Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 2A in Denmark 1930­2021: A Nationwide Population-Based Retrospective Study

Studies of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) shows divergence in frequency, disease definition, reporting of clinical characteristics and traces of selection bias. This is a nationwide population-based retrospective study of PHPT in MEN 2A, suggesting a representative frequency, with complete reporting and a strict PHPT definition. The Danish MEN 2A cohort 1930-2021 was used. Of 204 MEN 2A cases, 16 had PHPT, resulting in a frequency of 8% (CI, 5-12). Age-related penetrance at 50 years was 8% (CI, 4-15). PHPT was seen in the American Thyroid Association moderate (ATA-MOD) and high (ATA-H) risk groups in 62% and 38% of carriers, respectively. Median age at PHPT diagnosis was 45 years (range, 21-79). A total of 75% were asymptomatic and 25% were symptomatic. Thirteen underwent parathyroid surgery, resulting in a cure of 69%, persistence in 8% and recurrence in 23%. In this first study with a clear PHPT definition and no selection bias, we found a lower frequency of PHPT and age-related penetrance, but a higher age at PHPT diagnosis than often cited. This might be affected by the Danish RET p.Cys611Tyr founder effect. Our study corroborates that PHPT in MEN 2A is often mild, asymptomatic and is associated with both ATA-MOD and ATA-H variants. Likelihood of cure is high, but recurrence is not infrequent and can occur decades after surgery.

Intra- and postoperative complications using LigaSure™ Small Jaw in patients undergoing thyroidectomy: a register-based study.

PURPOSE: LigaSure™ Small Jaw (LSJ) reduces operation duration and intraoperative blood loss in patients undergoing thyroidectomy. However, the evidence is sparse regarding postoperative complications and among relevant patients subgroups. In a large cohort of patients including relevant patient subgroups, we evaluated intra- and postoperative complications using LSJ. METHODS: Single-centre register-based study evaluating 3346 patients undergoing hemi- or total thyroidectomy. We compared differences in intra- and postoperative complications using LSJ compared to conventional technique. Multivariate analyses were conducted to adjust for potential confounders. RESULTS: Compared to the conventional technique, LSJ was associated with less postoperative drainage (OR 0.4, p = 0.02) and postoperative haemorrhage (OR 0.3, p = 0.02) among patients undergoing hemi- and total thyroidectomy with benign histology, respectively, but with increased risk of postoperative infection [3 (6.4%) vs. 0 (0.0%) patients, p = 0.04] among patients undergoing total thyroidectomy with malignant histology. LSJ was associated with reduced operation duration (- 12.2 min, p < 0.001, - 7.9 min, p < 0.001 and - 13.2 min, p = 0.002) and intraoperative blood loss (- 52.1 ml, p < 0.001, - 13.6 ml, p < 0.001 and - 12.9 ml, p = 0.02) compared to conventional technique among patients undergoing total and hemithyroidectomy with benign histology and hemithyroidectomy with malignant histology, respectively. CONCLUSION: LSJ was associated with a reduced risk of postoperative haemorrhage and less postoperative drainage but increased risk of postoperative infection depending on the type of thyroidectomy and histology of the thyroid gland. LSJ was associated with only a small reduction in operation duration and intraoperative blood loss. TRIAL REGISTRATION: The study was based on data prospectively registered in the Danish national database THYKIR.

Incidental and Non-incidental Papillary Thyroid Microcarcinoma in Denmark 1996-2015: A national study on incidence, outcome and thoughts on active surveillance.

BACKGROUND: Incidental and non-incidental papillary microcarcinomas (PMC) are associated with different outcomes and treatment options may vary. The least favourable outcome is typically seen when carcinoma is suspected prior to surgery. Only a few studies have addressed the prognosis based on the way of detection for PMC, and they have been limited to retrospective single-center studies. We hypothesize that the "way of detection" may predict prognosis. The aim was to calculate the incidence and outcome of PMC based on the way of detection and to identify patients that may be suitable for active surveillance. METHOD: This national cohort study consists of 803 patients diagnosed with PMC in Denmark from 1996 to 2015. Patients were identified from the DATHYRCA database and allocated into groups according to the way of detection leading to surgery: Incidental at surgery (n = 527), non-incidental with symptoms suspected from the index tumor (n = 134) and non-incidental with symptoms suspected from a metastasis (n = 142). RESULTS: Age-standardized incidence rates increased from 0.35 per 100,000 per year in 1996 to 1.19 per 100,000 per year in 2015. A significant rise in incidence was found for both the incidental group and non-incidental group with symptoms suspected from a metastasis. Recurrence free survival was significantly worse for patients with suspicion of metastasis prior to surgery than patient groups without. No difference in mortality was found between groups. CONCLUSION: PMC patients without suspicion of metastasis have the same low risk of recurrence as incidental cases and may be candidates for active surveillance.

