PubMed Health⌕ Search

Biomedical subjects

Jeremy L Freeman

Publications and source records attributed to Jeremy L Freeman.

34 records · Page 2Linked to original sources
PubMed2003

Intratumoral lymphatics and lymph node metastases in papillary thyroid carcinoma.

OBJECTIVE: To examine the relationship between lymphatic vessel density and clinical and pathological variables in patients with well-differentiated papillary thyroid carcinoma. SUBJECTS: Clinical information was retrieved on 109 previously untreated patients with well-differentiated papillary thyroid carcinoma treated with total thyroidectomy and postoperative iodine I 131 ablation. Median follow-up was 38 months. DESIGN: Archived tissue specimens were sectioned and stained with hematoxylin-eosin and anti-LYVE-1 antibody, a highly specific marker for lymphatic endothelium. The size of the tumor and its multifocality were noted and lymphatic vessel density was measured by means of Chalkley point counting. RESULTS: Numerous intratumoral lymphatics were seen in papillary thyroid carcinoma. There was a highly significant association between the presence of intratumoral lymphatics and the presence of neck node metastases (P<.001). There was also a significant association with male sex (P =.03) and the presence of multifocal disease (P =.05). The presence of intratumoral lymphatics remained significantly associated with the presence of nodal metastases at presentation (P =.003) on multivariate analysis. Intratumoral lymphatics were not a significant predictor of tumor recurrence (P =.42, log-rank test). CONCLUSIONS: The development of intratumoral lymphatics in well-differentiated papillary thyroid carcinoma appears to be associated with the spread of tumor to regional lymph nodes. The antimetastatic potential of targeting these lymphatics may be of potential therapeutic benefit in the future.

Carcinoma, Papillary↗
PubMed2003

Transcervical superior mediastinal lymphadenectomy in the management of papillary thyroid carcinoma.

AIM: Surgery is the treatment of choice for lymph node metastases in papillary thyroid carcinoma. When adequately treated by surgical extirpation, the presence of lymph node involvement does not seem to have a negative impact on cure rates or survival. Surgical lymphadenectomy for metastatic papillary thyroid carcinoma has been well described for both the central and the lateral compartments of the neck. Superior mediastinal lymphadenectomy, however, has only sporadically been mentioned. We describe our experience with transcervical superior mediastinal lymphadenectomy (TSML) that avoids the morbidity of the traditional sternal split. MATERIALS AND METHODS: This retrospective analysis included 30 patients (24 women and 6 men; age range, 17-72 years) who underwent TSML by the senior author (JLF) for papillary carcinoma metastatic to the superior mediastinum between 1985 and 1999. Histopathologic examination confirmed positive nodes in all the mediastinal dissections. All patients received postoperative I(131). RESULTS: All the patients are alive after a median follow-up of 5 years (range, 1-14 years). Twenty-nine of 30 patients remain free of disease, whereas one patient is alive with lung and bone metastases. No patient has had local or regional relapse. The only significant complication was a high incidence of temporary (70%) and later permanent (50%) hypoparathyroidism. CONCLUSIONS: TSML is a safe and effective treatment for superior mediastinal metastases in papillary thyroid carcinoma.

Adolescent↗
PubMed2003

Predictive value of serum thyroglobulin after surgery for thyroid carcinoma.

OBJECTIVE: To determine the relationship between stimulated serum thyroglobulin levels (taken 3 months after total thyroidectomy) and tumor stage and recurrence in patients with well-differentiated thyroid carcinoma. STUDY DESIGN: Retrospective chart review in a tertiary care institution. METHODS: Two hundred thirteen consecutive patients with well differentiated thyroid carcinoma treated between 1983 and 1998 were identified. Data were collected on clinicopathological variables, stimulated serum thyroglobulin levels obtained 3 months after total thyroidectomy prior to 131I therapy and recurrence. RESULTS: A high postoperative thyroglobulin level was significantly associated with advanced-stage disease at presentation (P =.005, Kruskall-Wallis) but not with any of the other clinicopathological variables. Patients with a thyroglobulin level greater than 20 pmol/L had a significantly increased risk of disease recurrence on univariate analysis (n = 213 [P =.0001, log rank test]), and in the Cox proportional-hazards model, both advanced tumor stage (P =.001, relative hazard, 3.4 [95% confidence interval [CI]: 2.4-4.9]) and a thyroglobulin level greater than 20 pmol/L (P =.001, relative hazard, 5.1 [95% CI: 2.0-13.1]) were significant predictors of recurrence. No other variables significantly altered the hazards model. CONCLUSIONS: Advanced tumor stage at diagnosis and a stimulated thyroglobulin level greater than 20 pmol/L taken 3 months after total thyroidectomy were independent predictors of disease recurrence. Patients with a thyroglobulin level greater than 20 pmol/L are at increased risk of recurrence and may be candidates for more intensive follow-up or additional treatment.

