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PubMed1988

Gallium nitrate for acute treatment of cancer-related hypercalcemia. A randomized, double-blind comparison to calcitonin.

STUDY OBJECTIVE: To determine whether gallium nitrate therapy is superior to maximally approved doses of calcitonin for acute control of cancer-related hypercalcemia. DESIGN: Randomized, double-blind comparison of active treatments. SETTING: Comprehensive cancer center. PATIENTS: One hundred ninety-eight consecutive hypercalcemic events in 164 patients screened for entry. ELIGIBILITY CRITERIA: hospitalization and intravenous hydration for at least 2 days; persistent elevated serum calcium levels of 2.99 mmol/L or greater (adjusted for serum albumin); serum creatinine levels of 221 mumol/L or less; no cytotoxic chemotherapy, radiation, or mithramycin within the preceding 7 days or during study; no concurrent use of aminoglycoside antibiotics; life expectancy greater than 4 weeks; lymphoma and parathyroid carcinoma excluded. Patients were stratified by histologic type of tumor (epidermoid or nonepidermoid). Fifty patients were randomized and treated. INTERVENTIONS: Gallium nitrate 200 mg/m2 body surface area for 5 days by continuous intravenous infusion, or salmon calcitonin 8 IU/kg body weight every 6 hours for 5 days by intramuscular injection. Patients randomized to receive gallium nitrate received sham injections of saline to simulate calcitonin; patients randomized to receive calcitonin received 1000 mL 5%-dextrose solution to simulate gallium nitrate. MEASUREMENTS AND MAIN RESULTS: All patients were evaluable. Eighteen of twenty-four patients who received gallium nitrate achieved normocalcemia compared with 8 of 26 patients who received calcitonin for an observed difference of 44% (95% confidence interval, 19% to 69%; P = 0.002). Median duration of normocalcemia before other cytotoxic or hypocalcemic therapy was 6 days for patients treated with gallium nitrate compared with 1 day for patients treated with calcitonin (P less than 0.001). Median duration of normocalcemia regardless of intercurrent treatment and without adjustment for serum albumin was 11+ days for patients treated with gallium nitrate and 2 days for patients treated with calcitonin (P less than 0.01). Mean daily fluid intake and mean daily dose of furosemide were similar in both treatment groups. No additional benefit was seen in 9 patients randomized to receive calcitonin who incidentally received corticosteroids. CONCLUSIONS: Gallium nitrate therapy is highly effective and superior to maximally approved doses of calcitonin for acute control of cancer-related hypercalcemia.

Adult↗
PubMed1999

Learning curves and certification for breast cancer lymphatic mapping.