Survival and Long-Term Biochemical Cure in Medullary Thyroid Carcinoma in Denmark 1997-2014: A Nationwide Study.

BACKGROUND: Survival of medullary thyroid carcinoma (MTC) subgroups in relation to the general population is poorly described. Data on the factors predicting long-term biochemical cure in MTC patients are nonexistent at a population level. A nationwide retrospective cohort study of MTC in Denmark from 1997 to 2014 was conducted, aiming to detect subgroups with survival similar to that of the general population and to identify prognostic factors for disease-specific survival and long-term biochemical cure. METHODS: The study included 220 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. As a representative sample of the general population, a reference population matched 50:1 to the MTC cohort was used. RESULTS: Patients diagnosed with hereditary MTC by screening (hazard ratio [HR] = 1.5 [confidence interval (CI) 0.5-4.3]), patients without regional metastases (HR = 1.4 [CI 0.9-2.3]), and patients with stage I (HR = 1.3 [CI 0.6-3.1]), stage II (HR = 1.1 [CI 0.6-2.3]), and III (HR = 1.3 [CI 0.4-4.2]) disease had an overall survival similar to the reference population. On multivariate analysis, the presence of distant metastases (HR = 12.3 [CI 6.0-25.0]) predicted worse disease-specific survival, while the absence of regional lymph node metastases (odds ratio = 40.1 [CI 12.0-133.7]) was the only independent prognostic factor for long-term biochemical cure. CONCLUSIONS: Patients with hereditary MTC diagnosed by screening, patients without regional metastases, and patients with stages I, II, and III disease may have similar survival as the general population. The presence of distant metastases predicted worse disease-specific survival, while the absence of regional metastases predicted long-term biochemical cure.

Completeness of RET testing in patients with medullary thyroid carcinoma in Denmark 1997-2013: a nationwide study.

BACKGROUND: The completeness of REarranged during Transfection (RET) testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending RET testing in all MTC patients, improved completeness in Denmark. We conducted a nationwide retrospective cohort study aiming to evaluate the completeness of RET testing in the Danish MTC cohort. Additionally, we aimed to assess the completeness before and after publication of the first Danish guidelines and characterize MTC patients who had not been tested. METHODS: The study included 200 patients identified from the nationwide Danish MTC cohort 1997-2013. To identify RET tested MTC patients before December 31, 2014, the MTC cohort was cross-checked with the nationwide Danish RET cohort 1994-2014. To characterize MTC patients who had not been RET tested, we reviewed their medical records and compared them with MTC patients who had been tested. RESULTS: Completeness of RET testing in the overall MTC cohort was 87% (95% CI: 0.81-0.91; 173/200). In the adjusted MTC cohort, after excluding patients diagnosed with hereditary MTC by screening, completeness was 83% (95% CI: 0.76-0.88; 131/158). Completeness was 88% (95% CI: 0.75-0.95; 42/48) and 81% (95% CI: 0.72-0.88) (89/110) before and after publication of the first Danish guidelines, respectively. Patients not RET tested had a higher median age at diagnosis compared to those RET tested. Median time to death was shorter in those not tested relative to those tested. CONCLUSION: The completeness of RET testing in MTC patients in Denmark seems to be higher than reported in other cohorts. No improvement in completeness was detected after publication of the first Danish guidelines. In addition, data indicate that advanced age and low life expectancy at MTC diagnosis may serve as prognostic indicators to identify patients having a higher likelihood of missing the compulsory RET test.

Replication of newly proposed TNM staging system for medullary thyroid carcinoma: a nationwide study.

