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Biomedical subjects

R J Robbins

Publications and source records attributed to R J Robbins.

At least 19 recordsLinked to original sources
PubMed2002

Serum vascular endothelial growth factor levels are elevated in metastatic differentiated thyroid cancer but not increased by short-term TSH stimulation.

Solid tumor formation requires the development of a blood supply adequate to meet the metabolic demands of the enlarging tumor mass that cannot be sustained by simple diffusion. One principal stimulant to endothelial cell growth and migration, vascular endothelial growth factor (VEGF), is synthesized and secreted by thyroid cancer cells. Furthermore, VEGF overexpression is associated with an aggressive thyroid cancer phenotype in both animal models and clinical-pathological studies. In other malignancies, elevated serum levels of VEGF often correlate with stage of disease and other poor prognostic clinical features. Therefore, we hypothesized that serum VEGF levels would be significantly higher in patients with persistent or recurrent thyroid cancer than in those cured of the disease. Because TSH stimulates both normal and neoplastic thyroid cells, we also proposed that serum VEGF would be further increased by TSH stimulation. Sixty-nine patients with either papillary or follicular thyroid cancer, status post total thyroidectomy, and prior radioactive iodine ablation, who had undergone routine recombinant human TSH (rhTSH, Thyrogen, Genzyme Transgenics Corp., Cambridge, MA) assisted whole-body radioactive iodine scanning, were included in this study. This cohort (mean age 53 +/- 16 yr, 51% female) included 21 patients with no evidence of disease and 48 patients with local or distant metastases. Stored serum samples obtained for standard Tg determinations before and 72 h following standard rhTSH stimulation were identified and assayed for VEGF 165 (R \[amp ]\ D Systems, Minneapolis, MN). Baseline serum VEGF levels obtained at a time of TSH suppression were significantly higher in patients with known metastatic disease than in those with no evidence of disease (416 +/- 62 pg/ml vs. 185 +/- 25 pg/ml, P = 0.001). Patients with distant metastases had baseline serum VEGF levels that did not differ significantly from patients with only cervical recurrences (455 +/- 90 pg/ml in distant metastases vs. 330 +/- 44 pg/ml for local cervical recurrences). Short-term TSH stimulation, although causing a significant rise in serum Tg, resulted in no significant increase in serum VEGF measured 72 h after rhTSH injection in either the patients with known metastatic disease (416 +/- 62 pg/ml baseline vs. 419 +/- 71 pg/ml after TSH stimulation) or in cured patients (185 +/- 25 pg/ml baseline vs. 191 +/- 33 pg/ml after TSH stimulation). Subgroup analysis revealed that patients with metastatic disease arising from well differentiated primary thyroid cancers had significantly higher serum VEGF levels than patients with metastatic disease arising from poorly differentiated thyroid cancer primaries (485 +/- 74 pg/ml vs. 167 +/- 32 pg/ml, P = 0.003 by ANOVA). Poorly differentiated metastatic thyroid cancers had serum VEGF levels indistinguishable from patients cured of disease (167 +/- 32 pg/ml vs. 186 +/- 25 pg/ml). In summary, serum VEGF is significantly elevated in patients with metastatic differentiated thyroid cancer but not in those with poorly differentiated thyroid cancer metastases. No measurable increase in serum VEGF levels can be detected 72 h after short-term TSH stimulation with rhTSH. We conclude that serum VEGF may serve as a clinical useful marker of residual differentiated thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed2001

Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin.

Radioiodine ablation (RA) of normal thyroid remnants after thyroidectomy for differentiated thyroid carcinoma improves the sensitivity of subsequent radioiodine scans and serum thyroglobulin measurements for detection of residual thyroid carcinoma. Local cancer recurrences are also lower after RA. One standard preparation for RA involves rendering the patient hypothyroid in order to stimulate endogenous thyrotropin (TSH) secretion and sodium iodide symporter (NIS) activity. An alternative approach is to prescribe thyroxine after thyroidectomy and to stimulate NIS with exogenous recombinant human thyrotropin (rhTSH). This latter approach was used in 10 patients at our medical center. Complete resolution of all visible 131I thyroid bed uptake was achieved in all when follow-up scans were performed 5 to 13 months later. This approach has the potential to successfully ablate thyroid remnants without the need to induce hypothyroidism.