To determine the usefulness of lymphatic mapping and SLN biopsy, two distinct aspects of the technique must be evaluated, mapping success rates and mapping accuracy. The mapping success rate simply reflects the ability to successfully map a SLN. Mapping accuracy is reflected by the false-negative rate defined as the proportion of patients with axillary metastases among those in whom the SLN is negative for disease. It is critical within each institution that these two measurements be obtained to validate the multidisciplinary collaborative effort. It seems that surgeons with appropriate training should be able to map with 85% efficiency with zero or one false-negative cases in their first 10 patients with metastatic disease. It is our recommendation that individual surgeons join together and follow an institutional (IRB approved) protocol for lymphatic mapping in which each surgeon is required to perform at least 30 procedures of SLN biopsy followed by completion axillary lymph node dissections (phase I). There are several advantages for surgeons and patients to participate in national trials as a new technique is established: 1. Patients are fully informed. 2. For those patients who have SLN biopsy followed by a CLND (phase I), there is still an added advantage in that the SLN can be scrutinized more closely resulting in more accurate staging. 3. The surgeon and the institution can be reimbursed even while the surgeon is on the learning curve. 4. It provides for good publicity for the institution. The data should be reviewed for each surgeon after completing the first 30 cases. If the aforementioned goals of 85% success with one or fewer false-negative cases is achieved, then the individual surgeon may move on to a second (phase II) mapping protocol. In phase II, a SLN biopsy is performed and a CLND is performed only if a SLN cannot be located or the SLN contains metastases. Should the aforementioned criteria not be met, then additional procedures or onsite intraoperative mentoring may be required to further evaluate the deficiencies of the mapping procedure by the surgeon or institution. Remember that failure to map may be a function of surgical skill, nuclear medicine injection methodology, or the pathologic evaluation of the SLN. Should institutional problems arise, onsite mentoring may be helpful by someone with adequate mentoring skills to troubleshoot a potential problem. The previously outlined recommendations are similar to the recently published requirements of the American Society of Breast Surgeons that recommend documentation of 30 cases or more with an 85% or higher success rate in identifying a SLN and 5% or greater false-negative rate (single false-negative SLN in the series). A national network of training centers is being established for radioguided surgery. This new technology has the potential of being applicable to 350,000 new cases of cancer diagnosed annually in the United States. Applications include breast cancer, melanoma, and other skin tumors like Merkel cell carcinoma and poorly differentiated squamous cell carcinoma, parathyroid localization, vulvar and vaginal lesions, and bone localization. This network of training centers will provide an opportunity for surgeons, nuclear medicine physicians, and pathologists to come together and learn about this new technology. Training will include didactic sessions, live surgery, and hands-on experience with animal models. The faculty will consist of leading experts from across the country. Participating centers include the H. Lee Moffitt Cancer Center and Research Institute, John Wayne Cancer Institute, and the M.D. Anderson Cancer Center. Training sites will also be available in Durham, NC; Pittsburgh, PA; Seattle, WA; Little Rock, AR; and St. Louis, MO. The network provides access to a national lymphatic mapping database (http:/(/)mapping.rad.usf.edu), participation in national trials, and web site listings (melanoma.net, or breastdoctor.com, and endocrine

Axilla↗
PubMedDate not supplied

[Clinical characteristics and course of severe hypercalcemia caused by primary hyperparathyroidism in surgically treated patients].

AIM: To describe presentation, diagnosis, management and outcome of severe hypercalcemia due to primary hyperparathyroidism in a series of patients. METHODS: Clinical characteristics, presentation, diagnosis, acute preoperative medical management, surgical findings and strategy, short outcome and complications of a cohort of 21 patients with primary hyperparathyroidism (HPT) and severe hypercalcemia (serum calcium > or = 14 mg/dL) were analyzed. This group was selected from a total of 118 patients who underwent surgery for HPT in the time period. RESULTS: Mean age was 47 +/- 17 years-old and the male:female ratio was 4:17. A total of 95% of patients presented one or more symptoms related to hypercalcemia while 62% had an abnormal EKG and 76% also had radiological abnormalities. All patients received intense hydration often associated to diuretics. Uniglandular disease was found in 13 patients, multiglandular involvement was identified in 4 and parathyroid carcinoma was documented in other 4. Normalization of the calcemia was achieved in all patients with benign disease. CONCLUSIONS: Severe hypercalcemia was relatively frequent in our patients with HPT. Most patients were symptomatic and presented radiological or cardiac abnormalities. Surgical normalization of the calcemia was achieved in all patients with benign disease.

Adolescent↗
PubMed2001

[Fifteen years experience in the surgical treatment of primary hyperparathyroidism].

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.

Humans↗
PubMed2002

Anesthesia for one-stage bilateral pheochromocytoma resection in a patient with MEN type IIa: attenuation of hypertensive crisis by magnesium sulfate.

Multiple endocrine neoplasia (MEN) type IIa, manifesting as an autosomal dominant trait, consists of medullary thyroid carcinoma, parathyroid adenoma or hyperplasia, and pheochromocytoma. We report our experience of a 42-year-old woman, MEN type IIa with a large bilateral pheochromocytoma, who underwent one-stage bilateral tumor resection under a combined continuous epidural technique with 0.25 per cent bupivacaine and general anesthesia using vecuronium, fentanyl, nitrous oxide, and isoflurane. An initial intra-operative hypertensive response was acceptably controlled by nitroprusside and a beta-blocker but during tumor handling the hypertensive crisis worsened and she developed acute pulmonary edema despite a continuing high dose of nitroprusside infusion. After receiving intermittent i.v. MgSO4 up to 3 g in 15 min, her condition gradually improved and the cardiovascular response was under control throughout the period of tumor handling. Hypotension encountered post-pheochromocytoma resection was treated by volume replacement, metaraminol, CaCl2, and dopamine infusion. The patient's post-operative course was uneventful.

