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Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer.

Although once reserved for the management of metastatic prostate cancer, androgen deprivation therapy (ADT) is being used increasingly to treat lower stages of disease. We sought to assess patterns of ADT use in a contemporary cohort of men newly diagnosed with prostate cancer. Men with newly diagnosed prostate cancer who had > or =12 months of follow-up evaluation were identified in a national disease registry of patients with prostate cancer. The patterns of ADT use, both primary and secondary, were characterized and stratified by risk according to prostate-specific antigen levels, clinical stage, and Gleason score. In a cohort of 1485 men, 46% underwent ADT at some point during their treatment: 41% as primary therapy (either sole therapy or neoadjuvant therapy), and 5% as secondary therapy. In all, 50% of men receiving initial ADT had low- or intermediate-risk disease characteristics. Among patients treated with radical prostatectomy and radiation therapy, neoadjuvant ADT was administered in 20% and 48% of patients, respectively. Secondary hormonal manipulation was observed in 5% and 7% of patients treated initially with surgery or radiation, respectively. ADT is commonly used to treat men with prostate cancer. Much of the use of ADT is in men with low- and intermediate-risk disease characteristics. The appropriateness of such therapy requires further study, including its effect, not only on disease endpoints, but also on resource utilization and health-related quality of life.

Androgen Antagonists↗

Clinical characteristics of metastatic orbital tumors.

The authors reviewed the clinical and histopathologic records of 38 patients with metastatic orbital tumors. Diplopia, ocular motility limitation, and mass effect with displacement, proptosis, or palpable mass were common signs and symptoms. Enophthalmos occurred in 25% of cases. The authors found that the clinical presentations could be broken down into four generalized syndromes of presentation: infiltrative (20 cases, 53%); mass (14 cases, 37%); inflammatory (2 cases, 5%); and functional (1 case, 3%). An infiltrative pattern of presentation may be a clue to the metastatic nature of the orbital tumor. There may be no history of systemic cancer; in 25% of the patients in this series, the orbital tumor was the initial manifestation of systemic disease. Although the prognosis is poor for patients with metastatic cancer (average survival in this series, 10.2 months), modern treatment methods continue to improve and long-term palliation is often possible. The ophthalmologist plays a vital role in the diagnosis, histologic evaluation, and referral of these patients.

Adult↗

[Metastatic carcinoma of the sigmoid colon to the thyroid gland].

A case of metastatic thyroid cancer from sigmoid colon cancer is presented. A 52-year-old woman had a sigmoidectomy due to adenocarcinoma of the sigmoid colon in April 1988. Serum carcinoembryonic antigen (CEA) levels gradually rose from July 1990 along with multiple metastatic lesions which appeared in the lung. They were resected in January 1991. Two months later the subject noticed a painless and firm lump on the left anterior neck. She was found to have a solitary mass in the left thyroid lobe. Thyroid function remained within normal range. Cytological findings obtained by fine-needle aspiration biopsy showed tall columnar carcinoma cells with an acinar pattern. Subtotal thyroidectomy was performed, and histological examination revealed metastatic adenocarcinoma from colon cancer. Immunohistochemical staining by anti-CEA was positive but anti-thyroglobulin was negative.

Adenocarcinoma↗

Patterns of care survey (PCS) in lung cancer: how well does current U.S. practice with chemotherapy in the non-metastatic setting follow the literature?