Adult↗
PubMed2003

Clinical course of thyroid carcinoma after neck dissection.

OBJECTIVES/HYPOTHESIS: The objective was to compare the rate and site of recurrences in patients with well-differentiated thyroid carcinoma who underwent a central compartment dissection, a posterolateral neck dissection, or a combination of both procedures. STUDY DESIGN: Retrospective chart review. METHODS: The charts of 522 consecutive patients with well-differentiated thyroid carcinoma were reviewed, and 74 patients who had undergone a neck dissection were identified. The rates of recurrence in three sites were noted: the central compartment nodes (levels VI, superior mediastinum), posterolateral compartment neck nodes (levels II-V), and distant sites. These rates were compared in patients who underwent a central compartment dissection (level VI, superior mediastinum) and in patients who underwent a posterolateral neck dissection (levels II-V). RESULTS: Six patients underwent only a central compartment dissection, 47 patients had only a posterolateral neck dissection, and 21 patients had both a central compartment and a posterolateral neck dissection. In these three groups there were zero, two, and two central compartment node recurrences; two, nine, and seven posterolateral neck recurrences; and zero, two, and three distant recurrences, respectively. There were no significant differences in the rate of recurrence in any of the three sites examined between any of the three treatment groups (Fisher's Exact test, all P values >.20). CONCLUSION: In patients with well-differentiated thyroid carcinoma, dissection of only the central or posterolateral compartments of the neck with clinical or radiographic evidence of disease is advocated.

Adolescent↗
PubMed2003

The anatomy and embryology of the hypothalamus in relation to hypothalamic hamartomas.

The hypothalamus is involved in a variety of autonomic, endocrine, neurological and behavioural functions including temperature, osmostatic and autonomic nervous system regulation, pituitary, thyroid, adrenal and gonadal control, thirst, appetite and weight control, memory and emotional behaviour including aggression and laughter, and biological (circadian) rhythms. The functional anatomy of the hypothalamus and its major afferent and efferent neurological connections are described, with particular reference to hypothalamic hamartomas (HH), gelastic seizures, MRI of the hypothalamus, and potential effects of surgery for HH. Normal development of the hypothalamus is reviewed in relation to models of forebrain development, descriptive hypothalamic embryology and the importance of known transcription factors. Potential environmental antecedents to HH development are discussed, and the significance for sporadic, isolated HH of several syndromes associated with HH is explored.

Animals↗
PubMed2003

The endocrinology of hypothalamic hamartoma surgery for intractable epilepsy.

Intractable epilepsy has replaced central precocious puberty (CPP) as the main indication for surgery in patients with hypothalamic hamartoma (HH). However, concern about endocrine complications and the paucity of published endocrine data may dissuade clinicians from recommending HH surgery. We report the preoperative endocrine status and postoperative endocrine findings of patients undergoing HH surgery at our centre. Twenty-nine patients aged 4-23 years (mean 10 years) underwent detailed clinical assessment and biochemical testing of the hypothalamic-pituitary axis before and after transcallosal resection of their HH. The perioperative evaluation included comprehensive evaluation of pubertal status, growth, weight, thyroid and adrenal function, and osmoregulation. Forty-five percent of patients had CPP at presentation and this was not altered by HH surgery. Asymptomatic deficiencies in thyroid hormone, growth hormone and cortisol response were identified in several patients prior to surgery, and biochemical CPP was present in four, clinically prepubertal children. Free thyroxine fell after surgery in the majority, and to clinically significant levels prompting treatment in 5 patients. Low growth hormone was present in 5/8 patients who had had previous HH surgery and in 6/29 following transcallosal surgery at our centre; short stature did not result during the period of follow-up. Hypernatraemia developed in most patients postoperatively with sodium >150 mmol/L seen in 16 (55%) patients; however, this was asymptomatic, not often associated with polyuria, and transient; no patient required ongoing antidiuretic hormone replacement. Appetite stimulation and early postoperative weight gain occurred in 45% patients, but resolved in half. Disturbance of endocrine function may be clinically silent and should be routinely evaluated prior to HH surgery for intractable epilepsy. Following surgery, hypernatraemia, low thyroxine, low growth hormone, and weight gain are the main endocrine problems encountered. Prior, unsuccessful surgery may be a risk factor for endocrinopathy. Except for weight gain in some patients, these postoperative endocrine disturbances appear to be transient, mild or asymptomatic, and easily treated where necessary. Long term follow-up of growth and sexual development in a large series of patients is required.

