Thymic anaplastic carcinoma successfully controlled by combination chemotherapy

Thymic carcinomas are rare tumors for which the main treatments have been surgery, radiotherapy, or both. However, the role of chemotherapy is less well-defined. Here, we report a case of advanced thymic anaplastic carcinoma which was suspected to be the primary lesion, yet was successfully controlled despite brain metastases by EACUM combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, 5-FU, and methtrexate. Pathohistological findings on metastatic lesions of the right supracuravicular lymph nodes led to a diagnosis of anaplastic carcinoma. We could not give a diagnosis of thymic carcinoma because the biopsy specimen had not been taken from the thymus. There was no evidence of a primary neoplastic tumor other than thymoma. The patient was still alive 6 years and 9 months after the start of anticancer treatment and was working normally. The findings from this case should be of value to the establishment of effective combination chemotherapy regimens for advanced thymic carcinoma.     

Treatment strategies for lung cancer brain metastases]

Forty-one patients suffered initial relapses with brain metastasis after surgery for non-small lung cancer at our hospital between 1978 and 1995. These patients were a total of 8.4% of all cases of surgical removal, and had an average relapse period of 8.6 months +/- 8.0 months after surgery on the primary lesions. Of these, surgical removal of metastasized lesions was performed on 18 patients (43%), in which the 5-year post-operative survival rate was 35.7%, and the median survival time was good at 28 months. It was found that the survival period was significantly extended in the group whose relapse period was less than one year after surgery on the primary lesions, and in the group who received cranial irradiation post-operatively on the metastasized brain lesion. Following surgery on the metastasized lesion, second relapses occurred in nine patients, and six patients suffered from second relapses in the brain, of which four did not receive cranial irradiation post-operatively. Cases of radiotherapy in patients of 70 years of age or more frequently manifested post-radiotherapy subacute neuropathy. From the above, it is thought that the following procedures should be adopted: 1. Periodic examination for brain metastasis during the 24 months following surgery for non-small cell lung carcinoma for purposes of early detection; 2. in cases where brain metastasis is detected, if no metastasis is identified in other organs, a policy of surgical removal should be adopted where possible; and, 3. in cases of 70 years of age or less following surgery on the metastasized lesion, cranial irradiation should be considered.     

Thermal oral-pharyngeal stimulation and elicitation of swallowing

Anaplastic thyroid carcinoma is one of the most lethal neoplasms, with poor prognosis being reported by most authors. The benefits of surgery for most cases of advanced disease remain controversial. In this study we asked the following question: Does surgical intervention alter outcomes for patients with advanced anaplastic thyroid carcinoma? Forty-six patients with advanced anaplastic thyroid carcinoma were analyzed. There were 20 patients with advanced localized disease (group 1), 15 of whom received surgery. Of the other 26 patients with evidence of distant metastases (group 2), 13 received surgery. For group 1 patients, the mean survival was 12.8 months versus 8.6 months in the surgical and nonsurgical subgroups (p = 0.46). For group 2 patients, the mean survival was 3.5 months versus 2.8 months in the surgical and nonsurgical subgroups (p = 0.72). These data suggest that surgery does not improve survival for patients with advanced anaplastic thyroid carcinoma. In conclusion, the mean survival showed no significant differences between surgical and nonsurgical patients (p = 0.43). This study suggests that surgical resection does not improve the survival of patients with advanced anaplastic thyroid carcinoma.     

Metastases of the heart and pericardium

Tumours metastasizing to the heart are one of the least investigated subjects in clinical oncology. Nevertheless, this problem holds great practical significance in relation to the operability and type of treatment of neoplastic patients. Of 4769 patients autopsied at the Institute of Pathological Anatomy of Trieste from 1994 through 1995, 1148 males (42%) and 780 females (38%) had a primary tumour. Among them, 162 subjects had cardiac metastases (8.4%) of all cancers), with a significant decrease in frequency in elderly patients. Mesothelioma, melanoma and lung cancer showed the highest frequency of heart involvement in males (100, 50 and 31%, respectively). Melanoma, lung tumours and renal neoplasms had the highest percentages of secondary heart lesions in females (45, 26 and 20%, respectively). In lung cancer, anaplastic small-cell carcinoma (37%) and adenocarcinoma (33%) showed the most frequent heart involvement in males, while squamous carcinoma (43%) and anaplastic small-cell carcinoma (29%) had the highest frequency of heart metastases in females. Adenocarcinoma (82%) and anaplastic small-cell carcinoma (74%) of the lung, mesothelioma (100%) and breast tumours (73%) had the highest frequency of metastases to the pericardium. A particularly high frequency of myocardial involvement was observed in squamous cell carcinoma of the lung (62%), urinary tract tumours (60%) and melanoma (45%).     

