Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regional toxicity of an anticancer agent for normal liver tissue following hepatic arterial infusion chemotherapy (HAI) was evaluated in terms of morphology, function, and histopathology. Forty-two patients(M:F = 30:12; mean age, 59.9 years) with liver metastases from colorectal cancer were treated with HAI using a totally implantable vascular access port system from July 1994 to March 1999. The regimen used here was so-called weekly high-dose 5-fluorouracil(5-FU) infusion(5-FU, 1,000 mg/m2/week). Volume measurement of the liver demonstrated not only whole liver atrophy including the tumor but also volume reduction of the non-tumorous lobe. Atrophic change of the liver was seen in patients who were administered over 20 g/m2 of 5-FU(p < 0.01). The CT attenuation values of the liver were examined, and fatty infiltration was seen in six patients. Histologic examination of liver biopsies from the non-tumorous part revealed steatosis and infiltration of inflammatory cells in the portal triad, which were not seen in specimens prior to HAI. On clinical laboratory findings, enzymes representing bile duct, including alkaline phosphatase, leucine amino peptidase, and gamma-glutamyltranspeptidase, were increased in 22 patients. In terms of regional toxicity for long-term HAI, 20 g/m2 of 5-FU, is the key dose at which to consider temporary cessation or dose reduction.
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PMID:[Evaluation of hepatic toxicity following high-dose 5-FU arterial infusion chemotherapy: analysis of 42 cases of colorectal liver metastases]. 1074 Nov 16

Patients with metastatic rectal cancer precluding curative low anterior resection (LAR) or abdominoperineal resection (APR) can require palliation for impending obstruction. LAR or APR is frequently not optimal because of the associated operative morbidity. Lesser procedures such as diverting colostomy require patients to live with a permanent stoma. Endoscopic transanal resection (ETAR) has been used for excision of rectal lesions. To determine whether ETAR provides palliation equivalent to LAR or APR, we reviewed the outcomes of 49 patients with rectal adenocarcinoma and unresectable liver metastases who required palliative intervention between January 1989 and July 1996. Of these 49 patients, 24 underwent ETAR; the intraluminal tumor was resected using the urologic resectoscope to achieve a hemostatic, patent lumen. The outcomes of these patients were compared to those of the other 25 patients who had palliative LAR, APR, or a Hartmann procedure during the same period. The median distance of the tumors from the anal verge was similar (5 cm; range 1 to 15 cm). ETAR patients had a higher percentage of poorly differentiated tumors (35% vs. 6%, P = 0.034) and higher preoperative alkaline phosphatase values (478 +/- 75 mg/dl vs. 231 +/- 24 mg/dl; P < 0.015), suggesting more aggressive disease and greater hepatic tumor burden, respectively. Despite these differences, overall survival and time spent outside the hospital were similar in the two groups. The median number of debulking procedures required in the 24 ETAR patients was two (range 1 to 17). Resections in the 25 LAR/APR patients included LAR in 20, APR in two, and Hartmann procedures in three. There was a trend toward more stomas in the LAR/APR group (28% vs. 17%). More important, morbidity was significantly higher in the LAR/APR patients (24% vs. 4%; P = 0.049). In conclusion, ETAR is a safe alternative for the palliation of incurable rectal tumors. Compared to transabdominal resection, ETAR provides equivalent palliation as measured by survival and proportion of the patient's life spent outside the hospital, with a lower stoma rate and significantly less morbidity. Therefore, in select patients with metastatic rectal cancer, ETAR is an important palliative option.
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PMID:Endoscopic transanal resection provides palliation equivalent to transabdominal resection in patients with metastatic rectal cancer. 1136 51

Liver metastasis of colorectal cancer is a life-threatening prognostic factor. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). The diagnosis has been carried out by clinical examination, abnormal alkaline phosphatase, lactic acid dehydrogenase and tumor markers, abdominal liver echography and computed tomography scan. Angiography and intraoperative echography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems useful combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review reports the possibilities of intraarterial chemotherapy and other novel hepatic directed approaches to the treatment of liver metastases from this common disease.
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PMID:Locoregional therapy for liver metastases from colorectal cancer: the possibilities of intraarterial chemotherapy, and new hepatic-directed modalities. 1137 96

