Høie J

Distant metastases in papillary thyroid cancer. A review of 91 patients.

Of 731 patients with papillary thyroid cancer, 91 had metastases outside regional lymph nodes. The most common site was intrathoracic, occurring in 73 of the 91 patients. Miliary, micronodular pulmonary metastases, with iodine 131 (I‐131) uptake and “curable” by I‐131 treatment were encountered in seven patients. It has not been established whether this was a transient stage in additional patients. In 38 patients rounded, macrohodular pulmonary metastases were found. Another 21 patients had unilateral pulmonary infiltration and mediastinal enlargement. Pulmonary infiltrations may be hematogenic, or may possibly occur via regional, mediastinal lymph nodes. Mortality within 1 year of the diagnosis of distant metastases exceeded 50%. Occurrence of distant metastases showed a slight but highly significant association with male sex, advanced age, and advanced local tumor stage. Better prognostic determinants are, however, required if adequate treatment of the individual patient with papillary thyroid cancer is to be achieved.

Systemic relapse of patients with osteogenic sarcoma. Prognostic factors for long term survival.

Background. A retrospective study of long term outcome after the development of metastases from osteosarcoma was performed, with emphasis on the impact of different treatment strategies and the identification of prognostic factors.

Histology of tumor residuals following chemotherapy in patients with advanced nonseminomatous testicular cancer

A total of 111 patients with advanced nonseminomatous testicular cancer underwent cisplatin-based combination chemotherapy, followed by surgical removal of residual masses in 101. Surgery included retroperitoneal lymph node dissection in 92 patients, thoracotomy in 19 and hepatic resection in 1 (11 patients underwent 2 operations). Complete necrosis and/or fibrosis was found in 52 operative specimens, mature teratoma in 37 and vital malignant tumor in 12. Of the 11 patients who underwent 2 operations 4 had complete necrosis and/or fibrosis in both histological specimens. After a median observation of 55 months 83 of 89 patients with complete necrosis and/or fibrosis or mature teratoma were without evidence of disease. Only 7 of 12 patients with vital malignant tumor in the operative specimen survived without evidence of disease. Relapses were observed in 16 patients, 4 of them in the retroperitoneal space. Of the 16 relapses 5 were in 12 patients with residual vital malignant tumor, 5 in 37 patients with post-chemotherapy mature teratoma and 4 in 52 patients with complete necrosis and/or fibrosis after chemotherapy. Two patients with recurrence did not undergo an operation. In patients in whom post-chemotherapy retroperitoneal lymph node dissection is considered complete necrosis and/or fibrosis can be predicted by the combination of several factors, including absence of teratomatous elements in the testicular tumor, complete response on post-chemotherapy computerized tomography, and normal alpha-fetoprotein and human chorionic gonadotropin levels after chemotherapy (sensitivity 83%, specificity 76% and correctly predicted 79%). With the knowledge of these factors it seems possible to omit post-chemotherapy retroperitoneal lymph node dissection in approximately 20% of the patients with advanced metastatic nonseminomatous testicular cancer with initial retroperitoneal tumors.

Pattern of expression of intermediate cytokeratin filaments in the thyroid gland: an immunohistochemical study of simple and stratified epithelial-type cytokeratins

The expression of simple and stratified epithelial-type cytokeratin (CK) intermediate filaments was evaluated by immunohistochemistry in a series of 41 papillary carcinomas, 10 follicular carcinomas, 2 poorly differentiated carcinomas and 34 specimens of normal thyroid parenchyma and lymphocytic thyroiditis. The aim of the study was to establish the CK profile of normal thyroid and thyroid carcinomas in order to clarify the putative application of CK immunostaining in diagnostic surgical pathology, and to evaluate whether the process of neoplastic transformation and tumour progression in the thyroid may be associated with any particular change in CK expression. Normal thyroid strongly expressed simple epithelial-type CKs 7 and 18 and, to a lesser degree, CKs 8 and 19, but did not express stratified epithelial-type CKs. The same pattern was found in lymphocytic thyroiditis, though the CK 19 immunoreactivity was stronger in these lesions than in the normal thyroid. Papillary and follicular thyroid carcinomas shared the expression of simple epithelial-type CKs 7, 8, 18 and 19. Immunoreactivity for CK 19 was frequently stronger and more widely distributed within each particular tumour in papillary than in follicular carcinomas, but it could also be detected, at least focally, in every follicular carcinoma. Strong expression of CK 19 highlighted small foci of papillary carcinoma not easily identifiable by conventional histological examination. Stratified epithelial-type CKs 5/6 and 13 were detected in a high percentage of papillary carcinomas, in contrast to their absence in follicular carcinomas and normal thyroid. The CK pattern was similar in primary and metastatic papillary carcinomas. We conclude that papillary carcinoma of the thyroid presents a distinct CK profile that may be used for diagnostic purposes.

Post-Chemotherapy Tumor Residuals in Patients with Advanced Nonseminomatous Testicular Cancer. Is it Necessary to Resect All Residual Masses?

A total of 15 patients with advanced nonseminomatous testicular cancer underwent 2 sequential operations (4 in 1 patient) to remove residual masses after cisplatin-based combination chemotherapy. All patients had normal human chorionic gonadotropin and alpha-fetoprotein levels but persistent radiographic masses after chemotherapy. The operations included retroperitoneal lymph node dissection in 13 patients, thoracotomy in 15, hepatic resection in 3 and craniotomy in 1. Histological comparison of the specimens resected during post-chemotherapy operations 1 and 2 demonstrated different patterns in 7 of 15 patients. Of these 7 patients 4 had less favorable pathological features in the specimen removed during the second procedure. Residual malignant tumor or mature teratoma was found in at least 1 site in 12 of the 15 patients and only 3 had complete necrosis or fibrosis in both specimens examined. These data indicate the favorable impact of excising all post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. However, in patients with no teratomatous elements in the testicular tumor and complete necrosis or fibrosis in the initial post-chemotherapy operation specimen the probability of complete necrosis or fibrosis in remaining tumors appears to be high.