Adult↗
PubMed2001

Preparation by recombinant human thyrotropin or thyroid hormone withdrawal are comparable for the detection of residual differentiated thyroid carcinoma.

Clinical recurrences of differentiated thyroid carcinoma occur in 20% of patients after thyroid surgery. We performed a retrospective analysis of a cohort of patients undergoing routine follow-up testing to detect recurrent thyroid carcinoma over a 2-yr period. One group was prepared for testing by thyroid hormone withdrawal (THW), and the other group remained on thyroid hormone and received injections of recombinant human TSH (rhTSH) before diagnostic whole-body radioiodine scanning (DxWBS). We hypothesized that no differences in the ability to detect residual disease would exist between these 2 groups. Two hundred and eighty-nine patients were examined by both DxWBS and by measurement of the serum thyroglobulin (Tg) response to elevated TSH levels. THW was used for 161 patients, and rhTSH preparation was used for 128 patients. Based on all available testing results, we categorized patients as having metastatic disease, thyroid bed uptake only, or no evidence of disease. We examined the sensitivity, specificity, positive and negative predictive values of the DxWBS, and the stimulated Tg after preparation by THW or rhTSH. Patients with thyroid bed were not considered in accuracy testing. The sensitivity and specificity of the 2 tests were comparable between groups. No significant differences were present in the positive or negative predictive values between groups. The highest negative predictive value (97%) was in patients who had both a negative DxWBS and low stimulated Tg levels after rhTSH. In summary, we were unable to demonstrate a difference in the diagnostic accuracy of DxWBS and/or Tg between patients prepared by either THW or rhTSH. We conclude that preparing patients by rhTSH is diagnostically equivalent to preparing them by THW.

Adult↗
PubMed2000

Inhibition of metabolic activity in papillary thyroid carcinoma by a somatostatin analogue.

Two patients with widely metastatic papillary thyroid cancer demonstrated progressive growth of diffuse pulmonary lesions. One patient had no apparent response to high doses of 131I and the other hand no 131I uptake. 111In-pentetreotide scans revealed that many of the metastatic lesions expressed somatostatin receptors. The baseline metabolic activity and three-dimensional volume of the lesions were determined by 18F-fluoro-de-oxyglucose positron emission tomography (FDG-PET). After 3 or 4 months of octreotide (Sandostatin LAR Depot; Novartis Pharmaceutical, East Hanover, NJ) therapy, repeat FDG-PET scans revealed reductions in tumor volume and decreases in the standard uptake values of FDG. We conclude that octreotide therapy can change the biological activity of metastatic thyroid cancer lesions that exhibit somatostatin receptors.

Antineoplastic Agents, Hormonal↗
PubMed2000

Bone metastases from thyroid carcinoma: clinical characteristics and prognostic variables in one hundred forty-six patients.

To describe the clinical characteristics and define the indicators that best predict survival in patients with bone metastases from thyroid carcinomas. We collected data from medical records of 146 patients with documented bone metastases from thyroid carcinoma seen at our medical center over a 38-year period. Univariate and multivariate analyses of prognostic indicators for survival were performed. Bone metastases were present at the initial diagnosis in 47% of patients. Vertebrae (29%), pelvis (22%), ribs (17%), and femur (11%) were the most common sites of metastases. Multiple lesions were present in 53% of the cases. The overall 10-year survival rate from the time of diagnosis of thyroid cancer was 35%, and from diagnosis of initial bone metastasis was 13%. By univariate analysis from the time of the initial bone metastasis, radioiodine uptake by skeletal metastases, the absence of nonosseous metastases and treatment with radioiodine were significant prognostic factors. By multivariate analysis, radioiodine uptake by skeletal metastases and the absence of nonosseous metastases were independent favorable prognostic variables for survival. In a subgroup of patients in which histologic specimens were available and were reviewed, Hurthle cell carcinoma was the most favorable histologic subtype for survival with the undifferentiated subtype being the worst. The spread of thyroid carcinoma to bone is more common in patients over 45 years of age, is usually symptomatic, and is often multicentric. Overall survival is best in those whose lesions concentrate radioactive iodine and those who have no nonosseous metastases.

