Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine the feasibility and efficacy of multiple courses of high-dose cyclophosphamide, carboplatin and thiotepa with peripheral blood progenitor cell (PBPC) transplantation in women with advanced breast cancer. Forty-one patients with advanced hormone-refractory breast cancer were enrolled in the study. The treatment started with two courses of 5-fluorouracil 500 mg/m(2), epirubicin 120 mg/m(2) and cyclophosphamide 500 mg/m(2) (FE(120)C) followed by PBPC harvesting. The high-dose regimen consisted of three subsequent courses of 'tiny' CTC, cyclophosphamide 4000 mg/m(2), thiotepa 320 mg/m(2) and carboplatin 1060 mg/m(2) (target AUC 13.3 mg/ml/min) (tCTC) divided over 4 consecutive days. The second and third courses were scheduled to begin on day 28 after the previous transplantation. A total of 86 tCTC courses was given to 33 of the 41 enrolled patients. Major toxicities consisted of hemorrhagic cystitis (six patients), prolonged gastro-intestinal toxicity (three patients) and veno-occlusive disease (two patients). There was one therapy-related death (unknown cause). Twenty patients (49%) achieved a complete response, nine (22%) a partial response and three patients stable disease after treatment. The median follow-up of the surviving patients was 43 months (range 25-61). Six patients remain in complete remission beyond 3 years. At 4 years, the progression-free survival (PFS) and overall survival (OS) for the whole patient group were 23 and 30% with a median duration of 12 and 27 months, respectively and for FE(120)C-responsive patients 32 and 36%, respectively with a median duration of 15 and 33 months. In the patient group with a PFS > or = 18 months all patients had limited disease (metastatic disease in only one or two sites) and fewer patients had bone or liver metastases compared to the overall patient group (33% vs 51%). This report shows that three closely spaced courses of tCTC are feasible, with acceptable toxicity. Triple tCTC can achieve complete or partial remission in most patients and long-term PFS in a selected subgroup of patients who have limited metastatic disease and are responsive to conventional-dose chemotherapy.
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PMID:Phase II study of a multi-course high-dose chemotherapy regimen incorporating cyclophosphamide, thiotepa, and carboplatin in stage IV breast cancer. 1150 35

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are mostly limited to individuals who are immunosuppressed. In transplant recipients, BKV has been associated with ureteral stenosis, interstitial nephritis, and hemorrhagic cystitis. The role of BKV in the development of human tumors is intriguing but uncertain. BKV has been identified in various tumor types including urothelial carcinoma, but the ubiquitous presence of BKV as a latent infection has confounded efforts to validate any causal role in cancer development. We report the case of a simultaneous pancreas and kidney transplant recipient who developed BKV interstitial nephritis and carcinoma of the bladder with widespread metastases. High level expression of BKV large T antigen in the primary and metastatic carcinoma, but not in the nonneoplastic urothelium, implicates BKV as an etiologic agent in the development of this tumor.
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PMID:Bladder carcinoma in a transplant recipient: evidence to implicate the BK human polyomavirus as a causal transforming agent. 1213 91

Bladder neoplasia in humans consists of 2 diseases, a low-grade papillary tumor that does not invade or metastasize, and a high-grade lesion that usually invades and metastasizes. Bladder carcinogenesis in rats is most like the low-grade, papillary tumor, although it eventually does progress and invade. In the mouse, models are available that mimic each of these disease processes. Preneoplastic lesions in humans and rodents include various types of hyperplasia, proliferative cystitis, and dysplasia. These preneoplastic and neoplastic lesions arise throughout the urothelium, from the renal pelvis to the urethra, although most commonly in the bladder. Rarely, benign and malignant mesenchymal lesions occur in rats and mice, with a unique submucosal mesenchymal lesion present in some strains of mice. In addition, eosinophilic and clear inclusions in the superficial layer of urothelium in mice, which do not appear to be associated with toxicity or carcinogenesis, have been reported. An approach to evaluation of carcinogenic mechanisms involved in the urothelium is presented. It focuses on distinguishing between DNA reactive carcinogens vs those that act by increasing cell proliferation. Although rodent models do not precisely mimic the human disease, they have provided useful models for furthering our understanding of the carcinogenic process in the urothelium as it pertains to human diseases.
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PMID:Comparative pathology of proliferative lesions of the urinary bladder. 1251 66

