Biomedical subjects

O H Clark

Publications and source records attributed to O H Clark.

At least 37 records · Page 2Linked to original sources

PubMed2001

Monitoring signal transduction in cancer: cDNA microarray for semiquantitative analysis.

This study targeted the development of a novel microarray tool to allow rapid determination of the expression levels of 58 different tyrosine kinase (tk) genes in small tumor samples. The goals were to define a reference probe for multi-sample comparison and to investigate the variability and reproducibility of the image acquisition and RT-PCR procedures. The small number of tk genes on our arrays enabled us to define a reference probe by artificially mixing all genes on the arrays. Such a probe provided contrast reference for comparative hybridization of control and sample DNA and enabled cross-comparison of more than two samples against one another. Comparison of signals generated from multiple scanning eliminated the concern of photo bleaching and scanner intrinsic noise. Tests performed with breast, thyroid, and prostate cancer samples yielded distinctive patterns and suggest the feasibility of our approach. Repeated experiments indicated reproducibility of such arrays. Up- or downregulated genes identified by this rapid screening are now being investigated with techniques such as in situ hybridization.

Breast Neoplasms↗

PubMed2000

Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

BACKGROUND: The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial. METHODS: The study group consisted of 104 patients with MTC or C-cell hyperplasia managed at the hospitals of the University of California, San Francisco, between January 1960 and December 1998. Patients were classified as having sporadic MTC, familial non-multiple endocrine neoplasia (MEN) MTC, MEN 2A, or MEN 2B. The TNM, European Organization for Research and Treatment of Cancer (EORTC), National Thyroid Cancer Treatment Cooperative Study (NTCTCS), and Surveillance, Epidemiology, and End Results (SEER) extent-of-disease stages were determined for each patient. The predictive values of these staging or prognostic scoring systems were compared by calculating the proportion of variance explained (PVE) for each system. RESULTS: Fifty-six percent of the patients had sporadic MTC, 22% had familial MTC, 15% had MEN 2A, and 7% had MEN 2B. The overall average age at diagnosis was 38 years, and patients with sporadic MTC presented at an older age (P < 0.05). Thirty-two percent of the patients with hereditary MTC were diagnosed by screening (genetic and/or biochemical). These patients had a lower incidence of cervical lymph node metastasis (P < 0.05) and 94.7% were cured at last follow-up (P < 0.0001) compared with patients not screened. Patients with sporadic MTC who had systemic symptoms (diarrhea, bone pain, or flushing) had widely metastatic MTC and 33.3% of those patients died within 5 years. Overall, 49.4% of the patients were cured, 12.3% had recurrent MTC, and 38.3% had persistent MTC. The mean follow-up time was 8.6 years (median, 5.0 years) with 10.7% (n=11) and 13.5% (n=14) cause specific mortality at 5 and 10 years, respectively. Patients with persistent or recurrent MTC who died of MTC lived for an average of 3.6 years (ranging from 1 month to 23.7 years). Patients who had total or subtotal thyroidectomy were less likely to have persistent or recurrent MTC (P < 0.05), and patients who had total thyroidectomy with cervical lymph node clearance required fewer reoperations for persistent or recurrent MTC (P < 0.05) than patients who underwent lesser procedures. In univariate analysis, age, gender, clinical presentation, TNM stage, sporadic/hereditary MTC, distant metastasis, and extent of thyroidectomy were significant prognostic factors. Only age and stage, however, remained independent prognostic factors in multivariate analysis. The TNM, EORTC, NTCTCS, and SEER staging systems were all accurate predictors of survival, but the EORTC prognostic scoring system had the highest PVE in this cohort. CONCLUSIONS: Screening for MTC and early treatment (total thyroidectomy with central neck lymph node clearance) had nearly a 100% cure rate. Patients with postoperative hypercalcitoninemia without clinical or radiologic evidence of residual tumor after apparently curative surgery may enjoy long term survival but have occult MTC. Only patient age at presentation and TNM stage were independent predictors of survival. The EORTC criteria, which included the greatest number of significant prognostic factors in our cohort, had the highest predictive value.

Adult↗

PubMed2000

Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer.