Adult↗
PubMed2000

Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer.

Poorly differentiated thyroid cancer lesions often lose the ability to concentrate radioactive [131I]iodine (RAI) and exhibit increased metabolic activity, as evidenced by enhanced glucose uptake. We incorporated [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning into the routine follow-up of a cohort of thyroid cancer patients undergoing annual evaluations. One hundred and twenty-five patients who had previous thyroidectomies were included. They had diagnostic RAI whole body scans, serum thyroglobulin measurements, and additional imaging studies as clinically indicated. During 41 months of follow-up, 14 patients died. Univariate analysis demonstrated that survival was reduced in those with age over 45 yr, distant metastases, PET positivity, high rates of FDG uptake, and high volume of the FDG-avid disease (>125 mL). Survival did not correlate with gender, RAI uptake, initial histology, or grade. Multivariate analysis demonstrated that the single strongest predictor of survival was the volume of FDG-avid disease. The 3-yr survival probability of patients with FDG volumes of 125 mL or less was 0.96 (95% confidence interval, 0.91, 1.0) compared with 0.18 (95% confidence interval, 0.04, 0.85) in patients with FDG volume greater than 125 mL. Only 1 death (of leukemia) occurred in the PET-negative group (n = 66). Of the 10 patients with distant metastases and negative PET scans, all were alive and well. Patients over 45 yr with distant metastases that concentrate FDG are at the highest risk. Once distant metastases are discovered in patients with differentiated thyroid carcinoma, FDG-PET can identify high and low risk subsets. Subjects with a FDG volume greater than 125 mL have significantly reduced short term survival.

Adult↗
PubMed2000

Bone metastases from thyroid carcinoma: a histopathologic study with clinical correlates.

CONTEXT: Only limited information exists on the pathologic aspects of thyroid carcinomas with bone metastases, most large studies having concentrated mainly on their clinical features. OBJECTIVE: To study in detail the morphologic features of thyroid carcinomas with skeletal metastases. DESIGN: Seventy-nine cases of thyroid carcinoma with bone metastases treated at Memorial Sloan-Kettering Cancer Center, New York, NY, between 1964 and 1998 were investigated, with emphasis on the pathology of the primary and/or metastatic tumors and comparison of the morphologic features of the tumors at both the sites, wherever possible. The tumors were also compared for various clinical parameters. RESULTS: The cohort consisted of 22 papillary, 17 follicular, 16 insular, 10 anaplastic, 9 Hürthle cell, and 5 medullary carcinomas. Of these cases, 68% had poorly differentiated or undifferentiated features in the primary and/or metastatic tumors. The metastatic tumors were better differentiated than the primary in one third of the cases (6 of 18). Only one case showed a less differentiated metastasis. The overall 5- and 10-year survival probabilities after the bone metastases were 29% and 13%, respectively (Kaplan-Meier method). Although both the tumor type and differentiation seemed to affect survivals after bone metastasis (P =.007 and.012, respectively) (log-rank test), this was primarily due to the much worse prognosis in the cases of anaplastic and medullary carcinoma. Cases of Hürthle cell carcinoma showed the longest median survival. There was no significant difference in survival among patients up to or older than 45 years at the time of metastases (P =.31). CONCLUSIONS: Most thyroid carcinomas with bone metastases are of papillary type, and most have poorly differentiated or undifferentiated features. The influence of the microscopic tumor type and tumor differentiation on survival after bone metastasis primarily appears to be due to the much worse prognosis among anaplastic and medullary carcinomas. Age at diagnosis of bone metastases does not influence survivals.

