PubMed Health⌕ Search

Biomedical subjects

Robert Udelsman

Publications and source records attributed to Robert Udelsman.

13 recordsLinked to original sources

Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing.

Thyroid-stimulating hormone receptor (TSHR) expression is frequently silenced in epithelial thyroid cancers associated with decreased or absent TSH-promoted iodine uptake. To study the underlying molecular mechanism of decreased TSHR expression, we examined the methylation status of the TSHR gene promoter by sequencing bisulfite-treated DNA from thyroid tumors. After identification of methylated sites by sequencing bisulfite-treated DNA, we used methylation-specific polymerase chain reaction and found frequent CpG methylation in papillary thyroid cancer (23 of 39 patients; 59%) and follicular thyroid cancers (7 of 15 patients; 47%). In contrast, we saw no methylation in normal thyroid tissues and benign adenomas (0 of 8 patients; 0%). In human thyroid tumor cell lines, we observed that TSHR was normally expressed at the protein and mRNA level in cells where the TSHR gene was unmethylated, whereas it was silenced in cell lines where the TSHR promoter was hypermethylated. Treatment of the latter cells with a demethylating agent partially restored TSHR expression. We thus demonstrate aberrant methylation of human TSHR as a likely molecular pathway responsible for the silencing of this gene in thyroid cancers. We propose that methylation of TSHR may provide a novel diagnostic marker of malignancy and a basis for potential use of demethylating agents in conjunction with TSH-promoted radioiodine therapy for epithelial thyroid cancers.

Adenoma↗

Utilization of fine-needle aspiration in patients undergoing thyroidectomy at two academic centers across the Atlantic.

Although fine-needle aspiration (FNA) has been accepted as a first-line test in patients with thyroid masses, the utilization of FNA varies even among experienced surgeons. To determine its utility we compared FNA results, pathology, and clinical results in patients who underwent thyroidectomy in two major endocrine centers on both sides of the Atlantic: one in the United States (US) and another in the United Kingdom (UK). Between January 1997 and March 1998 a total of 84 patients underwent thyroid surgery at the UK center, and 143 underwent thyroidectomy at the US center. The most common indication for thyroidectomy at the UK center was compressive goiter (CG), whereas follicular neoplasm (FN) was the most common indication at the US center. Bilateral thyroid resections, frozen section utilization, and thyroid cancer surgery were more common at the US center. Thyroidectomy for symptomatic multinodular goiter and Graves' disease was more prevalent at the UK center. Thyroid gland weights were also significantly greater in the UK, indicating a higher incidence of endemic goiter. FNA was more commonly employed in the US center (84% vs. 52%; p < 0.001). Despite the differing utilization of FNA at these major endocrine centers, only one thyroid cancer at each institution was not detected preoperatively (both patients had a benign FNA result). Therefore there were no clinically significant thyroid cancers found in patients who did not undergo preoperative FNA. In conclusion, FNA appears to be differentially utilized depending on the incidence of endemic goiter, Graves' disease, and thyroid cancer. In this series no clinically significant thyroid cancers were found in patients who did not undergo preoperative FNA. Therefore in the hands of experienced thyroid surgeons, FNA can be utilized selectively based on the clinical presentation.

Biopsy, Needle↗

Parathyroid tumors.

Parathyroid tumors causing primary hyperparathyroidism are common and often remain undiagnosed, despite that the diagnostic work-up is uncomplicated in most patients. The patients often do not receive the appropriate curative treatment, which is surgical. Recent studies show that surgery is beneficial in patients with mild asymptomatic disease, especially in the reversal of bone disease, neuropsychologic symptoms, and dyslipoproteinemia. All patients with the disease deserve a referral to an endocrine surgeon for discussions regarding surgical intervention. Minimally invasive techniques performed in the ambulatory setting have evolved rapidly and show an extraordinary high success rate, low-morbidity rate, and are likely to become the standard treatment for most patients with primary hyperparathyroidism.

Humans↗

Minimally invasive parathyroidectomy.

Efforts to minimize the incision, extent of exploration, length of hospital stay, and cost associated with parathyroidectomy have resulted in the development of a number of new surgical techniques, including minimally invasive, "concise," radio-guided, and endoscopic parathyroid exploration. With minimally invasive parathyroidectomy, a small incision is used in combination with a cervical block and sedation to perform a unilateral neck exploration. In so doing, risks of bilateral neck exploration are avoided, and the procedure can be done on an outpatient basis. This minimally invasive strategy has been shown to maintain the outstanding success of conventional bilateral neck exploration. All of the new surgical techniques necessitate pre-operative localization, which allows for unilateral neck exploration, and are facilitated by use of the intra-operative parathyroid hormone assay, which provides surgeons with feedback in the operating room regarding whether the patient has undergone adequate resection.

Humans↗

Rapid parathyroid hormone analysis during venous localization.