Florid von Brunn nests may mimic the nested variant of urothelial carcinoma. We examined formalin-fixed, paraffin-embedded tissue from 21 cases of florid von Brunn nests and 11 cases of nested variant of urothelial carcinoma. Morphologic features were recorded in detail. Also, cases were stained with monoclonal antibodies against MIB-1, p53, p27, and cytokeratin 20. Percentage positivity was calculated by counting 300 to 500 cells from each case. Clinical follow-up information was also obtained. Florid von Brunn nests from the bladder were comprised of large nests with regular spacing, and all the nests extended to the same horizontal level at the base of the proliferation. Central lumen formation was often seen within florid von Brunn nests, at times with cystic dilatation, such that there was a spectrum from proliferating von Brunn nests to cystitis glandularis to cystitis cystica. Small, crowded nests with variable spacing and an infiltrative base characterized nested variant of urothelial carcinoma. Four cases showed detrusor muscle invasion on biopsy with an additional case showing detrusor muscle invasion at cystectomy. One additional patient with nested variant of urothelial carcinoma had distant metastases and another had prostatic invasion. Nine of 21 florid von Brunn nests cases were from either the ureter or renal pelvis, whereas all cases of nested variant of urothelial carcinoma arose in the bladder. The ureteral and pelvic florid von Brunn nest cases showed smaller, more variable nests with irregular spacing closely mimicking nested variant of urothelial carcinoma but had a noninfiltrative base and often areas with either a lobular or linear array. Immunohistochemical studies showed nested variant of urothelial carcinoma to have higher MIB-1 expression (8.8% vs. 2.8%, P = 0.01). Nested variant of urothelial carcinoma had nonsignificantly higher p53 positivity (4.2% vs. 1.5%, P = 0.06) and lower p27 positivity (4.7% vs. 7.8%, P = 0.22). Cytokeratin 20 staining was not discriminatory. However, staining with each antibody was widely variable. Wide variation in staining for MIB-1, p53, p27, and cytokeratin 20 was seen in both florid von Brunn nests and nested variant of urothelial carcinoma, such that except for a few cases, a specific cutoff value could not be determined for diagnostic purposes. The findings underscore the importance of morphologic assessment in the distinction of florid von Brunn nests and nested variant of urothelial carcinoma.
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PMID:Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. 1296 Aug 9

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/- 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.
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PMID:Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma. 1620 80

Case 1: A 34-year-old woman,who had a right breast cancer with axillary lymph node metastasis and multiple bone metastases, was referred to our clinic. She developed paralysis of lower extremities and disorder of the bladder and rectum due to metastasis to the thoracic vertebra, and also had renal dysfunction due to severe hypercalcemia and hemorrhagic cystitis. Correcting the serum calcium level with intravenous infusion, elcatonin, pamidronate and betamethasone, she underwent radiation therapy for the vertebral metastasis. The first hormonal therapy (leuprorelin/exemestane) had been effective for about 4 months, however the second hormonal therapy (leuprorelin/tamoxifen) was not effective. Chemotherapy with paclitaxel (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about a stable general condition and a normal level of serum calcium with zoledronate in the ninth month of treatment. Case 2: A 32-year-old woman, who had a right breast cancer with multiple bone metastases and axillary and hilar lymph node metastases, came to our clinic, complaining of nausea due to severe hypercalcemia. After successful correction of hypercalcemia by the intravenous infusion and administration of elcatonin, pamidronate and dexamethasone, the hormonal therapy(goserelin/tamoxifen) caused rapid re-elevation of serum calcium and tumor marker, so that a tumor flare was suspected. After 3 cycles of EC therapy (EPI 90 mg/m(2), CPM 600 mg/m(2), every 3 weeks), 2 cycles of paclitaxel therapy (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about tumor reduction and the normal level of serum calcium. After 7 cycles of paclitaxel therapy,the hormonal therapy (goserelin/tamoxifen) proved effective for several months. To achieve tumor reduction and stabilize the serum calcium level, we need to start immediately the treatment of breast cancer with severe hypercalcemia, considering the general condition of the patient.
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PMID:[Two cases of stage IV breast cancer with severe hypercalcemia]. 1648 60

