline phosphatase, i-PTH levels, and tumour size. The mean S phase fraction and PI were 2.25% and 4.78% in diploid glands, and 4.5% and 7.7% in aneuploid cases. CONCLUSION: Aneuploid DNA content may be present in benign parathyroid diseases, but not in normal parathyroid glands. Aneuploid DNA histograms and higher PI occur more often in adenomas compared with hyperplasias, but the nuclear DNA analysis is unable to make a distinction between adenomas and hyperplasias.

Technetium-99m-sestamibi/pertechnetate subtraction scintigraphy vs ultrasonography for preoperative localization in primary hyperparathyroidism.

A prospective study was performed to evaluate the efficacy of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scanning and US for imaging parathyroid glands in primary hyperparathyroidism. Sixty-three patients were surgically treated for primary hyperparathyroidism (HPT). Preoperative scintigraphy and US were performed in all cases. Bilateral neck exploration was carried out on each patient. Results of radionuclide studies and US were compared with surgical and histological findings. In 57 patients with primary HPT the radionuclide scanning gave true-positive results. Four false-negative and two false-positive scintigrams were obtained. The sensitivity and the positive predictive value (PPV) of scintigraphy were 93 and 97%, respectively. Forty-one cases were correctly localized by the US. Seventeen US results were false negative and five were false positive. The sensitivity and the PPV for US were 71 and 89%, respectively. There was a statistically significant difference between the sensitivity of the scintigraphy compared with the US ( p=0.001). Sensitivities of radionuclide scans and US were higher for adenomas (100 and 83%) than for hyperplastic glands (75 and 40%). The sensitivity of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scintigraphy was significantly higher compared with US. This sensitive method could help surgeons in performing a rapid and directed parathyroidectomy.

[Changes in cardiovascular risk factors after renal transplantation]. / A cardiovascularis rizikófaktorok alakulása vesetranszplantáció után.

Authors examined the serum concentration of creatinine, uric acid, homocysteine, cystatine C, total cholesterol and triglyceride in 115 male and 77 female patients six months after the transplantation. The change of the BMI (Body Mass Index) was studied, fat and water body weight was determined by bioelectrical impedance analysis, and the ratio of intra- and extracellular volume was calculated. Both creatinine and cystatine C levels decreased significantly compared to the levels before the transplantation (p < 0.001) because of the good renal function, and there was a good correlation between creatinine, cystatine C and homocysteine levels (r = 0.5315 in females, r = 0.3189 in males). Elevated BMI (36.49%) and hypercholesterolaemia along with moderate hyperhomocysteinaemia was found in a considerable part of the patients. Increase in body weight was confirmed by the increase in fat body weight and volume determined by bioelectrical impedance analysis. In patients with adequate compliance the ratio of intra- and extracellular volume was between 1.67 and 1.79. Blood pressure values showed frequently the non-dipper phenomenon despite appropriate antihypertensive therapy, and negative diurnal index was found with high nocturnal blood pressure levels. The mean blood pressure was 148/81 +/- 13.2/4.8 mmHg in males and 133/84 +/- 15.3/9.8 mmHg in females. Authors enhance the importance of regular monitoring of cardiovascular risk factors in the prevention of cardiovascular complications.

[Acute pancreatitis after kidney transplantation]. / Vesetranszplantált betegek akut hasnyálmirigy-gyulladása.

UNLABELLED: Pancreatitis following kidney transplantation was first described by Starzl in 1964 [19]. The incidence rate of the disease involving severe complications ranges from 1.2 to 6.8%. The number of risk factors, besides those of the normal population, is increased by a number of other factors, i.e. uremia, disorder of lipid metabolism, polycystic kidney, immunosuppressive drugs, cytomegalovirus infection, etc. The mortality of acute pancreatitis in a kidney transplant patient is, in spite of treatment with the most up-to-date methods, is much higher (53-60%) than that for a non-transplant patient. In the period between 27 June 1991 and 31 December 2000 the number of cadaver kidney transplants performed in the Transplantation Division of the 1st Department of Surgery of the Medical and Health-Science Centre of the University of Debrecen was 349. During this period 9 incidences of acute pancreatitis were found in 8 patients. The frequency of incidence was 2.56%. In the present communication we analyse the prognosis of 9 kidney transplant patients, with special respect to immunosuppression. RISK FACTORS: One patient was administered Cyclosporin alone, four were given Cyclosporin and Steroids, a further one Cyclosporin, Steroids and Azathioprine, the remaining three were treated with Cyclosporin, steroids and Mycophenolate Mophetil. In six cases out of nine multiorgan insufficiency (kidney, lung, liver) was encountered on presentation, three cases were accompanied by peritonitis. In spite of early jejunal nutrition, intensive therapy, antibiotic treatment, CT monitoring, if needed, necrectomy and oncotomy, three of our patients died from multiorgan insufficiency induced by septico-toxic state (mortality 33.3%). Other six patients recovered. CONCLUSIONS: The mortality rate of acute pancreatitis is much higher in immunosuppressed patients. The role of the etiological factors is not unequivocal in the development of pancreatitis. Nevertheless, all possible risk factors have to be taken into consideration when starting the immunosuppressive treatment of transplant patients and during their follow-up. By optimally adjusting the immunosuppressants we can decrease the risk of pancreatitis, however, the prognosis of the diseases, in agreement with the data in the literature, cannot be considerably improved even with the most up-to-date methods.