The ulcer-associated cell lineage: the gastrointestinal repair kit?

We describe a 79 year old lady who presented with a cytologically confirmed anaplastic carcinoma of the thyroid gland eleven years after administration of radio-iodine for thyrotoxicosis. This is, we believe, the first such occurrence documented in the Irish literature.     

The role of surgery in the management of small cell lung carcinoma

Small cell lung carcinoma is responsive to chemotherapy and radiotherapy, but long-term survival of patients is rarely seen. We analyzed resected 19 patients with small cell lung carcinoma. The overall 5-year survival rate of resected patients was approximately 30% and mean survival time (MST) was 50 months. 2 patients of them survived more than 5 years. The survivors were received chemotherapy and radiotherapy several times after surgery. When we consider the role of resection in the treatment of small cell lung carcinoma, we can realize multimodality therapy including resection is important to obtain long-term survival. Moreover, the surgical resection can identify mixed type with non-small cell elements or residual tumors after chemotherapy and determine optimal treatment methods from their histopathologic findings.     

Radioiodine I-31 therapy in the management of thyroid cancer. A prospective study

The therapeutic value of I-131 ablation therapy following thyroidectomy for thyroid cancer was evaluated in 54 patients in a prospective study of 25 years. Thirteen (24%) patients had follicular, 24 (44%) papillary, 13 (24%) mixed papillary-follicular, two (4%) Hurthle cell and two (4%) had undifferentiated cell type tumor. Twenty-four (44.5%) patients had metastases at the time of I-131 therapy mainly to cervical and mediastinal lymph nodes, and less frequently to bone, brain, lung, and liver. After surgical thyroidectomy, the mean cumulative dose of I-131 required to achieve therapeutic ablation of functioning post-surgical remnants or tumor metastases was 163.4 mCi. The recurrence rate for patients with metastases was 56% and those without metastases was 25%. Ten patients showed recurrence of I-131 accumulating tissue five to 10 years after initial total ablation. The total mean cumulative dose of I-131 administered for both followup diagnostic studies, and initial and follow-up therapy was 245.3 mCi. Seven deaths were attributable to thyroid cancer, five with differentiated and two with anaplastic cell type tumors. Three of the four patients with differentiated cell type tumors had metastases to brain or bone. Their response to therapy was similar to those patients with anaplastic cell type tumors. In contrast, there were no deaths due to thyroid cancer when total ablation was achieved and maintained. After ablation, all patients were maintained on maximum tolerated doses of thyroid extract or thyroxin. No significant complications attributable to the therapeutic doses of I-131 employed in this series were noted.     

Metastatic esophageal tumors from distant primary lesions: report of three esophagectomies and study of 1835 autopsy cases

Three cases of esophagectomy for secondary esophageal carcinoma metastasized from the ovary, breast and lung are reported. Long-term survival, 14 and 4 years, after esophagectomy was achieved in two patients. The intervals between surgery for primary cancer and dysphagia onset in these two patients were 16 and 7 years, respectively. An aggressive surgical approach appears to be the therapeutic procedure of choice for metastatic esophageal carcinoma when the primary tumor growth rate is suspected to be slow. Autopsy data on 1835 cases revealed 112 (6.1%) had metastasis to the esophagus. The lung was the most common primary tumor-bearing organ and the diffusely infiltrative type was the most common esophageal tumor observed macroscopically which corresponded to the findings in our three patients. When an esophageal stricture with normal mucosa is encountered, a metastatic tumor must be taken into consideration.     

Successful treatment of solitary extracranial metastases from non-small cell lung cancer

BACKGROUND: Recurrence after resection of non-small cell lung carcinoma is generally associated with a poor outcome and is treated with either systemic agents or palliative irradiation. Recently, long-term survival has been reported after resection of isolated brain metastases from non-small cell lung carcinoma, but resection of other metastatic sites has not been explored fully. METHODS: We have identified 14 patients who had solitary extracranial metastases treated aggressively after curative treatment of their non-small cell lung carcinoma. The histology was squamous carcinoma in 5, adenocarcinoma in 8, and large cell carcinoma in 1. Initially, 3 patients had stage I, 5 stage II, and 6 stage IIIa disease. RESULTS: The sites of metastases included extrathoracic lymph nodes (six), skeletal muscle (four), bone (three), and small bowel (one). The median disease-free interval before metastases was 19.5 months (range, 5 to 71 months). Complete surgical resection of the metastatic site was the treatment in 12 of 14 patients. Two patients received only curative irradiation to the metastatic site, with complete response. The overall 10-year actuarial survival (Kaplan-Meier) was 86%. To date, 11 patients are alive and well after treatment of their metastases (17 months to 13 years), 1 has recurrent disease, 1 died of recurrent widespread metastases, and 2 died of unrelated causes. CONCLUSION: Long-term survival is possible after treatment of isolated metastases to various sites from non-small cell lung carcinoma, but patient selection is critical.     