BACKGROUND: In LD-SCLC, combined modality therapy has emerged as the standard of practice in good performance status (PS) patients (pts). Pignon's meta-analysis [N Engl J Med 1992;327:1618-24] showed that combination chemotherapy (CT) and thoracic radiation (XRT) in LD-SCLC yielded an absolute 5.4% increase in 3-year survival versus chemotherapy alone. Concurrent chemoradiation upfront has generated the highest survival rates [Murray. J Clin Oncol 1993;11:336-44; Jeremic. J Clin Oncol 1996;15:893-900; Takada. J Clin Oncol 2002;20:3054-60]. In stage III NSCLC, multiple studies have shown therapeutic superiority for combination chemotherapy and XRT versus RT alone; and recent literature suggests a therapeutic advantage for concurrent chemoradiation versus chemotherapy followed by XRT [Curran. ASCO 2000;19:484a; Furuse. JCO 1999;17:2692-9; Zatloukal. ASCO 2002;A-1159]. Data are less secure regarding the role of chemotherapy in stage I and II NSCLC. MATERIAL AND METHODS: A stratified two-step cluster sampling technique was used for data collection. Five hundred and forty-one individuals diagnosed between 1998 and 1999 with lung cancer, either LD-SCLC or stages I-III NSCLC were sampled from 58 institutions featuring radiotherapy facilities, giving a weighted sample size (wss) of 42,335 patients. All pts had Karnofski performance status (KPS) >or=60. We determined the percentage who received chemotherapy; the nature of chemotherapy and its timing with respect to XRT. SUDAAN statistical software was used to allow the incorporation of the design elements and weights to reflect the relative contribution of each institution and each patient in the analysis RESULTS: Of 72 (wss=6138) pts with LD-SCLC, 100% received XRT and 95% received chemotherapy (CT); 66% received concurrent (con) CT and XRT, of whom 29% also received CT pre XRT; 22% received CT post XRT as well, and 23% received both: 63% received sequential CT-->XRT+/-con CT; and 38% received some CT after XRT. Fifty-two percent received cisplatin (DDP), and 38% received carboplatin (CBDCA); 73% received etoposide (VP-16), while 10% received paclitaxel. Of 469 pts (wss=36,197) with NSCLC, 52% received CT, including 30% with stage I disease, 48% with stage II NSCLC, 60% with stage III NSCLC, and 50% with unknown stage. Thirty-nine percent received sequential CT-->XRT+/-CT, of whom 49% received CT pre XRT only. Seventy-four percent received con CT and XRT; and 27% received posterior CT, of whom 84% also received con CT/XRT. Forty-five received some CT in the pre-op setting and 15% in the post-op setting. Twelve percent received DDP-based therapy, while only 13% and 7% received VP-16 or vincas, respectively; 67% received CBDCA. Seventy-two percent received taxanes, of whom 96% received paclitaxel. Gemcitabine was administered to 3% of NSCLC pts. CONCLUSIONS: Combined modality therapy is typically employed in the therapy of LD-SCLC and LA-NSCLC. The majority of those treated for SCLC receive concurrent CT/XRT, while nearly 3/4 of those treated with CT and XRT for LA-NSCLC received concurrent CT/XRT. Current practice in the US generally matches evidence-based literature, although a significant percentage of practitioners substitute CBDCA for DDP in both venues and use paclitaxel in lieu of vincas or etoposide in NSCLC.

Adult↗

Imaging findings of extrapulmonary metastases of osteosarcoma.

PURPOSE: To review imaging findings of extrapulmonary metastasis from osteosarcoma and to evaluate them for any consistent pattern and correlation between imaging findings. MATERIALS AND METHODS: This study was retrospectively conducted in 13 patients with extrapulmonary metastasis of pathologically confirmed osteosarcoma. We evaluated the radioisotope (RI) scans (n=16), ultrasonography (USG) (n=4), computed tomography (CT) scans (n=10), MRIs (n=6), clinical records, and pathological reports for assessment of imaging findings and correlation between radiologic findings and RI uptake of the lesions. Points evaluated were the following: uptake on RI scans, presence of mineralization on CT, and MRI, size, enhancement pattern, attenuation on CT, signal intensity (SI) on MRI, and echogenicity on USG. RESULTS: Extrapulmonary metastatic sites were diverse, including another bone other than the primary site (n=6), lymph node (n=4), pleura (n=2), liver (n=2), pancreas (n=1), kidney (n=1), peritoneum (n=1), muscle (n=1), and subcutaneous fat layer (n=1). One patient had tumor growth within the pulmonary artery and jejunum. Among 21 metastatic sites in 13 patients, bone scan was performed in 16 cases and RI uptake was detected in 10 lesions. Calcification was detected in eight lesions on radiologic imaging, including plain radiography, USG, CT, and MRI. Two lesions showed RI uptake without definite calcification or ossification on MRI and plain radiography, respectively. We analyzed the enhancement pattern and mass size in 18 metastatic sites and these factors had poor correlation with uptake on RI scans. CONCLUSION: The sites and imaging findings of extrapulmonary metastasis of osteosarcoma were variable. All the lesions with mineralization were detectable on RI scans prior to radiologic imaging. RI scan has a limited role in the evaluation of metastatic lesions without mineralization.

Adipose Tissue↗

Necrosis in 84 ovarian carcinomas: a morphologic study of primary versus metastatic colonic carcinoma with a selective immunohistochemical analysis of cytokeratin subtypes and carcinoembryonic antigen.

