Uwe Mäder

Life expectancy is reduced in differentiated thyroid cancer patients ≥ 45 years old with extensive local tumor invasion, lateral lymph node, or distant metastases at diagnosis and normal in all other DTC patients.

OBJECTIVE Differentiated thyroid carcinoma (DTC) generally has a good prognosis. As yet, however, it is unclear whether life expectancy is reduced in these patients and, if so, to what extent. The aim of this study was to determine how the all-cause mortality rate in DTC patients compares to that of the general population. DESIGN A prospective database study was conducted. PATIENTS The study included 2011 DTC patients treated in our hospital from 1980-2011. All patients received total thyroidectomy with subsequent (131)I ablation, except for those with an isolated papillary microcarcinoma. Survival data for the general German population were obtained from the German Federal Statistics Agency and matched to our DTC population for age and sex. RESULTS Patients who were at least 45 yr old at diagnosis and had extensive perithyroidal invasion (UICC/AJCC TNM system, 7th edition, stages IVa and IVb), lateral cervical lymph node metastases (TNM stage IVa), or distant metastases (TNM stage IVc) showed a clearly reduced life expectancy [relative cumulative survival rate (observed:expected) for stage IVc after 20 yr, 0.295; 95% confidence interval, 0.033-0.556]. In patients over 60 yr of age at diagnosis, the loss of life expectancy was (much) greater than for those aged 45-59 yr in all groups. Life expectancy was not reduced in patients with TNM stages I, II, or III (86% of patients). CONCLUSION Life expectancy is not significantly reduced in 86% of DTC patients; only patients at least 45 yr old with extensive local invasion, lateral lymph node metastases, and/or distant metastases (TNM stages IVa, IVb, and IVc) at diagnosis showed a clearly lower life expectancy.

Changing trends of incidence and prognosis of thyroid carcinoma in lower Franconia, Germany, from 1981-1995.

BACKGROUND A population-based registry (PBR) in Lower Frankonia in southern Germany was conducted to evaluate the changes of incidence and prognosis of thyroid carcinoma (TC) in this area. METHODS The study comprised 476 patients with differentiated thyroid carcinoma (DTC) from Lower Franconia (1.3 x 10(6) inhabitants) registered between 1981 and 1995 at the Regional Tumor Center. The incidence was assessed with respect to gender, age, histology, tumor stage, lymph node involvement and distant metastases in 5-year intervals (1981-1985, 1986-1990, and 1991-1995). RESULTS An increasing rate of papillary thyroid carcinoma PTC and a decreasing rate of follicular thyroid carcinoma (FTC) were observed over the three time periods (1981-1985, 1986-1990, and 1991-1995). The overall incidence revealed no significant change with time for both females from 3.22 to 3.25 and 3.73 and males (1.07 to 1.54 and 1.69) between the three time periods. There was a significant improvement in outcome of patients with DTC with respect to life expectancy. CONCLUSIONS Iodine prophylaxis does influence the distribution of the histologic types of thyroid cancer and leads to an increase in the ratio of papillary versus follicular carcinoma. Our study supports the hypothesis that the benefits of correcting iodine deficency outweigh the risks of iodine supplementation.

Characteristics of differentiated thyroid carcinoma in children and adolescents with respect to age, gender, and histology

Because of its rarity there have been only a few detailed studies on differentiated thyroid carcinoma (DTC) in children. The current investigation was undertaken to assess the characteristics of DTC with respect to age, gender, and histology in children and adolescents.

Potency and Tolerance of Calcitonin Stimulation with High-Dose Calcium Versus Pentagastrin in Normal Adults

OBJECTIVE The objectives of the study was to compare pentagastrin- and calcium-stimulated serum human calcitonin (hCT) levels for nonsmoking healthy adults without evidence of thyroid disorders and determine reference ranges of basal and pentagastrin- and calcium-stimulated serum hCT levels. DESIGN This was a healthy volunteer study including within-group and intergroup comparisons. SETTING The study was conducted at a tertiary referral center. SUBJECTS Subjects included 50 healthy, nonsmoking volunteers (25 female; aged 22-57 yr) without evidence of thyroid abnormality. INTERVENTIONS hCT was measured using a calcitonin two-site automated chemiluminescent immunometric assay (the most common hCT assay in clinical practice) in serum samples obtained before and 2, 5, and 15 min after iv stimulation using pentagastrin, 0.5 microg/kg body weight, or calcium gluconate, 2.5 mg/kg. MAIN OUTCOME MEASURES Reference ranges for basal, unstimulated, and pentagastrin- or calcium-stimulated hCT and pentagastrin and calcium tolerability in healthy adults were measured. RESULTS The 95th percentile basal hCT values did not differ between males and females (5.0 vs. 5.7 pg/ml). The 95th percentile maximal stimulated hCT values rose distinctly after pentagastrin (peak men, 37.8 pg/ml; women, 26.2 pg/ml) and even more so after calcium (peak men, 131.1 pg/ml, women, 90.2 pg/ml). No hCT increase was detected in four of 25 men and 12 of 25 women after pentagastrin vs. none of 24 men and two of 18 women after calcium. Calcium was associated with fewer and less intense adverse effects than was pentagastrin. CONCLUSION High-dose calcium is a more potent and better-tolerated hCT stimulator than is pentagastrin. The reference ranges for basal and stimulated hCT established via automated chemiluminescent assay were lower than those reported for other assays.