Adolescent↗
PubMed2003

Transcallosal resection of hypothalamic hamartomas in patients with intractable epilepsy.

A variety of surgical treatments for intractable epilepsy with hypothalamic hamartoma (HH) are described, although most are derived from limited patient experience gathered from several centres. We describe the results of transcallosal resection of HH in 29 consecutive patients undergoing surgery at one centre. Twenty-nine patients aged 4-23 years (mean 10 years) underwent HH surgery with a minimum of 12 months follow-up. A comprehensive, presurgical epilepsy evaluation, supplemented with endocrine and ophthalmological assessments was performed in all cases. HH were resected via a transcallosal, interforniceal approach to the third ventricle, with the assistance of frameless stereotaxy, limiting the resection to the margins of the third ventricular walls and floor and minimising traction and diathermy. Complete or near-complete (>95%) resection of the HH was achieved in 18/29 patients, 75-95% resection was achieved in seven patients (four of whom had complete or near-complete disconnection of residual HH) and less than 50% resection was achieved in four. Postoperatively (follow-up 12-70 months, mean 30 months), 15 became seizure-free (nine off antiepileptic medication), seven had >90% reduction in seizure frequency, three had 55-80% reduction in seizure frequency, and four had less than 40% reduction in seizure frequency. Of 16 patients who had seizures in the early postoperative period, six became seizure. No patient or lesion characteristics were associated with postoperative seizure freedom, including features of symptomatic generalised epilepsy. Neurobehavioural improvement and resolution of EEG abnormalities were seen in the majority. Complications were transient hemiparesis in two, transient hypernatraemia in 17, short-term memory impairment in 14 (persistent in four), weight gain in ten (persistent in five), need for supplemental thyroxine in five, and lowered growth hormone (uncertain clinical significance) in six. Transcallosal resection of HH is an effective treatment for intractable epilepsy, with 76% patients in our seizures being seizure-free or having >90% seizure reduction. The operative risks include stroke, short-term memory disturbance, weight gain and minor endocrine disturbances. Based on published data, the transcallosal approach appears to be safer and more effective than other operative strategies.

Adolescent↗
PubMed2002

Underexpression of p27/Kip in thyroid papillary microcarcinomas with gross metastatic disease.

OBJECTIVE: Papillary microcarcinomas (PMCs) of the thyroid (measuring less than 1 cm in maximum dimension) are extremely common incidental histologic findings, and most of these tumors are not considered clinically significant. However, rare PMCs behave aggressively and metastasize early, giving rise to clinically significant metastatic disease. We hypothesized that p27 and MIB-1/Ki-67 immunoreactivity would allow us to identify this small subgroup of PMCs that have the potential to behave aggressively. METHODS: We reviewed the histopathology reports of 2000 patients who underwent thyroid surgery at our institution between 1995 and 1999 and identified 22 patients who presented with gross regional metastases from a primary PMC. The primary and metastatic tumors were stained for ret, p53, p27, and MIB-1 using the avidin-biotin-peroxidase complex technique. A control group of 33 nonmetastasizing PMCs was also analyzed. RESULTS: Immunoreactivity for ret, p53, and MIB-1 showed no difference between metastasizing and nonmetastasizing PMCs. In most tumors, ret was present, while p53 immunoreactivity was absent in all tumors. MIB-1 staining was present in a small number of cells in both groups of tumors. Immunoreactivity for p27 was quantitated by the intensity of expression as well as the distribution of positive cells within each tumor. All tumors showed lower p27 expression than normal thyroid tissue. However, metastasizing PMCs demonstrated a significantly lower expression of p27 than nonmetastasizing PMCs (P<.001). CONCLUSION: Our results suggest that p27 immunohistochemical analysis may be a valuable diagnostic tool in predicting aggressive potential in PMCs.

Antigens, Nuclear↗
PubMed2002

Impact of nodal metastases on prognosis in patients with well-differentiated thyroid cancer.

