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)

In a pilot study the effect of palliative chemotherapy on the detection rates of circulating tumour cells in peripheral venous blood of stage IV colorectal cancer patients was investigated. The results indicate a recruitment of tumour cells during chemotherapy and suggest a poorer survival for tumour cell positive patients. Circulating tumour cells have been shown to be a potential prognostic factor in patients who undergo curative resection for colorectal cancer. The effect of chemotherapy on the detection rates of disseminated tumour cells in blood has not yet been adequately investigated. Objective of this pilot-study was to analyze circulating tumour cells in peripheral venous blood of colorectal cancer patients undergoing chemotherapy in order to evaluate its potential value as a surrogate-marker for predicting clinical outcome after chemotherapy. Our hypothesis was that chemotherapy results in a reduction of the detection rates of circulating tumour cells in colorectal cancer patients. Forty-two Stage IV patients were examined at three different time points before and during palliative chemotherapy for the presence of disseminated tumour cells, using a previously described RT-PCR-assay for cytokeratin 20. 80.1% of the patients showed disseminated tumour cells at least once. Before chemotherapy, patients with multi-organ metastases were positive in 62.5%, patients with locally limited disease in only 14.3%. After the first chemotherapy, the detection rates in the latter group increased to 62.5%, for all patients in the same time from 46.3% to 57.5%. Clinical therapy responders showed an increase in the detection rates from 28.5% before to 71.4% after chemotherapy. In contrast, chemotherapy had no effect on tumour cell detection rates of patients with progressive disease (57% before vs. 60% after therapy). Patients with detected circulating tumour cells showed a shorter overall survival than patients without circulating tumour cells (83 vs. 53 weeks). Clinical therapy responders on average lived only 3 weeks longer than non-responders. In contrast to the original hypothesis, our data suggest a recruiting of circulating tumour cells during chemotherapy in advanced colorectal cancer. Further investigations are needed to clarify the potential role of circulating tumour cells for monitoring chemotherapy in these patients.
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PMID:Detection of disseminated tumour cells as a potential surrogate-marker for monitoring palliative chemotherapy in colorectal cancer patients. 1574 34

Among 125 patients with peritoneal dissemination (P1-3) of colorectal cancer, including those with other synchronous metastases, the 5-year overall survival (OS) rate was 13.3% for P1 patients (n=30), 12.8% for P2 patients (n=39), and 1.8% for P3 patients (n=56) (P1 vs. P2, p=N.S.; P2 vs. P3, p=0.02; P1 vs. P3, p=0.001), while the median survival time (MST) was 12.0, 14.1, and 3.1 months, respectively. The 5-year OS rates for patients who had peritoneal dissemination without other metastases were 17.6% (n=17), 12.5% (n=19), and 3.4% (n=28) (P1 vs. P2, p=N.S.; P2 vs. P3, p=N.S.; P1 vs. P3, p=0.039), while the MST was 25.1, 15.1, and 12.5 months, respectively. In the P3 short survival group (SSG; n=13), TS expression was high in 7.7% (1/13) and low in 92.3% (12/13) of tumors, while DPD expression was high in 38.5% (5/13) and low in 61.5% (8/13) of tumors. In the P3 long survival group (LSG; n=15), the corresponding values were 80.0% (12/15), 20.0% (3/15), 33.3% (5/15), and 66.7% (10/15). High TS and low DPD expression was found in only 7.7% (1/13) of the SSG tumors vs. 46.7% (7/15) of the LSG tumors (p=0.028). These results suggest that the prognosis of stage IV colorectal cancer with P3 peritoneal dissemination is extremely poor. In addition, patients fitting the SSG criteria are unlikely to respond to treatment with 5-FU+LV, and may need combination chemotherapy using CPT-11 and/or L-OHP.
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PMID:Long-term survival and tumor 5-FU sensitivity in patients with stage IV colorectal cancer and peritoneal dissemination. 1659 84

BACKGROUND There is no consensus regarding the appropriate management of asymptomatic and minimally symptomatic patients with stage IV colorectal cancer and irresectable metastases. METHODS A literature search was conducted on Medline and Embase. Outcome measures included: survival; postoperative morbidity and mortality; complications from the primary tumor and the need for surgery to manage complications; the likelihood of curative surgery after initial response to primary therapy; and length of hospital stay. Quantitative meta-analysis was performed where appropriate. RESULTS Eight retrospective studies, including 1,062 patients, met the criteria for inclusion in this study. Meta-analysis has shown an improvement in the survival of patients managed with palliative resection of their primary tumor, with an estimated standardized median difference of 6.0 months (standardized difference, 0.55; 95% confidence interval (CI), 0.29, 0.82; p < 0.001). Patients managed with chemotherapy alone were 7.3 times more likely to have a complication from the primary tumor (95% CI, 1.7, 34.4; p = 0.008). There was no difference in the response rates to chemotherapy, making metastatic disease amendable to curative resection (0.85; 95% CI 0.40, 1.8; p = 0.662). CONCLUSIONS To date, only retrospective data are available, showing that palliative resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV colorectal cancer is associated with longer survival. Resection of the primary tumor reduces the likelihood of complications from the primary tumor and avoids the need for emergency procedures.
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PMID:Meta-analysis of survival of patients with stage IV colorectal cancer managed with surgical resection versus chemotherapy alone. 2044 Jun 14