OBJECTIVE: To determine the usefulness of the rapid parathyroid hormone (PTH) assay during venous localization for primary hyperparathyroidism (1 degrees HPTH). SUMMARY BACKGROUND DATA: Remedial exploration for persistent 1 degrees HPTH poses a significant challenge when noninvasive preoperative localization studies are negative. Based on experience with the intraoperative rapid PTH assay, this technique was extrapolated to the interventional radiology suite and generated near real-time data for the interventional radiologist employing on-site hormone analysis, with a 12-minute turnaround time from blood sampling to assay result. METHODS: Between November 1997 and July 2002, 446 patients with 1 degrees HPTH were referred for treatment. Of these, 56 (12.5%) represented remedial patients who had each undergone one or more previous cervical explorations. Noninvasive imaging studies were positive for or suggestive of localized disease in 49/56 (87.5%) of these patients, who therefore proceeded directly to surgical exploration. Seven patients with persistent 1 degrees HPTH and negative noninvasive studies underwent selective venous sampling employing a rapid PTH assay in the interventional suite. RESULTS: Venous localization demonstrated an apparent PTH gradient in six of the seven patients. In three, a subtle gradient demonstrated in near real-time prompted additional sampling, which confirmed an unequivocal hormone gradient. In an additional case, the absence of a gradient on initial sampling prompted further sampling, which was positive. All of the patients were explored, and in five of the six patients with a positive PTH gradient, a parathyroid adenoma (mean weight 636 +/- 196 mg) was resected from a location predicted by venous localization. In the sixth patient with a positive gradient, parathyroid tissue was not identified; however, there was a significant fall in the intraoperative PTH values, and immediate postoperative and follow-up laboratory data at 1 month are indicative of a cure. In the one patient with negative localization, abnormal parathyroid tissue could not be located during surgical exploration. CONCLUSIONS: The rapid PTH assay is a major adjunct for obtaining informative venous localization in patients with persistent 1 degrees HPTH. This information is extremely helpful to the surgeon in this challenging group of patients and resulted in a 100% cure rate when a venous gradient was demonstrated. The authors now employ this technique routinely in remedial patients with negative noninvasive imaging studies.

Adenoma↗

Primary thyroid lymphoma: can the diagnosis be made solely by fine-needle aspiration?

BACKGROUND: Primary malignant lymphoma of the thyroid accounts for <5% of all thyroid malignancies and is primarily treated with chemotherapy and external beam radiation. With the advent of modern immunophenotypic analyses, fine-needle aspiration (FNA) can potentially obviate the need for surgical procedures. METHODS: To investigate the utility of FNA, data from 23 consecutive patients with primary malignant thyroid lymphoma evaluated at the Johns Hopkins Hospital from July 1985 to April 2000 were analyzed. RESULTS: Patients were categorized into two groups: those diagnosed before 1993 (group 1, n = 12) and those diagnosed after 1993 (group 2, n = 11). Although patients in group 1 were slightly older, there were no other differences between the groups with regard to sex, tumor grade, or tumor stage. Although no patient in group 1 was successfully diagnosed by FNA alone, seven patients (63%) in group 2 were diagnosed solely by FNA (P =.019, chi(2) analysis). Therefore, all 12 patients in group 1, but only 4 of 11 patients in group 2, required open surgical biopsy. CONCLUSIONS: Primary thyroid lymphoma is an uncommon malignancy usually treated nonsurgically once the diagnosis is established. In most patients with malignant lymphoma of the thyroid, FNA, should obviate the need for open surgical biopsy.

Adult↗

Anaplastic pseudothyroiditis.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumours. It generally presents as a rapidly enlarging thyroid mass and produces local symptoms associated with mass effect. One of the very rare presentations of ATC is thyrotoxicosis. We report a patient with ATC whose course was complicated by severe thyrotoxicosis. His symptoms were controlled with beta-blockers. Two weeks into hospitalization, the patient became hypothyroid. Histopathology showed destruction of the normal thyroid follicles by the invasion of the tumour. As this form of thyrotoxicosis resembles various thyroiditides, we hereby refer this condition as "anaplastic pseudothyroiditis".

Carcinoma↗

Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism.

BACKGROUND: Delayed technetium-99m sestamibi single photon emission computed tomography (SPECT) scans were prospectively analyzed in a large series of patients with primary hyperparathyroidism. METHODS: Three hundred thirty-eight patients underwent sestamibi-SPECT and were explored. Prospective data included preoperative demographics, clinical, sestamibi, and operative findings, laboratory values, and pathologic and follow-up laboratory results from all patients. RESULTS: Between 1994 and 2000, 287 unexplored patients (85%) and 51 re-explored patients (15%) participated. The abnormal parathyroid glands excised from 336 of 338 patients included 299 single adenomas (88%) and 23 double adenomas (7%), and 14 patients had multigland hyperplasia (4%). Sestamibi SPECT correctly lateralized 349 of 400 abnormal parathyroid glands, with an overall sensitivity of 87%, an accuracy of 94%, and a positive predictive value of 86%. Precise localization occurred in 82% of the abnormal parathyroid glands. Sestamibi sensitivity was similar in unexplored (87%) and reoperative (92%) cases; two hundred eighty-six of 299 (96%) solitary adenomas, 38 of 46 (83%) double adenomas, but only 25 of 55 (45%) hyperplastic glands were identified. The mean weight of the true-positive glands (1252 +/- 1980 mg) was greater than that of the false-negative glands (297 +/- 286 mg) (P <.005). Three patients had persistent primary hyperparathyroidism, in spite of the excision of sestamibi-identified lesions in 2 cases. Follow-up indicated curative resection in 99% of the unexplored cases and 94% of the remedial cases. CONCLUSIONS: Sestamibi SPECT is highly accurate for the localization of parathyroid adenomas in unexplored and re-explored cases, where it is often the only imaging required. Its sensitivity is limited in multiglandular disease.

