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The stromelysin gene encodes a potent tissue-degrading proteinase whose activity is important in tissue-remoldeling processes such as wound healing, the inflammatory reaction, rheumatoid arthritis, tumor invasion, and possibly embryonic development. In light of the ability of interleukin-1 to amplify, and ability of glucocorticoids to attenuate the inflammatory response, we tested interleukin-1 and dexamethasone for regulatory effects on stromelysin gene expression. We report that interleukin-1 induces the stromelysin gene, and dexamethasone diminishes the level of induction by interleukin-1, epidermal growth factor, phorbol ester, and cAMP elevation (elicited by cholera toxin). Similar responses are conferred upon a chloramphenicol acetyltransferase coding sequence by a 700-base pair stromelysin 5'-flanking fragment, implying transcription regulation by sequence elements in this region.
The presence and/or depth of myometrial invasion of endometrial adenocarcinoma has important prognostic and therapeutic implications. Fifteen patients with histologically proven endometrial cancer underwent preoperative evaluation with sonography (US) and magnetic resonance imaging (MRI) to assess depth of invasion. Using criteria of greater than or equal to 50% of myometrial wall involvement as representing deep invasion, and less than 50% as superficial invasion, US was more accurate than MRI in five cases; in three MRI was more accurate than US; both MRI and US were equally accurate in four; neither was accurate in three. Polypoid lesions caused the greatest number of false positive reports of deep invasion with both MRI and US. Preliminary results indicate that US and MRI have promise as preoperative tests to assess the extent of myometrial invasion.
Female genital tract involvement by hematologic neoplasms is uncommon and is usually associated with disseminated disease. Lymphoid neoplasms, which involve the cervix and uterus primarily, are usually of either diffuse large cell or small cleaved cell type, and rarely Burkitt's (small non-cleaved) lymphoma or granulocytic sarcoma. In this report the authors describe young woman with acute stem cell leukemia which was terminal deoxyribonucleotidyl transferase positive, and involved the bone marrow and peripheral blood. After induction of remission and a 2-year disease-free interval, she relapsed with involvement localized to the uterus and cervix. At relapse the leukemic cells expressed CD1, CD2, CD5, CD7, and CD4 or CD8, antigens of the common thymocyte compartment. The authors postulate that the T-cell antigens, known extracellular matrix receptors, may have determined the tissue infiltration: an unusual pattern of relapse.
Parathyroid carcinoma is a rare endocrine tumor infrequently seen in the mediastinum. This report describes a patient who underwent en bloc resection of a primary mediastinal parathyroid carcinoma. The tumor originated from the thymus and extended from the aortic arch to the thyroid; local invasion suggested malignancy. En bloc resection of this carcinoma with all surrounding tissue provided local control of the tumor and relief of symptomatic hypercalcemia.
Twenty-two iatrogenic vascular injuries caused by resection of tumors with local recurrences or adjuvant chemotherapy were treated over a 42-month period in 11 female and 8 male patients with cancer (58% had documented metastases). Sixteen of 22 vascular injuries were caused by intraarterial administration of chemotherapy (8 emboli; 8 direct catheter trauma), and six were caused by resection of tumors with local invasion. The injuries were extremity ischemia (15 extremities in 13 patients), pseudoaneurysm (4), expanding hematoma (3 injuries in 2 patients). Twenty-two surgical repairs included bypass of severely damaged arteries in five, embolectomy in five, interposition grafts in three, pseudoaneurysm resection and primary repair in three, primary repair of three vascular injuries, and one patch angioplasty. Leg amputation was required in two patients. Seventeen of 19 patients had successful vascular repairs with resolution of preoperative indications for vascular repair without intraoperative or postoperative deaths. Long term follow-up (mean, 17 months) showed no recurrence of vascular problems; however, two patients died of metastatic cancer at 6 and 24 weeks after vascular repair. This study supports an aggressive approach to the management of vascular injuries caused by therapeutic interventions for malignancy despite the presence of metastatic disease.
We have stratified the cancer risk implications of lobular pattern in situ neoplasias of the breast by separating marked examples of this histologic spectrum (lobular carcinoma in situ [LCIS]) from lesser examples (atypical lobular hyperplasia). The lesser-developed examples have been shown previously to have a lower relative risk (RR) of later invasive carcinoma of the breast (IBC). Forty-eight examples of LCIS were found in 10,542 otherwise benign breast biopsies, representing an incidence of 0.5%. Nine patients were excluded from follow-up because of bilateral mastectomy within 6 months of entry biopsy, IBC within 6 months of entry biopsy, or prior IBC. Follow-up of the remaining 39 patients was complete, averaged 18 years, and revealed an RR of subsequent IBC of 6.9 (P less than .00001). Average overall follow-up for LCIS patients was 19 years; it was 25 years for those alive and free of IBC at the time of their follow-up interview. Neither family history of IBC nor postmenopausal estrogen therapy further affected risk. The absolute risk of IBC after LCIS was 17% at 15 years (adjusted for withdrawals), and the RR was 8.0 in the first 15 years of follow-up compared with the general population. An analysis based on a time-dependent hazards model found that during the first 15 years following biopsy women with LCIS had 10.8 times the risk of breast cancer compared with biopsied women of comparable age who lacked proliferative disease. Some previously published articles reporting lobular neoplasia (LN) suggest that those series with the greatest incidences of LN (whether termed LN or LCIS) have the lowest RR of subsequent breast cancer. Those series with higher incidences of LN include less well-developed histologic patterns of LN (atypical lobular hyperplasia). We conclude that our study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower). This relative cancer risk is probably not constant over more than 15 years; thus, cancer risk 15 to 25 years after initial diagnosis of LCIS is uncertain.