Adrenal Gland Neoplasms↗
PubMed1992

Fine needle aspiration cytology, sonography and radionuclide scanning in solitary thyroid nodule.

One hundred and ninety three consecutive patients with solitary thyroid nodule (STN), with a mean age of 36.0 +/- 12.8 years and male to female ratio of 5.6:1, were studied. Ninety five percent of patients came from iodine deficient regions. Seventy two percent presented for local neck swelling, 12.4% for hyperthyroid state and in 7.7% STN was discovered incidentally. Scintigraphically, 77.7% of nodules were cold, 12.4% hot and 8.5% warm. Sonographic evaluation did not reveal any characteristic echotexture diagnostic of malignancy, but detected clinically nonpalpable accessory nodules in 20.6% of patients. Fine needle aspiration cytology was positive for malignancy in 6.2% of patients. Features of follicular and Hurthle cell neoplasm were seen in 12.9% of aspirates. Eighty eight (45.6%) STN were resected surgically. Histologically, there was one false positive and one false negative aspirate and a case of parathyroid adenoma on aspiration proved to be parathyroid carcinoma on histology.

Adult↗
PubMed1991

Primary hyperparathyroidism during pregnancy.

Historically, primary hyperparathyroidism during pregnancy was associated with significant risk of maternal morbidity and fetal death. Maternal hypercalcemia results in fetal hypercalcemia, leading to suppression of fetal parathyroid gland function. Neonatal hypocalcemia with tetany is a common occurrence after birth when maternal calcium flow is interrupted. From 1930 to 1990, 109 cases of women with primary hyperparathyroidism associated with pregnancy have been reported, 39 of whom were treated surgically before delivery. Although fetal mortality rates for medically treated women have improved, fetal morbidity continues to remain higher than in women who undergo surgical treatment of parathyroid disease during pregnancy. Of 850 patients treated surgically for primary hyperparathyroidism since 1960, 12 were pregnant. Four of the patients were treated medically during pregnancy and underwent surgery after delivery; all four infants had neonatal hypocalcemia and tetany. The remaining eight patients were treated surgically during pregnancy: six in the second trimester and two (one with associated pancreatitis and one with hypercalcemic crisis) during the first trimester. There was no fetal or maternal morbidity or death in the surgical group. Parathyroid adenomas were present in 10 of the patients, hyperplasia in one, and parathyroid carcinoma in one. The management of maternal primary hyperparathyroidism diagnosed during pregnancy should be based on the patient's symptoms and severity of disease. Hyperparathyroidism characterized by progressive symptoms should be treated surgically, preferably during the second trimester. Symptom-free patients and those with mild hypercalcemia diagnosed in the third trimester may be managed medically, postponing operation until after delivery.

Female↗
PubMed1977

Delayed fracture healing in primary hyperparathyroidism.

The incidence of fractures in primary hyperparathyroidism is highly variable. The possibility that there might be an increased susceptibility to fracture is discussed. Healing in most is without delay. Three cases of delayed or nonunion following fracture are presented. In all three, healing accelerated dramatically after excision of a parathyroid adenoma. A pathological fracture secondary to the hyperparathyroidism of parathyroid carcinoma healed after excision of the tumor allowed regression of the osseous lesions. The endocrinologic mechanisms which cause nonunion in a small percentage of cases have not been clearly elucidated.

Female↗
PubMed1993

Primary hyperparathyroidism in children: report of a case and a brief review of the literature.