A recent study proposed new TNM groupings for better survival discrimination among stage groups for medullary thyroid carcinoma (MTC) and validated these groupings in a population-based cohort in the United States. However, it is unknown how well the groupings perform in populations outside the United States. Consequently, we conducted the first population-based study aiming to evaluate if the recently proposed TNM groupings provide better survival discrimination than the current American Joint Committee on Cancer (AJCC) TNM staging system (seventh and eighth edition) in a nationwide MTC cohort outside the United States. This retrospective cohort study included 191 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. In multivariate analysis, hazard ratios for overall survival under the current AJCC TNM staging system vs the proposed TNM groupings with stage I as reference were 1.32 (95% CI: 0.38-4.57) vs 3.04 (95% CI: 1.38-6.67) for stage II, 2.06 (95% CI: 0.45-9.39) vs 3.59 (95% CI: 1.61-8.03) for stage III and 5.87 (95% CI: 2.02-17.01) vs 59.26 (20.53-171.02) for stage IV. The newly proposed TNM groupings appear to provide better survival discrimination in the nationwide Danish MTC cohort than the current AJCC TNM staging. Adaption of the proposed TNM groupings by the current AJCC TNM staging system may potentially improve accurateness in survival discrimination. However, before such an adaption further population-based studies securing external validity are needed.

Incidence and prevalence of multiple endocrine neoplasia 2A in Denmark 1901-2014: a nationwide study.

BACKGROUND: The incidence and prevalence of multiple endocrine neoplasia 2A (MEN2A) have only been reported once in a nationwide setting. However, it is unclear whether the figures are representative of other populations, as the major component of the syndrome, hereditary medullary thyroid carcinoma (MTC), has been reported as rare in the same country. We conducted a nationwide retrospective cohort study of MEN2A in Denmark from 1901 to 2014, aiming to describe the incidence and prevalence. METHODS: This study included 250 unique MEN2A patients born or resident in Denmark before December 31, 2014. Patients were identified through the Danish REarranged during Transfection (RET) cohort, linkage of MEN2A pedigrees, the Danish MTC cohort, a nationwide collaboration of MEN2 centers, cross-checking of other relevant cohorts, and a systematic literature search. RESULTS: The incidence from 1971 to 2000 was 28 (95% CI: 21-37) per million live births per year. Incidence for the specific mutations or for the overall MEN2A group did not change significantly from 1901 to 2014 (P>0.05). Point prevalence at January 1, 2015, was 24 per million (95% CI: 20-28). CONCLUSION: The incidence and prevalence of MEN2A in Denmark seem higher than those reported in other countries. This is likely explained by the Danish C611Y founder effect. Also, our data indicate no significant change in MEN2A incidence during the last century.

Is serum TSH a biomarker of thyroid carcinoma in patients residing in a mildly iodine-deficient area?

PURPOSE: To investigate the association between the pre-operative serum TSH (s-TSH) level and differentiated thyroid carcinoma (DTC) in a mildly iodine-deficient area. METHODS: Patients undergoing surgery for thyroid nodular disease (TND) were included from three tertiary surgical departments. Data were collected from a national thyroid surgery database (THYKIR) and from patient charts. Individuals with overtly coexisting thyroid disorders were excluded for subgroup analyses. Patients were compared with the Danish background population, employing previous data from DanThyr, a study initiated to monitor the iodine fortification program in Denmark. RESULTS: Nine-hundred ninety-eight patients [cases/controls: 265/733; female/male: 794/204; age (mean ± SD): 51 ± 15 years] were included. S-TSH was significantly higher in the DTC group [median (IQR): 1.3 (0.9-1.9 mIU/L)] compared with the benign TND group [0.9 (0.6-1.5 mIU/L)] (p < 0.0001). The median s-TSH in the background population was similar to that found among DTC patients (p = 1.00), but markedly higher than the s-TSH level in the benign TND group (p < 0.0001). There was no association between s-TSH and DTC disease stage (p = 0.08-0.87). CONCLUSIONS: s-TSH was significantly higher in patients with DTC than in those with benign TND. However, this difference can be explained by abnormally lower s-TSH level in the latter group, probably caused by subtle nodular functional autonomy. Due to the huge overlap and the small difference in median s-TSH between patients with benign and malignant TND, s-TSH is not suitable as a biomarker of DTC in a clinical setting.

Incidence and prevalence of sporadic and hereditary MTC in Denmark 1960-2014: a nationwide study.

