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ABSTRACT: OBJECTIVES:: This prospective single-arm study investigated both laryngeal physiology and voice acoustic measures in patients undergoing minimally invasive parathyroidectomy (MIP) due to primary hyperparathyroidism (primary HPTH). BACKGROUND:: Avoidance of recurrent or superior laryngeal nerve injury and maintenance of normal laryngeal physiology and vocal function are key goals in the treatment of primary HPTH. No data are available comparing pre- and postoperative MIP laryngeal physiology and voice acoustics. METHODS:: Patients served as their own controls and underwent identical pre- and postoperative assessment. True vocal fold mobility was assessed and recorded using transnasal fiber-optic laryngoscopy. Vocal capacity was recorded with maximum phonation time and vocal stability by frequency-based voice measures, that is, mean fundamental frequency (F0), standard deviation of the fundamental frequency (F0SD), and jitter and shimmer as measured by relative average perturbation and mean shimmer in decibels, respectively. RESULTS:: A total of 104 patients were enrolled [26 men, mean age = 53 years, range 29-79 years; 78 women, mean age = 56 years, range 16-83 years). All completed the protocol and were analyzed according to intent to treat. MIP was accomplished in 95 patients, and 9 were converted to general anesthesia. The cure rate was 100%, as evidenced by normalization of serum calcium levels. Both real-time agreement and blinded inter- and intrarater reliability testing for laryngeal physiology ratings were 100%. One patient (<1%) exhibited a recurrent laryngeal nerve injury. No significant differences (P > 0.05) were found for any voice acoustic parameter between pre- and postoperative MIP (ie, maximum phonation time, F0, F0SD, relative average perturbation, or shimmer in decibels). CONCLUSIONS:: MIP can be performed with exquisite disease control and without significant effects on laryngeal physiology or voice acoustic measures. For the first time, both physiologic and acoustic data support the use of MIP.
Annals of surgery 03/2013; · 7.90 Impact Factor
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ABSTRACT: Clinical Context:The prevalence of hyperparathyroidism, especially primary hyperparathyroidism, has increased in recent decades due to improvements in diagnostic techniques with a corresponding surge in parathyroid surgery, leading to the development of focused, minimally invasive surgical approaches. Focused parathyroidectomy is predicated on preoperative localization of suspected parathyroid pathology. As a result, there has been a proliferation of parathyroid imaging modalities and protocols, resulting in confusion about their indications and applications.Evidence Acquisition:Bibliographies from clinical trials and review articles published since 2000 were reviewed and supplemented with targeted searches using biomedical databases. We also employed our extensive clinical experience.Evidence Synthesis:The best-studied modalities for parathyroid localization are nuclear scintigraphy and sonography and are widely applied as initial studies. Multiple variations exist, and several additional noninvasive imaging techniques, such as computed tomography and magnetic resonance, are described. The exquisite anatomical detail of 4-dimensional computed tomography must be balanced with significant radiation exposure to the thyroid gland. Invasive venous PTH sampling and parathyroid arteriography have important roles in remedial cases. Due to considerable heterogeneity in imaging, multidisciplinary collaboration between endocrinologists, surgeons, and radiologists is beneficial.Conclusions:Parathyroid localization is indicated in surgical candidates. Crucial considerations when selecting an imaging study include availability, cost, radiation exposure, local expertise, and accuracy. Additional factors include the patient's anticipated pathology and whether it is de novo or refractory disease. An approach to imaging for patients with primary hyperparathyroidism is presented.
