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Orlo H Clark

Publications and source records attributed to Orlo H Clark.

At least 55 records · Page 3Linked to original sources
PubMed2004

Persistent and recurrent hyperparathyroidism.

More than 95% of patients with primary hyperparathyroidism (HPT) will be cured at initial operation by an experienced surgeon. Despite this success rate, persistent and recurrent HPT remain challenging clinical entities. The most cost effective and safest treatment for persistent and recurrent HPT is avoidance by successful first operation. The contributors to treatment failure can be categorized into factors related to the initial surgical procedure, anatomic variability, and the biology of disease. An understanding of the factors that commonly contribute to treatment failure can help prevent persistent and recurrent disease and plays an integral role in planning subsequent surgical approaches. Once a biochemical diagnosis of persistent or recurrent HPT is confirmed, a thorough evaluation of previous operative, pathology, and radiology reports is essential. Localization procedures supplement this information and help direct the reoperative approach. When complementary noninvasive studies, such as ultrasound, sestamibi, and magnetic resonance imaging are negative, equivocal, or discordant, invasive tests (eg, selective venous sampling for parathyroid hormone levels) are warranted. Intraoperative ultrasound and gamma-probe localization are of questionable value, but intraoperative parathyroid hormone assays help facilitate these challenging repeat dissections. Repeat parathyroid exploration is associated with more complications and fewer cures compared to the initial explorations and should only be undertaken by an experienced surgeon in a center that can provide expert preoperative localization, adjunctive intraoperative tools, and cryopreservation of parathyroid tissue when necessary. Although controversy exists regarding indications for reoperative treatment for persistent or recurrent HPT, parathyroidectomy remains the only curative treatment option. Surgery should be considered first-line treatment in most circumstances.

Diet↗
PubMed2004

Redifferentiation therapy for thyroid cancer.

Thyroid tumorigenesis and carcinogenesis accompany progressive loss of thyroid-specific differentiated functions. Some thyroid cancers are or become dedifferentiated, and they become refractory to efficacy-proven conventional therapies such as radioiodine ablation therapy and thyrotropin (TSH)-suppressive therapy. Redifferentiation therapy by either redifferentiating agents or gene transfer of differentiation-related genes may retard tumor growth and make tumors respond to conventional therapies.

Antimetabolites, Antineoplastic↗
PubMed2004

Surgical treatment of insulinomas.

Differential diagnosis of hypoglycemic patients should include insulinoma. Plasma insulin-to-glucose ratio greater than 0.3 or C-peptide levels of 2 nmol/L or greater suggest insulinoma. Abdominal CT scan can exclude metastatic disease and identify uncommonly large islet cell tumors, but has poor sensitivity for localizing insulinomas; transgastric endoscopic ultrasound is the most sensitive technique. Palpation combined with intraoperative ultrasound identifies most tumors at operation and gives vital information about surrounding structures. If no tumor is found, blind distal pancreatectomy should not be performed, and the patient should be referred to an endocrinologist or endocrine surgeon for diagnostic confirmation and further localization. Laparoscopy is a viable alternative to open tumor resection; laparoscopic ultrasound can facilitate localization and guide safe resection.

Endocrine Surgical Procedures↗
PubMed2004

Should pheochromocytoma size influence surgical approach? A comparison of 90 malignant and 60 benign pheochromocytomas.

BACKGROUND: Diagnostic tests cannot reliably distinguish malignant from benign pheochromocytomas. Laparoscopic adrenalectomy for pheochromocytomas >6 cm is controversial because of a perceived increased risk of malignancy that is based on anecdotal reports and small series. The aim of this study was to determine if pheochromocytoma size should affect the choice of surgical approach. METHODS: Malignant pheochromocytomas in the Surveillance Epidemiology and End Results (SEER) database (1988-2000) were compared to benign pheochromocytomas in our institutional database (1993-2003). The sensitivity, specificity and likelihood ratio for tumor size to predict malignancy were calculated for both groups. RESULTS: Ninety malignant and 60 benign pheochromocytomas were compared. Overall, malignant pheochromocytomas were larger than benign pheochromocytomas (7.6 +/- 4.2 cm vs 5.3 +/- 2.3 cm). However, tumor size was not significantly different between malignant pheochromocytomas without local invasion or metastases and benign pheochromocytomas (6.1 +/- 3.1 cm vs 5.3 +/- 2.3 cm). In pheochromocytomas with local disease only, maximum likelihood ratio to predict malignancy was at a tumor size of greater than 8 cm (2.84). CONCLUSIONS: Although risk of malignancy increases with size for all pheochromocytomas, size does not reliably predict malignancy in pheochromocytomas with local disease only. Regardless of tumor size, laparoscopic adrenalectomy for pheochromocytoma should be converted to open adrenalectomy for difficult dissection, invasion, adhesions, or surgeon inexperience.

