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)

A 68 year old man with prostatic carcinoma and extensive painful osteoblastic metastases was discovered to have hypocalcemia (serum calcium 7.1 mg/dl) without evidence of hypoalbuminemia, renal failure or malabsorption. Baseline studies revealed hypocalciuria (24 hour urine calcium less than 5 mg/day), normal serum phosphate (3.4 mg/dl), low tubular reabsorption of phosphate (68 percent), undetectable serum calcitonin, normal serum 25-hydroxyvitamin D, slightly elevated serum parathyroid hormone level and increased urinary cyclic AMP (8.87 mumol/g creatinine). These studies were compatible with secondary hyperparathyroidism. The intravenous administration of parathyroid extract produced no further change in urinary phosphate but a 25-fold increase in nephrogenous cyclic AMP. Three days administration of intramuscular parathyroid extract slowly and temporarily restored serum calcium to normal levels while increasing urinary cyclic AMP and phosphate. Chemotherapy with cyclophosphamide and 5-fluorouracil rendered the patient free of pain while reducing serum acid and alkaline phosphatase levels and restoring serum total and ionized calcium and urinary cyclic AMP excretion to normal.
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PMID:Hypocalcemia with osteoblastic metastases in patient with prostate carcinoma. A cause of secondary hyperparathyroidism. 724 80

The urinary excretion of Hydroxyproline (OH-P), evaluated as OH-P/creatinine ratio, has been examined in the follow up of 142 breast cancer patients. The mean value obtained in the women with bone lytic lesions, prior to treatment, was 5.3 +/- 1.9 (min. 3, max. 9), whereas in the women without bone metastases it was 1.7 +/- 0.5 (min. 0.6, max. 3), similar to the control group. The patients affected by osteoplastic lesions had a normal OH-P/creatinine ratio. The highest values of OH-P/creatinine ratio were found in women with bone marrow infiltration, ascertained by bone needle biopsy. In the group of patients with bone lytic metastases, a good correlation between changes of OH-P/creatinine ratio and response to hormonal or chemotherapeutic treatment has been observed. Therefore the OH-P/creatinine ratio could be effectively useful, with other clinical parameters, in the follow up of breast cancer patients.
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PMID:[Hydroxyprolinuria and bone metastases of breast cancer]. 744 2

Serum electrolytes, creatinine, urea, protein, albumin, bilirubin and glucose were examined every 4 days until time of death in rabbits with VX-2 carcinoma implanted in one kidney. The rabbits were treated with doxorubicin, nephrectomy or combinations thereof and observed for up to 1 year. Rabbits treated with doxorubicin only showed a slight creatinine rise initially, but over time creatinine reached almost the same concentration as that in nephrectomized rabbits receiving equivalent doses of doxorubicin. Creatinine concentrations increased significantly above the normal range following nephrectomy combined with doxorubicin. Doxorubicin nephrotoxicity in rabbits occurs at lower doses than previously reported. In all rabbits the parameters except creatinine remained stable within the established normal ranges, except for the last 4 days before time of death in the animals with metastatic disease. Weight loss was the best parameter for making a prognosis for an individual rabbit, since peak weight was noted 16-20 days before death. In experimental work with VX-2 carcinoma, weight is thus the most important indicator of the time at which rabbits not responding to treatment can be put to death to avoid unnecessary suffering before the end of the experiment.
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PMID:Doxorubicin treatment of rabbit renal VX-2 carcinoma: nephrotoxicity, serum parameters and weight. 748 43

The efficacy of radionuclide bone scans in monitoring metastatic bone activity remains controversial. Objective measurement of bone tumor burden would be useful for the evaluation of new therapies for metastatic carcinoma of the prostate. The recent discovery of the urinary excretion of pyridinoline (cross-link of mature collagen found in cartilage and bone) and deoxypyridinoline (collagen cross-link specific to bone) measured by high pressure liquid chromatography has provided sensitive specific indexes of cartilage and bone breakdown in rheumatoid arthritis, osteoporosis and metabolic bone diseases. We compared the urinary excretion of deoxypyridinoline,pyridinoline and hydroxyproline relative to urinary creatinine (nmol./mmol.creatinine) in 27 patients with benign prostatic hyperplasia (patient age 70.0 +/- 8.5 years, standard deviation), 29 with clinically confined prostate cancer (age 70.2 +/- 9.7 years), and 26 with prostate cancer and bone metastases (age 71.1 +/- 7.7 years). No diurnal variation of deoxypyridinoline or pyridinoline urinary excretion was detected in 5 patients with metastases. Urinary excretion of pyridinoline and deoxypyridinoline was significantly greater in patients with metastatic carcinoma of the prostate compared with patients with either benign prostatic hyperplasia (Mann-Whitney-Wilcoxon rank sum analysis, p < 0.00004 and 0.002, respectively) or localized prostate cancer (Mann-Whitney-Wilcoxon, p < 0.00001 and 0.00005, respectively). Urinary hydroxyproline levels failed to separate the 3 groups. Pyridinoline and deoxypyridinoline excretion in prostate cancer patients with metastases directly correlated with bone scan Soloway scores (r = 0.55, p < 0.005 and r = 0.57, p < 0.004 respectively), whereas serum prostate specific antigen did not (r = 0.36, p = 0.08). Serial measurements of pyridinoline and deoxypyridinoline progressively increased in 3 patients with clinical progression documented by new metastatic lesions by bone scan. Measurement of pyridinoline and deoxypyridinoline excretion cannot diagnose metastatic disease. However, these markers should be evaluated further for quantitative assessment of bone metastases.
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PMID:Collagen cross-link metabolites in urine as markers of bone metastases in prostatic carcinoma. 751 Mar 46

