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PubMed1997

Short echo time projection reconstruction MR imaging of cartilage: comparison with fat-suppressed spoiled GRASS and magnetization transfer contrast MR imaging.

PURPOSE: To evaluate short echo time (TE) projection reconstruction magnetic resonance (MR) imaging in the detection of cartilage lesions. MATERIALS AND METHODS: Twenty-seven cartilage regions of 10 human patellar specimens were examined with the following MR sequences: short TE projection reconstruction (repetition time msec/TE msec, 400/0.15), fat-suppressed three-dimensional spoiled gradient-recalled acquisition in the steady state (Spoiled GRASS) (50/10, 60 degrees flip angle), and magnetization transfer contrast (MTC) subtraction (400/6). MR findings were correlated with histopathologic grading of the cartilage. RESULTS: For detection of cartilage lesions, sensitivity of projection reconstruction imaging (100%) was significantly greater (P = .03) than that of MTC (62%) but not significantly greater (P > .05) than that of Spoiled GRASS (81%) imaging. Accuracy of projection reconstruction was significantly greater than that of MTC (P = .004) and Spoiled GRASS (P = .03) imaging. Unmasking of collagen fibers was most predictive of abnormal signal intensity of the cartilage with all sequences. CONCLUSION: In vitro, short TE projection reconstruction MR imaging provides superior delineation of cartilage lesions when compared with two other sequences. On Spoiled GRASS and MTC images, signal intensity of the superficial layer of cartilage is not a reliable sign for surface integrity.

Aged↗
PubMed2006

Similitude of transperitoneal permeability in different rodent species.

Transgenic mice facilitate mechanistic studies of altered peritoneal transport, but the majority of transport studies have been carried out in rats. We hypothesized that mouse transport parameters, normalized to the peritoneal contact area, would be similar to those of the rat. To address this, we affixed small ( approximately 10-mm diameter) plastic chambers to the serosa of the abdominal wall of anesthetized CD1 and C57BL mice. The chamber constrained transfer across the area of the chamber base and facilitated mixing, volumetric, and concentration measurements vs. time for mannitol, serum albumin, and osmotic and hydrostatic pressure-driven convection. The mass transfer coefficient of mannitol (MTC(M)) and of serum albumin (MTC(BSA)), hydrostatic pressure-driven flux (J(P)), and osmotic filtration (J(osm)) were calculated from the time-dependent volume and concentration data. The units of all parameters (microl x min(-1) x cm(-2)) were compared with previously derived parameters from SD rats with a one-way ANOVA. Results indicated small but significant differences in MTC(BSA) (x10(2)): CD1, 9.72 +/- 1.97, n = 6; C57BL, 7.13 +/- 1.52, n = 10; rat, 12.5 +/- 1.6, n = 17 (P = 0.03). ANOVAs of all other parameters were not significant and confirmed our hypothesis: MTC(M) (CD1, 3.20 +/- 0.38, n = 7; C57BL, 2.34 +/- 0.41, n = 6; rat, 2.72 +/- 0.23 n = 19), J(P) (CD1, 0.77 +/- 0.15, n = 10; C57BL, 0.33 +/- 0.13, n = 15; rat, 0.51 +/- 0.16, n = 9), or J(osm) (CD1, 0.92 +/- 0.35, n = 6; C57BL, 0.49 +/- 0.35, n = 6; rat 1.72 +/- 0.35, n = 6). We conclude that elimination of the variable peritoneal transfer area normalizes calculated transport characteristics and facilitates comparison between species.

Algorithms↗
PubMed1984

Canine gastrocnemius disuse atrophy: resistance to paralysis by dimethyl tubocurarine.

Ten dogs developed unilateral gastrocnemius disuse atrophy after unilateral hindlimb immobilization in a cast for 25 days. Dose-response curves to dimethyl tubocurarine (MTC) were determined during anesthesia with pentobarbital sodium-N2O. Bolus and continuous infusion increments of MTC every 30 min provided steady-state blood levels at each stage of paralysis. Both gastrocnemius tendons were sectioned and attached to transducers. Both sciatic nerves were stimulated every 30 min: 2 Hz for 2 s, a 15-s pause, 50 Hz for 2 s. Dose-response curves, computer calculated by nonlinear regression using a sigmoid maximal effect model of the Hill equation, were parallel for the data relating blocking of tetanus to dose of MTC. The 50% paralyzing dose (tetanus) for control vs. casted gastrocnemius muscle was 64 vs. 813 mg/kg; corresponding plasma concentrations were 0.12 vs. 2.0 micrograms/ml. Thus in vivo simultaneous tension measurements of both gastrocnemius muscles, one casted and one uncasted, demonstrated resistance to paralysis by MTC in muscle with disuse atrophy.

