Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study

Background Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Methods Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. Results DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63–2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09–8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. Conclusions The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.BioMed Central open acces

Оптимизация энергопотребления электроплавильных печей с использованием технологий предварительного подогрева шихты

Материалы ХI Международной науч.-техн. конф. студентов, магистрантов и аспирантов [28-29 апреля 2011 г., г. Гомель]. - Гомель, 2011

Calcium Homeostasis After Thyroid Surgery

Calcium homeostasis after thyroid surgery was studied during the immediate postoperative period and after one year. One day after hemithyroidectomy ionised calcium decreased whereas basal PTH did not change. EDTA stimulated maximal and total PTH secretion and set-point decreased on postoperative day 1 and normalised on day 7. One year after hemithyroidectomy (n=10) total calcium and 1.25(OH)2D3 decreased. EDTA and calcium infusion tests showed that maximal and total PTH secretion were unaltered. However, ionised calcium at maximal PTH secretion was reduced, the set-point slightly decreased and the ionised calcium/PTH relation curve left shifted. One year after hemithyroidectomy (n=45) ionised calcium decreased from 1.25±0.05 to 1.22±0.04 mmol/L (p=0.001) despite an unaltered PTH level (2.8±1.0 vs. 3.1±1.5 pmol/L, p=0.50). The marker of bone resorption 1CTP decreased. A reduction in ionised calcium was seen only in groups with reduced FT4. An independent association was found between reduced ionised calcium and altered TSH and FT4 levels. The peripheral effects of PTH were studied by using a six hour hPTH-(1-34) infusion protocol. Induced changes in serum levels of ionised calcium and 1.25(OH)2D3 and in urinary excretion of phosphate and n-cAMP, were not altered by a slight reduction in thyroid hormones at 3 months after hemithyroidectomy. Intraoperative PTH, measured immediately after total or near-total thyroidectomy, showed an independent association with postoperatively reduced serum calcium levels. Intraoperative PTH was lower among patients who developed biochemical hypocalcemia (p<0.001). Low intraoperative PTH identified the patients who required calcium intravenously within 24 hours postoperatively and predicted biochemical hypocalcemia with a sensitivity and specificity of 90 % and 75 %, respectively. In summary, reduced PTH secretion is the main determinant of transient hypocalcemia after thyroid surgery. Low intraoperative PTH is a feasible predictor of postoperative hypocalcemia. Even minor thyroid surgery, i.e. hemithyroidectomy has sustained effects on calcium homeostasis due to the influence of reduced thyroid hormones on bone remodelling

Hegemonin reviderad? Manshistoriskt seminarium i Jyväskylä 5–6.11.2009

En seminar-rapport om Manshistoriskt seminarium i Jyväskylä 5–6.11.200

Measurement of intraoperative parathyroid hormone predicts long-term operative success.

HYPOTHESIS: A decrease in the intraoperative parathyroid hormone (PTH) level predicts long-term operative success. DESIGN: A case series of consecutive patients undergoing parathyroidectomy with intraoperative PTH measurement. SETTING: A university hospital. PATIENTS AND INTERVENTION: One hundred two patients with sporadic primary hyperparathyroidism underwent parathyroidectomy according to the principles of unilateral exploration with intraoperative PTH measurement. MAIN OUTCOME MEASURES: Longitudinal effects on levels of serum calcium and PTH. RESULTS: In 94 of 98 patients who underwent primary exploration because of a solitary adenoma, intraoperative PTH decreased at least 60% 15 minutes after gland excision. The 4 cases in which PTH fell to less than 60% were classified as false negatives. Patients examined for multiglandular disease (n = 4) were correctly predicted not to have an adenoma. Twenty-two patients (22%) were unavailable for 5-year follow-up. These patients were followed up for 2 months to 48 months (median, 24 months), and none developed recurrent primary hyperparathyroidism. Of the remaining 80 patients (78%), all but 1 patient had normal or slightly decreased serum calcium levels (mean +/- SD, 9.24 +/- 0.4 mg/dL [2.31 +/- 0.10 mmol/L]) at 5-year follow-up. One patient with hypercalcemia (10.6 mg/dL [2.65 mmol/L]) was interpreted to have developed renal failure with secondary hyperparathyroidism. Thirty-four patients had elevated serum PTH levels at least once during the postoperative study period, with normal or slightly decreased calcium concentrations. The prediction of late postoperative normocalcemia by means of intraoperative PTH measurement had an overall accuracy of 95%. CONCLUSIONS: The measurement of intraoperative PTH during surgery for primary hyperparathyroidism accurately differentiates between single- and multiple-gland disease and ensures good long-term results

Low parathyroid hormone levels after thyroid surgery: a feasible predictor of hypocalcemia.

BACKGROUND: Selecting patients with a low risk of hypocalcemia is mandatory if patients are to be discharged on the first day after bilateral thyroidectomy. This study investigated the predictive value of intraoperative parathyroid hormone (PTH). METHODS: Thirty-eight patients underwent total or near-total thyroidectomy. Patients with or without biochemical and symptomatic hypocalcemia were compared regarding intraoperative PTH levels and previously suggested risk factors. The accuracy of intraoperative PTH to predict patients at risk for postoperative hypocalcemia was compared with a calcium concentration of less than 2.00 mmol/L (8.0 mg/dL) on the first postoperative day. RESULTS: PTH levels after resection of the second lobe, age, and number of parathyroid glands identified intraoperatively were independently associated with the reduction in serum calcium concentration measured at nadir on the first or second postoperative day. PTH levels after resection of the second lobe were lower among patients who developed biochemical (P <.001) and symptomatic hypocalcemia (P <.01) compared with those who did not. Low levels of intraoperative PTH identified the 3 patients who required intravenous calcium during the first 24 postoperative hours. An intraoperative PTH level below reference range and a calcium concentration of less than 2.00 mmol/L measured 1 day postoperatively both predicted biochemical hypocalcemia with a similar sensitivity (90% vs 90%) and specificity (75% vs 82%). Intraoperative PTH was slightly better than a serum calcium concentration of less than 2.00 mmol/L on postoperative day 1 to predict symptomatic hypocalcemia, with a sensitivity of 71% vs 52% and a specificity of 81% vs 76%, respectively. CONCLUSIONS: Parathyroid gland insufficiency is the main determinant of transient hypocalcemia after bilateral thyroid surgery. Low intraoperative PTH levels during thyroid surgery are therefore a feasible predictor of postoperative hypocalcemia