HYPOTHESIS: Reoperation benefits patients with locoregional, persistent, or recurrent medullary thyroid cancer (MTC). Currently available localizing studies have limited utility for detecting all foci of residual MTC. DESIGN: A retrospective study with a mean follow-up time of 7.5 years (median, 13 years; range, 2.2-29 years). SETTING: A tertiary referral medical center. PATIENTS: Thirty-three patients who underwent 46 reoperations for locoregional residual MTC. RESULTS: Sixty-four percent of residual MTC was located in the lateral cervical nodes, 22% in the central cervical nodes or thyroid bed, and 14% in the anterior mediastinum (197 of 1128 nodes resected were positive for MTC). After reoperation, basal calcitonin levels were undetectable in 2 patients, reduced by greater than 50% in 10 patients, and either increased or were not reduced by greater than 50% in the remaining patients. On reoperation, one patient had a thoracic duct injury that required reexploration and ligation. Patients who had a greater than 50% decrease in calcitonin levels after reoperation were less likely to develop distant metastases compared with patients who did not have a greater than 50% decrease (P<.05). The sensitivities of magnetic resonance imaging (n = 31), computed tomographic scan (n = 16), ultrasound (n = 9), and dimercaptosuccinic acid scan (n = 3) were 91%, 86%, 88%, and 100%, respectively. CONCLUSIONS: Although reoperation in patients with residual MTC rarely results in biochemical cure, cervical reexploration is safe and in selected patients may limit MTC progression. Lateral cervical node dissection could be beneficial at the time of initial surgical treatment because of the high frequency of residual MTC in the lateral cervical nodes. Noninvasive imaging studies were helpful but far from perfect for guiding the reexploration for locoregional residual MTC.

Adult↗

PubMed2000

Laparoscopic posterior adrenalectomy: technical considerations.

HYPOTHESIS: Although laparoscopic posterior adrenalectomy (LPA) offers a more direct access to the adrenal gland, it is not as popular as laparoscopic transabdominal adrenalectomy, and the worldwide experience has been limited. We hypothesized that LPA is a safe and efficacious procedure that could best serve certain patients with adrenal tumors. DESIGN: Case series of patients undergoing laparoscopic adrenalectomy in a single institution. SETTING: University teaching hospital. PATIENTS: Medical records of 31 patients with 33 tumors who underwent LPA were reviewed. Indications for operation included hormone secretion in 23 patients (74%), suspected or known malignant neoplasms in 7 patients (23%), and local symptoms in 1 patient (3%). INTERVENTION: The LPAs were performed with the patients in prone position. Preoperative ultrasonography localized the adrenal tumor and kidney to guide balloon trocar placement for the creation of a working retroperitoneal space. The LPAs were performed with three 10-mm trocars using laparoscopic ultrasound to localize the tumor and the harmonic scalpel to perform the dissection. MAIN OUTCOME MEASURES: Demographic data, type and size of tumor, operative time, blood loss, intraoperative and postoperative complications, and hospital stay were analyzed. RESULTS: All operations were successfully completed without conversion. Excluding the bilateral cases, the mean +/- SD operative time was 176 +/- 104 minutes. Estimated blood loss averaged 32 mL (range, 10-200 mL). There were no intraoperative complications. The mean +/- SD tumor size was 3.2 +/- 1.8 cm (range, 0.8-7.0 cm). Pathological evaluation revealed benign tumors in 25 patients (81%) and malignant tumors in 6 patients. The average hospital stay was 1.4 days (range, 1-3 days). There were no deaths. CONCLUSIONS: Although technically more demanding, LPA should be considered in patients with tumors less than 6 cm, bilateral tumors, or extensive previous abdominal surgery.

Adrenal Gland Neoplasms↗

PubMed2000

Differentiated thyroid cancer: "complete" rational approach.

Controversy continues regarding the optimal management of patients with differentiated thyroid cancer because no prospective randomized studies evaluating the merits of (1) extent of thyroidectomy, (2) postoperative radioactive iodine ablation, or (3) thyroid-stimulating hormone (TSH) suppressive therapy exist. Patients with low risk differentiated thyroid cancer enjoy a relatively good prognosis with a mortality rate of about 2% to 5% and a recurrence rate of about 20%. Despite the excellent prognosis in patients considered to be at low risk, total or near-total thyroidectomy in patients with differentiated thyroid cancer has the advantages that: (1) postoperative radioactive iodine can be used to detect and treat residual normal thyroid tissue and local or distant metastases; (2) follow-up serum thyroglobulin levels are a more sensitive marker of persistent or recurrent disease when all thyroid tissue has been removed; and (3) total or near-total thyroidectomy with postoperative (131)I ablation and TSH suppressive therapy is associated with better survival and lower recurrence rates. Patients with occult papillary thyroid cancer and minimally invasive follicular thyroid cancer can be treated by thyroid lobectomy because they have a near-normal life expectancy. Virtually all other patients with differentiated thyroid cancer appear to benefit from more extensive initial treatment.

