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Sample records for asymptomatic metastatic colorectal

  1. Metastatic paediatric colorectal carcinoma.

    LENUS (Irish Health Repository)

    Woods, R

    2012-03-01

    A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

  2. TAS-102 for Metastatic Colorectal Cancer

    Science.gov (United States)

    A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati

  3. Ziv-aflibercept in metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Patel A

    2013-12-01

    Full Text Available Anuj Patel, Weijing Sun Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: The combination of cytotoxic chemotherapy and antiangiogenic agents has become a conventional treatment option for patients with metastatic colorectal cancer. Ziv-aflibercept is a fusion protein which acts as a decoy receptor for vascular endothelial growth factor (VEGF-A, VEGF-B, and placental growth factor (PlGF; it was approved in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing fluoropyrimidine-based regimen. Herein we review the role of tumor angiogenesis as the rationale for antiangiogenic therapy, the clinical data associated with ziv-aflibercept, and its current role as a treatment option compared to other antiangiogenic agents, such as bevacizumab and regorafenib. Keywords: aflibercept, angiogenesis, colorectal cancer

  4. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie;

    2012-01-01

    presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along......Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC and...

  5. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon T;

    2013-01-01

    The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast......-enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2......-based or cytotoxic chemotherapy), local treatment (stereotactic radiotherapy, whole-brain radiotherapy or surgery), or best supportive care only. The survival was significantly shorter for patients with asymptomatic brain metastases compared with patients without brain metastases (P...

  6. [Biotherapies in metastatic colorectal cancers in 2014].

    Science.gov (United States)

    Jouinot, Anne; Coriat, Romain; Huillard, Olivier; Goldwasser, François

    2014-10-01

    The treatment of metastatic colorectal cancer has been transformed during the last decade with biotherapies, two of them were marketed in 2013. Four agents are monoclonal antibodies, while the fifth agent is a tyrosine kinase inhibitor. Two agents are inhibitors of the EGF-receptor pathway, cetuximab and panitumumab, and have as class-toxicity, cutaneous toxicity. The other three agents are bevacizumab, aflibercept and regorafenib, and interact with angiogenesis, they are associated with a risk of vascular toxicity, mainly hypertension. These agents participate to an improvement of disease control at the metastatic stage, and in some cases, favour the curative surgical resection of metastases. Their use is discussed in multidisciplinary meetings dedicated to gastrointestinal cancers, in the presence of liver surgeons. PMID:25065664

  7. Intrahepatic therapy for liver-dominant metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Kerlijne; De; Groote; Hans; Prenen

    2015-01-01

    In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for locoregional treatment of liver metastases in metastatic colorectal cancer.

  8. Management of recurrent and metastatic colorectal carcinoma.

    Science.gov (United States)

    Asbun, H J; Hughes, K S

    1993-02-01

    When metastatic or recurrent disease from colorectal carcinoma is detected, the surgeon must decide whether a patient is a candidate for resection. Although long-term survival after resection is not optimal, the relegation of patients to nonresective treatment means denying them the only chance for cure currently available. When isolated disease involving the liver, lung, or region of the primary carcinoma is documented, curative resection must be considered. Symptomatic patients may also obtain maximal palliation from resection, diversion, or a bypass procedure. Chemotherapy for the treatment of recurrent disease is palliative and probably should be considered only within clinical trials. Future alternative methods of treatment or new chemotherapeutic regimens need to be studied to improve survival and quality of life. PMID:8426994

  9. Molecularly targeted drugs for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Cheng YD

    2013-11-01

    Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

  10. BRAF-Directed Therapy in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Korphaisarn, Krittiya; Kopetz, Scott

    2016-01-01

    Activating BRAF (V-raf murine sarcoma viral oncogene homolog B) mutations occur in approximately 5% to 10% of patients with metastatic colorectal cancer, mostly V600E mutation, and it is associated with distinct clinical and pathological features. To date, there are no approved treatments to target this mutation. BRAF inhibitor monotherapy has limited efficacy, in contrast to metastatic melanoma. Combination strategies that block not only BRAF mutated kinase but other alternative pathways are ongoing and have demonstrated improved activity. This review aims to provide data about new strategies to target to BRAF gene mutation in metastatic colorectal cancer. PMID:27341594

  11. Metastatic colorectal cancer-past, progress and future

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The clinical management of metastatic (stage Ⅳ)colorectal cancer (CRC) is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage Ⅳ disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies,improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition.This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.

  12. Personalizing medicine for metastatic colorectal cancer: Current developments

    OpenAIRE

    Marques, Andrea Marin; Turner, Alice; de Mello, Ramon Andrade

    2014-01-01

    Metastatic colorectal cancer (mCRC) is still one of the tumor types with the highest incidence and mortality. In 2012, colorectal cancer was the second most prevalence cancer among males (9%) and the third among females (8%). In this disease, early diagnosis is important to improve treatment outcomes. However, at the time of diagnosis, about one quarter of patients already have metastases, and overall survival of these patients at 5-years survival is very low. Because of these poor statistics...

  13. Management of Metastatic Colorectal Cancer: Defining the Role of Capecitabine

    OpenAIRE

    Lynda R. Wiseman; Katherine A. Lyseng-Williamson

    2005-01-01

    Colorectal cancer (CRC), one of the most common cancers, is associated with significant morbidity, mortality, and medical costs. Treatment options in metastatic CRC are largely palliative, and aim to provide symptom relief, improve health-related quality of life, and prolong survival. Chemotherapy is the mainstay of treatment for metastatic disease. Fluorouracil/leucovorin with or without oxaliplatin or irinotecan is the most widely used regimen. These agents are administered intravenously (b...

  14. Visualising and quantifying angiogenesis in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Jakobsen, Anders; Sørensen, Flemming Brandt

    2013-01-01

    Angiogenesis plays an important role in tumour growth and dissemination. We have recently shown that blood vessel density, determined by image analysis based on microRNA-126 (miRNA-126) in situ hybridization (ISH) in the primary tumours of metastatic colorectal cancers (mCRC), is predictive of...

  15. A metastatic colorectal carcinoma: A curative approach?

    Directory of Open Access Journals (Sweden)

    Basara Nadezda

    2014-01-01

    Full Text Available Background: Unresectable colorectal liver metastases can be resected after response to chemotherapy. The use of neoadjuvant chemotherapy with or without targeted monoclonal antibodies increases the proportion of resectable liver metastasis and conferred a long term survival of 40%. Methods: The current ongoing studies regarding neodjuvant treatment strategies aiming to increase a proportion of patients with resectable liver metastases is going to be presented. Results: Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression free survival in resected patients. The results of the CELIM study confirm a favourable long-term survival for patients with initially suboptimal or unresectable colorectal liver metastasis who respond to conversion therapy and undergo secondary resection. The New EPOC randomised trial does not support the addition of cetuximab to chemotherapy and surgery for operable colorectal liver metastasis in KRAS exon 2 wild-type patients. Conclusion: The ability of anti-epidermal growth factor receptor agents to increase response rate and resection when added to chemotherapy has been clearly shown in a number of trials. The resection rates are higher with chemotherapy plus Cetuximab, in general, a conversion is contributes to the better overall survival.

  16. Targeting metastatic colorectal cancer – present and emerging treatment options

    Directory of Open Access Journals (Sweden)

    Ciombor KK

    2014-07-01

    Full Text Available Kristen K Ciombor,1 Jordan Berlin21Division of Medical Oncology, Department of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 2Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USAAbstract: Metastatic colorectal cancer is a significant cause of morbidity and mortality in the US and around the world. While several novel cytotoxic and biologic therapies have been developed and proven efficacious in the past two decades, their optimal use in terms of patient selection, drug combinations, and regimen sequences has yet to be defined. Recent investigations regarding anti-epidermal growth factor receptor therapies include the comparison of single-agent panitumumab and cetuximab, the benefit of adding cetuximab to chemotherapy in the conversion therapy setting, the comparison of cetuximab and bevacizumab when added to first-line chemotherapy, and predictive biomarkers beyond KRAS exon 2 (codons 12 and 13 mutations. With respect to anti-vascular endothelial growth factor therapies, new data on continuing bevacizumab beyond disease progression on a bevacizumab-containing chemotherapy regimen, the addition of bevacizumab to triplet chemotherapy in the first-line setting, maintenance therapy with bevacizumab plus either capecitabine or erlotinib, the addition of aflibercept to chemotherapy, and regorafenib as monotherapy have emerged. Recent scientific and technologic advances in the field of metastatic colorectal cancer promise to elucidate the biological underpinnings of this disease and its therapies for the goal of improving personalized treatments for patients with metastatic colorectal cancer.Keywords: cetuximab, panitumumab, bevacizumab, aflibercept, regorafenib, biomarker

  17. miR-345 in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Schou, Jakob V; Rossi, Simona; Jensen, Benny V; Nielsen, Dorte L; Pfeiffer, Per; Høgdall, Estrid; Yilmaz, Mette; Tejpar, Sabine; Delorenzi, Mauro; Kruhøffer, Mogens; Johansen, Julia S

    2014-01-01

    overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. METHODS: From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood......INTRODUCTION: MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic for...

  18. Anti-angiogenic agents in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Colorectal cancer (CRC) is a major public health concernbeing the third leading cause of cancer mortality inthe United States. The availability of better therapeuticoptions has led to a decline in cancer mortality in thesepatients. Surgical resection should be considered in allstages of the disease. The use of conversion therapyhas made surgery a potentially curative option even inpatients with initially unresectable metastatic disease.In this review we discuss the role of various antiangiogenicagents in patients with metastatic CRC(mCRC). We describe the mechanism of action of theseagents, and the rationale for their use in combinationwith chemotherapy. We also review important clinicalstudies that have evaluated the safety and efficacy ofthese agents in mCRC patients. Despite the discoveryof several promising anti-angiogenic agents, mCRCremains an incurable disease with a median overallsurvival of just over 2 years in patients exposed to allavailable treatment regimens. Further insights intotumor biology and tumor microenvironment may helpimprove outcomes in these patients.

  19. Prevalence of colorectal adenomas in asymptomatic young adults: a window to early intervention?

    Science.gov (United States)

    Kwak, Ji Yeong; Kim, Kwang Min; Yang, Hae Jin; Yu, Kil Jong; Lee, Jae Gon; Jeong, Yeon Oh; Shim, Sang Goon

    2016-06-01

    Objective The prevalence of colorectal adenoma is increasing in the average-risk population. However, little research is available on colorectal adenoma in young adults under age 40. The aim of this study was to investigate the prevalence and risk factors of colorectal adenoma in 20- to 39-year-old adults. Methods We evaluated 4286 asymptomatic young adults aged 20 to 39 years who underwent first colonoscopy screening as part of an employer-provided health wellness programme at the Health Promotion Centre of Samsung Changwon Hospital, Korea from January 2011 to December 2013. Logistic regression modelling was used to identify risk factors for colorectal adenoma in asymptomatic young adults. Results The prevalence of colorectal adenoma and advanced adenoma was 11.6% (497/4286) and 0.9% (39/4286), respectively. By age group, the prevalence of colorectal adenoma was 5.4% (33/608) in participants aged 20 to 29 years and 12.6% (464/3678) in participants aged 30 to 39. Colorectal adenoma was found in 13.1% (403/3072) of men and 7.7% (94/1214) of women. Increased risk of colorectal adenoma was associated with age over 30 years (OR, 2.37; 95% CI, 1.64-3.42), current smoker status (OR, 1.48; 95% CI, 1.14-1.91), and alcohol consumption (OR, 1.29; 95% CI, 1.03-1.63). Conclusions Our findings indicate that even if the prevalence of colorectal adenoma was low in young adults aged 20 to 39, being over 30, cigarette smoking, and alcohol consumption can affect young adults who have no other CRC risks. PMID:26863602

  20. Metastatic Colorectal Cancer: Review of Diagnosis and Treatment Options

    Directory of Open Access Journals (Sweden)

    Madalina Palaghia

    2015-04-01

    Full Text Available Colorectal cancer (CRC is currently considered the third most common neoplasm in the world according to the World Cancer Research Fund International with 1.4 million cases diagnosed in 2012, and the second malignity as cause of death. Approximately 1/5 of patients present directly with metastatic disease (mCRC, and 30 to 50% develop metastasis after surgical treatment for initially localized disease. The aims of the current study are to review the diagnostic particularities, treatment options and clinical evolution of mCRC. Metastatic process in CRC is long and complex, involving several mechanisms, molecular pathways and cellular types. Advances in medical imaging now allow an early and accurate diagnosis of metastatic lesions no matter their location. The progress of fundamental research in CRC led to understanding the molecular basis of the metastatic process that was further translated into novel chemotherapic and biological agents, thus increasing overall survival and and progression-free survival rates. Resection of liver, lung and brain metastases is crucial for survival when achievable and is more effective when completed by an oncological treatment and rigorous follow-up. All patients with mCRC should be discussed by a multidisciplinary team (surgeon, oncologist, radiologist, and gastroenterologist in order to identify the most appropriate therapeutic management.

  1. MRI of metastatic adenocarcinomas to the brain. Differential diagnosis of colorectal and pulmonary cancer

    International Nuclear Information System (INIS)

    To clarify the characteristic features of MR imagings of metastatic adenocarcinomas to the brain and search for differential points between the lesions from colorectal cancer and those of lung cancer, we evaluated retrospectively intraparenchymal metastatic lesions of 13 colorectal origins and 13 pulmonary origins on MR imagings, compared with resected specimens. Metastatic lesions from colorectal cancer showed marked hypointense solid components on T2WI, which correspond to the dense tumor cells and coagulated necrosis pathologically. Metastatic lesions from lung cancers showed mixed intensity and various components on T2WI, which correspond to various histological components, such as solid tumor cell's nests, hemorrhage, necrosis and cystic fluid collection. Pathological specimens suggested that the low signal intensity on T2WI of MRI derived from concentration of tumor cells and coagulated necrosis including macrophages and lymphocytes. This study may contribute to make the differential diagnosis of metastatic adenocarcinomas to the brain from colorectal and pulmonary cancers. (author)

  2. Cetuximab in the treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Moosmann, Nicolas; Heinemann, Volker

    2007-02-01

    Cetuximab is a chimeric monoclonal antibody that binds to the epidermal growth factor receptor and thereby inhibits cell proliferation, metastasis and angiogenesis. Preclinical studies indicate that cetuximab induces synergistic antitumor activity when combined with chemotherapy or radiation. This observation is supported by clinical trials demonstrating that cetuximab improves tumor response when used in conjunction with modern chemotherapy in patients with metastatic colorectal cancer. Improved treatment efficacy may help to increase the rate of hepatic metastasis resection after downsizing of initially unresectable lesions. In pretreated patients, cetuximab may restore the sensitivity to irinotecan and, therefore, has been registered in this setting. Ongoing studies are investigating the integration of anti-epidermal growth factor receptor and anti-vascular endothelial growth factor strategies into new treatment regimens. Promising results have already been obtained in a trial combining irinotecan, bevacizumab and cetuximab. PMID:17250462

  3. Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer: single center experience

    OpenAIRE

    Ocvirk Janja; Moltara Maja Ebert; Mesti Tanja; Boc Marko; Rebersek Martina; Volk Neva; Benedik Jernej; Hlebanja Zvezdana

    2016-01-01

    Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients’ register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer.

  4. Treatment with capecitabine + bevacizumab following induction treatment with FOLFIRI + bevacizumab in metastatic colorectal carcinoma

    OpenAIRE

    Tatlı, Ali Murat; COŞKUN, HASAN ŞENOL; Uysal, Mükremin; Arslan, Deniz; Sezgin Göksu, Sema; Güenay Gündüz, Şeyda; Çakal, Selda; Bozcuk, Hakan Şat; Savaş, Burhan

    2014-01-01

    Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, and it has been found to increase both progression-free survival and overall survival when it is combined with chemotherapeutic agents in the first-line and subsequent treatment of metastatic colorectal carcinoma. The objective of this study was to show the efficacy of maintenance treatment with capecitabine plus bevacizumab in patients with metastatic colorectal cancer who responded to treatment ...

  5. Concomitant parenteral nutrition and systemic cytotoxic therapy in a metastatic colorectal cancer patient

    Directory of Open Access Journals (Sweden)

    A. A. Popov

    2015-02-01

    Full Text Available Pathologic nutrients metabolism presents a severe problem in metastatic colorectal cancer patients, especially those with canceromatosis. A hypermetabolism-catabolism syndrome frequently develops in in patients with progressing canceromatosis. This leads to cachexia anorexia syndrome, which significantly impedes available treatment options. Artificial nutrition allows to improve available treatment in such patients. We present a successful case of concomitant parenteral nutrition and systemic cytotoxic therapy in metastatic colorectal cancer patient with peritoneal canceromatosis.

  6. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert B. Sims

    2011-01-01

    Full Text Available Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  7. Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

    Directory of Open Access Journals (Sweden)

    Yo-Han Han

    2016-08-01

    Full Text Available Arctigenin (ARC has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC. In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2 and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

  8. The clinical significance of circulating tumor cells in non-metastatic colorectal cancer - A review

    DEFF Research Database (Denmark)

    Thorsteinsson, M; Jess, Per

    2011-01-01

    BACKGROUND: Finding a clinical tool to improve the risk stratification and identifying those colorectal cancer patients with an increased risk of recurrence is of great importance. The presence of circulating tumor cells (CTC) in peripheral blood can be a strong marker of poor prognosis in patients...... and prognosis. METHODS: The PubMed and Cochrane database and reference lists of relevant articles were searched for scientific literature published in English from January 2000 to June 2010. We included studies with non-metastatic colorectal cancer (TNM-stage I-III) and CTC detected pre- and/or post...... of CTC to be a prognostic marker of poor disease-free survival. CONCLUSION: The presence of CTC in peripheral blood is a potential marker of poor disease-free survival in patients with non-metastastic colorectal cancer. The low abundance of CTC in non-metastatic colorectal cancer requires very...

  9. A meta analysis of cetuximab plus oxaliplatin based chemotherapy regimen for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Y L Zhu

    2014-01-01

    Full Text Available Background: Oxaliplatin based chemotherapy regimen was one of the most used chemotherapy modality for metastatic colorectal cancer. The purpose of this meta-analysis was to assess the clinical activity and toxicities of cetuximab plus oxaliplatin-based chemotherapy regimen for metastatic colorectal Cancer. Methods: We searched the clinical studies about the cetuximab plus oxaliplatin-based chemotherapy regimen versus oxaliplatin-based chemotherapy alone for metastatic colorectal cancer in the databases of PubMed, EMBASE, Cochran, and CNKI. The data of response and toxicities were extracted and pooled by random or fixed effects model. And publication bias was evaluated by begg′s funnel plot and egger′s regression test. Results: Seven papers were included in this study. Adding cetuximab to oxaliplatin-based chemotherapy regime can significant increase response rate in K-RAS mutation metastatic colorectal patients (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.17-1.80, Z = 3.38, P = 0.001 and metastatic colorectal patients without knowing the K-RAS status (OR: 1.36, 95% CI: 1.11-1.65, Z = 1.89, P = 0.003. But for patients with mutated K-RAS, the improvement for objective response rate was not statistical significant (OR: 0.70, 95% CI: 0.49-1.01, Z = 3.00, P = 0.058 when adding cetuximab to oxaliplatin-based chemotherapy regime. The pooled results indicating the rash and diarrhea risk was significantly increased in the combined treatment group (P 0.05. Significant publication bias was found in toxicities evaluation. Conclusion: Cetuximab plus oxaliplatin-based chemotherapy regimen significant increase the response rate for metastatic colorectal cancer. But the some toxicities such rash and diarrhea risk was also increased.

  10. Outcomes in Patients with Obstructive Jaundice from Metastatic Colorectal Cancer and Implications for Management

    Science.gov (United States)

    Nichols, Shawnn D.; Albert, Scott; Shirley, Lawrence; Schmidt, Carl; Abdel-Misih, Sherif; El-Dika, Samer; Groce, J. Royce; Wu, Christina; Goldberg, Richard M.; Bekaii-Saab, Tanios; Bloomston, Mark

    2016-01-01

    Introduction Patients with metastatic colorectal cancer can develop jaundice from intrahepatic or extrahepatic causes. Currently, there is little data on the underlying causes and overall survival after onset of jaundice. The purpose of this study was to characterize the causes of jaundice and determine outcomes. Methods Six hundred twenty-nine patients treated for metastatic colorectal cancer between 2004 and 2010 were retrospectively reviewed. Those developing jaundice were grouped as having intrahepatic or extrahepatic obstruction. Demographics, clinicopathologic, and outcome data were analyzed. Results Sixty-two patients with metastatic colorectal cancer developed jaundice. Intrahepatic biliary obstruction was most common, occurring in younger patients. Time from metastatic diagnosis to presentation of jaundice was similar between groups, as was the mean number of prior lines of chemotherapy. Biliary decompression was successful 41.7 % of the time and was attempted more commonly for extrahepatic causes. Median overall survival after onset of jaundice was 1.5 months and it was similar between groups, but improved to 9.6 months in patients who were able to receive further chemotherapy. Conclusions Jaundice due to metastatic colorectal cancer is an ominous finding, representing aggressive tumor biology or exhaustion of therapies. Biliary decompression is often difficult and should only be pursued when additional treatment options are available. PMID:25300799

  11. Mechanisms of resistance to anti-EGFR monoclonal antibody treatment in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Zacharenia; Saridaki; Vassilis; Georgoulias; John; Souglakos

    2010-01-01

    Metastatic colorectal cancer (mCRC) continues to be counted as a major health problem. The introduction of newer cytotoxics, irinotecan and oxaliplatin, has achieved a significant improvement in survival rates. Novel targeted therapies (bevacizumab, and cetux-imab) in combination with most efficient chemotherapy regimens have pushed the median survival beyond the 2-year mark and increased the proportion of patients which could benefit from resection of metastatic lesions. In addition, several studies have p...

  12. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

    OpenAIRE

    E. Van Cutsem; Cervantes, A.; Adam, R.; Sobrero, A; van Krieken, J. H.; Aderka, D; Aranda Aguilar, E; Bardelli, A.; Benson, A; Bodoky, G; Ciardiello, F; D'Hoore, A; Diaz-Rubio, E; Douillard, J-Y; Ducreux, M.

    2016-01-01

    Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. ...

  13. Gemcitabine and capecitabine for heavily pre-treated metastatic colorectal cancer patients

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Pallisgaard, Niels; Andersen, Rikke F;

    2014-01-01

    AIM: We investigated the efficacy and safety of capecitabine and gemcitabin (GemCap) in heavily pre-treated, therapy-resistant metastatic colorectal cancer (mCRC) patients and the clinical importance of cell-free DNA (cfDNA) measurement. PATIENTS AND METHODS: Patients' inclusion criteria included...

  14. Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Boisen, M K; Johansen, J S; Dehlendorff, Christian;

    2013-01-01

    There is an unmet need for predictive markers for the antiangiogenic agent bevacizumab in metastatic colorectal cancer (mCRC). We aimed to assess whether the location of the primary tumor is associated with bevacizumab effectiveness when combined with capecitabine and oxaliplatin (CAPEOX) in the ...

  15. Changes in mutational status during third-line treatment for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Pallisgaard, Niels; Andersen, Rikke Fredslund; Jakobsen, Anders

    2014-01-01

    KRAS and BRAF mutations are responsible for primary resistance to epidermal growth factor receptor (EGFR) MoAbs in metastatic colorectal cancer (mCRC), but it is unknown what causes wildtype (wt) patients to develop resistance during treatment. We measured circulating free DNA (cfDNA), KRAS and B...

  16. Concomitant parenteral nutrition and systemic cytotoxic therapy in a metastatic colorectal cancer patient

    OpenAIRE

    Popov, A.A.; I. L. Chernikovsky; O. L. Fakhrutdinova; E V Tkachenko

    2012-01-01

    Pathologic nutrients metabolism presents a severe problem in metastatic colorectal cancer patients, especially those with canceromatosis. A hypermetabolism-catabolism syndrome frequently develops in in patients with progressing canceromatosis. This leads to cachexia anorexia syndrome, which significantly impedes available treatment options. Artificial nutrition allows to improve available treatment in such patients. We present a successful case of concomitant parenteral nutrition and systemic...

  17. Bevacizumab for metastatic colorectal cancer: a NICE single technology appraisal.

    Science.gov (United States)

    Whyte, Sophie; Pandor, Abdullah; Stevenson, Matt

    2012-12-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of bevacizumab (Roche Products) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with metastatic colorectal cancer (mCRC), as part of the Institute's Single Technology Appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper provides a description of the company submission, the ERG review and NICE's subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology provided within the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a phase III, multicentre, multinational, two-arm, randomized, open-label study with the primary objective of confirming the non-inferiority of oxaliplatin plus capecitabine (XELOX) compared with oxaliplatin plus 5-fluorouracil and folinic acid (FOLFOX-4) in adult patients with histologically confirmed mCRC who had not previously been treated. The ERG considered that the NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free and overall survival when bevacizumab is added to either XELOX or FOLFOX-4. The ERG considered that the size of the actual treatment effect of bevacizumab was uncertain due to trial design limitations, imbalance of a known prognostic factor, relatively short treatment duration compared with that allowed within the trial protocol, and interpretation of the statistical analyses. The manufacturer's submission included a de novo economic evaluation using a cost-effectiveness model built in Microsoft® Excel. The ERG

  18. Critical appraisal of bevacizumab in the treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Zoratto F

    2012-09-01

    Full Text Available Federica Zoratto,1 Luigi Rossi,1 Angelo Zullo,2 Anselmo Papa,1 Eleonora Zaccarelli,1 Luigi Tomao,3 Erika Giordani,1 Maria Colonna,4 Giovanni Baiano,5 Silverio Tomao11Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University, Oncology Unit, “SM Goretti” Hospital, Latina; 2Gastroenterology and Digestive Endoscopy Unit, “Nuovo Regina Margherita” Hospital, Rome; 3Biology Department, “Regina Elena National Cancer Institute”, Rome; 4Oncology Unit, “Don Luigi di Liegro” Hospital, Gaeta, 5Surgery Unit, “San Giovanni di Dio” Hospital, Fondi, ItalyAbstract: Colorectal cancer is one of the most common cancers worldwide. The prognosis of patients with metastatic colorectal cancer in recent years has increased from 5 months with best supportive care to nearly 2 years with chemotherapy combined with bevacizumab, an antivascular endothelial growth factor monoclonal antibody. New prognostic and predictive biomarkers have been identified to guide chemotherapy in metastatic colorectal cancer, such as KRAS and BRAF oncogenes. However, the status of these oncogenes does not affect the efficacy of bevacizumab, and biomarkers predicting response to treatment with bevacizumab are still lacking. Addition of bevacizumab to regimens based on fluoropyrimidines or irinotecan has been shown to improve overall survival in treatment-naïve patients with metastatic colorectal cancer. Similarly, a significant increase in overall survival rate is achieved by adding bevacizumab to fluoropyrimidines and oxaliplatin in patients with disease progression. Bevacizumab has been found to be effective even when used as third-line therapy and later. In addition, cohort studies have shown that bevacizumab improves survival significantly despite disease progression. Finally, bevacizumab therapy in the neoadjuvant setting for the treatment of liver metastasis is well tolerated, safe, and effective.Keywords: metastatic colorectal cancer

  19. Clinical significance of subcellular localization of KL-6 mucin in primary colorectal adenocarcinoma and metastatic tissues

    Institute of Scientific and Technical Information of China (English)

    Qian Guo; Masatoshi Makuuchi; Wei Tang; Yoshinori Inagaki; Yutaka Midorikawa; Norihiro Kokudo; Yasuhiko Sugawara; Munehiro Nakata; Toshiro Konishi; Hirokazu Nagawa

    2006-01-01

    AIM: To assess subcellular localization of KL-6 mucin and its clinicopathological significance in colorectal carcinoma as well as metastatic lymph node and liver tissues.METHODS: Colorectal carcinoma tissues as well as metastatic lymph node and liver tissues were collected from 82 patients who underwent colorectomy or hepatectomy. Tissues were subjected to immunohistochemical analysis using KL-6 antibody.RESULTS: Of the 82 colorectal carcinoma patients, 6showed no staining, 29 showed positive staining only in the apical membrane, and 47 showed positive staining in the circumferential membrane and/or cytoplasm.Positive staining was not observed in non-cancerous colorectal epithelial cells surrounding the tumor tissues.The five-year survival rate was significantly lower in cases showing positive staining in the circumferential membrane and/or cytoplasm (63.0%) than those showing positive staining only in the apical membrane (85.7%) and those showing no staining (100%).Statistical analysis between clinicopathological factors and subcellular localization of KL-6 mucin showed that KL-6 localization in the circumferential membrane and/or cytoplasm was significantly associated with the presence of venous invasion (P=0.0003), lymphatic invasion (P<0.0001), lymph node metastasis (P<0.0001),liver metastasis (P=0.058), and advanced histological stage (P<0.0001). Positive staining was observed in all metastatic lesions tested as well as in the primary colorectal carcinoma tissues.CONCLUSION: The subcellular staining pattern of KL-6 in colorectal adenocarcinoma may be an important indicator for unfavorable behaviors such as lymph node and liver metastasis, as well as for the prognosis of patients.

  20. Current treatment for colorectal cancer metastatic to the liver

    NARCIS (Netherlands)

    Cromheecke, M; de Jong, KP; Hoekstra, HJ

    1999-01-01

    Surgery is currently the only available treatment option which offers the potential for cure for patients with liver metastases from colorectal cancer. Of those who undergo a potentially curative operation for their primary tumour but subsequently recur, almost 80% will develop evidence of metastati

  1. Clinical impact of FDG PET-CT in patients with potentially operable metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Aim: To assess the clinical impact of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography–computed tomography (PET-CT) in patients with potentially resectable metastatic colorectal cancer. Materials and methods: One hundred and two patients with potentially resectable metastatic colorectal cancer underwent FDG PET-CT in addition to conventional imaging over an 18-month period. The findings were compared to conventional imaging, with histological or clinico-radiological validation. The impact on subsequent management was evaluated using information from clinico-radiological databases. Results: Of 102 patients (mean age 67 years, range 27–85 years), 94 had liver, five had isolated lung, and three had limited peritoneal metastases. In 31 patients (30%) PET-CT had a major impact on subsequent management, by correctly clarifying indeterminate lesions on conventional imaging as inoperable metastatic disease in 16 patients, detecting previously unsuspected metastatic disease in nine patients, identifying occult second primary tumours in three patients, and correctly down-staging three patients. PET-CT had a minor impact in 12 patients (12%), no impact in 49 cases (48%), and a potentially negative impact in 10 cases (10%). Following PET-CT, 36 (35%) patients were no longer considered for surgery. Of those remaining operative 45 of 66 (68%) underwent potentially curative metastatic surgery. In this cohort PET-CT saved 16 futile laparotomies. Conclusion: FDG PET-CT has a valuable role in selected patients with metastatic colorectal cancer by improving staging accuracy and characterizing indeterminate lesions and helps triage patients to the appropriate treatment.

  2. Clinical impact of FDG PET-CT in patients with potentially operable metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, R.H. [Department of Radiology, Calderdale and Huddersfield NHS Foundation Trust, Huddersfield (United Kingdom); Chowdhury, F.U. [Departments of Radiology and Nuclear Medicine, St James' s University Hospital, Leeds (United Kingdom); Lodge, J.P.A. [HPB and Transplant Unit, St James' s University Hospital, Leeds (United Kingdom); Scarsbrook, A.F., E-mail: andrew.scarsbrook@leedsth.nhs.uk [Departments of Radiology and Nuclear Medicine, St James' s University Hospital, Leeds (United Kingdom)

    2011-12-15

    Aim: To assess the clinical impact of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography-computed tomography (PET-CT) in patients with potentially resectable metastatic colorectal cancer. Materials and methods: One hundred and two patients with potentially resectable metastatic colorectal cancer underwent FDG PET-CT in addition to conventional imaging over an 18-month period. The findings were compared to conventional imaging, with histological or clinico-radiological validation. The impact on subsequent management was evaluated using information from clinico-radiological databases. Results: Of 102 patients (mean age 67 years, range 27-85 years), 94 had liver, five had isolated lung, and three had limited peritoneal metastases. In 31 patients (30%) PET-CT had a major impact on subsequent management, by correctly clarifying indeterminate lesions on conventional imaging as inoperable metastatic disease in 16 patients, detecting previously unsuspected metastatic disease in nine patients, identifying occult second primary tumours in three patients, and correctly down-staging three patients. PET-CT had a minor impact in 12 patients (12%), no impact in 49 cases (48%), and a potentially negative impact in 10 cases (10%). Following PET-CT, 36 (35%) patients were no longer considered for surgery. Of those remaining operative 45 of 66 (68%) underwent potentially curative metastatic surgery. In this cohort PET-CT saved 16 futile laparotomies. Conclusion: FDG PET-CT has a valuable role in selected patients with metastatic colorectal cancer by improving staging accuracy and characterizing indeterminate lesions and helps triage patients to the appropriate treatment.