Animals↗
PubMed2001

Measurement of cell microrheology by magnetic twisting cytometry with frequency domain demodulation.

Magnetic twisting cytometry (MTC) (Wang N, Butler JP, and Ingber DE, Science 260: 1124-1127, 1993) is a useful technique for probing cell micromechanics. The technique is based on twisting ligand-coated magnetic microbeads bound to membrane receptors and measuring the resulting bead rotation with a magnetometer. Owing to the low signal-to-noise ratio, however, the magnetic signal must be modulated, which is accomplished by spinning the sample at approximately 10 Hz. Present demodulation approaches limit the MTC range to frequencies <0.5 Hz. We propose a novel demodulation algorithm to expand the frequency range of MTC measurements to higher frequencies. The algorithm is based on coherent demodulation in the frequency domain, and its frequency range is limited only by the dynamic response of the magnetometer. Using the new algorithm, we measured the complex modulus of elasticity (G*) of cultured human bronchial epithelial cells (BEAS-2B) from 0.03 to 16 Hz. Cells were cultured in supplemented RPMI medium, and ferromagnetic beads (approximately 5 microm) coated with an RGD peptide were bound to the cell membrane. Both the storage (G', real part of G*) and loss (G", imaginary part of G*) moduli increased with frequency as omega(alpha) (2 pi x frequency) with alpha approximately equal to 1/4. The ratio G"/G' was approximately 0.5 and varied little with frequency. Thus the cells exhibited a predominantly elastic behavior with a weak power law of frequency and a nearly constant proportion of elastic vs. frictional stresses, implying that the mechanical behavior conformed to the so-called structural damping (or constant-phase) law (Maksym GN, Fabry B, Butler JP, Navajas D, Tschumperlin DJ, LaPorte JD, and Fredberg JJ, J Appl Physiol 89: 1619-1632, 2000). We conclude that frequency domain demodulation dramatically increases the frequency range that can be probed with MTC and reveals that the mechanics of these cells conforms to constant-phase behavior over a range of frequencies approaching three decades.

Algorithms↗
PubMed2003

Interaction between fascicles and tendinous structures during counter movement jumping investigated in vivo.

Behavior of fascicles and tendinous structures of the m. gastrocnemius medialis (MG) was quantitatively examined during human jumping in vivo. Eight male subjects performed maximal-effort counter movement jumping (CMJ) motions. Kinematic and kinetic data were obtained using a high-speed camera and a force platform. Behavior of fascicles and tendinous structures was determined using ultrasonography and electromyography. Although the muscle-tendon complex (MTC) shortened by only 1.6% during the downward phase of the counter movement, fascicles shortened as much as 10.4%. This shortening of fascicles caused elongation of tendinous structures by 2.2%. Although the MTC remained at almost constant length during the upward-I phase (-250 to -100 ms before toe-off), fascicles shortened by 19.2% of the initial length with an elongation of tendinous structures by 4.4%. The MTC shortened rapidly by 5.3% of the initial length during the upward-II phase (-100 to 0 ms), whereas fascicles shortened slightly during the first half of this phase and contracted in a quasi-isometric manner during the latter half of this phase. These findings implied that elastic energy was stored in tendinous structures throughout the latter half of the downward phase (1.0 J) and upward-I phase (5.6 J), which was thereafter rapidly released during the upward-II phase (3.8 J). It was found that muscle fibers of the MG were not stretched during counter movement; therefore, stretch reflex and potentiation of the contractile component of the MG might not contribute to the work enhancement in CMJ. It was suggested that the interaction between fascicles and tendinous structures was essential in a generation of higher joint power during the late push-off phase. This behavior of the MTC of the MG in CMJ was quite similar to what was observed in squat jumping performed without counter movement.

