Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer.

OBJECTIVE: The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues. MATERIALS AND METHODS: Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of BRAF, NRAS, HRAS and KRAS were also tested. RESULTS: CYP24A1 mRNA expression was markedly increased in 52 cases (52%) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level CYP24A1 in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased CYP24A1 expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in CYP27B1 gene expression between neoplastic and normal tissues. CONCLUSIONS: A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.

Is there any connection between the presence of kidney stones in primary hyperparathyroidism and the location of an underlying adenoma?

The majority of the patients with primary hyperparathyroidism (pHPT) recurrently produce kidney stones, while the rest have other clinical manifestations. The aim of this study was to examine the possibility of an association between the presence of kidney stones and the location of an underlying adenoma. This was a retrospective evaluation of the records of 91 patients (10 males, 81 females, mean age: 61.9 years [20 - 70 yrs]) operated for primary hyperparathyroidism between 1995 and 2000. One patient was excluded due to carcinoma. Kidney stones were found in 55 cases and other clinical symptoms in 35 cases. In 50 of the 55 patients (91 %) with kidney stones, the adenoma was located in the left inferior parathyroid gland (chi2 = 67.5, p < 0.00,001), while in 24 of the 35 patients (69 %) without kidney stones, the adenoma was in the right inferior parathyroid gland (chi2 = 43.9, p < 0.0001). These results suggest that the location of the adenoma may influence the presence of kidney stones in pHPT. It is proposed that the biologic effects of parathyroid hormone could differ depending on which of the four parathyroid glands it was secreted in, or the four glands may produce different biologically active fragments.

Parathyroid surgical failures with misleading falls of intraoperative parathyroid hormone levels.

According to earlier reports, a decrease below 50% of baseline of intraoperative PTH levels measured 5 min after resection of the parathyroid adenoma predicts a cure of hyperparathyroidism. To reveal previously unrecognized pitfalls of intraoperative PTH measurements, we reviewed surgical failures in our series of parathyroidectomies combined with intraoperative PTH sampling. PTH measurements were performed in 251 patients with primary hyperparathyroidism (PHPT) between November 1999 and December 2002. PHPT due to parathyroid hyperplasia were found in 8 cases, double parathyroid adenomas in 6 cases, parathyroid carcinoma in 1 case and single parathyroid adenomas in 236 cases, all confirmed by histological examination. Of the 236 cases of single adenomas, initial surgery failed to cure PHPT in 4 patients. In 3 patients a false-positive decrease of intraoperative PTH (from 269 to 40 pg/ml, from 211 to 27 pg/ml, and from 140 to 59 pg/ml) was observed, whereas in the fourth patient a true-negative decrease of intraoperative PTH (from 758 to 401 pg/ml) was mistakenly interpreted as indication for a cure of PHPT. In each of the 4 patients in whom initial surgery failed the intervention included thyroid surgery and reoperative parathyroid surgery resulted in a permanent cure of PHPT. These observations support the possibility that thyroid surgery may compromise the blood supply of parathyroid adenomas resulting in a misleading drop of intraoperative PTH levels. Therefore, a careful evaluation of intraoperative PTH levels and, perhaps, other intraoperative aids such as histological evaluation of frozen sections are recommended when parathyroid surgery is combined with simultaneous thyroid intervention.

[New intraoperative diagnostic methods in parathyroid surgery: intraoperative measurement of parathyroid hormone]. / Mútét alatti új diagnosztikus módszerek a mellékpajzsmirigy-sebészetben: intraoperatív parathormonszint-ellenórzés.

In thirty-seven patients undergoing parathyroidectomy from November 1999 to July 2000 with diagnosis of primary hyperparathyroidism the intraoperative intact parathyroid hormone level were studied. Preoperative samples of blood were taken from a peripheral vein before the beginning the operation. The second sample was taken 5 minutes after removal of parathyroid adenoma. The plasma intact parathyroid hormone concentration was measured by quick IRMA method. The preoperative high PTH levels reduced after excision of adenoma to the mean 18%. 33 patients had normal PTH levels after 5 minutes of removing. The total measuring time of quick PTH assay was about 30 minutes. The QPTH assay was a quantitative adjunct for the surgeon to ensure a successful parathyroidectomy. When the intraoperative QPTH level is not reduced to 50%, then the exploration should be continued and the probability of reoperation is decreased. They propose the application of the routine intraoperative measurement of QPTH level in all parathyroidectomy.

[Dual-energy x-ray absorptiometry and quantitative ultrasound bone density examinations in primary hyperparathyroidism]. / Kettós energiájú röntgenabsorptiometriás és kvantitatív ultrahang-osteodensitometriás vizsgálatok primer hyperparathyreosisban.

The aim of this study was the analysis and comparison of bone density data obtained by dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS) and the follow up of bone density after parathyroidectomy of our patients with primary hyperparathyroidism. The authors performed bone mineral density (BMD) measurements using DEXA (Hologic QDR 4500 C) and QUS (Lunar Achilles Plus) devices in 22 patients with primary hyperparathyroidism between 1997 and 1999 (19 sporadic, 1 MEN 1., 2 MEN II.). Fifteen patients underwent parathyroidectomy (13 adenoma, 2 carcinoma). According to DEXA measurements all patients had osteoporosis. The lowest bone mineral density was detected at the wrist: the mean t-score was -4.00 +/- 1.79. After parathyroidectomy nine patients were followed for a mean of 12.8 months. After one year following surgery the most significant increase in BMD was 14.6%. The QUS values did not correlate with the DEXA data before the operation and no significant changes in stiffness were detected after surgery. The QUS values do not reflect the severity of the BMD decrease by DEXA in patients with primary hyperparathyroidism.