Verrucous carcinoma of the oral cavity: management by radiotherapy and surgery

Verrucous carcinoma is a distinct nonmetastasizing variant of well differentiated squamous cell carcinoma. It is frequently found in the oral mucosa, often in association with the more common type of metastasizing squamous cell carcinoma. In many centres radiotherapy is not used to treat verrucous carcinoma because this tumour is thought to be radioresistant and because "anaplastic transformation" has been reported following such therapy. In a series of 37 patients, 30 received radiotherapy, either alone or combined with surgery. Anaplastic transformation was not encountered. The best results were obtained with aggressive treatment which included both surgery and radiotherapy.     

Astrocytomas and choroid plexus tumors in two families with identical p53 germline mutations

Germline p53 mutations carry an increased risk of development of breast cancer, soft tissue and osteosarcomas, brain tumors, leukemia and adrenocortical carcinomas. Cerebral neoplasms are usually of astrocytic lineage and occur in 40% of affected families. This report presents clinical, neuropathological and molecular genetic data from 2 families in France with an identical p53 germline mutation in codon 248 (CGG->TGG; Arg->Trp) and a clustering of CNS tumors. The youngest patient in each family developed a malignant choroid plexus tumor while several young adults of both kindred succumbed to low-grade astrocytoma, anaplastic astrocytoma or glioblastoma. The only non-neural neoplasm was an adrenocortical carcinoma in a boy aged 4 years who developed an anaplastic choroid plexus papilloma 2 years later. Of 2 previously reported inherited choroid plexus tumors, 1 occurred in a family which also carried a germline mutation in codon 248. It remains to be shown whether this unusual pattern of CNS tumors is due to an organ-specific effect of this particular p53 mutation or whether it reflects the genetic background of the affected families.     

A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see commetns

BACKGROUND: The National Cancer Data Base (NCDB) represents a national electronic registry system now capturing nearly 60% of incident cancers in the U. S. In combination with other Commission on Cancer programs, the NCDB offers a working example of voluntary, accurate, cost-effective "outcomes management" on a both a local and national scale. In addition, it is of particular value in capturing clinical information concerning rare cancers, such as those of the thyroid. METHODS: For the accession years 1985-1995, NCDB captured demographic, patterns-of-care, stage, treatment, and outcome information for a convenience sample of 53,856 thyroid carcinoma cases (1% of total NCDB cases). This article focuses on overall 10-year relative survival and American Joint Committee on Cancer (AJCC) (3rd/4th edition) stage-stratified 5-year relative survival for each histologic type of thyroid carcinoma. Care patterns also are discussed. RESULTS: The 10-year overall relative survival rates for U. S. patients with papillary, follicular, Hürthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%, 75%, and 14%, respectively. For papillary and follicular neoplasms, current AJCC staging failed to discriminate between patients with Stage I and II disease at 5 years. Total thyroidectomy +/- lymph node sampling/dissection represented the dominant method of surgical treatment rendered to patients with papillary and follicular neoplasms. Approximately 38% of such patients receive adjuvant iodine-131 ablation/therapy. At 5 years, variation in surgical treatment (i.e., lobectomy vs. more extensive surgery) failed to translate into compelling differences in survival for any subgroup with papillary or follicular carcinoma, but longer follow-up is required to evaluate this. NCDB data appeared to validate the AMES prognostic system, as applied to papillary cases. Younger age appeared to influence prognosis favorably for all thyroid neoplasms, including medullary and undifferentiated/anaplastic carcinoma. NCDB data also revealed that unusual patients diagnosed with undifferentiated/anaplastic carcinoma before age of 45 years have better survival. CONCLUSIONS: The NCDB system permits analysis of care patterns and survival for large numbers of contemporaneous U. S. patients with relatively rare neoplasms, such as thyroid carcinoma. In this context, it represents an unsurpassed clinical tool for analyzing care, evaluating prognostic models, generating new hypotheses, and overcoming the volume-related drawbacks inherent in the study of such neoplasms. [See editorial on pages 2434-6, this issue.]     