A case of primary hyperparathyroidism in an 11-year-old boy who presented with bowlegs is reported and the literature is reviewed. From the literature, it appears that the pathologic findings, clinical manifestations and sex distribution of primary hyperparathyroidism is different in adults than in children and young infants. In adults, primary hyperparathyroidism is commonly caused by adenoma and is often found unexpectedly on a biochemical screen of the serum. Elderly women are most at risk. Renal stones or other renal complications are more frequently seen in adults than in children. Neonatal hyperparathyroidism is often genetically transmitted and is fatal unless recognized and treated early. The characteristic pathologic change is chief cell hyperplasia of the parathyroid glands. On the other hand, adenoma is the most common pathologic finding in older children. No case of childhood parathyroid carcinoma was found in our review of the literature. In children, primary hyperparathyroidism is more frequent in boys than in girls and osseous lesions are more common than in adults. Prognosis is good if the disease is recognized early and appropriate surgical treatment is received.

Child↗
PubMed1993

[Two cases of hypercalcemic nephropathy associated with primary hyperparathyroidism].

We present two cases of hypercalcemic nephropathy associated with primary hyperparathyroidism. Case 1 is a 37-year-old man who had repeated bone fractures and recurrent ureteral stones, which led to the diagnosis of primary hyperparathyroidism. Case 2 is a 35-year-old man in whom parathyroid carcinoma was discovered because of secondary nephrogenic diabetes insipidus, resulting from severe hypercalcemia. Both patients developed mild renal dysfunction during the course of hyperparathyroidism. In the renal biopsy materials obtained from case 1, the renal interstitium showed chronic inflammatory changes. The tubules were partly damaged (focal necrosis). Deposition of calcium was sometimes noted within the mitochondria of the tubular epithelial cells. Some glomeruli showed glomerular sclerosis. In biopsy materials obtained from case 2 after resection of the carcinoma, similar histological features were observed, but tubular atrophy and necrosis were advanced. Polyuria and hypercalcemia were ameliorated after resection. These findings indicate that severe hypercalcemia might induce tubular dysfunction as well as organized changes.

Adult↗
PubMed1993

Recurrent hyperparathyroidism from benign neoplastic seeding: a review with recommendations for management.

Benign neoplastic seeding represents a rare cause of hyperparathyroidism found at parathyroid reoperations. It consists of pathologically benign neoplastic parathyroid tissue scattered throughout a previous parathyroid surgical site. We describe a case of recurrent and then persistent hyperparathyroidism occurring in a patient during an 18-year period. The patient's third operation showed nonmalignant parathyroid tissue throughout the right neck bed, which necessitated extensive parathyroid and fibrofatty tissue dissection and a thyroidectomy. This unexpected finding of extensive parathyroid seeding has only been described in detail in ten other patients in the past. A review of these 11 patients shows several features: initial operations were for large parathyroid tumors or cysts in six patients; rupture and spillage of contents occurred in six; and initial hypercalcemia was severe in several patients, perhaps indicating inherently more aggressive tumors. The appearance of benign neoplastic seeding resembled parathyroid carcinoma in its local invasiveness. Therefore the presence of anaplasia, mitoses, capsular invasion, and cellular spindling must be relied on as distinguishing factors. When confronted with this presentation, we recommend removal of all nodal bearing, thyroid, and fibrofatty tissue from the level of the thyroid cartilage to the superior mediastinum and a thyroidectomy if necessary.

Female↗
PubMed2002

[Results of treatment of parathyroid gland cancer].

Carcinoma of parathyroid glands is characterized by relatively slow course, frequent recurrence after performance of operation. Authors were observed 8 patients, operated in 1967-2001, what had constituted 6% of all quantity of the primary hyperparathyroidism observations. Early diagnosis and performance of adequate surgical intervention promote the efficacy of treatment raising and the prognosis improvement. Most favourable prognosis was noted after performance of primary radical operation. In most observations the performance of reoperation guarantee long-lasting remission, but rarely constitutes the radical measure.

Adult↗
PubMed2005

Synchronous parathyroid and papillary thyroid carcinoma.