Colorectal cancer (CRC) is one of the most common malignant tumors in adults. Twenty-five percent of patients are not amenable to surgical resection because they have locally advanced or metastatic disease. For these patients, median survival time is between 4 and 13 months, and chemotherapy is used mainly with palliative intent. We conducted this study to evaluate potential prognostic factors for time to progression and survival. A retrospective review of 91 patients with metastatic CRC treated with bolus 5-fluorouracil-based chemotherapy (Mayo Clinic schedule) was performed. Univariate and multivariate analyses of clinical prognostic factors were carried out. Median follow-up time was 53 months (range, 17-107 months). Median time to disease progression was 9.6 months, and median survival time was 15.4 months. Actuarial 5-year survival was 17%. In the univariate analyses, factors predictive of time to progression were visceral metastases, elevated alkaline phosphatase (AP) levels, performance status (PS), and elevated carcinoembryonic antigen (CEA) and CA 19-9 levels. Multivariate analyses confirmed the independent prognostic value of PS and AP levels. In the univariate analyses for survival, significant prognostic factors were visceral metastases, hypoalbuminemia, elevated lactate dehydrogenase levels, elevated AP levels, PS, and elevated CEA and CA 19-9 levels. In the multivariate analyses, only PS, elevated CEA and CA 19-9 levels, and liver involvement retained prognostic significance. This study confirms the prognostic value of PS for both time to progression and survival. AP levels are significantly related to time to progression. Additional factors influencing survival time are elevated tumor marker levels and the existence of liver metastases.
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PMID:Analysis of clinical prognostic factors for survival and time to progression in patients with metastatic colorectal cancer treated with 5-fluorouracil-based chemotherapy. 1262 Jan 43

A technique for measuring the alkaline phosphatase activity of serum protein fractions separated by electrophoresis on cellulose acetate strips is described. Alkaline phosphatase activity in alpha 2, alpha 1, and beta globulins and in albumin is present in varying proportions in normal and pathological sera. In normal sera peak activity is in the alpha 2 globulins and beta globulins have a little more than half the alpha 2 activity. Albumin activity is often more than 10% of the total, but alpha 1 and gamma globulin activity is less than this. In bone disorders with a high serum alkaline phosphatase a large, and sometimes predominant, part of the increase is due to raised beta globulin phosphatase activity, and alpha 2 activity is also raised. Alpha 1 activity, though usually low, may be increased. In hepatobiliary disorders with a high phosphatase concentration the increase is due mainly to raised alpha 2 phosphatase activity, and there is also an increase in alpha 1 phosphatase. Beta activity is usually, but not always, low, and albumin activity may be somewhat increased in obstructive jaundice and liver metastases. There is some overlap between these two patterns of alkaline phosphatase distribution. The findings are consistent with the possibility that alkaline phosphatases in different protein fractions are derived from different tissues.
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PMID:Distribution of alkaline phosphatase in serum protein fractions. 1445 63

The purpose of this study was to determine whether there is evidence for hepatocellular radiation injury following treatment with (90)Y-SMT487 ((90)Y-DOTA-tyr3-octreotide, OctreoTher(TM)) in patients with extensive liver metastases from neuroendocrine tumors. Patients reported in this study participated in a Phase II trial of efficacy and safety of (90)Y-SMT487. The trial design called for three treatment cycles of 120 mCi each (4400 MBq) of (90)Y-SMT487. (111)In-pentetreotide SPECT images were used to determine the extent of liver metastases. Serum AST, ALT, and alkaline phosphatase levels were obtained at baseline and following each cycle of therapy. Least squares fit was applied to the serial liver enzyme measurements in patients with extensive liver metastases. Post-therapy liver enzyme measurements were also evaluated using WHO common toxicity criteria. Repeated-measures ANOVA and paired t-test were applied to the serial enzyme measures. There were 21 subjects. Fifteen of these had hepatic metastases with 12 demonstrating extensive (defined as 25% or more) liver involvement. In only 4 of these 15 did any of the three enzyme levels increase in WHO toxicity grade from baseline to final follow-up. We conclude that patients with diffuse SSTR positive hepatic metastases can be treated with a cumulative administered activity of 360 mCi (90)Y-SMT487 with only a small chance of developing mild acute or subacute hepatic radiation injury.
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PMID:Assessment of hepatic toxicity from treatment with 90Y-SMT 487 (OctreoTher(TM)) in patients with diffuse somatostatin receptor positive liver metastases. 1450 53

