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PubMed1998

Determinative factors of biochemical cure after primary and reoperative surgery for sporadic medullary thyroid carcinoma.

Normalization of calcitonin levels after surgery has been regarded as the most powerful prognostic factor for medullary thyroid carcinoma (MTC). Although the prognosis of patients with persistent hypercalcitoninemia may be acceptable, the biochemical cure rate can be improved by new microdissection techniques. This raises certain questions: Can extension of locoregional lymphadenectomy (LA) further improve biochemical cure and survival after primary or reoperative MTC surgery? Which factors concerning TNM categories are associated with the possibility of postoperative normalization of calcitonin levels? This study included 64 patients with sporadic MTC operated on from 1986 to 1997. Altogether 27 patients underwent primary surgery, and 37 patients were reoperated, performing a microdissection of all four locoregional compartments (four-compartment lymphadenectomy, or 4CLA). For primary MTC the biochemical cure rate was 100% in node-negative patients and 33% in node-positive patients; the latter could be improved to 45% after 4CLA. In contrast to reoperative MTC, the rate of lymph node metastases (LNMs) with primary MTC correlated with the pT category (pT1 33%, pT2 53%, pT3 100%, pT4 100%) but not with age or sex. Again in contrast to reoperative MTC, mediastinal LNMs in primary MTC were present only in patients with a pT4 tumor. At reoperation, 4CLA was able to cure 22% of node-positive patients, 28% without proved distant metastases. No patient with extrathyroidal tumor involvement or distant metastases was biochemically cured after either primary or reoperative surgery. For all node-positive MTC patients, in addition to cervicocentral LA at least a bilateral cervicolateral LA is recommended. Transsternal mediastinal lymph node dissection is indicated in patients with LNMs in the cervicomediastinal transition, facilitating biochemical cure in up to 45% after the first operation and 22% after reoperative surgery of sporadic MTC.

Adult↗
PubMed2000

Regulation of proliferation and apoptosis in sporadic and hereditary medullary thyroid carcinomas and their putative precursor lesions.

C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients affected by germline mutations of the RET oncogene represent an exceptional opportunity to study the regulation of proliferation and apoptosis during tumour initiation and progression. In 56 specimens [CCH, n=1; MTC with CCH, n=26; MTC, n=20; lymph-node metastasis (LNM), n=9] from 46 patients [multiple endocrine neoplasia type 2a (MEN2a), n=24; MEN2b, n=2; familiar MTC (FMTC), n=4; sporadic MTC, n-16] and 3 cases of non-neoplastic CCH, proliferation activity (MIB1), the rate of apoptosis [dUTP nick end labelling (TUNEL)] and expression of p53, bcl-2, bcl-x and bax were investigated and compared with clinical data. In MEN-associated CCH and small MTC, bcl-2 was strongly expressed, bcl-x was moderately expressed and bax was only weakly expressed. Advanced tumours and LNM did show a more heterogeneous bcl-2 staining accompanied by an increased bax expression and accelerated proliferation. The rate of apoptosis was extremely low in all investigated tumours. P53 was detectable in three patients with rapidly growing and extensively metastasising MTC. No somatic p53 mutations were found. Hereditary MTC with germline RET mutations at codon 918 (MEN2b) and codon 634 revealed a bias towards a higher proliferation activity at a younger age and are more frequently accompanied by LNM. CCH and MTC are characterised with a preponderance of bcl-2 as a factor blocking the programmed cell death. While MTC, in general, is a slowly growing tumour, a minority of tumours do progress rapidly with high proliferation. The factors leading to an accelerated tumour progression do not seem to take their effect via the regulation of apoptosis. Certain alterations of RET are supposed to have a direct or indirect implication on proliferation and, because of this, an effect on the clinical course.

Adolescent↗
PubMed1999

Multiple endocrine neoplasia type 2A: a 25-year review.