Diagnosis, Differential↗

PubMed2000

Total thyroidectomy or thyroid lobectomy in patients with low-risk differentiated thyroid cancer: surgical decision analysis of a controversy using a mathematical model.

There is a general consensus that total or near-total thyroidectomy is the optimal treatment for patients with high risk differentiated thyroid cancer (DTC), but the optimal extent of thyroidectomy in patients with low risk DTC continues to be controversial. To determine the optimal extent of thyroidectomy in patients with low risk DTC, we used decision analysis to compare the trade-offs of total thyroidectomy (TT) to thyroid lobectomy (TL). The decision analysis model included the probabilities of thyroidectomy complications, risk of DTC recurrence, and death from DTC. This information was obtained from the literature and from outcome data for patients with low risk DTC from our institution. In addition, the concept of utilities was used in the analysis. To determine the utility of each health outcome state (thyroidectomy complication, DTC recurrence, and DTC mortality for low risk patients) a survey was conducted. Overall, prospective patients viewed DTC recurrence as less desirable than thyroidectomy complication. The utilities assigned by the survey participants varied over a wide range, with 61.5% of the individuals viewing the occurrence of a thyroidectomy complication as better than DTC recurrence. At baseline utilities and probabilities, TT had a higher expected utility than TL. One-way sensitivity analysis varying the rates of (1) thyroidectomy complication, (2) DTC recurrence, and (3) DTC mortality over the possible range showed that complication from initial thyroidectomy was the most important factor that determined the preferred extent of thyroidectomy. TL was the preferred surgical approach only if a complication rate of > 33:1, TT/TL complication rate ratio, was assumed. When no differences in DTC recurrence between the two approaches was assumed in the model, TL had a higher expected utility using the baseline utilities of thyroidectomy complication and DTC mortality. The analysis indicates that TT in patients with low risk DTC is preferable to TL. However, TL is preferred if (1) no difference in the DTC recurrence rate between the two approaches is assumed, (2) a higher complication rate for TT is used (> 33 times higher), or (3) the utility ratio of thyroidectomy complication to DTC recurrence is < 0.8 TL. We believe this decision analysis model provides an objective approach that others can use to select the optimal extent of thyroidectomy based on patient preference of health outcome states, institution-specific outcome data for DTC recurrence or mortality, and the surgeon-specific complication rate.

Adenocarcinoma, Follicular↗

PubMed2000

Intraoperative parathyroid aspiration and parathyroid hormone assay as an alternative to frozen section for tissue identification.

Most people would agree that successful parathyroidectomy depends on two important variables: the surgeon's recognition and excision of the abnormal parathyroid gland(s) and the pathologist's confirmation that the removed tissue is parathyroid tissue. Frozen section is usually employed to confirm the identity of parathyroid tissue, but occasionally confirmation cannot be made without a permanent section, as with intrathyroidal glands. This study proposes a new method of expeditious and easy confirmation of parathyroid tissue utilizing the immunoassay for quick measurement of intraoperative parathyroid hormone (IOPTH). By directly aspirating the suspected adenoma, the assay becomes a rapid diagnostic tool that can be used as an alternative to frozen section. In cases where the surgeon is already planning to employ the assay, the elimination of frozen section is cost-effective. Intraoperative aspiration of histologically confirmed parathyroid adenomas was performed on 12 consecutive patients undergoing parathyroid surgery. Parathyroid glands were aspirated with a 22-gauge syringe after gland excision. Aspirates were placed in 1 to 3 ml of buffered saline. A similar process was performed on 12 thyroid controls. Specimens were centrifuged, aliquotted, and stored at -70 degrees C. The parathyroid hormone value was analyzed electively by rapid assay and the values recorded. For all parathyroid aspirates, the rapid assay value was > 1500 pg/ml, exceeding the uppermost limit of the diagnostic chart. Values for thyroid aspirates ranged from 58 to 85 pg/ml (mean 75.7 pg/ml). In all cases tissue confirmation was achieved with permanent section. Values were 100% sensitive and specific. Measurement of PTH from intraoperative aspiration of suspected parathyroid adenomas is clinically useful in patients for whom frozen section would routinely be employed. Values > 1500 pg/ml secure the tissue diagnosis. There is no additional cost in cases where IOPTH monitoring is already being utilized to confirm cure. The elimination of frozen section could be cost-effective and, for some institutions, actually decrease the operating time as the IOPTH assay takes only 15 minutes. PTH assay is an accurate diagnostic technique and to date is 100% sensitive and specific for differentiating between parathyroid tumors and thyroid nodules.