Metastatic colorectal cancer traditionally has been considered incurable. Over the past 3 decades, however, resection of low-volume hepatic disease has been recognized as beneficial in some cases. More recently, resection of isolated pulmonary metastases has been shown to offer long-term survival in carefully selected patients. Resection of metastases to more unusual sites (ovary, brain, peritoneal cavity) is more controversial; nevertheless, retrospective data suggest that a few patients may be cured with resection of these tumors. In this article, we review the history and current status of metastasectomy in stage IV colorectal cancer.
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PMID:Metastasectomy for stage IV colorectal cancer. 2055 64

A 44-year-old female was referred to our hospital with a complaint of abdominal fullness. Computed tomography(CT) showed multiple liver masses and a huge ovarian tumor. Colonoscopy revealed a type 4 advanced cancer in the sigmoid colon. She was diagnosed with unresectable liver and ovarian metastases from advanced sigmoid colon cancer, for which we were obliged to select chemotherapy. As the first line, FOLFOX was applied and performed for 6 cycles, followed by FOLFOX plus bevacizumab(BV)for 5 cycles. While no deterioration of liver and ovarian metastases was observed during the course of those chemotherapy regimens, the patient developed a considerable level of acute sensorimotor neuropathic symptoms associated with oxaliplatin-induced peripheral neurotoxicity, forcing us to replace FOLFOX plus BV with FOLFIRI plus BV. Three cycles of FOLFIRI plus BV, however, turned out to be progressive disease with deterioration of liver and ovarian metastases. Since her oxaliplatin-induced neurotoxicity was improved, a regimen of FOLFOX plus BV was once again applied to her for 3 cycles, which failed to prevent her from having a progressive disease. The sequencing of K-RAS genes from the biopsy specimens of sigmoid colon cancer revealed an expression of a wild-type K-RAS. Thus, an addition of panitumumab to FOLFOX was made. Surprisingly, after 3 cycles of the chemotherapy regimen over 3 months, a significant reduction in the size of liver and ovarian metastases was observed. Her sense of abdominal fullness was apparently reduced and was even lower than what it was at admission. Panitumumab has great potential for effective treatment of patients with unresectable stage IV colorectal cancer, even after having acquired resistance to prior chemotherapy regimens.
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PMID:[A case of sigmoid colon cancer with liver and ovarian metastases effectively treated by panitumumab after acquiring resistance to prior chemotherapy regimens]. 2191 57

Morphological and clinical heterogeneity of advanced colorectal cancer is probably caused by genetic variability in putative cancer stem cell genes, including Lgr5. Here, we investigated 23 variants of the Lgr5 gene in normal tissue, primary tumors, lymph node metastases and distant metastases of stage III and stage IV colorectal cancer patients. These data were compared to results of immunohistochemical Lgr5 expression analysis and to prognostic clinical parameters. No differences were found comparing germline and somatic Lgr5 genotype in primary tumors, but additional Lgr5 gene alterations could be demonstrated in lymph node and distant metastases. Significant negative correlation was seen between Lgr5 allelic variation and Lgr5 protein expression (p=0.0394), which mainly can be attributed to the negative influence of non-coding Lgr5 gene variations on Lgr5 protein expression (p=0.0166). Lgr5 gene variants could be found more frequently in primary tumors of stage III patients with increased time to recurrence, in distant metastases of patients with better survival and in lymph node metastases of patients with poorer survival compared to patients with Lgr5 wild type in primary and metastatic tissues, respectively. However, the analytic power of these prognostic data was low due to small sample size in the investigated groups. In conclusion, our data indicate that Lgr5 allelic variation affect Lgr5 protein expression in colorectal carcinomas. The somatic Lgr5 genotype seems to be relatively stable in primary tumors, but becomes vulnerable during the metastatic process of colorectal cancer. This instability has possibly prognostic importance, which has to be further evaluated by large cohort studies.
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PMID:Single nucleotide polymorphisms of the adult intestinal stem cell marker Lgr5 in primary and metastatic colorectal cancer. 2293 6

