Importance of tumour size in papillary and follicular thyroid cancer.

BACKGROUND: The most controversial change in the new pathological tumour node metastasis (pTNM) classification of thyroid tumours is the extension of the pT1 classification to include tumours up to 20 mm. METHODS: Four hundred and three patients with pT1 or pT2 differentiated thyroid carcinomas were divided into three groups according to tumour diameter (group 1, 10 mm or less; group 2, 11-20 mm; group 3, 21-40 mm). They were analysed retrospectively with respect to carcinoma-specific and disease-free survival. RESULTS: No patient in group 1 died from papillary thyroid carcinoma, compared with three patients in group 2 and six in group 3. There was a statistically significant difference in carcinoma-specific survival between groups 1 and 2 (P = 0.033). Two patients in group 1, six in group 2 and eight in group 3 developed recurrence. The difference in disease-free survival between groups 1 and 2 was significant (P = 0.025). One patient in group 1, three in group 2 and four in group 3 died from follicular thyroid carcinoma, but there were no significant differences in survival between the three groups. CONCLUSION: Extension of the pT1 classification to cover all tumours up to 20 mm does not appear to be justified for papillary thyroid carcinoma.

Cytotoxic activity of camptothecin and paclitaxel in newly established continuous human medullary thyroid carcinoma cell lines.

At the time of diagnosis, more than one quarter of patients with medullary thyroid carcinoma (MTC) has distant metastases. Only few of these patients can be cured by surgery. Standard chemotherapy is characterized by low response rates and short response time. The establishment of eight human MTC cell lines provides a new basis for in vitro investigation of cytotoxic drugs. Camptothecin (CPT) and paclitaxel, which never have been investigated in the treatment of MTC, were tested for their cytotoxic profile in comparison with the clinically ineffective dacarbazine. Eight MTC cell lines were established from seven patients with MTC. IC(50) values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1). IC(50) values were 3.5 +/- 1.2 nmol/liter for CPT and 8.2 +/- 1.9 nmol/liter for paclitaxel. Dacarbazine showed no reduction of cell proliferation at concentrations 10-fold higher than clinically achievable. Given peak plasma concentrations of 65 +/- 20 nmol/liter for CPT and 1 micro mol/liter for paclitaxel, these promising in vitro results provide a basis for the performance of clinical trials in patients with advanced MTC.

Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region.

Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodine-replete endemic goiter region. Six hundred and three patients with DTC treated within a 35-year-period were retrospectively analyzed with respect to carcinoma-specific survival. Prognostic factors were tested for their significance using univariate and multivariate analysis. The histological type (PTC versus FTC) was found to be a highly significant factor - carcinoma-specific survival both in univariate (P<0.001) and multivariate analyses (P=0.003) was significantly different. Univariate analysis revealed patients' age, extra-thyroid tumor spread, lymph node and distant metastases, increasing tumor size, and the tall cell variant to be significant prognostic factors for PTC patients. Age > or =45 years, positive lymph nodes and increasing tumor size were confirmed as independent prognostic factors. Univariate analysis of FTC patients revealed age at presentation, gender, extrathyroidal tumor spread, lymph node and distant metastases, increasing tumor size, multifocality, widely invasive tumor growth and oxyphilic variant to be factors bearing prognostic significance. The presence of distant metastases and increasing tumor size could be identified as independent prognostic factors for FTC patients. This study shows distinctive differences in prognostic factors of PTC and FTC: independent factors predicting poor prognosis are age > or =45 years, positive lymph nodes and increasing tumor size for PTC, and distant metastases and increasing tumor size for FTC. PTC and FTC patients should be analyzed and reported separately.

Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism.