Recent studies have shown a significant increase in the temporal trend of medullary thyroid carcinoma (MTC) incidence. However, it remains unknown to which extent sporadic medullary thyroid carcinoma (SMTC) and hereditary MTC (HMTC) affect the MTC incidence over time. We conducted a nationwide retrospective study using previously described RET and MTC cohorts combined with review of medical records, pedigree comparison and relevant nationwide registries. The study included 474 MTC patients diagnosed in Denmark between 1960 and 2014. In the nationwide period from 1997 to 2014, we recorded a mean age-standardized incidence of all MTC, SMTC and HMTC of 0.19, 0.13 and 0.06 per 100,000 per year, respectively. The average annual percentage change in incidence for all MTC, SMTC and HMTC were 1.0 (P = 0.542), 2.8 (P = 0.125) and -3.1 (P = 0.324), respectively. The corresponding figures for point prevalence at January 1, 2015 were 3.8, 2.5 and 1.3 per 100,000, respectively. The average annual percentage change in prevalence from 1998 to 2015 for all MTC, SMTC and HMTC was 2.8 (P < 0.001), 3.8 (P < 0.001) and 1.5 (P = 0.010), respectively. We found no significant change in the incidence of all MTC, SMTC and HMTC possibly due to our small sample size. However, due to an increasing trend in the incidence of all MTC and opposing trends of SMTC (increasing) and HMTC (decreasing) incidence, it seems plausible that an increase for all MTC seen by others may be driven by the SMTC group rather than the HMTC group.

Anaplastic thyroid carcinoma in Denmark 1996-2012: A national prospective study of 219 patients.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the least common but most malignant thyroid cancer. We aimed to examine the characteristics as well as evaluate the incidence, prognostic factors, and if introduction of a fast track cancer program might influence survival in a cohort of ATC patients. METHODS: A cohort study based on prospective data from the national Danish thyroid cancer database DATHYRCA and the national Danish Pathology Register including 219 patients diagnosed from 1996 to 2012, whom were followed until death or through September 2014. RESULTS: We found the median age in the 7th decade, the majority of patients being women presenting with a growing mass at the neck, diagnosed with stage T4b disease. At diagnosis, 56% of the patients had lymph node metastasis and 38% distant metastasis. We observed one- and five-year survival of 20.7% and 11.0%, respectively. Both univariate and multivariate analyses showed age (above 73.6 years), respiratory impairment, T4b stage, and distant metastasis at diagnosis to be significant prognostic factors. Further, introduction of a national fast track cancer program increased survival nearly two-fold. CONCLUSION: As new information, our study adds "respiratory impairment at diagnosis" and "introduction of a national fast track cancer program" to the list of already established prognostic indicators for ATC.

Thyroid malignancy markers on sonography are common in patients with benign thyroid disease and previous iodine deficiency.

OBJECTIVES: The purpose of this study was to evaluate the characteristics of benign thyroid nodules on sonography and ultrasound elastography in a population exposed to iodine deficiency. METHODS: We conducted a prospective systematic evaluation of preoperative thyroid sonography and elastography in patients assigned for surgical excision of benign thyroid nodules. Two experienced sonographers performed all sonographic and elastographic examinations. Thyroid nodules were evaluated by 7 generally accepted sonographic malignancy risk markers and assigned an elasticity score on elastography. The final diagnosis of a benign thyroid nodule was based on histopathologic analysis of resected thyroid gland tissue. RESULTS: We evaluated 232 thyroid nodules in 105 patients (86 women and 19 men). In total, 57% of the examined nodules had 1 or 2 malignancy risk markers present, and 24% did not have any markers present. A solid nodule larger than 15 mm was the most common malignancy risk marker observed (63%), followed by low elasticity (33%), microcalcifications (26%), and hypoechogenicity (15%). In an analysis stratified according to the number of nodules (solitary versus multiple), low elasticity was described more frequently in solitary nodules (61.9% versus 30.4%; P= .004). A large nodular volume was a predictor (P < .05) of microcalcifications and intranodular vascularization, whereas an absent halo sign and a solid nodule were found less frequently in nodules with larger volumes. CONCLUSIONS: Our results show that routine preoperative malignancy risk evaluation of presumably benign thyroid nodules is of little value when performed on patients exposed to iodine deficiency.

Papillary thyroid carcinoma in Denmark, 1996-2008: outcome and evaluation of established prognostic scoring systems in a prospective national cohort.