BACKGROUND/PURPOSE: Before 1970, treatment decisions for the thyroid lesions in patients with multiple endocrine neoplasia (MEN) were based on physical findings. For the next 20 years, biological markers assumed a preeminent role, and at present, DNA testing is being used to define the need for therapeutic intervention. This report presents a 25-year review of 22 children with MEN-2A, with a mean follow-up of 12.5 years. METHODS: All 22 children underwent a total thyroidectomy, and four (18%) were rendered permanently hypoparathyroid. Since 1976, however, only one patient (6.7%) has lost parathyroid function. Despite the fact that biological screening studies routinely were performed once a year in the majority of our patients and surgery was recommended for any elevation in the serum calcitonin (CT) levels, medullary carcinoma of the thyroid (MTC) developed in 17 children (77%) and only five had C cell hyperplasia (CCH). Thirteen of the 17 had macroscopic tumor described by the pathologist, evidence of recurrent disease (MTC-REC) has developed in four children (24%). RESULTS: There was considerable overlap in both the basal and stimulated CT levels among the five children with CCH, the 13 with localized MTC (MTC-NED), and the four who later had recurrent MTC. The basal calcitonin levels were between 25 and 110 (mean, 58) in the CCH patients, 30 to 1,130 (mean, 184) in the MTC-NED group, and 108 to 201 (mean, 140) in those with recurrent MTC. The corresponding stimulated calcitonin levels were 45 to 417 (mean, 179) in CCH, 111 to 9,510 (mean, 1,407) in MTC-NED, and 449 to 5,093 (mean, 3,383) in MTC-REC. CONCLUSIONS: (1) Basal and pentagastrin-stimulated CT levels did not reliably discriminate between CCH and MTC and should not be used to define the timing of thyroid surgery in children with MEN-2A. (2) Surgical therapy should be undertaken early in childhood on the basis of molecular genetic testing. (3) Postoperative complications are infrequent in the modern era.

Adolescent↗
PubMed2001

Population-based study of familial medullary thyroid cancer.

BACKGROUND: We wanted to carry out a population-based study on medullary thyroid cancer (MTC) in order to quantify familial risks. METHODS: MTC was studied in the Swedish Family-Cancer Database, updated in 1999 to cover individuals and offspring, born after 1934 with their biological parents, totaling 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from year 1958 to 1996 and included 2,435 thyroid cancers among offspring. RESULTS: 65 offspring were identified with MTC, which was coded as a separate entity since 1985. 62% had neither affected parent nor sib. Most familial cases were diagnosed at ages 15 to 24 and sporadic cases 25 years later. The familial SIRs of MTC were 3,080 and 3,650 when either a parent or a sib had MTC; when both had MTC the SIR was 35,800. All the familial risks were highest in young age groups, 0-9 years. MEN 2 or MEN 2-like families were considered when one family member had a TC and an adrenal pheochromocytoma. SIR of MTC in offspring was 61,000 when a parent had a MEN 2-like cancer and a sib had MTC. CONCLUSIONS: We described familial and sporadic MTC in a population-based database. The familial risks of MTC may be the highest ever reported in population based studies.

Adolescent↗
PubMed2002

Role of conventional ultrasound and color Doppler sonography in the diagnosis of medullary thyroid carcinoma.

Early diagnosis of medullary thyroid carcinoma (MTC) can improve long-term prognosis. MTC can be detected at an early stage by calcitonin screening in all patients with thyroid nodules. This approach, however, is controversial due to high costs and a limited specificity of calcitonin. It was the aim of the present study to investigate whether ultrasonography may contribute to the diagnosis of MTC in patients with thyroid nodules. The study included 19 patients with newly diagnosed MTC. Ten patients had sporadic MTC, 7 had multiple endocrine neoplasia (MEN) type 2A, and 2 patients had MEN 2B. In all subjects conventional ultrasound, and in 14 patients color Doppler sonography were performed before primary surgery. For comparison, ultrasound appearance of 139 benign thyroid nodules was evaluated. In conventional ultrasound, MTC in 17/19 (89%) patients were hypoechoic, contained intranodular calcifications, and had no "halo sign". The combination of these criteria were found in only 8/139 (6%) of benign thyroid nodules. Intranodular blood flow was found in 11/14 patients with MTC (79%), perinodular blood flow in 7/14 MTC (50%). In conclusion, conventional ultrasound reveals a combination of hypoechogenicity, intranodular calcifications, and absence of "halo sign" in the vast majority of MTC. Since this sonographic pattern only rarely occurs in benign thyroid nodules, the results indicate that thyroid ultrasound can contribute to the diagnosis of MTC. In addition, the findings may have implications for calcitonin screening in nodular thyroid disease.