Concomitant thyroid disease is not unusual among patients with primary hyperparathyroidism. However, the simultaneous occurrence of parathyroid and thyroid carcinoma is extremely rare. We report a 38-year-old man with primary hyperparathyroidism who presented with osteitis fibrosa cystica complicated with pathologic femoral neck fracture. Preoperative investigation for exclusion of multiple endocrine neoplasia did not find evidence of medullary thyroid carcinoma or pheochromocytoma, but imaging studies revealed the presence of nodules in the right lobe and a parathyroid lesion over the left inferior pole of the thyroid gland. Total thyroidectomy, left parathyroidectomy, and bipolar hemiarthroplasty of the left hip were then performed simultaneously. The resected specimens were pathologically identified as papillary thyroid carcinoma and parathyroid carcinoma, respectively. After the operation, 131I ablation therapy was administered at a dose of 120 mCi. Additional doses of 30 mCi were given yearly as serum thyroglobulin level became elevated. Serum calcium level remained normal during yearly follow-up. Although parathyroid carcinoma is an uncommon cause of parathyroid hormone-dependent hypercalcemia, it should nonetheless be given due consideration because its surgical approach differs from that of parathyroid adenoma. As the coexistence of parathyroid and non-medullary thyroid carcinoma has previously been reported, the possibility of both malignancies must also be considered in the setting of primary hyperparathyroidism with thyroid nodules. If confirmed with preoperative parathyroid scintigraphic and other laboratory studies, an optimal outcome may be achieved with complete resection of both tumors at the time of initial operation, followed by adjunctive therapy.

Adult↗
PubMed1984

Histological diagnosis of carcinoma of the parathyroid gland.

During the period 1950-81, 678 cases of primary hyperparathyroidism were surgically treated at University College Hospital, London. The causes were a single adenoma in 575, two adenomas in 25, carcinoma in 20 (two of which had coexistent adenomas), chief cell hyperplasia in 56, and water clear cell hyperplasia in two. Histological diagnosis is not difficult except in some cases of carcinoma and in a few in which differentiation between recurrent hyperplasia and recurrent carcinoma is exceptionally difficult. In this paper we review all the cases of primary carcinoma of the parathyroid seen during this period to define those pathological features of value in the diagnosis.

Adenoma↗
PubMedDate not supplied

Life-threatening hypercalcemia from a hepatocellular carcinoma secreting intact parathyroid hormone: localization by sestamibi single-photon emission computed tomographic imaging.

OBJECTIVE: To describe a patient with severe hypercalcemia and elevated intact parathyroid hormone (iPTH) levels associated with a hepatocellular carcinoma. METHODS: We present a case report, detailing the laboratory, surgical, and sestamibi scanning findings. Moreover, the literature relating to paraneoplastic ectopic production of iPTH is reviewed. RESULTS: A 72-year-old man had the following laboratory results at the time of initial assessment: serum calcium of 14.5 mg/dL, ionized calcium of 6.8 mg/dL, serum iPTH of 92 pg/mL, and a PTH-related peptide of <0.7 pg/mL. Findings on preoperative sestamibi scanning were suggestive of a parathyroid adenoma, with additional uptake in the dome of the liver. He was diagnosed as having primary hyperparathyroidism, and a neck exploration was undertaken. The right superior, right inferior, and left superior parathyroid glands were mildly enlarged and were excised. The left inferior parathyroid gland could not be identified, despite an extensive neck exploration. Bilateral internal jugular vein sampling demonstrated elevated iPTH levels, an indication of a systemic origin of the hormone. Postoperatively, a repeated sestamibi scan confirmed hyperactivity in the liver, and a subsequent computed tomographic scan revealed masses in segments IV, VII, and VIII of the liver in conjunction with portal vein involvement. Tissue biopsy confirmed the presence of hepatocellular carcinoma, and the fluid obtained with the biopsy specimen was strongly positive for iPTH. The patient was treated with transarterial chemoembolization but subsequently died. CONCLUSION: This case demonstrates the rare occurrence of hepatocellular carcinoma producing iPTH as the cause of life-threatening hypercalcemia. Sestamibi scans were accurate in detecting focal hyperactivity that correlated with the malignant involvement.

Aged↗