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)

Prognosis and outcome of patients with pancreatic carcinoma is poor. The aim of the study was to investigate (1) which factors of medical history and clinical status as well as which laboratory parameters determine survival in pancreatic carcinoma and (2) whether specific data can be used as prognostic parameters or for early diagnosis of pancreatic carcinoma. In total, 287 patients with pancreatic carcinoma were enrolled in the study. In 193 subjects, only palliative treatment was possible. Survival was assessed using univariate survival probability curves by Kaplan-Meier. Comparison of patient groups with regard to survival was achieved using the log-rank test. Multivariate analysis was carried out using the Cox regression model. Overall, 22 factors, showing a significant impact on survival in pancreatic carcinoma were found, e.g., tumor-associated factors such as (1) tumor stage according to the UICC classification including TNM-based staging, grading, tumor site, and vascular infiltration; (2) preoperative habits and signs and symptoms (physical condition, pain, loss of appetite, ethanol consumption); (3) change of laboratory parameters (CA 19-9, bilirubin, prothrombin time, urea, C-reactive protein), and (4) type of intervention (surgical approach, R0/1/2 resection). Using multivariate analysis, seven factors (UICC tumor stage and site, surgical intervention including number of resected lymph nodes, chemotherapy, occurence of a carcinoma in relatives, preoperative physical condition, night sweat) were determined. In the 193 patients with palliative treatment, only ten factors (among them UICC tumor stage including the presence of metastases; data from the medical history such as physical condition, loss of appetite, and carcinoma in relatives, and laboratory parameters including prothrombin time, protein content, and aspartate aminotransferase levels) were found to be important. Chemotherapy had the strongest impact on survival which was confirmed by multivariate analysis, followed by tumor stage (UICC) and preoperative appetite. Besides tumor-associated determinants, data from the medical history, and pathological laboratory parameters, the prognosis in pancreatic carcinoma is considerably determined by the treatment such as interventional and/or using antineoplastic agents.
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PMID:Prognostic parameters determining survival in pancreatic carcinoma and, in particular, after palliative treatment. 1138 55

A 59-year-old man who had received chronic hemodialysis developed left occipital pain and hypoglossal nerve palsy. He was diagnosed as having skull base metastasis from renal cell carcinoma related to acquired cystic kidney. Retrospective analysis revealed the patient had had elevated serum C-reactive protein and alkaline phosphatase levels before the symptoms appeared. Radiotherapy to the skull base relieved the pain. Finally he died with generalized metastases. Serum interleukin-6 levels measured during admission had been elevated, and interleukin-6 mRNA was detected in the autopsy specimen of renal cell carcinoma. Interleukin-6 might be involved in the etiology of paraneoplastic signs.
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PMID:Renal cell carcinoma with skull base metastasis preceded by paraneoplastic signs in a chronic hemodialysis patient. 1157 58

The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +/- 8.2 pg/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +/- 16.8 and 84.1 +/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.
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PMID:Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation? 1238 57

The purpose of the study was to identify a comprehensive prognostic system of pretreatment clinical parameters in 425 patients (pts) with metastatic renal-cell carcinoma treated with different subcutaneous (s.c.) recombinant cytokine-based home therapies in consecutive trials. Treatment consisted of (A) s.c. interferon-alpha 2a (INF-alpha), s.c. interleukin-2 (IL-2) (n=102 pts), (B) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-fluorouracil (5-FU) (n=235 pts) or (C) s.c. IFN-alpha 2a, s.c. IL-2, and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (13cRA) (n=88 pts). Kaplan-Meier survival analysis, log-rank statistics, and Cox regression analysis were employed to identify risk factors and to create a multiple risk factor model. The following pretreatment risk factors were identified by univariate analysis: (1) three and more metastatic sites, (2) presence of liver, lymph node or bone metastases, (3) neutrophil count > or = 6500 cells microl(-1), (4) serum lactate dehydrogenase level (LDH) > or = 220 U l(-1), and (5) serum C-reactive protein level (CRP) > or = 11 mg l(-1). Cox regression analysis with forward stepwise variable selection identified neutrophil count as the major prognostic factor (hazard ratio=1.9, P<0.001), while serum levels of LDH and CRP, time between diagnosis of tumour and onset of metastatic disease, number of metastatic sites, and bone metastases were significant but somewhat less important prognostic variables within the multiple risk factor model (hazard ratio < or = 1.5). Patients were assigned to one of the three risk groups according to cumulative risk defined as the sum of simplified risk s.c.ores for six pretreatment variables. Low-, intermediate-, and high-risk patients achieved a median overall survival of 32+ months (95% CI 24, 43; 5-year survival of 27%), 18+ months (95% CI 15, 20; 5-year survival of 11%), and 8+ months (95% CI 6, 10; 5-year survival of 5%), respectively. These prognostic categories are helpful both in individual patient care and in the assessment of patients entering prospective clinical trials.
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PMID:Metastatic renal carcinoma comprehensive prognostic system. 1256 75