Sarcoid reaction of hilar and paratracheal lymph nodes in patients treated for testicular cancer

Bilateral hilar lymph node enlargement developed in four patients 1 to 8 years after successful radiotherapy for testicular cancer Stage I was performed. Two had additional paratracheal involvement. Biopsy showed sarcoid reaction in all four cases. An increased frequency of sarcoid reaction is assumed in patients treated for testicular cancer. The pathogenesis remains unknown. The clinical and radiologic findings should not be misinterpreted as showing recurrent malignant disease. In an otherwise disease‐free patient in whom mediastinal lymph node enlargement develops, a biopsy should always be performed.

Extremity and non-extremity high-grade osteosarcoma -- the Norwegian Radium Hospital experience during the modern chemotherapy era.

Of 103 patients with high-grade osteosarcoma, 27% had tumours localized outside the extremities. Non-extremity patients were significantly older at diagnosis than patients with extremity tumours (median 38 vs. 17 years). More than 90% of patients with extremity tumours received adequate treatment (aggressive chemotherapy plus at least marginal surgery), compared with only 25% of patients with non-extremity tumours. Failure of adequate treatment was due to inoperable tumour, intralesional surgery and age preventing aggressive chemotherapy. There was a highly significant difference in both local tumour control and overall survival, both favouring patients with extremity tumours. Within the extremity tumour group, patients who were treated in prospective multicentre trials had a significantly better outcome than non-trial patients. Our results show that the fraction of patients with high-grade tumours that fall outside trials designed for classical osteosarcoma may be larger than is usually acknowledged, and that the results reported for the classical group are by no means representative of the whole patient population. Improved and new treatment approaches are needed for patients with non-extremity tumours, particularly in the older age groups.

Salvage treatment in male patients with germ cell tumours

The outcome of salvage treatment was reviewed in 55 patients relapsing during or after their primary chemotherapy for advanced malignant germ cell tumours. Fifty-two patients had been given cisplatin-based chemotherapy as their primary treatment, whereas three patients had received carboplatin-based chemotherapy. The median time to relapse was 2 months (range: 0-96 months) from discontinuation of the primary treatment. Two patients underwent radical surgery only, and one patient had radiotherapy to a brain metastasis as his only curatively intended salvage treatment. Six patients did not receive any treatment for their recurrent malignancy (refusal, terminal condition) except for purely palliative measures. The disease-free survival for the total group was 27% at 5 years. Complete response to primary treatment lasting for > or = 6 months was the only parameter which significantly predicted a favourable outcome (45% 5 year disease-free survival in 12 eligible patients).

Treatment and outcome of patients with extragonadal germ cell tumours - The Norwegian Radium Hospital's experience 1979-94

This report reviews 48 patients who from 1979 to 1994 were treated at the Norwegian Radium Hospital for newly diagnosed noncerebral extragonadal malignant germ cell tumour (EGGCT). Based on histology and/or serum tumour markers, 12 patients had a seminoma and 36 a non-seminoma. At diagnosis, 33 and 15 patients were classified as having abdominal and mediastinal EGGCT respectively. At the time of diagnosis 13 patients, all with non-seminomatous tumours, had metastases to bone, liver or brain. One patient with abdominal seminoma was cured by radiotherapy alone, whereas cisplatin-based chemotherapy (with or without surgery) was planned in the 47 remaining patients. Twenty-seven out of 42 patients receiving four or more chemotherapy cycles were rendered tumour free by induction chemotherapy, including 5 of the 13 patients with extralymphatic non-pulmonal disease. An additional tumour-free patient died of septicaemia after only two cycles of chemotherapy. Late relapses (after > 2 years) were observed in three patients, and a testicular primary was diagnosed during follow-up in three cases. Seven patients died of treatment-related complications, five of these because of neutropenic septicaemia. The median age of these patients was 52 years compared with 35 years in the remaining 41 patients (P < 0.05). The 5-year overall survival for all 48 patients was 60% (95% CI 46-74%) [cancer-specific 5-year survival 71% (95% CI 50-92%)]. EGGCT is a potentially curable disease, even in patients with very advanced disease. Special attention should, however, be devoted to patients above the age of 40 years because of an increased risk of treatment-related side-effects. Late relapses and the subsequent development of testicular tumours indicate the need for long-term follow-up.

Immunohistochemical detection of nm23/NDP kinase and cathepsin D in medullary carcinomas of the thyroid gland

Reduced expression of nm23/NDP kinase and increased expression of cathepsin D seem to be correlated with the high metastatic potential in a variety of malignancies. The expression of nm23/NDP kinase and that of cathepsin D have been evaluated by means of an immunohistochemical technique in paraffin-embedded tissues from 44 primary medullary carcinomas of the thyroid gland (MCT) and from the corresponding lymph node metastases in 32 of these cases. In addition, lymph node metastases from 4 cases were studied. We found that 36 of 44 (82%) primary and 26 of 36 (72%) lymph node metastatic MCT were nm23/NDP kinase positive, whereas 14 of the 44 (32%) primary and 17 of the 36 (47%) lymph node metastatic MCT were cathepsin D positive. We found no indication that the nm23/NDP kinase level has any prognostic significance in MCT. The cathepsin D level is close to being prognostically significant in this study, and we cannot exclude the possibility that it could be of prognostic value. However, it seems to be quite weak, and therefore of little use in a clinical situation.