The Journal of clinical endocrinology and metabolism 01/2013; · 6.50 Impact Factor
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Ogechukwu P Eze,
Guoping Cai,
Zubair W Baloch,
Ashraf Khan,
Renu Virk,
Lynwood Hammers, Robert Udelsman,
Sanziana Roman,
Julie Ann Sosa,
Tobias Carling,
David C Chhieng,
Constantine G A Theoharis,
Manju L Prasad
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ABSTRACT: Background: Fine-needle aspiration (FNA) is the most accurate and cost-effective method for evaluating thyroid nodules. However, FNA induced secondary changes completely replacing thyroid tumors ('vanishing' tumors) may create a novel problem. In this study we highlight the diagnostic and management issues associated with the unintended consequences of ultrasound guided FNA. Methods: Fourteen thyroids glands (11 women:3 men, ages 33-64 years) with 'vanishing tumors' were prospectively identified between 2009-2012 upon surgical resection. Cytology and histopathology slides were reviewed, and second opinions were obtained when necessary. Results: The cytology of the 14 'vanishing tumors' was suspicious/positive for papillary thyroid carcinoma (PTC) in 5, indeterminate (atypia of unknown significance, AUS) in 5, benign in 2, follicular neoplasm in 1, and non-diagnostic in 1 nodule. Upon thyroidectomy, the 'vanishing tumors' ranged in size from 0.4 to 3.5 cm (median 0.7 cm). Microscopically, the nodules showed cystic degeneration, organizing hemorrhage, granulation tissue, fibrosis and microcalcifications. In seven tumors a few residual malignant cells (PTC in 5) or residual benign follicles (hemorrhagic cyst in 2) at the periphery of the 'vanishing tumors' helped with the final diagnosis. The remaining seven tumors were completely replaced by FNA induced secondary changes, and had the cytology diagnosis of benign in one, follicular neoplasm in one, and suspicious/positive for PTC in five. Of the latter five, two showed additional separate foci of PTC while three 'vanishing' tumors (0.5 cm, 1.2 cm, 1.6 cm) had no residual malignant cells and no additional carcinoma leading to a final diagnosis of 'negative' for malignancy. Conclusions: Ultrasound guided FNA may lead to complete obliteration of thyroid nodules, rendering final diagnosis upon thyroidectomy difficult or impossible. In these unusual circumstances, the possibility that the surgical pathology may be 'non-representative' should be considered if the cytologic features on FNA are sufficient by themselves to support a definitive diagnosis of PTC.
Thyroid: official journal of the American Thyroid Association 08/2012; · 2.60 Impact Factor
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Renu K Virk,
Alison L Van Dyke,
Alexander Finkelstein,
Avinash Prasad,
Joanna Gibson,
Pei Hui,
Constantine G Theoharis,
Tobias Carling,
Sanziana A Roman,
Julie A Sosa, Robert Udelsman,
Manju L Prasad
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ABSTRACT: BRAF(V600E) mutation has emerged as a marker of aggressive behavior in papillary thyroid carcinoma but its significance in microcarcinoma is not entirely clear. One-hundred and twenty-nine papillary thyroid microcarcinomas were tested for BRAF(V600E) mutation by single-strand conformation polymorphism, and their clinicopathologic features (age, sex, tumor size, multifocality, nodal metastases, histologic subtype, tumor cell morphology, architecture, tumor-associated stromal reaction, tumor interface to non-neoplastic thyroid (well circumscribed vs infiltrative), extrathyroidal extension, lymphovascular invasion, intratumoral multinucleated giant cells, and adjacent non-neoplastic thyroid pathology) were examined. Compared with tumors without the mutation (39/129, 30%), the mutated microcarcinomas (90/129, 70%) showed significantly higher prevalence of infiltrative tumor borders (78/90 vs 23/39, P=0.001), tumor-associated stromal desmoplasia/fibrosis and/or sclerosis (80/90 vs 25/39, P=0.002), classic nuclear features of papillary thyroid carcinoma (90/90 vs 35/39, P=0.008) and cystic change (43/90 vs 11/39, P=0.05). BRAF(V600E) mutation was more frequent in classic (75%), tall cell (91%), and other variants (>70%) than in follicular variant (21%) of papillary thyroid microcarcinoma. Tumors without the mutation were significantly more likely to be solid, well circumscribed, and lacked desmoplasia/fibrosis or sclerosis. However, on multivariate analysis, only the follicular variant of papillary microcarcinoma was significantly associated with the absence of mutation (odds ratio (95% confidence interval): 0.09 (0.01-0.54)). Lymph node metastases (n=24) were more frequent in microcarcinomas with mutation than without (21/24 vs 3/24, P=0.02). All patients with lateral cervical node metastasis (n=9), and all but one tumor with extrathyroidal extension (n=17/18) showed BRAF(V600E) mutation. No significant differences were noted in age, sex, tumor size, multifocality, lymphovascular invasion, psammoma bodies, stromal calcification, intratumoral multinucleated osteoclastic-type giant cells, and lymphocytic infiltration between the two groups of tumors. BRAF(V600E) mutation is an early event in thyroid carcinogenesis, and is associated with distinctive morphology and aggressive features even in papillary thyroid microcarcinomas.Modern Pathology advance online publication, 24 August 2012; doi:10.1038/modpathol.2012.152.