BACKGROUND: Regional as well as national series show an increasing incidence of thyroid cancer largely small size papillary thyroid carcinoma (PTC). Prognostic scoring systems have been developed, but these do not take into account the rapidly changing case mix, and adjustments may be required. The purposes of this study were to evaluate treatment outcomes and to analyze the value of older prognostic scoring systems tested on a relatively new, unselected national cohort of PTC patients. METHODS: This was a national prospective cohort study conducted in Denmark, which has a population of 5.5 million. RESULTS: A total of 1350 patients were diagnosed with PTC during 1996-2008, and the median follow-up time was 7.9 years. The 10-year recurrence-free survival rate was 90.2%, and the 10-year crude and cause-specific survival (CSS) rates were 83.7% and 93.8% respectively. By multivariate Cox regression, it was possible to confirm age, metastases (distant and nodal), extrathyroidal extension, and tumor size as predictors of mortality, whereas only nodal metastases, extrathyroidal extension, and tumor size were predictors of recurrence. In analyses of older prognostic scoring systems, a significant correlation between the risk group ranks was found for survival as well as recurrence. The c-index for CSS was highest for MACIS (0.92) and lowest for AMES (0.80). In the TNM, MACIS, and EORTC systems, most patients were classified as stage 1, and for these patients, the 10-year CSS rate was approximately 99.5%, confirming the generally excellent survival. CONCLUSION: This national study provides further evidence that a favorable prognosis is to be expected for patients diagnosed with PTC. Also, it was possible to confirm age, metastases, extrathyroidal extension, and tumor size as predictors of mortality, whereas only nodal metastases, extrathyroidal extension, and tumor size were predictors of recurrence. All the scoring systems evaluated were able to produce a highly significant risk group stratification, showing that in spite of the changes in the case mix of PTC, these systems are still applicable, and in fact contain valuable prognostic information useable for treatment planning.

Completeness and validity in a national clinical thyroid cancer database: DATHYRCA.

BACKGROUND: Although a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid cancer database: DATHYRCA. STUDY DESIGN AND SETTING: National prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference. RESULT: The database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration was around or above 90% in most instances. Perfect agreement on the diagnosis of thyroid carcinoma was found, both inter- and intra-observer, and κ values of selected variables showed overall good to excellent agreement. CONCLUSION: In a setup with public health insurance, personal identity numbers and extended governmental databases, it is possible to establish national clinical cancer databases with a satisfactory completeness and validity. The DATHYRCA database is considered reliable in terms of describing thyroid carcinoma at a national level.

Risk factors for recurrent nerve palsy after thyroid surgery: a national study of patients treated at Danish departments of ENT Head and Neck Surgery.

Recurrent laryngeal nerve (RLN) injury is a well-known and serious complication to thyroid surgery. The objective was to estimate the frequency of post-thyroidectomy RLN palsy and to identify possible risk factors. Based on the Danish national thyroid surgery database, 6,859 patients treated with thyroid surgery from 1 January 2001 to the 31 December 2008 at the Danish departments of ENT-HNS were analyzed. Unilateral RLN palsy was found in 2.1 % and bilateral in 0.1 %. In benign histology, RLN palsies were registered in 1.3 %. Malignant histology and accordingly neck dissection were the most predominant risk factors with a relative risk (RR) of 5.4 and 5.8, respectively. In benign cases previous performed thyroid surgery had a RR of 10.4. High volume departments with more than 150 thyroid procedures per year seem to perform significantly better. Malignant histology, neck dissection and previous performed thyroid surgery are the strongest predictors for RLN palsy and patient information should be given accordingly. Incomplete resections should be reserved for isthmectomy only. Centralization of thyroid surgery in larger units might improve quality.

Papillary thyroid microcarcinoma in Denmark 1996-2008: a national study of epidemiology and clinical significance.

BACKGROUND: With an observed general rise in papillary thyroid carcinoma incidence, papillary microcarcinoma (PMC) is accordingly found more frequently and often incidentally by histological examination of surgical specimens from presumed benign thyroid disease. Only a few studies have specifically addressed the prognosis of incidentally found PMC, and they have been limited to retrospective single-center studies. METHODS: This was a national, unselected, prospective cohort study of 406 papillary thyroid microcarcinoma patients diagnosed in Denmark from 1996 to 2008. OBJECTIVE: The aim of this study was to evaluate incidence, outcome, and extent of necessary treatment, with special attention given to incidentally detected PMC. RESULTS: Age-standardized ratios were found to increase from 0.35 per 100,000 per year in 1996 to 0.74 per 100,000 per year in 2008. A total of 240 out of 406 cases were found incidentally, and a significant rise in incidence was only found for the incidental cases. Median follow-up was 7.6 years for the incidental cases, and in this time span, five cases of recurrence and no deaths from thyroid cancer occurred. The five-year recurrence-free survival was 98.1%, and only occurrence of lymph-node metastasis was found to affect the recurrence rate. A total of 160 incidental cases were initially treated with lobectomy, and the incidence of recurrence was not significantly different in the cases receiving completion thyroidectomy. CONCLUSION: The rising incidence of PMC in Denmark is explained by incidental cases. When the carcinoma is not the index tumor for surgery, this study implies that completion thyroidectomy does not improve prognosis.