  3. Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Erkasap, N.; Ozkurt, M. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Erkasap, S.; Yasar, F. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uzuner, K. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Ihtiyar, E. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uslu, S.; Kara, M. [Department of Biochemistry, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Bolluk, O. [Department of Biostatistics, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey)

    2013-03-19

    The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

  4. Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

    International Nuclear Information System (INIS)

    The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis

  5. Leptin receptor (Ob-R mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    N. Erkasap

    Full Text Available The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases and metastatic colon (13 cases cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

  6. Durable response using regorafenib in an elderly patient with metastatic colorectal cancer: case report

    Directory of Open Access Journals (Sweden)

    Tang R

    2015-11-01

    Full Text Available Ronald Tang,1 Tatiana Kain,2 June Herman,2 Tara Seery1 1Division of Hematology-Oncology, 2Division of Nuclear Medicine and Molecular Imaging, University of California, Irvine, Orange, CA, USA Abstract: Regorafenib, an oral multikinase inhibitor, was approved in September 2012 by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer. Since this time, however, few case reports outlining real-world usage have been published in the literature. Here, we detail the clinical history of an elderly woman with KRAS wild-type colon cancer who received regorafenib after prior treatment with other agents. We show that by employing dose modification strategies to address adverse events, this patient was able to remain on therapy for 11 months and achieve stable disease. Keywords: regorafenib, metastatic colorectal cancer, oral multikinase inhibitor

  7. Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial

    Institute of Scientific and Technical Information of China (English)

    Janja; Ocvirk; Thomas; Brodowicz; Fritz; Wrba; Tudor; E; Ciuleanu; Galina; Kurteva; Semir; Beslija; Ivan; Koza; Zsuzsanna; Pápai; Diethelm; Messinger; Ugur; Yilmaz; Zsolt; Faluhelyi; Suayib; Yalcin; Demetris; Papamichael; Miklós; Wenczl; Zrinka; Mrsic-Krmpotic; Einat; Shacham-Shmueli; Damir; Vrbanec; Regina; Esser; Werner; Scheithauer; Christoph; C; Zie-linski

    2010-01-01

    AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B ...

  8. Bevacizumab-containing regimens after cetuximab failure in Kras wild-type metastatic colorectal carcinoma

    OpenAIRE

    LAM, KA ON; LEE, VICTOR HO FUN; LIU, RICO KIN YIN; Leung, To Wai; Kwong, Dora Lai Wan

    2012-01-01

    Bevacizumab and cetuximab both improve treatment efficacy when administered with chemotherapy for metastatic colorectal carcinoma (mCRC). Cetuximab has enhanced efficacy in Kras wild-type tumors. However, inferior outcomes have been demonstrated concerning the concurrent use of bevacizumab and cetuximab with chemotherapy. There is an urgent need to define the optimal sequence of use of these two agents. With regard to the pre-clinical data that increased VEGF expression is associated with acq...

  9. Oxidative stress may cause metastatic disease in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Søndergaard, Edith Smed; Gögenur, Ismail

    2014-01-01

    Despite surgical treatment of stage II colorectal cancer many patients will experience relapse. Inflammatory and immunologic reactions created due to the surgical stress response result in the production of reactive oxygen species. Oxidative stress in turn, may result in the stimulation of cancer...... cells that have not been cleared by the immune system to metastasize. In this paper we present an overview of studies where oxidative stress in relation to surgery has been linked to the development of metastatic disease....

  10. Treatment with capecitabine + bevacizumab following induction treatment with FOLFIRI + bevacizumab in metastatic colorectal carcinoma

    Science.gov (United States)

    Tatlı, Ali Murat; Coşkun, Hasan Şenol; Uysal, Mükremin; Arslan, Deniz; Sezgin Göksu, Sema; Güenay Gündüz, Şeyda; Çakal, Selda; Bozcuk, Hakan Şat; Savaş, Burhan

    2014-01-01

    Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, and it has been found to increase both progression-free survival and overall survival when it is combined with chemotherapeutic agents in the first-line and subsequent treatment of metastatic colorectal carcinoma. The objective of this study was to show the efficacy of maintenance treatment with capecitabine plus bevacizumab in patients with metastatic colorectal cancer who responded to treatment with FOLFIRI plus bevacizumab. The study included patients with metastatic colorectal cancer who received FOLFIRI plus bevacizumab as a first-line treatment. Patients who had objective response with FOLFIRI plus bevacizumab treatment after an average period of 6 months received a maintenance treatment with capecitabine plus bevacizumab (capecitabine 2 x 1000 mg/m2, 1 - 14 days, every 21 days, bevacizumab 7.5 mg/m2, every 21 days) until disease progression or toxicity. The time to progression on bevacizumab treatment was evaluated. A total of 29 patients (15 male, 14 female) were included. The mean age was 62 years. The mean number of cycles for maintenance treatment with capecitabine plus bevacizumab was 12. The median PFS was 16 ± 3 months, and OS was 42 ± 11 months. PFS and OS were remarkably higher in patients with a complete or near complete response to induction treatment. Fourteen patients (48%) experienced hand-foot syndrome associated with capecitabine plus bevacizumab treatment, without any severe toxicity. Inselected patients with metastatic colorectal carcinoma who had a remarkable objective response to FOLFIRI plus bevacizumab treatment, a maintenance treatment with capecitabine plus bevacizumab following FOLFIRI plus bevacizumab until disease progression may be a suitable, effective and tolerable regimen, which requires further studies. PMID:25232406

  11. Capecitabine for locally advanced and metastatic colorectal cancer: A review

    OpenAIRE

    Koukourakis, Georgios V; Zacharias, Georgios; Tsalafoutas, John; Theodoridis, Dimitrios; Kouloulias, Vassilios

    2010-01-01

    Capecitabine (Xeloda®) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specific conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to trials that compared Capeci...

  12. Comparative study of proteome between primary cancer and hepatic metastatic tumor in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Bo Yu; Shi-Yong Li; Ping An; Ying-Nan Zhang; Zhen-Jia Liang; Shu-Jun Yuan; Hui-Yun Cai

    2004-01-01

    AIM: To identify the differential proteins associated with colorectal cancer genesis and hepatic metastasis. METHODS: Hydrophobic protein samples were extracted from normal colorectal mucosa, primary cancer lesion and hepatic metastatic foci of colorectal cancer. With twodimensional electrophoresis and image analysis, differentially expressed protein spots were detected, and the proteins were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and peptide mass fingerprint analysis.RESULTS: Significant alterations of the proteins in number and expression levels were discovered in primary cancer and hepatic metastatic foci, the expression of a number of proteins was lost in 25-40 ku, but protein spots was increased in 14-21ku, compared with normal mucosa. Nine differentially expressed protein spots were identified. Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized ascalmodulin, ribonuclease 6 precursor and mannosidase-α.Proapolipoprotein was expressed progressively from normal mucosa to primary cancer and hepatic metastasis. The differentially expressed protein of beta-globin was found in normal mucosa and hepatic metastatic tumor, but lost in primary cancer lesion. Cdc 42, a GTP-binding protein, was identified in hepatic metastasis. The protein spots of C4 from primary cancer, M7 and M9 from hepatic metastasis had less homology with the proteins in database. CONCLUSION: Variations of hydrophobic protein expression in colorectal cancer initiation and hepatic metastasis are significant and can be observed with two-dimensionalelectrophoresis. The expression of calmodulin, ribonuclease6 precursor and mannosidase-α is lost but the expression of proapolipoprotein is enhanced which is associated with colorectal cancer genesis and hepatic metastasis. Cdc 42 and beta-globin are expressed abnormally in hepaticmetastasis. Protein C4, M7 and M9 may be associated withcolorectal

  13. A Comprehensive Review of Clinical Trials on EGFR Inhibitors Such as Cetuximab and Panitumumab as Monotherapy and in Combination for Treatment of Metastatic Colorectal Cancer

    OpenAIRE

    Yazdi, Mohammad Hossein; Faramarzi, Mohammad Ali; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2015-01-01

    Metastatic colorectal cancer is the fourth most common cause of death due to cancer after those of lung, stomach, and liver. Anti epidermal growth factor receptor drugs as a targeting therapy seem to be good candidates for curing metastatic colorectal cancer. Two available anti epidermal growth factor receptor monoclonal antibodies are cetuximab and panitumumab which have been approved for metastatic colorectal cancer treatment. Through the available literature on NCBI and clinical trials, 31...

  14. Trifluridine/tipiracil and regorafenib: new weapons in the war against metastatic colorectal cancer.

    Science.gov (United States)

    Weinberg, Benjamin A; Marshall, John L; Salem, Mohamed E

    2016-08-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Approximately 20% of patients have metastatic disease at diagnosis, and a vast number of these patients die within 5 years. The advent of modern chemotherapeutics has improved median overall survival for these patients; nonetheless, we must keep striving for better outcomes. Trifluridine/tipiracil (TAS-102) and regorafenib are agents newly approved by the US Food and Drug Administration that show promise in the treatment of metastatic colorectal cancer. These drugs have the benefit of being formulated for oral administration and have different side effect profiles. These differences are important in the selection of the best therapy for each patient, especially if the patient is prone to a side effect that is unique to just one of the treatments. In this review, we discuss the mechanism of action, side effect profile, and clinical efficacy of trifluridine/tipiracil, and compare them with those of regorafenib. Future trials will evaluate the use of these drugs in earlier lines of therapy, alone and in combination with other agents. We now have 2 more agents in the arsenal against metastatic colorectal cancer and the future is looking brighter for patients, although we still have a long way to go. PMID:27487107

  15. Massive portal vein tumor thrombus from colorectal cancer without any metastatic nodules in the liver parenchyma: report of a case

    Directory of Open Access Journals (Sweden)

    Yasushi Rino

    2011-10-01

    Full Text Available Metastatic lesions in the liver derived from colorectal cancer rarely invade the portal vein macroscopically. Portal vein tumor thrombus is commonly associated with hepatocellular carcinoma. Colorectal liver metastases are usually accompanied by microscopic tumor invasion into the intrahepatic portal vein, and the incidence of macroscopic tumor thrombus in the trunk of the portal vein is rare. Here, we provide unique appearance of metastatic colorectal cancer. To the best of our knowledge, macroscopically, the right portal vein filled with the tumor thrombus without any tumor in liver parenchyma has been quite rare.

  16. Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models

    Science.gov (United States)

    Alamo, Patricia; Gallardo, Alberto; Pavón, Miguel A.; Casanova, Isolda; Trias, Manuel; Mangues, Maria A.; Vázquez, Esther; Villaverde, Antonio; Mangues, Ramon; Céspedes, Maria V.

    2014-01-01

    Mouse colorectal cancer (CRC) models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT). This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT) group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of β1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC. PMID:24487410

  17. Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models

    Directory of Open Access Journals (Sweden)

    Patricia Alamo

    2014-03-01

    Full Text Available Mouse colorectal cancer (CRC models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT. This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of β1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC.

  18. Management of asymptomatic primary tumours in stage Ⅳ colorectal cancer: Review of outcomes

    Institute of Scientific and Technical Information of China (English)

    Kate; Jessica; Wilkinson; Wei; Chua; Weng; Ng; Aflah; Roohullah

    2015-01-01

    AIM: To compare outcomes for patients presenting withstage IV colorectal cancer and an asymptomatic primary tumour, undergoing primary tumour resection(PTR) plus palliative chemotherapy vs primary chemotherapy up-front.METHODS: A literature search was conducted using MEDLINE and EMBASE. The primary outcome was overall survival. Secondary outcomes included perioperative mortality, morbidity and delayed surgical intervention rates in patients undergoing PTR and subsequent complication rates in patients with an un-resected primary tumour. Tertiary outcomes included impact on systemic treatment and identification of prognostic factors relevant for survival in this cohort. RESULTS: Twenty non-randomised studies met the inclusion criteria. Eleven studies included comparative overall survival data. Three studies showed an overall survival advantage for PTR, 7 studies showed no statistically significant advantage, and 1 study showed a significant worsening in survival in the surgical group. The perioperative mortality rate ranged from 0% to 8.5%, and post-operative morbidity rate from 10% to 35%, mainly minor complications that did not preclude subsequent chemotherapy. The rate of delayed primarytumour related symptoms, most commonly obstruction, in patients with an un-resected primary tumour ranged from 3% to 46%. The strongest independent poor prognostic factor was extensive hepatic metastases, in addition to poor performance status, M1 b stage and non-use of modern chemotherapy agents.CONCLUSION: Based on the current literature, both PTR and up front chemotherapy appear appropriate initial management strategies, with a trend towards an overall survival advantage with PTR. The procedure has a low post-operative mortality, and most complications are transient and minor. The results of recruiting randomised trials are eagerly anticipated.

  19. Management of asymptomatic primary tumours in stage IV colorectal cancer: Review of outcomes

    Science.gov (United States)

    Wilkinson, Kate Jessica; Chua, Wei; Ng, Weng; Roohullah, Aflah

    2015-01-01

    AIM: To compare outcomes for patients presenting with stage IV colorectal cancer and an asymptomatic primary tumour, undergoing primary tumour resection (PTR) plus palliative chemotherapy vs primary chemotherapy up-front. METHODS: A literature search was conducted using MEDLINE and EMBASE. The primary outcome was overall survival. Secondary outcomes included perioperative mortality, morbidity and delayed surgical intervention rates in patients undergoing PTR and subsequent complication rates in patients with an un-resected primary tumour. Tertiary outcomes included impact on systemic treatment and identification of prognostic factors relevant for survival in this cohort. RESULTS: Twenty non-randomised studies met the inclusion criteria. Eleven studies included comparative overall survival data. Three studies showed an overall survival advantage for PTR, 7 studies showed no statistically significant advantage, and 1 study showed a significant worsening in survival in the surgical group. The perioperative mortality rate ranged from 0% to 8.5%, and post-operative morbidity rate from 10% to 35%, mainly minor complications that did not preclude subsequent chemotherapy. The rate of delayed primary-tumour related symptoms, most commonly obstruction, in patients with an un-resected primary tumour ranged from 3% to 46%. The strongest independent poor prognostic factor was extensive hepatic metastases, in addition to poor performance status, M1b stage and non-use of modern chemotherapy agents. CONCLUSION: Based on the current literature, both PTR and up front chemotherapy appear appropriate initial management strategies, with a trend towards an overall survival advantage with PTR. The procedure has a low post-operative mortality, and most complications are transient and minor. The results of recruiting randomised trials are eagerly anticipated. PMID:26691885

  20. Large scale systematic proteomic quantification from non-metastatic to metastatic colorectal cancer

    Science.gov (United States)

    Yin, Xuefei; Zhang, Yang; Guo, Shaowen; Jin, Hong; Wang, Wenhai; Yang, Pengyuan

    2015-07-01

    A systematic proteomic quantification of formalin-fixed, paraffin-embedded (FFPE) colorectal cancer tissues from stage I to stage IIIC was performed in large scale. 1017 proteins were identified with 338 proteins in quantitative changes by label free method, while 341 proteins were quantified with significant expression changes among 6294 proteins by iTRAQ method. We found that proteins related to migration expression increased and those for binding and adherent decreased during the colorectal cancer development according to the gene ontology (GO) annotation and ingenuity pathway analysis (IPA). The integrin alpha 5 (ITA5) in integrin family was focused, which was consistent with the metastasis related pathway. The expression level of ITA5 decreased in metastasis tissues and the result has been further verified by Western blotting. Another two cell migration related proteins vitronectin (VTN) and actin-related protein (ARP3) were also proved to be up-regulated by both mass spectrometry (MS) based quantification results and Western blotting. Up to now, our result shows one of the largest dataset in colorectal cancer proteomics research. Our strategy reveals a disease driven omics-pattern for the metastasis colorectal cancer.

  1. Current status of treatment of metastatic colorectal cancer with special reference to cetuximab and elderly patients

    Directory of Open Access Journals (Sweden)

    Per Pfeiffer

    2008-12-01

    Full Text Available Per Pfeiffer, Camilla Qvortrup, Jon K BjerregaardDepartment of Oncology, Odense University Hospital. Institute of Clinical Research, University of Southern Denmark. Odense C, DenmarkPurpose: Elderly cancer patients often have co-morbidities and other characteristics that make the selection of optimal treatment more complex. The introduction of targeted therapies in colorectal cancer has further complicated this problem. This review will focus on the role of the EGFR antibody cetuximab in elderly patients.Methods: We have reviewed the available evidence in the literature to evaluate the results of therapy with cetuximab, alone or in combination with chemotherapy, with a focus on elderly patients with metastatic colorectal cancer (mCRC.Results: In patients with mCRC, combination chemotherapy prolongs median survival to more than 18 months and even around 24 months in combination with cetuximab in selected patients. No prospective studies have evaluated cetuximab in elderly patients. However, subgroup analyses from randomized trials and retrospective analysis suggest that the efficacy of chemotherapy and cetuximab is maintained in fit elderly patients, but with slightly increased but acceptable toxicity.Conclusion: No prospective cetuximab studies have been conducted solely in a population of elderly patients. However, available data suggest that outcomes in the fit elderly mirror results observed in younger patients.Keywords: metastatic colorectal cancer, cetuximab, elderly patients

  2. STUDY ON ADHERENCE TO CAPECITABINE AMONG PATIENTS WITH COLORECTAL CANCER AND METASTATIC BREAST CANCER

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    Adiel Goes de FIGUEIREDO JUNIOR

    2014-09-01

    Full Text Available Context Capecitabine, an oral drug, is as effective as traditional chemotherapy drugs. Objectives To investigate the adhesion to treatment with oral capecitabine in breast and colorectal cancer, and to determine any correlation with changes in patient’s quality of life. Methods Patients with colorectal cancer or breast cancer using capecitabine were included. The patients were asked to bring any medication left at the time of scheduled visits. The QLQ-C30 questionnaire was applied at the first visit and 8-12 weeks after treatment. Results Thirty patients were evaluated. Adherence was 88.3% for metastatic colon cancer, 90.4% for non-metastatic colon cancer, 94.3% for rectal cancer and 96.2% for metastatic breast cancer. No strong correlation between adherence and European Organisation for Research and Treatment of Cancer QLQ-C30 functional or symptom scale rates had been found. There was no statistically significant correlation between compliance and the functional and symptom scales of the questionnaire before and after chemotherapy, with the exception of dyspnea. Conclusions Although no absolute adherence to oral capecitabine treatment had been observed, the level of adherence was good. Health professionals therefore need a greater focus in the monitoring the involvement of patients with oral treatment regimens. Patients with lesser degrees of dyspnea had greater compliance.

  3. Challenging chemoresistant metastatic colorectal cancer: therapeutic strategies from the clinic and from the laboratory.

    Science.gov (United States)

    Sartore-Bianchi, A; Loupakis, F; Argilés, G; Prager, G W

    2016-08-01

    As survival has improved for patients with metastatic colorectal cancer (mCRC), there is an increasing need for effective and well-tolerated third-line and subsequent-lines of treatment. Despite recent advances with the development of new-targeted therapies in this setting, there remains an unmet need to exploit oncogenic drivers of colorectal cancer and overcome acquired resistance. Potential treatment strategies include revisiting old targets such as human epidermal growth factor receptor 2, RAS, and BRAF and investigating new targets such as c-MET, the PI3 kinase, and Wnt pathways, and also the use of immune-checkpoint inhibitors. Here, we review recent phase III trials exploring approved agents, early trials investigating new drugs for chemorefractory mCRC, and the potential of capturing tumour dynamics during its evolution by liquid biopsy analysis. PMID:27154421

  4. Ex vivo electrical impedance measurements on excised hepatic tissue from human patients with metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Point-wise ex vivo electrical impedance spectroscopy measurements were conducted on excised hepatic tissue from human patients with metastatic colorectal cancer using a linear four-electrode impedance probe. This study of 132 measurements from 10 colorectal cancer patients, the largest to date, reports that the equivalent electrical conductivity for tumor tissue is significantly higher than normal tissue (p < 0.01), ranging from 2–5 times greater over the measured frequency range of 100 Hz–1 MHz. Difference in tissue electrical permittivity is also found to be statistically significant across most frequencies. Furthermore, the complex impedance is also reported for both normal and tumor tissue. Consistent with trends for tissue electrical conductivity, normal tissue has a significantly higher impedance than tumor tissue (p < 0.01), as well as a higher net capacitive phase shift (33° for normal liver tissue in contrast to 10° for tumor tissue). (paper)

  5. Palliative radiotherapy in patients with a symptomatic pelvic mass of metastatic colorectal cancer

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    Chun Ho Kyung

    2011-05-01

    Full Text Available Abstract Background To evaluate the palliative role of radiotherapy (RT and define the effectiveness of chemotherapy combined with palliative RT (CCRT in patients with a symptomatic pelvic mass of metastatic colorectal cancer. Methods From August 1995 to December 2007, 80 patients with a symptomatic pelvic mass of metastatic colorectal cancer were treated with palliative RT at Samsung Medical Center. Initial presenting symptoms were pain (68 cases, bleeding (18 cases, and obstruction (nine cases. The pelvic mass originated from rectal cancer in 58 patients (73% and from colon cancer in 22 patients (27%. Initially 72 patients (90% were treated with surgery, including 64 complete local excisions; 77% in colon cancer and 81% in rectal cancer. The total RT dose ranged 8-60 Gy (median: 36 Gy with 1.8-8 Gy per fraction. When the α/β for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED, the median RT dose was 46.8 Gy10 (14.4-78. Twenty one patients (26% were treated with CCRT. Symptom palliation was assessed one month after the completion of RT. Results Symptom palliation was achieved in 80% of the cases. During the median follow-up period of five months (1-44 months, 45% of the cases experienced reappearance of symptoms; the median symptom control duration was five months. Median survival after RT was six months. On univariate analysis, the only significant prognostic factor for symptom control duration was BED ≥40 Gy10 (p Conclusions RT was an effective palliation method in patients with a symptomatic pelvic mass of metastatic colorectal cancer. For improvement of symptom control rate and duration, a BED ≥ 40 Gy10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status.

  6. Palliative radiotherapy in patients with a symptomatic pelvic mass of metastatic colorectal cancer

    International Nuclear Information System (INIS)

    To evaluate the palliative role of radiotherapy (RT) and define the effectiveness of chemotherapy combined with palliative RT (CCRT) in patients with a symptomatic pelvic mass of metastatic colorectal cancer. From August 1995 to December 2007, 80 patients with a symptomatic pelvic mass of metastatic colorectal cancer were treated with palliative RT at Samsung Medical Center. Initial presenting symptoms were pain (68 cases), bleeding (18 cases), and obstruction (nine cases). The pelvic mass originated from rectal cancer in 58 patients (73%) and from colon cancer in 22 patients (27%). Initially 72 patients (90%) were treated with surgery, including 64 complete local excisions; 77% in colon cancer and 81% in rectal cancer. The total RT dose ranged 8-60 Gy (median: 36 Gy) with 1.8-8 Gy per fraction. When the α/β for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the median RT dose was 46.8 Gy10 (14.4-78). Twenty one patients (26%) were treated with CCRT. Symptom palliation was assessed one month after the completion of RT. Symptom palliation was achieved in 80% of the cases. During the median follow-up period of five months (1-44 months), 45% of the cases experienced reappearance of symptoms; the median symptom control duration was five months. Median survival after RT was six months. On univariate analysis, the only significant prognostic factor for symptom control duration was BED ≥40 Gy10 (p < 0.05), and CCRT was a marginally significant factor (p = 0.0644). On multivariate analysis, BED and CCRT were significant prognostic factors for symptom control duration (p < 0.05). RT was an effective palliation method in patients with a symptomatic pelvic mass of metastatic colorectal cancer. For improvement of symptom control rate and duration, a BED ≥ 40 Gy10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status

  7. First-line targeted therapies in the treatment of metastatic colorectal cancer – role of cetuximab

    Directory of Open Access Journals (Sweden)

    Giuseppe Tonini

    2009-04-01

    Full Text Available Giuseppe Tonini, Alice Calvieri, Bruno Vincenzi, Daniele SantiniMedical Oncology, University Campus Bio-Medico, Rome, ItalyAbstract: Worldwide, colorectal cancer (CRC is the fourth most commonly diagnosed malignant disease and the second leading cause of cancer-related death in Western nations. In 2008 there were an estimated 148,810 new cases and 49,960 deaths in the US. For several years different chemotherapeutic regimens, based on floropyrimidines, irinotecan and oxaliplatin, have been used in advanced CRC, but survival is still unsatisfactory. New targeted therapies, including drugs and monoclonal antibodies (MoABs , show great promise in the fight against CRC and have shown activity in different disease settings. Cetuximab, a chimeric IgG1 monoclonal antibody that binds to the extracellular domain of epidermal growth factor receptor (EGFR, is active in metastatic colorectal cancer (mCRC. As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. The combination of this drug with classical chemotherapies has shown better clinical profiles reflected in an improvement in overall and progression-free survival. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. Whereas cetuximab has a clear indication in the salvage setting, its role in first-line therapy remains investigational. It is particularly encouraging that cetuximab may enhance curative opportunities in patients with early metastatic disease, suggesting that adding cetuximab in first-line therapy may downstage disease in some patients, and, as a result, allow potentially curative resection of previously unresectable metastases. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit, and the role of cetuximab in first-line treatment of metastatic CRC

  8. Panitumumab: the evidence for its use in the treatment of metastatic colorectal cancer

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    Rossana Berardi

    2010-09-01

    Full Text Available Rossana Berardi1, Azzurra Onofri2, Mirco Pistelli2, Elena Maccaroni2, Mario Scartozzi1, Chiara Pierantoni1, Stefano Cascinu11Clinica di Oncologia Medica, Università Politecnica delle Marche, Ospedali Riuniti Umberto I-GM Lancisi-G Salesi di Ancona, Italy; 2Scuola di Specializzazione in Oncologia Medica, Università Politecnica delle Marche, Ancona, ItalyAbstract: Panitumumab is the first fully human monoclonal antibody to Epidermal Growth Factor Receptor (EGFR to enter clinical trials for the treatment of solid tumors. The anti-tumor activity of panitumumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in numerous cancer models, particularly lung, kidney and colorectal (CRC. Preclinical and clinical studies have established a role for panitumumab in metastatic colorectal cancer (mCRC refractory to multiple chemotherapeutic regimens. Based on these encouraging findings, panitumumab was approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing mCRC refractory to fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic regimens. The improvement in progression free survival (PFS and response rate (RR produced by panitumumab monotherapy was significantly greater in patients with non mutated (wild-type K-RAS than in those with mutant K-RAS. Therefore implementing routine K-RAS screening and limiting the use of EGFR inhibitors to patients with wild-type K-RAS appears the better strategy for select only the patients who could benefit from the therapy with panitumumab and also may have the potential for cost savings. The purpose of this review was to evaluate the patient-related, disease-related and economic-related evidence for the use of panitumumab in the treatment of metastatic colorectal cancer in clinical practice.Keywords: colorectal cancer, EGFR; K-RAS, panitumumab 

  9. Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC)

    DEFF Research Database (Denmark)

    Winther, Stine Braendegaard; Zubcevic, Kanita; Qvortrup, Camilla;

    2016-01-01

    BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate....... In general, therapy was well tolerated; main non-hematological toxicities were fatigue and diarrhea. CONCLUSION: S-1 monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients. These regimens are now further evaluated...

  10. FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study

    DEFF Research Database (Denmark)

    Geva, Ravit; Vecchione, Loredana; Kalogeras, Konstantinos T;

    2015-01-01

    OBJECTIVE: We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled. DESIGN: To show a HR advantage of...... patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated with cetuximab alone or in combination with chemotherapy. Fc gamma receptor (FCGR) status was centrally genotyped. Two additional externally genotyped series were included. RESULTS: Incidences of FCGR2A...

  11. Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer

    OpenAIRE

    Walker Mark S; Pharm Elaine; Kerr Jiandong; Yim Yeun; Stepanski Edward J; Schwartzberg Lee S

    2012-01-01

    Abstract Background Bevacizumab (B) and cetuximab (C) are both approved for use in the treatment of metastatic colorectal cancer (mCRC) in the second-line. We examined patient reported symptom burden during second-line treatment of mCRC. Methods Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O) and who had completed ≥ 1 Patient Care Monitor (PCM) surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. ...

  12. Intraarticular hemorrhage due to bevacizumab in a patient with metastatic colorectal cancer: a case report

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    Uysal Mukremin

    2012-07-01

    Full Text Available Abstract Introduction Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. It is widely used in the treatment of metastatic colorectal cancer. It has some specific side effects including severe bleeding, wound healing problems, gastrointestinal perforation, proteinuria and hypertension. Case presentation We present the case of a 65-year old Asian man with synovial metastasis of the knee who experienced intraarticular hemorrhage after bevacizumab treatment. He presented with monoarthritis of the left knee. Conclusion Bevacizumab-related hemorrhage can cause serious morbidity and unusual sites of hemorrhage may be seen.

  13. Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management

    International Nuclear Information System (INIS)

    Regorafenib is a broad-spectrum oral multikinase inhibitor that targets several angiogenic, oncogenic, and stromal receptor tyrosine kinases that support the tumor microenvironment. Results from the pivotal Phase III Patients with Metastatic Colorectal Cancer Treated with Regorafenib or Placebo After Failure of Standard Therapy (CORRECT) trial showed that the addition of regorafenib to best supportive care resulted in a significant improvement in median overall survival and progression-free survival compared with placebo plus best supportive care in patients with metastatic colorectal cancer (mCRC) following all available approved therapies. Thus, regorafenib is the first oral multikinase inhibitor indicated for mCRC; it currently has approval in the USA, EU, Japan, Canada, and Singapore for the treatment of mCRC patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy, and, if the tumor is KRAS wild-type, an anti-epidermal growth factor receptor therapy. In this review, we highlight regorafenib’s mechanism of action, present key efficacy data from the CORRECT trial, and discuss how to proactively manage common adverse events (eg, hand-foot skin reaction, hypertension, oral mucositis, diarrhea, and fatigue) experienced by patients receiving regorafenib. Increased awareness of potential adverse events associated with regorafenib and the implementation of proactive strategies to prevent, monitor, and manage these events early in the course of treatment will be instrumental in ensuring optimal patient management and continuation of regorafenib therapy

  14. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Tabernero, Josep; Pfeiffer, Per; Cervantes, Andrés

    2008-01-01

    The primary purpose of this paper is to present the available evidence for the administration of cetuximab on an every-2-weeks basis in combination with irinotecan in metastatic colorectal cancer (mCRC). Cetuximab is an epidermal growth factor receptor-targeted IgG(1) monoclonal antibody that is ......The primary purpose of this paper is to present the available evidence for the administration of cetuximab on an every-2-weeks basis in combination with irinotecan in metastatic colorectal cancer (mCRC). Cetuximab is an epidermal growth factor receptor-targeted IgG(1) monoclonal antibody...... that is approved for use in combination with irinotecan or as monotherapy in the treatment of mCRC. The currently approved dosing regimen for cetuximab is a 400-mg/m(2) initial dose followed by 250 mg/m(2) weekly. Many commonly used chemotherapy agents for mCRC (including irinotecan alone or in combination with 5....... The efficacy and safety of the every-2-weeks dosing regimen were similar to those reported for the approved weekly dosing regimen. The indication from these preliminary findings is that every-2-weeks administration of cetuximab (500 mg/m(2)) may be a potentially convenient alternative to the approved weekly...

  15. Role of capecitabine in treating metastatic colorectal cancer in Chinese patients

    Directory of Open Access Journals (Sweden)

    Wang F

    2014-04-01

    Full Text Available Feng Wang,* Feng-Hua Wang,* Long Bai, Rui-Hua XuDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China *These authors contributed equally to this workAbstract: The China Food and Drug Administration approved the use of capecitabine in patients with metastatic colorectal cancer (mCRC in 2004. This paper reviews the available information of capecitabine in Chinese patients with mCRC, focusing on its effectiveness and safety against mCRC. Identification of all eligible studies was made by searching the PubMed and Wanfang database from 2000 to 2013. Published data examining various aspects of clinical response and tolerability with capecitabine alone or in combination with other chemotherapeutic or biological agents for first- and second-line mCRC were examined. Capecitabine and its combination displayed high efficacy in Chinese patients with mCRC. Toxicities are generally manageable, and elderly patients can tolerate capecitabine well.Keywords: capecitabine, metastatic colorectal cancer, Chinese

  16. Vertebral compression fractures after spine irradiation using conventional fractionation in patients with metastatic colorectal cancer

    International Nuclear Information System (INIS)

    To evaluate the risk of vertebral compression fracture (VCF) after conventional radiotherapy (RT) for colorectal cancer (CRC) with spine metastasis and to identify risk factors for VCF in metastatic and non-metastatic irradiated spines. We retrospectively reviewed 68 spinal segments in 16 patients who received conventional RT between 2009 and 2012. Fracture was defined as a newly developed VCF or progression of an existing fracture. The target volume included all metastatic spinal segments and one additional non-metastatic vertebra adjacent to the tumor-involved spines. The median follow-up was 7.8 months. Among all 68 spinal segments, there were six fracture events (8.8%) including three new VCFs and three fracture progressions. Observed VCF rates in vertebral segments with prior irradiation or pre-existing compression fracture were 30.0% and 75.0% respectively, compared with 5.2% and 4.7% for segments without prior irradiation or pre-existing compression fracture, respectively (both p < 0.05). The 1-year fracture-free probability was 87.8% (95% CI, 78.2-97.4). On multivariate analysis, prior irradiation (HR, 7.30; 95% CI, 1.31-40.86) and pre-existing compression fracture (HR, 18.45; 95% CI, 3.42-99.52) were independent risk factors for VCF. The incidence of VCF following conventional RT to the spine is not particularly high, regardless of metastatic tumor involvement. Spines that received irradiation and/or have pre-existing compression fracture before RT have an increased risk of VCF and require close observation.

