Biomedical subjects

Alan P B Dackiw

Publications and source records attributed to Alan P B Dackiw.

13 recordsLinked to original sources

PubMed2006

Laparoscopic resection of a paraganglioma of the organ of Zuckerkandl in a patient with a carotid body tumor.

Paragangliomas of the organ of Zuckerkandl are rare tumors with only several case reports noted in the literature. Synchronous paraganglioma occur sporadically, and on occasion, in association with several genetic syndromes. Paraganglioma of the organ of Zuckerkandl with synchronous carotid body paraganglioma is described herein. Traditionally, surgical resection of abdominal paraganglioma involved an exploratory laparotomy. In this manuscript, we describe one of the first reported laparoscopic resections of this tumor and review the literature on multiple paragangliomas and their associated genetic syndromes.

Adult↗

PubMed2005

Follicular thyroid lesions, elements that affect both diagnosis and prognosis.

The precise diagnosis of follicular thyroid lesions is frequently debated because of the subjective nature of capsular invasion as well as both the histological and cytological characteristics. Furthermore, several different prognostic indices have been devised to examine prognosis associated with thyroid cancer. Herein, we describe how these confounding elements can affect the ability to accurately predict prognosis for patients with follicular thyroid lesions.

Adenocarcinoma, Follicular↗

PubMed2005

A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression.

BACKGROUND: Thyroid nodules are common; fine-needle aspirations commonly are read as indeterminate, necessitating surgery to exclude carcinoma. We developed a 6-gene array-based predictor model to diagnose benign versus malignant thyroid lesions. In this study, we verified whether quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using this model reliably can differentiate benign from malignant thyroid nodules. METHODS: Molecular profiles of benign (follicular adenomas, hyperplastic nodules) and malignant tumors (papillary thyroid carcinomas, follicular variants of papillary thyroid carcinomas) were analyzed using qRT-PCR from our 6-gene model (kit, Hs.296031, Hs.24183, LSM7, SYNGR2, C21orf4). The gold standard was standard pathologic criteria. A diagnosis-predictor model was built by using the training samples and was then used to predict the class of 10 additional samples analyzed as unknowns. RESULTS: Our predictor model using 47 training samples correctly predicted 9/10 unknowns. One sample diagnosed as benign by standard histologic criteria was diagnosed as malignant by our model (sensitivity 75%; specificity, 100%; positive predictive value, 100%; negative predictive value, 85.7%). CONCLUSIONS: Molecular diagnosis with our 6-gene model can differentiate between benign and malignant thyroid tumors with high sensitivity and specificity. In combination, these genetic markers may be a reliable test to preoperatively diagnose the malignant potential of thyroid nodules.

Adenoma↗

PubMed2005

25-hydroxyvitamin D deficiency is a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy.

BACKGROUND: Patients with primary hyperparathyroidism who undergo minimally invasive parathyroidectomy (MIP) may have postoperative symptoms of hypocalcemia or secondary hyperparathyroidism. This study sought to identify factors predictive of these events. METHODS: Between 1998 and 2004, 190 patients with primary hyperparathyroidism underwent MIP with excision of a single adenoma. Age, gender, race, prior head and neck surgery, use of preoperative thyroid hormone or calcium-channel blockers, preoperative levels of calcium, 25-hydroxyvitamin D (25[OH]D) and intact parathyroid hormone (iPTH), the presence of osteopenia or osteoporosis, intraoperative iPTH levels, and adenoma weight were evaluated by univariate analysis as predictors of postoperative symptoms of hypocalcemia and secondary hyperparathyroidism. RESULTS: None of the following were predictors of postoperative symptoms of hypocalcemia: age, gender, race, prior head and neck surgery, preoperative medications, preoperative calcium and iPTH levels, osteopenia or osteoporosis, intraoperative iPTH levels, or adenoma weight. However, patients with postoperative symptoms of hypocalcemia had significantly lower preoperative 25[OH]D levels (P = .01). Further, higher preoperative iPTH levels (P < .01) and lower preoperative 25[OH]D levels (P = .05) were associated with secondary hyperparathyroidism postoperatively. CONCLUSIONS: A low preoperative 25[OH]D level is associated with postoperative symptoms of hypocalcemia and secondary hyperparathyroidism in patients undergoing MIP. One might consider instituting empiric calcium supplementation postoperatively in patients with low 25[OH]D levels.