Spasskyellina mandi n. sp. (Proteocephalidea:Monticelliidae), parasite of Pimelodus ornatus Kner, 1857 (Pisces:Pimelodidae) of the Paraná River, Paraná, Brazil

Indium-111 pentetreotide scintigraphy was performed in two patients for the localization of recurrent medullary thyroid carcinoma treated by surgery and external radiotherapy 1 and 10 years earlier. A marked uptake of the radiopharmaceutical was demonstrated in the lung areas that had been irradiated. These cases strongly suggest that this uptake is related to pulmonary fibrosis, a well-known complication of radiotherapy, even long after the irradiation. Therefore, attention must be paid to the avoidance of false-positive interpretation of somatostatin receptor scintigraphy in patients previously treated by radiotherapy.     

Fatal thyroid carcinoma. Anaplastic transformation of adenocarcinoma

Prognosis of well-differentiated carcinoma of the thyroid gland is generally favorable, while that of anaplastic carcinoma, extremely poor. Well-differentiated carcinoma may sometimes be fatal; the most common underlying cause is considered to be due to anaplastic transformation of the original well-differentiated carcinoma to a less differentiated form. We studied 27 consecutive autopsy cases of fatal thyroid cancer treated at the Ito Hospital, Tokyo, during a five-year period, 1969-1973. We found uniform histological features of anaplastic carcinoma in 10 cases and of well differentiated carcinoma in four cases. In addition, co-existence of well-differentiated and anaplastic carcinomas was observed in nine cases and well differentiated and squamous cell carcinomas in four. Circumstantial evidence strongly suggests that malignant transformation is a part of the natural history of thyroid carcinoma, from well-differentiated carcinoma to less differentiated forms, either squamous cell or anaplastic carcinoma.     

Effect of potassium channel openers on the firing rate of hippocampal pyramidal cells and A10 dopaminergic neurons in vitro

The clinical relevance of grading in ependymomas is almost always regarded as controversial. According to the classification of brain tumours revised by the World Health Organization (WHO) in 1993, brain tumours of ependymal origin are differentiated as subependymomas Grade I, ependymomas Grade II, and anaplastic (malignant) ependymomas Grade III. The purpose of the present retrospective study of 126 patients with intracranial ependymomas was to assess the clinical and prognostic significance of the topical classification and grading system by a uni- and multivariate statistical analysis. 87 Grade II ependymomas were predominantly located in the midline and in the fourth ventricle, whereas 39 anaplastic ependymomas Grade III were most often found in the cerebral hemispheres. Excluding the localization-linked operative mortality, progression-free survival (PFS) was significantly dependent on the histological grading. Median PFS time was 7.5 years in Grade II, but only 1.5 years in Grade III ependymomas. Stratifying for the two time intervals 1951-1970 and 1971-1990, and excluding the operative mortality, a multivariate Cox' model analysis of the covariates age, localization, grading, extent of surgery, and radiation therapy revealed that only the histological grading and radiation therapy had a significant impact on PFS. Thus, the WHO grading system has a statistically significant relevance for the long-term prognosis of intracranial ependymomas. However, the therapeutic management including radical tumour resection and additional local irradiation should be independent of the grading.     

Successful management for chemorefractory testicular cancer with brain and lung metastases. A case report

This is a report of successful management for a far advanced, chemorefractory testicular cancer patient. A 29-year-old male was referred to our hospital for the treatment of progressive lung metastases with elevated hCG level, which had recurred after complete remission following 3 courses of BEP chemotherapy and progressed after transient partial regression following 2 courses of intensified EP chemotherapy. In addition, a 3 cm in diameter, solitary brain metastasis was detected on CT. First, we performed wedge resection of bilateral pulmonary lower lobe for chemorefractory pulmonary metastases. Histological examination revealed viable embryonal carcinoma identical to the primary one. Thereafter, whole brain irradiation in combination with VIP chemotherapy (etoposide 100 mg/m2, cisplatin 20 mg/m2 and ifosfamide 1200 mg/m2 daily for 5 consecutive days) was carried out to treat brain metastasis. By 2 cycles of VIP therapy and irradiation (36 Gy), partial tumor regression and normalization of hCG level were achieved, leading to salvage surgery of the brain metastasis which histologically proved to be necrosis. Following an additional cycle of VIP therapy, the patient has been free of recurrence 24 months after completion of the treatment.     