Adenoma↗

Six hundred fifty-six consecutive explorations for primary hyperparathyroidism.

OBJECTIVE: To review the outcomes of 656 consecutive parathyroid explorations performed by a single surgeon and to compare the results of conventional and minimally invasive parathyroidectomy (MIP) techniques. SUMMARY BACKGROUND DATA: Traditional surgery for primary hyperparathyroidism (HPTH) involves bilateral cervical exploration, which is usually accomplished under general endotracheal anesthesia. The MIP technique involves preoperative localization with sestamibi scans, surgeon-administered cervical block anesthesia, directed exploration through a small incision, intraoperative rapid parathyroid hormone assay, and discharge within 2 to 3 hours of surgery. METHODS: Six hundred fifty-six consecutive patients with primary HPTH underwent exploration between January 1990 and March 2001. RESULTS: MIP was used with ever-increasing frequency beginning in March 1998. Four hundred one procedures (61%) were performed using the standard technique and 255 patients (39%) were selected for MIP. The success rate for the entire series was 98%, with no significant differences comparing traditional and MIP techniques. The overall complication rate of 2.3% reflects 3.0% and 1.2% rates in the standard and MIP groups, respectively. MIP was associated with approximately a 50% reduction in operating time, a sevenfold reduction in length of hospital stay, and a mean cost savings of $2,693 per procedure, which represents nearly a 50% reduction in total hospital charges. CONCLUSIONS: A dramatic and sustained shift has occurred in the surgical treatment of primary HPTH: MIP has replaced traditional exploration for most patients.

Cost Savings↗

Surgery in primary hyperparathyroidism: the patient without previous neck surgery.

The indications for surgical exploration in the "asymptomatic" patient with primary hyperparathyroidism (1 degrees HPTH) have changed since the 1990 National Institutes of Health Consensus Development Conference. This seems to be, at least in part, caused by the introduction of minimally invasive parathyroidectomy (MIP) techniques. The concept of MIP is based on the fact that the majority of patients (80-85%) with 1 degrees HPTH have a single adenoma that can usually be identified on preoperative imaging. The incident adenoma can be resected under local or regional anesthesia, and an intraoperative adjunct, such as the rapid parathyroid hormone (PTH) assay, can be used to show an adequate decrement in plasma PTH levels. There are no randomized prospective trials comparing the results obtained with conventional and MIP techniques. However, a recent series of 656 consecutive parathyroid explorations compared the results obtained using conventional (n = 401) and MIP (n = 255) surgery. The success rate for the entire series was 98%, and there were no significant differences in cure rates between traditional (97%) and MIP (99%) techniques. The overall complication rates were also similar. However, MIP was associated with a 50% reduction in operating time, a 7-fold reduction in length of hospital stay, and a mean cost savings of $2693 per case. It seems likely that the majority of patients with 1 degrees HPTH can now be cured on an outpatient basis with MIP, which has already replaced conventional parathyroid exploration in several endocrine centers. Limitations to this procedure include the need for sophisticated adjuncts and a surgeon highly experienced in this new technique.

Adenoma↗

Do future general surgery residents have adequate exposure to endocrine surgery during medical school?

During their general surgical rotations, medical students should ideally have exposure to a wide breadth of surgical procedures, especially if they are interested in pursuing surgical careers. To determine their exposure to endocrine surgery during medical school, we surveyed students from more than 20 medical schools who interviewed for general surgery residency positions at our institution over a 2-year period. Questions focused on the total number of index surgical procedures observed during all of their medical school education. Of 211 surveys sent, 146 were returned (66%). The mean age of the students was 26.0 +/- 0.3 years, and 21% were women. The average times spent on general surgery and surgery subspecialty rotations during medical school were 11.1 +/- 0.6 weeks and 7.6 +/- 0.4 weeks, respectively. The mean number of thyroidectomies (2.8 +/- 0.3), parathyroidectomies (1.9 +/- 0.3), and adrenalectomies (0.5 +/- 0.1) observed by the medical students were significantly lower than operations such as mastectomies (9.4 +/- 0.3), coronary bypass surgeries (8.7 +/- 1.4), and laparoscopic cholecystectomies (10.0 +/- 0.7). Furthermore, of these 146 future surgical residents, 34% failed to observe a single thyroid resection, 42% did not see a parathyroidectomy, and 65% failed to see an adrenalectomy. In conclusion, future general surgery residents seem to observe a wide variety of surgical cases, but most have little or no exposure to endocrine surgery. This paucity of exposure may have significant educational and career ramifications.

Adrenalectomy↗