Adenoma↗

PubMed2005

Modern approaches to age-old questions about thyroid tumors.

There is a compelling need for improvement in the diagnosis of thyroid nodules, in predicting thyroid cancer prognosis and, in the treatment of recurrent well-differentiated and anaplastic thyroid cancer. In this review we discuss the impact of genomic technologies such as microarrays, SAGE, and proteomics on the diagnosis, prognosis and treatment of thyroid cancer. Gene expression profiling using these technologies has shown promising results in the molecular classification of different types of cancer, including thyroid. Furthermore, microarrays have been successfully used to identify prognostic markers in other cancer-types, offering the possibility to better tailor thyroid cancer treatment schemes. Lastly, novel therapeutic targeting against tyrosine kinases have shown promising results in the treatment of several cancers and might prove to be beneficial for patients with recurrent or undifferentiated thyroid cancer.

Humans↗

PubMed2004

Vitamin D3 administration induces nuclear p27 accumulation, restores differentiation, and reduces tumor burden in a mouse model of metastatic follicular thyroid cancer.

We have previously demonstrated in vitro that 1alpha,25-dihydroxyvitamin D3 (calcitriol) treatment increases p27 expression and decreases cell proliferation in cultured thyroid carcinoma cell lines. We hypothesized that in vivo treatment with calcitriol would have a beneficial effect on thyroid carcinoma growth and progression. Five x 10(6) WRO (human thyroid follicular carcinoma derived) cells were implanted in the neck in 4- to 5-wk-old female SCID mice in an orthotopic xenograft model. Animals (n = 15) were treated i.p. three times a week for 21 d with 0.75 microg/kg calcitriol or vehicle. Mice were killed 21 d after tumor implantation, tumor volume was measured, and excised tumor tissue was examined by light microscopy and immunohistochemistry for p27 and thyroglobulin reactivity. Average tumor volume in control mice after 21 d of vehicle treatment was 2002 +/- 207 mm3 compared with a mean tumor volume of 1241 +/- 115 mm3 in animals receiving calcitriol, reflecting a 38% reduction in tumor volume size (P < 0.003). Tumors from vehicle-treated animals demonstrated morphological features of epithelial malignancies with characteristics of insular carcinoma and multiple metastases to the lungs. Tumors excised from calcitriol-treated animals demonstrated signs of differentiation with restoration of thyroglobulin staining. This was associated with a marked accumulation of p27 immunoreactivity in the nuclear compartment. These studies demonstrate that in vivo calcitriol administration can effectively restore p27 accumulation in thyroid carcinoma cells, an effect associated with appreciably enhanced cellular differentiation, reduction in tumor burden, and prevention of metastatic growth.

Adenocarcinoma, Follicular↗

PubMed2004

Extent of surgery for differentiated thyroid cancer.

The authors believe that total or near total thyroidectomy followed by 131I ablation and thyroid hormone suppression therapy are there commended extent of surgery and treatment of choice in differentiated thyroid cancer. This is based on retrospective data showing that total thyroidectomy plus 131I and thyroid stimulating hormone (TSH) suppression reduces disease recurrence and mortality, removes all intrathyroidal cancer, and facilitates the use of 131I scans and thyroglobulin measurements to monitor for recurrence. Recent decision analyses supporting this recommendation are summarized in this article. The recommendation comes with the caveat that total thyroidectomy must be performed safely with a low complication rate. With the institution of this appropriate treatment regimen, the prognosis for the majority of our patients with differentiated thyroid cancer is excellent.

Humans↗

PubMed2004

Effect of calcium channel blockers on the sensitivity of preoperative 99mTc-MIBI SPECT for hyperparathyroidism.

