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)

Recombinant interferon alfa-2a (rIFN alpha-2a) synergistically augments the cytotoxic effects of the antimetabolite fluorouracil (5-FU) against two human colon cancer cell lines. A pilot clinical trial was initiated to determine whether this same combination of agents would show clinical utility greater than that expected with 5-FU alone in patients with advanced colorectal carcinoma. 5-FU was administered at 750 mg/m2/d for 5 days as a continuous intravenous infusion followed by weekly bolus therapy. rIFN alpha-2a was administered at 9 million units subcutaneously three times per week starting on day 1. Doses of 5-FU were modified for mucosal toxicities and myelo-suppression, and doses of rIFN alpha-2a were modified for fatigue and neurologic toxicities. Thirty-two previously untreated patients with advanced colorectal carcinoma were entered into a clinical trial. With the exception of one patient with a destructive lesion of the sacrum, all patients had metastases to visceral organs, abdominal wall, or pelvis. Twenty patients (63%) achieved a partial response, seven remained stable, and five had progressive disease. Mucosal toxicities limited delivery of full projected dose. Two patients died following episodes of watery diarrhea progressing to sepsis. A third died suddenly, secondary to an interstitial pneumonitis. The remainder of the toxicities were managed with dose reductions. At the median follow-up of 8 months, 23 of 32 patients remain alive. Nine are alive at 16 to 30+ months. The early results of this single-institution study are promising, but will require confirmation in a multi-institutional setting currently being conducted by the Eastern Cooperative Oncology Group.
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PMID:Clinical update on the role of fluorouracil and recombinant interferon alfa-2a in the treatment of colorectal carcinoma. 240 91

Cisplatin, vinblastine and bleomycin (PVB) is very effective therapy in disseminated testicular cancer, but toxicity is severe. A further reduction of vinblastine might reduce the acute toxicity of PVB without compromising the response rate in good-risk patients. Starting in March 1982, 42 consecutive patients with minimal or intermediate advanced disease (lymph node metastases less than 10 cm, lung nodules less than 5 cm) began a 0.2-mg/kg vinblastine PVB regimen, provided that serum alpha-fetoprotein (AFP) levels were not greater than 1000 ng/ml and human chorionic gonadotropin (HCG) values were not greater than 50,000 mIU/ml. Only 9 patients (21.4%) had leukocyte counts less than 1000/mm3, 6 (14%) had infections, but none had documented sepsis. Gastrointestinal and neuromuscular toxicities were mild. Of the 42 patients, 41 (97.6%) entered complete remission (CR), 8 with surgery. After a median follow-up period of 26 months (range, 19-40 months), 35 patients (83.3%) are continuously disease-free. Of the 6 patients with AFP levels greater than 400 ng/ml and/or HCG values greater than 1000 mIU/ml, only 2 (33.3%) entered continuous CR, versus 33 (91.6%) of the 36 patients with normal or less elevated markers (P less than 0.01). PVB with a 0.2-mg/kg vinblastine dosage is very effective and well-tolerated therapy in selected good-risk patients with disseminated germinal testis cancer.
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PMID:Successful treatment of good-risk disseminated testicular cancer with cisplatin, bleomycin, and reduced-dose vinblastine. 242 65

The early and late results of bypass surgery in 124 patients with unresectable oesophageal cancer are reported. Patients were grouped according to the extent of disease: group A, tumour localized to the oesophagus where severe pulmonary disease contra-indicated oesophagectomy (n = 9); group B, tumour less than or equal to 10 cm in length with mediastinal invasion (n = 81); group C, tumour greater than 10 cm in length with mediastinal invasion and/or fixed malignant lymph nodes (n = 33). Extent of disease was not recorded in one patient. The operative mortality was 4 per cent but 9 other patients died in hospital (hospital mortality, 11 per cent). Mortality was increased in patients undergoing colon bypass and in those with a large tumour load but these differences failed to reach statistical significance. The most frequent complication was neck sepsis, secondary to leakage from the proximal end of the excluded oesophagus. Eighty-nine per cent of the survivors could eat a normal, unrestricted diet on discharge and eighty-two per cent of survivors had complete and lasting relief from dysphagia. Median survival after bypass was 5 months but survival was significantly improved by radiotherapy to the tumour (P less than 0.001). Gastric bypass with radiotherapy is indicated in patients with extra-oesophageal spread of malignancy and in patients with tumours localized to the oesophagus who are unfit for resection. Bypass surgery may be contra-indicated in patients with a primary tumour greater than 10 cm in length and/or fixed lymph node metastases because mortality is increased and survival after operation is short.
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PMID:Bypass surgery for unresectable oesophageal cancer: early and late results in 124 cases. 245 Jun 15