  17. Vertebral compression fractures after spine irradiation using conventional fractionation in patients with metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ree, Woo Joong; Kim, Kyung Hwan; Chang, Jee Suk; Kim, Hyun Ju; Choi, Seo Hee; Koom, Woong Sub [Dept.of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul (Korea, Republic of)

    2014-12-15

    To evaluate the risk of vertebral compression fracture (VCF) after conventional radiotherapy (RT) for colorectal cancer (CRC) with spine metastasis and to identify risk factors for VCF in metastatic and non-metastatic irradiated spines. We retrospectively reviewed 68 spinal segments in 16 patients who received conventional RT between 2009 and 2012. Fracture was defined as a newly developed VCF or progression of an existing fracture. The target volume included all metastatic spinal segments and one additional non-metastatic vertebra adjacent to the tumor-involved spines. The median follow-up was 7.8 months. Among all 68 spinal segments, there were six fracture events (8.8%) including three new VCFs and three fracture progressions. Observed VCF rates in vertebral segments with prior irradiation or pre-existing compression fracture were 30.0% and 75.0% respectively, compared with 5.2% and 4.7% for segments without prior irradiation or pre-existing compression fracture, respectively (both p < 0.05). The 1-year fracture-free probability was 87.8% (95% CI, 78.2-97.4). On multivariate analysis, prior irradiation (HR, 7.30; 95% CI, 1.31-40.86) and pre-existing compression fracture (HR, 18.45; 95% CI, 3.42-99.52) were independent risk factors for VCF. The incidence of VCF following conventional RT to the spine is not particularly high, regardless of metastatic tumor involvement. Spines that received irradiation and/or have pre-existing compression fracture before RT have an increased risk of VCF and require close observation.

  18. Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Sørensen, Morten; Pallisgaard, Niels;

    2013-01-01

    Background. Patients with chemotherapy refractory metastatic colorectal cancer and KRAS mutations have no effective treatment option. The present study evaluated the efficacy of temsirolimus in chemotherapy refractory mCRC with KRAS mutations. Furthermore, we wanted to investigate if resistance t...

  19. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse

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    Rabeah A. Al-Temaimi

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT. Resultant genes were classified based on gene ontology (GO, which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.

  20. Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Frederiksen, C.; Qvortrup, C.; Christensen, I.J.; Glimelius, B.; Berglund, Å.; Jensen, B.V.; Nielsen, S.E.; Keldsen, N.; Nielsen, H.J.; Brunner, Nils; Pfeiffer, P.

    2011-01-01

    associations between baseline TIMP-1 or CEA levels and best response to treatment or progression-free survival (PFS) could be demonstrated. In contrast, high baseline plasma TIMP-1 levels were associated with poor overall survival (OS), P = 0.008, hazard ratio (HR) = 1.80 [95% confidence interval (CI): 1......BACKGROUND: The aim was to evaluate the association between plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) and serum carcinoembryonic antigen (CEA) levels and outcome in patients with metastatic colorectal cancer (mCRC) receiving XELOX (combination chemotherapy with capecitabine and...... oxaliplatin) as first-line treatment. PATIENTS AND METHODS: One hundred and twenty patients were included. Blood samples were collected before treatment and 3 weeks later before the next treatment cycle. Plasma TIMP-1 and serum CEA levels were correlated to treatment outcome. RESULTS: No significant...

  1. Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients

    DEFF Research Database (Denmark)

    Sorbye, Halfdan; Pfeiffer, Per; Cavalli-Björkman, Nina;

    2009-01-01

    oncological consideration at 3 hospitals in Scandinavia covering defined populations were registered consecutively during 2003 to 2006. Clinical trial enrollment, patient characteristics, and treatment were recorded prospectively, and the follow-up was complete. RESULTS: Palliative chemotherapy was initiated...... was then only 2.1 months. The median survival for all 760 nonresectable mCRC patients was 10.7 months. CONCLUSIONS: mCRC patients enrolled into clinical trials differ in characteristics from patients receiving chemotherapy outside protocol and have better survival, even when given the same treatment. Although......BACKGROUND: Trial accrual patterns were examined to determine whether metastatic colorectal cancer (mCRC) patients enrolled in trials are representative of a general cancer population concerning patient characteristics and survival. METHODS: A total of 760 mCRC patients referred for their first...

  2. Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management

    Directory of Open Access Journals (Sweden)

    Khan G

    2014-03-01

    Full Text Available Gazala Khan,1 Rebecca A Moss,2 Fadi Braiteh,3,4 Marc Saltzman5 1Department of Hematology and Oncology, Henry Ford Hospital, Detroit, MI, USA; 2Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; 3US Oncology Research, Las Vegas, NV, USA; 4Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA; 5Innovative Medical Research of South Florida, Inc, Aventura, FL, USA Abstract: Regorafenib is a broad-spectrum oral multikinase inhibitor that targets several angiogenic, oncogenic, and stromal receptor tyrosine kinases that support the tumor microenvironment. Results from the pivotal Phase III Patients with Metastatic Colorectal Cancer Treated with Regorafenib or Placebo After Failure of Standard Therapy (CORRECT trial showed that the addition of regorafenib to best supportive care resulted in a significant improvement in median overall survival and progression-free survival compared with placebo plus best supportive care in patients with metastatic colorectal cancer (mCRC following all available approved therapies. Thus, regorafenib is the first oral multikinase inhibitor indicated for mCRC; it currently has approval in the USA, EU, Japan, Canada, and Singapore for the treatment of mCRC patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy, and, if the tumor is KRAS wild-type, an anti-epidermal growth factor receptor therapy. In this review, we highlight regorafenib's mechanism of action, present key efficacy data from the CORRECT trial, and discuss how to proactively manage common adverse events (eg, hand-foot skin reaction, hypertension, oral mucositis, diarrhea, and fatigue experienced by patients receiving regorafenib. Increased awareness of potential adverse events associated with regorafenib and the implementation of proactive strategies to prevent, monitor, and manage these

  3. Bevacizumab treatment in the elderly patient with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Di Bartolomeo M

    2015-01-01

    Full Text Available Maria Di Bartolomeo,1 Claudia Maggi,1 Francesca Ricchini,1 Filippo Pietrantonio,1 Roberto Iacovelli,1 Filippo de Braud,1 Alessandro Inno2 1Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 2Department of Medical Oncology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy Abstract: Metastatic colorectal cancer (mCRC, like many cancers, is primarily a disease of elderly people. Despite this prevalence, such patients are often excluded from randomized trials or represent a minority of enrolled patients. Moreover, the criteria for establishing benefit or side effects of treatment strategies in this population are uncertain and not well recognized. Bevacizumab improves the outcome of mCRC when used in combination with standard first-line and second-line chemotherapy and beyond the first disease progression when given with a chemotherapy backbone different from that used in the precedent line. The particular toxicity profile of this antiangiogenesis agent (in particular hypertension, thromboembolic events, hemorrhage, and renal failure may discourage its use in elderly patients with comorbidities. Data from subgroup analyses of randomized trials and the results of recent cohort studies suggest a significant benefit from the addition of bevacizumab to standard chemotherapy for elderly patients comparable with that observed in younger patients, except for the increased risk for thromboembolic events. Age alone should not be a barrier to use of bevacizumab, and further research with a more complete geriatric assessment should investigate the role of bevacizumab in elderly patients with mCRC to avoid undertreatment of this patient population due to a ­historical conservative approach. Keywords: bevacizumab, elderly, metastatic colorectal cancer, antivascular treatment, review

  4. Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer

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    K M Galal

    2011-01-01

    Full Text Available Background: The relationship of epidermal growth factor receptors (EGFR pathway, such as PI3K, K-ras, and B-raf, with response to EGFR-targeted antibodies is less well studied. Aim: To assess sorafenib with cetuximab in treating metastatic colorectal cancer. Settings and Design: Thirty-five patients with metastatic colorectal cancer were randomized to receive cetuximab with or without oral sorafenib. Patients and Methods: Patients received cetuximab IV weekly for four weeks and oral sorafenib twice daily on days 1 - 28, with recycling every four weeks. The primary end point was the response rate (partial and complete, while the secondary end points were the adverse effects, time to progression and overall survival. Statistical Analysis was made using the Statistical Product and Service Solutions, using SPSS 10.0, with estimation of both time to progression and overall survival time by the Kaplan-Meier method and comparing the two groups with the use of a log-rank test. Results: Partial response was higher in cetuximab-sorafenib (EN, which constituted 33.3% compared to 17.6% in the cetuximab group (P = 0.44. Progression-free survival had a statistically higher significant difference in wild K-ras compared to mutant K-ras cases (P = .0001. Median overall survival was seven and five months in the (EN and (E groups respectively (P = 0.49. Conclusion: K-ras and B-raf was a predictor of response, so genotyping of tumors was needed for defining the patient population that was likely to benefit from the targeted therapy. A combination of therapy that simultaneously targets K-ras and B-raf could be a useful approach to increase the number of patients who may benefit from anti-EGFR therapy.

  5. Anti-VEGF agents in metastatic colorectal cancer (mCRC: are they all alike?

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    Saif MW

    2013-06-01

    Full Text Available Muhammad Wasif Saif GI Oncology Program, Tufts University School of Medicine, Boston, MA, USA Abstract: Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States, VEGF receptors (eg, ramucirumab, and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors. The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012, using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking. Keywords: aflibercept, antiangiogenesis, metastatic colorectal cancer (mCRC, tyrosine kinase inhibitor (TKI, vascular endothelial growth factor (VEGF

  6. Mitomycin-C+fluoropyrimidines in heavily pretreated metastatic colorectal cancer: a systematic review and evidence synthesis.

    Science.gov (United States)

    Petrelli, Fausto; Ghidini, Antonio; Inno, Alessandro; Barni, Sandro

    2016-07-01

    Mitomycin-C (MMC) combined with fluoropyrimidines has historically been used for pretreated patients with some activity in this setting, in particular, as third-line chemotherapy (CT) or beyond. We have evaluated the efficacy and safety of MMC-based therapy as a further line of CT in advanced colorectal cancer. Prospective or retrospective studies of MMC-based CT were included in the pooled analysis. PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library database and CINAHL were searched systematically. The outcomes were progression-free survival, overall survival, overall response rate and grades 3-4 drug-related adverse events. Seventeen trials involving 681 patients were included in the analysis. Overall, the pooled average weighted progression-free survival and overall survival were 2.84 [95% confidence interval (CI) 2.5-3.1] and 7.47 (95% CI 6-8.9) months, respectively. The corresponding pooled overall response rate was 7.2% (95% CI 5.2-9.9%) and the pooled disease control rate was 38.7% (95% CI 31.7-46.3%). The G3-4 neutropenia and anaemia were the most frequent haematological toxicities (range 0-20%). Nonhaematological G3-4 toxicities were compatible with the associated agent. MMC with fluoropyrimidines represents a viable and active combination for pretreated metastatic colorectal cancer patients. It is thus an option when other agents have failed, or are unavailable or not indicated. PMID:27186954

  7. Prolyl Hydroxylase 3 Attenuates MCL-1-Mediated ATP Production to Suppress the Metastatic Potential of Colorectal Cancer Cells.

    Science.gov (United States)

    Radhakrishnan, Praveenkumar; Ruh, Nadine; Harnoss, Jonathan M; Kiss, Judit; Mollenhauer, Martin; Scherr, Anna-Lena; Platzer, Lisa K; Schmidt, Thomas; Podar, Klaus; Opferman, Joseph T; Weitz, Juergen; Schulze-Bergkamen, Henning; Koehler, Bruno C; Ulrich, Alexis; Schneider, Martin

    2016-04-15

    Hypoxia is a common feature of solid tumors. Prolyl hydroxylase enzymes (PHD1-3) are molecular oxygen sensors that regulate hypoxia-inducible factor activity, but their functions in metastatic disease remain unclear. Here, we assessed the significance of PHD enzymes during the metastatic spread of colorectal cancer. PHD expression analysis in 124 colorectal cancer patients revealed that reduced tumoral expression of PHD3 correlated with increased frequency of distant metastases and poor outcome. Tumorigenicity and metastatic potential of colorectal tumor cells over and underexpressing PHD3 were investigated in orthotopic and heterotopic tumor models. PHD3 overexpression in a syngeneic tumor model resulted in fewer liver metastases, whereas PHD3 knockdown induced tumor spread. The migration of PHD3-overexpressing tumor cells was also attenuated in vitro Conversely, migratory potential and colony formation were enhanced in PHD3-deficient cells, and this phenotype was associated with enhanced mitochondrial ATP production. Furthermore, the effects of PHD3 deficiency were accompanied by increased mitochondrial expression of the BCL-2 family member, member myeloid cell leukemia sequence 1 (MCL-1), and could be reversed by simultaneous inhibition of MCL-1. MCL-1 protein expression was likewise enhanced in human colorectal tumors expressing low levels of PHD3. Therefore, we demonstrate that downregulation of PHD3 augments metastatic spread in human colorectal cancer and identify MCL-1 as a novel downstream effector of oxygen sensing. Importantly, these findings offer new insight into the possible, context-specific deleterious effects of pharmacologic PHD inhibition. Cancer Res; 76(8); 2219-30. ©2016 AACR. PMID:26921340

  8. A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Johnsson, Anders; Hagman, H; Frödin, J-E;

    2013-01-01

    The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC)....

  9. Anti-epidermal or anti-vascular endothelial growth factor as first-line metastatic colorectal cancer in modified Glasgow prognostic score 2' patients

    OpenAIRE

    Dréanic, Johann; Dhooge, Marion; Barret, Maximilien; Brezault, Catherine; Mir, Olivier; Chaussade, Stanislas; Coriat, Romain

    2015-01-01

    Background In metastatic colorectal cancer, the modified Glasgow prognostic score (mGPS) has been approved as an independent prognostic indicator of survival. No data existed on poor prognosis patients treated with molecular-targeted agents. Methods From January 2007 to February 2012, patients with metastatic colorectal cancer and poor predictive survival score (mGPS = 2), treated with 5-fluorouracil-based chemotherapy in addition to an anti-epidermal growth factor receptor (EGFR) or anti-vas...

  10. Comparison of PET metabolic indices for the early assessment of tumour response in metastatic colorectal cancer patients treated by polychemotherapy

    OpenAIRE

    Maisonobe, Jacques-Antoine; Garcia, Camilo A.; Necib, Hatem; Vanderlinden, Bruno; Hendlisz, Alain; Flamen, Patrick; Buvat, Irène

    2012-01-01

    Purpose To compare the performance of eight metabolic indices for the early assessment of tumour response in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. Methods Forty patients with advanced mCRC underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy initiation. For each lesion, eight metabolic indices were calculated: four standardized uptake values (SUV) without correction for the partial volume effect (PVE), two SUV with correction for ...

  11. Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

    OpenAIRE

    Kim, J. C.; Ha, Y J; Roh, S A; Choi, E. Y.; Yoon, Y.S.; Kim, K P; Hong, Y S; Kim, T. W.; Cho, D H; Kim, S. Y.; Kim, Y.S.

    2013-01-01

    Background: Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy. Methods: A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of t...

  12. Co-evolution of somatic variation in primary and metastatic colorectal cancer may expand biopsy indications in the molecular era.

    Directory of Open Access Journals (Sweden)

    Richard Kim

    Full Text Available Metastasis is thought to be a clonal event whereby a single cell initiates the development of a new tumor at a distant site. However the degree to which primary and metastatic tumors differ on a molecular level remains unclear. To further evaluate these concepts, we used next generation sequencing (NGS to assess the molecular composition of paired primary and metastatic colorectal cancer tissue specimens.468 colorectal tumor samples from a large personalized medicine initiative were assessed by targeted gene sequencing of 1,321 individual genes. Eighteen patients produced genomic profiles for 17 paired primary:metastatic (and 2 metastatic:metastatic specimens.An average of 33.3 mutations/tumor were concordant (shared between matched samples, including common well-known genes (APC, KRAS, TP53. An average of 2.3 mutations/tumor were discordant (unshared among paired sites. KRAS mutational status was always concordant. The overall concordance rate for mutations was 93.5%; however, nearly all (18/19 (94.7% paired tumors showed at least one mutational discordance. Mutations were seen in: TTN, the largest gene (5 discordant pairs, ADAMTS20, APC, MACF1, RASA1, TP53, and WNT2 (2 discordant pairs, SMAD2, SMAD3, SMAD4, FBXW7, and 66 others (1 discordant pair.Whereas primary and metastatic tumors displayed little variance overall, co-evolution produced incremental mutations in both. These results suggest that while biopsy of the primary tumor alone is likely sufficient in the chemotherapy-naïve patient, additional biopsies of primary or metastatic disease may be necessary to precisely tailor therapy following chemotherapy resistance or insensitivity in order to adequately account for tumor evolution.

  13. Computed Tomographic Virtual Colonoscopy to Screen for Colorectal Neoplasia in asymptomatic adults

    International Nuclear Information System (INIS)

    We evaluated the performance characteristics of computed tomographic (CT) virtual colonospy for the detection of colorectal neoplasia in an average-risk screening population. A total of 1233 symptomatic adults (mean age, 57.8 years) underwent same-day virtual and optical colonoscopy. Radiologists used the three-dimensional endoluminal display for the initial detection of polyps on CT virtual colonoscopy. For the initial examination of each colonic segment, the colonoscopists were unaware of the findings on virtual colonoscopy, which were revealed to them before any subsequent reexamination. The sensitivity and specificity of virtual colonoscopy and the sensitivity of optical colonoscopy were calculated with the use of the findings of the final, unblinded optical colonoscopy as the reference standard. The sensitivity of virtual colonoscopy for adenomatous polyps was 93.8 percent for polyps at least 10 mm in diameter, 93.9 percent for polyps at least 8 mm in diameter, and 88.7 percent for polyps at least 6 mm in diameter. The sensitivity of optical colonoscopy for adenomatous polyps was 87.5 percent, 91.5 percent, and 92.3 percent for the three sizes of polyps, respectively. The specificity of virtual colonoscopy for adenomatous polyps was 96.0 percent for polyps at least 10 mm in diameter, 92.2 percent for polyps at least 8 mm in diameter, and 79.6 percent for polyps at least 6 mm in diameter.Two polyps were malignant; both were detected on virtual colonoscopy, and one of them was missed on optical colonoscopy before the results on virtual colonoscopy were revealed. CT virtual colonoscopy with the use of a three-dimensional approach is an accurate screening method for the detection of colorectal neoplasia in symptomatic average-risk adults and compares favorably with optical colonoscopy in terms of the detection of clinically relevant lesions

  14. Sodium hyaluronate enhances colorectal tumour cell metastatic potential in vitro and in vivo.

    LENUS (Irish Health Repository)

    Tan, B

    2012-02-03

    BACKGROUND: Sodium hyaluronate has been used intraperitoneally to prevent postoperative adhesions. However, the effect of sodium hyaluronate on tumour growth and metastasis in vitro and in vivo is still unknown. METHODS: Human colorectal tumour cell lines SW480, SW620 and SW707 were treated with sodium hyaluronate (10-500 microg\\/ml) and carboxymethylcellulose (0.125-1 per cent), and tumour cell proliferation and motility were determined in vitro. For the in vivo experiments male BD IX rats were randomized to a sodium hyaluronate group (n = 11; intraperitoneal administration of 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml 0.4 per cent sodium hyaluronate) or a phosphate-buffered saline group (n = 11; 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml phosphate-buffered saline intraperitoneally). Four weeks later the intraperitoneal tumour load was visualized directly. RESULTS: In vitro sodium hyaluronate increased tumour cell proliferation and motility significantly. Sodium hyaluronate-induced tumour cell motility appeared to be CD44 receptor dependent, whereas sodium hyaluronate-induced tumour cell proliferation was CD44 receptor independent. In vivo there was a significantly higher total tumour nodule count in the peritoneal cavity of the sodium hyaluronate-treated group compared with the control (P = 0.016). CONCLUSION: Sodium hyaluronate enhances tumour metastatic potential in vitro and in vivo, which suggests that use of sodium hyaluronate to prevent adhesions in colorectal cancer surgery may also potentiate intraperitoneal tumour growth. Presented to the Patey Prize Session of the Surgical Research Society and the annual scientific meeting of the Association of Surgeons of Great Britain and Ireland, Brighton, UK, 4-7 May 1999

  15. Accomplishments in 2008 in the Management of Curable Metastatic Colorectal Cancer

    OpenAIRE

    Adam, René; Hoti, Emir; Folprecht, Gunnar; Benson, Al B.

    2009-01-01

    Overview of the Disease IncidencePrognosisCurrent Therapy Standards Colorectal Liver Metastases (CRLM) Resectable TumorsStrategies to Convert Nonresectable Liver Metastases to Resectable StatusSynchronous Colorectal Liver MetastasesPredictors of Survival After Resection of CRLMPeritoneal Carcinomatosis (PC) From Colorectal CancerColorectal Pulmonary Metastases (CRPM)Colorectal Liver Metastases With Extrahepatic DiseaseAccomplishments (or Lack of Accomplishments) During the Year Th...

  16. Adverse event management strategies: optimizing treatment with regorafenib in patients with metastatic colorectal cancer.

    Science.gov (United States)

    Mitchell, Jessica; Khoukaz, Taline; McNeal, Deborah; Brent, Lori

    2014-04-01

    Patients with metastatic colorectal cancer (mCRC) frequently experience treatment-related adverse events (AEs), which may lead to nonadherence or discontinuation from their treatment regimen. In the phase 3 CORRECT study, the addition of regorafenib to best supportive care (BSC) significantly increased overall survival and progression-free survival compared with placebo plus BSC in patients with mCRC who had progressed on all approved standard care therapies. Although regorafenib showed an acceptable safety profile, patients experienced treatment-related AEs such as hand-foot skin reaction, hypertension, oral mucositis, diarrhea, fatigue, and liver abnormalities. The goal of this article is to help oncology nurses implement a strategic, proactive approach to AE management in patients mCRC treated with regorafenib. The article reviews the most common AEs associated with regorafenib in patients who participated in the CORRECT study and provides a strategy and practical measures that nurses can apply to AE management. In addition, the article provides direction and guidance for educating patients and their caregivers on recognizing and managing potential side effects of regorafenib. PMID:24675266

  17. Oxaliplatin-induced severe anaphylactic reactions in metastatic colorectal cancer: Case series analysis

    Directory of Open Access Journals (Sweden)

    Chao-Wen Hsu

    2012-01-01

    Full Text Available AIM: To investigate oxaliplatin-induced severe anaphylactic reactions (SAR in metastatic colorectal cancer in a retrospective case series analysis and to conduct a systemic literature review. METHODS: During a 6-year period from 2006 to 2011 at Kaohsiung Veterans General Hospital, a total of 412 patients exposed to oxaliplatin-related chemotherapy were retrospectively reviewed. Relevant English-language studies regarding life-threatening SAR following oxaliplatin were also reviewed in MEDLINE® and PubMed® search. RESULTS: Eight patients (1.9%, 8 of 412 cases were identified. Seven patients were successful resuscitated without any sequelae and one patient expired. We changed the chemotherapy regimen in five patients and rechallenged oxaliplatin use in patient 3. Twenty-three relevant English-language studies with 66 patients were reported. Patients received a median of 10 cycles of oxaliplatin (range, 2 to 29. Most common symptoms were respiratory distress (60%, fever (55%, and hypotension (54%. Three fatal events were reported (4.5%. Eleven patients (16% of the 66 cases were rechallenged by oxaliplatin. CONCLUSION: SAR must be considered in patients receiving oxaliplatin-related chemotherapy, especially in heavily pretreated patients. Further studies on the mechanism, predictors, preventive methods and management of oxaliplatin-related SAR are recommended.

  18. A synonymous EGFR polymorphism predicting responsiveness to anti-EGFR therapy in metastatic colorectal cancer patients.

    Science.gov (United States)

    Bonin, Serena; Donada, Marisa; Bussolati, Gianni; Nardon, Ermanno; Annaratone, Laura; Pichler, Martin; Chiaravalli, Anna Maria; Capella, Carlo; Hoefler, Gerald; Stanta, Giorgio

    2016-06-01

    Genetic factors are known to affect the efficiency of therapy with monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer (mCRC). At present, the only accepted molecular marker predictive of the response to anti-EGFR mAbs is the somatic mutation of KRAS and NRAS as a marker of resistance to anti-EGFR. However, only a fraction of KRAS wild-type patients benefit from that treatment. In this study, we show that the EGFR gene polymorphism rs1050171 defines, independently of RAS mutational status, a sub-population of 11 % of patients with a better clinical outcome after anti-EGFR treatment. Median PFS for patients with the GG genotype was 10.17 months compared to 5.37 of those with AG + AA genotypes. Taken together, our findings could be used to better define CRC populations responding to anti-EGFR therapy. Further studies in larger independent cohorts are necessary to validate the present observation that a synonymous polymorphism in EGFR gene impacts on clinical responsiveness. PMID:26666825

  19. Common toxicities and objective response rate in metastatic colorectal cancer patients treated with irinotecan based regimens

    Institute of Scientific and Technical Information of China (English)

    Liu Huang; Xin Liao; Qianqian Yu; Qiang Fu; Kai Qin; Huanlei Wu; Lihong Zhang; Xianglin Yuan

    2013-01-01

    Objective: The aim of our study was to investigate if common toxicities are correlated to objective response rate (ORR) in metastatic colorectal cancer (mCRC) patients treated by irinotecan based regimens. Methods: Univariate and multivariate logistic regression analyses were performed to evaluate correlations between common toxicities and binary ORR in 106 mCRC patients from a prospective cohort treated with irinotecan based regimens. Results: The most frequent severe toxicities (Grade 3/4) were as follows: neutropenia (27.4%), diarrhea (16.9%), leucopenia (12.6%), vomiting (3.2%) and thrombocytopenia (2.1%). Thrombocytosis was observed in 25 (26.3%) patients. ORR was 25.3%. Thrombocytopenia (P = 0.014), line of chemotherapy (P = 0.028) and thrombocytosis (P = 0.033) were correlated with ORR in univariate analysis. In multivariate analysis, thrombocytopenia (odds ratio [OR] = 8.600, 95% confidence interval [CI] = 1.705–43.385, P = 0.009) and first line chemotherapy (OR = 5.155, 95% CI = 1.153–23.256, P = 0.032) positively related to ORR. Conclusion: Throm-bocytopenia may be an indicator of ORR in mCRC patients treated by irinotecan plus 5-fluorouracil/capecitabine. Evidence is not strong enough to prove that irinotecan based regimens-induced diarrhea, leucopenia, neutropenia or vomiting is associ-ated with ORR.

  20. Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Kristoffer Watten Brudvik

    2013-01-01

    Full Text Available Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months. Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

  1. Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Walker Mark S

    2012-06-01

    Full Text Available Abstract Background Bevacizumab (B and cetuximab (C are both approved for use in the treatment of metastatic colorectal cancer (mCRC in the second-line. We examined patient reported symptom burden during second-line treatment of mCRC. Methods Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O and who had completed ≥ 1 Patient Care Monitor (PCM surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. Primary endpoints were rash, dry skin, itching, nail changes, nausea, vomiting, fatigue, burning in hands/feet, and diarrhea. Linear mixed models examined change in PCM scores across B, C and O (B = reference. Results 182 patients were enrolled (B: n = 106, C: n = 38, O: n = 38. Patients were 51% female, 67% Caucasian, with mean age of 62.0 (SD = 12.6. Groups did not differ on demographic or clinical characteristics. The most common second-line regimens were FOLFIRI ± B or C (23.1% and FOLFOX ± B or C (22.5%. Results showed baseline scores to be strongly predictive of second-line symptoms across all PCM items (all p’s  Conclusions Patients receiving second-line treatment for mCRC with B report less symptom burden, especially dermatologic, compared to patients treated with C.

  2. [Bevacizumab in combination with mFOLFOX6 or FOLFIRI for previously treated metastatic colorectal cancer].

    Science.gov (United States)

    Koyama, Motoi; Murata, Akihiko; Kimura, Yutaka; Sakamoto, Yoshiyuki; Morohashi, Hajime; Kimura, Norihisa; Gasa, Fujihiko; Sato, Junya; Terui, Kazushi; Awatsu, Akemi; Hakamada, Kenichi

    2010-06-01

    We retrospectively investigated the safety and efficacy on outpatient chemotherapy including bevacizumab(BV)as secondline therapy for inoperable metastatic colorectal cancer. Analytical subjects were thirty patients treated with chemotherapy including BV as second-line therapy after first disease progression. All patients were treated with BV 5mg/kg. Concurrent therapy was given mFOLFOX6(2 patients)and FOLFIRI(28 patients). The BV treatment frequency and all course treatment frequency including the prior regimens averaged 20 and 37 times, respectively. The overall response rate was 24. 1%(PR, 7 patients; SD, 17 patients; PD, 5 patients), and the median duration of progression-free survival was 8. 0 months. The median duration of survival after addition of BV was 20. 3 months. The adverse events were 84%(>grade 3, 9%), BV-associated adverse events were GI perforation(1 patient), GI hemorrhage(1 patient), grade 3 hypertension(1 patient)and grade 2 epitaxis(2 patient). Although it is necessary to be careful about GI hemorrhage and GI perforation, we could safely continue the treatment with BV on outpatient chemotherapy. We confirmed that the chemotherapy including BV as second-line therapy had high antitumor effect and patient benefit. PMID:20567110

  3. Biologic therapies in the metastatic colorectal cancer treatment continuum--applying current evidence to clinical practice.

    Science.gov (United States)

    Peeters, Marc; Price, Timothy

    2012-08-01

    More therapeutic options are now available than ever before for patients with metastatic colorectal cancer (mCRC) and, as such, treatment decisions have become more complex. A multidisciplinary approach is, therefore, required to effectively manage these patients. In the past few years, many trials have reported on the value of combining biological agents, such as those targeting vascular endothelial growth factor A and epidermal growth factor receptors, with chemotherapy. However, despite the plethora of information now available, the optimal treatment strategy for patients with mCRC remains unclear. Indeed, the propensity of investigators to conduct clinical trials utilising a variety of chemotherapy backbones combined with the increased complexity of retrospectively incorporating analyses of genetic mutation status (e.g. KRAS and BRAF) have led to conflicting results for seemingly similar endpoints, particularly overall survival. As a result, guidelines that have been developed, whilst having some similarities, have distinct differences in terms of suggested therapeutic combinations. Therefore, here, we review and distil the currently available data reported from phase III trials of biologic agents in the first-, second- and third-line mCRC settings. PMID:21899955

  4. A Comprehensive Review of Clinical Trials on EGFR Inhibitors Such as Cetuximab and Panitumumab as Monotherapy and in Combination for Treatment of Metastatic Colorectal Cancer.

    Science.gov (United States)

    Yazdi, Mohammad Hossein; Faramarzi, Mohammad Ali; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2015-01-01

    Metastatic colorectal cancer is the fourth most common cause of death due to cancer after those of lung, stomach, and liver. Anti epidermal growth factor receptor drugs as a targeting therapy seem to be good candidates for curing metastatic colorectal cancer. Two available anti epidermal growth factor receptor monoclonal antibodies are cetuximab and panitumumab which have been approved for metastatic colorectal cancer treatment. Through the available literature on NCBI and clinical trials, 31 clinical trials in which cetuximab or panitumumab as monotherapy or in combination with chemotherapy were used for the treatment of metastatic colorectal cancer patients in different line settings and 12 clinical trials in which bevacizumab was used for being compared with anti epidermal growth factor receptor monoclonal antibodies or chemotherapy were chosen for reviewing and comparing the results of overall survival, progression free survival and adverse effects. Cetuximab and panitumumab are well accepted for the treatment of mCRC patients at all stages in different line settings. Although cetuximab administration in metastatic colorectal cancer patients is mostly associated with better overall survival and panitumumab results in better progression free survival, to confirm the superiority of each of them in the treatment protocol of epidermal growth factor receptor monoclonal antibodies, more clinical trials with larger sample size are needed. Through current available data from clinical studies, it can be concluded that the best treatment outcome is achieved by a combination of anti epidermal growth factor receptor monoclonal antibodies with conventional chemotherapy. PMID:26605007

  5. Bevacizumab plus chemotherapy as salvage treatment in chemorefractory patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Geva R

    2013-01-01

    Full Text Available Ravit Geva,1,2 Loredana Vecchione,2 Sabine Tejpar,2 Hubert Piessevaux,3 Eric Van Cutsem,2 Hans Prenen21Gastrointestinal Malignancies Service, Oncology Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Department of Gastroenterology, Digestive Oncology Unit, University Hospitals Leuven, Leuven, Belgium; 3Department of Gastroenterology, Cliniques Universitaires Saint-Luc, Brussels, BelgiumPurpose: The combination of chemotherapy and bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor, is consistently being used as first- and second-line treatment in patients with metastatic colorectal cancer (mCRC. There is little data of the activity of bevacizumab in chemorefractory mCRC patients. The aim of this retrospective single center study was to evaluate the activity of bevacizumab combined with chemotherapy in this study population.Methods: Forty-six consecutive mCRC patients treated in the University Hospital Gasthuisberg (Leuven, Belgium receiving bevacizumab in advanced lines following failure of conventional chemotherapy were included in this study. Treatment regimen consisted of bevacizumab 5 mg/kg in combination with leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX or leucovorin, 5-fluorouracil, and irinotecan (FOLFIRI.Results: Bevacizumab plus chemotherapy was used in third-line treatment in eight (17% patients and in fourth-line treatment or more in 38 patients (83%. All patients previously failed irinotecan-based chemotherapy, 44 (96% failed oxaliplatin-based regimens, and 40 (87% failed treatment with cetuximab. Bevacizumab was given in combination with irinotecan-based chemotherapy in 36 patients, oxaliplatin-based chemotherapy in nine patients, and with single agent 5-fluorouracil in one patient. Objective response was demonstrated in ten patients (22% and disease control in 38 (83% with a median progression-free survival of 8.9 months and a median overall survival of 13.8 months. Only four

  6. Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice

    Institute of Scientific and Technical Information of China (English)

    Volker Schmitz; Miroslaw Kornek; Tobias Hilbert; Christian Dzienisowicz; Esther Raskopf; Christian Rabe; Tilman Sauerbruch; Cheng Qian; Wolfgang H Caselmann

    2005-01-01

    AIM: Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor (VEGF) via stimulating endothelial cell proliferation, migration, and survival.Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities.Here, we tested a recombinant adenovirus, AdsFlt1-3,that encodes an antagonistically acting fragment of the VEGF receptor 1 (Flt-1), for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice.METHODS: Murine colorectal carcinoma cells (CT26) were inoculated subcutaneously into Balb/c mice forin vivo studies. Tumor size and survival were determined. 293cell line was used for propagation of the adenoviral vectors.Human lung cancer line 4549 and human umbilical vein endothelial cells were transfected forin vitro experiments.RESULTS: Infection of tumor cells with AdsFlt1-3 resulted in protein secretion into cell supernatant, demonstrating correct vector function. As expected, the secreted sFlt1-3 protein had no direct effect on CT26 tumor cell proliferation in vitro, but endothelial cell function was inhibited by about 46% as compared to the AdLacZ control in a tube formation assay. When AdsFlt1-3 (5×109 PFU/animal) was applied to tumor bearing mice, we found a tumor inhibition by 72% at d 12 after treatment initiation. In spite of these antitumoral effects, the survival time was not improved.According to reduced intratumoral microvessel density in AdsFlt1-3-treated mice, the antitumor mechanism can be attributed to angiostatic vector effects. We did not detect increased systemic VEGF levels after AdsFlt1-3 treatment and liver toxicity was low as judged by serum alanine aminotransferase determination.CONCLUSION: In this study we confirmed the value of a systemic administration of AdsFlt1-3 to block VEGF signaling as antitumor therapy in an experimental metastatic colorectal carcinoma model in mice.