OBJECTIVES: To study the clinical and pathological variables predicting lymph node metastases in patients with well-differentiated thyroid carcinoma and to examine the impact of these metastases on recurrence and survival. DESIGN: Cohort study. Median follow-up, 56 months. SETTING: Tertiary referral university teaching hospital. PATIENTS: The study included 522 consecutive patients with well-differentiated thyroid carcinoma treated between 1964 and 1999. Data were collected on age, sex, family history of thyroid disease, prior radiation exposure, stage of disease, pathological diagnosis, size of tumor, multifocality of disease, recurrence, and survival. INTERVENTION: Total thyroidectomy and postoperative iodine 131 ablation. MAIN OUTCOME MEASURES: Disease-free and overall survival. RESULTS: A total of 347 patients with stage I disease and 118 with stage II disease were identified. The median age of patients with neck disease was 3 years younger than those without neck disease and most had papillary carcinoma. Patients with multifocal disease were more likely to have neck disease (P =.02). On univariate analysis, disease-free and overall survival rates were significantly lower in patients who presented with neck node metastases (P<.001 and P =.005); this difference in survival remained highly significant on multivariate analysis for disease-free survival (P =.001), with a relative hazard of 6.27. CONCLUSIONS: When treated with total thyroidectomy and routine postoperative iodine 131 ablation, patients with well-differentiated thyroid carcinoma who present with neck node metastases outside the central compartment of the neck have an approximately 6-fold risk of developing recurrences, most of which occur in the neck.

Adolescent↗
PubMed2002

Thyroid calcification and its association with thyroid carcinoma.

AIM: Calcification within the thyroid gland may occur in both benign and malignant thyroid disease, and its detection on ultrasonography is frequently dismissed by many clinicians as an incidental finding of little significance. As a tertiary referral center, most of our thyroid patients will have had thyroid ultrasonography before being referred to us, and in our experience, the incidence of malignancy in a thyroid nodule containing calcification seems to be higher than that in the average thyroid nodule. To assess this risk, we conducted this retrospective review. MATERIALS AND METHODS: Our analysis included 462 consecutive patients who underwent thyroid surgery at our institution between 1995 and 1999. We reviewed all the patients' charts for data regarding clinical findings, preoperative diagnostic investigations, and histopathologic diagnosis. Of the 462 patients, 361 (78.1%) had thyroid ultrasonography before surgery, and 49 (13.6%) of these ultrasounds showed intrathyroidal calcification. RESULTS: Of the 49 patients whose ultrasounds showed intrathyroidal calcification, 29 (59.2%) were found on histopathologic examination to have thyroid carcinoma. Twelve of the remaining 20 patients had multinodular goiters. Of the 29 patients with malignancy, seven (24.1%) had preoperative fine-needle aspirates that were reported as benign. After excluding patients who were initially seen with multinodular disease, in the subset of 37 patients who presented with a solitary thyroid lesion with calcification, 28 (75.7%) were found to have carcinoma. CONCLUSIONS: When calcification is noted within a solitary thyroid nodule, the risk of malignancy is very high. Surgery should be recommended regardless of the result of fine-needle aspiration cytologic findings.

Calcinosis↗
PubMed2002

Correlation of biochemical parameters with single parathyroid adenoma weight and volume.

OBJECTIVE: To determine the relationship of the biochemical parameters serum phosphate, serum calcium, and serum parathyroid hormone levels with respect to parathyroid adenoma weight and volume in primary hyperparathyroidism. STUDY DESIGN: Retrospective review of 63 cases of primary hyperparathyroidism from 1992 to 1998. METHODS: Single parathyroid adenomas were identified from surgical pathology reports. Preoperative calcium, phosphate, and parathyroid hormone levels were collected from charts. The volume of the adenoma was calculated using a mathematical equation for the volume of an ellipsoid object. The data were analyzed using a multiple analysis of variance, and a correlation coefficient was calculated. The level of significance was set at p < or = .05. RESULTS: With respect to adenoma volume, there was a significant correlation with serum calcium and parathormone levels (p = .0001 and p = .0001, respectively). There was no significant correlation between serum phosphate and adenoma volume. With respect to adenoma weight, there was a significant correlation with serum calcium and parathormone levels (p = .0001 and p = .0001, respectively). There was no significant correlation between serum phosphate and adenoma weight. CONCLUSIONS: Preoperative serum calcium and parathormone levels may be able to predict adenoma weight and volume in primary hyperparathyroidism for a single adenoma.

