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 high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 +/- 1.5 years (x +/- SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 +/- 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 +/- 0.22 vs. -0.12 +/- 0.25, +0.03 +/- 0.19 vs. -0.54 +/- 0.24, and +0.08 +/- 0.14 vs. -0.02 +/- 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 +/- 0.04 vs. 0.40 +/- 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (-2.1 +/- 1.1 vs. +7.0 +/- 3.3 micrograms/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 +/- 2.5% vs. -0.3 +/- 1.4%, and +8.1 +/- 4.7 vs. -0.9 +/- 1.7, after 10.3 +/- 0.4 and 17.3 +/- 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.
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PMID:Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer. 880 93

Hypertension and norepinephrine hypersecretion in a 59-year-old woman suffering from malignant pheochromocytoma with multiple metastases were appropriately controlled with alpha- and beta- blockers, and alpha-methyltyrosine (alpha-MT), a catecholamine-synthesis inhibitor. Metastasized vertebrae were treated with external radiation to relieve pain, but this treatment had to be interrupted at a total dose of 20 Gy because the patient suffered acutely exacerbated hypertension (200/110 mmHg), tachycardia (160 beats/min) and a low-grade fever. Simultaneously her serum levels of LDH, potassium, urea nitrogen, creatinine, white blood cell count, CRP and norepinephrine were significantly increased, suggesting that this episode was due to radiation-induced tissue destruction and the leakage of catecholamines and possibly interleukin-6, a cytokine mediating inflammation which is reportedly present in pheochromocytoma. The marked hypertension was controlled by continuous i.v. administration of phentolamine and propranolol. Although radiation therapy effectively relieves pain due to neoplasmic metastasis to the bone, physicians should be aware that life-threatening complications such as the above occur in malignant pheochromocytoma. Sufficient pretreatment with adrenergic blocking agents and/or alpha-MT and careful monitoring of the patient's general condition during radiation therapy, even at a low dose, are highly recommended.
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PMID:Acutely exacerbated hypertension and increased inflammatory signs due to radiation treatment for metastatic pheochromocytoma. 898 Aug 90

1,25-dihydroxyvitamin D (1,25-(OH)2D) stimulates differentiation and controls proliferation in breast cancer cells. The role of endogenous 1,25-(OH)2D and its relation to PTH related protein (PTHrP) during the progression of breast cancer is not known; we therefore investigated these hormones in two studies. In a cross-sectional study of patients with breast cancer at different stages of disease, serum 1,25-(OH)2D levels (mean +/- SE) were highest in early disease (102 +/- 3.7 pmol/L), fell in normocalemic patients with bone metastases (52 +/- 5.3 pmol/L; P < 0.01), and were lowest in hypercalcemic patients (33 +/- 5.6 pmol/L; P < 0.001). PTHrP was detectable in the serum of only one normocalcemic patient with progressive metastases but was present in 11 of the 12 hypercalcemic patients, thus PTHrP did not stimulate 1,25-(OH)2D synthesis. In a 6-month longitudinal study of normocalcemic patients with bone metastases undergoing hormonal therapy, serum 1,25-(OH)2D concentrations fell in patients whose disease progressed (P = 0.0056), but remained constant in those who were stable or responded to treatment. These changes in 1,25-(OH)2D preceded clinical signs of progression and predicted disease response. In the progressive group, five of whom died during the study, 1,25-(OH)2D decreased between the initial and final samples, PTH fell significantly from 24.8 to 13.5 ng/L (P = 0.025), serum calcium rose from 2.27 to 2.39 mmol/L (P = 0.017), and the urinary calcium/creatinine ratio rose from 0.37 to 0.68 (P = 0.046). PTH and 1,25-(OH)2D were significantly correlated in the final samples from this group, Spearman's rank correlation = 0.80, P = 0.022. The results indicate that normocalcemia in these patients is maintained, at the expense of suppressing PTH and 1,25-(OH)2D, in the face of increased calcium released from lytic lesions in bone. Loss of the antiproliferative effects of 1,25-(OH)2D may then permit more rapid secondary growth of the tumor.
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PMID:Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases. 932 98