Carcinomas metastatic to the ovary are often difficult to distinguish from primary ovarian carcinomas. Adenocarcinoma of the colon may simulate both primary endometrioid and mucinous ovarian tumors. The histologic finding of "dirty" necrosis in association with a "garland" or cribriform pattern has been suggested as a useful feature in distinguishing metastatic colonic carcinomas from primary endometrioid ovarian carcinomas. This study was performed to determine the use of "dirty" necrosis in distinguishing primary ovarian carcinoma from metastatic colonic carcinoma by studying 71 of the former and 10 of the latter. At least focal dirty necrosis was found in 68% of primary ovarian epithelial cancers, including 92% of the endometrioid subtype, and in 100% of the metastatic colonic carcinomas. A subgroup of cases was evaluated immunohistochemically using cytokeratin (CK) 7, CK 20 and carcinoembryonic antigen (CEA). The phenotype of CK 7 +/CK 20-/CEA-was present in 92% of primary ovarian carcinomas studied, whereas, 90% of metastatic colonic carcinomas were CK 7-/CK 20 +/CEA+. The finding of dirty necrosis is not specific for metastatic colonic cancer, and differential cytokeratin immunostaining is a useful adjunct in this differential diagnosis.

Adolescent↗

Tenascin-C expression in Merkel cell carcinoma lymph node metastasis.

Expression of tenascin-C (Tn-C) has been shown to correlate with invasion and metastasis in Merkel cell carcinoma (MCC). Cytokeratin-20 (CK-20) is used in differential diagnostics of the primary tumour. The aim of this study was to demonstrate the expression of Tn-C in MCC lymph node metastases. Immunohistochemical staining was performed for five metastatic lymph nodes using a monoclonal antibody against Tn-C and CK-20. All five metastatic lymph nodes expressed Tn-C. The expression concentrated around the vascular structures, invasion borders and fibrotic septae. One of the metastatic lymph nodes was strongly positive for CK-20 while the others showed a focal or negative pattern. The normal lymphoid tissue was negative for Tn-C. Tn-C detected metastatic MCC tissue within the lymph nodes undisputedly. There was a clear distinction between the metastatic and normal lymphatic tissue. Furthermore, invasion to the surrounding tissue was easily demonstrated. Contrary to previous studies, CK-20 expression seemed to fluctuate.

Biomarkers, Tumor↗

Zosteriform eruption of herpes simplex virus after vertebral metastases.

Described herein is a fifty-nine-year-old man with pulmonary adenocarcinoma metastatic to the spine who experienced a recurrent herpes simplex virus eruption in a zosteriform pattern on his lower back. This eruption corresponded to an area of the lumbosacral vertebrae that contained metastatic lesions.

Adenocarcinoma↗

Cavitary lung disease. How to read the radiographic patterns.

Many disorders and abnormalities are accompanied by cavitary lesions of the lung, including various diseases that may destroy or replace lung tissue. The most common causes of cavitary lung disease are primary and metastatic neoplasms, granulomas, and necrotizing pulmonary infections. These diseases often have radiographic patterns, clinical signs, and symptoms that are characteristic and may suggest a diagnosis.

Adult↗

Adenosquamous carcinoma of skin appendages (adenoid squamous cell carcinoma, pseudoglandular squamous cell carcinoma, adenocanthoma of sweat gland of Lever) of the vulva: a clinical and ultrastructural study.

History and clinical findings of 18 cases of adenosquamous carcinoma of the skin appendages found among 135 cases of primary carcinoma of the vulva seen at the University of Minnesota Hospital between 1951 and 1970 were analyzed. In addition, two recent cases of this tumor were studied with conventional transmission electron microscopy. Adenosquamous carcinoma of the vulva showed poorer survival and a higher rate of lymph node metastases than squamous cell carcinoma of the corresponding stages (carcinoma in situ excluded). In four out of thirteen cases, the metastatic lesions in the lymph nodes retained glandular pattern. The ultrastructure showed mucin-producing columnar cells lining glandular lumina, and poorly differentiated squamous cells elsewhere; further, cells of the intermediate type between the two were present. This study indicates that adenosquamous carcinoma of the vulva is a distinctively separate entity from squamous cell carcinoma of the vulva, and possibly arises from mucin-producing cells of the skin appendages as suggested by Johnson and Helwig.

Adenocarcinoma↗

Metastatic basal cell carcinoma: a clinicopathologic study of seventeen cases.

Basal cell carcinoma is a common cutaneous neoplasm that rarely metastasizes. We studied the clinical and pathologic features of 17 patients with metastatic basal cell carcinoma as recorded in the files of the Armed Forces Institute of Pathology (AFIP). Sixteen of the patients were male, and as far as it could be determined, all were white. The most frequent site of metastasis was lung (9 cases), followed by bone (5), lymph nodes (4), liver (3), spleen (1), and adrenal gland (1). Thirteen of the patients had metastatic lesions involving only one organ system. Mean survival time after metastasis was 1.6 years. Features of metatypical (basosquamous) basal cell carcinoma were common in the primary and recurrent tumors, and metastatic lesions generally had a metatypical or adenoid pattern. Two of the five bony metastases demonstrated shadow cells characteristic of pilomatrixoma. The metatypical pattern of a basal cell carcinoma is a feature of an aggressive lesion with the ability to metastasize.