Among the many sites for primary small cell cancer is the genitourinary system. The majority of cases have been observed in the bladder and prostate. Small cell carcinoma accounts for less than 1% of all bladder tumors. Definitive predisposing factors are unknown; however, small cell carcinoma of the bladder has been associated with cigarette smoking, long-standing cystitis, bladder calculus, and augmented cystoplasty. Contrary to the early theory of derivation from Kulchitsky cells, it is now believed that small cell carcinoma of the bladder originates from the totipotent stem cells present in the submucosa of the bladder wall. A number of chromosomal aberrations have been reported in small cell cancer of the bladder. There are no specific clinical features that differentiate these patients from transitional cell carcinoma of the bladder; however, some patients may have associated paraneoplastic conditions. Diagnosis is established by cystoscopic-assisted biopsy. Like small cell carcinoma of the lung, small cell carcinoma of the bladder has a propensity for early metastases. There is no standard therapy for small cell carcinoma of the bladder and the prognosis is poor; however, patients treated with cisplatin-based chemotherapy regimens seem to have a better prognosis.
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PMID:Extrapulmonary small cell carcinoma of the bladder. 1727 Jun 61

Prostatic urothelial-type adenocarcinoma arises through a process of glandular metaplasia of the prostatic urethral urothelium and subsequent in situ adenocarcinoma sometimes associated with villous adenoma. These prostatic adenocarcinomas are analogous to nonurachal adenocarcinomas arising in the bladder from cystitis glandularis. Only 2 cases of urothelial-type adenocarcinoma from an institution other than our own have been previously described. The distinction between adenocarcinoma from another organ secondarily involving the prostate, usual adenocarcinoma of the prostate, and prostatic urothelial-type adenocarcinoma can present a significant diagnostic challenge and has significant therapeutic implications. Fifteen cases of prostatic urothelial-type adenocarcinoma were retrieved from the consult files of one of the authors. Mean patient age at diagnosis was 72 years (range 58 to 93 y). All men had negative colonoscopies, clinically excluding a colonic primary. Bladder primaries were ruled out clinically or pathologically in radical resection specimens. Follow-up was available on all men with a mean of 50.3 months (range 2 to 161 mo). All men presented with urinary obstruction symptoms with 3 (20%) also having mucusuria and 2 (13.3%) also having hematuria. Four men (26.7%) developed metastatic disease and 8 (53.3%) died of disease. In 8/15 (53%) cases, glandular metaplasia of the prostatic urethra and contiguous transition to adenocarcinoma were identified. Multiple histologic patterns were observed including dissection of the stroma by mucin pools 15/15 (100%), villous features 7/15 (47%), necrosis 2/15 (13.3%), signet ring cells 3/15 (20%), perineural invasion 1/15 (6.7%), focal squamous differentiation 1/15 (6.7%), and a granulomatous inflammatory response 1/15 (6.7%). Immunohistochemical stains were negative for prostate specific antigen, prostate specific acid phosphatase, CDX2, and beta-catenin in all cases. Stains were positive for high molecular weight cytokeratin in 12/12 cases (100%), and CK7 and CK20 in 10/12 cases (83.3%). Prostatic urothelial-type adenocarcinoma is a rare aggressive cancer arising in the prostate. The differential diagnosis includes conventional prostatic mucinous adenocarcinoma and secondary infiltration from a colonic or bladder adenocarcinoma. Immunohistochemistry for prostate specific antigen, prostate specific acid phosphatase, and high molecular weight cytokeratin along with morphology can help rule out conventional prostate carcinoma. beta-catenin, CDX2, and clinical studies are needed to rule out colonic adenocarcinoma. As prostatic urothelial-type adenocarcinoma is entirely analogous to bladder adenocarcinoma in both, its morphology and immunophenotype, only clinical studies or in some cases pathologic examination of the cystoprostatectomy specimen can exclude infiltration from a primary bladder adenocarcinoma.
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PMID:Primary mucin-producing urothelial-type adenocarcinoma of prostate: report of 15 cases. 1772 Nov 86