Biopsy, Needle↗

PubMed2000

Recurrent or persistent thyroid cancer of follicular cell origin.

Most patients with differentiated thyroid cancer of follicular cell origin have a favorable postoperative course, and their prognosis often appears to be unrelated to the extent of initial surgical treatment in some studies. Important questions that need to be addressed include whether the extent of the initial operation has any impact on the subsequent tumor-free survival and total survival, and whether patients with persistent or recurrent disease benefit from reoperation.

Adenocarcinoma, Follicular↗

PubMed2000

Medullary thyroid cancer.

Patients with clinically evident medullary thyroid cancer should have a total extracapsular thyroidectomy with bilateral central neck dissection and an ipsilateral prophylactic or therapeutic modified (functional) radical neck dissection when the primary tumor is greater than 1 cm and when the central neck nodes are positive. A prophylactic contralateral neck dissection should be done when the primary tumor is bilateral and when there is extensive lymphadenopathy on the side of the primary tumor. Patients who have gross, unresectable residual medullary thyroid cancer should receive postoperative external radiotherapy. Patients who are carriers of germ-line RET proto-oncogene point mutations or have an elevated (basal or stimulated) calcitonin levels on screening should have a prophylactic total thyroidectomy before age 6 years. In patients with an elevated basal or stimulated plasma calcitonin level and an intrathyroidal nodule on ultrasound, a total thyroidectomy and central neck lymph node dissection should be done. Patients with persistent or recurrent medullary thyroid cancer should have a complete thyroidectomy (if not done initially) and bilateral central and modified radical neck dissection, including upper mediastinal lymphadenectomy. Patients who are symptomatic from distant medullary thyroid cancer metastases (diarrhea, flushing, weight loss, or bone pain) should be treated with somatostatin analogs. Bone metastases should be resected if possible, and symptomatic lesions that are unresectable should be treated with external radiotherapy. Cytoreductive procedures such as radiofrequency ablation or cryoablation for liver metastases should be considered in symptomatic patients to reduce tumor burden. Localized pulmonary metastases should be resected. Chemotherapy or radioactive immunotherapy (iodine 131 labeled carcinoembryonic antigen monoclonal antibody) protocols should be considered in patients with nonoperative widely metastatic progressing medullary thyroid cancer.

Antineoplastic Agents↗

PubMed2000

Treatment of Graves' disease: the advantages of surgery.

The authors and others believe that surgery (thyroidectomy) is underused in the treatment for patients with Graves' disease. It is the most rapid and consistent method of making the patient euthyroid; it avoids the possible long-term risks of radioactive iodine; and it provides tissue for histologic examination. Children, young women, pregnant women, and patients with coexistent thyroid nodules are ideal candidates for thyroidectomy. It also is the treatment of choice for patients with Graves' ophthalmopathy. Patients should be rendered euthyroid before thyroidectomy. Although the operation is technically more difficult than operating on patients with nontoxic goiter or thyroid neoplasms because of the vascularity of the thyroid gland, this difference is small, and the complication rates are low. The authors recommend the Hartley-Dunhill operation (total thyroidectomy on one side and subtotal thyroidectomy on the other side, leaving about 4 to 5 g of thyroid tissue) for most patients and total thyroidectomy for patients with Graves' ophthalmopathy. In patients with recurrent or persistent thyroid cancer who fail to respond to surgery and radioactive iodine ablation, immunosuppressive therapy should be considered.