BACKGROUND: Technetium 99m ( 99m Tc)-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) is frequently used in the evaluation of patients with hyperparathyroidism. Calcium channel blockers (CACBs) may affect 99m Tc-MIBI uptake by parathyroid cells. This study examines the effect of CACB therapy on the sensitivity of 99m Tc-MIBI SPECT localization for hyperparathyroidism. METHODS: Two hundred fifty-three operated patients with hyperparathyroidism were retrospectively reviewed. The potential effect of CACB therapy on 99m Tc-MIBI scan sensitivity was examined by using logistic regression analysis. Possible confounding factors were considered. RESULTS: Among 235 patients, those with multiple endocrine neoplasia, type I (MEN-I), MEN-IIA, 4-gland hyperplasia, secondary hyperparathyroidism, and tertiary hyperparathyroidism exhibited no difference associated with CACB use. Of the remaining 198 patients with primary hyperparathyroidism, 7/30 (23%) with negative 99m Tc-MIBI SPECT scans compared to 24/168 (14%) with positive scans used CACBs. After correcting for age, gender and gland weight, the odds ratio (OR) for a negative study in patients taking CACBs was 2.88 (95% CI, 1.03-8.10; P = .045). Atherosclerosis, hypertension, diabetes mellitus, preoperative calcium and parathyroid hormone levels, and thyroid hormone use were not confounding factors. CONCLUSIONS: CACB therapy reduces the sensitivity of 99m Tc-MIBI parathyroid SPECT in patients with primary hyperparathyroidism. Further studies are required to determine the potential reversibility of this effect with termination of CACB therapy.

Calcium Channel Blockers↗

PubMed2003

Insulinoma.

Insulinomas are the most common islet cell tumors and are located almost exclusively in the pancreas. Most of these tumors are sporadic, but they may also be associated with the multiple endocrine neoplasia type I syndrome. More than 90% of insulinomas are benign. Preoperative radiographic localization may prove difficult. Intraoperative palpation and ultrasound remain the gold standard for detection and appropriately planned resection. Although many options are available to treat the patient with malignant and metastatic disease, the mainstay of treatment remains surgery. Laparoscopic ultrasound and enucleation/resection may be increasingly used in the management of patients with insulinoma.

Humans↗

PubMed2002

Current national health insurance policies for thyroid cancer prophylactic surgery in the United States.

The efficacy of prophylactic thyroidectomy in patients with positive RET mutational analysis, familial thyroid cancer, or both has been reported. As cost has become critical to medical decision-making, this study was designed to evaluate currently existing coverage policies for prophylactic thyroidectomy. A confidential detailed cross-sectional nationwide survey of 481 medical directors from the American Association of Health Plans, Medicare, and Medicaid was conducted. Of the 150 respondents, 65% (n = 97) had 100,000 or more enrolled members, and 35% (n = 53) had fewer than 100,000 enrolled members. Only 9% of private plans have specific policies for coverage of prophylactic thyroidectomy for patients with a strong family history of thyroid cancer, 19% provided no coverage, and 72% had no policy. Only 9% of private plans have specific policies for patients with a known thyroid cancer genetic mutation, 12% provided no coverage, and 79% had no policy. Governmental carriers were less likely to provide coverage for prophylactic surgery: 4% for a strong family history and 6% for a genetic mutation. Altogether, 52% of government carriers provided no coverage for patients with a strong family history, and 50% provided no coverage in patients with a known genetic mutation; 44% of governmental carriers had no policy for either clinical scenario. Limited health insurance coverage for prophylactic thyroidectomy is offered in both private and governmental plans, with variations in coverage. As genetic testing becomes more widespread and with the potential identification of a gene predisposing to familial nonmedullary thyroid cancer, more uniform policies should be established to enable appropriate high risk candidates broader, equal coverage and access to these procedures.

Elective Surgical Procedures↗

PubMed2002

Carcinoid tumors.