Histology does not influence prognosis in differentiated thyroid carcinoma when accounting for age, tumour diameter, invasive growth and metastases

OBJECTIVE Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) show considerable differences in disease stage at initial presentation. The aim of this study was to investigate whether there are differences in tumour-specific survival if initial staging is accounted for. DESIGN Retrospective chart review study. PATIENTS The study sample comprised 875 PTC and 350 FTC patients (856 females, 369 males, mean age 47.8 years) treated in our hospital from 1978 to 2002. All patients received total thyroidectomy with subsequent I-131 ablation except for those patients with an isolated papillary microcarcinoma. METHODS Kaplan-Meier analyses and Cox-regression analyses were performed to assess the influence of histology on thyroid cancer-specific survival. RESULTS FTC patients were on average older, more likely to be male, presented with a larger tumour and more frequently had multifocal carcinoma and distant metastases than PTC patients, whereas they presented less frequently with extrathyroidal invasion or lymph node metastases. Twenty-year tumour-specific survival in PTC was 90.6% and in FTC 73.7% (P<0.001). In multivariate analysis the presence of distant metastases (P<0.001), age (P<0.001), tumour size (P=0.001) and the presence of extrathyroidal invasion (P=0.007), but not histology (P=0.26), were independent determinant variables for tumour-specific survival. CONCLUSION There is no difference in tumour-specific survival between PTC and FTC when accounting for the presence of metastases, age, tumour size and the presence of extrathyroidal invasion.

Long-Term Survival in Differentiated Thyroid Cancer Is Worse After Low-Activity Initial Post-Surgical 131I Therapy in Both High- and Low-Risk Patients

CONTEXT Recent trial results have revived interest in low-activity initial (131)I therapy (RIT) of differentiated thyroid cancer (DTC). OBJECTIVE This study sought to compare different initial (131)I activities for outcome. DESIGN AND SETTING A database study was performed in a University hospital. PATIENTS 1298 DTC patients were included (698 low risk, 434 high risk M0, and 136 M1), grouped according to ablation activity (I, ≤ 2000 MBq [54 mCi]; II, 2000-3000 MBq [54-81 mCi]; and III, >3000 MBq [81 mCi]), subdivided by age (<45 and ≥ 45 y at diagnosis). MAIN OUTCOME MEASURES Complete remission (CR, defined as thyroglobulin [Tg] below functional sensitivity combined with visually negative (131)I diagnostic whole-body scintigraphy), recurrence, DTC-specific mortality, and relative survival rates were studied. RESULTS Low-risk patients: In patients <45 years, a lower median cumulative activity was required to achieve CR in group III (3590 MBq) than in groups I (8050 MBq) and II (6300 MBq). In patients at least 45 years of age, DTC-specific mortality was significantly higher in group I than in groups II and III (15-y: 16.1 ± 7.7%, 0.8 ± 0.8%, and 7.2 ± 5.5%, respectively; P = .004). High-risk M0 patients: In patients at least 45 years of age, the recurrence rate (15-y: 44.4 ± 16.6%, 24.1 ± 7.6%, and 8.6 ± 3.9%; P = .001) and DTC-specific mortality (15-y: 51.8 ± 15.8%, 13.2 ± 4.4%, and 9.5 ± 3.7%; P = .004) were significantly higher in group I than in groups II and III. M1 patients: There were no significant differences in survival results between different activity groups in either age category. CONCLUSION Before adopting low initial activity RIT for, especially older, low-risk patients, results of long-term followup should be regarded critically. Low-activity RIT in older, high-risk patients is not to be recommended.

Primary tumour diameter as a risk factor for advanced disease features of differentiated thyroid carcinoma

Objective  To study the relationship between primary tumour size and the risk of advanced disease features (multifocal or locally invasive disease, lymph‐node or distant metastases) in differentiated thyroid carcinoma (DTC).

A comparison of prognostic classification systems for differentiated thyroid carcinoma

Objective  To identify and compare prognostic classification systems based on basic tumour characteristics that were developed and/or validated for differentiated thyroid carcinoma (DTC).

Impact of moderate vs stringent TSH suppression on survival in advanced differentiated thyroid carcinoma

Objectives  To assess (i) the influence of Thyrotropin (TSH) suppression at a level of <0·1 mU/l and (ii) whether FT3 and FT4 levels have a prognostic significance independently of TSH values with regard to survival in patients with differentiated thyroid carcinoma (DTC) and distant metastases.

Delineation of distinct tumour profiles in mantle cell lymphoma by detailed cytogenetic, interphase genetic and morphological analysis.

Mantle cell lymphoma (MCL) is an aggressive lymphoid tumour characterized by the translocation t(11;14)(q13;q32) and a poor clinical outcome (median survival: 3–4 years). Recent studies revealed that increased proliferation of the tumour cells and certain chromosomal aberrations, such as deletions of 17p13 and 9p21 represent major adverse biological markers in this disease, although the molecular targets of chromosomal imbalances in MCL have not been identified for the large majority of loci affected. To correlate histomorphological and proliferation features of MCL with genetic findings, we investigated 223 MCL by fluorescence in situ hybridization (FISH) (n = 157) and/or classical cytogenetic banding analysis (n = 129). FISH analysis turned out to be distinctly more sensitive in the delineation of aberrations. Complex karyotypic alterations were associated with higher proliferation indices and inferior prognosis. A comprehensive analysis of biological features including genetic alterations in MCL by hierarchical clustering resulted in the delineation of four tumour subgroups differing with respect to their genetic constitution and suggesting different transformation or progression pathways. Moreover, in one of the groups identified, a more indolent clinical behaviour was associated with few secondary aberrations and fewer known high‐risk chromosomal aberrations, which points to the importance of the quality of karyotypic evolution in MCL tumours.