Vitronectin, also known as serum-spreading factor or S-protein, mediates cell adhesion and inhibits formation of the membrane-lytic complex of complement and the rapid inactivation of thrombin by antithrombin III in the presence of heparin. Vitronectin is normally present in plasma at a concentration of approximately 300 micrograms/mL. The investigators quantified plasma vitronectin with an enzyme-linked immunosorbent assay and visualized reduced and nonreduced vitronectin by immunoblotting after separation of plasma or serum by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The concentration of plasma vitronectin was markedly reduced in some patients with disseminated intravascular coagulation, especially in those with liver failure; it was near normal in patients with metastatic cancer and acute leukemia. Patients with vitronectin levels less than 40% normal invariably had low fibrinogen and antithrombin III and a prolonged prothrombin time. In both normal and patient plasmas there was heterogeneity in the ratio of the 75,000- and 65,000-mol wt polypeptides of reduced vitronectin: 18% had mostly the 75,000-mol wt polypeptide, 59% had roughly equal amounts of the two polypeptides, and 22% had mostly the 65,000-mol wt polypeptide. This polymorphism is inherited and appears to be due to two alleles that are present with approximately equal frequency. The blotting patterns of vitronectin in reduced and nonreduced plasmas were largely unaltered in plasma of patients with defibrination syndrome, fibrinolysis, liver failure, sepsis, metastatic cancer, and acute leukemia. There was no evidence of fragmentation of vitronectin or formation of the disulfide-bonded complex of vitronectin and thrombin-antithrombin III that is found when blood is clotted. Thus these results corroborate in vitro observations that the liver is the major source of plasma vitronectin, suggest that vitronectin may become depleted during disseminated intravascular coagulation, and define a genetic polymorphism of vitronectin.
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PMID:Plasma vitronectin polymorphism in normal subjects and patients with disseminated intravascular coagulation. 245 67

The best treatment of advanced rectal cancer remains uncertain. The aim of this study was to determine the outcome after palliative procedures in patients with advanced rectal cancer. One hundred and three patients treated over a seven-year period were identified, including 30 with local invasion, 18 with local metastases, and 55 with distant metastases. Patients were grouped into two groups: those who underwent palliative resection (68) and those who were treated without rectal resection (55). The nonresected group included patients who underwent diverting colostomies (28) and those who received multimodality therapy without surgery (7). The average age of all patients was 63.1 years. Patients in the nonresected group had more distant disease (68 percent) than the resected group (46 percent). Significant pelvic pain was a more common problem in the nonresected group (15 percent) than in the resected group (4 percent). Similarly, pelvic sepsis was more common in the nonresected group (14 percent) than in the resected group (9 percent). Postoperative mortality was 4.3 percent after palliative resection and 3.8 percent after diverting colostomy. Survival of the resected group at one year was 65 percent and at two years 20 percent. Survival of the nonresected group at one year was 20 percent and at two years 0 percent. Survival in the resected group was significantly (P less than .01) better than the nonresected group but probably can be attributed to the more extensive disease generally present in the patients who did not undergo resection. These results suggest that patients with advanced rectal cancers should undergo palliative resection whenever possible because resection decreases pelvic complications and may improve quality of life.
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PMID:Advanced rectal cancer. What is the best palliation? 246 Feb 99

Eighteen patients with measurable or evaluable lesions from squamous cancer of the esophagus received a regimen combining four active agents on an outpatient basis. Nine of 14 evaluable patients (64%, or 50% of 18 patients entered) responded: four of five with previously untreated regional disease and five of nine with recurrent or metastatic disease. Median duration of response in the latter group was 5 months (longest response, 13). Treatment was well-tolerated in all patients but one, who developed signs of severe methotrexate toxicity and died of sepsis.
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PMID:Chemotherapy for esophageal cancer with mitoguazone, methotrexate, bleomycin, and cisplatin. 257 14

Liver abscesses present a severe problematic medical entity. The traditional treatment modality consists of surgical drainage, which cannot be accomplished in all circumstances. Other modes of therapy include systemic antibiotics or percutaneous catheter drainage under ultrasonography or computerized tomography. Despite new treatment regimes liver abscesses, to date, are a potentially lethal disease, with a mortality rate of about 50%. We report an innovative approach of high dosage intrahepatic arterial antibiotic infusion for the therapy of hepatic abscesses, which are resistant to conventional treatments. A patient who underwent mastectomy for breast carcinoma, developed liver metastases one year later. She was prescribed systemic chemotherapy for one year, but no antitumor response was evident. Since ther was no evidence for extra-hepatic metastases, intraarterial hepatic chemotherapy was instituted, using an Infusaid (Mi-400) implantable pump. Marked regression of liver metastases was observed. Therapy was withheld after 19 months because of biliary sclerosis development. At this stage, the patient developed liver abscesses, which were resistant to systemic antibiotic therapy. Intraarterial antibiotic therapy, using the implantable pump, was initiated. Following the treatment, a marked improvement in the patients' clinical condition was recorded and shrinkage of the abscesses was evident by ultrasonography. The patient was free of symptoms for three months, when she was readmitted with evidence of terminal metastatic disease and sepsis. It is suggested that intrahepatic arterial antibiotic therapy is an additional mode of treatment for patients with persistent liver abscesses which fail to respond to conventional treatment.
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PMID:Hepatic intraarterial antibiotic therapy for resistant hepatic abscesses. 260 21