Adult↗
PubMed2000

Demonstration and diagnostic significance of pro-gastrin-releasing peptide in medullary thyroid carcinoma.

The expression of pro-gastrin-releasing peptide (proGRP) in medullary thyroid carcinoma (MTC) and other histological types of thyroid carcinoma was studied by an immunohistochemical technique, using polyclonal anti-proGRP antiserum. Immunoreactivity for proGRP was detected exclusively in MTC (n = 7); other histological types (n = 12) were all negative for proGRP. In addition, serum proGRP levels were elevated in patients with primary or recurrent MTC (n = 3), and they changed in parallel with serum calcitonin (CT), and carcinoembryonic antigen (CEA). These results show that proGRP, which is considered to be a specific marker for small-cell lung carcinoma, may be also a potential tumor marker for MTC, in addition to CT and CEA.

Biomarkers, Tumor↗
PubMed1997

RET proto-oncogene mutations in multiple endocrine neoplasia type 2 and medullary thyroid carcinoma.

Multiple endocrine neoplasia type 2 (MEN-2) is a familial cancer syndrome inherited in an autosomal dominant fashion with age-related penetrance. The main tumour type present in all manifestations of this syndrome. MEN-2A, MEN-2B and familial medullary thyroid carcinoma (FMTC), is medullary thyroid carcinoma (MTC). MTC arises from the parafollicular or C cells of the thyroid. MEN-2A is characterised by the triad of MTC, phaeochromocytoma, and parathyroid hyperplasia. MEN-2B is characterised by features similar to those of MEN-2A, except for the absence of clinically apparent parathyroid hyperplasia, and additional stigmata including a marfanoid habitus, mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract. FMTC families have MTC as their only phenotype. Missense mutations affecting conserved cysteine codons adjacent to the transmembrane domain of the RET proto-oncogene have been identified in the germline DNA of patients with MEN-2A and FMTC. A single mutation at codon 918 in the tyrosine kinase domain of the RET receptor has been associated with the MEN-2B phenotype. In a small number of FMTC families, missense point mutations have also been identified in the intracellular domain of the RET protein. RET mutation analysis of MEN-2 families has allowed the identification of genotype-phenotype correlations. While 25% of all MTCs are hereditary, the great majority of MTCs, 75%, are sporadic. Various somatic RET mutations have been identified in sporadic MTCs. In a small number of hereditary MTCs with germline mutations in RET, an additional somatic missense RET mutation has been identified. The discovery of RET mutations in MEN-2 has made possible accurate DNA-based diagnosis and predictive testing. The clinical significance of somatic RET mutations has yet to be determined.

Carcinoma, Medullary↗
PubMed1986

Effect of metoclopramide treatment on thyrotropin and prolactin levels in sick neonates.

The present study was carried out to define whether dopaminergic mechanisms contribute to the regulation of thyrotropin (TSH) and prolactin PRL release in the immediate neonatal period. 14 full-term neonates with a mean birth weight of 3,240 g and a mean gestational age of 39.1 weeks were administered metoclopramide (MTC), a specific dopamine antagonist, in a dose of 0.1 mg/kg/day to treat delayed gastric emptying, regurgitation and abdominal distension. Prior to and after 3-day MTC administration, blood samples were taken to determine serum TSH and PRL levels using a radioimmunoassay method. It has been demonstrated that in response to MTC administration PRL increased significantly from 4,010 +/- 383 to 5,478 +/- 441 mU/l (p less than 0.01), while TSH showed only a tendency to rise independent of the pretreatment hormone levels (from 2.85 +/- 0.44 to 3.06 +/- 0.38 mU/L. In healthy control infants and in those infants with similar functional gastrointestinal disturbances who were treated without MTC, serum PRL levels fell significantly from days 3-4 to days 6-7, serum TSH, triiodothyronine and free thyroxine, however, remained unaltered. It is concluded that dopaminergic inhibitory mechanism may be involved in the control of pituitary PRL and TSH release already in the neonatal period.

Gastrointestinal Diseases↗
PubMed2005

Review of fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the follow-up of medullary and anaplastic thyroid carcinomas.