  7. Developments in treating metastatic colorectal cancer: Recent international reports from ASCO 2007 and 2008

    Directory of Open Access Journals (Sweden)

    Michel Ducreux

    2009-02-01

    Full Text Available Michel DucreuxGastro-Intestinal Unit, Institut Gustave-Roussy, Villejuif Cedex, France; Department of Oncology, Paul Brousse University Hospital, Villejuif, France; Paris-Sud XI University, Le Kremlin Bicêtre, FranceIntroduction: Treatment for metastatic colorectal cancer (mCRC, employing various schedules, combinations, and regimens utilizing 5-fluorouracil (5-FU, irinotecan, oxaliplatin, capecitabine, bevacizumab, and cetuximab, currently achieves an overall survival that extends to approximately two years. Major questions regarding optimal management of mCRC await resolution.Methods: A thorough review was conducted of all mCRC abstracts, posters, and other presentations at the 2007 meeting of the American Society of Clinical Oncology (ASCO. Information was analyzed in relationship to previously published research to determine the potential impact of new data on current and future mCRC management strategies and patient outcomes. Updated data presented at ASCO 2008 relevant to these findings was also analyzed.Discussion: Ongoing challenges in mCRC treatment include defining the optimal role of targeted agents such as cetuximab and bevacizumab, elaborating the mechanisms underlying their toxicities, resolving the benefits of adjuvant and neoadjuvant chemotherapy in patients who are candidates for surgical resection, establishing whether there are substantive differences between sequential and combination chemotherapy regimens, and determining the safety and tolerability of chemotherapy in elderly subjects.Conclusion: Recent reports presented at ASCO 2007 and 2008 indicate incremental improvements in care of patients with mCRC. Nevertheless, irinotecan, oxaliplatin, 5-FU, and to an increasing extent the targeted biologic agents bevacizumab and cetuximab continue unchallenged as first-line and later selections.Keywords: chemotherapy, combination chemotherapy, irinotecan, bevacizumab, cetuximab

  8. Serum Ferritin as a Prognostic Biomarker for Survival in Relapsed or Refractory Metastatic Colorectal Cancer

    Science.gov (United States)

    Lee, Sookyung; Song, Anna; Eo, Wankyu

    2016-01-01

    Background: This study investigated the prognostic impact of serum ferritin for survival in patients with relapsed or refractory metastatic colorectal cancer (mCRC). Methods: This retrospective cohort study reviewed clinicopathological characteristics and laboratory biomarkers in 120 mCRC patients being treated with Korean Medicine (KM). The overall survival (OS) of patients was calculated using the Kaplan-Meier method, and statistical significance was assessed using the log-rank test. Univariate and multivariate analyses of Cox proportional hazards regression were used to evaluate the prognostic impact for survival in relapsed or refractory mCRC patients. Results: Of the patients, 62.5% had liver metastases, 74.1% underwent greater than second-line chemotherapy, and 80.8% underwent surgery. Median OS was 7.6 months for all patients after the initiation of KM treatment, which was begun 13.7 months, on average, after mCRC diagnosis. Concerning prognostic factors such as the presence of liver metastasis (p = 0.024), high carcinoembryonic antigen level (CEA > 5 ng/mL, p = 0.044), elevated C-reactive protein (CRP ≥ 10.0 mg/L, p = 0.000), high absolute monocyte count (AMC > 413.3 cells/μL, p = 0.034), elevated serum ferritin (ferritin ≥ 150 ng/mL, p = 0.002), low hemoglobin level (Hb 5 ng/mL; HR 2.040, 95% CI 1.203 - 3.460, p = 0.008), and serum ferritin (ferritin ≥ 150 ng/mL; HR 1.763, 95% CI 1.169 - 2.660, p = 0.007) were independent prognostic biomarkers of survival in mCRC patients. Conclusions: These results indicate that serum ferritin acts as an independent prognostic biomarker for survival in relapsed or refractory mCRC patients.

  9. Capecitabine Maintenance Therapy after First-Line Chemotherapy in Patients with Metastatic Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Jing Li; Ming Lu; Xi-cheng Wang; Lin Shen

    2010-01-01

    Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC)patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from first-line chemotherapy,patients with mCRC in our hospital received two different treatment strategies.Thirty-three patients non-maintenance group did not receive any further chemotherapy.Results:Patients in maintenance group and non-maintenance group both received FOLFOX,FOLFIRI and XELOX as first-line therapy.The median chemotherapy cycles the two groups received were the same(6 vs 6).The response rates of first-line chemotherapy were 33.3% in maintenance group and 32.7% in non-maintenance group.Patients in maintenance group received 3-9 cycles of capecitabine therapy(median cycle 4).29/33(87.9%)patients in maintenance group and 47/52(90.4%)in non-maintenance group received following second-line chemotherapy,and no patients underwent targeted therapy.The median survival time and TTP were 40.4 months(95%CI:24.2-56.6)and 9.0 months(95%CI:6.7-11.3)in maintenance group,as compared with 21.5 months(95%CI:14.9-28.0,P=0.015)and 6.5 months(95%CI:4.4-8.5,P=0.007)in non-maintenance group.No severe adverse event was observed in the capecitabine maintenance group.Conclusion:mCRC patients could benefit from capecitabine maintenance therapy by prolonging survival time and TTP.

  10. Feasibility and response of helical tomotherapy in patients with metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Ho [Dept. of Radiation Oncology, Catholic Kwandong University International St. Mary' s Hospital, Incheon (Korea, Republic of); Bae, Sun yun; Moon, Seong Kwon; Cho, Kwang Hwan; Shin, Eung Jin; Lee, Moon Sung; Ryu, Chang Beom; Ko, Bong Min; Yun, Ji Na [Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2015-12-15

    To investigate the treatment outcome and the toxicity of helical tomotherapy (HT) in patients with metastatic colorectal cancer (mCRC). We retrospectively reviewed 18 patients with 31 lesions from mCRC treated with HT between 2009 and 2013. The liver (9 lesions) and lymph nodes (9 lesions) were the most frequent sites. The planning target volume (PTV) ranged from 12 to 1,110 mL (median, 114 mL). The total doses ranged from 30 to 70 Gy in 10-30 fractions. When the alpha/beta value for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the total doses ranged from 39 to 119 Gy{sub 10} (median, 55 Gy{sub 10}). Nineteen lesions were treated with concurrent chemotherapy (CCRT). With a median follow-up time of 16 months, the median overall survival for 18 patients was 33 months. Eight lesions (26%) achieved complete response. The 1- and 3-year local progression free survival (LPFS) rates for 31 lesions were 45% and 34%, respectively. On univariate analysis, significant parameters influencing LPFS rates were chemotherapy response before HT, aim of HT, CCRT, PTV, BED, and adjuvant chemotherapy. On multivariate analysis, PTV < or =113 mL and BED >48 Gy{sub 10} were associated with a statistically significant improvement in LFPS. During HT, four patients experienced grade 3 hematologic toxicities, each of whom had also received CCRT. The current study demonstrates the efficacy and tolerability of HT for mCRC. To define optimal RT dose according to tumor size of mCRC, further study should be needed.

  11. MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer.

    Science.gov (United States)

    Abdallah, Emne Ali; Fanelli, Marcello Ferretti; Souza E Silva, Virgílio; Machado Netto, Marcelo Calil; Gasparini Junior, José Luiz; Araújo, Daniel Vilarim; Ocea, Luciana Menezes Mendonça; Buim, Marcilei Eliza Cavicchioli; Tariki, Milena Shizue; Alves, Vanessa da Silva; Piana de Andrade, Victor; Dettino, Aldo Lourenço Abbade; Abdon Lopes de Mello, Celso; Chinen, Ludmilla Thomé Domingos

    2016-08-15

    Circulating tumor cells are important markers of tumor progression and can reflect tumor behavior in metastatic colorectal cancer (mCRC). Identification of proteins that confer resistance to treatment is an important step to predict response and better selection of treatment for patients. Multidrug resistance-associated protein 1 (MRP1) and Multidrug resistance-associated protein 4 (MRP4) play a role in irinotecan-resistance, and Excision Repair Cross-Complementation group 1 (ERCC1) expression can confer resistance to platinum compounds. Here, we included 34 patients with mCRC and most of them received FOLFIRI or FOLFOX chemotherapy (91.1%). CTCs were isolated by ISET(®) Technology and identified in 30 patients (88.2%), with a median of 2.0 CTCs/mL (0-31.0). We analyzed the immunocytochemical expression of MRP1, MRP4 and ERCC1 only in patients who had previously detectable CTCs, accordingly to treatment received (n = 19, 15 and 13 patients, respectively). Among patients treated with irinotecan-based chemotherapy, 4 out of 19 cases with MRP1 positive CTCs showed a worse progression free survival (PFS) in comparison to those with MRP1 negative CTCs (2.1 months vs. 9.1 months; p = 0.003). None of the other proteins studied in CTCs had significant association with PFS. We analyzed also histological sections of primary tumors and metastases by immunohistochemistry, and found no association with clinicopathological characteristics or with PFS. Our results show MRP1 as a potential biomarker of resistance to treatment with irinotecan when found in CTCs from mCRC patients. This is a small proof-of-principle study and these early findings need to be validated in a larger cohort of patients. PMID:26950035

  12. Predictive biomarkers with potential of converting conventional chemotherapy to targeted therapy in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Jensen, Niels Frank; Smith, David Hersi; Nygård, Sune Boris;

    2012-01-01

    Abstract The availability of systemic chemotherapy regimens for the treatment of patients with metastatic colorectal cancer (mCRC) is based on the results from large prospective, randomized studies. The main chemotherapeutic drugs used in treatment of mCRC are the fluoropyrimidines (5-fluorouracil...... (5-FU); capecitabine) in combination with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). The objective response rate to either combination is approximately 50%, where no significant differences with regard to progression free survival or overall survival have been observed. Interestingly, a...

  13. Relationship of increased aurora kinase A gene copy number, prognosis and response to chemotherapy in patients with metastatic colorectal cancer

    OpenAIRE

    Dotan, E; Meropol, N J; Zhu, F; Zambito, F; Bove, B; Cai, K Q; Godwin, A. K.; Golemis, E A; Astsaturov, I; Cohen, S. J.

    2012-01-01

    Background: Increased Aurora kinase A gene copy number (AURKA-CN) has been reported in metastatic colorectal cancer (mCRC), with unknown relationship to clinical outcome. We correlated increased AURKA-CN in mCRC tumours with KRAS mutation status, overall and progression-free survival (OS, PFS). Methods: Sixty-one mCRC tumours were analysed for AURKA-CN using q-PCR, and KRAS mutation status by direct sequencing. Expression of AURKA protein was analysed by immunohistochemistry. Cox-proportional...

  14. Maintenance Therapy With Cetuximab Every Second Week in the First-Line Treatment of Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Pfeiffer, Per; Sorbye, Hafdan; Qvortrup, Camilla;

    2015-01-01

    BACKGROUND: In the NORDIC-7.5 trial, how cetuximab might safely and conveniently be added to an intermittent treatment strategy in patients with prospectively selected Kirsten rat sarcoma viral oncogene homolog wild type (KRASwt) metastatic colorectal cancer (mCRC) was investigated. Patients were...... (95% CI, 7.5-8.9) and median overall survival was 23.2 (95% CI, 18.1-27.4) months. Twenty-one patients (14%) had later R0-resection of metastasis. FLOX with cetuximab was reintroduced in 47 of 85 patients (55%). The most common Grade 3/4 nonhematologic adverse events were diarrhea in 14 patients (9...

  15. Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM).METHODS: IL-8 expression was assessed by quantitative real-time PCR (Q-RT-PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6)colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16).RESULTS: IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues. However, in the CRC specimens IL-8 revealed a significantly more pronounced overexpression in relation to the CRA and UC tissues with an average 30-fold IL-8 protein up-regulation in the CRC specimens in comparison to the CRA tissues. Moreover, IL-8 expression revealed a close correlation with tumor grading. Most interestingly, IL-8 up-regulation was most enhanced in synchronous and metachronous CRLM, if compared with the corresponding primary CRC tissues.Herein, an up to 80-fold IL-8 overexpression in individual metachronous metastases compared to normal tumor neighbor tissues was found.CONCLUSION: Our results strongly suggest an association between IL-8 expression, induction and progression of colorectal carcinoma and the development of colorectal liver metastases.

  16. Identification of Novel Biomarkers for Metastatic Colorectal Cancer Using Angiogenesis-Antibody Array and Intracellular Signaling Array.

    Directory of Open Access Journals (Sweden)

    Seyung Chung

    Full Text Available Colorectal cancer (CRC is one of the three leading causes for cancer mortality. CRC kills over 600,000 people annually worldwide. The most common cause of death from CRC is the metastasis to distant organs. However, biomarkers for CRC metastasis remain ill-defined. We compared primary and metastatic CRC cell lines for their angiogenesis-protein profiles and intracellular signaling profiles to identify novel biomarkers for CRC metastasis. To this end, we used primary and metastatic CRC cell lines as a model system and normal human colon cell line as a control. The angiogenesis profiles two isogenic CRC cell lines, SW480 and SW620, and HT-29 and T84 revealed that VEGF was upregulated in both SW620 and T84 whereas coagulation factor III, IGFBP-3, DPP IV, PDGF AA/AB, endothelin I and CXCL16 were downregulated specifically in metastatic cell lines. Furthermore, we found that TIMP-1, amphiregulin, endostatin, angiogenin were upregulated in SW620 whereas downregulated in T84. Angiogenin was downregulated in T84 and GM-CSF was also downregulated in SW620. To induce CRC cell metastasis, we treated cells with pro-inflammatory cytokine IL-6. Upon IL-6 treatment, epithelial-mesenchymal transition was induced in CRC cells. When DLD-1 and HT-29 cells were treated with IL-6; Akt, STAT3, AMPKα and Bad phosphorylation levels were increased. Interestingly, SW620 showed the same signal activation pattern with IL-6 treatment of HT-29 and DLD-1. Our data suggest that Akt, STAT3, AMPKα and Bad activation can be biomarkers for metastatic colorectal cancer. IL-6 treatment specifically reduced phosphorylation levels of EGFR, HER2 receptor, Insulin R and IGF-1R in receptor tyrosine kinase array study with HT-29. Taken together, we have identified novel biomarkers for metastatic CRC through the angiogenesis-antibody array and intracellular signaling array studies. Present study suggests that those novel biomarkers can be used as CRC prognosis biomarkers, and as

  17. An interview with Alfredo Falcone and Lisa Salvatore: RECOURSE and trifluridine/tipiracil in metastatic colorectal cancer.

    Science.gov (United States)

    Falcone, Alfredo; Salvatore, Lisa

    2016-09-01

    Professor Alfredo Falcone and Dr Lisa Salvatore speak to Roshaine Gunawardana, Managing Commissioning Editor: Professor Alfredo Falcone is the Director of the Department of Oncology and the Specialization School at the University Hospital of Pisa, Italy. He trained in Pisa and Genoa, Italy, and has held major positions in Italian oncology since 2000. He currently has more than 300 publications, including papers in peer-reviewed international and national journals, book chapters, and more than 600 abstracts of presentations to international and national conferences. The majority of his papers regard clinical and translational research, with a particular focus on metastatic colorectal cancer. Dr Lisa Salvatore is a medical oncologist in the Department of Translational Research and New Technologies in Medicine and Surgery at the University of Pisa. She has been an author on about 40 publications in major peer-reviewed publications and has made numerous presentations in national and international conferences. Her main interest is focused on clinical and translational research in metastatic colorectal cancer. PMID:27266889

  18. The impact of bone marrow micrometastases on metastatic disease-free survival in patients with colorectal carcinoma.

    LENUS (Irish Health Repository)

    O'Connor, O J

    2012-02-03

    AIMS: The biological relevance of bone marrow micrometastases (BMM) in colorectal cancer remains unknown. Here, we investigate their nature by examining the impact of the presence of BMM on metastatic disease-free survival in a cohort of patients with this disease. METHODS: Sixty-three consecutive patients undergoing surgery for colorectal cancer of any stage were studied after approval of the study protocol by the local ethics committee and with full individual informed consent. All had bilateral iliac crest bone marrow aspirates prior to operation. Aspirates were then examined for the presence of aberrant cytokeratin-18-positive cells by a blinded observer using both flow cytometric and APAAP immunohistochemical techniques. RESULTS: Mean follow-up after surgery was 4.6 years (range 1.9-6.9) for those without hepatic metastases at diagnosis. Seven of 34 patients with Dukes\\' stage A or B developed metastatic disease after a mean interval of 4.7 years (range 3.8-6.8). However, only 2 of these patients demonstrated BMM at the time of surgery. Nine of 15 patients with Dukes\\' C carcinoma at the time of surgery subsequently developed metastases after a mean interval of 4.4 years (range 1.9-6.9). Again, only two of these patients had BMM detectable initially. In only three of the 14 patients known to have metastases at the time of operation (i.e. Dukes\\'\\'D\\' disease) were BMM found. CONCLUSION: The presence of BMM as detected by this methodology was not predictive of tumour recurrence or metastasis. This study does not support the consideration of adjuvant therapy based on the presence of BMM at a single pre-operative time point in patients with colorectal cancer.

  19. Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF.

    Science.gov (United States)

    Yamamoto, Nobuto; Suyama, Hirofumi; Nakazato, Hiroaki; Yamamoto, Nobuyuki; Koga, Yoshihiko

    2008-07-01

    Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans. Macrophages treated with GcMAF (100 microg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/ human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32-50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients. PMID:18058096

  20. Accomplishments in 2008 in the Management of Curable Metastatic Colorectal Cancer

    Science.gov (United States)

    Adam, René; Hoti, Emir; Folprecht, Gunnar; Benson, Al B.

    2009-01-01

    SUMMARY Overview of the Disease IncidencePrognosisCurrent Therapy Standards Colorectal Liver Metastases (CRLM) Resectable TumorsStrategies to Convert Nonresectable Liver Metastases to Resectable StatusSynchronous Colorectal Liver MetastasesPredictors of Survival After Resection of CRLMPeritoneal Carcinomatosis (PC) From Colorectal CancerColorectal Pulmonary Metastases (CRPM)Colorectal Liver Metastases With Extrahepatic DiseaseAccomplishments (or Lack of Accomplishments) During the Year Therapy New Staging SystemSystemic Chemotherapy in Resectable Liver MetastasesSystemic Chemotherapy in Nonresectable Liver MetastasesSelective Internal Radiation Therapy (SIRT)Selection of Patients for Liver ResectionRadiofrequency AblationBiomarkersWhat Needs To Be Done? Optimizing Patient CareFuture Directions Comments on ResearchObstacles to Overcome PMID:20011559

  1. High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Rasmussen, Mads Heilskov; Jensen, Niels; Tarpgaard, Line Schmidt;

    2013-01-01

    Abstract The backbone of current cytotoxic treatment of metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine together with either oxaliplatin (XELOX/FOLFOX) or irinotecan (XELIRI/FOLFIRI). With an overall objective response rate of approximately 50% for either treatment combination,...

  2. Comparison of EORTC criteria and PERCIST for PET/CT response evaluation of patients with metastatic colorectal cancer treated with irinotecan and cetuximab

    DEFF Research Database (Denmark)

    Skougaard, Kristin; Nielsen, Dorte; Jensen, Benny Vittrup;

    2013-01-01

    The study aim was to compare European Organization for Research and Treatment of Cancer (EORTC) criteria with PET Response Criteria in Solid Tumors (PERCIST) for response evaluation of patients with metastatic colorectal cancer treated with a combination of the chemotherapeutic drug irinotecan and...

  3. Phase III Trial of Cetuximab With Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) Versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Tveit, Kjell Magne; Guren, Tormod; Glimelius, Bengt;

    2012-01-01

    The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation...

  4. The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Bergmann, Troels K; Henrichsen-Schnack, Tine; Ladelund, Steen; Nilbert, Mef

    2014-01-01

    BACKGROUND: In metastatic colorectal cancer, mutation testing for KRAS exon 2 is widely implemented to select patients with wild-type tumors for treatment with the monocloncal anti-EGFR antibodies cetuximab and panitumumab. The added predictive value of additional biomarkers in the RAS-RAF-MAPK a...

  5. A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification

    DEFF Research Database (Denmark)

    Tarpgaard, Line S; Qvortrup, Camilla; Nygård, Sune B;

    2016-01-01

    UNLABELLED: ᅟ: The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TO...

  6. Assessment of the topoisomerase I gene copy number as a predictive biomarker of objective response to irinotecan in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Nygård, Sune Boris; Christensen, Ib Jarle; Nielsen, Signe Lykke;

    2014-01-01

    (TOP1) copy number and objective response following irinotecan treatment in patients with metastatic colorectal cancer. Materials and methods. Formalin-fixed, paraffin-embedded tumor samples from 78 patients, who received irinotecan monotherapy in second line, were included. TOP1 was assessed by...

  7. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis

    DEFF Research Database (Denmark)

    De Roock, Wendy; Claes, Bart; Bernasconi, David;

    2010-01-01

    with KRAS wild-type tumours still do not respond. We studied the effect of other downstream mutations on the efficacy of cetuximab in, to our knowledge, the largest cohort to date of patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab plus chemotherapy in the pre...

  8. Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Pallisgaard, Niels; Vogelius, Ivan Storgaard; Jakobsen, Anders

    2012-01-01

    The present study investigated the levels of circulating cell-free DNA (cfDNA) in plasma from patients with metastatic colorectal cancer (mCRC) in relation to third-line treatment with cetuximab and irinotecan and the quantitative relationship of cfDNA with tumor-specific mutations in plasma....

  9. Single nucleotide polymorphisms in the vascular endothelial growth factor A gene predicts response to chemotherapy in patinets with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund; Lindebjerg, Jan; Brandslund, Ivan; Jakobsen, Anders

      Single nucleotide polymorphisms in the vascular endothelial growth factor A gene predicts response to chemotherapy in patients with metastatic colorectal cancer. Torben Frøstrup Hansen, Karen-Lise Garm Spindler, Rikke Fredslund Andersen, Jan Lindebjerg, Ivan Brandslund and Anders Jakobsen Danish...... Colorectal Cancer Group South, University of Southern Denmark, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark. Background: Besides the cytotoxic effect on cancer cells, chemotherapy may exert a similar effect on the rapidly dividing endothelial cells involved in the tumour associated neoangiogenesis...... of chemotherapy has not been elucidated. The aim of this study was to investigate the predictive and prognostic role of SNP's in the VEGF-A gene in relation to first line treatment with capecitabine and oxaliplatin in patients with metastatic colorectal cancer (mCRC). Materials and methods: The study...

  10. Cetuximab Plus Oxaliplatin May Not Be Effective Primary Treatment for Metastatic Colorectal Cancer

    Science.gov (United States)

    In a randomized phase III trial, the addition of the targeted therapy cetuximab to oxaliplatin and fluoropyrimidine chemotherapy did not prolong survival or time to disease progression of patients with advanced colorectal cancer.

  11. Treatment of asymptomatic metastatic cancer to the liver from primary colon and rectal cancer by the intraarterial administration of chemotherapy and radioactive isotopes

    International Nuclear Information System (INIS)

    Forty patients with asymptomatic metastatic cancer to the liver discovered at the time of laparotomy were treated by combined intrahepatic arterial chemotherapy and internal irradiation in the form of 90Y microspheres. One group of 25 patients were treated by a catheter inserted at the time of operation and received 100 mCi; of 90Y microspheres and 5-fluorouracil on a continuing basis. They survived an average of 26 mo (varying from 9 to 60 mo). The second series of 15 patients referred after surgery were treated by the percutaneous insertion of the catheter into the hepatic artery and received a bolus of combined chemotherapy consisting of PlatinolTM, Methotrexate, and 5-fluorouracil. They survived an average of 31 mo, which varied from 12 to 60 mo. The dose of 100 mCi of 90Y was well tolerated by the liver. Prospective studies are in progress, limiting the treatment to the internal irradiation to determine its precise role in the overall treatment of metastatic cancer to the liver

  12. TIMP-1 and CEA as biomarkers in third-line treatment with irinotecan and cetuximab for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Christensen, Ib Jarle; Nielsen, Hans Jørgen; Jakobsen, Anders; Brünner, Nils

    2015-01-01

    colorectal cancer (CRC). The aim of the present study was to investigate the clinical value of TIMP-1 in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. Patients with chemotherapy-resistant mCRC referred to third-line treatment with cetuximab (initial 400 mg/m(2......) followed by weekly 250 mg/m(2))/irinotecan (350 mg/m(2) q3w) were prospectively included in the biomarker study, as previously published. Pre-treatment blood samples were collected, and plasma TIMP-1 was measured by a validated in-house ELISA assay. In addition, carcinoembryonic antigen (CEA) measurement...... tumour localisation) or to differences in PFS or OS. The rank correlation between CEA and TIMP-1 was r = 0.50, and a test for interaction between TIMP-1 and CEA (dichotomised at 5 ng/ml) in survival analysis was not significant (p = 0.18). A multivariate analysis for PFS and OS resulted in a model with...

  13. 111In-cetuximab as a diagnostic agent by accessible epidermal growth factor (EGF) receptor targeting in human metastatic colorectal carcinoma.

    Science.gov (United States)

    Shih, Ying-Hsia; Peng, Cheng-Liang; Lee, Shin-Yu; Chiang, Ping-Fang; Yao, Cheng-Jung; Lin, Wuu-Jyh; Luo, Tsai-Yueh; Shieh, Ming-Jium

    2015-06-30

    Colorectal adenocarcinoma is a common cause death cancer in the whole world. The aim of this study is to define the 111In-cetuximab as a diagnosis tracer of human colorectal adenocarcinoma. In this research, cell uptake, nano-SPECT/CT scintigraphy, autoradiography, biodistribution and immunohitochemical staining of EGF receptor were included. HCT-116 and HT-29 cell expressed a relatively high and moderate level of EGF receptor, respectively. The nano-SPECT/CT image of 111In-cetuximab showed tumor radiation uptake of subcutaneous HCT-116 xenograft tumor was higher than SW-620. Autoradiography image also showed that tumor of HCT-116 had high 111In-cetuximab uptake. Mice that bearing CT-26 in situ xenograft colorectal tumors showed similar high uptake in vivo and ex vivo through nano-SPECT/CT imaging at 72 hours. Metastatic HCT-116/Luc tumors demonstrated the highest uptake at 72 hours after the injection of 111In-cetuximab. Relatively, results of 111In-DTPA showed that metabolism through urinary system, especially in the kidney. The quantitative analysis of biodistribution showed count value of metastatic HCT-116/Luc tumors that treated with 111In-cetuximab had a significant difference (P < 0.05) compared with that treated with 111In-DTPA after injection 72 hours. Result of immunohistologic staining of EGF receptor also showed high EGF receptor expression and uptake in metastatic colorectal tumors. In summary, we suggested that 111In-cetuximab will be a potential tool for detecting EGF receptor expression in human metastatic colorectal carcinoma. PMID:26062654

  14. A single-institution experience with bevacizumab in the treatment of metastatic colorectal cancer and in conjunction with liver resection

    Directory of Open Access Journals (Sweden)

    Osterlund P

    2014-07-01

    Full Text Available Pia Osterlund,1,2 Reetta Peltonen,2,3 Tuomo Alanko,1 Petri Bono,1,2 Helena Isoniemi2,3 1Department of Oncology, Helsinki University Central Hospital, Helsinki, 2Institute of Clinical Medicine, University of Helsinki, Helsinki, 3Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland Background: Bevacizumab is active in the treatment of metastatic colorectal cancer (mCRC. However, efficacy of bevacizumab has predominantly been evaluated on selected patients with relatively good performance status and minor comorbidities. We evaluated the efficacy and safety of bevacizumab in unselected patients with mCRC, some of whom underwent liver resection. Material and methods: All patients with inoperable mCRC, fit for combination chemotherapy (n=180, who were initially not resectable, not included into studies and without contraindications to bevacizumab, and initiated on bevacizumab at the Helsinki University Central Hospital between April 2004 and December 2005 were included (n=114. Most (n=70 received 5-fluorouracil/leucovorin/irinotecan plus bevacizumab as first-line therapy. The remainder (n=44 of the patients received bevacizumab in combination with oxaliplatin or irinotecan with or without 5-fluorouracil or capecitabine. Minimum follow-up was 7 years. Treatment response was evaluated every 8–10 weeks according to RECIST criteria. Results: Median age was 59.6 years (range 35–79; male/female ratio was 54%/46%; World Health Organization performance status 0/1/2–3 was 33%/55%/11%, respectively; and the number of metastatic sites, one/two/three or more, was 31%/21%/48%, respectively. Median duration of bevacizumab therapy was 7.8 months (range 0.5–70.5 with pauses. In first-line (n=40, response rate (RR was 62%, progression-free survival (PFS 11.7 months, and overall survival (OS 22.1 months. In second-line (n=43, RR was 44%, PFS 8.7 months, and OS 18.7 months. In later lines (n=31, RR was 14%, PFS 6.7 months, and OS 14

  15. The role of colorectal cancer stem cells in metastatic disease and therapeutic response.

    Science.gov (United States)

    Anderson, Eric C; Hessman, Crystal; Levin, Trevor G; Monroe, Marcus M; Wong, Melissa H

    2011-01-01

    Colorectal cancer is the third-leading cause of cancer related mortality in the United States. The intricate molecular mechanisms involved in the regenerative process of the normal intestine and the identity of putative somatic intestinal stem cells have become clear. In parallel with this, experiment evidence has emerged supporting the century old hypothesis that solid tumor initiation, progression, chemoresistance and recurrence is the result of a small population of cancer cells with self-renewal and pluripotency capabilities. These "cancer stem cells" (CSCs) present a unique opportunity to better understand the biology of solid tumors in general, as well as targets for future therapeutics. In this review, we will summarize the current understanding of intestinal stem cell biology and translate it to colorectal CSCs to provide a basis for understanding chemoresistance, cancer recurrence and metastasis. A more complete understanding of the biology of colorectal CSCs will translate into the development of better chemotherapeutic and biological agents for the treatment of colorectal cancer. PMID:21318087

  16. The Role of Colorectal Cancer Stem Cells in Metastatic Disease and Therapeutic Response

    Directory of Open Access Journals (Sweden)

    Melissa H. Wong

    2011-01-01

    Full Text Available Colorectal cancer is the third-leading cause of cancer related mortality in the United States. The intricate molecular mechanisms involved in the regenerative process of the normal intestine and the identity of putative somatic intestinal stem cells have become clear. In parallel with this, experiment evidence has emerged supporting the century old hypothesis that solid tumor initiation, progression, chemoresistance and recurrence is the result of a small population of cancer cells with self-renewal and pluripotency capabilities. These “cancer stem cells” (CSCs present a unique opportunity to better understand the biology of solid tumors in general, as well as targets for future therapeutics. In this review, we will summarize the current understanding of intestinal stem cell biology and translate it to colorectal CSCs to provide a basis for understanding chemoresistance, cancer recurrence and metastasis. A more complete understanding of the biology of colorectal CSCs will translate into the development of better chemotherapeutic and biological agents for the treatment of colorectal cancer.