Adolescent↗
PubMed2004

GCMB gene, a master regulator of parathyroid gland development, expression, and regulation in hyperparathyroidism.

BACKGROUND: The glial cell missing gene, GCMB , encodes a transcription factor, which is a master regulator of parathyroid development. We postulated that the GCMB gene might play a role in parathyroid tumorigenesis in hyperparathyroidism. METHODS: We used real-time quantitative reverse transcriptase polymerase chain reaction to study GCMB mRNA expression in parathyroid tissue: normal (n = 3), hyperplastic (n = 16), adenomas (n = 19), and cancers (n = 8). In primary parathyroid culture, the effect of CaCl 2 on parathyroid hormone secretion and GCMB mRNA expression was studied by using enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction, respectively. RESULTS: GCMB mRNA expression was lower in normal (0.4 +/- 0.1, mean +/- standard error of mean) parathyroid glands as compared to adenoma (3.5 +/- 1.7), hyperplasia (3.2 +/- 1.3 primary hyperparathyroidism [n = 11] and 7.6 +/- 4.8 secondary hyperparathyroidism [n = 5]), and cancer (3.6 +/- 1.3) ( P = .001). There was no difference in the level of GCMB mRNA expression between parathyroid adenoma, hyperplasia, and cancer. In primary culture of parathyroid adenoma (n = 9) and hyperplasia (n = 2), parathyroid hormone secretion was increased 2- to 15-fold with low calcium concentration (0.5 to 4.0 mmol/L CaCl 2 from 2 to 6 hours, P < .005). The level of GCMB mRNA expression was down-regulated with lower extracellular CaCl 2 concentration ( P < .005). CONCLUSIONS: GCMB expression is upregulated in abnormal parathyroid glands of hyperparathyroidism and decreases in response to hypocalcemia. The GCMB transcription factor might mediate the effect of calcium on parathyroid cell parathyroid hormone expression/secretion.

Adenoma↗
PubMed2004

False-negative fine-needle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma.

Clinicians have become reliant on fine-needle aspiration (FNA) cytology in the diagnosis of thyroid nodules. We encountered several patients who had thyroid cancer at operation despite having had FNAs that never showed malignant or suspicious cells. Hence, we retrospectively studied 100 consecutive patients with histologically proven thyroid cancer who had undergone preoperative FNA. Fourteen of these patients had cancers that were not detected by FNA, three of whom developed widespread disease. The sensitivity of FNA was 79%, the false-negative rate 21%, and the inadequate rate 12%. FNA was less sensitive in detecting follicular and Hürthle cell carcinomas compared to papillary carcinomas. FNAs interpreted by cytopathologists at a major university center were more sensitive than those performed elsewhere. A single false-negative FNA delayed surgical treatment by 28 months, sometimes despite clinical evidence suggesting malignancy. Subjects whose tumors were not detected by FNA experienced delayed treatment, had higher rates of vascular and capsular invasion, and were more likely to have persistent disease at follow up (hazard ratio 2.28). False-negative results remain a concern in the cytologic diagnosis of thyroid cancer. Although FNA is a useful test, clinical findings should overrule cytologic data in order for timely treatment to occur.

Adenocarcinoma, Follicular↗
PubMed2004

Latency period of thyroid neoplasia after radiation exposure.