Small cell anaplastic carcinoma of lung. Reappraisal of current management

The relative roles of radiotherapy, intensive chemotherapy, and a combination of both were evaluated by an analysis of 157 of 188 patients who were registered at Tumor Registry and the Department of Radiation Medicine at Massachusetts General Hospital with a diagnosis of small cell anaplastic carcinoma of the lung between 1968 and 1974. Stage of the tumor was the single most important prognostic factor. Bone marrow involvement was found in 29% of patients studied. For extensive tumor, better survival was obtained by a combination of intensive chemotherapy and radiotherapy than with radiotherapy alone. However, no improvement of survival was noted with combination of concomitant or sequential intensive COPP or COP chemotherapy and radiotherapy over that obtained with radiotherapy followed by subsequent chemotherapy for progressive disease in patients with localized tumor. For localized tumor, primary radiotherapy should be given with an intention of local control or cure. Conclusions regarding the proper timing of chemotherapy and radiotherapy in apparently localized small cell anaplastic carcinoma require further prospective evaluation.     

Survival of infants with malignant astrocytomas. A Report from the Childrens Cancer Group

BACKGROUND: Very young children with central nervous system malignant brain tumors have a poor prognosis. As compared with older children, survival is less likely, and those children who do survive frequently have severe impairment of growth and cognitive abilities, resulting partly from treatment with radiotherapy. Therefore, an intensive chemotherapeutic regimen was used to treat children younger than 2 years of age with a diagnosis of malignant astrocytomas. PATIENTS AND METHODS: Thirty-nine children younger than 24 months of age who were diagnosed with malignant astrocytoma were treated on a Childrens Cancer Group protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytosine arabinoside, prednisone, and dimethyl-triazenoimidazole-carboxamide) after surgery and postoperative staging. Radiation therapy was to be deferred until the completion of chemotherapy. RESULTS: The objective response rate after two cycles of chemotherapy was 24%. Most patients did not receive radiotherapy. Progression-free survival (PFS) and survival at 3 years was 36% (standard error, 8%) and 51% (8%), respectively. The PFS of those children with anaplastic astrocytoma was 44% (11%), significantly better than that of glioblastoma multiforme (GBM) (0%). Extent of resection was not associated significantly with PFS, but tumors within the cerebral hemispheres were associated with a more favorable prognosis. Tumor progression occurred locally in almost all cases and early in treatment (median PFS, 8 months). CONCLUSION: Chemotherapy appears to be effective primary adjuvant treatment for some very young children with anaplastic astrocytomas. Overall, however, survival remains poor, especially for children with GBM. Strategies to improve outcome require early intervention, because tumor progression occurs soon after diagnosis in the majority of patients.     

Prognostic factors in malignant gliomas

The most important prognostic factor in malignant gliomas is histopathological diagnosis of the tumor. The survival of patients with anaplastic astrocytoma is much longer than that of patients with glioblastoma. The median survival of the former has been improved up to almost 4 years by the recent progress of multidisciplinary treatment, whereas that of the latter has still remained in less than 1.5 years. Other important factors proved to be associated with survival of patients with malignant gliomas are the age of patients, Karnofsky performance status on admission, surgery, radiotherapy and chemotherapy. There is substantial evidence suggesting an association between younger patient age and longer survival in adults with supratentorial anaplastic astrocytoma as well as glioblastoma. It is also consistent with evidence that the patients with better performance status on admission live longer after treatment. Gross total resection of supratentorial anaplastic astrocytoma is directly associated with longer and better survival when compared to subtotal or partial resection. For glioblastoma, however, gross total resection has not been proved to have a significant survival advantage over subtotal or partial removal. Radiotherapy has been proved to be associated with longer survival of patients with supratentorial anaplastic astrocytoma and glioblastoma. Chemotherapy has not proved effective in prolonging the survival of patients with glioblastoma. Multidrug chemotherapy with CCNU, procarbazine and vincristine has proved to have significant survival advantage over BCNU alone, suggesting chemotherapy is also a prognostic factor in patients with anaplastic astrocytoma.     

Premalignant lesions of the vocal cords. A retrospective study of 62 cases treated with CO2 laser

A series of 62 patients treated by (repeated) CO2 laser excision and/or vaporization for premalignant lesions of the vocal cords was analysed retrospectively. Of the 54 patients available for follow-up (ranging from 1 to 15 years), five patients (9%) developed an invasive glottic carcinoma and needed radiotherapy. Only two patients (4%) needed extensive surgery (total laryngectomy). One patient (2%) died of a recurrent carcinoma despite radiotherapy and laryngectomy, and six patients (11%) died of a metachronic lung carcinoma. The therapeutic results of (repeated) laser therapy were comparable to those in other reports regarding radiotherapy or stripping. The subjective functional results were satisfactory and tended to improve along with refinement of laser surgery techniques. Follow-up of patients who once had a premalignant laryngeal lesion is mandatory ad vitam, regardless of the grade of the lesion. For the screening of lung cancer, there is still no consensus on a standard-of-care. The classical chest X-ray remains the most accessible and comfortable screening procedure.