  17. Review on TAS-102 development and its use for metastatic colorectal cancer.

    Science.gov (United States)

    Mota, Jose Mauricio; Fonseca, Leonardo G; Braghiroli, Maria Ignez; Hoff, Paulo M

    2016-08-01

    TAS-102 is the combination of trifluridine (TFT) with tipiracil (TPI) in a 1:0.5 molar ratio. TFT is a fluoropyrimidine that retains cytotoxic activity in 5-fluorouracil resistant cell lines. Due to TFT short half-life, early clinical development was discouraging. Thereafter, TFT was shown to be promptly degraded by thymidine phosphorylase, also known as platelet-derived endothelial cell growth factor, a pro-angiogenic protein and a poor prognosis marker in colorectal cancer. TPI is a specific antagonist of thymidine phosphorylase and led to an increase in TFT serum levels when both agents are combined. Moreover, TPI is a potential anti-angiogenic molecule and could exert antitumor actions per se. TAS-102 was tested in several Phase I studies published in the early 21st century. The best regimen was settled as 70mg/m(2)/day, q12h, orally given at days 1-5 and days 8-13, each 28days. Recently, the first Phase III trial evaluating TAS-102 in refractory colorectal cancer patients was published. The RECOURSE trial demonstrated a survival advantage of the agent over supportive care, and definitely established TAS-102 as a novel strategy in the current armamentarium against colorectal cancer. Here we review the preclinical data regarding TFT and TPI that led to the development of TAS-102, and the set of clinical data that ultimately proved that TAS-102 improved outcomes in colorectal cancer patients. PMID:27296058

  18. Cost-effectiveness analysis of cetuximab in treatment of metastatic colorectal cancer in Iranian pharmaceutical market

    Directory of Open Access Journals (Sweden)

    Majid Davari

    2015-01-01

    Conclusions: The FOLFOX regimen + cetuximab provides lower costs per additional life years gained (more cost-effective compared with its alternatives in the treatment of patients with unresectable metastatic CRC. However, according to the WHO indicator, none of the cetuximab regimens could be considered as cost effective for the Iranian health care market.

  19. The efficacy and safety of panitumumab in the treatment of patients with metastatic colorectal cancer: a meta-analysis from five randomized controlled trials

    OpenAIRE

    Zheng, Lei-lei

    2015-01-01

    Ruo-feng Liang,1 Lei-lei Zheng2 1General Department, University Hospital, Affiliated to Zhejiang Science-Technology University, Hangzhou, People’s Republic of China; 2Department of Psychiatry, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China Background: The efficacy of adding panitumumab to chemotherapy remains controversial in the treatment of metastatic colorectal cancer (mCRC). Thus, we conducted this meta-anal...

  20. The efficacy and safety of panitumumab in the treatment of patients with metastatic colorectal cancer: a meta-analysis from five randomized controlled trials

    OpenAIRE

    Liang, Ruo-feng; Zheng, Lei-lei

    2015-01-01

    Background The efficacy of adding panitumumab to chemotherapy remains controversial in the treatment of metastatic colorectal cancer (mCRC). Thus, we conducted this meta-analysis to assess the efficacy and safety of this combination regimen in patients with mCRC. Methods The PubMed, Embase, and Web of Science databases were comprehensively searched. Eligible studies included randomized controlled trials (RCTs) that estimated the efficacy of panitumumab with or without chemotherapy in the trea...

  1. The efficacy and safety of panitumumab in the treatment of patients with metastatic colorectal cancer: a meta-analysis from five randomized controlled trials

    OpenAIRE

    Liang RF; Zheng LL

    2015-01-01

    Ruo-feng Liang,1 Lei-lei Zheng2 1General Department, University Hospital, Affiliated to Zhejiang Science-Technology University, Hangzhou, People’s Republic of China; 2Department of Psychiatry, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China Background: The efficacy of adding panitumumab to chemotherapy remains controversial in the treatment of metastatic colorectal cancer (mCRC). Thus, we conducted this meta-analysis to ...

  2. Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? An evidence-based review

    OpenAIRE

    Palomaki, Glenn E; Bradley, Linda A.; Douglas, Michael P.; Kolor, Katherine; Dotson, W. David

    2009-01-01

    This evidence-based review addresses the question of whether testing for UGT1A1 mutations in patients with metastatic colorectal cancer treated with irinotecan leads to improvement in outcomes (e.g., irinotecan toxicity, response to treatment, morbidity, and mortality), when compared with no testing. No studies were identified that addressed this question directly. The quality of evidence on the analytic validity of current UGT1A1 genetic testing methods is adequate (scale: convincing, adequa...

  3. Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer

    International Nuclear Information System (INIS)

    MicroRNAs (MiRNAs) are short non-coding RNAs that control protein expression through various mechanisms. Their altered expression has been shown to be associated with various cancers. The aim of this study was to profile miRNA expression in colorectal cancer (CRC) and to analyze the function of specific miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA expression profile in eight CRC cell line models, 45 human CRC samples of different stages, and four matched normal colon tissue samples. SW620 CRC cells were stably transduced with miR-143 or miR-145 expression vectors and analyzed in vitro for cell proliferation, cell differentiation and anchorage-independent growth. Signalling pathways associated with differentially expressed miRNAs were identified using a gene set enrichment analysis. The expression analysis of clinical CRC samples identified 37 miRNAs that were differentially expressed between CRC and normal tissue. Furthermore, several of these miRNAs were associated with CRC tumor progression including loss of miR-133a and gain of miR-224. We identified 11 common miRNAs that were differentially expressed between normal colon and CRC in both the cell line models and clinical samples. In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model. The pathways targeted by miR-143 and miR-145 showed no significant overlap. Furthermore, gene expression analysis of metastatic versus non-metastatic isogenic cell lines indicated that miR-145 targets involved in cell cycle and neuregulin pathways were significantly down-regulated in the metastatic context. MiRNAs showing altered expression at different stages of CRC could be targets for CRC therapies and be further developed as potential diagnostic and prognostic analytes. The identified biological processes and signalling pathways collectively targeted by co-expressed miRNAs in

  4. The Role of Colorectal Cancer Stem Cells in Metastatic Disease and Therapeutic Response

    OpenAIRE

    Wong, Melissa H.; Levin, Trevor G.; Anderson, Eric C.; Crystal Hessman; Monroe, Marcus M.

    2011-01-01

    Colorectal cancer is the third-leading cause of cancer related mortality in the United States. The intricate molecular mechanisms involved in the regenerative process of the normal intestine and the identity of putative somatic intestinal stem cells have become clear. In parallel with this, experiment evidence has emerged supporting the century old hypothesis that solid tumor initiation, progression, chemoresistance and recurrence is the result of a small population of cancer cells with self-...

  5. Perioperative Tumor Cell Dissemination In Patients With Primary Or Metastatic Colorectal Cancer

    OpenAIRE

    Tralhão, J. G.; Hoti, E.; Serôdio, M.; Laranjeiro, P.; Paiva, A.; Abrantes, A.M.; Pais, M.L.; Botelho, M. F.; Sousa, F. Castro

    2010-01-01

    Abstract Introduction Although there is general correlation between TNM stage of colorectal cancer (CRC) and its prognosis, there is often significant variability of tumor behaviour and individual patient outcome, which is unaccounted for by pathologic factors alone. Our aim was to estimate the perioperative tumor cell dissemination in patients with primary or CRC liver metastases as a possible factor influencing the outcome. Methods Forty patients ...

  6. 交替化疗方案治疗转移性结直肠癌%Alternating chemotherapy for metastatic colorectal cancel

    Institute of Scientific and Technical Information of China (English)

    杨宇辉

    2008-01-01

    以氟尿嘧啶、奥沙利铂、伊立替康为基础的化疗是转移性结直肠癌的主要治疗方法.近年来许多研究探讨了这些不同活性药物之间的联合应用,并进行了多种联合治疗模式的尝试.多项临床试验表明,交替方案化疗有效率高且毒性较低,为转移性结直肠癌的联合化疗拓展了新的领域.%Fluorouracil,oxaliplatin and irinotecan、are generally accepted as the standard chemothera-peutic agents for metastatic colorectal cancer.In recent years,the research advances on metastatic colorectal cancer treatment focus on the combination between different active drugs,and try to search advisable combined therapy methods.Clinical trials suggest that ahemating regimen is effective and has lower toxicity which provides platform for further study of combined chemotherapy for metastatic colorectal cancer.

  7. BRAF V600E Mutation as a Predictive Factor of Anti-EGFR Monoclonal Antibodies Therapeutic Effects in Metastatic Colorectal Cancer:a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Jia Wei

    2014-01-01

    Objective To investigate the correlation between BRAF V600E mutation and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) therapeutic effects in metastatic colorectal cancer. Methods Studies were included into meta-analysis to investigate the association between BRAF V600E mutation and clinical outcome in metastatic colorectal cancer patients treated with anti-EGFR MoAbs. Results A total of 7 studies were included in this meta-analysis. The 7 studies included 1352 patients in total, sample sizes ranged from 67 to 493. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were collected from included studies and were used to assess the strength of the relation. In patients with wild-type KRAS, the pooled odds ratio for ORR of mutant BRAF over wild-type BRAF was 0.27 (95%CI=0.10-0.70). BRAF mutation predicted a deterioration in PFS and OS in wild-type KRAS patients treated with anti-EGFR MoAbs (hazard ratio=2.78, 95% CI=1.62-4.76;hazard ratio=2.54, 95%CI=1.93-3.32). Conclusion BRAF V600E mutation is related to lack of response and worse survival in wild-type KRAS metastatic colorectal cancer patients treated with anti-EGFR MoAbs.

  8. Orbital Apex Syndrome Caused by Invasive Aspergillosis as an Adverse Effect of Systemic Chemotherapy for Metastatic Colorectal Cancer: a Case Report.

    Science.gov (United States)

    Miyamoto, Yuji; Sakamoto, Yasuo; Ohuchi, Mayuko; Tokunaga, Ryuma; Shigaki, Hironobu; Kurashige, Junji; Iwatsuki, Masaaki; Baba, Yoshifumi; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

    2016-02-01

    Continuous therapy with cytotoxic drugs suppresses humoral immune function and may result in local infection. We present a case of orbital apex syndrome caused by Aspergillus infection during chemotherapy for metastatic colorectal cancer. A 74-year-old man with colorectal liver metastases under long-term continuous systemic chemotherapy presented with painful, progressive orbital apex syndrome. Magnetic resonance imaging disclosed a small enhancing lesion around the right ethmoid sinus. We initially diagnosed colorectal cancer metastasis and he underwent biopsy via the endoscopic endonasal transethmoid approach. However, pathological examination of the cultured specimen revealed Aspergillus fumigatus. The patient was treated with voriconazole and the orbital apex syndrome resolved after 1 month. Orbital aspergillosis is a life-threatening disease and should be listed as a differential diagnosis of uncommon local infections during continuous chemotherapy. PMID:26851046

  9. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients

    International Nuclear Information System (INIS)

    Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown. We assessed immune cells infiltrate (CD56, CD68, CD3, CD4, CD8, Foxp3) in the primary tumor of metastatic colorectal cancer (mCRC) patients treated with a first-line cetuximab-based chemotherapy in the framework of prospective trials (treatment group) and in a matched group of mCRC patients who received the same chemotherapy regimen without cetuximab (control group). The relationship between intra-tumoral immune effector cells, the K-ras status and the efficacy of the treatment were investigated. We also evaluated in vitro, the ADCC activity in healthy donors and chemonaive mCRC patients and the specific contribution of CD56+ cells. ADCC activity against DLD1 CRC cell line is maintained in cancer patients and significantly declined after CD56+ cells depletion. In multivariate analysis, K-ras wild-type (HR: 4.7 (95% CI 1.8-12.3), p = 0.001) and tumor infiltrating CD56+ cells (HR: 2.6, (95%CI:1.14-6.0), p = 0.019) were independent favourable prognostic factors for PFS and response only in the cetuximab treatment group. By contrast CD56+ cells failed to predict PFS and response in the control group. CD56+ cells, mainly NK cells, may be the major effector of ADCC related-cetuximab activity. Assessment of CD56+ cells infiltrate in primary colorectal adenocarcinoma may provide additional information to K-ras status in predicting response and PFS in mCRC patients treated with first-line cetuximab-based chemotherapy

  10. Safety and efficacy of the addition of simvastatin to panitumumab in previously treated KRAS mutant metastatic colorectal cancer patients.

    Science.gov (United States)

    Baas, Jara M; Krens, Lisanne L; Bos, Monique M; Portielje, Johanneke E A; Batman, Erdogan; van Wezel, Tom; Morreau, Hans; Guchelaar, Henk-Jan; Gelderblom, Hans

    2015-09-01

    Panitumumab has proven efficacy in patients with metastatic or locally advanced colorectal cancer patients, provided that they have no activating KRAS mutation in their tumour. Simvastatin blocks the mevalonate pathway and thereby interferes with the post-translational modification of KRAS. We hypothesize that the activity of the RAS-induced pathway in patients with a KRAS mutation might be inhibited by simvastatin. This would theoretically result in increased sensitivity to panitumumab, potentially comparable with tumours with wild-type KRAS. A Simon two-stage design single-arm, phase II study was designed to test the safety and efficacy of the addition of simvastatin to panitumumab in colorectal cancer patients with a KRAS mutation after failing fluoropyrimidine-based, oxaliplatin-based and irinotecan-based therapy. The primary endpoint of this study was the proportion of patients alive and free from progression 11 weeks after the first administration of panitumumab, aiming for at least 40%, which is comparable with, although slightly lower than, that in KRAS wild-type patients in this setting. If this 40% was reached, then the study would continue into the second step up to 46 patients. Explorative correlative analysis for mutations in the KRAS and related pathways was carried out. One of 14 patients was free from progression at the primary endpoint time. The median progression-free survival was 8.4 weeks and the median overall survival status was 19.6 weeks. We conclude that the concept of mutant KRAS phenotype expression modulation with simvastatin was not applicable in the clinic. PMID:26053280

  11. Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy.

    Science.gov (United States)

    Trotta, Anna Maria; Ottaiano, Alessandro; Romano, Carmela; Nasti, Guglielmo; Nappi, Anna; De Divitiis, Chiara; Napolitano, Maria; Zanotta, Serena; Casaretti, Rossana; D'Alterio, Crescenzo; Avallone, Antonio; Califano, Daniela; Iaffaioli, Rosario Vincenzo; Scala, Stefania

    2016-04-01

    Cetuximab is a monoclonal antibody to the EGFR that induces antibody-dependent cell cytotoxicity (ADCC) through Fcγ receptors on immune cells. Although SNPs in genes encoding Fcγ receptors are functionally relevant to cetuximab-mediated ADCC in colorectal cancer, a direct correlation betweenin vitroADCC and clinical response to cetuximab is not defined. We therefore enrolled 96 consecutive metastatic colorectal cancer (mCRC) patients at diagnosis in a study that assessed FcγR status and cetuximab-mediated ADCC. Patients carrying the FcγRIIaHalleles 131H/Hand 131H/Rhad significantly higher ADCC compared with patients with the 131R/Ralleles (P= 0.013). Patients carrying FcγRIIIa genotypes with theValleles 158V/Vand 158V/Fdisplayed higher ADCC compared with patients carrying the 158F/Fgenotype (P= 0.001). Progression-free survival of patients with an FcγRIIIa 158Vallele was significantly longer compared with patients carrying 158F/F(P= 0.05), whereas no significant difference was observed for overall survival. Twenty-eight of 50 mCRC patients with wild-type KRAS received cetuximab. The average ADCC-mediated killing was 30% of assay targets for patients who experienced cetuximab complete or partial response, 21% in patients with stable disease and 9% in patients with progressive disease. To characterize basal natural killer (NK) activity, cytotoxicity was evaluated in 39 of 96 mCRC patients. Patients who responded to first-line treatment had higher NK-cell cytotoxicity. Thus, although limited to this cohort of patients,in vitrocetuximab-mediated ADCC correlated with FcγR polymorphisms and predicted cetuximab responsiveness.Cancer Immunol Res; 4(4); 366-74. ©2016 AACR. PMID:26817995

  12. Tiam1 transgenic mice display increased tumor invasive and metastatic potential of colorectal cancer after 1,2-dimethylhydrazine treatment.

    Directory of Open Access Journals (Sweden)

    Li-Na Yu

    Full Text Available BACKGROUND: T lymphoma invasion and metastasis 1 (Tiam1 is a potential modifier of tumor development and progression. Our previous study in vitro and in nude mice suggested a promotion role of Tiam1 on invasion and metastasis of colorectal cancer (CRC. In the present study, we generated Tiam1/C1199-CopGFP transgenic mice to investigate the tumorigenetic, invasive and metastatic alterations in the colon and rectum of wild-type and Tiam1 transgenic mice under 1,2-dimethylhydrazine (DMH treatment. METHODS: Transgenic mice were produced by the method of pronuclear microinlectlon. Whole-body fluorescence imaging (Lighttools, Edmonton, Alberta, Canada, PCR, and immunohistochemical techniques (IHC were applied sequentially to identify the transgenic mice. The carcinogen DMH (20 mg/kg was used to induce colorectal tumors though intraperitoneal (i.p. injections once a week for 24 weeks from the age of 4 weeks on Tiam1 transgenic or non-transgenic mice. RESULTS: We successfully generated Tiam1/C1199-CopGFP transgenic mice and induced primary tumors in the intestine of both wild type and Tiam1 transgenic mice by DMH treatment. In addition, Tiam1 transgenic mice developed larger and more aggressive neoplasm than wild-type mice. Moreover, immunohistochemical staining revealed that upregulation of Tiam1 was correlated with increased expression of β-Catenin and Vimentin, and downregulation of E-Cadherin in these mice. CONCLUSIONS: Our study has provided in vivo evidence supporting that Tiam1 promotes invasion and metastasis of CRC, most probably through activation of Wnt/β-catenin signaling pathway, in a Tiam1 transgenic mouse model.

  13. Prognostic value of the Glasgow Prognostic Score in metastatic colorectal cancer in the era of anti-EGFR therapies.

    Science.gov (United States)

    Dréanic, Johann; Maillet, Marianne; Dhooge, Marion; Mir, Olivier; Brezault, Catherine; Goldwasser, François; Chaussade, Stanislas; Coriat, Romain

    2013-01-01

    The Glasgow Prognostic Score (GPS), combination of C-reactive protein and albumin, has proven its prognostic value in metastatic colorectal cancer (mCRC) patients receiving conventional cytotoxic therapy. More recently, anti-EGFR therapies have been validated in mCRC and roll forward the patients' overall survival (OS). We aimed to evaluate the prognostic accuracy of the GPS in patients receiving anti-EGFR therapy in addition to conventional chemotherapy. From January 2007 to February 2012, consecutive mCRC patients who received 5-fluorouracil-based chemotherapy plus cetuximab were included in the present analysis. Patients were eligible for the study if they met the following criteria: advanced pathologically proven MCRC, age >18 years, adequate renal function (creatinine clearance >40 ml/min), C-reactive protein and albumin and performance status evaluation before treatment initiation. A total of 49 patients received cetuximab plus 5-fluorouracil-based chemotherapy (colon, n = 34; rectum, n = 15) and were treated with a median follow-up of 35 months (16.5-74.7). Median age was 48 years old. In addition to cetuximab, patients received oxaliplatin- (n = 34, 60%) or irinotecan (n = 15, 30%)-based chemotherapy. At time of diagnosis, 55, 29 and 16% of patients had a GPS of 0 (n = 27), 1 (n = 14) and 2 (n = 8), respectively. Fifty-five, 29 and 14 % of patients add one, two or ≥3 metastatic sites, respectively. Considering two groups (GPS = 0 and GPS ≥1), median progression-free survivals were significantly different (p = 0.0084). Median OS in the GPS 0, 1 and 2 groups were 38.2, 14 and 12.1 months, respectively (p = 0.0093). The results of the present study confirm that the GPS is still a simple and effective prognostic factor in the era of cetuximab therapy in mCRC patients. PMID:23839775

  14. Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: A single center study

    Directory of Open Access Journals (Sweden)

    Ulivi Paola

    2012-05-01

    Full Text Available Abstract Background KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC patients. As only 20% of KRAS wild type (WT patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding KRAS WT patients. We retrospectively analyzed objective tumor response rate, (ORR progression-free (PFS and overall survival (OS with respect to the mutational status of KRAS, BRAF, PIK3CA and PTEN expression in mCRC patients treated with a cetuximab-based regimen. Methods 67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were analyzed by direct sequencing, PIK3CA was evaluated by pyrosequencing and PTEN expression by immunohistochemistry. Results BRAF and PIK3CA mutations were independently associated with worse PFS (p = 0.006 and p = 0.028, respectively and OS (p = 0.008 and p = 0.029, respectively. No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for KRAS, BRAF and PIK3CA mutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations. Conclusions BRAF and PIK3CA mutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.

  15. Aflibercept, a New Way to Target Angiogenesis in the Second Line Treatment of Metastatic Colorectal Cancer (mCRC).

    Science.gov (United States)

    Scartozzi, Mario; Vincent, Loic; Chiron, Marielle; Cascinu, Stefano

    2016-08-01

    Colorectal cancer (CRC) is a leading tumour worldwide, and the median survival of metastatic patients with the latest therapeutic options today reaches 30 months. Therefore, it is important to plan a therapeutic strategy, able to optimize the use of the available drugs (fluoropyrimides, oxaliplatin, irinotecan and target biologic therapy), with the objective of maximizing the long-term efficacy, reducing toxicities and assuring better quality of life for the patients with mCRC. Among the most recently available drugs for the treatment of mCRC, aflibercept, a new antiangiogenetic agent, should be considered a promising therapeutical option for the second line setting. In this review, the mechanism of action and preclinical evidence, as well as pharmacological and clinical aspects of aflibercept will be analysed. In particular, this drug has a peculiar and unique mechanism of action, inhibiting VEGF-A, -B and PlGF pathways, which may help to overcome tumour escape mechanisms to bevacizumab treatment. From a clinical point of view, the addition of aflibercept to FOLFIRI regimen was able to significantly improve all the clinical outcome with respect to the chemotherapy alone in second line treatment of mCRC patients, regardless of age, RAS status, and prior use of bevacizumab. Finally, the safety profile of aflibercept is well known and manageable in most of the patients. Aflibercept can be considered a novel standard of care in the second line setting and an important therapeutic option for mCRC patients. PMID:27412031

  16. Combination Chemotherapy of Azacitidine and Cetuximab for Therapy-Related Acute Myeloid Leukemia following Oxaliplatin for Metastatic Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Akari Hashimoto

    2014-05-01

    Full Text Available Therapy-related leukemia (TRL has been reported to occur after treatment with alkylating agents and/or topoisomerase II inhibitors. Oxaliplatin (OXP is used as a key drug for the treatment of colorectal cancer (CRC. Cisplatin and carboplatin have been linked with TRL, but the involvement of OXP is questionable. A 74-year-old male was diagnosed with peritoneal metastasis from CRC in July 2011. The patient received nine cycles of 5-fluorouracil (5-FU, leucovorin (LV, and OXP (mFOLFOX-6 regimen and three cycles of 5-FU and LV only, resulting in a clinical complete response. However, recurrence of CRC was detected by CT within 3 months after the last course of chemotherapy. In April 2013, laboratory tests showed pancytopenia and 15% blast cells. A bone marrow examination revealed multilineage dysplasia and 20.4% myeloblasts. Cytogenetic analysis indicated a complex karyotype that included chromosome 5 and 7 abnormalities. The patient was diagnosed with TRL and treated with a combination of azacitidine (AZA and cetuximab (Cmab for both cancers. AZA might be useful in TRL when a patient needs to be treated simultaneously for more than one primary cancer because of its low toxicity. Moreover, Cmab is an effective therapeutic tool in TRL patients with metastatic CRC with the wild-type K-ras gene.

  17. EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Frifeldt Sanne K

    2011-03-01

    Full Text Available Abstract Background As supplement to KRAS mutational analysis, BRAF and PIK3CA mutations as well as expression of PTEN may account for additional non-responders to anti-EGFR-MoAbs treatment. The aim of the present study was to investigate the utility as biomarkers of these mutations in a uniform cohort of patients with metastatic colorectal cancer treated with third-line cetuximab/irinotecan. Methods One-hundred-and-seven patients were prospectively included in the study. Mutational analyses of KRAS, BRAF and PIK3CA were performed on DNA from confirmed malignant tissue using commercially available kits. Loss of PTEN and EGFR was assessed by immunohistochemistry. Results DNA was available in 94 patients. The frequency of KRAS, BRAF and PIK3CA mutations were 44%, 3% and 14%, respectively. All were non-responders. EGF receptor status by IHC and loss of PTEN failed to show any clinical importance. KRAS and BRAF were mutually exclusive. Supplementing KRAS analysis with BRAF and PIK3CA indentified additional 11% of non-responders. Patient with any mutation had a high risk of early progression, whereas triple-negative status implied a response rate (RR of 41% (p Conclusion Triple-negative status implied a clear benefit from treatment, and we suggest that patient selection for third-line combination therapy with cetuximab/irinotecan could be based on triple mutational testing.

  18. Update on optimal treatment for metastatic colorectal cancer from the ACTG/AGITG expert meeting: ECCO 2015.

    Science.gov (United States)

    Price, Timothy J; Thavaneswaran, Subotheni; Burge, Matthew; Segelov, Eva; Haller, Daniel G; Punt, Cornelis Ja; Arnold, Dirk; Karapetis, Christos S; Tebbutt, Niall C; Pavlakis, Nick; Gibbs, Peter; Shapiro, Jeremy D

    2016-05-01

    The treatment of metastatic CRC (mCRC) has evolved over the last 20 years, from fluoropyrimidines alone to combination chemotherapy and new biologic agents. Median overall survival is now over 24 months for RAS mutated (MT) patients and over 30 months for RAS wild-type (WT) patients. However, there are subgroups of patients with BRAF V600E MT CRC who have a significantly poorer outlook. Newer treatment options are also being explored in select subgroups of patients (anti-HER 2 in HER2 positive mCRC and immunotherapy in patients with defective mismatch repair (dMMR)). The best use of these systemic treatment options, as well as surgery in well-selected patients requires careful consideration of predictive biomarkers and importantly, the optimal sequence in which therapies should be given to derive maximal benefit. A group of colorectal subspecialty medical oncologists from Australia, USA, The Netherlands and Germany met during ECCO 2015 in Vienna to review current practice. PMID:27010906

  19. Current role of antibody therapy in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Pfeiffer, P; Qvortrup, C; Eriksen, J G

    2007-01-01

    In less than 10 years, the number and importance of non-surgical treatment modalities in patients with colorectal cancer (CRC) have increased dramatically, both in the adjuvant and the advanced settings. However, despite the improvement of cytotoxic therapy in CRC, many patients still develop...... arsenal in CRC to a great extent, but they will also add to the complexity of treatment of CRC. In this review, we summarize the current status of antibody therapy in patients with CRC...... progressive disease and unfortunately in patients with disease resistant to 5-fluorouracil/folinic acid, irinotecan and oxaliplatin, no effective cytotoxic therapy is known. The rapidly expanding knowledge in tumor biology has encouraged optimism for the possibility to find and target tumor...

  20. Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients

    Science.gov (United States)

    Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai-Ming, Jr.; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

    2016-04-01

    Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

  1. Anti-VEGF agents in metastatic colorectal cancer (mCRC): are they all alike?

    International Nuclear Information System (INIS)

    Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF)-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States), VEGF receptors (eg, ramucirumab), and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors). The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012), using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking

  2. Metabolic activation of irinotecan during intra-arterial chemotherapy of metastatic colorectal cancer.

    Science.gov (United States)

    Czejka, M; Kiss, A; Koessner, C; Terkola, R; Ettlinger, D; Schueller, J

    2011-10-01

    Biotransformation of irinotecan (CPT-11) into its pharmacologic active metabolite SN-38 was investigated in patients treated for advanced colorectal cancer. A dose of 180 mg/m(2) CPT-11 was administered to 6 patients by 60 min hepatic intra-arterial infusion (HAI) via a surgically implanted Port-a-Cath® system. Blood samples were collected from 0 to 360 min after start of HAI, and CPT-11 plus metabolites were analysed by a selective reversed phase HPLC method. The objective of this study was to evaluate the extent to which SN-38 is generated after HAI of irinotecan given at a low dose of 180 mg/m(2). In a second investigation, CPT-11 was administered via conventional intravenous infusion (dose 180 mg/m(2), 60 min infusion time, 11 patients) and CPT-11 plus metabolites were quantified using identical analytical procedure. Compared to i.v. infusion, the pharmacokinetics of CPT-11 and SN-38 were altered by HAI. The mean c(max) of CPT-11 after HAI was reduced by 37%, whereas the mean c(max) of SN-38 increased by 60%. HAI resulted in a desired, increased metabolic conversion of CPT-11 into SN-38 and might improve the regional availability of the pharmacologic active metabolite SN-38 at the site of tumor. Plasma concentrations of the metabolites SN-38 glucuronide and APC remained unaffected by the route of administration. PMID:21965780

  3. Molecular constituents of colorectal cancer metastatic to the liver by imaging infrared spectroscopy

    Science.gov (United States)

    Coe, James V.; Chen, Zhaomin; Li, Ran; Nystrom, Steven V.; Butke, Ryan; Miller, Barrie; Hitchcock, Charles L.; Allen, Heather C.; Povoski, Stephen P.; Martin, Edward W.

    2015-03-01

    Infrared (IR) imaging spectroscopy of human liver tissue slices has been used to identify and characterize liver metastasis of colorectal origin which was surgically removed from a consenting patient and frozen without formalin fixation or dehydration procedures, so that lipids and water remain in the tissues. First, a k-means clustering analysis, using metrics from the IR spectra, identified groups within the image. The groups were identified as tumor or nontumor regions by comparing to an H and E stain of the same sample after IR imaging. Then, calibrant IR spectra of protein, several fats, glycogen, and polyvinyl alcohol were isolated by differencing spectra from different regions or groups in the image space. Finally, inner products (or scores) of the IR spectra at each pixel in the image with each of the various calibrants were calculated showing how the calibrant molecules vary in tumor and nontumor regions. In this particular case, glycogen and protein changes enable separation of tumor and nontumor regions as shown with a contour plot of the glycogen scores versus the protein scores.

  4. A single-institution experience with bevacizumab in the treatment of metastatic colorectal cancer and in conjunction with liver resection

    Science.gov (United States)

    Osterlund, Pia; Peltonen, Reetta; Alanko, Tuomo; Bono, Petri; Isoniemi, Helena

    2014-01-01

    Background Bevacizumab is active in the treatment of metastatic colorectal cancer (mCRC). However, efficacy of bevacizumab has predominantly been evaluated on selected patients with relatively good performance status and minor comorbidities. We evaluated the efficacy and safety of bevacizumab in unselected patients with mCRC, some of whom underwent liver resection. Material and methods All patients with inoperable mCRC, fit for combination chemotherapy (n=180), who were initially not resectable, not included into studies and without contraindications to bevacizumab, and initiated on bevacizumab at the Helsinki University Central Hospital between April 2004 and December 2005 were included (n=114). Most (n=70) received 5-fluorouracil/leucovorin/irinotecan plus bevacizumab as first-line therapy. The remainder (n=44) of the patients received bevacizumab in combination with oxaliplatin or irinotecan with or without 5-fluorouracil or capecitabine. Minimum follow-up was 7 years. Treatment response was evaluated every 8–10 weeks according to RECIST criteria. Results Median age was 59.6 years (range 35–79); male/female ratio was 54%/46%; World Health Organization performance status 0/1/2–3 was 33%/55%/11%, respectively; and the number of metastatic sites, one/two/three or more, was 31%/21%/48%, respectively. Median duration of bevacizumab therapy was 7.8 months (range 0.5–70.5 with pauses). In first-line (n=40), response rate (RR) was 62%, progression-free survival (PFS) 11.7 months, and overall survival (OS) 22.1 months. In second-line (n=43), RR was 44%, PFS 8.7 months, and OS 18.7 months. In later lines (n=31), RR was 14%, PFS 6.7 months, and OS 14.2 months. Ten patients with initially unresectable liver metastases became operable and R0 resection was achieved in 90% (9/10 resections). In 23% (7/31) of operated metastases, no vital tumor cells were found in histologic examination. Operative morbidity was low: two mild infections, no increased bleeding tendency

  5. Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Yang Q

    2015-09-01

    Full Text Available Qiong Yang,1–4,* Chenxi Yin,1,3,4,* Fangxin Liao,1,3,4 Yuanyuan Huang,1,3,4 Wenzhuo He,1,3,4 Chang Jiang,1,3,4 Guifang Guo,1,3,4 Bei Zhang,1,3,4 Liangping Xia1,3,41VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 4Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workBackground: Currently available third- or later-line therapy for metastatic colorectal cancer (mCRC is limited in its efficacy, with a weak survival benefit in patients who progressed after two or more lines of standard therapy. Our retrospective study aimed to explore the value of bevacizumab plus chemotherapy in this setting.Methods: Patients with mCRC who received fluoropyrimidine, oxaliplatin, and irinotecan as first- and second-line chemotherapy were selected for inclusion. Treatment consisted of bevacizumab plus chemotherapy. Chemotherapy consisted mainly of oxaliplatin, irinotecan, and fluoropyrimidine.Results: Between February 2010 and December 2012, 35 consecutive patients with mCRC were treated with bevacizumab plus chemotherapy as a third- or later-line treatment. No complete responses, seven partial responses (20%, 22 stable disease responses (62.9%, and six progressive disease responses (17.1% were obtained, producing an objective response rate of 20% and a disease control rate of 82.9%. With a median follow-up of 11.3 months (range: 0.7–48.0 months, the median progression-free survival was 5.98 months (95% confidence interval: 4.76–7.2 months, and the median overall survival was 14.77 months (95% confidence interval: 11.45–18.1 months. In the univariate analysis

  6. The predictive and prognostic value of the Glasgow Prognostic Score in metastatic colorectal carcinoma patients receiving bevacizumab.