Carcinoids are rare endocrine tumors that can develop in several organs in the body. Clinically, patients can have a wide spectrum of signs and symptoms that range from incidental findings of a polyp during endoscopy to the carcinoid syndrome characterized by severe flushing, diarrhea, abdominal cramping, and life-threatening right-sided heart failure. Most carcinoid tumors are indolent but can metastasize to regional lymph nodes and to other organs, including the liver, bone, and the central nervous system. Treatment is determined by tumor location and by the presence of distant metastasis. Surgical resection of the tumor is advocated in patients with localized disease and can often be curative. Long-acting somatostatin analogs, including octreotide, octreotide long-acting repeatable, and lanreotide prolonged release, are effective in providing symptom relief in patients with the carcinoid syndrome. Patients with metastatic disease to the liver that is refractory to somatostatin treatment should be considered for hepatic artery occlusion. Overall, 5- and 10-year survival rates in patients with metastatic disease are favorable, although tumors can be resistant to most forms of medical or surgical therapy.

Antineoplastic Agents↗

PubMed2002

Computer-assisted evoked electromyography with stimulating surgical instruments for recurrent/external laryngeal nerve identification and preservation in thyroid and parathyroid operation.

BACKGROUND: The reported incidence of recurrent laryngeal nerve (RLN) palsy/paralysis in thyroid and parathyroid operation ranges from 2% to 13%. Injury to the external branch of the superior laryngeal nerve (EBSLN) is less clearly documented. We hypothesized that a novel evoked electromyography system using an audio warning alarm might be beneficial for detection and preservation of the RLN and EBSLN. METHODS: A total of 117 thyroid/parathyroid operations were performed using a nerve locator/monitor (Neurovision SE, RLN Systems Inc, Jefferson City, Mo). Dissection was performed using a stimulating hemostat with conduction to an endotracheal surface electrode. RESULTS: A total of 97 thyroidectomies (50 total, 47 lobectomies) and 20 parathyroidectomies (16 directed, 4 bilateral) were performed representing 176 RLN and 152 EBSLN at risk. Of 176 RLN, 161 were correctly identified by the nerve stimulator alarm including 2 nonrecurrent nerves. The cricothyroid space and the superior pole vessels were scanned to identify the EBSLN by observing for cricothyroideus contraction or an alarm. Fourteen of 152 (8.9%) cases of type 2 anatomy were suggested where meticulous dissection of superior pole vessels prevented EBSLN injury. CONCLUSIONS: Computer-assisted evoked electromyography with stimulating surgical instruments is a useful surgical tool. This technology may be especially useful in reoperation in dense scar tissue and preserving the EBSLN in thyroid operation.

Diagnosis, Computer-Assisted↗

PubMed2002

Monocyte adhesion and transmigration induce tissue factor expression: role of the mitogen-activated protein kinases.

The expression of tissue factor (TF) by monocytes that have transmigrated across the endothelium to sites of extravascular inflammation acts both to focus and amplify the inflammatory response. Because clustering of the integrins responsible for endothelial adhesion and transmigration induces tyrosine phosphorylation and activation of the mitogen-activated protein (MAP) kinases, we postulated that transmigration might lead to monocyte activation and TF production. Monocytes were migrated across TNFalpha-primed ECV304 cells grown on fibronectin-coated Transwell chambers in response to FMLP (10(-8) M). After transmigration, monocytes showed a time-dependent increase in surface TF expression and biological procoagulant activity. TF expression was dependent on monocyte adhesion to ECV304 cells. Specifically, TF was not induced by FMLP treatment of suspended monocytes, by migration across fibronectin alone, or by soluble factors induced during migration, whereas monocyte-ECV304 adhesion was sufficient to stimulate TF. Antibodies against CD29 (beta1 integrin), but not against CD18 (beta2 integrin) or CD31 (PECAM-1), inhibited TF expression. Monocyte adhesion to ECV304 cells induced tyrosine phosphorylation of cellular proteins and specifically of the ERK and p38 MAP kinases. Tyrosine kinase inhibition with genistein (10 microg/mL) blocked transmigration, whereas selective ERK inhibition with PD98059 (50 microM) or p38 inhibition with SB203580 (20 microM) did not. However, both ERK and p38 inhibition dose dependently abolished TF expression. These studies suggest that an extravascular focus of infection or inflammation can promote both intravascular thrombosis and extravascular fibrin deposition during the process of adhesion and transmigration across the endothelial barrier. The selective inhibition of the mitogen-activated protein kinases may offer a novel therapeutic means of modulating this inflammatory sequence.

Antibodies↗