General anaesthesia for laparascopic adrenalectomy.

Surgical treatment of adrenal disorders is increasingly performed under laparascopic approach. Both pneumoperitoneum and adrenal tumour manipulation may induce haemodynamic variations. The aim of this study was to compare the inhalational and intravenous anaesthetic management for laparascopic adrenalectomy. Between 1977 and 1999 there were performed 28 laparascopic adrenalectomies. At patients with functioning adenoma and hypertension the anaesthesia was maintained with isoflurane in 8 cases and sevoflurane in 6 cases, et 14 patients with non-functioning adrenal masses with propofol and fentanyl (TIVA). In addition to the circulatory and respiratory monitoring there were made serial laboratory determinations (acid-base state, serum potassium, blood glucose) during the operation. On the basis of measured parameters isoflurane and sevoflurane anaesthesia proved to be favourable in case of functioning adrenal adenoma and TIVA with propofol and fentanyl in case of non-functioning adenoma.

Laparoscopic adrenalectomy. New experiences.

Authors have performed 23 laparoscopic adrenalectomies between 03.04.1997 and 02.04.1999. They have removed 16 cortical adenomas, 2 nodular hyperplasias, 2 cysts, 1 carcinoma, 1 pheochromocytoma and 1 myolipoma. The operation time was 90-260 minutes that gradually has been decreased by using "Ultracision" ultrasonic shear. They have made simultaneously two cholecystectomies and one liver wedge biopsy. During removing pheochromocytoma they have not detected extremely high blood pressure data. They had one intraoperative complication, the perforation of the diaphragm which required a temporary thoracic suction drainage. All operations were completed laparoscopically. Patients have been released on the 2nd-3rd postoperative day. Their experiences confirm the literary data that the laparoscopic approach to adrenalectomy is the method of choice today.

[Laparoscopic adrenalectomy]. / Laparoszkópos adrenalectomia.

The authors performed three left and one right sided laparoscopic adrenalectomies between 3rd April and 8th August 1997. The indication of surgery was hormonally active cortical adenoma of about 2 cm size in three cases, a 6 cm large hormonally inactive tumour in one case respectively. For the operation on the left side three, on the right side four trocars with 11 mm diameter was used. The duration of the operations was between 115 and 220 min. The patients left one the second or third postoperative day, no complication was observed. The authors' opinion based on both literature data and their own experience is that laparoscopic approach to adrenalectomies is the method of choice today.

Ultrastructural study of a black insulinoma.

A case of black insulinoma is reported. The color was due to a cytoplasmic pigment. Immunostaining for neuron-specific enolase and chromogranin was positive in the tumor cells, and the pigment granules themselves reacted with the chromogranin antibody. Numerous beta cell type dense core granules as well as atypical granules were found by electron microscopy. An important finding was that the dense core granules contribute to the lipofuscin pigment formation.

[Excision of a splenic cyst using a surgical stapler in partial splenectomy]. / Lépcysta eltávolítása kapocsvarrógéppel végzett részleges léprezekcióval.

The authors extirpated the splenic cyst of a young girl with the use of stapler in such a way that the distal part of the spleen was preserved. During this case the types of splenic preservative operations and the question of fulminant sepsis found in the patients went under splenectomy were surveyed. According to us the advantage of using stapler in partial splenectomy than the others is that firstly it is technically simple, less time consuming, and the haemostasis is safe. This is thought to be a valuable additional procedure to the ultimately known and the procedures which are used.

[Insulin production of isolated fresh and cryopreserved islands of Langerhans of rats]. / Untersuchung der Insulinproduktion der isolierten frischen bzw. kryopräservierten Langerhans-Inseln von Ratten.

The effect of glucose and Domperidon (R 33812, pharmaceutical factory Gedeon Richter, Budapest) on the insulin secretion were investigated in the isolated islets of Langerhans of rats. The insulin secretion was increased by glucose and also by Domperidon, however, in a smaller size. The insulin secretion of cryopreserved islets--stored in liquid nitrogen of -196 degrees C during 2-6 months--was equal with the secretion of fresh isolated islets. Thus the cryopreservation had not impaired the insulin secretion ability of the islets.

[Transplantation of islands of Langerhans: inclusion of living cells into a polymer forming a net-like structure]. / Fragen zur Transplantation von Langerhans-Inseln: Der Einschluss von lebenden Zellen in ein Polymer, welches eine netzförmige Struktur bildet.

A two-component polyacrylic amide gel forming a net-like structure was built up on pancreatic cells. In such a way the transplanted cells could be protected from the damage by immune protein with big molecule. The method was tested in yeast cells before, human erythrocytes, and wether erythrocytes. It was shown that the polymerisation and the inclusion method do not influence essentially the vitality of the examined cells. It was demonstrated by means of the complement fixation reaction that the included erythrocytes cannot be damaged by the immune protein with big molecule. Metabolic processes of the included pancreas beta cells were provable by diffusion. The experiments promise that the included cells survive after the transplantation and the polyacrylic amide gel protects the cells from the impairing effect of the immune protein.