Adenoma↗
PubMed2002

Hemiconvulsion-hemiplegia-epilepsy syndrome: characteristic early magnetic resonance imaging findings.

We report three patients with hemiconvulsion-hemiplegia-epilepsy syndrome who presented acutely and were shown to have striking neuroimaging findings suggestive of diffuse cytotoxic edema confined to one hemisphere, including extensive diffusion-weighted imaging abnormalities in two cases. Two patients subsequently developed progressive and extensive atrophy of the involved hemisphere. These findings are consistent with earlier descriptions of the classic neuroradiologic features of this syndrome and are helpful in the differential diagnosis of acute infantile hemiplegia. Further, the findings support the previously proposed pathogenetic mechanism of neuronal injury caused by status epilepticus.

Aspartic Acid↗
PubMed2002

Cyclin D1 protein expression predicts metastatic behavior in thyroid papillary microcarcinomas but is not associated with gene amplification.

Overexpression of cyclin D1 occurs in several malignancies, often due to gene amplification, and this has been associated with aggressive tumor behavior, a higher incidence of lymph node metastases, and a poorer prognosis. The role of cyclin D1 in the pathogenesis of thyroid malignancy is unknown; however, cyclin D1 expression has been reported to occur in a proportion of well differentiated thyroid carcinomas. Micropapillary carcinomas of the thyroid are common incidental findings that almost always behave in an indolent manner and remain quiescent. However, rare microcarcinomas behave aggressively and metastasize early, giving rise to clinically significant disease. We hypothesized that cyclin D1 might play a role in the aggressive behavior of metastasizing papillary microcarcinomas. We reviewed the histopathology reports of 2,000 patients who underwent thyroid surgery at our institution between 1995-1999 and identified 22 patients who presented with gross regional metastases from a primary papillary microcarcinoma. These patients formed the index cohort for this analysis. As controls, we selected 34 patients with nonmetastasizing microcarcinomas. We studied these tumors for immunoreactivity to cyclin D1 on immunohistochemistry and analyzed 13 tumors that diffusely expressed cyclin D1 for gene amplification by differential PCR. Twenty of the 22 (90.9%) metastasizing papillary microcarcinomas expressed cyclin D1, compared with 3 of the 34 (8.8%) nonmetastasizing papillary microcarcinomas (P < 0.001). However, of the 13 tumors that showed diffuse immunoreactivity for cyclin D1 on immunohistochemistry, none showed amplification of the cyclin D1 gene on differential PCR. We conclude that cyclin D1 is significantly overexpressed in metastasizing papillary microcarcinomas of the thyroid. This is likely due to mechanisms other than gene amplification. Cyclin D1 immunohistochemistry may be a valuable tool in predicting metastatic potential in papillary microcarcinomas.

Carcinoma, Papillary↗
PubMed2002

Overexpression of cyclin D1 and underexpression of p27 predict lymph node metastases in papillary thyroid carcinoma.

Lymph node metastasis in papillary thyroid carcinoma increases the morbidity of treatment and the risk of local regional relapse and may also affect cure rates and survival. Factors that predict lymph node metastasis are, however, unclear. We analyzed 125 patients with papillary thyroid carcinoma for factors that predict lymph node metastasis. On univariate analysis, age, extrathyroidal extension, tumor focality, overexpression of cyclin D1, and underexpression of p27 predicted lymph node metastasis, whereas patient gender and tumor size did not. On multivariate analysis, extrathyroidal extension, overexpression of cyclin D1, and underexpression of p27 proved to be strong independent predictors of lymph node metastasis. We suggest that immunohistochemistry for cyclin D1 and p27 will prove valuable in identifying papillary thyroid carcinomas with metastatic potential.

Adolescent↗
PubMed2002

Parotid gland tumours in 255 consecutive patients: Mount Sinai Hospital's quality assurance review.

Parotid neoplasms represent a diverse group of tumours found in the head and neck. Complications following parotidectomy, including Frey's syndrome, facial nerve paralysis, sialoceles, and parotid fistulae, have been well documented. A retrospective review of 255 patients treated surgically for parotid masses over an 8-year period at Mount Sinai Hospital in Toronto was reviewed as part of a quality assurance program. The sensitivity, specificity, and predictive values for fine-needle aspiration cytology were analyzed. The incidence of benign and malignant lesions is presented. The complications following parotidectomy are reviewed and in our series are consistent with the figures published in the literature.

Adolescent↗