BACKGROUND: Nesidioblastosis in adults has been reintroduced into the differential diagnosis of organic hyperinsulinism by the description of 'noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS)'. MATERIALS AND METHODS: Pathologic specimens of all adult patients (n = 66) operated on for organic hyperinsulinism were re-examined. Five patients fulfilled the histomorphological criteria of nesidioblastosis. Retrospective review of clinical presentation, results of 72-h fasts, intravenous tolbutamide tolerance tests, pre- and intraoperative localization studies and surgical therapy was performed. RESULTS: In contrast to NIPHS, fasting tests became positive after 8-14 h. Tolbutamide tests were positive and preoperative imaging showed negative results in all patients. At first operation distal pancreatic resections were performed in three patients, resection of the pancreatic body in one patient and biopsy of the pancreatic tail in one patient. Two of three patients with recurrent disease had to be reoperated. One patient showed a coexistence of nesidioblastosis and multiple small insulinomas and is part of a kindred with autosomal dominantly inherited 'familial islet-cell adenomatosis'. CONCLUSIONS: Surgical exploration is indicated only after thorough biochemical diagnosis. An aggressive strategy for preoperative localization including selective arterial calcium stimulation testing seems justified. There may be a combination of nesidioblastosis and islet cell tumours. A link between beta-cell hyperplasia and progression to insulinoma based on not yet known genetic causes can be suspected.

Minimally invasive open parathyroidectomy in an endemic goiter area: a prospective study.

HYPOTHESIS: Single-gland disease identified by preoperative localization studies in combination with rapid intraoperative parathyroid hormone monitoring seems to allow a limited exploration of the neck in sporadic primary hyperparathyroidism. Minimally invasive open parathyroidectomy by lateral approach (oMIP) in sporadic primary hyperparathyroidism seems feasible in an endemic goiter region. DESIGN: One hundred consecutive patients with sporadic primary hyperparathyroidism underwent preoperative double-phase technetium Tc 99m sestamibi scanning with single-photon emission computed tomography and high-resolution ultrasonography with color Doppler imaging of the cervical region. All patients were operated on with the use of quick parathyroid hormone assay to confirm the surgical success "on-line." Patients with localized single-gland disease, irrespective of additional ipsilateral thyroid disease requiring surgery, were selected for oMIP. Success of the preoperative localization studies, postoperative (at least 6 months) serum calcium levels, and operating time were analyzed. SETTING: University hospital, section of endocrine surgery. RESULTS: Of 100 patients, 83 (83%) were considered suitable for oMIP. In 69 patients, oMIP was finished successfully. Nine of these had had previous neck surgery, and another 24 underwent additional ipsilateral thyroid resection. Permanent normocalcemia was achieved in 67 (97.1%) of 69 patients and 98 (98%) of 100 patients. CONCLUSION: The oMIP in combination with quick parathyroid hormone assay may become the treatment of choice for sporadic primary hyperparathyroidism in an endemic goiter region in centers with high experience in thyroid and parathyroid surgery. It allows treatment of concomitant ipsilateral thyroid disease and is feasible in reoperations.

Advanced insular thyroid carcinoma in a fourteen-year-old girl: twenty-four years of follow-up.

Insular thyroid carcinoma has become a separate entity among thyroid malignancies. It is regarded as intermediate in aggressiveness between well-differentiated and anaplastic thyroid carcinomas. Reports on the clinical course of children with insular thyroid carcinoma are rare. We report the case of a 14-year-old girl who was admitted to our thyroid outpatient ward in 1975 with a scintigraphic cold thyroid nodule and multiple enlarged cervical lymph nodes. Chest radiography showed metastases in both lungs. After total thyroidectomy and, central and modified unilateral radical neck dissection, the girl was given a dose of 80 mCi 131I. Posttherapeutic scan demonstrated diffuse tracer uptake in both lungs. A second dose of 200 mCi 131I was administered 4 months later and another dose of 150 mCi 131I in July 1976. Subsequently, whole-body scans showed inconspicuous tracer distribution and chest x-rays were normal. The patient was treated with levothyroxine and followed until 1982, when she left Vienna. In 1999, the patient was contacted for reexamination. She has been well and had had two healthy children. The patient was taking 150 microg levothyroxine daily; she had a normal TSH value and her thyroglubulin was 0.3 ng/mL. Chest radiography and sonography of the neck showed no pathological findings. The paraffin sections of the patient's tumor were reexamined in 1999 and demonstrated the histologic characteristics of a poorly differentiated insular thyroid carcinoma (pT4a, pN1a, M1). These findings demonstrate that even in advanced stages, insular thyroid carcinoma treatment can be successful.