Nested urothelial carcinoma (UC) is a rare histologic variant of UC, characterized by deceptively bland histologic features resembling von Brunn's nests but usually with a poor outcome. In our experience, this variant is frequently misclassified or underrecognized as its clinicopathologic spectrum is not well defined. In addition, its relationship to usual UC and response to traditional bladder cancer management are largely unknown. Herein we report the largest series to date of 30 UC cases with pure or predominant nested morphology to identify its associated histopathologic findings, clinical outcome, and immunophenotype. Patient age ranged from 41 to 83 years (average, 63 years) with a male-female ratio of 2.3:1. The architectural pattern of the nested component ranged from a predominantly disorderly proliferation of discrete, small, variably sized nests (90%) to focal areas demonstrating confluent nests (40%), cordlike growth (37%), and cystitis cystica-like areas (33%) to tubular growth pattern (13%). The deep tumor-stroma interface was invariably (100%) jagged and infiltrative. Despite overall banal cytology, tumor nests demonstrated focal random cytologic atypia (90%) and focal high-grade cytologic atypia centered within the base of the tumor (40%). The tumor stroma ranged from having minimal stromal response to focally desmoplastic and myxoid. A component of usual UC was present in 63% of cases. The nested component demonstrated an immunophenotype identical to usual UC, with CK7, CK20, p63, and CK903 expression in 93%, 68%, 92%, and 92% of cases, respectively. At resection, all but 1 case demonstrated invasive carcinoma-9% into lamina propria, 4% into muscularis propria, 65% into perivesical fat, and 17% into adjacent organ(s). When compared with pure high-grade UC, nested UC was associated with muscle invasion at transurethral resection (31% versus 70%; P < .0001), extravesical disease at cystectomy (33% versus 83%; P < 0.0001), and metastatic disease (19% versus 67%; P < .0001). Follow-up was available on 29 patients (97%) with a median of 12 months (range, 1-31 months) of follow-up; 3 (10%) died of disease, 16 (55%) are alive with persistent or recurrent disease, and 10 (34%) are alive without disease. Response to neoadjuvant chemotherapy was observed in 2 (13%) of 15 patients. Nested UC seen either in pure form or with a component of usual UC had similarly unfavorable outcomes (P = .78). Increased awareness and familiarity with the clinicopathologic spectrum is critical for confident recognition and adequate management of this very aggressive variant of UC.
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PMID:Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases. 1980 Jan

BK virus (BKV) is known to cause subclinical infection in childhood. The virus remains latent in the human body, mainly in the urinary tract epithelium. After initiation of an immunosuppressive treatment, reactivation can occur in renal transplant recipients. BKV can cause hemorrhagic cystitis, ureteral stenosis and BKV nephropathy in immunocompromised patients. Furthermore, a number of case reports suggest an association between BKV infection and the development of urinary tract cancer. So far, an oncogenic potential of BKV has been observed in vitro and in animal models; however, its oncogenic capacity in humans remains unclear. We report the case of a 59-year-old patient who developed a poorly differentiated renal cell carcinoma in her renal allograft, with pulmonary and abdominal metastasis. Surgical removal of the allograft and cessation of the immunosuppressive therapy resulted in complete resolution of the metastatic disease.
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PMID:Renal cell carcinoma in the allograft: what is the role of polyomavirus? 2319 68


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