Urethral bladder substitution is traditionally suggested to good prognosis cystectomized patients. In our series this diversion was chosen for all but the salvage cystectomized men. Between the 1st of February 1991 and the 30th of April 1996, one hundred consecutive men underwent lower urinary tract reconstruction after radical cystoprostatectomy for bladder cancer. An orthotopic ileal neobladder was constructed (in 84 cases according to Kock's technique and in 16 to Studer's technique). Total early complication rate was 29% (29/100), including one perioperative death due to sepsis (mortality rate 1%). 13 patients required surgery (6 retroperitoneal hematomas, 2 wound dehiscences, 1 urinary fistula, 1 lymphocele, 1 rectal-neobladder fistula, 1 rectal-cutaneous fistula, 1 necrosis of the terminal ureter). The late complication rate was 19% (19/100); in 8 cases reparative surgery was required (1 mechanical ileus, 2 bladder neck stenoses, 3 stenoses of the ureteral anastomosis, 2 laparoceles). Four patients were lost at the follow-up; out of the 96 remaining patients only 85 were evaluable for continence: continence during the day was achieved in a period between there to six months in 78 patients (91.7%); night continence was achieved with planned awakenings in 60 patients (70.5%). Eight patients recovered potency, another 7 had successful intercourses after PGE1 intracavernous injection. Renal function based on creatinine value was mildly impaired in 5/78 evaluable patients (6.4%) (peak creatinine 2.8 mg%). In 29 patients tumour progression was observed (29%): 9 pelvic and 20 metastatic. Among the latter 2 urethral recurrences were observed (2%). Twenty-four patients died for metastatic cancer, one for primitive lung cancer, one patient for postoperative septic shock. Adjuvant chemotherapy was administered in 11 patients without complication with an indwelling catheter in the neobladder to avoid drug reabsorption. Four patients showed complete response (2 are alive after a mean of 12 months), 6 were non responders and 1 had a partial response. In our series the ileal neobladder is a feasible method of urinary diversion when urethral cancer involvement is ruled out. Early and late complications are proportionally decreasing with experience and overall continence is satisfactory. The fate of the neobladder depends on both the technique and patient's compliance. Only educated patients can cope successfully with neobladder diversion without major complications. All the patients operated for non salvage cystectomy deserve to be diverted with a continent urethral bladder substitution.
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PMID:[100 orthotopic neobladders in men after cystectomy: a 5-year experience]. 902 35

Between 1980 and 1995, 13 patients with end-stage renal disease due to Wegener's granulomatosis received 14 renal transplants (10 cadaveric, 4 living related). The mean follow-up in the 13 successfully transplanted patients was 50 months (4-107 months). One patient had primary nonfunction and received another graft 4 months later. Three episodes of acute rejection occurred in two patients, and one of these patients lost her graft due to severe vascular rejection 4 months after transplantation. Two patients died with well-functioning grafts (one of metastatic cancer and one of sepsis). One patient presented with perisinusitis and had a mild recurrence of Wegener's disease. None of the patients developed recurrent disease in the transplanted organ. At the last follow-up, the mean creatinine (+/-SD) in the 12 patients with functioning grafts was 1.6 +/- 0.6 mgdl. We conclude that renal transplantation is an excellent treatment for renal failure due to Wegener's granulomatosis. Recurrence of the disease is uncommon in patients under immunosuppression, but careful monitoring is extremely important.
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PMID:Single-center experience with renal transplantation in patients with Wegener's granulomatosis. 909 4

This is a phase II study to evaluate the efficacy and toxicity of short-course carboplatin in advanced-stage nasopharyngeal carcinoma (NPC). Thirty-three previously untreated stage III-IV NPC patients were studied. Carboplatin was given as a rapid intravenous injection every 3 weeks. The dose of carboplatin was calculated according to the individual patient's creatinine clearance and desired platelet nadir of 75,000/microliter according to the Egorin formula. Response and toxicity were evaluated. Thirty-two patients were evaluated for response. The median age was 54 years, range 30-70 years. Twenty-four patients had local regional disease and 8 patients had metastatic disease. The median dose of carboplatin given was 415 mg/m2 (range 91-791 mg/m2). Fourteen (44%) patients had a partial response with a 95% confidence interval of 26-62%. Fifteen (47%) patients had stable disease and 3 (9%) progressive disease. The overall median survival rate was not reached at 43 months. Overall toxicity was tolerable. Grade III-IV myelosuppression occurred in 4 (12%) patients. There were no other major toxicity- or treatment-related deaths. We conclude that carboplatin has a significant anticancer effect in advanced NPC. Thus carboplatin combination chemotherapy for the treatment of NPC is worthy of future clinical investigations.
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PMID:A phase II study of carboplatin in nasopharyngeal carcinoma. 914

The levels of probable markers of bony metastatic disease were measured to evaluate their efficacy as predictors of disease and therapeutic outcome. Urinary pyridinoline and deoxypyridinoline were measured in patients with benign prostatic hyperplasia, clinically localized prostate cancer and prostate cancer with bone metastases. Also, urinary pyridinoline and deoxypyridinoline were compared in 2 groups of patients with metastatic prostate cancer of the bone who demonstrated progression or positive response to treatment. Urinary pyridinoline and deoxypyridinoline were determined by high performance liquid chromatography and were normalized to urinary creatinine. Levels of urinary pyridinoline and deoxypyridinoline in urine in patients with bony metastatic prostate cancer were significantly greater than levels in patients with benign prostatic hyperplasia or localized prostate cancer. Serial measurement of urinary pyridinoline and deoxypyridinoline was correlated with a positive response to treatment (decreased) and with clinical progression of disease (increased) before detection of new bone lesions by bone scintigraphy. Measurement of urinary pyridinoline and deoxypyridinoline may provide a useful marker of prostate cancer metastatic to bone and may be useful in monitoring the response to treatment.
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PMID:[The clinical usefulness of urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer]. 975 May 11