Adult↗
PubMed1999

Is medullary thyroid cancer predictable? A prospective study of 86 patients with abnormal pentagastrin tests.

BACKGROUND: The aim of this prospective study was to distinguish biochemically between C-cell hyperplasia (CCH) and medullary thyroid cancer (MTC) before surgery. METHODS: Eighty-six consecutive patients with an abnormal stimulated calcitonin level (> 100 pg/mL) underwent thyroidectomy and lymph node dissection. In sporadic MTC, histopathologic findings and postoperative biochemical outcomes were documented prospectively and correlated with preoperative basal and stimulated calcitonin levels. RESULTS: Analysis of variance revealed a highly significant difference in basal/stimulated calcitonin levels (P < .0001), with a comparison of CCH (n = 39 patients) and sporadic MTC (n = 38 patients). With a comparison of sporadic MTC N0 M0 (n = 25 patients) and N1 M0/1 (n = 12 patients), the basal calcitonin level was significantly different (P < .05). There was a close correlation between the n-log of basal/stimulated calcitonin level and the n-log of the tumor volume; there were also different distributions of the n-log of basal/stimulated calcitonin level among CCH, MTC N0, and MTC N1. Assuming that a basal calcitonin level of more than 64 pg/mL and/or a stimulated calcitonin level of more than 560 pg/mL implies MTC, 31 of 38 patients with sporadic MTC were detected before surgery. Three patients were predicted false positive (neoplastic CCH). Patients with stimulated calcitonin levels of less than 129 pg/mL had CCH only. Patients with basal calcitonin levels of less than 22 pg/mL and sporadic MTC (7/38 patients) were node negative. CONCLUSIONS: All patients with abnormal pentagastrin tests showed C-cell pathologic evidence. Sporadic MTC was predicted in 81% of the patients; CCH or N0 was predicted in 36% of the patients. Central neck dissection is recommended to avoid difficult reoperations. Lateral neck dissection is possible "on demand."

Adult↗
PubMed2004

Thyroid carcinomas involving follicular and parafollicular C cells: seventeen cases with characterization of RET oncogenic activation.

Recent studies have focused on the occurrence of concomitant medullary-papillary thyroid carcinomas (MTC-PTC). The aims of this report were to compare the frequency of occult PTC in a population with MTC versus a control population that had undergone thyroidectomies and to check whether differences could be related to particular phenotype or genotype. To achieve these goals, we determined the frequency of occult PTC among patients operated for MTC (n = 82) or undergoing total thyroidectomy mainly for goiter and/or nodules (n = 7313) between 1994-2001. We then examined the clinical, histologic, and genetic characteristics (using a bio-chemical family inquiry and screening for RET germline mutations) of patients with associated PTC-MTC. Results show a significantly higher frequency of occult PTC in MTC (14.7%) than in total thyroidectomy (6.8%; p < 0.01). Seventeen cases of MTC or bilateral C-cell hyperplasia (CCH) and separate occult PTC were identified from 16 different families. Although common RET mutations providing evidence of familial forms of MTC were identified in only 3 of 16 families, clinical and histologic features usually seen in inherited forms of MTC such as young age of occurrence, bilateral CCH or associated case in family were found in 11 of the remaining 14 patients. In conclusion, results suggest that the association of MTC-PTC is not only a coincidence. Surprisingly, 11 of 17 MTC-PTC patients exhibited clinical, histologic, and/or family features usually encountered in familial forms despite the fact that no RET defect were present. This suggests the possible involvement of another gene or uncommon abnormality of RET gene.

Adult↗
PubMed1978

Medullary thyroid carcinoma: relationship of method of diagnosis to pathologic staging.