Although an aggressive phenotype of renal cell carcinoma (RCC) is known to frequently be associated with inflammatory paraneoplastic syndrome including serum C-reactive protein (CRP) elevation, the molecular mechanism underlying this clinical phenomenon as well as what yields the malignant phenotype leading to the progression of RCC has yet to be elucidated. Based on the increased level of inflammatory cytokines such as interleukin-6 in advanced cases of RCC, a cytokine-inducible transcription factor, namely, nuclear factor-kappa B (NF-kappa B), may thus play a role in the progression of RCC. An electrophoretic mobility shift assay (EMSA) was carried out to determine the activity of NF-kappa B. Out of 45 cases of RCC, 15 cases (33%) showed a >200% increase in the NF-kappa B activity in comparison with that seen in normal renal tissue. In locally advanced cases (> or =pT3), 64% (9/14) showed an increased activity whereas it was only observed in 19% (6/31) of localized cases (< or =pT2). All three cases with metastases showed an increased NF-kappa B activity. The NF-kappa B activity determined by EMSA was further confirmed by an immunohistochemical analysis using an antibody recognizing the nuclear localization signal (NLS) in p65 subunit of NF-kappa B. The serum CRP elevation correlated with the increased NF-kappa B activation, and therefore NF-kappa B may be a causative transcription factor of inflammatory paraneoplastic syndrome. A high NF-kappa B activity was associated with an increased expression of both the p65 and p50 subunits of NF-kappa B and a concomitant decreased expression of I kappa B alpha. No functional mutations of the I kappa B alpha gene were detected. The NF-kappa B activity may therefore be a late event in carcinogenesis related to tumor development, thereby representing a possible molecular target in the treatment of RCC.
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PMID:Increased nuclear factor-kappa B activation is related to the tumor development of renal cell carcinoma. 1266 95

Positron emission tomography (PET) has emerged as a powerful tool in clinical oncology which allows to detect pathological changes in the metabolic characteristics of different tissues. In recent years the PET with the radiopharmakon 18F-2-fluoro-2-deoxyglucose has proved to be valuable for the diagnostic approach in inflammatory diseases. We report the case of a 69 year old female patient who was admitted for the diagnostic evaluation of a single pulmonary nodule in the right upper lobe which was suspicious for malignancy in the CT scanning. In the last three month the patient lost 13 kg weight, and was complaining about weakness, fatigue, enhanced body temperature up to 101 degrees F and night sweets. In the laboratory findings a microcytic anemia (80 g/L, 74,4 fL), an enhanced C-reactive protein (133 mg/L) and an accelerated ESR of 100 mm Hg/h was remarkable. The pulmonary nodule located in the second segment of the right upper lobe was not accessible in the bronchoscopic examination. Abdominal and cerebral CT scannings showed no pathological findings. In the positron emission tomography an enhanced accumulation of 18F-2-fluoro-2-deoxyglucose could be detected in the complete aorta and the large-sized arteries of the aortic arch consistent with the diagnosis of a giant-cell arteritis. The suspicious pulmonary nodule of the CT scanning showed no metabolic activity as provable with the PET. The 18F-FDG PET which is used in the initial staging of newly diagnosed lung cancer and known to be superior to CT in the evaluation of lymph node and distant metastases, is applicable in the diagnostic assessment of chronic inflammatory diseases. As the diagnostic approach in patients presenting with clinical symptoms as fatigue, weight loss, night sweets and fever is often arduous and time-consuming, the PET might become a more central role in the future.
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PMID:[PET-imaging proves giant-cell arteritis as the cause of FUO in a patient with a pulmonary nodule of unknown malignancy]. 1286 94