In normal adults, the maintenance of phosphate balance involves the reabsorption of 85-90% of filtered phosphate by the proximal tubule. At a glomerular filtration rate (GFR) of 125 ml min-1 and a plasma phosphate concentration of 1.3 mmol l-1, the filtered phosphate is approximately 235 mmol day-1. Following intravenous administration, 25-50% of 32P is excreted over 4-6 days in normal subjects. In spite of such extensive renal handling of phosphate and, therefore, of 32P, there are no data in the literature concerning possible 32P-related nephrotoxicity. Adult dosimetry values for the kidney after 32P are reported as 4.8 rad mCi-1 h-1 (0.048 mSev 37 MBq-1 h-1). The entry criteria for 32P therapy insist on a normal serum creatinine value, reflecting awareness of potential renal damage. To answer the fundamental question of whether there is demonstrable renal damage after 32P, we undertook serial measurements of GFR in patients given 32P for treatment of pain from skeletal metastases. Twenty-one patients who had normal pre-treatment renal function as shown by normal serum creatinine values were administered 32P orally in doses ranging from 277.5 to 466.2 MBq, with a mean of 425.5 MBq. Pre-treatment, GFR was estimated with 99Tcm-diethylenetriamine pentaacetate renography using the Gates protocol. Post-treatment, GFR was estimated serially as far as possible, at weeks, 1, 2, 3 and 4 and then every 4 weeks for another 3 months, at which point follow-up ceased. Serum creatinine was assessed pre-treatment and every 2 weeks until the end of follow-up, in addition to all other parameters and a clinical evaluation. Mean pre-treatment GFR was 87.5 ml min-1, with a range of 48.7-110 ml min-1. Not all patients could fulfil the entire follow-up schedule as designed, but we obtained a minimum of four follow-up tests, two before and two after 4 weeks post-treatment. GFR fell to 72% of the pre-therapy value during the first 4 weeks following therapy. By the sixteenth week, however, the mean value had returned to or exceeded the pre-treatment value. There was no change in serum creatinine values. At a time when multiple therapies are being considered, this early depression of GFR may be of importance. A closer assessment of altered renal function may be warranted and other sensitive tests of renal damage like microalbuminuria could be used.
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PMID:Does renal damage occur after the administration of 32P for palliation of pain from skeletal metastases? 985 50

The immune system of the patients with colorectal cancer is activated. Urinary neopterin is an index of this systemic immune activation, reflecting the circulating activity of interferon-gamma. We have measured urinary neopterin excretion in 34 patients with colorectal cancer. This excretion was significantly higher in our patients compared to reference group (325 +/- 267 vs 169 +/- 62 mumol/mol creatinine, neopterin concentrations were considerably higher in Dukes' stage D disease compared with Dukes' stage B and C disease/561 +/- 372 vs 188 +/- 47 and 250 +/- 142 mu/mol creatinine. Increased neopterin detected the presence of metastatic disease with 90% sensitivity and 87.5% specificity. Authors conclude that urinary neopterin measurement may be useful in the staging of colorectal cancer.
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PMID:[Activation of the immune system in colorectal carcinoma and its assessment]. 1010 45

In adults, the haemolytic-uraemic syndrome (HUS) is associated with probable causative factors in the minority of all cases. Cytotoxic drugs are one of these potential causative agents. Although metastatic cancer by itself is a recognized risk-factor for the development of HUS, therapy with mitomycin-C, with cis-platinum, and with bleomycin carries a significant, albeit extremely small, risk for the development of HUS, compared with all other cytotoxic drugs. Gemcitabine is a novel cytotoxic drug with promising activity against pancreatic adenocarcinoma. We are reporting on one patient with metastatic duodenal papillary carcinoma developing HUS while on weekly gemcitabine therapy. The presenting features in this patient were non-cardiac pulmonary oedema, renal failure, thrombocytopenia and haemolytic anaemia. The diagnosis of HUS was made on the day of admission of the patient to this institution. Upon aggressive therapy, including one single haemodialysis and five plasmaphereses, the patient recovered uneventfully, with modestly elevated creatinine-values as a remnant of the acute illness. Re-exposure to gemcitabine 6 months after the episode of HUS instituted for progressive carcinoma, thus far has not caused another episode of HUS.
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PMID:Elevated reticulocyte count--a clue to the diagnosis of haemolytic-uraemic syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal papillary carcinoma: a case report. 1018


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