[Changes in calcium metabolism after kidney transplantation]. / Változások a calcium anyagcserében vesetranszplantációt követóen.

Prospective study was performed to measure the changes in calcium metabolism after kidney transplantation. 139 recipients received calcium substitution (1st group) and 81 patients were treated with alfacalcidol (2nd group). Serum Ca, P, Mg, alkaline phosphatase (AP) and intact PTH levels were determined before transplantation and at 1, 3, 6, 12 and 24 months thereafter in the two groups. Femoral and vertebral bone mineral density was measured with bone densitometer at the same period. The serum Ca level elevated and the serum P concentration decreased significantly in both group. The mean serum Mg and AP concentration changed in the normal range after the transplantation. The intact PTH level decreased significantly in both group at 2 years following transplantation. The intact PTH concentration changed from 17.1 pmol/l to 9.3 pmol/l in the 1st group, and it is decreased from 17.7 pmol/l to 7.9 pmol/l in the 2nd group. Bone densitometry showed osteoporosis in both group. At 12 months and at 24 months after kidney transplantation bone mineral density (BMD) of lumbar spine was 90.8% and 86.9% in the 1st group and 85.3% and 81% in the 2nd group. At the same time BMD of the femoral region was 84.4% and 85.5% in the 1st group and 82.0% and 81.3% in the 2nd group. The BMD did not changed significantly in the 1st compared to the 2nd group. During this period osteonecrosis was diagnosed in 6 patients in the 1st group and in 9 cases in the 2nd group. In conclusion, the serum Ca and P levels were in the normal range after kidney transplantation. The alfacalcidol treatment significantly decreased the intact PTH concentration compared to the calcium substitution. Moderate osteopenia was observed in both groups after the transplantation, despite of the administration of alfacalcidol treatment.

[Fifteen years experience in the surgical treatment of primary hyperparathyroidism]. / Tizenöt év alatt szerzett tapasztalataink a primer hyperparathyreosis sebészi kezelésében.

We measured the efficacy of preoperative localization techniques and results of parathyroidectomy in patients with primary hyperparathyroidism (HPT). From 1986 to 2001, 92 patients were treated with primary HPT. Preoperative localization technique was used in all patients (US n = 85, Tc-99m-sestamibi/Tc-99m-pertechnetate subtraction scintigraphy n = 67, CT n = 18, MRI n = 14) to visualize the abnormal parathyroids. Results of localization studies were compared with surgical and pathological findings. Bilateral neck exploration was carried out in each patient for the identification of all parathyroid glands. If parathyroid adenoma was diagnosed, exstirpation of the abnormal parathyroid was performed. If diffuse hyperplasia was diagnosed, subtotal parathyroidectomy (3 1/2) was performed. The overall sensitivity was 94% for scintigraphy, 74% for US, 67% for CT and 50% for MRI. The PPV was 97% for scintigraphy, 92% for US, 100% for CT and for MRI. At surgery 66 patients had single adenomas and 3 patients had double adenomas. Diffuse hyperplasia was diagnosed in 21 and parathyroid carcinoma was found in 2 patients. Persistent HPT was noted in 1 patient. Recurrent HTP occurred 4 times. After a second operation their HPT disappeared. In conclusion, the sensitivity of Technetium-99m-sestambi and Technetium-99m-pertechnetate subtraction scanning was significantly superior compared to other localization methods. The use of these sensitive preoperative technique can improve the success rate, and decrease the incidence of persistent and recurrent HPT.

[Results and complications of parathyroidectomy in secondary hyperparathyroidism]. / Szekunder hyperparathyreosis miatt végzett parathyroidectomiák eredményessége és szövódményei.