Currently, there is no universally accepted system to classify the stage IV colorectal cancer. Here, we analyze the prognostic impact of radical resection for colorectal liver metastases and propose a new staging system for stage IV colorectal cancer. A retrospective review was undertaken of 126 consecutive patients who underwent surgical treatment for colorectal liver metastases from January 1997 to January 2004. Based on the overall survival rates (Kaplan-Meier method) and surgical outcomes, we propose a new staging system for stage IV colorectal cancer. Patients were divided into two groups: patients who underwent initial hepatic resections (R0 resection) for liver metastases (group 1, n = 22), and patients who underwent palliative resection for unresectable liver metastases (group 2, n = 104). The overall survival rates in group 1 at 1, 3, and 5 years were 68.2% (15/22), 40.9% (9/22), and 18.2% (4/22), respectively. The overall survival rates in group 2 at 1, 3, and 5 years were 54.8% (57/104), 16.3% (17/104), and 0% (0/104), respectively. There was a significant difference in overall survival rates between both groups (p < 0.05). Based on the study results, we propose a new staging system where all distant metastases are grouped within stage IV and subclassified into resectable (R0 resection) and unresectable stages. Curative surgical treatment is a critical prognostic factor in colorectal liver metastases. The proposed new staging system for stage IV colorectal cancer is simple and is clinically useful to estimate the prognosis.
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PMID:Classifying the stage IV colorectal cancer: prognostic impact of radical resection for colorectal liver metastases and proposal for a new staging system. 2353 8

The best management choice in colorectal cancer patients with unresectable liver-only metastases should be represented by conversion chemotherapy aiming to reduce liver cancer deposits, thereby permitting curative surgery. Forty-eight consecutive stage IV colorectal cancer patients were treated with different chemotherapeutic regimens including biological drugs. Objective responses to chemotherapy were seen in 27 patients (56.2%; 95% CI 42.1-70.2%). Four patients (8.3%) showed complete response, 23 patients (47.9%) partial and 13 patients (27.1%) stable response. Eight patients (16.7%) progressed. The conversion rate was 35.4% (95% CI 21.8-48.9%) with 17 patients suitable for liver resection. Four complete responder patients refused surgery. The remaining 13 patients underwent curative hepatic resection (resection rate 27.1%; 95% CI 14.5-39.6%). The likelihood of a successful conversion chemotherapy appeared significantly related to the best response and to the K-Ras status. Wild-type K-Ras patients undergoing cetuximab therapy showed the best conversion rate. The four-year survival rate was significantly enhanced in converted compared to non-converted patients (57.1 and 0%, respectively), and in resected compared to non-resected patients (53.3 and 10.1%, respectively). Synchronous metastases and no conversion were shown to be the only covariates independently associated with a poorer long-term outcome. The possibility of curative liver surgery significantly prolongs outcome for colorectal cancer patients with unresectable liver-limited metastases. Prospective randomized trials are required to define the conversion rates with biological drugs.
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PMID:Conversion chemotherapy followed by hepatic resection in colorectal cancer with initially unresectable liver-limited metastases. 2412 55

Current concepts in the management of hepatic metastases have changed dramatically over the past two decades. Multidisciplinary therapies including chemotherapy, surgery, and regional therapy have alone and in combination significantly improved the survival of patients with metastatic colorectal cancer. Conditions that were previously considered hopeless and treated merely for palliation can now be approached with curative intent. In this paper, we review the surgical treatment for colorectal cancer liver metastasis (CRLM) and describe a paradigm-shift in the management of complex heretofore-considered unresectable CRLM. Utilizing advanced multidisciplinary treatment strategies has improved the prognosis of patients with stage IV colorectal cancer to the point where we may question whether CRLM are now a chronic disease.
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PMID:Designing liver resections and pushing the envelope with resections for hepatic colorectal metastases. 2442 56

Treatment strategies for patients with stage IV colorectal cancer have changed markedly in the last decade. Patients with colorectal cancer metastases to the liver have always been a fascinating group to consider biologically and for local-regional treatment strategies. In the late 1980s through the 1990s, resection was performed for a select subset of patients who had resectable disease. However, a high proportion of patients had bilobar unresectable disease and were treated with either 5-fluorouracil-based systemic chemotherapy or implanted hepatic arterial infusion pumps. The advent of the new millennium was associated with the availability of several new cytotoxic and biologic agents active in colorectal cancer. These agents have completely changed the approach to the treatment of patients with colorectal cancer liver metastases and thus have increased the complexity of the decision-making process for treatment of these patients.
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PMID:Surgical treatment of colorectal cancer liver metastases. 2445 36


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