BACKGROUND: The goal of posttreatment follow-up for medullary and anaplastic thyroid cancer (MTC and ATC) is the early diagnosis of recurrence or metastases. However, routine follow-up protocols, including physical examination and clinically oriented investigations, are not standardized, and their sensitivity in accurately detecting recurrent or metastatic disease is often suboptimal. A valuable addition to posttreatment follow-up of oncology patients is positron emission tomography using fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG-PET). METHODS: We review the role of FDG-PET imaging in the follow-up of patients previously treated for MTC and ATC. RESULTS: Based on the encouraging literature data, FDG-PET appears to be useful in detecting recurrent or metastatic disease in patients with MTC and ATC, providing a higher sensitivity (66% to 100%) and specificity (79% to 90%) than conventional imaging methods. However, the PET technique is limited by less accurate spatial assignment of small lesions, especially in the lung and liver. CONCLUSIONS: Supporting evidence indicates that FDG-PET has a significant role in the follow-up of patients with MTC and ATC.

Carcinoma↗
PubMed1996

An evaluation of telemedical support for a minor treatment centre.

A low-cost telemedicine link was established from an accident and emergency department in Belfast to support nurse practitioners running a minor treatment centre (MTC) in London. During the 12 months before the introduction of the telemedicine link, 6729 patients were seen in the MTC. Of these, 155 (2.3%) were referred to the nearest accident and emergency department and 802 (11.9%) were referred to their general practitioner (GP). During the first 12 months of the use of the telemedicine link, 9972 patients were seen in the MTC. Of these, 147 (1.5%) were referred to the accident and emergency department and 383 (3.8%) were referred to their GP. During the evaluation period, 51 patients were seen using the telemedicine link, representing 0.5% of all MTC attenders during that period. The total number of teleconsultations was less than expected. The reasons for this difference include random variation, but could also include confidence resulting from the presence of the link and a training effect. The telemedicine link for trauma and minor injuries was an extremely cost-effective way of providing medical expertise to cover the clinical risk of the 0.5-1.5% of the case load that required expert medical opinion. The direct costs of on-site medical staff would have been 50,000 pounds per annum, excluding overhead charges. The annual cost of the videolink, including overheads, was 7250 pounds, amounting to a saving of some 42,000 pounds per annum.

Emergency Medical Services↗
PubMed2006

Somatic VHL gene alterations in MEN2-associated medullary thyroid carcinoma.

BACKGROUND: Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a "second hit" mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. METHODS: We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. RESULTS: First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. CONCLUSION: These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC.

Carcinoma, Medullary↗
PubMed2006

Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anti-carcinoembryonic-antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor Group.

PURPOSE: No effective therapy is currently available for the management of patients with metastatic medullary thyroid carcinoma (MTC). The efficacy of pretargeted radioimmunotherapy (pRAIT) with bispecific monoclonal antibody (BsMAb) and a iodine-131 (131I) -labeled bivalent hapten is evaluated. PATIENTS AND METHODS: Twenty-nine patients with advanced, progressive MTC, as documented by short serum calcitonin doubling times (Ct DTs), received an anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA) -indium BsMAb, followed 4 days later by a 131I-labeled bivalent hapten. Overall survival (OS) was compared with 39 contemporaneous untreated MTC patients with comparable prognostic indicators. RESULTS: OS was significantly longer in high-risk, treated patients (Ct DT < 2 years) than in high-risk, untreated patients (median OS, 110 v 61 months; P < .030). Forty-seven percent of patients, defined as biologic responders by a more than 100% increase in CtDT, experienced significantly longer survival than nonresponders (median OS, 159 v 109 months; P < .035) and untreated patients (median OS, 159 v 61 months; P < .010). Treated patients with bone/bone-marrow disease had a longer survival than patients without such involvement (10-year OS, 83% v 14%; P < .023). Toxicity was mainly hematologic and related to bone/bone-marrow tumor spread. CONCLUSION: pRAIT against CEA induced long-term disease stabilization and a significantly longer survival in high-risk patients with Ct DTs less than 2 years, compared with similarly high-risk, untreated patients. Ct DT and bone-marrow involvement appear to be prognostic indicators in MTC patients who undergo pRAIT.

Antibodies, Monoclonal↗
PubMed2004

Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer: implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase.