Adrenal Gland Neoplasms↗

Retiform differentiation in ovarian Sertoli-Leydig cell tumors. A clinicopathologic study of six cases from a Gynecologic Oncology Group study.

This report analyzes six ovarian Sertoli-Leydig cell tumors that showed retiform differentiation. The patients were young (6-29 years; average age, 17). The tumors were all limited to one ovary, and the patients have remained disease-free, with one exception, a patient who died of recurrent neoplasm 3.5 years after operation. On microscopic examination, the retiform areas were predominant in three cases and focal in the other three. The retiform areas consisted of an irregular anastomosing network of spaces lined by cuboidal cells, often with papillary formations and sometimes with tubules compressed to form slit-like spaces. In three cases the retiform areas appeared mature, and in three they were less differentiated. All tumors also had areas of typical Sertoli-Leydig cell tumor of either poor or intermediate differentiation. In the patient with metastatic disease, the metastases had a pure sarcomatoid pattern without any retiform areas.

Adolescent↗

Genetic background of different cancer cell lines influences the gene set involved in chromosome 8 mediated breast tumor suppression.

Several lines of evidence suggest that chromosome 8 is likely to harbor tumor-suppressor genes involved in breast cancer. We showed previously that microcell-mediated transfer of human chromosome 8 into breast cancer cell line MDA-MB-231 resulted in reversion of these cells to tumorigenicity and was accompanied by changes in the expression of a breast cancer-relevant gene set. In the present study, we demonstrated that transfer of human chromosome 8 into another breast cancer cell line, CAL51, strongly reduced the tumorigenic potential of these cells. Loss of the transferred chromosome 8 resulted in reappearance of the CAL51 phenotype. Microarray analysis identified 78 probe sets differentially expressed in the hybrids compared with in the CAL51 and the rerevertant cells. This signature was also reflected in a panel of breast tumors, lymph nodes, and distant metastases and was correlated with several prognostic markers including tumor size, grading, metastatic behavior, and estrogen receptor status. The expression patterns of seven genes highly expressed in the hybrids but down-regulated in the tumors and metastases (MYH11, CRYAB, C11ORF8, PDGFRL, PLAGL1, SH3BP5, and KIAA1026) were confirmed by RT-PCR and tissue microarray analyses. Unlike with the corresponding nontumorigenic phenotypes demonstrated for the MDA-MB-231- and CAL51-derived microcell hybrids, the respective differentially expressed genes strongly differed. However, the majority of genes in both gene sets could be integrated into a similar spectrum of biological processes and pathways, suggesting that alterations in gene expression are manifested at the level of functions and pathways rather than in individual genes.

Animals↗

Coamplification of simple repetitive DNA fingerprint fragments and the EGFR gene in human gliomas.

DNA fingerprints were generated by the oligonucleotide probe (GTG)5 from surgically removed tissue and/or primary cell culture of 36 intracranial tumors (31 gliomas, 1 medulloblastoma, 4 metastatic carcinomas) and compared with the constitutional banding pattern obtained from the peripheral blood leukocytes of each patient. A multitude of somatic changes was detected and found to reflect the chromosome alterations identified by parallel karyotype analysis. Gain and/or loss of bands or significant band intensity shifts could be demonstrated in the fingerprints of more than 80% of the tumors investigated. This included a highly amplified fingerprint fragment in five independent gliomas (four of them had double minutes, dmin) which appeared not individual- but tumor-specific (2.4 kilobases, kb, after HaeIII digestion). Rehybridization with the oligonucleotide probes (GT)8 and (GATA)4, respectively, revealed additional amplified fingerprint fragments in the tumor DNA of these patients. While a (ca/gt)n fragment (2.6 kb. HaeIII) was also found to be amplified in all five cases, one band detected with (GATA)4 (1.4 kb, HaeIII) represented a unique feature for one of these tumors only. Amplification of the epidermal growth factor receptor (EGFR) gene via Southern blot hybridization was revealed only in those tumors showing the amplified DNA fingerprint fragments as well. Thus in many gliomas the amplification unit harbors two simple repetitive DNA fingerprint loci, (cac/gtg)n and (ca/gt)n, in addition to the EGFR gene.