OBJECTIVE: To determine the temporal sequence for developing benign and malignant thyroid neoplasms after radiation. SUMMARY BACKGROUND DATA: Therapeutic radiation is associated with thyroid neoplasms in humans and animals. Some question whether thyroid cancers develop de novo or from benign thyroid neoplasms. Little information, however, is available concerning the time to development of benign and malignant thyroid neoplasms after radiation exposure. METHODS: We retrospectively analyzed the records of 171 consecutive patients who had a history of exposure to radiation and were treated surgically at University of California, San Francisco-affiliated hospitals for thyroid neoplasms between 1960 and 1999. RESULTS: There were 66 men and 105 women aged 9 to 80 years (mean, 47.0 years). One hundred patients had benign and 71 had malignant tumors (58 papillary cancers, 10 follicular cancers, 1 Hurthle cell cancer, 1 medullary cancer, and 1 carcinosarcoma). The mean latency period for benign tumors was longer than that for malignant lesions (mean, 34.1 and 28.4 years, P = 0.018; median, 38.0 years and 30.0 years, P = 0.001). Follicular carcinomas developed sooner (mean, 20.5 years; median, 20 years) than did follicular adenomas (mean, 35.3 years; median, 36.5 years; P = 0.003, P = 0.0009). Patients with papillary thyroid cancers presenting as occult papillary cancers (<1 cm) and as a dominant nodule had similar latency periods (mean, 34.0 and 28.0 years P = 0.29; median, 37.5 and 30.5 years, P = 0.09), respectively. CONCLUSION: Although there could be selection bias regarding referral of patients, our data document that malignant thyroid tumors after radiation exposure, including follicular carcinomas, present earlier than do benign thyroid tumors. Occult and manifest papillary thyroid cancers present at about the same time interval after radiation exposure. Our findings question whether benign thyroid neoplasms progress to malignant thyroid neoplasms and that most occult thyroid cancers do not progress to malignant thyroid cancers in radiation-exposed patients.

Age Factors↗
PubMed2004

The NIH criteria for parathyroidectomy in asymptomatic primary hyperparathyroidism: are they too limited?

OBJECTIVE: To determine whether preoperative and postoperative symptoms and outcome differ in patients who meet or fail to meet the NIH criteria for parathyroidectomy. SUMMARY BACKGROUND DATA: The NIH Consensus Conference on primary hyperparathyroidism in 1990 defined criteria for surgical intervention suggesting that some patients can be safely managed without surgery. METHODS: Over a 3-year period, 202 consecutive patients undergoing parathyroidectomy for primary hyperparathyroidism at a tertiary referral center were prospectively given a questionnaire regarding their symptoms and associated conditions during their initial and follow-up office visits as were 63 thyroid control patients. The 178 patients who completed the follow-up questionnaire were assigned to 2 groups according to the NIH criteria for parathyroidectomy. The frequency of preoperative symptoms and conditions associated with primary hyperparathyroidism as well as postoperative improvement in symptoms and surgical outcome were compared. RESULTS: Of the 178 parathyroid patients, 103 met the NIH criteria for parathyroidectomy whereas 75 did not. Patient profiles were similar in each group except mean ages, 55 versus 65, and preoperative serum calcium levels, 11.5 mg/dL versus 11.0 mg/dL (NIH and non-NIH groups, respectively; P < 0.001). The incidence of preoperative nonspecific somatic and neuropsychiatric symptoms and associated conditions was equivalent in both groups and more common than in the 63 thyroid control patients. After parathyroidectomy, symptomatic improvement was dramatic and equal between the 2 parathyroid groups. Postoperative mean serum calcium levels were similar (8.78 mg/dL, NIH group, versus 8.75 mg/dL, non-NIH group). CONCLUSION: Symptoms were more common in patients with primary hyperparathyroidism versus thyroid controls, but were not different between those patients who met the NIH criteria for parathyroidectomy and those who did not. Patients in both parathyroid groups benefited symptomatically after successful parathyroidectomy.

Adult↗
PubMed2004

Id1 gene expression is up-regulated in hyperplastic and neoplastic thyroid tissue and regulates growth and differentiation in thyroid cancer cells.

The Id (inhibitor of DNA binding) proteins are a family of helix-loop-helix (HLH) proteins (Id1, Id2, Id3, and Id4) that lack the basic domain necessary for DNA binding. The Id1 protein enhances cell proliferation and inhibits cellular differentiation in a variety of cell types. We have previously demonstrated that the Id1 gene is up-regulated in papillary and medullary thyroid cancers. In this study we characterized the expression and distribution of the Id1 protein in normal, hyperplastic, and neoplastic human thyroid tissue. We also evaluated the effect of the Id1 gene on thyroid cancer cell growth and markers of thyroid cell differentiation. We used semiquantitative immunohistochemistry to characterize Id1 protein expression in normal, hyperplastic (multinodular goiter and Graves' disease), and neoplastic thyroid tissue from 103 patients. Normal thyroid tissue had the lowest level of Id1 protein expression (P < 0.0001). Anaplastic thyroid cancer had the highest level (vs. benign and malignant thyroid tissues, P < 0.01). Id1 protein expression was higher in malignant thyroid tissue than in hyperplastic thyroid tissue (P < 0.02). We found no significant association between the level of Id1 protein expression and patient age, sex, tumor-node-metastasis stage, tumor size, primary tumor vs. lymph node metastasis, primary tumor vs. recurrent tumors, and extent of tumor differentiation. Inhibiting Id1 mRNA expression in thyroid cancer cell lines using Id1 antisense oligonucleotides resulted in growth inhibition (P < 0.03) and decreased thyroglobulin and sodium-iodine symporter mRNA expression (P < 0.02). In conclusion, Id1 is overexpressed in hyperplastic and neoplastic thyroid tissue and directly regulates the growth of thyroid cancer cells of follicular cell origin, but is not a marker of aggressive phenotype in differentiated thyroid cancer.

