Differential expression of kinase genes in primary hyperparathyroidism: adenoma versus normal and hyperplastic parathyroid tissue.

CONTEXT: Differentiation between adenoma and hyperplasia or even normal parathyroid tissue is difficult and based mainly on the surgeon's skill. Exploration of genes that express differentially in these various tissues using microarrays and other sophisticated research tools will enable identification and perhaps development of new methods of perioperative diagnosis. OBJECTIVE: To assemble a panel of kinase genes to differentiate parathyroid adenoma from normal and hyperplastic parathyroid tissue. DESIGN: RNA was extracted from adenoma, hyperplasia, and normal parathyroid tissue and hybridized to a microarray containing 359 human cDNAs of known kinase genes. Signals of exposure were scanned and quantified with software for digital image analysis. Semiquantitative reverse transcriptase polymerase chain reaction analysis of sample genes was performed, up-regulated or down-regulated, to validate the microarray results. RESULTS: The ratio values considered significant (<0.5 or >1.5) suggest that genes up-regulated in parathyroid adenoma are those responsible for blood vessel angiogenesis and genes belonging to the cyclin-dependent kinase inhibitor groups. Genes down-regulated in parathyroid adenoma are related to cellular growth and apoptosis--genes from the mitogen-activated protein kinase group and DNA-dependent protein kinase group. An interesting gene down-regulated in the parathyroid adenoma samples is related to the serine/threonine protein kinases that exert a key function in calcium handling. A panel of 5 genes was defined: p19, p21 and the gene for vascular endothelial growth factor from the up-regulated group, and the gene for protein kinase C and SGK from the down-regulated group. Reverse transcriptase polymerase chain reaction confirmed the microarray results for these genes. CONCLUSIONS: The kinase genes panel presented can be used to differentiate parathyroid adenoma from normal and hyperplastic parathyroid tissue in particular when histopathology fails to provide a decisive diagnosis.

Preoperative technetium Tc 99m sestamibi SPECT imaging in the management of primary hyperparathyroidism in patients with concomitant multinodular goiter.

HYPOTHESIS: Preoperative parathyroid and thyroid imaging using technetium Tc 99m sestamibi scintigraphy-single-photon emission computed tomography (Tc 99m MIBI SPECT) and technetium Tc 99m sodium pertechnetate, respectively, in patients with parathyroid adenomas and concomitant multinodular goiters enables the selection of those suitable for minimally invasive radio-guided surgery. DESIGN: One hundred thirty patients with primary hyperparathyroidism were treated surgically during a 30-month period. Forty-one of these 130 patients had an associated multinodular goiter. All patients underwent planar and SPECT parathyroid scintigraphy using Tc 99m MIBI, and thyroid scintigraphy with technetium Tc 99m pertechnetate 2 to 5 days before surgery. On the morning of surgery each patient was reinjected with Tc 99m MIBI for intraoperative localization and validation. Minimally invasive radio-guided parathyroidectomy was performed using a handheld gamma-detection device with a thyroid probe. Removed glands were submitted for histopathologic examination for comparison with the scintigraphic results. Quantitative analysis of parathyroid activity was performed. RESULTS: Minimally invasive, radioguided parathyroidectomy was successfully performed in 21 (51%) of 41 patients who had a concomitant multinodular goiter. The remaining 20 patients underwent standard neck exploratory surgery because of associated thyroid disease; 5 of them had malignant thyroid disease. Among the 41 patients planar scintigraphy correctly identified 28 adenomas (68%). Single-photon emission computed tomographic imaging identified an additional 11 adenomas for a sensitivity of 95% and a specificity of 100%. Moreover, SPECT imaging correctly identified malignant thyroid nodules in 4 of 5 patients. Technetium Tc 99m MIBI retention was noted in only 25 adenomas (61%) while the remaining adenomas demonstrated a rapid washout. The average uptake ratio of parathyroid counts to maximum thyroid activity was significantly correlated with parathyroid hormone levels before surgery (P = .04). CONCLUSIONS: Our data encourage the use of preoperative SPECT imaging of parathyroid adenomas in patients who have multinodular goiters to select those suitable for minimally invasive radioguided surgery. This technique also offers important information regarding thyroid nodules that are suspicious for malignancy. The intraoperative gamma-probe technique enables the surgeon to focus his or her search, provides instant feedback regarding the progress of the operation, reduces surgical trauma and complications, and yields better cosmetic results. Patients with higher presurgical parathyroid hormone levels may especially benefit from radioguided surgery.