Modern Pathology 08/2012; · 4.79 Impact Factor
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ABSTRACT: Context: The underlying molecular alterations causing sporadic parathyroid adenomas that drive primary hyperparathyroidism have not been thoroughly defined. Objective: The aim of the study was to investigate the occurrence of somatic mutations driving tumor formation and progression in sporadic parathyroid adenoma using whole-exome sequencing. Design: Eight matched tumor-constitutional DNA pairs from patients with sporadic parathyroid adenomas underwent whole-exome capture and high-throughput sequencing. Selected genes were analyzed for mutations in an additional 185 parathyroid adenomas. Results: Four of eight tumors displayed a frame shift deletion or nonsense mutation in MEN1, which was accompanied by loss of heterozygosity of the remaining wild-type allele. No other mutated genes were shared among the eight tumors. One tumor harbored a Y641N mutation of the histone methyltransferase EZH2 gene, previously linked to myeloid and lymphoid malignancy formation. Targeted sequencing in the additional 185 parathyroid adenomas revealed a high rate of MEN1 mutations (35%). Furthermore, this targeted sequencing identified an additional parathyroid adenoma that contained the identical, somatic EZH2 mutation that was found by exome sequencing. Conclusion: This study confirms the frequent role of the loss of heterozygosity of chromosome 11 and MEN1 gene alterations in sporadic parathyroid adenomas and implicates a previously unassociated methyltransferase gene, EZH2, in endocrine tumorigenesis.
The Journal of clinical endocrinology and metabolism 06/2012; 97(9):E1774-81. · 6.50 Impact Factor
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ABSTRACT: Patients receiving lithium therapy are at elevated risk of developing hyperparathyroidism. In lithium-associated hyperparathyroidism (LAH), the incidence of multiglandular disease (MGD) is unclear, and the need for routine bilateral cervical exploration remains controversial. Therefore, in LAH patients, surgical approaches, pathologic findings, cure rates, and factors associated with persistent or recurrent disease were investigated.
Retrospective analysis of 27 patients with LAH undergoing parathyroidectomy with the intraoperative parathyroid hormone (PTH) assay.
The median postoperative follow-up was 7 months; 17 patients had >6 months follow-up. Cervical exploration was unilateral in 9, bilateral in 18 (3 were converted from unilateral). Sixteen patients (62 %) had MGD, 12 with four-gland hyperplasia and 4 with double adenomas. Ten patients (38 %) had a single adenoma. Twenty-five (93 %) of 27 patients had initially successful surgery. Of the 17 patients with >6 months follow-up, two had persistent disease and two experienced recurrent disease. All patients with a single adenoma remain free of disease. Three (75 %) of four patients with persistent/recurrent disease had MGD and were receiving lithium at the time of surgery. Patients with persistent/recurrent disease were older (p = 0.01) and had experienced a longer duration of hypercalcemia (p = 0.04).
LAH patients have a high incidence of MGD, and bilateral exploration is frequently necessary. With access to the intraoperative PTH assay, it is reasonable to initiate a unilateral approach because many patients will harbor single adenomas and can be reliably rendered normocalcemic. Patients with MGD remain at higher risk of persistent/recurrent disease.