Child↗

PubMed2000

Surgical approaches to primary hyperparathyroidism.

Primary hyperparathyroidism, once thought to be a rare disease entity, is now a common problem. It can be diagnosed with nearly 100% accuracy. Surgical therapy is the only definitive cure for this disease, and normocalcemia is achieved in 95% of patients at initial operation when performed by an experienced surgeon. Even when the operation is initially unsuccessful, most of the patients with persistent disease can subsequently be cured. Although some clinicians have proposed that asymptomatic patients can be medically managed, the cost of such treatment, problems with patient compliance with long-term follow-up, the increased risk of premature death associated with primary hyperparathyroidism, and the low morbidity of operation support a liberal policy for exploration in most patients. The authors believe that nonoperative therapy should be limited to older patients with multiple comorbid conditions and minimal hypercalcemia and clinical manifestations.

Female↗

PubMed2000

Hyperparathyroidism after thyroid surgery and autotransplantation of histologically normal parathyroid glands.

BACKGROUND: Parathyroid autotransplantation is a well-established method to prevent hypoparathyroidism during parathyroid and thyroid operations. The reported success rate of parathyroid autotransplantation ranges from 75% to 100%. Recurrent hyperparathyroidism may develop after parathyroid autotransplantation, especially after the transplantation of hyperplastic or adenomatous parathyroid tissue. Hyperparathyroidism recurs most frequently after subtotal parathyroidectomy or total parathyroidectomy and autotransplantation, in patients with renal failure and secondary hyperparathyroidism, and in patients with familial primary hyperparathyroidism or MEN I or MEN II syndrome. We report three patients who experienced primary hyperparathyroidism after autotransplantation of normal parathyroid tissue during thyroid operations (two patients) or after a long period of hypoparathyroidism. STUDY DESIGN: We reviewed our records from 1983 to May 1998 and identified three patients in whom hyperparathyroidism developed after thyroid operations. RESULTS: One patient had a thyroidectomy with left modified radical neck dissection for papillary thyroid cancer, followed by radioiodine ablative therapy. Two patients had thyroid operations for benign thyroid disease. One of these patients had a history of radiation exposure for acne, and in the other one secondary hyperparathyroidism arose 6 years after a thyroidectomy for hyperthyroidism. CONCLUSIONS: Our study documents that hyperparathyroidism may develop after autotransplantation of histologically normal parathyroid tissue and after a period of hypoparathyroidism after thyroid operations. For this reason, it is important to mark the site of the parathyroid transplantation.

Adult↗

PubMed2000

Death from thyroid cancer of follicular cell origin.

BACKGROUND: Although patients with differentiated thyroid cancer (DTC) of follicular cell origin usually have an excellent prognosis, some patients die from progressive tumor. Numerous postoperative criteria have been used to predict prognosis in patients with DTC. The purpose of this investigation was to determine whether the TNM and metastases, age, completeness of resection, invasion, size (MACIS) classifications predicted survival time and why patients died from DTC. The extent of initial treatment and causes of death were also evaluated in these patients who died from thyroid cancer. STUDY DESIGN: Between 1965 and 1995, 102 of 1,224 patients with DTC treated at the University of California at San Francisco (UCSF) and UCSF/Mount Zion Medical Centers died from DTC. Risk factors including age at diagnosis, gender, histologic characteristics, TNM and MACIS classifications, the intervals among initial treatment, recurrence, and death, and the initial and subsequent treatments were documented in these 102 patients. RESULTS: Among the 102 patients who died of DTC 50% were men and 50% were women. The mean age of patients with DTC at diagnosis was 58 years at recurrence, 62 and 65 years at death. Thirty percent of these patients initially had unilateral thyroid operations and 70% had a bilateral operation. Tumors at presentation ranged from 0.6 to 13.0 cm (mean 4.4 cm); 46% of patients presented with late-stage tumors (TNM stage III, IV; MACIS score > 8). At presentation 46% of the patients had locally recurrent disease or regional metastases and 18% had distant metastases. Patients with persistent disease had a significantly shorter survival time than those with recurrent disease (p < 0.001). Both TNM and MACIS classifications were good predictors of survival time. Reoperations were performed in 51% of papillary, 26% of follicular, and 67% of Hürthle cell thyroid cancer patients. Fifty percent of patients with papillary thyroid cancer, 50% of patients with Hürthle cell thyroid cancer, and 11% of patients with follicular cell thyroid cancer died of locally advanced disease. CONCLUSIONS: As expected, patients with local or regional recurrence and those with TNM stage I or MACIS score < 6 survived longer than patients with distant metastasis and TNM stage III or IV, MACIS score > 6, but some patients thought to be at low risk (TNM stage I; MACIS < 6) also died from thyroid cancer.