Retrospective study was performed to measure the results of parathyroidectomy in patients with secondary hyperparathyroidism. From 1987 to 2000, 48 patients underwent surgery for secondary hyperparathyroidism. There were 30 of 48 patients on haemodialysis treatment, and 11 patients were in pre-dialysis stage. Parathyroidectomy was performed after successful kidney transplantation in 4 cases. Indication of the surgery was extremely elevated serum level of parathyroid hormone (at least 10 fold elevation), which was resistant for the conservative medical therapy. Subtotal parathyroidectomy (3 1/2) was performed in 30 patients. Five patients underwent total parathyroidectomy and autotransplantation. Only 2 or 3 parathyroid glands have been removed in 13 patients. Haematoma occurred in 3 cases after parathyroidectomy. Recurrent nerve injury or septic complication did not occur. Two patients died in the early postoperative period due to cardiac failure. Tetania was noted in 2 patients after surgery. Permanent postoperative hypocalcaemia (over 6 months) occurred in 3 cases. Persistent hyperparathyroidism was diagnosed in 5 patients. In these patients 2 parathyroid glands were removed during the primary operation. Recurrent hyperparathyroidism was detected in 2 patients. Subtotal parathyroidectomy was carried out in these cases previously. At the reoperation for persistent and recurrent hyperparathyroidism, total parathyroidectomy and autotransplantation was performed. Serum alkaline phosphatase level and serum parathyroid hormone value decreased after surgery, except those patients with persistent hyperparathyroidism. Bone pain decreased in 96% of the cases and pruritus decreased in 92% of the patients after parathyroidectomy. Soft tissue calcification showed improvement in 45% of cases. In conclusion, the subtotal parathyroidectomy or total parathyroidectomy with autotransplantation cause a rapid decrease of PTH level and the improvement of the clinical symptoms in patients with medical treatment resistant secondary hyperparathyroidism. Persistent hyperparathyroidism occurs in those cases when inadequate parathyroidectomy was performed.

[Nipple transposition on superomedial pedicle in reduction mammoplasties]. / A bimbó-areola komplexum superomedialis nyélen való elforgatása redukciós mellplasztikáknál.

BACKGROUND: Transposing the nipple-areola complex is a challenge at reduction mammaplasties, particularly when the distance between the sites is big and great amount of breast tissue has to be removed. Many techniques are used, all have to fulfill the following conditions: the blood supply and sensation of the nipple have to be preserved and closure must be tension-free. OBJECTIVE: To evaluate how the superomedial pedicle for nipple transposition fulfills the above requirements. METHOD: Fifteen reduction mammaplasties performed in this way (resection weight: 435 g/breast), postoperative patient examinations with emphasis on sensation. RESULTS: Nipple viability was good without necrosis, retaining sensation was also good with no loss of sensation. CONCLUSION: The technique is safe, giving good cosmetic results.

Relationship between the survival and the clinicopathological parameters of the patients with tumors in the pancreatic head region.

Retrospective study was performed to assess the possible prognostic factors for survival in patients after radical surgery with carcinoma of the pancreatic head region. Twenty-nine patients underwent pancreaticoduodenectomy for cancers of the pancreatic head (n = 22) and the papilla of Vater (n = 7). Using flow cytometry, authors measured the nuclear DNA content of tumor cells. DNA ploidy status was evaluated from paraffin-embedded tumor tissues. Fourteen DNA diploid and eight DNA-aneuploid pancreatic carcinomas occurred. Six DNA diploid and one DNA-aneuploid tumors were diagnosed in the group of papilla of Vater. Mean survival of patients with the carcinoma of pancreatic head was 9.3 months. Survival of the patients with the cancer of papilla of Vater was 20.5 months. The mean survival was 10 months in case of DNA-diploid pancreatic carcinoma, and it was 8 months in case of DNA-aneuploid cancer. The survival of the patients with DNA* diploid Vater papilla tumor was 17 months, and it was 40 months with the DNA-aneuploid cancer. The mean proliferative index (PI) of DNA-diploid pancreatic cancers was 9.7%, whereas that of the DNA-aneuploid cases was 13.3%. The mean PI of DNA-diploid tumors of papilla of Vater was 7.5% and that of the DNA aneuploid cases was 28%. There was no significant correlation between the PI and the survival. DNA-ploidy status and PI had no significant effect on the survival in patients with carcinoma of the pancreatic head region.

Flow cytometric studies on the relationship between DNA content and clinicopathologic features of pancreatic cancers.