1. Widespread visceral and intestinal wall metastases are present in women dying with ovarian cancer. Intestinal wall invasion is commonly found at autopsy and is associated with bowel obstruction. Liver parenchymal replacement by metastases in more extensive than that in the lung, where most metastases have a subpleural location. Multifocality characterizes metastases in both of these organs. 2. Neoplastic lymphatic invasion is common. Lymphatic and blood vascular invasion are associated with an increased incidence of metastases in lymph nodes, small bowel wall, pancreas, lungs, ureter, and liver. 3. The mean survival time from diagnosis to death is less than 2 years. Both increasing neoplastic histological grade and clinical stage at diagnosis are associated with decreased survival time. 4. The most common causes of death are carcinomatosis, infection, or a combination of these processes. Sepsis, pneumonia, or both of these account for most of the fatal infections. 5. Bowel and ureteral obstruction constitute the most common forms of tumor-induced morbidity. The former process tends to be multifocal, involving the small and large intestines, and it is found during the disease course as well as at autopsy. Ureteral involvement is usually associated with hydronephrosis and is bilateral in approximately one fourth of the cases.
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PMID:The pathology and biologic behavior of ovarian cancer. An autopsy review. 265 34

One hundred seventy-three patients were treated 256 times with chemotherapy supported by autologous bone marrow transplantation during the past 9 years. The two most commonly used protocols were (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 80 mg/m2 + ACNU 3 mg/kg) and (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 100 mg/m2 + CDDP 100-150 mg/m2). Among 115 patients in the therapeutic setting in which two courses were usually given, 75 were evaluable and the overall response rate was 42.7% with 12.0% CR rate. Breast and pediatric groups responded well; the response rate in breast cancer was 67.9% with 21.4% CR rate. Two patients with breast cancer who had multiple distant metastases and 2 pediatric patients are now alive with NED after 5 years of the treatment and seem to have been cured. The results in adjuvant settings have also been quite promising, e.g., 79.4% 5-year survival probability among breast patients mainly in stage III. Although drops of blood cell counts to the nadirs (WBC counts: less than 100-300) could not be prevented, the periods of myelosuppression appeared to have been effectively shortened so that the patients could be safely managed with intensified general supportive measures. Platelet counts are usually less affected, but the recovery is slower than for WBC counts. There were 13 patients who died within 10 weeks of the initiation of the treatment. Two of them succumbed to sepsis, and progressive disease was the cause of death in 8 patients whose terminal phases were undoubtedly affected by some infectious problems. We have shown that there are inverse relationships between infused numbers of CFU-GM and marrow recovery judged by the duration of neutropenia and the time required for neutrophils to recover over 500. Our recent laboratory experiments testing CFU-E, BFU-E and CFU-Mk in addition to MNC counts and CFU-GM showed that vulnerabilities of marrow progenitors seem to differ from cell lineage to cell lineage. This must therefore be taken into careful consideration in pursuing marrow transplantation.
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PMID:[Autologous bone marrow transplantation as a measure against myelosuppression in cancer chemotherapy]. 265 12

We treated 41 patients with transitional cell carcinoma with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy. Median patient age was 56 years. Of the patients 33 had either distant metastases or locoregional disease that could not be cured by an operation or radiation. Of these patients 30 had measurable disease and 12 responded (4 complete and 8 partial responses, response rate 40 per cent, 95 per cent confidence limits 23 to 59 per cent). Only 2 of these patients remain with an unmaintained complete response at 34 and 52 months. Of 5 patients 3 responded who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for locally advanced bladder cancer before radiation or cystectomy, and only 1 of these patients is free of disease. The remaining 3 patients were treated postoperatively because they were at high risk for recurrence and all are well. Toxicity of the regimen was severe: 41 per cent of the patients experienced neutropenic sepsis and 54 per cent required hospitalization for management of toxic complications. Three patients experienced pulmonary embolism and 1 had deep vein thrombosis. There was 1 drug-related death of sepsis. Although a patient occasionally may have long-term benefit from this chemotherapy our results suggest caution in the widespread application of this protocol.
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PMID:M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy for transitional cell carcinoma: the Princess Margaret Hospital experience. 274 45


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