Adenocarcinoma, Follicular↗

PubMed2000

Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo.

BACKGROUND: Without angiogenesis, tumor growth is limited to a few millimeters, the limit of diffusion. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen and a major regulator of angiogenesis. METHODS: To investigate the relationship between VEGF and thyroid tumor angiogenesis, we xenografted human dermal matrix inoculated with FTC-133 cells into nude mice or directly injected FTC-133 cells subcutaneously. To block the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6.1 (mAb A.4.6.1) was injected intraperitoneally twice weekly. As control, an antibody of the same isotype (Ab 5B6) or phosphate buffer saline solution (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, recombinant human VEGF was inoculated into the dermal matrix pocket and xenografted into mice. RESULTS: In the dermal matrix angiogenesis model, the number of blood vessels paralleled the concentration of recombinant human VEGF and was highest at 100 ng/mL. Mice that were treated with the mAb A4.6.1 developed fewer blood vessels (mean, 6.6 per HPF) than control mice (18 per HPF in Ab 5B6 and 22 per HPF in PBS; P <.01). Tumors from mice that were treated with mAb A.4.6.1 were much smaller (mean +/- SD, 0.09 +/- 0.02 gm) at 5 weeks, compared with the tumors treated with Ab 5B6 (5.38 +/- 1.15 gm) or PBS (4.0 +/- 0.72 gm; P <.001). CONCLUSIONS: VEGF is produced by the follicular thyroid cancer cell line and stimulates angiogenesis and growth of thyroid cancer. This stimulation can be blocked by mAb A.4.6.1.

Animals↗

PubMed2000

Is familial non-medullary thyroid carcinoma more aggressive than sporadic thyroid cancer? A multicenter series.

BACKGROUND: The aggressiveness of familial non-medullary thyroid cancer (FNMTC) has been a subject of debate. The purpose of the study was to determine whether FNMTC is more aggressive than sporadic thyroid cancer. METHODS: A multicenter retrospective matched-case control study of FNMTC versus sporadic non-medullary thyroid cancer was conducted. Disease-free survival (time to recurrence) for both groups was compared. RESULTS: Forty-eight familial cases were compared with 144 age-, gender-, and stage-matched controls. Patients with FNMTC had a significantly shorter disease-free survival compared with sporadic non medullary thyroid cancer. Patients with FNMTC who presented with evidence of distant metastasis, or who were from families with more than 2 thyroid cancer-affected members, had the worst prognosis. The available staging systems were less likely to predict the outcome in patients with FNMTC than in patients with sporadic non-medullary thyroid cancer unless one accounted for the strength of family history in the staging system. CONCLUSIONS: FNMTC is more aggressive than sporadic non-medullary thyroid cancer. The best predictors of a poor outcome in patients with FNMTC are the number of family members affected by thyroid cancer and evidence of distant metastasis.

Adult↗

PubMed2000

The helix-loop-helix transcription factor, Id-1, is overexpressed in medullary thyroid cancer.

BACKGROUND: The Id-1 helix-loop-helix protein inhibits differentiation and enhances cell proliferation. It is required for cell cycle progression. The Id-1 gene is highly expressed in a variety of tumor-derived cell lines. It increases after mitogen stimulation and is overexpressed in some human neoplasms. Therefore, we hypothesized that the Id-1 gene may play a role in medullary thyroid carcinogenesis. METHODS: The expression of the Id-1 protein in human medullary thyroid cancer (MTC) and the corresponding normal thyroid tissue was determined by Id-1 immunohistochemistry. In a human MTC cell line (TT), the effects of growth stimulation and redifferentiation on Id-1 expression were determined by Northern blot analysis. RESULTS: Id-1 immunostaining intensity in 9 MTC samples (6 sporadic, 2 familial, and 1 MEN 2A) was moderate to strong. However, it was absent or faint in the corresponding normal thyroid tissue. The Id-1 protein was significantly overexpressed in MTC compared with corresponding normal thyroid tissue on the basis of the percentage of positive cells and immunostaining intensity (P =.002). In the TT cell line, Id-1 messenger RNA (mRNA) expression was increased 4-fold after growth stimulation with serum. Phorbol ester (which induces redifferentiation in the TT cell line) downregulated Id-1 mRNA expression. CONCLUSIONS: Id-1 is overexpressed in MTC. The Id-1 gene may play a role in the regulation of MTC differentiation and proliferation.