The purpose of this study was to determine DNA (DI) and proliferation indices (PI) in 26 pancreatic and 10 ampulla of Vater carcinomas by flow cytometry using paraffin embedded tissue samples. Furthermore, we analysed the relationship between these parameters and the traditionally used prognostic parameters (type, stage and grade) of the tumor. Out of the 26 pancreas carcinomas 15 proved to be DNA diploid and 11 DNA aneuploid, while among the 10 ampulla of Vater tumors 7 DNA diploids and 3 DNA aneuploids were found. The PI-ces in both type of carcinomas were significantly higher than PI-ces in the surrounding nontumorous pancreatic tissue. The average of PI in aneuploid carcinomas significantly exceeded the one of diploid carcinomas. In group of grade III-IV tumors the ratio of aneuploids (59%), and the average of PI (11.59% +/- 5.27%) proved to be significantly higher (P < 0.05, both) than in grade I-II group (21%, PI = 8.16% +/- 4.03%). Among the tumors falling into the T1 class the ratio of aneuploids (29%) and of tumors (29%) characterized by a PI > 8% proved to be lower than among the tumors of T2-T3 class (46%, 62%). The ratio of aneuploids among cases with lymphnode positivity was higher (3/4), than among those without (8/22), the single case with distant metastasis was also found to be aneuploid. The results indicate a close correlation between the DNA ploidy and PI and the stage and grade of pancreatic cancers.

The importance of obesity and hyperlipidaemia in patients with renal transplants.

The authors studied dyslipidaemia and "obesity" in 137 patients (87 males and 50 females) following cadaver renal transplantation with regard to the applied immunosuppressive treatment and the patients' hypertension. The most extreme dyslipidaemic values, the highest levels of total cholesterol, LDL and Apo were found 6 to 18 months after successful transplantation; these values were significantly higher in women than in men. While in the dialysis programme only 21.89% of the patients had BMI values higher than 25.1 kg/m2, after transplantation their proportion was 36.49%. In addition to hyperlipidaemia, hyperuricaemia was encountered in 39.42%, erythrocytosis in 8.76% and diabetes mellitus in 9.48%, respectively. In the group of patients treated only with Cyclosporine-A the incidence of hyperlipidaemia and hypertension was significantly lower than in those receiving a combination of either corticosteroids and Cyclosporine-A or corticosteroids, Cyclosporine-A and azathioprine. There was a close relationship between the unfavourable tendency of obesity and the measured hyperlipidaemia. On the other hand, the extent of proteinuria did not always have a positive correlation with the increase of BMI and body weight, the severity of hypertension and hyperlipidaemia. The authors emphasize the importance of a systematic control of the lipid levels, the significance of a diet with an adequate carbohydrate and lipid content, and the necessity of avoiding obesity by selecting the optimal immunosuppressive treatment.

Effect of the DNA ploidity on survival in patients with carcinoma of papilla of Vater.

The authors investigated the possible prognostic factors for survival after pancreaticoduodenectomy for carcinoma of papilla of Vater. From 1984 to 1995, 8 patients underwent radical surgical intervention for tumor of papilla of Vater. The mean age of the patients was 58 years. Three of them were over 60 years. In one case Whipple procedure was performed, and pylorus-preserving pancreaticoduodenectomy was carried out in 7 patients. Using flow cytometry, the authors measured the nuclear DNA content of tumor cells. DNA ploidity status was evaluated from paraffin-embedded tumor tissues. Perioperative mortality occurred in one patient. Reoperation was performed on 2 patients, because of presence of anastomotic leakage. Survival was 50% at 1 year, 37.5% at 3 years, and 25% at 5 years. Tumor size (> 2 cm) was not negative prognostic factors for survival. The mean survival of patients with diploid cancer (n:6) was 17 months, and the mean survival of patients with aneuploid carcinoma (n:2) was 56 months. The proliferative index of the diploid carcinomas ranged from 3% to 11%. The proliferative index of the aneuploid tumors ranged from 17% to 28%. In conclusion, tumor size (> 2 cm), DNA ploidity status and proliferative index were not significantly negative prognostic factors for survival in patients with tumor of papilla of Vater.

Dyslipidaemia and hyperlipidaemia following renal transplantation.

The lipid metabolism of 93 patients with renal transplantation was prospectively studied. It was characterized by the serum levels of cholesterol, HDL, LDL, triglyceride, apolipoprotein Al, Apo B and lipoprotein (a) as well as by lipid electrophoresis. In addition to the examination of lipid concentrations, the authors looked for correlations with other metabolic changes, immunosuppressive treatment and the changes of body weight and hypertension following transplantation. Their conclusion is that hyperlipidaemic and dyslipidaemic changes, as reflected by the levels of total cholesterol, LDL and Apo B, are more considerable in women than in men. The levels of pre-beta and beta lipoprotein were not significantly lower in men than in women. With the passing of time after transplantation and with the reduction of the doses of cyclosporine and corticosteroids, the values of hypertension, hyperlipidaemia and dyslipidaemia decreased. According to the follow-up results, the lipid values measured in the winter and autumn months are higher than those found in the summer. The importance of early and follow-up examinations and of the reduction of pathological metabolic alterations is emphasized.