The combination of 5-fluorouracil (5-FU) and folinic acid (FA) has demonstrated activity in colorectal cancer (CC). Cisplatin is reported to have synergistic activity with 5-FU. We examined the combination FA + 5-FU + cisplatin in patients who had previously received chemotherapy with FA + 5-FU and relapsed. Two months after the last dose of FA + 5-FU and documentation of relapse, patients continued with the regimen consisting of cisplatin 20 mg/m2 in 15 min i.v. infusion followed by FA 500 mg/m2 in 1 h i.v. infusion, in the middle of which 5-FU 500 mg/m2 i.v. bolus was administered, with adequate post-hydration. This was repeated weekly for 4 weeks followed by a 2 week rest, for a maximum of six cycles. A total of 30 patients with CC that had relapsed to the combination of FA + 5-FU were treated; 23 had previous surgery and none had radiotherapy. Local recurrence was found in eight patients, metastases in the liver in 21, in lymph nodes in six, lung six and peritoneal metastases in seven. Seven patients responded partially. Toxicity requiring dose reduction or discontinuation of treatment included neutropenia 42% (grade 3:7%), mucositis 28% (grade 1:2), diarrhea 63% (Grade 3:10%), nausea-vomiting 55% (Grade 3:10%), increased creatinine value in three patients and peripheral neuropathy in two patients. We conclude that evaluation of this regimen shows substantial toxicity, with satisfactory response as a second line chemotherapy in these heavily pretreated patients.
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PMID:5-Fluorouracil, folinic acid and cisplatin in advanced colorectal cancer: a pilot study. 757 65

Bone metastases strongly affect skeletal metabolism by both their growth and their paracrine activities. However, so far no specific laboratory marker has been found to signal the spread of neoplastic disease to bone. We performed a cross-sectional study of 153 cancer patients and an equal number of healthy controls matched for sex and age, in which we determined serum levels of calcium and total alkaline phosphatase (TAP) as well as the fasting urinary excretion of calcium (uCa) and of the collagen cross-links pyridinoline (uPYD) and deoxypyridinoline (uDPD). The aim of the study was to analyze the diagnostic validity of the biochemical parameters measured with regard to neoplastic bone involvement. In the cancer group, 98 patients had overt bone metastases, as judged from radiographic and radioisotopic bone imaging. The remaining 55 patients were also in an advanced stage of disease, but there was no evidence of malignant bone involvement. In comparison to healthy controls, patients both with and without metastatic bone disease had significantly higher levels of TAP, uPYD, and uDPD (P < 0.0001). Only in cancer patients with bone metastases was the median serum calcium level higher than in the healthy controls (P < 0.02). uCa was the same in cancer patients and the control group. Within the collective of cancer patients, individuals with skeletal metastases had higher levels of serum calcium (P < 0.05), TAP (P < 0.01), and uPYD and uDPD (both P < 0.0001), than patients without evidence of malignant bone disease. uCa did not differ between the 2 groups of cancer patients. The cancer patients were then stratified into 4 subgroups according to the serum calcium level (< or = 2.6 mmol/L >) and the absence or evidence of bone metastases. This stratification revealed that in patients with bone metastases, uPYD and uDPD levels were similar in normocalcemic and hypercalcemic subjects, whereas in hypercalcemic patients, uCa levels significantly exceeded those in normocalcemic patients. When the efficacy of TAP, uCa, uPYD, and uDPD in discriminating between patients with and without bone metastases was evaluated by use of receiver-operating characteristic curves and stepwise multivariate regression analysis, uPYD was found to have the highest diagnostic validity. Using 50 mumol PYD/mol creatinine (i.e. the upper limit of normal range) as the cut-off level, the sensitivity of uPYD was 88.7%, whereas the specificity was only 41.8% (odds ratio, 5.598; 95% confidence interval, 2.547-12.306).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease. 782 46