Consecutive cancer referrals to a palliative medicine program were evaluated to assess nutritional status using a standard protocol. The study included 352 patients (180 men, 172 women; median age 61 years, range 22-94 years). The most common diagnosis was lung cancer. All had metastatic disease, 139 with gastrointestinal involvement. The most common gastrointestinal symptoms were weight loss ( n=307), anorexia ( n=285), and early satiety ( n=243). Of those with any weight loss, 71% had lost >or0% of their pre-illness weight. The most common factor identified which might have contributed to weight loss was hypophagia ( n=275/307). Men had lost weight more often and to a greater extent than women. Triceps skinfold (TSF) was measured in 337: 51% had values that suggested severe fat deficiency. Upper mid-arm muscle area (AMA) was measured in 349: 30% had evidence of significant muscle mass reduction. The body mass index (BMI) was normal or increased in most patients. Calculated resting energy expenditure (REE) ( n=324) was high in 41%. C-reactive protein was elevated in 74% of those measured ( n=50). We conclude that: (1).most of this group of cancer patients referred to palliative medicine had severe weight loss; (2).there was a gender difference in the severity and type of weight loss; (3).males lost more weight overall and more muscle than females; (4).males with any degree of weight loss had a higher REE than females; (5).a significant correlation existed between the time from diagnosis to death and the severity of weight loss in the prior month; (6).BMI was normal in most patients, suggesting precancer diagnosis obesity; and (7).both TSF and AMA correlated well with body composition of both fat and protein as determined by bioelectrical impedance.
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PMID:Evaluation of nutritional status in advanced metastatic cancer. 1292 Jun 23

We carried out an open, non-randomized phase II study including all patients treated with whatever chemotherapy or combined modality regimen for whatever cancer who were in clinical objective response (complete response, CR, or partial response, PR) or stable disease (SD). The treatment consisted of administration of recombinant interleukin-2 (rIL-2) at a dose of 1.8 MIU subcutaneously three times/week (every other day) for the first 2 weeks of every month plus medroxyprogesterone acetate (MPA) 500 mg/day every other day plus antioxidant agents alpha-lipoic acid 300 mg/day and N-acetyl cysteine 1800 mg/day or carbocysteine lysine salt oral solution 2.7 g/day. The treatment was administered for 1 year except when progression of disease occurred. The primary study endpoints were to define clinical outcome, i.e. duration of response, survival (overall survival, OS and progression-free survival, PFS), the toxicity profile, and the evaluation of quality of life (QL). As secondary endpoints, we measured the changes of lymphocyte count, serum levels of proinflammatory cytokines, IL-2, C-reactive protein (CRP) and leptin, blood levels of reactive oxygen species (ROS) and antioxidant enzymes (glutathione peroxidase, GPx and superoxide dismertase, SOD). From July 1998 to June 2003, 42 patients were enrolled in the study (M/F ratio, 39/3; mean age, 62.5 years). Twenty (47.6%) patients were elderly (> 65 years). The majority of patients had either head and neck cancer or lung cancer, 88% had locally advanced or metastatic disease at diagnosis, and 76% had ECOG 0. Forty patients were previously treated with chemotherapy (27 also with radiotherapy), two with IL-2 and interfiron (IFN), one with endocrine therapy and one with only surgery. We obtained an objective response to maintenance treatment of 50%. Median duration of response was 19 months and median PFS was 33 months. Median duration of maintenance treatment was 12 months, median follow-up duration from diagnosis to June 2003 was 40 months, and median follow-up duration from study entry to June 2003 was 17 months. The median overall survival has not been reached. Toxicity was negligible. As for QL, a significant improvement of cognitive functions was observed, whereas all other functioning and symptom scales did not change significantly. As for laboratory parameters, absolute lymphocyte count increased significantly, IL-6, IL-1 beta, tumor necrosis factor-alpha, CRP, and fibrinogen decreased significantly whereas IL-2 and leptin increased significantly after treatment. ROS decreased significantly, whereas GPx increased significantly after treatment. Patients alive at study end showed a significant increase in absolute lymphocyte count, IL-2, leptin, and GPx and a significant decrease of proinflammatory cytokines, CRP, fibrinogen, and ROS, whereas patients who died before study end exhibited only a significant increase in absolute lymphocyte count, IL-2, and GPx and a significant decrease of ROS. Long-term combined maintenance therapy with rIL-2 + MPA + antioxidant agents is feasible, has a very low toxicity, and results in the improvement of clinical outcome, QL, and laboratory parameters.
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PMID:Subcutaneous interleukin-2 in combination with medroxyprogesterone acetate and antioxidants in advanced cancer responders to previous chemotherapy: phase II study evaluating clinical, quality of life, and laboratory parameters. 1456 91