Early, postinjection MIBI-SPECT as the only preoperative localizing study for minimally invasive parathyroidectomy.

HYPOTHESIS: Early, postinjection technetium Tc 99m sestamibi scintigraphy-single-photon emission computed tomography (MIBI-SPECT) can be used as the only localizing study for focused parathyroidectomy in patients with primary hyperparathyroidism. DESIGN: During a 26-month period, 82 consecutive patients with primary hyperparathyroidism underwent a standard planar scan using a double-tracer subtraction technique for localization. On the morning of surgery, each patient received radiolabeled technetium Tc 99m sestamibi for intraoperative detection and validation. We performed an early, postinjection SPECT study for comparison with the planar study. RESULTS: The SPECT study revealed a sensitivity of 96% vs 78% for the planar study. The SPECT study was helpful in locating adenomas in 10 patients with multinodular goiter disease, of whom 3 patients had ectopic adenomas and 2 patients had 2 adenomas each. A significant correlation was noted between uptake ratio and preoperative parathyroid hormone levels (r = 0.41; P =.04). No recurrent or persistent hyperparathyroidism was reported during a follow-up period of at least 6 months. CONCLUSIONS: Our results encourage the use of preoperative SPECT as the only localizing study on the morning of the operation, both to select patients for minimally invasive radioguided surgery and to provide accurate 3-dimensional information on deeply seated or ectopic adenomas. This approach lowers the costs of preoperative localization and intraoperative validation to a single study. The intraoperative gamma probe technique enables the surgeon to focus the search, provides instant feedback regarding the progress of the operation, reduces surgical trauma and complications, and yields better cosmetic results.

Expression of kinase genes in primary hyperparathyroidism: adenoma versus hyperplastic parathyroid tissue.

BACKGROUND: Differentiation between parathyroid hyperplasia and adenoma is difficult and based on the surgeon's skill. Microarrays and other sophisticated research tools generate information about differential gene expression in various tissues. Exploration of genes that express differentially in 1 tissue will enable identification and perhaps development of new methods of preoperative or intraoperative diagnosis. METHODS: RNA was extracted from parathyroid hyperplasia and adenoma tissue and hybridized to a microarray containing 359 human complementary DNAs of known kinase genes. Signals of exposure were scanned and quantified with software for digital image analysis (Atlas-image, v. 2; Clontech Labs Inc, Palo Alto, Calif). The program generates a color schematic comparison view and numeric data in a tabular format for further analysis. RESULTS: The ratio values that are considered significant (< 0.5 or > 1.5) suggest that genes up-regulated in parathyroid adenoma are those responsible for angiogenesis and production of blood vessels. Genes down-regulated in parathyroid adenoma and expressed in hyperplasia are related to a decrease in apoptosis. Moreover, an interesting gene expressed only in the hyperplasia sample is increased in relation to in vivo proliferation activities. CONCLUSIONS: Parathyroid hyperplasia and adenoma are different physiologic conditions. Further analysis of kinase genes involved in angiogenesis and apoptosis will enable design of a chip that concentrates in the different key genes responsible for the transition between hyperplasia and adenoma. Identifying such genes will enable to target both diagnostic and therapeutic approaches.

The role of laparoscopy and laparoscopic ultrasound in the diagnosis of cystic lesions of the pancreas.

With the widespread use of advanced imaging techniques, cystic lesions of the pancreas are now diagnosed relatively frequently. The nature of these lesions vary from benign cysts (serous cvstadenoma) or an inflammatory process (pseudocyst), to premalignant (mucinous cystadenoma) or frankly malignant lesions (cystadenocarcinoma). Differentiation of various types of pancreatic cysts presents a diagnostic and therapeutic challenge, as clinical presentation may be vague. Laparoscopic ultrasonography (LAPUS), the biopsy of the cystic wall, and analysis of the cystic aspirate, although expensive and rather invasive procedures, significantly contribute to the differential diagnosis of pancreatic cystic lesions.