    Science.gov (United States)

    Maillet, Marianne; Dréanic, Johann; Dhooge, Marion; Mir, Olivier; Brezault, Catherine; Goldwasser, François; Chaussade, Stanislas; Coriat, Romain

    2014-11-01

    The Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, has shown its prognostic value in metastatic colorectal carcinoma (mCRC) patients receiving conventional cytotoxic therapy. Bevacizumab, a monoclonal antibody to vascular epidermal growth factor, improves the overall survival in mCRC. The aim of the present study was to assess the prognostic value of GPS in mCRC patients receiving antivascular epidermal growth factor therapy. From August 2005 to August 2012, consecutive patients with mCRC who received chemotherapy plus bevacizumab were eligible for the present analysis. The clinical stage, C-reactive protein, albumin and the Eastern Cooperative Oncology Group performance status were recorded at the time of initiation of bevacizumab. Patients received 5-fluorouracil-based chemotherapy plus bevacizumab in accordance with the digestive oncology multidisciplinary staff proposal and in line with the French recommendations for the treatment of mCRC. Eighty patients were eligible (colon n = 59, rectum n = 21), with a median follow-up of 14 months (range 1-58 months). Chemotherapy given with bevacizumab and 5-fluorouracil was oxaliplatin (n = 41, 51%) or irinotecan (n = 27, 34%). At baseline, 56, 31 and 13% of patients had a GPS of 0 (n = 45), 1 (n = 25) and 2 (n = 10), respectively. The median progression-free survival in these groups was 10.1, 6.5 and 5.6 months (P = 0.16), respectively. The median overall survival was 20.1, 11.4 and 6.5 months, respectively (P = 0.004). Our study confirmed the prognostic value of GPS in mCRC patients receiving chemotherapy plus bevacizumab. Given the poor survival observed in patients with an GPS of 2, studies dedicated to these patients could identify optimal treatment modalities. PMID:24858536

  7. FCGR2A, FCGR3A polymorphisms and therapeutic efficacy of anti-EGFR monoclonal antibody in metastatic colorectal cancer.

    Science.gov (United States)

    Ying, Hou-Qun; Wang, Feng; Chen, Xiao-Lin; He, Bang-Shun; Pan, Yu-Qin; Jie, Chen; Liu, Xian; Cao, Wei-Jun; Peng, Hong-Xin; Lin, Kang; Wang, Shu-Kui

    2015-09-29

    Anti-EGFR monoclonal antibodies (mAb) such as cetuximab, panitumumab are one kind of efficacious targeted drugs in treatment of metastatic colorectal cancer (mCRC). However, only a small proportion of patients harbored wild-KRAS genotype can benefit from it. We hypothesized that personal genetic heterogeneity might be the main cause leading to obvious difference in its clinical efficacy. A retrospective study including 82 mCRC patients treated with chemotherapy plus cetuximab and a comprehensive meta-analysis containing 2831 cases within sixteen eligible studies were conducted to investigate the possible association between FCGR2A H131R and FCGR3A V158F and clinical outcome of mCRC patients treated with anti-EGFR mAb based therapy. Results of the retrospective study showed that H131R within FCGR2A or V158F within FCGR3A were not associated with clinical outcome in 82 KRAS wild chemorefractory mCRC patients in co-dominant, dominant, recessive, over-dominant, allele genetic models. However, the comprehensive meta-analysis with the largest of sample size obtained the significant result between FCGR3A V158F and PFS (FV/VV vs. FF: Ph = 0.027, MSR = 0.680, 95%CI = 0.549-0.842 in overall population; Ph = 0.12, MSR = 0.728, 95%CI = 0.648-0.818 in KRAS wild population) and OS (VV vs. FF: Ph < 0.001, MSR = 0.733, 95%CI = 0.578-0.930 in overall population). These findings indicate that KRAS wild chemorefractory mCRC individual harbored genotype FF of V158Fcan benefit from anti-EGFR mAb adjuvant therapy in terms of PFS and OS, and it may be useful genetic biomarker to predict clinical survival of mCRC individuals with anti-EGFR mAb based therapy. PMID:26363448

  8. Raltitrexed (Tomudex administration in patients with relapsed metastatic colorectal cancer after weekly irinotecan/5-Fluorouracil/Leucovorin chemotherapy

    Directory of Open Access Journals (Sweden)

    Vadiaka Maria

    2002-01-01

    Full Text Available Abstract Purpose The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC in relapse (>8 weeks after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU+Leucovorin (LV. Methods Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47–70, median Karnovsky PS: 80 (70–90, and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days. Results Three patients (12% achieved a partial response (PR, 8 (32% had stable disease (SD, and the remaining 14 (56% developed progressive disease (PD. Median time-to-progression (TTP was 5.5 months (range, 2–8.5, and median overall survival (OS 8 months (range, 4.0–12.5. Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1–2: 52%-grade 3: 28%, and anemia grade 1–2 only: 36%. Mild mucositis grade 1–2 occured in 13.5% of patients and was the principal non-hematologic toxicity. Conclusion Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study.

  9. Survival and tolerability of liver radioembolization: a comparison of elderly and younger patients with metastatic colorectal cancer

    Science.gov (United States)

    Tohme, Samer; Sukato, Daniel; Nace, Gary W; Zajko, Albert; Amesur, Nikhil; Orons, Philip; Chalhoub, Didier; Marsh, James W; Geller, David A; Tsung, Allan

    2014-01-01

    Aim To evaluate the outcomes among elderly (≥70 years) and younger patients (<70 years) with liver-dominant metastatic colorectal cancer (mCRC) who received radioembolization (RE) as salvage therapy. Methods A retrospective review of 107 consecutive patients with unresectable mCRC treated with RE after failing first- and second-line chemotherapy. Results From 2002 to 2012, 44 elderly and 63 younger (<70 years) patients received RE. Patients had similar previous extensive chemotherapy and liver-directed interventions. Using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, either a stable or a partial radiographical response was seen in 65.8% of the younger compared with 76.5% of the elderly patients. RE was equally well tolerated in both groups and common procedure-related adverse events were predominantly grade 1–2 and of short duration. No significant difference was found with regard to overall median survival between younger [8.4 months; 95% confidence interval (CI) = 6.2–10.6] or elderly patients (8.2 months; 95% CI = 5.9–10.5, P = 0.667). The presence of extrahepatic disease at the time of RE was associated with a significantly worse median survival in both groups. Conclusion Radioembolization appears to be as well tolerated and effective for the elderly as it is for younger patients with mCRC. Age alone should not be a discriminating factor for the use of radioembolization in the management of mCRC patients. PMID:25123597

  10. Early post-treatment FDG PET predicts survival after 90Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with 90Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent 18F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUVmax) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p 25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using 18F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  11. LINE-1 methylation shows little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Long interspersed nucleotide element 1 (LINE-1) hypomethylation is suggested to play a role in the progression of colorectal cancer (CRC). To assess intra-patient heterogeneity of LINE-1 methylation in CRC and to understand its biological relevance in invasion and metastasis, we evaluated the LINE-1 methylation at multiple tumor sites. In addition, the influence of stromal cell content on the measurement of LINE-1 methylation in tumor tissue was analyzed. Formalin-fixed paraffin-embedded primary tumor tissue was obtained from 48 CRC patients. Matched adjacent normal colon tissue, lymph node metastases and distant metastases were obtained from 12, 18 and 7 of these patients, respectively. Three different areas were microdissected from each primary tumor and included the tumor center and invasive front. Normal mucosal and stromal cells were also microdissected for comparison with the tumor cells. The microdissected samples were compared in LINE-1 methylation level measured by multicolor MethyLight assay. The assay results were also compared between microdissected and macrodissected tissue samples. LINE-1 methylation within primary tumors showed no significant intra-tumoral heterogeneity, with the tumor center and invasive front showing identical methylation levels. Moreover, no difference in LINE-1 methylation was observed between the primary tumor and lymph node and distant metastases from the same patient. Tumor cells showed significantly less LINE-1 methylation compared to adjacent stromal and normal mucosal epithelial cells. Consequently, LINE-1 methylation was significantly lower in microdissected samples compared to macrodissected samples. A trend for less LINE-1 methylation was also observed in more advanced stages of CRC. LINE-1 methylation shows little intra-patient tumor heterogeneity, indicating the suitability of its use for molecular diagnosis in CRC. The methylation is relatively stable during CRC progression, leading us to propose a new concept for the

  12. The prognostic role of serum C-X-C chemokine receptor type 4 in patients with metastatic or recurrent colorectal cancer

    Science.gov (United States)

    Choi, Yoon Ji; Chang, Won Jin; Shin, Sang Won; Park, Kyong Hwa; Kim, Seung Tae; Kim, Yeul Hong

    2016-01-01

    Background C-X-C chemokine receptor type 4 (CXCR4) is involved in tumor progression including angiogenesis, metastasis, and survival. However, whether serum CXCR4 levels in metastatic or recurrent colorectal cancer have a prognostic role, have not been evaluated. Methods We analyzed serum samples from 55 patients with advanced colorectal cancer diagnosed between March 2008 and July 2011. Serum CXCR4 levels were quantified by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results The median age of the patients was 62 years, and all patients received systemic chemotherapy of two or more lines. The median serum CXCR4 level was 283.47 pg/mL (range: 77.48–846.52). Patients with two or more metastatic sites, liver metastasis, or higher CA 19-9 level (>37 IU/mL) showed significantly higher levels of serum CXCR4 than patients without. The median overall survival (OS) of all patients was 19.53 months. OS was significantly longer in patients with lower CXCR4 levels (≤240.45 pg/mL) compared with those having higher CXCR4 levels (>240.45 pg/mL) (median OS: 26.50 vs 17.03 months, P=0.046). Univariate analysis showed that liver metastasis, no palliative surgery, and higher levels of CXCR4 (>240.45 pg/mL) had a significantly poor prognostic value with regard to OS (POS according to the level of CXCR4 expression. These findings suggest that serum CXCR4 levels may be a useful surrogate marker of clinical outcome in metastatic or recurrent colorectal cancer. PMID:27330310

  13. AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin

    DEFF Research Database (Denmark)

    Kjersem, J B; Thomsen, M; Guren, T;

    2016-01-01

    The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples fro...... markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.54....

  14. High Plasma TIMP-1 and Serum CEA Levels during Combination Chemotherapy for Metastatic Colorectal Cancer Are Significantly Associated with Poor Outcome

    DEFF Research Database (Denmark)

    Aldulaymi, Bahir; Byström, Per; Berglund, Ake;

    2010-01-01

    Objective: To evaluate whether combination chemotherapy leads to early changes in plasma TIMP-1 and serum carcinoembryonic antigen (CEA) levels in patients with metastatic colorectal cancer (mCRC), and whether such changes relate to subsequent objective response, time to progression (TTP) and...... response. Moreover, high levels of plasma TIMP-1 before treatment and at weeks 2 and 4 were significantly associated with short TTP, while high levels of serum CEA at week 4 were significantly associated with short TTP. Finally, high levels of plasma TIMP-1 before and during treatment were significantly...

  15. Could baseline health-related quality of life (QoL) predict overall survival in metastatic colorectal cancer? The results of the GERCOR OPTIMOX 1 study

    OpenAIRE

    Diouf, Momar; Chibaudel, Benoist; Filleron, Thomas; Tournigand, Christophe; Hug De Larauze, Marine; Garcia-Larnicol, Marie-Line; Dumont, Sarah; Louvet, Christophe; Perez-Staub, Nathalie; Hadengue, Alexandra; De Gramont, Aimery; Bonnetain, Franck

    2014-01-01

    International audience Background: Health-related quality of life (QoL) has prognostic value in many cancers. A recent study found that the performance of prognostic systems for metastatic colorectal cancer (mCRC) were improvable. We evaluated the independent prognostic value of QoL for overall survival (OS) and its ability to improve two prognostic systems'performance (Köhne and GERCOR models) for patients with mCRC. Methods: The EQ-5D questionnaire was self-completed before randomization...

  16. Molecular markers and biological targeted therapies in metastatic colorectal cancer: expert opinion and recommendations derived from the 11th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2009.

    Science.gov (United States)

    Van Cutsem, E; Dicato, M; Arber, N; Berlin, J; Cervantes, A; Ciardiello, F; De Gramont, A; Diaz-Rubio, E; Ducreux, M; Geva, R; Glimelius, B; Glynne Jones, R; Grothey, A; Gruenberger, T; Haller, D; Haustermans, K; Labianca, R; Lenz, H J; Minsky, B; Nordlinger, B; Ohtsu, A; Pavlidis, N; Rougier, P; Schmiegel, W; Van de Velde, C; Schmoll, H J; Sobrero, A; Tabernero, J

    2010-06-01

    The article summarizes the expert discussion and recommendations on the use of molecular markers and of biological targeted therapies in metastatic colorectal cancer (mCRC), as well as a proposed treatment decision strategy for mCRC treatment. The meeting was conducted during the 11th ESMO/World Gastrointestinal Cancer Congress (WGICC) in Barcelona in June 2009. The manuscript describes the outcome of an expert discussion leading to an expert recommendation. The increasing knowledge on clinical and molecular markers and the availability of biological targeted therapies have major implications in the optimal management in mCRC. PMID:20534623

  17. Correlations of 18F-fluorothymidine uptake with pathological tumour size, Ki-67 and thymidine kinase 1 expressions in primary and metastatic lymph node colorectal cancer foci

    International Nuclear Information System (INIS)

    To examine correlations of 18F-fluorothymidine (FLT) uptake with pathological tumour size and immunohistochemical Ki-67, and thymidine kinase 1 (TK-1) expressions in primary and metastatic node colorectal cancer foci. Thirty primary cancers (PCs) and 37 metastatic nodes (MNs) were included. FLT uptake was assessed by visual scores (non-visible: 0-1 and visible: 2-4), standardized uptake value (SUV), and correlated with size, Ki-67, and TK-1. SUV was measured in visible lesions. FLT heterogeneity was assessed by visual scores (no heterogeneous uptake: 0 and heterogeneous uptake: 1-4). Forty-two lesions were visible. The visible group showed significantly higher values than the non-visible group in size, Ki-67, and TK-1 (each p 0.05). Heterogeneous FLT uptake was noted in 73 % (22/30) of PCs. FLT uptake correlated with size. Heterogeneous FLT distribution in colorectal cancers may be one of the causes of weak or lack of FLT uptake/Ki-67 or TK-1 correlation. (orig.)

  18. Wnt3a expression is associated with MMP-9 expression in primary tumor and metastatic site in recurrent or stage IV colorectal cancer

    International Nuclear Information System (INIS)

    The wnt/β-catenin signaling pathway is known to affect in cancer oncogenesis and progression by interacting with the tumor microenvironment. However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been thoroughly studied. In the present study, we investigated the expression of wnt protein and the concordance rate in primary tumor and metastatic sites in CRC. To determine the relationship of wnt proteins with invasion related protein, we also analyzed the association between wnt protein expression and the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2). Tumor tissue was obtained from eighty-three paraffin- embedded blocks which were using resected tissue from both the primary tumor and metastatic sites for each patient. We performed immunohistochemical staining for wnt3a, wnt5a, β-catenin, MMP-9 and VEGFR-2. Wnt3a, wnt5a, β-catenin, and MMP-9 expression was high; the proteins were found in over 50% of the primary tumors, but the prevalence was lower in tissue from metastatic sites. The concordance rates between the primary tumor and metastatic site were 76.2% for wnt5a and 79.4% for wnt3a and β-catenin, but VEGFR-2 was expressed in 67.4% of the metastatic sites even when not found in the primary tumor. Wnt3a expression in primary tumors was significantly associated with lymph node involvement (p = 0.038) and MMP-9 expression in the primary tumor (p = 0.0387), mesenchyme adjacent to tumor (p = 0.022) and metastatic site (p = 0.004). There was no other relationship in the expression of these proteins. Vascular invasion in primary tumor tissue may be a potential prognostic marker for liver metastasis, but no significant association was observed among the wnt protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, β-catenin expression was significantly correlated with overall survival (p = 0.05). Wnt3a and wnt5a expression had a concordance rate higher than 60% with a

  19. The prognostic values of EGFR expression and KRAS mutation in patients with synchronous or metachronous metastatic colorectal cancer

    International Nuclear Information System (INIS)

    The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway is an important pathway in the carcinogenesis, invasion and metastasis of colorectal cancers (CRCs). We conducted a retrospective study to determine the prognostic values of EGFR expression and KRAS mutation in patients with metastatic CRC (mCRC) based on synchronous or metachronous status. From October 2002 to March 2012, 205 patients with mCRC were retrospectively analyzed; 98 were found to have metachronous mCRC while 107 were found to have synchronous mCRC. The EGFR expressions were determinate by IHC (immunohistochemistry) analysis and categorized 1+ (weak intensity), 2+ (moderate intensity), and 3+ (strong intensity). Genomic DNA was isolated from frozen primary CRC tissues and direct sequencing of KRAS was performed. The clinicopathological features of these mCRC patients were retrospectively investigated according to EGFR expression and KRAS mutation status. Moreover, we analyzed the prognostic values of EGFR expression and KRAS mutation among these patients. Of the 205 patients with mCRC, EGFR expression was analyzed in 167 patients, and positive EGFR expression was noted in 140 of those patients (83.8%). KRAS mutation was investigated in 205 patients and mutations were noted in 88 of those patients (42.9%). In patients with metachronous mCRC, positive EGFR expression was significantly correlated with well-and moderately-differentiated tumors (P = 0.028), poorer disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P < 0.001). Furthermore, positive EGFR expression was a significant independent prognostic factor of DFS (P = 0.006, HR: 4.012, 95% CI: 1.130–8.445) and OS (P = 0.028, HR: 3.090, 95% CI: 1.477–10.900) in metachronous mCRC patients. KRAS mutation status was not significantly related to DFS and OS of patients with metachronous mCRC; likewise, KRAS mutation status was not significantly different in the progression-free survival (PFS) and OS of patients with

  20. A Novel Computational Tool for Mining Real-Life Data: Application in the Metastatic Colorectal Cancer Care Setting

    Science.gov (United States)

    Siegelmann-Danieli, Nava; Farkash, Ariel; Katzir, Itzhak; Vesterman Landes, Janet; Rotem Rabinovich, Hadas; Lomnicky, Yossef; Carmeli, Boaz; Parush-Shear-Yashuv, Naama

    2016-01-01

    Background Randomized clinical trials constitute the gold-standard for evaluating new anti-cancer therapies; however, real-life data are key in complementing clinically useful information. We developed a computational tool for real-life data analysis and applied it to the metastatic colorectal cancer (mCRC) setting. This tool addressed the impact of oncology/non-oncology parameters on treatment patterns and clinical outcomes. Methods The developed tool enables extraction of any computerized information including comorbidities and use of drugs (oncological/non-oncological) per individual HMO member. The study in which we evaluated this tool was a retrospective cohort study that included Maccabi Healthcare Services members with mCRC receiving bevacizumab with fluoropyrimidines (FP), FP plus oxaliplatin (FP-O), or FP plus irinotecan (FP-I) in the first-line between 9/2006 and 12/2013. Results The analysis included 753 patients of whom 15.4% underwent subsequent metastasectomy (the Surgery group). For the entire cohort, median overall survival (OS) was 20.5 months; in the Surgery group, median duration of bevacizumab-containing therapy (DOT) pre-surgery was 6.1 months; median OS was not reached. In the Non-surgery group, median OS and DOT were 18.7 and 11.4 months, respectively; no significant OS differences were noted between FP-O and FP-I, whereas FP use was associated with shorter OS (12.3 month; p <0.002; notably, these patients were older). Patients who received both FP-O- and FP-I-based regimens achieved numerically longer OS vs. those who received only one of these regimens (22.1 [19.9–24.0] vs. 18.9 [15.5–21.9] months). Among patients assessed for wild-type KRAS and treated with subsequent anti-EGFR agent, OS was 25.4 months and 18.7 months for 124 treated vs. 37 non-treated patients (non-significant). Cox analysis (controlling for age and gender) identified several non-oncology parameters associated with poorer clinical outcomes including concurrent use of

  1. The cost of systemic therapy for metastatic colorectal carcinoma in Slovenia: discrepancy analysis between cost and reimbursement

    International Nuclear Information System (INIS)

    The aim of the study was to estimate the direct medical costs of metastatic colorectal cancer (mCRC) treated at the Institute of Oncology Ljubljana and to question the healthcare payment system in Slovenia. Using an internal patient database, the costs of mCRC patients were estimated in 2009 by examining (1) mCRC direct medical related costs, and (2) the cost difference between payment received by Slovenian health insurance and actual mCRC costs. Costs were analysed in the treatment phase of the disease by assessing the direct medical costs of hospital treatment with systemic therapy together with hospital treatment of side effects, without assessing radiotherapy or surgical treatment. Follow-up costs, indirect medical costs, and nonmedical costs were not included. A total of 209 mCRC patients met all eligibility criteria. The direct medical costs of mCRC hospitalization with systemic therapy in Slovenia for 2009 were estimated as the cost of medications (cost of systemic therapy + cost of drugs for premedication) + labor cost (the cost of carrying out systemic treatment) + cost of lab tests + cost of imaging tests + KRAS testing cost + cost of hospital treatment due to side effects of mCRC treatment, and amounted to €3,914,697. The difference between the cost paid by health insurance and actual costs, estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009, was €1,900,757.80. The costs paid to the Institute of Oncology Ljubljana by health insurance for treating mCRC with systemic therapy do not match the actual cost of treatment. In fact, the difference between the payment and the actual cost estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009 was €1,900,757.80. The model Australian Refined Diagnosis Related Groups (AR-DRG) for cost assessment in oncology being currently used

  2. A Novel Computational Tool for Mining Real-Life Data: Application in the Metastatic Colorectal Cancer Care Setting.

    Directory of Open Access Journals (Sweden)

    Nava Siegelmann-Danieli

    Full Text Available Randomized clinical trials constitute the gold-standard for evaluating new anti-cancer therapies; however, real-life data are key in complementing clinically useful information. We developed a computational tool for real-life data analysis and applied it to the metastatic colorectal cancer (mCRC setting. This tool addressed the impact of oncology/non-oncology parameters on treatment patterns and clinical outcomes.The developed tool enables extraction of any computerized information including comorbidities and use of drugs (oncological/non-oncological per individual HMO member. The study in which we evaluated this tool was a retrospective cohort study that included Maccabi Healthcare Services members with mCRC receiving bevacizumab with fluoropyrimidines (FP, FP plus oxaliplatin (FP-O, or FP plus irinotecan (FP-I in the first-line between 9/2006 and 12/2013.The analysis included 753 patients of whom 15.4% underwent subsequent metastasectomy (the Surgery group. For the entire cohort, median overall survival (OS was 20.5 months; in the Surgery group, median duration of bevacizumab-containing therapy (DOT pre-surgery was 6.1 months; median OS was not reached. In the Non-surgery group, median OS and DOT were 18.7 and 11.4 months, respectively; no significant OS differences were noted between FP-O and FP-I, whereas FP use was associated with shorter OS (12.3 month; p <0.002; notably, these patients were older. Patients who received both FP-O- and FP-I-based regimens achieved numerically longer OS vs. those who received only one of these regimens (22.1 [19.9-24.0] vs. 18.9 [15.5-21.9] months. Among patients assessed for wild-type KRAS and treated with subsequent anti-EGFR agent, OS was 25.4 months and 18.7 months for 124 treated vs. 37 non-treated patients (non-significant. Cox analysis (controlling for age and gender identified several non-oncology parameters associated with poorer clinical outcomes including concurrent use of diuretics and proton

  3. Prognostic signiifcance ofthe pre-chemotherapy lymphocyte-to-monocyte ratio inpatients withpreviously untreated metastatic colorectal cancer receiving FOLFOX chemotherapy

    Institute of Scientific and Technical Information of China (English)

    GuiNanLin; PanPanLiu; DongYingLiu; JieWenPeng; JianJunXiao; ZhongJunXia

    2016-01-01

    Background:As a surrogate marker of systemic inlfammation, the lymphocyte‑to‑monocyte ratio (LMR) is an independent prognostic factor for various malignancies. This study investigated the prognostic signiifcance of the pre‑chemotherapy LMR in patients with previously untreated metastatic colorectal cancer (mCRC) receiving chemotherapy. Methods:The present study included newly diagnosed mCRC patients treated between January 2005 and Decem‑ber 2013 with FOLFOX chemotherapy, speciifcally oxaliplatin 180mg/m2 on day 1, with leucovorin 400mg/m2 administered as a 2‑hour infusion before the administration of 5‑lfuorouracil 400mg/m2 as an intravenous bolus injection, and 5‑lfuorouracil 2400mg/m2 as a 46‑h infusion immediately after 5‑lfuorouracil bolus injection. The LMR was calculated as the absolute count of lymphocytes divided by the absolute count of monocytes. COX proportional hazards analysis was performed to evaluate the association of LMR with survival outcomes. Results:A total of 488 patients were included. Patients with high pre‑chemotherapy LMR experienced signiif‑cant improvements in progression‑free survival (PFS, 9.2 vs. 7.6months,P<0.001) and overall survival (OS, 19.4 vs. 16.6months,P<0.001) compared with patients with low pre‑chemotherapy LMR. Subsequent COX multivariate analysis showed that high pre‑chemotherapy LMR (≥3.11) was an independent favorable prognostic factor for PFS and OS. Additionally, patients whose LMR remained high (high–high subgroup), increased (low–high subgroup), or decreased (high–low subgroup) following chemotherapy showed better results in terms of PFS and OS than patients whose LMR remained low (low–low subgroup) after chemotherapy. Conclusions:For patients with previously untreated mCRC receiving FOLFOX chemotherapy, an elevated pre‑chem‑otherapy LMR is an independent favorable prognostic factor for PFS and OS, and changes in the LMR before and after chemotherapy seem to predict the

  4. UGT1A1 gene polymorphism: Impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Christoph Schulz; Volker Heinemann; Andreas Schalhorn; Nikolas Moosmann; Thomas Zwingers; Stefan Boeck; Clemens Giessen; Hans-Joachim Stemmler

    2009-01-01

    AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 ( UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a lowdose weekly irinotecan chemotherapeutic regimen.METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC.RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) ( 6/6) 39.0%,heterozygous genotype ( 6/7) 49.5%, and homozygous genotype ( 7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the ( 6/7, 7/7) or the WT genotype ( 6/6) (44.3% vs 43.2%, P = 0.75).Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the ( 6/6) when compared to the ( 6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [( 6/7, 7/7) vs ( 6/6); 13.0% vs 6.2%, P =0.08], treatment delays [( 6/7, 7/7) vs ( 6/6); 25.1% vs 19.3%, P = 0.24] or dose reductions [( 6/7, 7/7) vs ( 6/6); 21.5% vs 27.2%, P = 0.07].CONCLUSION: This analysis demonstrates the nonsignificant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.

  5. Tumor infiltration by chemokine receptor 7 (CCR7)+ T-lymphocytes is a favorable prognostic factor in metastatic colorectal cancer

    OpenAIRE

    Correale, Pierpaolo; Rotundo, Maria Saveria; Botta, Cirino; del Vecchio, Maria Teresa; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

    2012-01-01

    The immune interactions occurring within the tumor microenvironment have a critical role in determining the outcome of colorectal cancer patients. We carried-out an immunohistochemical analysis of tumor infiltrating T-lymphocytes expressing chemokine receptor 7 (CCR7) in a series of colorectal cancer patients enrolled in a prospective clinical trial. We demonstrated that a high tumor infiltration score of this lymphocyte subset is predictive of longer progression free survival and overall sur...

  6. A systematic review of salvage therapy to patients with metastatic colorectal cancer previously treated with fluorouracil, oxaliplatin and irinotecan +/- targeted therapy

    DEFF Research Database (Denmark)

    Nielsen, Dorte Lisbet; Palshof, Jesper Andreas; Larsen, Finn Ole;

    2014-01-01

    third-line setting. We therefore performed a systematic review of the current literature on third or later lines of treatment to patients with metastatic colorectal cancer after the use of approved drugs or combinations. METHODS: A computer-based literature search was carried out using Pubmed and data...... capecitabine, mitomycin C, and gemcitabine have limited or no activity. Retreatment with oxaliplatin might be an option in selected patients. In addition, rechallenge with EGFR-directed therapy might be a valuable strategy. Data also suggest that angiogenetic drugs may postpone further progression and prolong...... survival. Lately, regorafinib has been approved. In conclusion, our current knowledge is based on many retrospective studies, some phase II studies and very few randomized clinical trials. Further prospective phase III trials comparing an investigational drug or combination with best supportive care in...

  7. Impact of third-line treatment with irinotecan plus cetuximab on non-tumor standardized uptake values in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Skougaard, Kristin; Nielsen, Anne Lerberg;

    2012-01-01

    The correct interpretation of metabolic response in cancer cells to therapy requires knowledge of how tumor-free tissue responds to the same treatment. The aim of this study was to evaluate standardized uptake values (SUVs) in tumor-free regions of patients with metastatic colorectal cancer prior...... to and following therapy, via the use of 18-fluoride fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). On baseline 18F-FDG PET/CT scans (n=51), volumes of interest (VOI) were obtained from tumor-free tissue (aortic arch, liver and spleen) and SUVs...... normalized to total body mass were registered. The procedure was repeated for a follow-up scan two weeks following a single administration of the third-line treatment with irinotecan plus cetuximab. The mean differences in SUV prior to and following therapy were non-significant (P>0.05) in all the registered...

  8. Human monoclonal antibody 99mTc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment

    International Nuclear Information System (INIS)

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%. (orig.). With 3 figs., 1 tab

  9. Human monoclonal antibody {sup 99m}Tc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment

    Energy Technology Data Exchange (ETDEWEB)

    Krause, B.J. [Department of Nuclear Medicine, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main (Germany); Baum, R.P. [Department of Nuclear Medicine, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main (Germany); Staib-Sebler, E. [Department of General and Abdominal Surgery, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main (Germany); Lorenz, M. [Department of General and Abdominal Surgery, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main (Germany); Niesen, A. [Department of Nuclear Medicine, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main (Germany); Hoer, G. [Department of Nuclear Medicine, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main (Germany)

    1997-01-01

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of {sup 99m}Tc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%. (orig.). With 3 figs., 1 tab.

  10. Human monoclonal antibody 99mTc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment.

    Science.gov (United States)

    Krause, B J; Baum, R P; Staib-Sebler, E; Lorenz, M; Niesen, A; Hör, G

    1997-01-01

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%. PMID:9044881

  11. EGF61A>G polymorphism as predictive marker of clinical outcome to first-line capecitabine and oxaliplatin in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Andersen, R F; Jensen, L H; Ploen, J; Jakobsen, Anders

    2010-01-01

    BACKGROUND: The purpose of the present study was to investigate polymorphisms related to the metabolism of fluoropyrimidine and oxaliplatin, thymidylate synthase (TS) and excision repair cross-complementing gene 1 (ERCC1) 118, in metastatic colorectal cancer patients treated with capecitabine and...... oxaliplatin (XELOX). We also investigated the importance of the EGF61A>G polymorphism, which holds a functional influence on the tyrosine kinase receptor regulation. Materials and methods: We included 68 patients treated with first-line XELOX. Polymorphism analyses were carried out on pretreatment blood...... samples. Response was evaluated according to the RECIST. Survival analysis was described by the Kaplan-Meier method and log-rank testing. RESULTS: The overall response rate was 38% and the median overall survival 19.4 months. A favorable outcome was seen in patients with the EGF61A/G genotype compared...

  12. High Plasma TIMP-1 and Serum CEA Levels during Combination Chemotherapy for Metastatic Colorectal Cancer Are Significantly Associated with Poor Outcome

    DEFF Research Database (Denmark)

    Aldulaymi, Bahir; Byström, Per; Berglund, Ake; Christensen, Ib J; Brünner, Nils; Nielsen, Hans Jørgen; Glimelius, Bengt

    overall survival. Materials and Methods: Eighty-eight patients with mCRC were included. Blood samples were collected before initiation and after 2, 4 and 6 weeks of treatment with an irinotecan-5-fluorouracil combination. Plasma TIMP-1 and serum CEA levels were determined by validated ELISA platforms. The...... associated with poor overall survival; p <0.0001 in all 4 determinations. A similar association between serum CEA and overall survival could only be demonstrated before treatment. Conclusion: Median plasma TIMP-1 or serum CEA levels do not change significantly during the first 6 weeks of chemotherapy for m......Objective: To evaluate whether combination chemotherapy leads to early changes in plasma TIMP-1 and serum carcinoembryonic antigen (CEA) levels in patients with metastatic colorectal cancer (mCRC), and whether such changes relate to subsequent objective response, time to progression (TTP) and...