Medullary thyroid carcinoma (MTC) develops in virtually all patients affected with multiple endocrine neoplasia type II (MEN II), a disease inherited as an autosomal dominant trait. The thyroid tumor cells secrete calcitonin (CT) and the detection of elevated plasma levels (>300 pg/ml) of this hormone in MEN II kindred members strongly suggests the presence of MTC even though it may not be evident clinically. Intravenously administered calcium ion (Ca(++)) and pentagastrin (Pg) are potent CT secretagogues which are of particular value in establishing the early diagnosis of MTC. In evaluating seven kindreds with MEN II, we detected 90 patients with MTC. Depending on the method of diagnosis, they could be divided into three categories: Group 1; patients with no clinical evidence of MTC whose undetectable basal plasma calcitonin levels became elevated following intravenous Ca(++) or Pg, Group II; patients with no clinical evidence of MTC who had elevated basal plasma CT levels, and Group III; patients with clinically evident MTC. At the time of diagnosis of MTC, the patients in Group I were younger (20.5 +/- 1.9 years) than the patients in Group II (32.5 +/- 4.7 years, p < 0.005) and Group III (34.3 +/- 2.0, p < 0.00005). The incidence of residual MTC, as indicated by an elevated plasma CT level following provocative testing postoperatively, was less frequent in patients diagnosed biochemically ([6/34]; Group I, 4/26 and Group II, 2/8) than in those diagnosed clinically (Group III, 15/26, p < 0.002). Furthermore, regional nodes were involved less often in patients diagnosed biochemically ([5/28]; Group I, 2/22 and Group II, 3/6) than in those diagnosed clinically (Group III, 15/24, p < 0.02). Distant metastases were only evident in Group III patients. Patients with MEN II who had the diagnosis of MTC established biochemically rather than clinically, had a more favorable pathological stage of disease at the time of thyroidectomy. This was especially true if the biochemical diagnosis had been by provocative testing.

Adolescent↗
PubMed1989

Characteristics of macrophage activation by gamma interferon for tumor cytotoxicity in peritoneal macrophages and macrophage cell line J774.1.

We investigated the characteristics of macrophage-mediated tumor cytotoxicity (MTC) against Meth A target, H2O2 generation and release of effector molecule(s) for MTC, by comparing with those of peritoneal macrophages (PMP) and macrophage cell line J774.1 during stimulation with recombinant gamma interferon (IFN-gamma). In PMP, MTC was demonstrated when they were stimulated with IFN-gamma for 12 hr (short-term stimulation) and was abrogated when they were stimulated for 48 hr (long-term stimulation). Enhanced H2O2 generation was observed in PMP activated by long-term stimulation followed by triggering with PMA, but not observed by triggering with Meth A cells. By contrast, whereas non-treated J774.1 cells have already attained a definite level of MTC, a higher MTC level was demonstrated both by short- and long-term stimulations. Conversely, J774.1 cells were unable to generate H2O2 at any stage of IFN-gamma stimulation followed by triggering both with PMA or Meth A cells. The time course for stimulation of PMP by IFN-gamma for release of cytotoxic factor (CF) corresponded to that for MTC by PMP, and activities of the CF released from both activated PMP and J774.1 cells also closely corresponded to those of MTC by both cells. The serological and physicochemical characteristics of CF released from both activated PMP and J774.1 cells were determined to be closely related to those of tumor necrosis factor (TNF). These results indicate that in contrast to PMP, the J774.1 cell line is free from suppression stage for MTC and CF release during stimulation with IFN-gamma. The results suggest that TNF-like CF plays a crucial role for MTC against Meth A target, and that H2O2 is irrelevant for MTC against Meth A.

Animals↗
PubMed2005

Human medullary thyroid carcinoma: a source and potential target for relaxin-like hormones.