Adult↗
PubMed2003

Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma.

BACKGROUND: We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, in sporadic parathyroid carcinoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism--hyperparathyroidism-jaw tumor (HPT-JT) syndrome--that carries an increased risk of parathyroid cancer. METHODS: We directly sequenced the full coding and flanking splice-junctional regions of the HRPT2 gene in 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also sought to confirm the somatic nature of the identified mutations and tested the carcinomas for tumor-specific loss of heterozygosity at HRPT2. RESULTS: Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of which were predicted to inactivate the encoded parafibromin protein. Two distinct HRPT2 mutations were found in tumors from five patients, and biallelic inactivation as a result of a mutation and loss of heterozygosity was found in one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of three patients were identified as germ-line mutations. CONCLUSIONS: Sporadic parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of pathogenetic importance. Certain patients with apparently sporadic parathyroid carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or a phenotypic variant.

Adult↗
PubMed2003

Incision length for standard thyroidectomy and parathyroidectomy: when is it minimally invasive?

HYPOTHESIS: Current techniques for open conventional thyroidectomy or parathyroidectomy have evolved to enable a shorter incision (main proposition), and the length of the incision is influenced by objective factors. DESIGN: Case series. SETTING: University referral center. PATIENTS AND INTERVENTION: Retrospective study of the most recent 200 primary consecutive routine thyroid and parathyroid operations (excluding neck dissections). MAIN OUTCOME MEASURES: The length of incision was routinely measured with a ruler before the incision. Univariate and multivariate analysis was performed to distinguish variables affecting length of incision. RESULTS: Mean length of the incision was 5.5 cm for total thyroidectomy, 4.6 cm for lobectomy, and 3.5 cm for parathyroidectomy (P<.001). It was 4.1 cm for bilateral parathyroid exploration, but was reduced to 3.2 and 2.8 cm for unilateral (P<.001) and focal (P<.001) explorations, respectively. By multiple regression analysis, thyroid specimen volume and patient body mass index were independent predictors of incision length in thyroidectomy. Extent of exploration and resident training level were independent predictors of incision length in parathyroidectomy. CONCLUSIONS: Current techniques for open conventional thyroidectomy or parathyroidectomy have evolved to enable a shorter incision. Thyroid volume, patient body mass index, extent of the planned parathyroid exploration, and the resident clinical training stage are important variables for incision length in open operation and should be taken into account when minimally invasive thyroidectomy and parathyroidectomy are evaluated.

Female↗
PubMed2003

Parathyroidectomy for primary hyperparathyroidism in octogenarians and nonagenarians: a plea for early surgical referral.

BACKGROUND: Surgical referral of elderly patients with PHPT is often deferred because of the perceived risks of general anesthesia, increased age, and comorbidities and also because many of the symptoms of PHPT are difficult to distinguish from the aging process. HYPOTHESIS: Parathyroidectomy for primary hyperparathyroidism (PHPT) in elderly patients is beneficial and safe. DESIGN: Retrospective study of patients with PHPT who were 80 years and older. SETTING: Tertiary academic referral medical center. PATIENTS: Fifty-four consecutive patients (43 women and 11 men) with a mean age of 83.6 years who underwent parathyroidectomy for PHPT. MAIN OUTCOME MEASURES: Delay in surgical referral; improvement in symptoms and normalization of serum calcium and parathyroid hormone levels; and perioperative morbidity and mortality. RESULTS: Twelve (22%) of 54 patients had a mean delay of 5 years (range, 1.2-10.0 years) before surgical referral for a known diagnosis of PHPT. No patient had asymptomatic PHPT. There was no significant difference in the preoperative mean serum calcium level and symptoms of PHPT resulting from delay in surgical referral. Parathyroidectomy resulted in significant improvement of PHPT-associated symptoms of fatigue, weight loss, nocturia, bone pain, constipation, and major depression (P<.05). All patients had normal serum calcium and parathyroid hormone levels postoperatively. The average length of hospitalization was 1.9 days. There were 3 complications (9%): 1 urinary tract infection, 1 bladder perforation, and 3 transient hypocalcemia. There was no perioperative mortality. CONCLUSIONS: Parathyroidectomy in elderly patients is safe, curative, and beneficial. Surgical referral for parathyroidectomy should be considered in elderly patients with PHPT.