Annals of Surgical Oncology 06/2012; 19(11):3465-71. · 4.17 Impact Factor
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ABSTRACT: The Bethesda 2007 Thyroid Cytology Classification defines follicular lesion of undetermined significance as a heterogeneous category of cases that are not convincingly benign nor sufficiently atypical for a diagnosis of follicular neoplasm or suspicious for malignancy. In our institution, we refer to these cases as indeterminate, and they are further sub-classified into two: (1) low cellularity with predominant microfollicular architecture and absence of colloid (IN(a)) and (2) nuclear features not characteristic of benign lesions (nuclear atypia) (IN(b)). We reviewed these indeterminate cases to document the follow-up trend using this two-tier classification. A search of the cytology records was performed for the period between January 2008 and June 2009. All thyroid fine-needle aspiration (FNA) cases were reviewed and the ones diagnosed as indeterminate were identified. Correlating follow-up FNA and/or surgical pathology reports were reviewed. The percentage of cases showing a malignancy was calculated. One hundred and seventy-one indeterminate cases were identified, representing 2.8% of the 6,205 thyroid FNA cases examined during the time under review (107 IN(a), 64 IN(b)). Records of follow-up procedures were available in 106 (61%) cases. Malignancy was identified in 27% of all indeterminate cases. This was disproportionately more in the IN(b) (56%) compared to the IN(a) (7%) cases. A diagnosis of "IN(a)" does not carry the same implication as that of "IN(b)". The IN(b) category needs a more aggressive follow-up than the IN(a) category and may justify an immediate referral for lobectomy. Despite the vague morphologic criteria for this diagnostic category, the indeterminate rate remains relatively low and falls within the NCI recommendation (<7%).
Diagnostic Cytopathology 05/2012; 40(5):410-5. · 1.16 Impact Factor
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Tobias Carling,
Sally E Carty,
Maria M Ciarleglio,
David S Cooper,
Gerard M Doherty,
Lawrence T Kim,
Richard T Kloos,
Ernest L Mazzaferri,
Peter N Peduzzi,
Sanziana A Roman,
Rebecca S Sippel,
Julie A Sosa,
Brendan C Stack,
David L Steward,
Ralph P Tufano,
R Michael Tuttle, Robert Udelsman
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ABSTRACT: The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury).
We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury.
Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.
Thyroid: official journal of the American Thyroid Association 03/2012; 22(3):237-44. · 2.60 Impact Factor
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Alexander Finkelstein,
Gillian H Levy,
Pei Hui,
Avinash Prasad,
Renu Virk,
David C Chhieng,
Tobias Carling,
Sanziana A Roman,
Julie A Sosa, Robert Udelsman,
Constantine G Theoharis,
Manju L Prasad
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ABSTRACT: The BRAF V600E mutation resulting in the production of an abnormal BRAF protein has emerged as the most frequent genetic alteration in papillary thyroid carcinomas (PTCs). This study was aimed at identifying distinctive features in tumours with and without the mutation.
Thirty-four mutation-positive and 22 mutation-negative tumours were identified by single-strand conformation polymorphism of the amplified BRAF V600E region in the tumour DNA. Mutation-positive tumours were more common in patients older than 45 years (24/33, P = 0.05), in classic (23/30, P = 0.01), tall cell (4/5) and oncocytic/Warthin-like (2/2) variants of PTC, and in subcapsular sclerosing microcarcinomas (4/4). In contrast, all 12 follicular variants (P < 0.0001) and two diffuse sclerosing variants were negative for the mutation. Mutation-positive tumours displayed infiltrative growth (32/34, P = 0.02), stromal fibrosis (33/34, P < 0.001), psammoma bodies (17/34, P = 0.05), plump eosinophilic tumour cells (22/34, P = 0.01), and classic fully developed nuclear features of PTC (33/34, P = 0.0001). Encapsulation was significantly associated with mutation-negative tumours (15/22, P = 0.02).
BRAF V600E mutation-positive and negative PTCs are morphologically different. Recognition of their morphology may help in the selection of appropriate tumours for genetic testing.