Medullary thyroid cancer (MTC) is a C cell neoplasm-secreting calcitonin. Surgery remains the only treatment as the primary tumor and metastases resist radio- and chemotherapies. MTC produces high amounts of prostaglandins (PGs). Nonsteroidal antiinflammatory drugs have an antitumoral effect, generally related to the decrease of PG levels. We assessed the therapeutic potential of indomethacin in a model of human (TT cells) tumors in nude mice. Indomethacin (1.5 or 2.0 mg/kg body weight.d for 7 wk) inhibited tumor volume by 49 or 77%, respectively, and decreased the plasma level of CT. Although the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling method revealed few apoptotic nuclei, the number of proliferating cells was significantly decreased (Ki-67 antigen study). Immunological effector recruitment and vascular network was not modified by treatment. The inducible synthesis enzyme, cyclooxygenase-2 (COX-2), was revealed only in infiltrating cells, both in treated and control tumors. The expression of the constitutive synthesis enzyme COX-1 was diminished, and the expression of 15-prostaglandin dehydrogenase, the key enzyme catabolizing PGs, was increased in treated tumors. Thus, our results demonstrated the potential of indomethacin, inhibitor of COX-1 and COX-2, to prevent MTC growth. The synthesis enzyme, COX-1, and the catabolism enzyme 15-prostaglandin dehydrogenase, could be involved in MTC development.

Animals↗
PubMed2001

Induction of a cellular and humoral immune response against preprocalcitonin by genetic i: a potential new treatment for medullary thyroid carcinoma.

Currently, no effective therapy exists for patients suffering from progressive medullary thyroid carcinoma (MTC), a calcitonin (CT)-secreting C cell tumor. As CT, which arises from the precursor protein preprocalcitonin (PPCT), is expressed by almost all MTC cases, these molecules may represent target antigens for immunotherapy against MTC. In our study we investigated whether DNA immunization is able to induce cellular and humoral immune responses against human PPCT (hPPCT) in mice. Antigen-encoding expression plasmids were delivered intradermally by gene gun. One group of mice received DNA encoding hPPCT only. Two groups were coinjected with mouse cytokine genes. We observed in lymphocyte proliferative assays substantial proliferation against hPPCT in mice coinjected with the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, in contrast to mice vaccinated with hPPCT expression plasmid only. In addition, codelivery of the GM-CSF gene augmented the frequency of anti-hPPCT antibody seroconversions in sera of immunized animals, as shown by enzyme-linked immunosorbent assay. These results illustrate that cellular and humoral immune responses against hPPCT can be generated by DNA immunization and increased by coinjection of the GM-CSF gene. Our findings may have implications for the use of DNA immunization as a potential novel immunotherapeutic treatment for patients suffering from progressive MTC.

Animals↗
PubMed2003

A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma.

Familial medullary thyroid carcinoma is related to germ-line mutations in the RET oncogene, mainly in cysteine codon 10 or 11, whereas noncysteine mutations in codons 13-15 are rare. We now report a new missense point mutation in exon 8 of the RET gene (1597G-->T) corresponding to a Gly(533)Cys substitution in the cysteine-rich domain of RET protein in 76 patients from a 6-generation Brazilian family with 229 subjects, with ascendants from Spain. It is likely that the mutation causes familial medullary thyroid carcinoma (FMTC), because no other mutation was found in RET, the mutation cosegregates with medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) in patients subjected to surgery, and family members without the mutation are clinically unaffected. The histological analysis of 35 cases submitted to thyroidectomy revealed that 21 patients had MTC after the age of 40 yr and 8 before the age of 40 yr, 4 presented MTC or CCH before the age of 18 yr, 2 died due to MTC at the age of 53 and 60 yr, and CCH was found in a 5-yr-old child, suggesting a clinical heterogeneity. To improve the diagnosis of FMTC, analysis of exon 8 of RET should be considered in families with no identified classical RET mutations.

Adolescent↗
PubMed2005

Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma?