We investigated the expression of H1, H2 relaxin and INSL-3, mRNA and protein, and LGR7 and LGR8 transcripts in human C-cell hyperplasia, primary medullary thyroid carcinoma (MTC) tissues, MTC metastases, and the human MTC-TT and mouse MTC-M cell lines. Relaxin-like peptide hormones were detected in C-cell hyperplasia and in MTC tissues, but were absent in human normal parafollicular C-cells of benign goiter tissues. In contrast to calcitonin, mRNA, and immunoreactive protein, no differences in the expression of relaxin and INSL3 were observed in MTC tissues of different pTNM classification or between primary and metastatic MTC tissues studied. All MTC tissues constitutively expressed LGR7 and LGR8 transcripts. Thus, relaxin-like hormones appear to be present early during C-cell hyperplasia and potentially functional relaxin/INSL3 ligand-receptor systems are present in human MTC tissues and in MTC cell lines.

Carcinoma, Medullary↗
PubMedDate not supplied

Magnetization transfer contrast imaging of liver cirrhosis.

BACKGROUND/AIMS: To test the feasibility of magnetization transfer contrast (MTC) imaging in the evaluation of liver cirrhosis. METHODOLOGY: Three normal volunteers and 22 cirrhotic liver patients (13 of them harbored hepatoma) were prospectively studied with on-resonance binomial pulsed MTC imaging using a 1.0 Tesla MR scanner. Both MTC and non-MTC images were acquired. The magnetization transfer (MT) effect (defined as: 1-signal intensity of MTC/signal intensity of non-MTC), was used as an indicator and was correlated with different disease status. Lesion-to-liver contrast of non-MTC versus MTC imaging was also compared. RESULTS: Chronic hepatitis and early fibrosis had a MT effect similar to that of the normal group. Frank cirrhosis had the strongest MT effect. Cirrhosis, when infiltrated by diffuse hepatoma, showed a significantly weaker MT effect than that of the normal group (p<0.05), early cirrhosis (P<0.005), and frank cirrhosis (p<0.05). Overall, the MT effects in these 22 patients were widely variable. There was no significant improvement in lesion contrast of MTC imaging when compared to that of non-MTC imaging due to complex signal attenuation behavior of either the background liver tissue or the tumor itself. CONCLUSIONS: The complex pathological change of the cirrhotic liver tissue may account for the wide variation of the MT effect and the compromised lesion contrast in cirrhotic patients. Caution should be taken when cirrhotic tissue has an unusually weak MT effect. Then, the possibility of a mixed disease process such as fatty metamorphosis or diffuse hepatoma should be highly suspected. Our experience shows that MTC imaging plays a potential role in the evaluation of the multi-facets of cirrhotic tissue change.

Adult↗
PubMed1992

Family members of patients with sporadic medullary thyroid carcinoma must be screened for hereditary disease.

BACKGROUND: Medullary thyroid carcinoma (MTC), a tumor arising from calcitonin-secreting C cells, appears in either a sporadic nonfamilial or a hereditary form as a component of a multiple endocrine neoplasia syndrome or familial non-multiple endocrine neoplasia MTC. Screening kindred of a patient with familial MTC to detect MTC in the early curable state is standard practice. Opinions conflict about whether it is necessary to screen relatives of patients with apparently nonfamilial MTC to exclude hereditary disease or whether the clinicopathologic features can differentiate between the two forms. METHODS: Clinically well kindred of a patient with MTC that was histopathologically characteristic of the sporadic type were screened for hereditary disease by measurement of plasma levels of basal and stimulated calcitonin. RESULTS: Three of four immediate relatives tested positive for excessive calcitonin secretion and underwent thyroidectomy. All had C-cell hyperplasia, the premalignant phase of MTC. CONCLUSIONS: The patient with apparently sporadic (nonfamilial) MTC was clearly an index case of familial disease. We conclude that clinical presentation and histopathologic examination are not adequate to reliably exclude hereditary MTC. Until genetic markers are readily available to distinguish between sporadic and familial forms, biochemical screening should be done in primary relatives of all patients with newly detected MTC.

Adult↗
PubMed1989

Human medullary thyroid carcinoma: characterization of the serotonergic and neuronal properties of a neurectodermally derived cell line.