The objective of this study was to identify prognostic factors for survival in patients with advanced oesophageal cancer, who are treated with cisplatin-based combination chemotherapy. We analysed the baseline characteristics of 350 patients who were treated in six consecutive prospective trials with one of the following regimens: cisplatin/etoposide, cisplatin/etoposide/5-fluorouracil, cisplatin/paclitaxel (weekly) and cisplatin/paclitaxel (biweekly). Predictive factors in univariate analyses were further evaluated using multivariate analysis (Cox regression). The median survival of all patients was 9 months. The 1, 2 and 5-year survival rates were 33, 12 and 4%, respectively. The main prognostic factors were found to be WHO performance status (0 or 1 vs 2), lactate dehydrogenase (normal vs elevated), extent of disease (limited disease defined as locoregional irresectable disease or lymph node metastases confined to either the supraclavicular or celiac region vs extensively disseminated disease) in addition to the type of treatment (weekly or biweekly cisplatin/paclitaxel regimen vs 4-weekly cisplatin/etoposide with or without 5-fluorouracil). Although weight loss, liver metastases and alkaline phosphatase were significant prognostic factors in univariate analyses, these factors lost their significance in multivariate analyses. The median survival for patients without any risk factors was 12 months, compared to only 4 months in patients with WHO 2 plus elevated LDH and extensive disease. The performance status, extent of disease, LDH and the addition of paclitaxel to cisplatin are independent prognostic factors in patients with advanced oesophageal cancer, who are treated with cisplatin-based combination chemotherapy.
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PMID:Prognostic factors for survival in patients with advanced oesophageal cancer treated with cisplatin-based combination chemotherapy. 1464 36

We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; alpha-fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was reevaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal.
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PMID:A case of leptospirosis simulating colon cancer with liver metastases. 1528 43

Neuroendocrine tumors, particularly those of gastrointestinal tract origin, have a predisposition for metastasizing to the liver, causing parenchymal substitution and paraneoplastic syndrome. Lipiodol embolization combined with anticancer drugs is a recent tool in regional therapy. It has been proven that chemoembolization reduces tumor bulk and hormone levels, and that it palliates the symptoms of many patients with liver-dominant neuroendocrine metastases. Beginning in December 1988, ten patients with unresectable and chemotherapy-refractory liver metastatic neuroendocrine tumors were treated with chemoembolization based on a mixture of lipiodol, mitomycin, cisplatin, epirubicin, followed by gelfoam powder and contrast media. Toxicity encountered included: upper right quadrant pain requiring narcotics, elevation of lactate dehydrogenase, alkaline phosphatase, and transaminases. One patient had liver abscess and persistent fever for 2 weeks. We obtained two complete remissions lasting 12 and 34 months and 5 partial remissions. The median survival was 22 months. Four patients had urinary elevation of 5-hydroxyindolacetic acid (5-HIAA). They showed more than a 75% decrease in urinary secretion after treatment. In a patient with transplanted liver we noticed a partial response lasting 7 months. We conclude that chemoembolization will improve the clinical condition of a significant percentage of patients with liver metastases, that future therapy of carcinoid tumors will be based on specific tumor biology and that treatment will be customized for each individual patient combining the use of cytoreductive procedures including radiofrequency ablation, laser treatment and chemoembolization.
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PMID:Intra-arterial hepatic chemoembolization in liver metastases from neuroendocrine tumors: a phase II study. 1533 Mar 28

A 65-year-old man was referred to our hospital for evaluation of his huge abdominal tumor. He was diagnosed as having a gastrointestinal stromal tumor arising from the stomach. Seven months after surgery, multiple liver metastases and mesenteric dissemination occurred. He was medicated with STI571, which works by blocking proliferation of malignant cells with expression of c-kit. The tumors shrank and serum lactate dehydrogenase and alkaline phosphatase concentrations fell to below the normal limit three months later. STI571 was effective medicine for the metastatic gastrointestinal stromal tumor for six months in this case.
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PMID:Efficacy of STI571 for a patient with metastatic gastrointestinal stromal tumor. 1633 74


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