Histopathology 02/2012; 60(7):1052-9. · 3.08 Impact Factor
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ABSTRACT: Familial primary hyperparathyroidism (FPHPT) may occur due to an underlying germ-line mutation in the MEN1, CASR, or HRPT2/CDC73 genes. The disease may be undiagnosed in the absence of a history suggestive of FHPT. Young PHPT patients (≤45 years of age) are more likely to harbor occult FPHPT. A total of 1,161 (136 were ≤45 years of age) PHPT patients underwent parathyroidectomy from 2001 to 2009. Thirty-four patients declined participation. Sixteen patients were diagnosed in the clinical routine with FPHPT (11 MEN1, four MEN2A, and one HPT-JT) and were not included in the genetic analysis. Eighty-six young (≤45 years of age) patients with clinically non-syndromic PHPT underwent genetic analysis. Sanger sequencing of all coding regions of the MEN1, CASR, and the HRPT2/CDC73 genes was performed. Eight of 86 (9.3%) young patients with clinically non-familial PHPT displayed deleterious germ-line mutations in the susceptibility genes (4 MEN1, 3 CASR, and 1 HRPT2/CDC73). There was one insertion, one deletion, two nonsense, and four missense mutations, all predicted to be highly damaging to protein function and absent in 3,244 control chromosomes. Germ-line mutations in known susceptibility genes within young patients with PHPT, including those diagnosed in the clinical routine, was 24/102 (23.5%; 15 MEN1, four RET, three CASR, and two HRPT2/CDC73). We demonstrate that germ-line inactivating mutations in susceptibility genes are common in young patients with clinically non-familial PHPT. Thus, enhanced use of genetic analysis may be warranted in clinically non-familial young PHPT patients.
Hormones and Cancer 12/2011; 3(1-2):44-51.
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Tobias Carling,
Sally E Carty,
Maria M Ciarleglio,
David S Cooper,
Gerard Doherty,
Lawrence T Kim,
Richard T Kloos,
Ernest Mazzaferri,
Peter N Peduzzi,
Sanziana Roman,
Rebecca S Sippel,
Julie Ann Sosa,
Brendan C Stack,
David Steward,
Ralph Tufano,
R Michael Tuttle, Robert Udelsman
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ABSTRACT: ABSTRACT Background: The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). Methods & Results: We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7 year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10 % after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e. persistent, recurrent or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5,840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. Conclusion: Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.
Thyroid: official journal of the American Thyroid Association 12/2011; · 2.60 Impact Factor
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ABSTRACT: Parathyroid four-dimensional computed tomography (4DCT) provides greater sensitivity than sestamibi with single photon emission CT (SPECT, or SeS) for preoperative localization of parathyroid tumors in patients with primary hyperparathyroidism (PHPT). The radiation dose imparted to the patient during preoperative parathyroid imaging, however, has not been analyzed.
Patients with biochemically unequivocal PHPT referred for minimally invasive parathyroidectomy underwent 4DCT or SeS. 4DCT was performed using a 64 detector row CT scanner, and SeS used a standardized protocol of 20 mCi of technetium-99m followed by planar and SPECT imaging. The CT radiation dose was estimated using the Imaging Performance Assessment of CT Scanners (ImPACT) calculator, and the SeS dose was estimated using the US Nuclear Regulatory Commission Regulation (NUREG) method.
The calculated effective doses of 4DCT and SeS were 10.4 and 7.8 mSv, respectively, in contrast to an estimated annual background radiation exposure of approximately 3 mSv. The dose to the thyroid with 4DCT, however, was about 57 times higher (92.0 vs. 1.6 mGy) than that with SeS. Based on age- and sex-dependent risk factors, the calculated risk of 4DCT-related thyroid cancer developing in a 20 year old woman was 1,040/million (i.e., about 0.1%).
4DCT, a superior preoperative imaging modality for locating parathyroid tumors, imparts a significantly higher thyroid radiation dose than SeS. Given the enhanced risk of thyroid cancer in individuals with radiation exposure at a young age, 4DCT should be used judiciously in young PHPT patients.
World Journal of Surgery 12/2011; 36(6):1335-9. · 2.36 Impact Factor
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ABSTRACT: Spontaneous adrenal hemorrhage associated with a mass is uncommon and treatment strategies are not standardized. Current treatment modalities range from supportive management and blood transfusion to embolization or immediate operative extirpation. Our objectives were to describe six cases from a single institution and to perform a literature review of the etiology of the condition and recommended management of patients with hemorrhagic adrenal masses.