Adult↗

PubMed1999

Laparoscopic vs open adrenalectomy for the treatment of primary hyperaldosteronism.

HYPOTHESIS: That the clinical presentations, biochemical profiles, and surgical outcomes of patients treated with laparoscopic vs open adrenalectomy for primary hyperaldosteronism are different. DESIGN, SETTINGS, PATIENTS, AND INTERVENTIONS: The medical records of 80 patients with primary hyperaldosteronism who underwent open adrenalectomy between 1975 and 1986 or laparoscopic adrenalectomy between 1993 and 1998 at the University of California-San Francisco were reviewed by a single unblinded researcher (W.T.S.). MAIN OUTCOME MEASURES: Severity of hypertension and hypokalemia at diagnosis, their improvement after adrenalectomy, and operative complications. RESULTS: Thirty-eight patients underwent open adrenalectomy and 42 patients underwent laparoscopic adrenalectomy. The patients who underwent open adrenalectomy had documented hypertension for a median of 5 years before surgery; all had diastolic blood pressures greater than 100 mm Hg. Laparoscopically treated patients had documented hypertension for a median of 2.5 years preoperatively, and 20 (48%) had diastolic blood pressures greater than 100 mm Hg. The median preoperative serum potassium levels for the open and laparoscopic groups were 2.6 mmol/L and 3.3 mmol/L, respectively; the mean serum aldosterone levels were 1.47 nmol/L and 1.30 nmol/L. Thirty-two (84%) of the 38 patients who underwent open surgery and 41 (98%) of the 42 patients treated laparoscopically had adrenal adenomas. The sensitivity of preoperative computed tomographic scanning for adenomas was 83% for the patients treated with open adrenalectomy and 93% for those treated laparoscopically. There were 4 postoperative complications in the open surgery group and none in the laparoscopic group. Postoperatively, 30(81%) of 37 patients (excluding 1 patient who died of adrenocortical carcinoma) in the open surgery group and 37 (88%) of 42 patients treated laparoscopically were normotensive. Post-operative values were 3.6 to 5.0 of serum potassium per liter and 3.5 to 4.9 of serum potassium per liter in the open and laparoscopic groups, respectively. CONCLUSIONS: Patients who are treated with laparoscopic adrenalectomy for primary hyperaldosteronism are being referred with less severe hypertension and hypokalemia than patients formerly treated with open adrenalectomy. Patients treated laparoscopically had fewer postoperative complications and were equally likely to improve in blood pressure and hypokalemia. Laparoscopic adrenalectomy has become the treatment of choice for patients with primary hyperaldosteronism because of lower morbidity.

Adrenalectomy↗

PubMed1999

Localization of insulinomas.

HYPOTHESIS: Intraoperative ultrasonography is more sensitive than preoperative and other intraoperative techniques for localizing insulinoma. DESIGN: Retrospective review. SETTING: A tertiary referral center. PATIENTS: All patients with a biochemical diagnosis of organic hyperinsulinism who were referred to University of California, San Francisco, from 1975 to 1998. METHODS: Sensitivities of the localization techniques for insulinoma were evaluated. RESULTS: The sensitivities of tumor localization with arteriography, computed tomography, preoperative ultrasonography, magnetic resonance imaging, magnetic resonance imaging with gadolinium, transhepatic venous sampling, palpation, and intraoperative ultrasonography were 47%, 24%, 50%, 30%, 40%, 55%, 76%, and 91%, respectively. Nine of the 11 nonpalpable and nonvisible tumors at operation were localized by intraoperative ultrasonography. CONCLUSION: The currently available preoperative localization tests are not reliable enough to be recommended when intraoperative ultrasonography is available.

Adult↗