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."

[The value of preoperative localization studies in primary hyperparathyroidism]. / Der Stellenwert präoperativer Lokalisationsmethoden beim primären Hyperparathyreoidismus.

Bilateral neck exploration is the standard procedure in primary hyperparathyroidism. Using a bilateral approach, preoperative localization studies are not mandatory. A localized single gland disease is the basis for a minimally invasive procedure. Therefore preoperative localization techniques play an important role in planning (minimally invasive) first time exploration for primary hyperparathyroidism. The combination of (99 m)Tc-SestaMIBI scintigraphy with ultrasound allows correct localization of the parathyroid adenoma in 86 % of all single gland diseases. Multiple gland disease could be predicted in isolated cases only. Computerized tomography and magnetic resonance imaging could not improve the results. Surgery for persistent or recurrent hyperparathyroidism should only be performed after positive localization studies.

Anaplastic (undifferentiated) thyroid carcinoma (ATC). A retrospective analysis.

BACKGROUND: Old age, reduced general condition and far advanced tumor stage associated with poor prognosis induced the belief that, apart from verifying the diagnosis of anaplastic thyroid carcinoma (ATC) by biopsy, no additional surgery would be justified. However, in some cases, an ultraradical approach was recommended in order to improve the quality of life and survival. METHODS: These are the results of a retrospective analysis involving 120 patients subjected to restricted radical surgery (excising as much as possible of the tumor and local metastases, foregoing ultraradical removal of vital organs such as esophagus, larynx and trachea). RESULTS: Irrespective of the surgical approach used, 6+/-2% of the patients were alive after 5 years (median survival time: 3.1 months). Patients without tumor residues (R0-resections; extending to soft tissue only; Kaplan-Meier estimate - cumulative survival 15+/-5%) had a significantly better prognosis than patients with tumor residues (R1/R2-resections; no patient survived 5 years; P<0.001). Tumor morphology (spindle cells, giant cells, mixed cells) or differentiated parts of the tumor as well as lymph-node involvement had no statistically significant impact on the prognosis. CONCLUSIONS: In ATC, the objective should be to remove as much of the carcinoma as possible (in the ideal case, a thyroidectomy); if lymph nodes are affected, neck dissection should be the goal, if possible (restricted radical approach, improving quality of life). Ultraradical surgery to include segmental resection of larynx, trachea or esophagus do not seem to be indicated, as prolonged survival is questionable and quality of life is certainly diminished.

[The value of fine-needle aspiration biopsy (FNAB) in the differential diagnosis of the "cold" thyroid nodule]. / Die Wertigkeit der Feinnadelaspirationsbiopsie (FNAB) in der Differential-diagnose des "kalten" Knotens.

INTRODUCTION: According to the literature, fine needle aspiration biopsy (FNAB) should be the first line test to assess thyroid nodules. The value of fine needle aspiration biopsy in the differential diagnosis of "cold" thyroid nodules is discussed. METHODS: 105 consecutive patients undergoing surgery for solitary cold nodule or a dominant cold nodule in multinodular goiter and having a preoperative fine needle aspiration biopsy, are analysed. RESULTS: The cytologic results were benign in 48 cases, malignant in 8 cases and indeterminate (follicular neoplasia) in 29. Twenty biopsies were inadequate. Excluding inadequate and indeterminate biopsy results and calculating microcarcinomas (as incidental findings) as "true negative", sensitivity was 56%, specify 94% and accuracy 88%. There was a negative predictive value of 92% and a positive predictive value of 63%. CONCLUSIONS: Fine needle aspiration biopsy is helpful as an additional test. The indication for surgery for a "cold" thyroid nodule must be established in conjunction with clinical findings and other investigation procedures.