A third-generation platinum analogue, zeniplatin, was administered at a dose of 145 mg/m2 intravenously over 60-90 minutes every 21 days as the initial chemotherapy to 21 patients with metastatic melanoma. Prehydration and mannitol diuresis was introduced after the first 7 patients. There were 17 males and 4 females. The median age was 52 (range: 29-81). ECOG performance status was 0 in 10 patients, 1 in 8 patients and 2 in 3 patients. Major disease sites were lymph nodes, skin, lung, liver, and bone. Patients received a median of 2 cycles (range: 1-7). Two patients achieved partial responses. One with nodal disease progressed after 166 days and the other with buccal mucosal disease after 142 days. A third patient showed partial regression of nodal disease but developed cerebral metastases. Gastrointestinal toxicity included WHO grade 3 vomiting in 8 patients and nausea in 2. Antiemetics were used, but ondansetron was not available. WHO grade 3 hematologic toxicities included neutropenia in 8 patients and anemia and thrombocytopenia in 1 patient. Thrombocytosis was seen in 35% of courses. Dosage reduction was required in 15% of courses and escalation in 5% of courses. Three patients developed phlebitis related to the infusion. One patient developed a reversible rise in serum creatinine, but, unlike other studies, no severe nephrotoxicity was reported. Zeniplatin demonstrated only modest activity in melanoma with significant gastrointestinal and hematologic toxicity.
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PMID:A phase II trial of zeniplatin in metastatic melanoma. 784 60

The serum levels of creatinine (CR), alkaline phosphatase (ALP), acid phosphatase (ACP) and tartrate inhibitable acid phosphatase (TIAP) were related to Gleason score, TM-category, disease progression and survival in 325 prostatic adenocarcinoma patients followed up for over 12 years. Elevated serum levels of CR, ALP, ACP and TIAP were related to invasive and metastatic disease as well as with a high Gleason score. Elevated serum levels of CR, ALP, ACP and TIAP, all significantly predicted prognosis in a univariate analysis. In the M0 tumours, ACP and TIAP and TIAP had prognostic value, as they did in the T1-2M0 tumours respectively. Cox's multivariate analysis showed that serum creatinine level at diagnosis had independent prognostic value additional to the TM-classification, Gleason score and patient age. In the M0 tumours, ALP had independent prognostic significance additional to the T-category, Gleason score and patient age. In the T1-2M0 tumours, TIAP had independent prognostic value supplementary to the Gleason score, T-category and patient age, whereas in the T1M0 tumours, the gleason score was an independent prognostic parameter. The results indicate that these simple laboratory tests give important prognostic information in prostatic adenocarcinoma.
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PMID:Biochemical parameters as prognostic factors in prostatic adenocarcinoma. 786 37

Twenty patients with either unresectable primary hepatocellular carcinoma or hepatic metastases were entered into a chemoembolization program with cisplatin and lipiodol; 19 patients were evaluable for response. Doses of cisplatin ranged from 40 to 100 mg/m2. Toxicity was tolerable and reversible and included abdominal pain, transient elevation in serum creatinine, serum bilirubin, and serum transaminases. Less common side effects include fever, ascites or pleural effusion, and hiccups. Two of four patients with ocular melanoma had partial responses. Duration of response was 10 and 11 months. Among 8 patients with unresectable hepatoma, 2 patients had partial response for 10+ and 13 months, 2 had minor response for 2 months and 4+ months, 1 patient had stable disease for 5+ months, and 3 patients failed to respond. Of the six colon cancer patients treated, one had a partial response in the liver, but developed progressive nodal disease, and another patient had a partial response for 3 months. Chemoembolization of the liver with cisplatin and lipiodol is feasible and doses of cisplatin at least 100 mg/m2 are tolerable. Antitumor activity in metastatic ocular melanoma is encouraging but requires further study.
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PMID:A phase I study of chemoembolization with cisplatin and lipiodol for primary and metastatic liver cancer. 809 12

Interleukin-2 (IL-2)-based therapy induces a vascular leak syndrome (VLS), manifested by hypotension, tachycardia, and oliguria, as is also seen with septic shock. The optimal method for treating such VLS is not known. A prospective randomized trial was undertaken to compare crystalloid and colloid fluid resuscitation for patients receiving bolus IL-2-based therapy for metastatic cancer. All patients received maintenance crystalloid fluid administration and were randomized to receive crystalloid (0.9% normal saline) or colloid (5% human serum albumin) fluid boluses to maintain acceptable vital signs and urine output. Patients refractory to fluid boluses were given dopamine for oliguria and/or phenylephrine for hypotension. Of 107 patients who completed one cycle of therapy on study, 76 completed a full treatment course (two cycles) on study. The total number of saline and albumin fluid boluses given were 9.5 +/- 0.9 versus 7.7 +/- 0.7 (p = 0.36, n = 107) for the first cycle and 19.2 +/- 1.8 versus 16.1 +/- 1.6 (p = 0.33, n = 76) for a complete course, respectively. Although patients receiving saline boluses had significantly more oliguria during a course of therapy, weight gain, number of IL-2 doses, tachycardia, hypotension, vasopressor use, hospital stay, and clinical response rates did not significantly differ between arms. Changes in hematocrit, hemoglobin, protein, albumin, blood urea nitrogen (BUN), and creatinine were analyzed, and patients receiving crystalloid showed greater decreases in albumin (p < 0.0001) and total protein (p < 0.05) as expected. A 40-fold greater cost associated with albumin suggested that crystalloid resuscitation be used to treat the VLS associated with IL-2 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A prospective randomized trial evaluating colloid versus crystalloid resuscitation in the treatment of the vascular leak syndrome associated with interleukin-2 therapy. 811 Jul 27


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