Papillary thyroid carcinoma in Denmark 1996-2008: an investigation of changes in incidence.

BACKGROUND: A rise in the incidence of thyroid cancer has been reported in several countries, and the increase is only seen in the papillary type. Increased detection due to higher resolution ultrasound and fine needle aspiration has been proposed as the explanation, recent registry studies however question this assumption. METHODS: National, unselected, prospective cohort study of 1350 papillary thyroid cancer patients in Denmark from 1996 to 2008. OBJECTIVE: To analyze changes in incidence by time and to identify factors which might influence detection rate. RESULTS: A rise in incidence is seen with age standardized ratios increasing from 1.43 per 100.000 per year in 1996 to 2.16 per 100.000 per year in 2008. The median age at presentation was 46 years and median tumor size was 18 mm. Male/female ratio was 1/2.9. By dichotomizing the material in a time period before and after the 30th of June 2001, no significant change in the proportion of diagnosed tumors smaller than 1 or 2 cm was found, and 42.8% of the rise in incidence was explained by tumors larger than 2 cm. No significant change in diagnostic use of ultrasound or fine needle aspiration was found, and a significant change toward more extensive thyroid surgery could not be confirmed. CONCLUSION: This study shows a significant rise in incidence of papillary thyroid carcinoma in Denmark from 1996 to 2008, which is not explained by increased use of preoperative diagnostic modalities. Other reasons need to be considered.

Post-thyroidectomy hemorrhage: a national study of patients treated at the Danish departments of ENT Head and Neck Surgery.

As bleeding in the neck region is a potentially life-threatening complication, we found it imperative to concretize the frequency and to identify possible reasons for this complication. A national database of all thyroid surgery performed inside the specialty of ENT Head and Neck Surgery (THYKIR) was established in January 2001. This nationwide cohort study represents 5,490 patients included until December 2007. Overall hemorrhage frequency was 4.2% with a wide variation among departments. Multiple regression analysis identified age, male gender, malignant histology and extent of surgery as independent risk factors for hemorrhage. Increased hospital stay and infection rates were found in patients treated with drainage. The median time for onset of postoperative hemorrhage was 3 h (range 0-105). Compared with international literature our incidence of post-thyroidectomy hemorrhage is relatively high. Improvement might be reached by the exchange of experience between departments with focus on adequate surgical technique and careful hemostasis.

Papillary microcarcinoma of the thyroid gland: is the immunohistochemical expression of cyclin D1 or galectin-3 in primary tumour an indicator of metastatic disease?

INTRODUCTION: Papillary microcarcinomas (PMC) of the thyroid gland are defined according to The WHO Committee as papillary carcinomas measuring 10 mm or less in diameter. A large proportion of these tumours are found coincidentally in the treatment of symptomatic goitre and most cases follow an indolent course with an excellent prognosis. However, a more aggressive behaviour with regional and distant metastases does occur. The aim of this study was to evaluate if the immunohistochemical markers cyclin D1 or galectin-3 might indicate the presence of metastatic disease in patients with PMC at the time of diagnosis. MATERIAL AND METHODS: From the 1(st) of January 1996 to 31(st) of December 2002 a total of 169 PMC patients were diagnosed and registered in the national Danish thyroid cancer database DATHYRCA and 131 of these were eligible for the study. Forty-three (33%) had histologically verified regional or distant metastases. Slides were cut from the primary tumour and immunostaining and quantification was subsequently performed. RESULTS: The percentage of positive cells was examined for patients with and without metastases. For cyclin D1 the median values were 31% (range: 0-59) and 21% (range: 0-75), respectively, showing a statistically significant difference (p=0.02). For galectin-3 the medians were 87% (range: 6-96) and 85% (range: 0-99) and no significant difference was found. CONCLUSION: Cyclin D1 showed significantly higher median expression in patients with metastases compared to those without, indicating a correlation to tumour aggressiveness. However, both groups showed large variation in expression, which disqualify the marker as a discriminator for the detection of metastases. Galectin-3 was without any significant correlation to the presence of metastases from PMC.