Angiogenesis is essential for breast cancer metastases formation and is mediated by vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2). We hypothesized that serum levels of VEGF and PGE2 are increased by the stress response to breast cancer surgery and attenuated by paravertebral anesthesia and analgesia (PVAA). Thirty women undergoing mastectomy were enrolled in this prospective, randomized study, to receive general anesthesia (GA) and postoperative opioid analgesia (morphine 0.1 mg/kg bolus and patient-controlled infusion) or GA and PVAA (72-h infusion). All patients received rectal diclofenac. Venous blood samples were taken preoperatively and at 4 and 24 h postoperatively for serum glucose, cortisol, C-reactive protein, VEGF, and PGE2. PVAA inhibited the surgical stress response, as indicated by significantly less plasma glucose, cortisol, and C-reactive protein. VEGF and PGE2 values did not differ significantly between the groups. Mean (SD) percentage change in VEGF at 4 and 24 h respectively were 3% +/- 44% versus 9% +/- 80%, P=0.29 and 5% +/- 43% versus -10% +/- 63%, P=0.41 for patients with combined general and PVAA and GA alone, respectively. Mean percentage change in postoperative PGE2 at 4 and 24 h respectively was 10% +/- 17% versus 11% +/- 69%, P=0.29 and 34% +/- 19% versus 47% +/- 18%, P=0.15. We conclude that despite inhibiting the surgical stress response, PVAA had no effect on serum levels of putative breast cancer angiogenic factors, VEGF and PGE2.
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PMID:Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2. 1561 85

Pathological characteristics, patient outcome, and preoperative examinations of 16 cases (4.1%) of chromophobe renal cell carcinoma (RCC) observed among 389 patients with RCC treated at Yokohama City University Hospital and Yokohama City University Medical Center between 1991 and 2004 were analyzed. The age distribution was 16 to 74 years old (average age; 50.9 +/- 17.0). Pathologically, 14 patients had pure chromophobe RCC, and two patients had chromophobe RCC coexisting with aggressive pathological elements, that is, sarcomatoid change in one patient and collecting duct carcinoma in the other. The average tumor size was 7.1 +/- 4.1 cm. On preoperative imaging studies with enhanced computed tomography or angiography, all cases showed a hypovascular pattern. C-reactive protein (CRP) and immunosuppressive acidic protein (IAP) were increased specifically in the two cases coexisting with aggressive pathological elements. Fourteen cases showing pure chromophobe RCC did not metastases on preoperative examination. Thirteen cases were treated by nephrectomy, and another was treated by partial nephrectomy. To date there have been no recurrences during the 6 to 160 months postoperative follow-up. The patient with a mixture of chromophobe RCC and sarcomatoid change (pT3aN0M0) died of multiple lung metastases 18 months after nephrectomy. The patient showing a mixture of chromophobe RCC and collecting duct carcinoma demonstrated metastases to the paraaortic lymph nodes at preoperative examination (pT1bN2M0), and died of multiple lung and bone metastases and carcinomatous peritonitis 8 months after nephrectomy. The patients with pure chromophobe RCC had a favorable prognosis, but those with a mixed type including aggressive elements such as sarcomatoid change or collecting duct carcinoma, showed a poor clinical course. The increase in CRP or IAP could predict poor prognosis in such cases.
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PMID:[Chromophobe renal cell carcinoma: a clinicopathological study of 16 cases]. 1647 80


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