Parafollicular (PF) cells have been found to be a good model system for the study of serotonergic cellular mechanisms relevant to neurons. PF cells are derived from the same region of the neural crest that gives rise to the neurons of the gut and are capable of extending neurofilament-bearing neuritic processes. PF cells also synthesize 5-hydroxytryptamine (5-HT) and costore 5-HT in the same vesicles as the specific 5-HT-binding protein, 45 kDa SBP. A hypothesis has been advanced that PF cells and enteric neurons share a common developmental precursor. The present investigation was undertaken in order to determine whether a human medullary thyroid carcinoma (MTC) cell line, which is derived from PF cells, sufficiently mimics PF cells that it can be substituted for them in investigations of serotonergic cellular biology. In contrast to PF cells, MTC cells can be propagated in vitro to provide adequate amounts of material for biochemical studies. MTC cells were found to contain neuropeptides, including calcitonin, calcitonin gene-related peptide, and somatostatin, which have also been reported to be present in PF cells and enteric neurons. MTC cells also were observed to store endogenous 5-HT, to be able to synthesize 3H-5-HT from 3H-L-tryptophan, and to take up 3H-5-HT from the ambient medium by a carrier-mediated mechanism very similar to that of serotonergic neurons. In addition, the longterm accumulation of 3H-5-HT in MTC cells was antagonized by reserpine, suggesting that the cells contain 5-HT storage vesicles that, like the synaptic vesicles of serotonergic neurons, are characterized by a reserpine-sensitive transporter of biogenic amines. MTC cells also contain type A, but not type B, monoamine oxidase. Finally, MTC cells were found to contain both 45 and 56 kDa SBP. MTC cells thus retain a great many of the properties of PF cells, and, like PF cells, they are serotonergic cells with characteristics similar to serotonergic neurons. Substantial differences were found in the content of immunoreactive 5-HT and neuropeptides in individual MTC cells. Moreover, the release of newly synthesized 5-HT to the medium exceeded the ability of the cells to store the amine. Studies of the ultrastructure of the MTC cells revealed a limited and highly variable number of secretory granules, probably accounting for their limited 5-HT storage capacity and for the heterogeneity of immunostaining with antisera to 5-HT or neuropeptides.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

A thermodynamic study of the interaction of tubulin with colchicine site ligands.

The bicyclic colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-on e (MTC) has been used to study the thermodynamics of specific ligand binding to the colchicine site of tubulin, employing isothermal reaction microcalorimetry. The binding of MTC to purified calf brain tubulin, in 10 mM sodium phosphate buffer, pH 7.0, is characterized by delta H degree = -19 +/- 1 kJ.mol-1, delta G degree = -31.8 +/- 0.6 kJ.mol-1, and delta S degree = 43 +/- 5 J.mol-1.K-1 at 298 K, with a slight variation in the temperature range from 283 to 308 K. The binding thermodynamics of colchicine and allocolchicine are similar to MTC under the conditions examined, suggesting related molecular interactions of the three ligands with the protein binding site. The standard enthalpy changes of binding of colchicine and MTC at 308 K coincide within experimental error. Therefore the more favorable free energy change of binding of colchicine must come from a larger binding entropy change (by about 20 J.mol-1.K-1). This difference could be attributed to the presence of the middle ring of colchicine, which is absent in MTC. Consistently, a similar entropy change is observed by the comparison of allocolchicine to MTC binding at several temperatures. In addition, allocolchicine binding is about 6 kJ.mol-1 less exothermic than MTC binding, which could be attributed to the presence in allocolchicine of a substituted phenyl ring instead of the colchicine-MTC tropolone ring. The present results and analysis are fully compatible with the previously proposed bifunctional binding of colchicine and MTC (through their trimethoxybenzene and tropolone moieties) to a bifocal protein binding site, and also with a partial immobilization of intramolecular rotation of MTC upon binding, which in colchicine is already constrained by its middle ring (Andreu, J. M., Gorbunoff, M. J., Lee, J. C., and Timasheff, S. (1984) Biochemistry 23, 1742-1752).

Animals↗
PubMed1983

Competitive nonspecific binding does not explain the potentiating effects of muscle relaxant combinations.