  13. Regorafenib: A novel tyrosine kinase inhibitor: A brief review of its therapeutic potential in the treatment of metastatic colorectal carcinoma and advanced gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    P Thangaraju

    2015-01-01

    Full Text Available Regorafenib is a novel oral multitargeted tyrosine kinase inhibitor having both antitumor and anti-angiogenic activities. Regorafenib was recently approved by US Food and Drug Administration in February 25, 2013 in the treatment for patients with advanced gastrointestinal stromal tumor and for the treatment of patients with metastatic colorectal carcinoma after disease progression or intolerance to imatinib mesylate and sunitinib therapy. Oral regorafenib demonstrates a high level of efficacy with acceptable tolerability with the 160 mg daily for 3 weeks followed by 1 week off schedule; a continuous schedule could be of interest. Hypertension, mucositis, hand foot skin reaction, diarrhea and asthenia are the most common side-effects. Regardless of these encouraging results, studies investigating, adjuvant and neoadjuvant settings are awaited, as well as trials using regorafenib in combination with chemotherapy or other targeted therapies. Clinical trials investigating regorafenib in other tumor types are ongoing.

  14. Correlations of {sup 18}F-fluorothymidine uptake with pathological tumour size, Ki-67 and thymidine kinase 1 expressions in primary and metastatic lymph node colorectal cancer foci

    Energy Technology Data Exchange (ETDEWEB)

    Nakajo, Masatoyo; Nakajo, Masayuki [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Kajiya, Yoriko; Tani, Atsushi [Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Goto, Yuko; Higashi, Michiyo [Kagoshima University, Department of Human Pathology, Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544 (Japan); Jinguji, Megumi; Fukukura, Yoshihiko [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Tanaka, Sadao [Nanpuh Hospital, Department of Pathology, Kagoshima (Japan)

    2014-12-15

    To examine correlations of {sup 18}F-fluorothymidine (FLT) uptake with pathological tumour size and immunohistochemical Ki-67, and thymidine kinase 1 (TK-1) expressions in primary and metastatic node colorectal cancer foci. Thirty primary cancers (PCs) and 37 metastatic nodes (MNs) were included. FLT uptake was assessed by visual scores (non-visible: 0-1 and visible: 2-4), standardized uptake value (SUV), and correlated with size, Ki-67, and TK-1. SUV was measured in visible lesions. FLT heterogeneity was assessed by visual scores (no heterogeneous uptake: 0 and heterogeneous uptake: 1-4). Forty-two lesions were visible. The visible group showed significantly higher values than the non-visible group in size, Ki-67, and TK-1 (each p < 0.05). Size correlated significantly with visual score (PC; ρ = 0.74 and MN; ρ = 0.63), SUVmax (PC; ρ = 0.49, and MN; ρ = 0.76), and SUVmean (PC; ρ = 0.40 and MN; ρ = 0.76) (each p < 0.05). Visual score correlated significantly with size (ρ = 0.86), Ki-67max (ρ = 0.35), Ki-67mean (ρ = 0.38), TK-1max (ρ = 0.35) and TK-1mean (ρ = 0.25) (each p < 0.05). No significant correlations were found between FLT uptake and Ki-67 or TK-1 in 42 visible lesions (each p > 0.05). Heterogeneous FLT uptake was noted in 73 % (22/30) of PCs. FLT uptake correlated with size. Heterogeneous FLT distribution in colorectal cancers may be one of the causes of weak or lack of FLT uptake/Ki-67 or TK-1 correlation. (orig.)

  15. Immunomodulatory effects in a phase II study of lenalidomide combined with cetuximab in refractory KRAS-mutant metastatic colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Anita K Gandhi

    Full Text Available This study assessed the immunomodulatory effects in previously treated KRAS-mutant metastatic colorectal cancer patients participating in a phase II multicenter, open-label clinical trial receiving lenalidomide alone or lenalidomide plus cetuximab. The main findings show the T cell immunostimulatory properties of lenalidomide as the drug induced a decrease in the percentage CD45RA(+ naïve T cells 3-fold while increasing the percentage HLA-DR(+ activated T helper cells and percentage total CD45RO(+ CD8(+ memory T cytotoxic cells, 2.6- and 2.1-fold respectively (p<0.0001. In addition, lenalidomide decreased the percentage of circulating CD19(+ B cells 2.6-fold (p<0.0001. Lenalidomide increased a modest, yet significant, 1.4-fold change in the percentage of circulating natural killer cells. Our findings indicate that lenalidomide significantly activates T cells, suggestive of an immunotherapeutic role for this drug in settings of maintenance therapy and tumor immunity. Furthermore, reported for the first time is the effect of lenalidomide in combination with cetuximab on T cell function, including increases in circulating naïve and central memory T cells. In summary, lenalidomide and cetuximab have significant effects on circulating immune cells in patients with colorectal carcinoma.ClinicalTrials.gov NCT01032291.

  16. Prognostic role of serum concentrations of high-sensitivity C-reactive protein in patients with metastatic colorectal cancer: results from the ITACa trial

    Science.gov (United States)

    Scarpi, Emanuela; Maltoni, Paolo; Dorizzi, Romolo M.; Passardi, Alessandro; Frassineti, Giovanni Luca; Cortesi, Pietro; Giannini, Maria Benedetta; Marisi, Giorgia; Amadori, Dino; Lucchesi, Alessandro

    2016-01-01

    Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized “Italian Trial in Advanced Colorectal Cancer (ITACa)” to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at −80°C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (≥ 13.1 mg/L) were associated with poorer median PFS (p < 0.0001) and OS (p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma. PMID:26848624

  17. Let-7 miRNA-binding site polymorphism in the KRAS 3′UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/− cetuximab

    Directory of Open Access Journals (Sweden)

    Kjersem Janne B

    2012-11-01

    Full Text Available Abstract Background Recent studies have reported associations between a variant allele in a let-7 microRNA complementary site (LCS6 within the 3′untranslated region (3′UTR of KRAS (rs61764370 and clinical outcome in metastatic colorectal cancer (mCRC patients receiving cetuximab. The variant allele has also been associated with increased cancer risk. We aimed to reveal the incidence of the variant allele in a colorectal cancer screening population and to investigate the clinical relevance of the variant allele in mCRC patients treated with 1st line Nordic FLOX (bolus 5-fluorouracil/folinic acid and oxaliplatin +/− cetuximab. Methods The feasibility of the variant allele as a risk factor for CRC was investigated by comparing the LCS6 gene frequencies in 197 CRC patients, 1060 individuals with colorectal polyps, and 358 healthy controls. The relationship between clinical outcome and LCS6 genotype was analyzed in 180 mCRC patients receiving Nordic FLOX and 355 patients receiving Nordic FLOX + cetuximab in the NORDIC-VII trial (NCT00145314. Results LCS6 frequencies did not vary between CRC patients (23%, individuals with polyps (20%, and healthy controls (20% (P = 0.50. No statistically significant differences were demonstrated in the NORDIC-VII cohort even if numerically increased progression-free survival (PFS and overall survival (OS were found in patients with the LCS6 variant allele (8.5 (95% CI: 7.3-9.7 months versus 7.8 months (95% CI: 7.4-8.3 months, P = 0.16 and 23.5 (95% CI: 21.6-25.4 months versus 19.5 months (95% CI: 17.8-21.2 months, P = 0.31, respectively. Addition of cetuximab seemed to improve response rate more in variant carriers than in wild-type carriers (from 35% to 57% versus 44% to 47%, however the difference was not statistically significant (interaction P = 0.16. Conclusions The LCS6 variant allele does not seem to be a risk factor for development of colorectal polyps or CRC. No statistically significant effect of the

  18. Observational cohort study focused on treatment continuity of patients administered XELOX plus bevacizumab for previously untreated metastatic colorectal cancer

    OpenAIRE

    Kotaka, Masahito

    2016-01-01

    Masahito Kotaka,1 Fusao Ikeda,2 Masaki Tsujie,3 Shinichi Yoshioka,4 Yoshihiko Nakamoto,5 Takaaki Ishii,6 Takahisa Kyogoku,7 Takeshi Kato,8 Akihito Tsuji,9 Michiya Kobayashi101Gastrointestinal Cancer Center, Sano Hospital, Kobe, Hyogo, 2Department of Surgery, Kohka Public Hospital, Koka, Shiga, 3Department of Colorectal Surgery, Sakai City Medical Center, Sakai, Osaka, 4Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, 5Department of Surgery, Seikei-kai Chiba M...

  19. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study

    International Nuclear Information System (INIS)

    Integument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial. Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity. 154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity. First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity. ClinicalTrials.gov NCT00508404

  20. Associations between deepness of response and clinical outcomes among Japanese patients with metastatic colorectal cancer treated with second-line FOLFIRI plus cetuximab

    Directory of Open Access Journals (Sweden)

    Osumi H

    2015-08-01

    Full Text Available Hiroki Osumi, Satoshi Matsusaka, Mitsukuni Suenaga, Eiji Shinozaki, Nobuyuki Mizunuma Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan Background: In the FIRE-3 trial, overall survival (OS was significantly longer in patients treated with FOLFIRI plus cetuximab (C-mab than in those treated with FOLFIRI plus bevacizumab (Bev, but progression-free survival (PFS was not significantly different. This may be associated with the deepness of response (DpR in patients treated with FOLFIRI plus C-mab. We aimed to evaluate the relationship between clinical outcome and DpR in metastatic colorectal cancer (mCRC patients treated with second-line FOLFIRI plus C-mab.Methods: A total of 112 patients with histopathologically confirmed mCRC treated with second-line FOLFIRI in combination with C-mab (N=42 or Bev (N=70 were retrospectively enrolled between October 2008 and June 2013. The relationship between DpR and clinical outcome in patients treated with FOLFIRI plus C-mab or Bev was determined.Results: Forty-two patients treated with FOLFIRI plus C-mab had a mean DpR of 6.1% (interquartile range: -13.7%, 20.8% and a minimum DpR of -62.7%. On the other hand, 70 patients treated with FOLFIRI plus Bev had a mean DpR of 0% (interquartile range: -16%, 10% and a minimum DpR of -111%. DpR ≥30% was associated with significantly longer OS and PFS when compared with DpR ≤30% in patients given FOLFIRI plus C-mab. DpR (≥30% was independently associated with prolongation of OS and PFS. In patients treated with FOLFIRI plus C-mab, there was a moderate positive correlation between DpR and clinical outcomes (OS: r=0.51, P<0.001; PFS: r=0.54, P<0.001.Conclusion: FOLFIRI plus C-mab yielded a stronger correlation between DpR and clinical outcomes. These results indicate the potential of DpR as a new measure of efficacy in mCRC patients treated with second-line chemotherapy plus C-mab. Keywords: deepness of

  1. Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level

    International Nuclear Information System (INIS)

    Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression. Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses. We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02). Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for

  2. Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level

    Directory of Open Access Journals (Sweden)

    Hall David A

    2008-07-01

    Full Text Available Abstract Background Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression. Methods Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses. Results We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005. A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02. Conclusion Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate

  3. A gene expression predictor of response to EGFR-targeted therapy stratifies progression-free survival to cetuximab in KRAS wild-type metastatic colorectal cancer

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    Black Esther P

    2009-05-01

    Full Text Available Abstract Background The anti-EGFR monoclonal antibody cetuximab is used in metastatic colorectal cancer (CRC, and predicting responsive patients garners great interest, due to the high cost of therapy. Mutations in the KRAS gene occur in ~40% of CRC and are a negative predictor of response to cetuximab. However, many KRAS-wildtype patients do not benefit from cetuximab. We previously published a gene expression predictor of sensitivity to erlotinib, an EGFR inhibitor. The purpose of this study was to determine if this predictor could identify KRAS-wildtype CRC patients who will benefit from cetuximab therapy. Methods Microarray data from 80 metastatic CRC patients subsequently treated with cetuximab were extracted from the study by Khambata-Ford et al. The study included KRAS status, response, and PFS for each patient. The gene expression data were scaled and analyzed using our predictive model. An improved predictive model of response was identified by removing features in the 180-gene predictor that introduced noise. Results Forty-three of eighty patients were identified as harboring wildtype-KRAS. When the model was applied to these patients, the predicted-sensitive group had significantly longer PFS than the predicted-resistant group (median 88 days vs. 56 days; mean 117 days vs. 63 days, respectively, p = 0.008. Kaplan-Meier curves were also significantly improved in the predicted-sensitive group (p = 0.0059, HR = 0.4109. The model was simplified to 26 of the original 180 genes and this further improved stratification of PFS (median 147 days vs. 56.5 days in the predicted sensitive and resistant groups, respectively, p Conclusion Our model of sensitivity to EGFR inhibition stratified PFS following cetuximab in KRAS-wildtype CRC patients. This study represents the first true external validation of a molecular predictor of response to cetuximab in KRAS-WT metastatic CRC. Our model may hold clinical utility for identifying patients responsive

  4. A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification

    DEFF Research Database (Denmark)

    Tarpgaard, Line S.; Qvortrup, Camilla; Nygård, Sune Boris;

    2016-01-01

    UNLABELLED: ᅟ: The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2...... in patients with breast cancer and thus could be an alternative option for patients with CRC and amplified TOP2A gene. We have previously analysed the frequency of TOP2A gene aberrations in CRC and found that 46.6 % of these tumors had TOP2A copy gain and 2.0 % had loss of TOP2A when compared to adjacent...... and the knowledge gained from treatment of breast cancer patients, we have initiated a prospective clinical, phase II protocol using epirubicin (90 mg/m2 iv q 3 weeks) in mCRC patients, who are refractory to treatment with oxaliplatin. METHODS/DESIGN: The study is an open label, single arm, phase II study...

  5. A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification

    DEFF Research Database (Denmark)

    Tarpgaard, Line S; Qvortrup, Camilla; Nygård, Sune B; Nielsen, Signe L; Andersen, Diana R; Jensen, Niels Frank; Stenvang, Jan; Detlefsen, Sönke; Brünner, Nils; Pfeiffer, Per

    2016-01-01

    knowledge gained from treatment of breast cancer patients, we have initiated a prospective clinical, phase II protocol using epirubicin (90 mg/m2 iv q 3 weeks) in mCRC patients, who are refractory to treatment with oxaliplatin. METHODS/DESIGN: The study is an open label, single arm, phase II study...... patients with breast cancer and thus could be an alternative option for patients with CRC and amplified TOP2A gene. We have previously analysed the frequency of TOP2A gene aberrations in CRC and found that 46.6% of these tumors had TOP2A copy gain and 2.0% had loss of TOP2A when compared to adjacent normal......UNLABELLED: The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2A...

  6. THE HIGH ACTIVITY OF VECTIBIX IN PATIENTS WITH METASTATIC COLORECTAL CANCER WITH THE RAS WILD-TYPE GENE

    Directory of Open Access Journals (Sweden)

    N. N. Semenov

    2015-02-01

    Full Text Available High-efficiency inhibitors of EGFR (panitumumab and cetuximab in combination with chemotherapy in patients with advanced colorectal cancer is the result of the targeting special group of the patients based on studies of genes. Previously it was shown that the presence of mutation in exon 2 of KRAS gene (40 % of patients determines the effectivity of this group of drugs. However, the search for additional indicators was continued. The result is that the presence of mutations in exons 3 and 4 of KRAS gene and in exons 2, 3 and 4 of NRAS gene also predict EGFR inhibitors efficacy. These mutations are defined in 10 % of patients. Analysis showed that the efficiency of panitumumab and cetuximab in combination with chemotherapy significantly increased in patients with wild-type KRAS and NRAS.

  7. Patterns of Resection among Patients with Hepatic-Only Metastatic Colorectal Cancer a Single Institution Experience and Review

    Directory of Open Access Journals (Sweden)

    K. I. Quintyne

    2012-01-01

    Full Text Available Problem statement: Hepatic-only metastasis in colorectal cancer is not a rare clinical finding and can account for 30% of cases. However, only 10-25% of cases are suitable for hepatic resection as part of their treatment pathway. We sought to document our own findings by reviewing patients with hepatic-only disease. Approach: A retrospective analysis was designed to include all patients seen at our institution from 1st January 2000 until 30th June 2010 and information as derived from the patients� records. Results: Forty-four (44 patients were found, with an average age of 60.8 years and a male preponderance. The majority of patients (approximately 57% with hepatic-only metastases developed their disease following adjuvant therapy. Better overall survival was seen when a primary tumor had a low grade of histological differentiation and fewer than 3 hepatic lesions appreciated on conventional radiology. Better outcome was seen in patients who underwent hepatic resection. Conclusion: Patients with hepatic-only metastases are not uncommon within our institution. Hepatic resection afforded better outcome and compares favorably with published literature.

  8. A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Suenaga M

    2015-03-01

    Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Keisho Chin,1 Toshiharu Yamaguchi2 1Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan Background: Triweekly capecitabine plus irinotecan (XELIRI is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI in metastatic colorectal cancer (mCRC because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV as second-line chemotherapy for mCRC.Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin and BV and had a UGT1A1 genotype of wild-type or heterozygous for UGT1A1*6 or *28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5 mg/kg on day 1 every 2 weeks. The phase I study consisted of two steps (irinotecan 150 and 180 mg/m2, and dose-limiting toxicity was assessed during the first treatment cycle. The primary endpoint of the phase II study was progression-free survival (PFS.  Results: The recommended dose of irinotecan was determined to be 180 mg/m2 in the phase I study. Between November 2010 and August 2013, 44 patients were enrolled in phase II. The patients’ characteristics were as follows (N=44: median age, 60 years (range 32–80; male/female, 21/23; and UGT1A1 wild-type/heterozygous, 29/15. The median PFS was 6.8 months (95% confidence interval, 5.3–8.2 months, and the primary endpoint was met. Median overall survival was 18.3 months. The response rate was 22.7%. There was no significant difference in PFS or overall survival according to UGT1A1 status. Grade 3 or higher adverse events were mainly neutropenia in six

  9. Sinusoidal obstruction syndrome (veno-occlusive disease in a patient receiving bevacizumab for metastatic colorectal cancer: a case report

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    Agarwal Vijay

    2008-07-01

    Full Text Available Abstract Introduction We present the case of a patient with colon cancer who, while receiving bevacizumab, developed sinusoidal obstruction syndrome (veno-occlusive disease (SOSVOD. Certain antitumour agents such as 6-mercaptopurine and 6-thioguanine have also been reported to initiate hepatic SOSVOD in isolated cases. There have been no reports so far correlating bevacizumab with SOSVOD. Case presentation A 77-year-old man was being treated with oxaliplatin and a modified de Gramont regimen of 5-fluorouracil for metastatic colon cancer. Bevacizumab (7.5 mg/kg was added from the seventh cycle onwards. Protracted neutropenia and thrombocytopenia led to discontinuation of oxaliplatin after the ninth cycle. A computed tomography scan showed complete response and bevacizumab was continued for another 3 months, after which time the patient developed right hypochondrial pain, transudative ascites, splenomegaly and abnormal liver function tests. Upper gastrointestinal endoscopy showed oesophageal varices. Liver biopsy showed features considered to be consistent with SOSVOD. Bevacizumab was stopped and a policy of watchful waiting was adopted. He tolerated the acute damage to his liver and subsequently the ascites resolved and liver function tests normalised. Conclusion We need to be aware that bevacizumab can cause sinusoidal obstruction syndrome (veno-occlusive disease and that the occurrence of ascites should not be attributed to progressive disease without appropriate evaluation.

  10. A Randomised Controlled Phase II Trial of the Combination of XELOX with Thalidomide for the First-line Treatment of Metastatic Colorectal Cancer

    International Nuclear Information System (INIS)

    To evaluate the efficacy and safety of the combination of XELOX regimen (oxaliplatin plus capecitabine) with thalidomide for the first-line treatment of metastatic colorectal cancer (MCRC). All of the 89 patients with MCRC who fulfilled eligibility criteria were randomly assigned to treatment group (n=44) and control group (n=45). The treatment group received a combination of XELOX with thalidomide and the control group received XELOX alone. Each patient received at least 2 cycles of treatment (1 cycle=21 d). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) as well as disease control rate (DCR). Drug safety and quality of life were also assessed. The median PFS of the treatment and control groups were 5.6 and 5.2 months, respectively. The difference did not have a statistical significance (P=0.307). The ORRs of the two groups also had no statistical difference (34.1% vs. 26.7%, P=0.446). The addition of thalidomide to XELOX significantly improved the DCR (63.6% vs. 42.2%, P=0.043). Among 24 patients with hepatic metastasis in the treatment group, 2 patients satisfied the surgical criteria after treatment but none of 23 patients in the control group did. Grade 3 or 4 constipation in patients treated with thalidomide was significantly increased (20.5% vs. 4.4%, P=0.022) but didn’t result in treatment interruption. The rate of lethargy was increased but the difference between the two groups had no statistical significance (13.6% vs. 4.4%, P=0.130). The quality of life had no statistical difference between the two groups. The combination of XELOX with thalidomide for the first-line treatment of MCRC was well tolerated. Statistically significant improvement was achieved for the DCR but not for PFS

  11. Early post-treatment FDG PET predicts survival after {sup 90}Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Aouf, Anas; Sabet, Amin; Ghamari, Shahab; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Meyer, Carsten; Pieper, Claus C. [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2014-10-29

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with {sup 90}Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent {sup 18}F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUV{sub max}) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p < 0.001) with a median OS of 10 months (95 % CI 3-16) versus 4 months (95 % CI 2-6). Hepatic tumour burden also had significant impact on treatment outcome (p < 0.001) with a median OS of 5 months (95 % CI, 3-7) for patients with >25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using {sup 18}F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  12. Survival improvements associated with access to biological agents: Results from the South Australian (SA) metastatic colorectal cancer (mCRC) registry.

    Science.gov (United States)

    Tomita, Yoko; Karapetis, Christos S; Ullah, Shahid; Townsend, Amanda R; Roder, David; Beeke, Carol; Roy, Amitesh C; Padbury, Rob; Price, Timothy J

    2016-01-01

    Background Randomized controlled trials evaluating biological therapy have shown improvements in survival from metastatic colorectal cancer (mCRC). Subjects in the trials represent a selected proportion of mCRC patients. We have the potential to assess the impact of biological therapy on mCRC outcomes, particularly the effect of bevacizumab, from a population-based clinical registry by comparing two time cohorts with differences in therapy accessibility. Material and methods A retrospective cohort study was performed by analyzing the South Australian (SA) mCRC registry data based on diagnosis in two time periods: 1 February 2006-31 May 2009 (Cohort A) versus 1 June 2009-30 June 2014 (Cohort B). The demarcation for these cohorts was chosen to reflect the change in accessibility of bevacizumab from July 2009. Results Between February 2006 and June 2014, 3308 patients were identified through the SA mCRC registry: 1464 (44%) in Cohort A and 1844 (56%) in Cohort B. 61 and 59% patients in Cohort A and B, respectively received systemic therapy (p = 0.26). Major differences in clinical characteristics were: biological therapy use 18 versus 33% (p rise in bevacizumab administration was observed in Cohort B. Its use in first-line therapy remained relatively low even after the reimbursement, potentially reflecting real world practice where comorbidities, primary in-situ and age may contraindicate its use. mOS improvement over time was attributed to increased access to biological therapy, especially bevacizumab and possibly advance in peri-operative and supportive care. PMID:26878155

  13. The predictive value of microRNA-126 in relation to first line treatment with capecitabine and oxaliplatin in patients with metastatic colorectal cancer

    International Nuclear Information System (INIS)

    MicroRNA-126 is the only microRNA (miRNA) known to be endothelial cell-specific influencing angiogenesis in several ways. The aim of the present study was to analyse the possible predictive value of miRNA-126 in relation to first line capecitabine and oxaliplatin (XELOX) in patients with metastatic colorectal cancer (mCRC). The study included 89 patients with mCRC. In situ hybridization (ISH) was performed to detect miRNA-126 in formalin-fixed paraffin embedded tissue from primary tumours. The expression of miRNA-126, area per image (μm2), was measured using image analysis. Clinical response was evaluated according to RECIST. Progression free survival (PFS) was compared using the Kaplan-Meier method and the log rank test. Tumours were classified as low or high miRNA-126 expressing tumours using the median value from the patients with response as cut-off. The median miRNA-126 expression level was significantly higher in patients responding to XELOX, 3629 μm2 (95% CI, 2566-4846), compared to the patients not responding, 1670 μm2 (95% CI, 1436-2041), p < 0.0001. The positive predictive value was 90%, and the negative predictive value was 71%. The median PFS of patients with high expressing tumours was 11.5 months (95% CI, 9.0-12.7 months) compared to 6.0 months (95% CI, 4.8-6.9 months) for patients with low expressing tumours, p < 0.0001. Angiogenesis quantified by ISH of miRNA-126 was related to response to first line XELOX in patients with mCRC, translating to a significant difference in PFS. The predictive value of miRNA-126 remains to be further elucidated in prospective studies

  14. Beyond KRAS mutation status: influence of KRAS copy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Mekenkamp Leonie JM

    2012-07-01

    Full Text Available Abstract Background KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor (EGFR antibodies in metastatic colorectal cancer (mCRC. Novel predictive markers are required to further improve the selection of patients for this treatment. We assessed the influence of modification of KRAS by gene copy number aberration (CNA and microRNAs (miRNAs in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab. Methods Formalin-fixed paraffin-embedded primary tumour tissue was used from 34 mCRC patients in a phase III trial, who were selected based upon their good (n = 17 or poor (n = 17 progression-free survival (PFS upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene copy number at the KRAS locus was assessed using high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR. Results Copy number loss of the KRAS locus was observed in the tumour of 5 patients who were all good responders including patients with a KRAS mutation. Copy number gains in two wild-type KRAS tumours were associated with a poor PFS. In KRAS mutated tumours increased miR-200b and decreased miR-143 expression were associated with a good PFS. In wild-type KRAS patients, miRNA expression did not correlate with PFS in a multivariate model. Conclusions Our results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS might further optimize the selection of mCRC eligible for anti-EGFR therapy.

  15. Evaluation of efficacy and safety of modified infusion of fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) in treatment of metastatic colorectal cancer: a retrospective study of 21 cases

    OpenAIRE

    Wang, Xi-cheng; Wei, Qing; Gao, Jing; Li, Yan-yan; Yan-shuo CAO; Shen, Lin

    2016-01-01

    Objective  To evaluate the safety and preliminary efficacy of mFOLFOXIRI (the combination of irinotecan, oxaliplatin and 5-fluorouracil with reducing dosages) in first-line treatment for Chinese patients with unresectable metastatic colorectal cancer (mCRC). Methods  A total of 21 patients received mFOLFOXIRI treatment: irinotecan 150mg/m2 on day 1, oxaliplatin 85mg/m2 on day 1, leucovorin 200mg/m2 on day 1, and 5-fluorouracil (5-FU) 2800mg/m2 in a 48-h continuous infusion starting on day 1. ...

  16. Asymptomatic dystrophinopathy

    Energy Technology Data Exchange (ETDEWEB)

    Morrone, A. [Univ. of Pittsburgh School of Medicine, PA (United States)]|[Univ. of Florence (Italy); Hoffman, E.P.; Hoop, R.C. [Univ. of Pittsburgh School of Medicine, PA (United States)] [and others

    1997-03-31

    A 4-year-old girl was referred for evaluation for a mild but persistent serum aspartate aminotransferase (AST) elevation detected incidentally during routine blood screening for a skin infection. Serum creatine kinase activity was found to be increased. Immuno-histochemical study for dystrophin in her muscle biopsy showed results consistent with a carrier state for muscular dystrophy. Molecular work-up showed the proposita to be a carrier of a deletion mutation of exon 48 of the dystrophin gene. Four male relatives also had the deletion mutation, yet showed no clinical symptoms of muscular dystrophy (age range 8-58 yrs). Linkage analysis of the dystrophin gene in the family showed a spontaneous change of an STR45 allele, which could be due to either an intragenic double recombination event, or CA repeat length mutation leading to identical size alleles. To our knowledge, this is the first documentation of an asymptomatic dystrophinopathy in multiple males of advanced age. Based on molecular findings, this family would be given a diagnosis of Becker muscular dystrophy. This diagnosis implies the development of clinical symptoms, even though this family is clearly asymptomatic. This report underscores the caution which must be exercised when giving presymptomatic diagnoses based on molecular studies. 28 refs., 4 figs., 1 tab.

  17. Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

    Science.gov (United States)

    Díaz-Rubio, Eduardo; Gómez-España, Auxiliadora; Massutí, Bartomeu; Sastre, Javier; Reboredo, Margarita; Manzano, José Luis; Rivera, Fernando; Safont, MªJosé; Montagut, Clara; González, Encarnación; Benavides, Manuel; Marcuello, Eugenio; Cervantes, Andrés; Martínez de Prado, Purificación; Fernández-Martos, Carlos; Arrivi, Antonio; Bando, Inmaculada; Aranda, E.; Gómez, A.; Massutí, B.; Yuste, A.; Rubio, E. Díaz; Sastre, J.; Valladares, M.; Abad, A.; Rivera, F.; Safont, MªJosé; Gallén, M.; González, E.; Benavides, M.; Marcuello, E.; Tobeña, M.; Cervantes, A.; Martínez de Prado, P.; Fernández-Martos, C.; Arrivi, A.; López-Ladrón, A.; Lacasta, A.; Llanos, M.; Remón, J.; Anton, A.; Vicent, J. Mª.; Gala´n, A.; Dueñas, R.; Tabernero, J. Mª.; Manzano, H.; Gómez, Mª. J.; Alfaro, J.; Losa, F.; Escudero, P.; García, T.; García López, J. L.; de Paredes, Mª L. García; Velasco, A.; Almenar, D.; Vera, R.; García Puche, J. L.; Carrato, A.; Lescure, A. Rodriguez; Jiménez, E.; Alberola, V.; García-Foncillas, J.; Constenla, M.; Ruiz, A.; Bueso, P.; Cabrera, E.; del Río,, L.; Ponce, J.; Oltra, A.; Checa, T.; Etxeberría, A.; Alonso, C.

    2012-01-01

    Background In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12–1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23–1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18–2.64). Conclusions/Significance This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses. PMID:23174912

  18. SLCO1B1 and SLC19A1 gene variants and irinotecan-induced rapid response and survival: a prospective multicenter pharmacogenetics study of metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Liu Huang

    Full Text Available BACKGROUND: Rapid response to chemotherapy in metastatic colorectal cancer (mCRC patients (response within 12 weeks of chemotherapy may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens. MATERIALS AND METHODS: Three SNPs were selected and genotyped in 137 mCRC patients from a Chinese prospective multicenter trial (NCT01282658. The chi-squared test, univariate and multivariable logistic regression model, and receiver operating characteristic analysis were used to evaluate correlations between the genotypes and rapid response. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate the associations between genotypes and survival outcomes. Benjamini and Hochberg False Discovery Rate correction was used in multiple testing. RESULTS: Genotype GA/AA of SNP rs2306283 of the gene SLCO1B1 and genotype GG of SNP rs1051266 of the gene SLC19A1 were associated with a higher rapid response rate (odds ratio [OR] =3.583 and 3.521, 95%CI =1.301-9.871 and 1.271-9.804, p=0.011 and p=0.013, respectively. The response rate was 70% in patients with both genotypes, compared with only 19.7% in the remaining patients (OR = 9.489, 95%CI = 2.191-41.093, Fisher's exact test p=0.002. Their significances were all maintained even after multiple testing (all p c < 0.05. The rs2306283 GA/AA genotype was also an independent prognostic factor of longer progression-free survival (PFS (hazard ratio = 0.402, 95%CI = 0.171-0.945, p=0.037. None of the SNPs predicted overall survival. CONCLUSIONS: Polymorphisms of solute carriers' may be useful to predict rapid

  19. Initial LDH level can predict the survival benefit from bevacizumab in the first-line setting in Chinese patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Yin CX

    2014-08-01

    Full Text Available Chenxi Yin,1,2,* Chang Jiang,1,2,* Fangxin Liao,1,2 Yuming Rong,1,2 Xiuyu Cai,1,2 Guifang Guo,1,2 Huijuan Qiu,1,2 Xuxian Chen,1,2 Bei Zhang,1,2 Wenzhuo He,1,2 Liangping Xia1,2 1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer, Medicine, 2VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this paper Background: Markers to predict the efficacy of bevacizumab treatment have been not fully validated in most cancers, including metastatic colorectal cancer (mCRC. The aim of this study was to investigate the potential role of lactate dehydrogenase (LDH in predicting the survival benefit from first-line bevacizumab treatment, in Chinese patients with mCRC. Methods: All the patients were diagnosed with mCRC at the Sun Yat-sen University Cancer Center from 2003 to 2013. The study group and the control group were classified by receiving bevacizumab or not. The serum LDH value of all the patients had been detected before the first-line treatment. The primary end point was progression-free survival (PFS. Results: The median PFS of the study and the control group (patients who received bevacizumab or not was 11.3 and 9.1 months, respectively (P=0.004. In the control group, the median PFS of the high LDH level and the low LDH level groups was 6.9 and 10.2 months, respectively (P<0.001. However, in the study group, the corresponding median PFS was 9.9 and 11.9 months, respectively (P=0.145. In addition, for the low LDH level group, the median PFS was 11.9 and 10.2 months for patients who received bevacizumab or not, respectively (P=0.066; however, the median PFS of patients receiving bevacizumab or not was significantly different in the high LDH level group (9.9 and 6.9 months, respectively (P=0.012. Conclusion: The addition of bevacizumab in the first-line treatment setting could improve the

  20. EGFR gene copy number as a predictive biomarker for the treatment of metastatic colorectal cancer with anti-EGFR monoclonal antibodies: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Yang Zu-Yao

    2012-08-01

    Full Text Available Abstract Background Epidermal growth factor receptor gene copy number (EGFR GCN has been heavily investigated as a potential predictive biomarker for the treatment of metastatic colorectal cancer (mCRC with anti-EGFR monoclonal antibodies (MAbs. The objective of this study was to systematically review current evidences on this issue. Methods PubMed, EMBASE, The Cochrane Library, Chinese Biomedical Literature Database, Wanfang Data, and the conference abstracts of American Society of Clinical Oncology and European Society of Medical Oncology were comprehensively searched. Studies that reported the objective response rate (ORR, progression-free survival, and/or overall survival of mCRC patients treated with anti-EGFR MAbs, stratified by EGFR GCN status, were included. The effect measures for binary outcome (response and time-to-event outcomes (progression-free survival and overall survival were risk difference and hazard ratio, respectively. Statistical heterogeneity among the studies was assessed by the Cochran’s Q-test and the I2 statistic. If appropriate, a quantitative synthesis of data from different studies would be conducted with a random-effects model. Results Nineteen eligible studies were identified. The criteria for increased EGFR GCN (GCN+ were highly inconsistent across different studies. The prevalence of GCN + ranged from 6.9% to 88.9%, and the difference in ORR between patients with GCN + and those with non-increased EGFR GCN (GCN- varied from −28% to 84%. Because of the significant heterogeneity, no quantitative synthesis of data was performed. There was a general trend towards higher ORR in patients with GCN+. The difference in ORRs between patients with GCN + and those with GCN- was even greater in KRAS wild-type patients, while in KRAS mutated patients the difference often did not exist. Almost all patients with EGFR amplification responded to the treatment. However, the prevalence of EGFR amplification was

  1. 111In-cetuximab as a diagnostic agent by accessible epidermal growth factor (EGF) receptor targeting in human metastatic colorectal carcinoma

    OpenAIRE

    Shih, Ying-Hsia; Peng, Cheng-Liang; Lee, Shin-Yu; Chiang, Ping-Fang; Yao, Cheng-Jung; Lin, Wuu-Jyh; Luo, Tsai-Yueh; Shieh, Ming-Jium

    2015-01-01

    Colorectal adenocarcinoma is a common cause death cancer in the whole world. The aim of this study is to define the 111In-cetuximab as a diagnosis tracer of human colorectal adenocarcinoma. In this research, cell uptake, nano-SPECT/CT scintigraphy, autoradiography, biodistribution and immunohitochemical staining of EGF receptor were included. HCT-116 and HT-29 cell expressed a relatively high and moderate level of EGF receptor, respectively. The nano-SPECT/CT image of 111In-cetuximab showed t...