Records from six patients diagnosed with adrenal hemorrhage and an associated mass at a single institution were reviewed. Clinical records and outcomes were analyzed. A comprehensive review of 133 reported cases in the literature was performed.
Six patients presented with spontaneous adrenal hemorrhage that appeared to be associated with a mass, with tumor sizes ranging from 3.7 to 15 cm. Three patients underwent adrenalectomy for pheochromocytoma or adrenocortical cancer. Three patients did not undergo adrenalectomy: one had a metastasis from lung cancer, one underwent embolization, and one had resolution of the mass on interval imaging. A comprehensive review of the literature identified 133 cases, with pheochromocytoma the most commonly reported lesion (48%).
Spontaneous adrenal hemorrhage is rare. When it does occur, a high level of suspicion for malignant disease or pheochromocytoma should be maintained. The possibility of a hematoma masquerading as a neoplasm should also be considered. In cases of ongoing hemorrhage, embolization may be a lifesaving temporizing measure. Acute surgical intervention should be considered in selected patients, and surgery may not be required in all patients. A cautious approach with a comprehensive biochemical and imaging work-up is advised prior to operation.
World Journal of Surgery 11/2011; 36(1):75-82. · 2.36 Impact Factor
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Robert Udelsman
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ABSTRACT: Reoperative parathyroid surgery may be required in patients who have persistent primary hyperparathyroidism after an unsuccessful operation and in patients who had an initially successful exploration but develop recurrent disease at an interval greater than 6 months postoperatively. Additionally, patients who have had significant surgery in the cervical region, particularly total thyroidectomy, should be considered in this group because they pose identical technical challenges that in the past have resulted in suboptimal cure and complication rates. These patients require a meticulous review of their historical, biochemical, imaging, and operative data to confirm the diagnosis, to evaluate the possibility of familial forms of hyperparathyroidism, and to confirm the indications for surgery. Once a patient is deemed an appropriate surgical candidate, sequential imaging is required to yield a roadmap to guide surgical intervention. These reoperative procedures require an experienced parathyroid surgeon armed with intraoperative adjuncts to locate the offending parathyroid gland(s) and remove them while minimizing collateral injury, particularly to the recurrent laryngeal nerves. These patients are also at increased risk of postoperative hypocalcemia that can be life-threatening. Despite these concerns, an experienced endocrine team can diagnose persistent or recurrent hyperparathyroidism, localize residual abnormal parathyroid glands, and perform surgical intervention with success and complication profiles that approximate those achieved in the unexplored patient.
The Journal of clinical endocrinology and metabolism 10/2011; 96(10):2950-8. · 6.50 Impact Factor
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ABSTRACT: Ectopic salivary gland tissue is common in the head and neck, usually associated with lymph nodes in lateral areas. It is rarely noted in the thyroid gland. Here we report the first case of a pleomorphic adenoma presenting as a midline nodule in the isthmus of thyroid in a 66-year-old man. We propose the possibility of origin in ectopic salivary gland tissue that may have aberrantly migrated with the median anlage from the foramen cecum in the base of the tongue during embryogenesis.
Human pathology 07/2011; 43(1):134-7. · 3.03 Impact Factor
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Annals of surgery 06/2011; 254(2):192-3. · 7.90 Impact Factor
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ABSTRACT: The role of DNA methylation of CpG islands in parathyroid tumorigenesis has not been analyzed in an unbiased, systematic fashion. DNA was isolated from normal and pathologic parathyroid tissues, bisulphite modified and analyzed using the Infinium HumanMethylation27 BeadChip. Distinct hierarchical clustering of genes with altered DNA methylation profiles in normal and pathologic parathyroid tissue was evident. Comparing normal parathyroid tissue with parathyroid adenomas, 367 genes were significantly altered, while 175 genes significantly differed when comparing parathyroid carcinomas and normal parathyroid tissues. A comparison between parathyroid adenomas and parathyroid carcinomas identified 263 genes with significantly distinct methylation levels. Results were confirmed for certain genes in a validation cohort of 40 parathyroid adenomas by methylation-specific PCR. Genes of known or putative importance in the development of parathyroid tumors showed significant and frequent hypermethylation. DNA hypermethylation of CDKN2B, CDKN2A, WT1, SFRP1, SFRP2, and SFRP4 was associated with reduced gene expression in both benign and malignant parathyroid tumors. Treatment with 5-aza-2'-deoxycytidine of primary cell cultures restores expression of hypermethylated genes in benign and malignant parathyroid tumors. In conclusion, the unbiased, genome-wide study of the parathyroid tumor DNA methylome identified a number of genes with altered DNA methylation patterns of putative importance to benign and malignant parathyroid tumorigenesis.