Adolescent↗

Lymph node metastases from osteoblastic osteogenic sarcoma visible on plain films.

The radiologic features of lymph node metastases from osteogenic sarcoma visible on plain films in two patients are described. In one patient the lymph node ossification was visible on presentation and in the other patient it was demonstrated six months after the initial diagnosis. The radiologic pattern in both cases was similar. Deposition of metastatic osteoid tissue in lymph nodes, to such a degree that it can be recognized on plain films, appears to be a distinctly uncommon complication of this malignant neoplasm. It is considered probable that this complication occurs with the osteoblastic type of osteogenic sarcoma. It is suggested that lymphography might be of value in the detection of such metastases at an earlier stage, thus influencing the plan of treatment.

Adolescent↗

Accumulation of tetrahydrofolates in human plasma after leucovorin administration.

Reduced folates in plasma after i.v. and oral leucovorin administration were estimated by a ternary complex assay based on the incorporation of CH2FH4 into a stable complex with Lactobacillus casei thymidylate synthase and [3H]FdUMP. Each of the reduced folates, CH2FH4, FH4, and 5CH3FH4, could be quantitatively recovered from plasma by this approach even in the presence of high concentrations of the parent compound leucovorin. Examination of the accumulation kinetics of these reduced folates showed that after i.v. administration of 20 mg D,L-leucovorin to a healthy volunteer, FH4 and, to a lesser extent, CH2FH4 accumulated to maximal levels very early (less than 15 min), with a subsequent depletion that had a half-life of approximately 30 min. Accumulation of FH4 reached a peak level that was 12% of the maximal level of 5CH3FH4 achieved and more than 3 times greater than the pretreatment level of this common, circulating reduced folate form. Similar accumulation patterns were observed in a female patient with metastatic colonic cancer who was undergoing methotrexate (MTX)/fluorouracil therapy followed by i.v. leucovorin (15 mg). FH4 also accumulated, but to a lesser extent and over a longer period of time, when the same dose of leucovorin given orally. When several similar doses of leucovorin were given prior to the experimental dose, greater accumulation and duration of the FH4 response was observed. We propose that accumulation of FH4 and CH2FH4 could provide a circulating source of the reduced folate thought to be the active form for both high-dose MTX with leucovorin rescue and enhancement of fluorouracil activity.

Administration, Oral↗

Hyaline inclusions (Pseudopsammoma bodies) in meningiomas: immunocytochemical demonstration of epithel-like secretion of secretory component and immunoglobulins A and M.

Three meningotheliomatous meningiomas showed prominent formation of hyaline inclusions (pseudopsammoma bodies). Immunocytochemical examination by means of indirect immunofluorescence and PAP techniques demonstrated strong labeling of these inclusions by antisera to human secretory component (SC), immunoglobulin (Ig) A and IgM. A similar staining pattern was found in intracytoplasmic globules of a metastatic carcinoma. Hyaline structures of various types in atypical, psammomatous, and hemangiopericytic meningiomas were not stained with the antisera employed. By histochemical, immunocytochemical, and ultrastructural criteria, pseudopsammoma bodies in meningiomas are identical with intracytoplasmic inclusions of some epithelial neoplasms, especially of mammary and gastric carcinomas. Our study strongly corroborates Kepes' (1961, 1975) concept of secretory differentiation in meningiomas, and demonstrates an epithelial character at least of some meningiomas.

Adult↗

Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications.

Activating mutations of ras-genes (Kirsten-ras, Harvey-ras, N-ras) and genes encoding for the alpha subunit of G-proteins (Gs, Gi2, Gi3, Go, Gz) were assessed in 32 differentiated thyroid cancer (DTC) tissues from German (n = 22) and American (n = 10) patients. Gs-protein (GSP) and/or ras mutations were found in 69% of all tissues with a heterogeneous distribution pattern. An increased prevalence could be demonstrated in metastatic (8 of 9 mutation positive) when compared to localized disease (13 of 23 mutation positive) (p less than 0.001) and in patients greater than 50 years of age (16 of 18 mutation positive), when compared to younger patients (6 of 14 mutation positive) (p less than 0.001). No activating mutations were found on H-ras and K-ras genes nor on genes encoding for the alpha subunits of Gi2, Gi3, Go, and Gz. Differentiated thyroid cancer tissue from German patients revealed a higher prevalence for GSP mutations (73%) than did DTC from American patients (20%) (p less than 0.001). We demonstrated a high frequency of ras and GSP mutations in DTC and suggest that these mutations may contribute to our basic understanding of this disease and might initiate a new search for more rational and individualized therapeutic approaches in patients with DTC.

Base Sequence↗