Combination of pancuronium (Pm) with d-tubocurarine (dTC) or metocurine (mTC) produces potentiation of neuromuscular effects. We tested the hypothesis that this effect is due to decreased plasma protein and/or nonspecific (noncholinergic) tissue binding by one or the other drug such that a greater than expected proportion of unbound drug reaches its neuromuscular site of activity. By varying the concentration of Pm, dTC, and mTC, competitive binding by Pm and dTC or Pm and mTC to plasma constituents was tested in vitro by equilibrium dialysis. Drug interaction and displacement from nonspecific binding sites in tissues was tested in vivo with Pm-mTC combinations. During recovery of mTC-induced neuromuscular paralysis, monitored by evoked twitch tension, 1 mg of Pm was administered intravenously. The twitch height and plasma mTC concentrations before and after Pm administration were noted. The in vitro plasma dTC or mTC binding was not significantly altered by the addition of Pm. Similarly, plasma mTC concentrations in vivo did not increase following the administration of Pm. Thus, there was no displacement of mTC from nonspecific tissue binding sites by Pm. Our in vitro and in vivo experiments both demonstrate that there is no interaction between Pm--dTC and Pm--mTC relative to plasma or tissue binding and thus cannot explain the potentiating effect of the drug combination.

Binding, Competitive↗
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↗
PubMed1995

Familial non-multiple endocrine neoplasia medullary thyroid carcinoma: report of a case confirming a new clinical entity in Japan.

Most hereditary medullary thyroid carcinomas (MTC) occur in association with multiple endocrine neoplasia (MEN) type 2 syndromes. Since Farndon et al. reported two kindreds, that is collections of relatives, with familial non-MEN MTC in 1986, only five kindreds with this disorder have been reported in the English literature. In this paper, we describe a rare Japanese kindred with familial non-MEN MTC, confirming the existence of this distinct clinical entity in Japan. A 42-year-old woman underwent a left hemithyroidectomy with modified neck dissection (MND) under a diagnosis of sporadic MTC at 28 years of age. She developed lymph node metastasis in the right neck region 7 years after the initial surgery, and underwent MND and right hemithyroidectomy. Although no findings of MTC were histologically confirmed in the resected right thyroid lobe, C-cell hyperplasia was observed. Hereditary MTC was strongly suspected, but we could not confirm specific manifestations associated with MEN type 2 in any family members. However, 7 years later, a paternal aunt and cousin were diagnosed with MTC. Other family members were evaluated by ultrasonography and calcium-pentagastrin provocation testing, and three additional patients with MTC across two generations were found. None of these patients had any extrathyroidal manifestations associated with MEN type 2, and the entity of familial non-MEN MTC was confirmed.

Adult↗
PubMed1999

Optimization of a contrast-detail-based method for electronic image display quality evaluation.

The authors previously reported a general technique based on contrast-detail methods to provide an overall quantitative evaluation of electronic image display quality. The figure-of-merit reflecting overall display quality is called maximum threshold contrast or MTC. In this work we have optimized the MTC technique through improvements in both the test images and the figure-of-merit computation. The test images were altered to match the average luminance with that observed for clinical computed radiographic images. The figure-of-merit calculation was altered to allow for contrast-detail data with slopes not equal to -1. Preliminary experiments also were conducted to demonstrate the response of the MTC measurements to increased noise in the displayed image. MTC measurements were obtained from five observers using the improved test images displayed with maximum monitor luminance settings of 30-, 50-, and 70-ft-Lamberts. Similar measurements were obtained from two observers using test images altered by the addition of a low level of image noise. The noise-free MTC and MTC difference measurements exhibited standard deviations of 0.77 and 1.55, respectively. This indicates good measurement precision, comparable or superior to that observed using the earlier MTC technique. No statistically significant image quality differences versus maximum monitor luminance were seen. The noise-added MTC measurements were greater than the noise-free values by an average of 4.08 pixel values, and this difference was statistically significant. This response is qualitatively correct, and is judged to indicate good sensitivity of the MTC measurement to increased noise levels.

Computer Terminals↗