Genes Chromosomes and Cancer 06/2011; 50(9):735-45. · 3.31 Impact Factor
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ABSTRACT: The BRAF V600E mutation has been reported in 50%-80% of papillary thyroid carcinoma (PTC) cases and is highly specific for PTC. Reflex BRAF testing may improve the diagnostic accuracy of thyroid fine-needle aspiration (FNA) tests having equivocal cytologic interpretations and provide prognostic information that helps guide management in patients with PTC.
Cases with equivocal thyroid FNA readings (indeterminate and suspicious for PTC) or a positive diagnosis for PTC and concomitant BRAF mutation analysis were included in this prospective study. BRAF mutation analysis was performed by polymerase chain reaction combined with single-strand conformation polymorphism gel electrophoresis using lavage fluid obtained from needle rinsing. The results of histopathologic follow-up were correlated with the cytologic interpretations and BRAF status.
One hundred fifty-seven FNAs with equivocal or positive cytologic interpretations were eligible for the study. All but one (99.4%) FNAs were found to have sufficient DNA quality and quantity for the assay. Based on the follow-up diagnosis of nodules after surgical resection, the sensitivity for diagnosing PTC was 63.3% with cytology alone and 80.0% with the combination of cytology and BRAF testing, respectively. No false positives were noted with either cytology or BRAF mutation analysis. All PTCs with extrathyroidal extension and of tall-cell variant were postive for BRAF mutation.
BRAF V600E mutation analysis can be easily performed on cytologic preparation using lavage fluids obtained from needle rinsing. By combining morphologic evaluation and BRAF testing, there is a substantial improvement in the preoperative identification of PTC when compared with cytology alone. Patients with equivocal cytologic diagnosis and BRAF V600E mutation are candidates for total thyroidectomy ± central lymph node dissection.
Thyroid: official journal of the American Thyroid Association 05/2011; 21(7):717-23. · 2.60 Impact Factor
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ABSTRACT: To compare the results of minimally invasive parathyroidectomy (MIP) and conventional parathyroid surgery.
Primary hyperparathyroidism is a common endocrine disorder often treated by surgical intervention. Outpatient MIP, employing image-directed focused exploration under cervical block anesthesia, has replaced traditional surgical approaches for many patients with primary hyperparathyroidism. This retrospective review of a prospective database compared MIP with conventional parathyroid surgery.
One thousand six hundred fifty consecutive patients underwent surgery for primary hyperparathyroidism by a single surgeon between 1990 and 2009 at 2 tertiary care academic hospitals. Conventional bilateral cervical exploration under general anesthesia was performed in 613 patients and MIP was performed in 1037 cases. Cure rates, complication rates, pathologic findings, length of hospital stay, and total hospital costs were compared.
Minimally invasive parathyroidectomy is associated with improvements in the cure rate (99.4%) and the complication rate (1.45%) compared to conventional exploration with a cure rate of 97.1% and a complication rate of 3.10%. In addition, the hospital length of stay and total hospital charges were also improved compared to conventional surgery.
Minimally invasive parathyroidectomy is a superior technique and should be adopted for the majority of patients with sporadic primary hyperparathyroidism.
Annals of surgery 03/2011; 253(3):585-91. · 7.90 Impact Factor
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Journal of the American College of Surgeons 01/2011; 212(3):413-7. · 4.55 Impact Factor