Aged↗
PubMed2003

Intraoperative parathyroid hormone assay and parathyroid reoperations.

BACKGROUND: The purpose of this study was to determine whether intraoperative parathyroid hormone (IOPTH) assay improved results of reoperations. METHODS: One hundred two patients with persistent/recurrent sporadic primary hyperparathyroidism underwent 108 reoperations (1996-2002). IOPTH was not used (n=58) from 1996-1998 (group 1). IOPTH was used (n=50) from 1999-2002 (group 2). Sensitivity and positive predictive value of IOPTH and its influence on surgical strategy were analyzed. A 50% decrease occurring 10 minutes after removal of parathyroid tumor was used to determine if all abnormal tissue had been removed. RESULTS: Groups 1 (58 patients) and 2 (50 patients) were comparable except for duration of follow-up. The cure rate was 84% (group 1, 87%; group 2, 82%, P=0.7). Hypocalcemia developed in 20 patients (permanent in 2 patients). There was 1 permanent vocal cord paralysis and 1 patient died of toxic shock syndrome. IOPTH successfully predicted cure in 44 of 49 patients (sensitivity, 90%); the positive predictive value was 90%. Values for parathyroid hormone level and the ratio parathyroid hormone/calcium at day 1 were at least as accurate as IOPTH in predicting cure. IOPTH was helpful in 1 patient but misleading in 4 patients. It failed to modify intraoperative strategy in most other patients. CONCLUSIONS: IOPTH testing was relatively reliable in patients with persistent or recurrent sporadic primary hyperparathyroidism, but the test unfortunately failed to improve the overall success rate at reoperation.

Adolescent↗
PubMed2003

Primary hyperparathyroidism: controversies in surgical management.

Controversy surrounds the optimal management of patients with mild or asymptomatic primary hyperparathyroidism (PHPT). Although many new medical therapies for this disorder have emerged in the past decade, existing evidence indicates that parathyroidectomy is the only curative option and reverses not only many of the classic, but also the more subtle, manifestations of PHPT. Moreover, parathyroidectomy can be performed successfully with minimal morbidity by experienced surgeons. With the recent development and widespread use of several preoperative localization studies, various focused approaches to neck exploration and intraoperative parathyroid hormone testing, management for this disorder will need to be tailored to individual patients.

Adenoma↗
PubMed2003

Prevention, evaluation, and management of complications following thyroidectomy for thyroid carcinoma.

The rate of complications during thyroid surgery has decreased because of better instrumentation, illumination, and surgical expertise. Despite these improvements, certain patients, those requiring reoperation, those with invasive cancers or with numerous nodal metastasis or recurrent tumors, and those with large substernal goiters have a low but appreciable risk for complications. When planning a thyroid operation, one should perform the operation that corrects these problems and decreases the risk for complications. Localization of at least one parathyroid gland is essential. No surgical procedure can be done, however, without a risk of complications. To decrease these possible risks the surgeon should understand the embryologic development of the thyroid and parathyroid glands, the anatomical position of key structures, and use meticulous operative technique. Experience in performing thyroid operations is essential for the best outcome with the fewest complications.

Humans↗
PubMed2003

Locally advanced differentiated thyroid cancer.

Although most patients with differentiated thyroid cancer (DTC) of follicular cell origin enjoy a relatively good prognosis, some patients unfortunately present with or develop locally advanced DTC which leads to significant local morbidity and mortality. DTC accounts for 54-94% of all locally advanced thyroid cancers. DTC invasion of the recurrent laryngeal nerve, strap muscles and trachea are the most common followed by invasion of the esophagus, internal jugular vein and carotid artery. Surgical resection is the primary treatment for locally advanced DTC. Although the optimal surgical approach (ranging from conservative shave excision to aggressive en bloc resection of tumor and vital structures) in patients with locally advanced DTC is controversial, a curative resection should be the goal unless complete tumor resection results in unwanted perioperative morbidity and mortality or widely metastatic disease is present. Postoperative radioiodine ablation with TSH suppression is imperative after surgical resection of locally advanced DTC. Patients with microscopic or small gross residual disease, after surgical resection, may benefit from postoperative external radiotherapy for local control of disease.

Chemotherapy, Adjuvant↗