Adenocarcinoma↗
PubMed1999

[18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography localizes residual thyroid cancer in patients with negative diagnostic (131)I whole body scans and elevated serum thyroglobulin levels.

Progressive dedifferentiation of thyroid cancer cells leads to a loss of iodine-concentrating ability, with resultant false negative, whole body radioactive iodine scans in approximately 20% of all differentiated metastatic thyroid cancer lesions. We tested the hypothesis that all metastatic thyroid cancer lesions that did not concentrate iodine, but did produce thyroglobulin (Tg), could be localized by [18F]2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET). We performed FDG-PET on 37 patients with differentiated thyroid cancer after surgery and radioiodine ablation who had negative diagnostic 131I whole body scans during routine follow-up. Serum Tg, Tg autoantibodies, neck ultrasounds, and other clinically indicated imaging procedures were performed to detect residual disease. In those with elevated Tg levels, FDG-PET localized occult disease in 71%, was false positive in one, and was false negative in five patients. The majority of false negative FDG-PET occurred in patients with minimal cervical adenopathy. Surgical resections, biopsies, 131 therapy, and differentiation therapy were performed based on the PET results. The FDG-PET result changed the clinical management in 19 of the 37 patients. In patients with elevated Tg levels, FDG-PET had a positive predictive value of 92%. In patients with low Tg levels, FDG-PET had a negative predictive value of 93%. No FDG-PET scans were positive in stage I patients; however, they were always positive in stage IV patients with elevated Tg levels. An elevated TSH level (i.e. hypothyroidism) did not increase the ability to detect lesions. FDG-PET is able to localize residual thyroid cancer lesions in patients who have negative diagnostic 131I whole body scans and elevated Tg levels, although it was not sensitive enough to detect minimal residual disease in cervical nodes.

Adenocarcinoma, Follicular↗
PubMed1998

Thoracoscopic surgery.

Video-assisted thorascopic surgery has evolved rapidly and has demonstrated utility in the diagnosis and management of a variety of chest disorders. An historical perspective, considerations on patient selection, anesthetic and operative management, and a summary of the Ochsner Clinic institutional experience with this procedure are presented. Special emphasis is given to the treatment of disorders of the autonomic nervous system, esophageal achalasia, and a rare symptomatic congenital pericardial defect. Video-assisted thorascopy provides a promising alternative to many of the more invasive open thoracic surgical procedures.

Adolescent↗
PubMed1997

Technique of right heart protection and deairing during heartmate vented electric LVAD implantation.

Continued experience with the TCI Heartmate Ventricular Assist System has led to improvements in our ability to avoid and manage right heart dysfunction during weaning from cardiopulmonary bypass. The advent of the electric device has intensified the need for these techniques because of its elevated minimal heart rate (50 beats/min) at start-up and the demands this places on the native right heart. We have developed and here describe a technique we have used successfully in our last 8 patients to assist in deairing and filling of the ventricular assist device, to partially support the right heart during the initial wean from cardiopulmonary bypass, and to avoid occasional overdistention of the right heart during early high left ventricular assist device flow.

Air↗
PubMed1996

Somatostatin and cancer.

The potential role of somatostatin (SRIF) in the diagnosis and treatment of nonendocrine human cancers is reviewed. There have been many reports of the growth-inhibitory activity of SRIF on normal and transformed cells in vitro. Many processes involved in malignant tumor growth depend on autocrine growth mechanisms, and somatostatin receptors (ssts) are present on many human cancers. It is possible that mutations in ssts result in a loss of check on proliferation in cancer cells. SRIF analogs may have a number of roles in clinical oncology. Use of radiolabeled tracers enables imaging of tumors bearing ssts; newer agents may enable positron emission tomography (PET) analyses or may be used to deliver lethal radiation doses to cells bearing a unique subset of sst. Although the ability of SRIF and its analogs to inhibit cellular proliferation has been shown in vitro, it has yet to be demonstrated in humans with cancer. Clinical improvements seen with SRIF or its analogs in cancer patients may be related to indirect effects, such as pain relief, reduction of gastrointestinal side effects of chemotherapeutic agents, effects on local production of growth factors, and inhibition of tumoral angiogenesis. Thus, with regard to their potential therapeutic role, SRIF analogs are likely to be used only in conjunction with other approaches, such as radiation, immunotherapy, chemotherapy, and growth factor modulation. Further research into the fundamental functions of each of the ssts and the intracellular actions of SRIF analogs will be needed to assess the potential usefulness of the latter in slowing the progression of human cancers.