Hemithyroidectomy: Long-term effects on parathyroid function-preliminary report

Early hypocalcemia after thyroid surgery has frequently been reported, whereas data regarding long-term effects on calcium homeostasis are scarce. We have previously studied patients after hemithyroidectomy with an oral calcium load test and found normal parathyroid hormone (PTH) suppression. However, the 1,25-dihydroxyvitamin D concentration was decreased and the phosphate concentration increased, implying parathyroid insufficiency. We therefore proceeded to investigate PTH secretion and suppression in 10 euthyroid patients subjected to hemithyroidectomy due to benign thyroid disease before and at 1 year after surgery. In addition, biochemical variables known to influence calcium homeostasis were analyzed. Basal, maximal, and total PTH secretion were unaltered 1 year postoperatively. However, maximal PTH secretion was reached at a lower serum level of ionized calcium, and there was a tendency toward increased parathyroid sensitivity to ionized calcium. Furthermore, compared to preoperatively, total serum calcium, 1,25-dihydroxyvitamin D, and free thyroxine (T-4) concentrations were decreased at follow-up. Total serum calcium and 1,25-dihydoxyvitamin D concentrations were decreased 1 year after hemithyroidectomy. These changes were not due to parathyroid insufficiency. Instead, our results imply increased parathyroid sensitivity to calcium and possibly reduced peripheral sensitivity to PTH

Unilateral Versus Bilateral Neck Exploration for Primary Hyperparathyroidism: A Prospective Randomized Controlled Trial

OBJECTIVE: To compare unilateral and bilateral neck exploration for primary hyperparathyroidism in a prospective randomized controlled trial. SUMMARY BACKGROUND DATA: Based on the assumption that unilateral neck exploration for a solitary parathyroid adenoma should reduce operating time and morbidity, a variety of minimally invasive procedures have challenged the idea that bilateral neck exploration is the gold standard for the surgical treatment of primary hyperparathyroidism. However, to date, no open prospective randomized trial has been published comparing unilateral and bilateral neck exploration. METHODS: Ninety-one patients with the preoperative diagnosis of primary hyperparathyroidism were randomized to unilateral or bilateral neck exploration. Preoperative scintigraphy and intraoperative parathyroid hormone measurement guided the unilateral exploration. Gross morphology and frozen section determined the extent of parathyroid tissue resection in the bilateral group. The primary end-point was the use of postoperative medication for hypocalcemic symptoms. RESULTS: Eighty-eight patients (97%) were cured. Histology and cure rate did not differ between the two groups. Patients in the bilateral group consumed more oral calcium, had lower serum calcium values on postoperative days 1 to 4, and had a higher incidence of early severe symptomatic hypocalcemia compared with patients in the unilateral group. In addition, for patients undergoing surgery for a solitary parathyroid adenoma, unilateral exploration was associated with a shorter operative time. The cost for the two procedures did not differ. CONCLUSIONS: Patients undergoing a unilateral procedure had a lower incidence of biochemical and severe symptomatic hypocalcemia in the early postoperative period compared with patients undergoing bilateral exploration. Unilateral neck exploration with intraoperative parathyroid hormone assessment is a valid surgical strategy in patients with primary hyperparathyroidism with distinct advantages, especially for patients with solitary parathyroid adenoma

Peripheral effects of PTH are not altered after thyroid surgery in euthyroid patients

Background. We have previously found decreased serum levels of both ionized calcium and 1,25(OH)(2)D and an increase in serum phosphate levels at 1 year after hemithyroidectomy. However, basal and stimulated parathyroid hormone (PTH) secretions were not altered. To investigate whether the observed biochemical changes after unilateral thyroid surgery may be due to a relative end-organ resistance to PTH, we studied the peripheral effects of infused hPTH-(1-34) in 6 patients preoperatively and 3 months after hemithyroidectomy. Methods: Serum levels of TSH, FT4 and FT3 were measured pre- and postoperatively. hPTH-(1-34) was infused at 0.9 IU/kg/h during 6 h. Blood samples for analysis of ionized calcium, intact PTH, phosphate, 25(OH)D, 1,25(OH)(2)D and urinary samples for calcium, phosphate and nephrogenous(n)-cAMP analysis were taken at baseline, when the infusion was discontinued after 6 h and at 24 h. Results: Three months after hemithyroidectomy, serum levels of FT3 were decreased and TSH levels increased. Pre- and postoperative hPTH-(1-34) infusions induced increased serum levels of ionized calcium, 1,25(OH)2D, increased urinary excretion of phosphate and elevated n-cAMP levels. The changes in the studied biochemical variables during the hPTH-(1-34) infusions did not differ between the two study occasions. Conclusion: By using a 6-hour hPTH-(1-34) infusion protocol, we have shown that the peripheral PTH effect is not altered by a slight reduction in thyroid hormone levels at 3 months after hemithyroidectomy