CONTEXT: Single-nucleotide polymorphisms (SNPs) of the RET protooncogene (RET) could modify disease susceptibility and clinical phenotype in patients with sporadic or familial medullary thyroid carcinoma (FMTC). OBJECTIVE/DESIGN OF THE STUDY: Because frequencies of RET SNPs have not yet been evaluated in patients with elevated serum concentrations of calcitonin (hCt), a biochemical marker for medullary thyroid carcinoma (MTC), we studied RET SNPs in patients with FMTC (n = 22), patients with sporadic MTC (n = 45), and 71 subjects presenting with moderately elevated hCt concentrations (basal, >10 pg/ml; pentagastrin stimulated, > 50 < 100 pg/ml) in comparison with an age- and gender-matched control group (n = 79) with basal hCt concentrations in the normal range (<5 pg/ml). METHODS: After DNA extraction from citrated whole blood, RET exons 10, 11, 13, 14, 15, and 16 and exon/intron boundaries were analyzed by PCR-based cycle sequencing for RET germ line mutations, exonic (G691S, L769L, S836S, S904S) and intronic (IVS13+158; NCBI rs2472737 = IVS14-24) SNPs. RESULTS: In FMTC patients, the F791Y mutation was found to be associated (P = 0.001) with the L769L SNP. The exonic SNPs (G691S, L769L, S836S, and S904S) were not different among the four groups. The intron 14 SNP (IVS14-24), however, was more frequent in individuals with elevated hCt serum concentrations (P = 0.016) and patients with sporadic MTC (P < 0.001) when compared with the control group. CONCLUSIONS: These data suggest that the exon 13 (L769L) and the intron 14 (IVS14-24) SNPs could act as genetic modifiers in the development of some forms of hereditary and sporadic MTC, respectively.

Adult↗
PubMed2005

"Hook effect" in calcitonin immunoradiometric assay in patients with metastatic medullary thyroid carcinoma: case report and review of the literature.

CONTEXT: Calcitonin is a well-established tumor marker for medullary thyroid carcinoma (MTC). Because surgery is the only effective treatment for patients with MTC, the postoperative level of serum calcitonin will dictate whether residual disease was left behind and whether reintervention is necessary. RESULTS: We describe here the case of a 41-yr-old man with metastatic MTC. Despite extensive disease in the neck as well as metastatic lesions in the liver, his serum calcitonin, measured with a commercial one-step immunoradiometric assay, was only minimally elevated (244 ng/liter). After serial dilutions, a nonlinear relationship became evident, suggesting the presence of a "hook effect." Treatment of the serum with heterophilic blocking reagent revealed no change. Calcitonin was then measured with a different immunoradiometric assay and revealed a much higher level. Similar discrepancies were found in different samples from various patients when analyzed with different calcitonin immunoassays. CONCLUSION: To our knowledge, this is the first reported case of a phenomenon such as the hook effect in a calcitonin immunoradiometric assay in patients with MTC. Being aware of this phenomenon is important, because a low calcitonin result could give false reassurance to both the patient and the clinician and could dramatically change the prognosis of the patient.

Adult↗
PubMed2006

Chemoembolization for liver metastases from medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a well-differentiated neuroendocrine tumor. Distant metastases are the main cause of cancer-related death. Systemic chemotherapy produces only rare tumor responses. Somatostatin analogs and other available modalities are poorly effective to control symptoms. AIMS: The aim of our study was to evaluate the impact of liver transarterial chemoembolization (TACE) in MTC patients with predominant and progressive liver metastases. PATIENTS AND METHODS: Twelve MTC patients underwent 18 TACE courses (mean, 1.5; range, 1-2). Response evaluation criteria in solid tumors were used to evaluate tumor responses. Symptomatic responses were defined by more than a 25% decrease of symptoms intensity. RESULTS: Partial radiological tumor response was obtained in five patients (42%) with a median duration of 17 months (mean, 19; range, 15-28 months), stabilization in five (42%) with a median duration of 24 months (mean, 24; range, 4-39 months), and progression in the remaining two (16%). The five partial tumor responses were observed in the nine patients with less than 30% liver involvement. Clinical response was observed in two of the five patients with diarrhea. Carcinoembryonic antigen did not appear to be a useful marker in this setting. Significant grade 3-4 toxicity was observed in one patient who had a major tumor necrosis after TACE. CONCLUSION: TACE should be considered for treating MTC patients with progressive and predominant liver metastasis, and preferably at an early stage during the course of metastatic disease.

Adult↗