Cell Division↗
PubMed1995

Psychiatric status after human fetal mesencephalic tissue transplantation in Parkinson's disease.

This report describes the prospective and systematic psychiatric assessment of nine patients who received transplantation of human fetal mesencephalic tissue into the caudate nucleus for treatment of Parkinson's disease. Unlike adrenal medullary transplantation, which often causes psychosis or delirium, this procedure appeared to have few perioperative sequelae. On longer-term follow-up, there was some statistical evidence of deterioration in psychiatric status, as manifested primarily in depressive and nonspecific emotional and behavioral symptoms. This group effect was partly attributable to the occurrence of discrete episodes of illness (major depression and panic disorder with agoraphobia) in some patients, but it was unclear whether such episodes occurred more often than would ordinarily be expected in Parkinson's disease. Differences in the neurobiological effects of fetal mesencephalic and adrenal medullary grafts may account for differences in the psychiatric sequelae of patients receiving these procedures.

Adult↗
PubMed1995

General cognitive ability following unilateral and bilateral fetal ventral mesencephalic tissue transplantation for treatment of Parkinson's disease.

OBJECTIVE: To contrast the neuropsychological profiles of Parkinsonian patients, before and after fetal ventral mesencephalic tissue transplantation. DESIGN: Case series of personally examined patients. SETTING: Patients were evaluated by neurologists, neurosurgeons, and neuropsychologists as outpatients at a university hospital. PATIENTS: Fetal mesencephalic tissue was implanted in the right caudate nucleus of three patients and both nuclei of one patient. These patients were evaluated prior to surgery and at 12, 24, and 26 months postoperatively. RESULTS: Factor analysis of the test battery identified four statistically orthogonal test clusters. No statistically significant changes were identified postoperatively for clusters assessing verbal cognitive ability, nonverbal cognitive ability, and information-processing speed. An improvement of verbal memory cluster index was observed 12 months after surgery, and the improvement reached the level of statistical significance at 24 months after surgery. However, the verbal memory of all patients declined between 24 and 36 months after surgery. CONCLUSIONS: Fetal tissue transplantation to one or both caudate nuclei did not permanently arrest cognitive dysfunction. Although there is some evidence of improved cognitive ability after transplantation, it is improbable that normal cognitive function can be restored by this procedure because the impairments of cognitive ability associated with Parkinson's disease do not appear to originate solely from dopamine deficiency.

Adult↗
PubMed1995

Self-esteem and neuroendocrine response to challenge: MacArthur studies of successful aging.

The role of self-esteem in modulating patterns of neuroendocrine response to challenge at older ages was examined in 16 healthy 70-yr-olds. Responses to two challenges were examined: (1) a driving simulation designed to reflect a 'real life' challenge situation; and (2) a pharmacologic, corticotropin-releasing-hormone (CRH) challenge (1 micrograms/kg). Both challenges evoked significant elevations in cortisol and adrenocorticotropic hormone (ACTH). Levels of self-esteem were significantly and negatively associated with peak elevations in cortisol in response to the driving simulation challenge (r = -0.51, p = 0.04). ACTH responses showed similar trends (r = -0.41, p = 0.12). Self-esteem levels were not correlated with responses to the CRH challenge. These data indicate that psychological characteristics such as self-esteem may play a role in modulating patterns of neuroendocrine response to cognitive/behavioral challenges in everyday life in older individuals.

Activities of Daily Living↗