  2. Chemotherapy of metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Colorectal cancer is one of the leading causes of cancer incidence and mortality. In 2008 inRussian Federation55 719 new cases of colorectal cancer were diagnosed and 37 911 patients died of this disease. A significant progress was achieved in metastatic colorectal cancer treatment during the last decades. A lot of treatment options became available: from 5-fluoruracil monotherapy to combined treatment treatment schemes including surgery. A group of patients with isolated liver metastases was distinguished, who can achieve 5-year survival rate of 40 % after systemic treatment and surgery. Today, based on clinical data and molecular analysis, we come close to individualized treatment of this patient group. In this literature review results of metastatic colorectal cancer chemotherapy are being analyzed and rational treatment tactic is proposed based on therapy goals. 

  3. Creactive protein and interleukin-6 as markers of systemic inflammatory response and as prognostic factors for metastatic colorectal cancer. Data from the randomized phase III NORDIC-VII study

    DEFF Research Database (Denmark)

    Thomsen, M.; Kersten, C.; Sorbye, H.;

    2015-01-01

    Background: A systemic inflammatory response (SIR) affects prognosis and treatment outcome in metastatic colorectal cancer (mCRC). The aim of the study was to explore the prognostic significance of several SIR-derived markers and the correlation between the best marker of SIR and plasma interleukin......-6 (IL-6). Methods: The study was based on data from the randomized phase III NORDIC-VII study (Nordic FLOX +/cetuximab as first line treatment of mCRC). The effect of different markers of SIR, including modified Glasgow Prognostic Score (mGPS), derived Neutrophil Lymphocyte Ratio (dNLR), levels of...... SIR and 393 were eligible for the final analysis related to CRP, IL-6 and RAF and BRAF mutation status. The prognostic significance of CRP was at least as good as the other markers of SIR. CRP together with IL-6 were selected for further investigation. Logtrans-formed CRP and IL-6 were highly...

  4. The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer : Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Christensen, René Depont; Andersen, Rikke Fredslund;

    2012-01-01

    PURPOSE: Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular...... rates also differed significantly between patients with C-allele containing genotypes (CC + CA) (39%) and patients homozygous for the A-allele (AA) (56%), p = 0.015. There was no correlation between response rates and the remaining SNPs. CONCLUSIONS: The VEGFR-1 319 C/A SNP is a potential predictive...... marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation....

  5. Assessment of metastatic colorectal cancer with hybrid imaging: comparison of reading performance using different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT in a short case series

    International Nuclear Information System (INIS)

    The purpose was to investigate the diagnostic performance of different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT for the evaluation of metastatic colorectal cancer lesions. Image data of 15 colorectal cancer patients (FDG-PET/CT and subsequent FDG-PET/MRI) were retrospectively evaluated by two readers in five reading sessions: MRI (morphology) alone, MRI/diffusion-weighted MRI (DWI), MRI/PET, MRI/DWI/PET; and PET/CT. Diagnostic performance of lesion detection with each combination was assessed in general and organ-based. The reference standard was given by histology and/or follow-up imaging. Separate analysis of mucinous tumours was performed. One hundred and eighty lesions (110 malignant) were evaluated (intestine n = 6, liver n = 37, lymph nodes n = 55, lung n = 4, and peritoneal n = 74). The overall lesion-based diagnostic accuracy was 0.46 for MRI, 0.47 for MRI/DWI, 0.57 for MRI/PET, 0.69 for MRI/DWI/PET and 0.66 for PET/CT. In the organ-based assessment, MRI/DWI/PET showed the highest accuracy for liver metastases (0.74), a comparable accuracy to PET/CT in peritoneal lesions (0.55), and in lymph node metastases (0.84). The accuracy in mucinous tumour lesions was limited in all modalities (MRI/DWI/PET = 0.52). PET/MRI including DWI is comparable to PET/CT in the evaluation of colorectal cancer metastases, with a markedly higher accuracy when using combined imaging data than the modalities separately. Further improvement is needed in the imaging of peritoneal carcinomatosis and mucinous tumours. (orig.)

  6. Assessment of metastatic colorectal cancer with hybrid imaging: comparison of reading performance using different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT in a short case series

    Energy Technology Data Exchange (ETDEWEB)

    Brendle, C.; Schwenzer, N.F.; Rempp, H.; Schmidt, H.; Pfannenberg, C.; Nikolaou, K.; Schraml, C. [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); La Fougere, C. [Eberhard Karls University, Nuclear Medicine, Department of Radiology, Tuebingen (Germany)

    2016-01-15

    The purpose was to investigate the diagnostic performance of different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT for the evaluation of metastatic colorectal cancer lesions. Image data of 15 colorectal cancer patients (FDG-PET/CT and subsequent FDG-PET/MRI) were retrospectively evaluated by two readers in five reading sessions: MRI (morphology) alone, MRI/diffusion-weighted MRI (DWI), MRI/PET, MRI/DWI/PET; and PET/CT. Diagnostic performance of lesion detection with each combination was assessed in general and organ-based. The reference standard was given by histology and/or follow-up imaging. Separate analysis of mucinous tumours was performed. One hundred and eighty lesions (110 malignant) were evaluated (intestine n = 6, liver n = 37, lymph nodes n = 55, lung n = 4, and peritoneal n = 74). The overall lesion-based diagnostic accuracy was 0.46 for MRI, 0.47 for MRI/DWI, 0.57 for MRI/PET, 0.69 for MRI/DWI/PET and 0.66 for PET/CT. In the organ-based assessment, MRI/DWI/PET showed the highest accuracy for liver metastases (0.74), a comparable accuracy to PET/CT in peritoneal lesions (0.55), and in lymph node metastases (0.84). The accuracy in mucinous tumour lesions was limited in all modalities (MRI/DWI/PET = 0.52). PET/MRI including DWI is comparable to PET/CT in the evaluation of colorectal cancer metastases, with a markedly higher accuracy when using combined imaging data than the modalities separately. Further improvement is needed in the imaging of peritoneal carcinomatosis and mucinous tumours. (orig.)

  7. Clinical Experience with Flexible Sigmoidoscopy in Asymptomatic and Symptomatic Patients

    OpenAIRE

    Meyer, Christopher T.; McBride, William; Goldblatt, Robert S.; Borak, Jonathan; Marignani, Pierluigi; Black, Henry R.; McCallum, Richard W.

    1980-01-01

    The purpose of this study was to evaluate the diagnostic yield of flexible sigmoidoscopy when performed as a routine procedure in asymptomatic patients over the age of 40 being referred for a complete physical examination. The preliminary results of this ongoing program are presented together with the diagnostic yield in 408 patients with symptoms and signs suggestive of colorectal disease who were of similar age (56.6 vs. 56.5 years) and sex distribution (79 percent male) to the asymptomatic...

  8. Asymptomatic bacteriuria in pregnancy.

    Science.gov (United States)

    Smaill, Fiona

    2007-06-01

    Screening for asymptomatic bacteriuria is a standard of obstetrical care and is included in most antenatal guidelines. There is good evidence that treatment of asymptomatic bacteriuria will decrease the incidence of pyelonephritis. All pregnant women should be screened for asymptomatic bacteriuria, and there are no new data that would indicate otherwise. Antibiotic treatment of asymptomatic bacteriuria is associated with a decrease in the incidence of preterm delivery or low birth weight, but the methodological quality of the studies means any conclusion about the strength of this association needs to be drawn cautiously. A better understanding of the mechanism by which treatment of asymptomatic bacteriuria could prevent preterm delivery is needed. While several rapid screening tests have been evaluated, none perform adequately to replace urine culture for detecting asymptomatic bacteriuria. Until there are data from well-designed trials that establish the optimal duration of therapy for asymptomatic bacteriuria, standard treatment courses are recommended. PMID:17347050

  9. Differentiation of Metastatic and Non-Metastatic Mesenteric Lymph Nodes by Strain Elastography in Surgical Specimens

    DEFF Research Database (Denmark)

    Havre, R F; Leh, S M; Gilja, O H;

    2016-01-01

    Purpose: To investigate if strain elastography could differentiate between metastatic and non-metastatic mesenteric lymph nodes ex-vivo. Materials and Methods: 90 mesenteric lymph nodes were examined shortly after resection from 25 patients including 17 patients with colorectal cancer and 8 patie...

  10. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  11. Three Rounds of External Quality Assessment in France to Evaluate the Performance of 28 Platforms for Multiparametric Molecular Testing in Metastatic Colorectal and Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Dequeker, Elisabeth M C; Keppens, Cleo; Egele, Caroline; Delen, Sofie; Lamy, Aude; Lemoine, Antoinette; Sabourin, Jean-Christophe; Andrieu, Catherine; Ligtenberg, Marjolijn; Fetique, Dominique; Tops, Bastiaan; Descarpentries, Clotilde; Blons, Hélène; Denoux, Yves; Aube, Cécile; Penault-Llorca, Frederique; Hofman, Paul; Leroy, Karen; Le Marechal, Cédric; Doucet, Laurent; Duranton-Tanneur, Valérie; Pedeutour, Florence; Soubeyran, Isabelle; Côté, Jean-François; Emile, Jean-François; Vignaud, Jean-Michel; Monhoven, Nathalie; Haddad, Véronique; Laurent-Puig, Pierre; van Krieken, Han; Nowak, Frederique; Lonchamp, Etienne; Bellocq, Jean-Pierre; Rouleau, Etienne

    2016-03-01

    Personalized medicine has gained increasing importance in clinical oncology, and several clinically important biomarkers are implemented in routine practice. In an effort to guarantee high quality of molecular testing in France, three subsequent external quality assessment rounds were organized at the initiative of the National Cancer Institute between 2012 and 2014. The schemes included clinically relevant biomarkers for metastatic colorectal (KRAS, NRAS, BRAF, PIK3CA, microsatellite instability) and non-small cell lung cancer (EGFR, KRAS, BRAF, PIK3CA, ERBB2), and they represent the first multigene/multicancer studies throughout Europe. In total, 56 laboratories coordinated by 28 regional molecular centers participated in the schemes. Laboratories received formalin-fixed, paraffin-embedded samples and were asked to use routine methods for molecular testing to predict patient response to targeted therapies. They were encouraged to return results within 14 calendar days after sample receipt. Both genotyping and reporting were evaluated separately. During the three external quality assessment rounds, mean genotype scores were all above the preset standard of 90% for all biomarkers. Participants were mainly challenged in case of rare insertions or deletions. Assessment of the written reports showed substantial progress between the external quality assessment schemes on multiple criteria. Several essential elements such as the clinical interpretation of test results and the reason for testing still require improvement by continued external quality assessment education. PMID:26752307

  12. First-Line XELOX Plus Bevacizumab Followed by XELOX Plus Bevacizumab or Single-Agent Bevacizumab as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: The Phase III MACRO TTD Study

    Science.gov (United States)

    Gómez-España, Auxiliadora; Massutí, Bartomeu; Sastre, Javier; Abad, Albert; Valladares, Manuel; Rivera, Fernando; Safont, Maria J.; Martínez de Prado, Purificación; Gallén, Manuel; González, Encarnación; Marcuello, Eugenio; Benavides, Manuel; Fernández-Martos, Carlos; Losa, Ferrán; Escudero, Pilar; Arrivi, Antonio; Cervantes, Andrés; Dueñas, Rosario; López-Ladrón, Amelia; Lacasta, Adelaida; Llanos, Marta; Tabernero, Jose M.; Antón, Antonio; Aranda, Enrique

    2012-01-01

    Purpose. The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). Patients and Methods. Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. Results. The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0–53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand–foot syndrome, and neuropathy. Conclusion. Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients. PMID:22234633

  13. Discussion of Traditional Chinese Medicine (TCM) Medication Strategy in Metastatic Colorectal Cancer (MCRC)%转移性结直肠癌的中医用药思路探讨

    Institute of Scientific and Technical Information of China (English)

    钱垠; 黄欣; 朱翔

    2013-01-01

    The pathogenesis of metastatic colorectal cancer (MCRC) is complicated and changeable.Accumulated dampness toxicity is its primary pathological basis."Supporting the healthy energy,dissipating dampness and removing toxicity" is its main therapeutic principle.The base of therapy is "build up healthful vital energy".The main treatment method is "invigorating spleen and supplementing qi ".Invigorating spleen for eliminating dampness is also a important therapy.When we treat the patient,we must treat them as differentiating stage,differentiate chills and fever,and differentiate disease location.%转移性结直肺癌病机复杂多变,湿毒蕴结乃转移性结直肠癌发生发展的主要病理基础.“扶正固本,化湿解毒”是其基本治疗原则,扶助正气是治疗的根本,健脾益气是治疗的基本手段,运脾化温是治疗的重要治法之一,治疗过程应分阶段、分寒热、分病位进行.

  14. Benign metastasizing pleomorphic adenoma in liver mimicking synchronic metastatic disease from colorectal cancer: a case report with emphasis on imaging findings

    International Nuclear Information System (INIS)

    Pleomorphic adenoma of the parotid gland with metastases to the liver is a rare etiology of focal liver lesions, and there are no described pathognomonic imaging features. We report a patient who presented with a newly diagnosed rectal cancer and multiple cystic liver lesions suspicious of mucinous synchronous liver metastases. Following chemotherapy no reduction in the number or size of the liver lesions was observed. The patient was re-evaluated and a biopsy of a lesion was performed. The specimen showed a metastasis from a pleomorphic adenoma of the parotid gland for which the patient had been treated 20 years earlier. The case illustrates how a thorough medical history can be crucial when a standard diagnostic imaging workup for colorectal cancer metastases is uncertain, and how a biopsy, though regarded as contraindicated due to the risk of tumor cell dissemination, can be required to secure a correct diagnosis

  15. Performance and Cost Efficiency of KRAS Mutation Testing for Metastatic Colorectal Cancer in Routine Diagnosis: The MOKAECM Study, a Nationwide Experience

    Science.gov (United States)

    Chatellier, Gilles; Côté, Jean-François; Pages, Jean-Christophe; de Fraipont, Florence; Boyer, Jean-Christophe; Merlio, Jean Philippe; Morel, Alain; Gorisse, Marie-Claude; de Cremoux, Patricia; Leroy, Karen; Milano, Gérard; Ouafik, L’Houcine; Merlin, Jean-Louis; Le Corre, Delphine; Aucouturier, Pascaline; Sabourin, Jean-Christophe; Nowak, Frédérique; Frebourg, Thierry; Emile, Jean-François; Durand-Zaleski, Isabelle; Laurent-Puig, Pierre

    2013-01-01

    Purpose Rapid advances in the understanding of cancer biology have transformed drug development thus leading to the approval of targeted therapies and to the development of molecular tests to select patients that will respond to treatments. KRAS status has emerged as a negative predictor of clinical benefit from anti-EGFR antibodies in colorectal cancer, and anti-EGFR antibodies use was limited to KRAS wild type tumors. In order to ensure wide access to tumor molecular profiling, the French National Cancer Institute (INCa) has set up a national network of 28 regional molecular genetics centers. Concurrently, a nationwide external quality assessment for KRAS testing (MOKAECM) was granted to analyze reproducibility and costs. Methods 96 cell-line DNAs and 24 DNA samples from paraffin embedded tumor tissues were sent to 40 French laboratories. A total of 5448 KRAS results were collected and analyzed and a micro-costing study was performed on sites for 5 common methods by an independent team of health economists. Results This work provided a baseline picture of the accuracy and reliability of KRAS analysis in routine testing conditions at a nationwide level. Inter-laboratory Kappa values were >0.8 for KRAS results despite differences detection methods and the use of in-house technologies. Specificity was excellent with only one false positive in 1128 FFPE data, and sensitivity was higher for targeted techniques as compared to Sanger sequencing based methods that were dependent upon local expertise. Estimated reagent costs per patient ranged from €5.5 to €19.0. Conclusion The INCa has set-up a network of public laboratories dedicated to molecular oncology tests. Our results showed almost perfect agreements in KRAS testing at a nationwide level despite different testing methods ensuring a cost-effective equal access to personalized colorectal cancer treatment. PMID:23935912

  16. Performance and cost efficiency of KRAS mutation testing for metastatic colorectal cancer in routine diagnosis: the MOKAECM study, a nationwide experience.

    Directory of Open Access Journals (Sweden)

    Hélène Blons

    Full Text Available PURPOSE: Rapid advances in the understanding of cancer biology have transformed drug development thus leading to the approval of targeted therapies and to the development of molecular tests to select patients that will respond to treatments. KRAS status has emerged as a negative predictor of clinical benefit from anti-EGFR antibodies in colorectal cancer, and anti-EGFR antibodies use was limited to KRAS wild type tumors. In order to ensure wide access to tumor molecular profiling, the French National Cancer Institute (INCa has set up a national network of 28 regional molecular genetics centers. Concurrently, a nationwide external quality assessment for KRAS testing (MOKAECM was granted to analyze reproducibility and costs. METHODS: 96 cell-line DNAs and 24 DNA samples from paraffin embedded tumor tissues were sent to 40 French laboratories. A total of 5448 KRAS results were collected and analyzed and a micro-costing study was performed on sites for 5 common methods by an independent team of health economists. RESULTS: This work provided a baseline picture of the accuracy and reliability of KRAS analysis in routine testing conditions at a nationwide level. Inter-laboratory Kappa values were >0.8 for KRAS results despite differences detection methods and the use of in-house technologies. Specificity was excellent with only one false positive in 1128 FFPE data, and sensitivity was higher for targeted techniques as compared to Sanger sequencing based methods that were dependent upon local expertise. Estimated reagent costs per patient ranged from €5.5 to €19.0. CONCLUSION: The INCa has set-up a network of public laboratories dedicated to molecular oncology tests. Our results showed almost perfect agreements in KRAS testing at a nationwide level despite different testing methods ensuring a cost-effective equal access to personalized colorectal cancer treatment.

  17. Magnitude of benefit of the addition of bevacizumab to first-line chemotherapy for metastatic colorectal cancer: meta-analysis of randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Falcone Alfredo

    2010-05-01

    Full Text Available Abstract Background Although the addition of bevacizumab to 1st line chemotherapy provides a significant survival benefit for advanced colorectal cancer, the magnitudes of both advantages and toxicities have not been extensively investigated. Methods A literature-based meta-analysis was conducted; Hazard Ratios were extracted from randomized trials for primary end-points (Progression Free Survival, PFS, Overall Survival OS. The log of event-based risk ratio were derived for secondary endpoints (objective/partial response rate, ORR/PR; severe hypertension, bleeding and proteinuria. Absolute differences and the number needed to treat/harm (NNT/NNH were calculated. A meta-regression analysis with clinical predictors and a sensitivity analysis according to the trial phase-design were conducted as well. Results Five trials (2,728 pts were selected. The addition of bevacizumab to 1st line chemotherapy significantly increased both PFS (although with significant heterogeneity and OS over exclusive chemotherapy by 17.1% and 8.6% (NNT 6 and 12, regardless of the study setting (non significant interaction between phase II and III. The chance to improve PR was significantly increased by 6.5% (NNT 15, with a trend for ORR. The risk of hypertension was significantly increased by 6.2% (NNH 16. According to the meta-regression analysis, female gender and rectal primary site were significant predictors for PFS benefit. Conclusions Notwithstanding all the concerns related to costs and the significant HTN risk, the significant outcome improvement provided by bevacizumab in first-line treatment for unselected advanced colorectal cancer patients, should be considered when choosing the appropriate up-front therapy.

  18. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  19. Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2014-06-10

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Colon Cancer; Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx

  20. A randomized, placebo-controlled, phase 1/2 study of tivantinib (ARQ 197) in combination with irinotecan and cetuximab in patients with metastatic colorectal cancer with wild-type KRAS who have received first-line systemic therapy.

    Science.gov (United States)

    Eng, Cathy; Bessudo, Alberto; Hart, Lowell L; Severtsev, Aleksey; Gladkov, Oleg; Müller, Lothar; Kopp, Mikhail V; Vladimirov, Vladimir; Langdon, Robert; Kotiv, Bogdan; Barni, Sandro; Hsu, Ching; Bolotin, Ellen; von Roemeling, Reinhard; Schwartz, Brian; Bendell, Johanna C

    2016-07-01

    Cetuximab in combination with an irinotecan-containing regimen is a standard treatment in patients with KRAS wild-type (KRAS WT), metastatic colorectal cancer (mCRC). We investigated the addition of the oral MET inhibitor tivantinib to cetuximab + irinotecan (CETIRI) based on preclinical evidence that activation of the MET pathway may confer resistance to anti-EGFR therapy. Previously treated patients with KRAS WT advanced or mCRC were enrolled. The phase 1, open-label 3 + 3, dose-escalation study evaluated the safety and maximally tolerated dose of tivantinib plus CETIRI. The phase 2, randomized, double-blinded, placebo-controlled study of biweekly CETIRI plus tivantinib or placebo was restricted to patients who had received only one prior line of chemotherapy. The phase 2 primary endpoint was progression-free survival (PFS). The recommended phase 2 dose was tivantinib (360 mg/m(2) twice daily) with biweekly cetuximab (500 mg/m(2) ) and irinotecan (180 mg/m(2) ). Among 117 patients evaluable for phase 2 analysis, no statistically significant PFS difference was observed: 8.3 months on tivantinib vs. 7.3 months on placebo (HR, 0.85; 95% confidence interval, 0.55-1.33; P = 0.38). Subgroup analyses trended in favor of tivantinib in patients with MET-High tumors by immunohistochemistry, PTEN-Low tumors, or those pretreated with oxaliplatin, but subgroups were too small to draw conclusions. Neutropenia, diarrhea, nausea and rash were the most frequent severe adverse events in tivantinib-treated patients. The combination of tivantinib and CETIRI was well tolerated but did not significantly improve PFS in previously treated KRAS WT mCRC. Tivantinib may be more active in specific subgroups. PMID:26891420

  1. Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study

    Directory of Open Access Journals (Sweden)

    Cals Laurent

    2009-04-01

    Full Text Available Abstract Background This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR inhibitor cetuximab combined with irinotecan, folinic acid (FA and two different doses of infusional 5-fluorouracil (5-FU in the first-line treatment of EGFR-detectable metastatic colorectal cancer. Methods The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs during part I of the study. Patients received cetuximab (400 mg/m2 initial dose and 250 mg/m2/week thereafter and every 2 weeks irinotecan (180 mg/m2, FA (400 mg/m2 and 5-FU (either low dose [LD], 300 mg/m2 bolus plus 2,000 mg/m2 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m2 bolus plus 2,400 mg/m2; n = 45. Results Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS was 8.6 months (counting all reported progressions and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%: of these, 10 patients (71% had no residual tumour after surgery, and these resections hindered the estimation of PFS. Conclusion The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial.

  2. Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

    Directory of Open Access Journals (Sweden)

    Smolich Beverly D

    2003-02-01

    Full Text Available Abstract Background Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Methods Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF receptor tyrosine kinase (RTK inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Results Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9 as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. Conclusions These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies.

  3. Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

    International Nuclear Information System (INIS)

    Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC) samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9) as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies

  4. Asymptomatic Disseminated Cysticercosis

    OpenAIRE

    Vaidya, Ashima; Singhal, Suman; Dhall, Sonia; Manohar, Ashish; Mahajan, Harsh

    2013-01-01

    Cysticercosis is a common problem world wide. However, disseminated cysticercosis is rare. Still rarer is asymptomatic disseminated cysticercosis. We are reporting here a rare case of asymptomatic disseminated cysticercosis which involved brain, face, orbit, lungs, heart, pancreas and spleen in a young Nigerian male, who sought medical attention for dysphagia which was diagnosed as achalasia cardia. Despite widespread dissemination of cysticercosis which involves multiple organs, the individu...

  5. Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes

    International Nuclear Information System (INIS)

    More than half of patients with KRAS-wild type advanced colorectal cancer (CRC) fail anti-EGFR monoclonal antibodies. We studied EGFR-axis messenger RNA (mRNA) expression and RAS, RAF, PIK3CA mutations in order to identify additional biomarkers of cetuximab efficacy. Previously genotyped (KRAS, NRAS, BRAF, PIK3CA mutations) formalin-fixed paraffin-embedded tumour biopsies of 226 cetuximab-treated CRC patients (1st to 3rd line therapy) were assessed for mRNA expression of epidermal growth factor receptor (EGFR) and its ligands EGF, Transofrming Growth Factor-a (TGFA), Amphiregulin (AREG) and Epiregulin (EREG) with real time quantitative PCR. Mutations were detected in 72 (31.9%) tumours for KRAS, in 6 (2.65%) for BRAF, in 7 (3.1%) for NRAS and in 37 (16.4%) for PIK3CA. Only PIK3CA mutations occasionally coexisted with other gene mutations. In univariate analysis, prognostic significance for survival (from metastases until death) was seen for BRAF mutations (Hazard Ratio HR 8.1, 95% CI 3.4-19), codon 12-only KRAS mutations (HR 1.62, 95% CI 1.1-2.4), high AREG mRNA expression only in KRAS wild type CRC (HR 0.47, 95% CI 0.3-0.7) and high EREG mRNA expression irrespective of KRAS mutation status (HR 0.45, 95% CI 0.28-0.7). EREG tumoural mRNA expression was significantly associated with a 2.26-fold increased likelihood of objective response to cetuximab therapy (RECIST 1.1). In multivariate analysis, favourable predictive factors were high AREG mRNA in KRAS wild type tumours, high EREG mRNA, low Ephrin A2 receptor mRNA. Cetuximab-treated patients with AREG-low KRAS wild type CRC fared very poorly, their survival being similar to KRAS mutant CRC. Patients with KRAS codon 13 or other non-codon 12 mutations had a median survival (30 months, 95% CI 20–35) similar to that of patients with KRAS wild-type (median survival 29 months, 95% CI 25–35), in contrast to patients with KRAS codon 12 mutations who fared worse (median survival 19 months, 95% CI 15–26). BRAF and codon

  6. Contemporary methods of treatment of colorectal cancer

    OpenAIRE

    Monika Kozłowska; Stanisław Głuszek

    2016-01-01

    Today, colorectal cancer (CRC) is the third most frequently diagnosed worldwide malignant cancer in males, and the second in females, with more than 1,200,000 new cases and more than 600,000 deaths, annually. Screening tests in oncology allow the detection of cancerous disease at an early, asymptomatic stage. The procedures most frequently performed in the case of colorectal cancer include: low anterior resection by the Dixon method (manual suture or staplers); abdominoperineal resection of t...

  7. SCREENING FOR COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    M. Bărbulescu

    2007-01-01

    Full Text Available The aim of this paper is a review of the main procedures for early diagnosis of colorectal cancer, especially for the asymptomatic individuals with high risk to develop this neoplasm, devise the risk groups to develop this cancer and to study the management of these. The advantages and disadvantages or limitations of screening modalities for colorectal cancer, such as faecal occult blood testing with old guaiac-based tests or the new tests for detecting faecal deoxyribonucleic acid of tumor cells, endoscopic screening by flexible sigmoidoscopy, colonoscopy, or CT-colonography and double contrast barium enema examination, are evaluated. The most accurate diagnosed sensibility (95-97% belong to total colonoscopy with biopsy, barium enema having a lower sensibility (83%; the easiest and cheaper screening method represent guaiac-based faecal occult blood tests but with a global predictive positive value of only 5-10%. In our country, as it’s known, most of the colorectal cancer patients presents to the doctor in an advanced local stage or with distant metastases or in other situations like perforation, obstructive or hemorrhaged complications. In all these cases the therapeutic resources are limited and the survival is much diminished. The situation would be different if in the precocious diagnosis in the incipient stage of the colorectal neoplasm, proper treatment resources may assure to these patients a higher life hope. A proper national healthy political program that will promote some fesabile screening programs could diagnose and treat patients with colorectal neoplasm in incipient stages, with the result of prolonged survival and disease-free interval and complete socio-professional reinstatement. These national screening programs may absolve the expensiveness on the patients care with the colorectal neoplasm cancer in the advanced stages that have a poor prognosis.

  8. Metastatic Cancer

    Science.gov (United States)

    ... Breast Bone, brain, liver, lung Colorectal Liver, lung, peritoneum Kidney Adrenal gland , bone, brain, liver, lung Lung ... brain, liver, lung, skin/muscle Ovary Liver, lung, peritoneum Pancreas Liver, lung, peritoneum Prostate Adrenal gland, bone, ...

  9. Role of MGMT as biomarker in colorectal cancer

    OpenAIRE

    Inno, Alessandro; Fanetti, Giuseppe; Di Bartolomeo, Maria; Gori, Stefania; Maggi, Claudia; Cirillo, Massimo; Iacovelli, Roberto; Nichetti, Federico; Martinetti, Antonia; de Braud, Filippo; Bossi, Ilaria; Pietrantonio, Filippo

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic co...

  10. Colorectal Cancer

    Science.gov (United States)

    ... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  11. Colorectal Cancer

    Science.gov (United States)

    ... and rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... both men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  12. Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label randomized phase III trial.

    Science.gov (United States)

    Correale, Pierpaolo; Botta, Cirino; Rotundo, Maria S; Guglielmo, Annamaria; Conca, Raffaele; Licchetta, Antonella; Pastina, Pierpaolo; Bestoso, Elena; Ciliberto, Domenico; Cusi, Maria G; Fioravanti, Antonella; Guidelli, Giacomo M; Bianco, Maria T; Misso, Gabriella; Martino, Elodia; Caraglia, Michele; Tassone, Pierfrancesco; Mini, Enrico; Mantovani, Giovanni; Ridolfi, Ruggero; Pirtoli, Luigi; Tagliaferri, Pierosandro

    2014-01-01

    The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m(2), day 1); oxaliplatin (85 mg/m(2), day 2); levofolinate (100 mg/m(2), days 1-2), 5-fluorouracil (5-FU) (400 mg/m(2) in bolus followed by 24 h infusion at 800 mg/m(2),days 1-2), sc. GM-CSF (100 μg, days 3-7); sc. aldesleukin (0·5 MIU bi-daily, days 8-14 and 17-30)] treatments. The study underwent early termination because of poor recruitment in the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed superiority over FOLFOX in terms of progression-free survival [median 9·23 (95% confidence interval (CI), 6·9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months; hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0·002] and response rate [66.1% (95% CI, 0.41-0.73) vs. 37·0% (95% CI, 0.28-0.59), P=0.002], with a trend to longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57 mo (95% CI, 9.07-20.07); HR: 0·79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs (18.5%), an increase in the number of monocytes, eosinophils, CD4(+) T lymphocytes, natural killer cells, and a decrease in immunoregulatory (CD3(+)CD4(+)CD25(+)FoxP3(+)) T cells. Taken together, these findings provide proof-of-principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC. PMID:24316553

  13. FCGR2A and FCGR3A polymorphisms and clinical outcome in metastatic colorectal cancer patients treated with first-line 5-fluorouracil/folinic acid and oxaliplatin +/- cetuximab

    International Nuclear Information System (INIS)

    Polymorphisms of genes encoding the Fcy receptors (Fc fragment of IgG receptor 2A (FCGR2A) and 3A (FCGR3A)), which influence their affinity for the Fc fragment, have been linked to the pharmacodynamics of monoclonal antibodies. Most studies have been limited by small samples sizes and have reported inconsistent associations between the FCGR2A and the FCGR3A polymorphisms and clinical outcome in metastatic colorectal cancer (mCRC) patients treated with cetuximab. We investigated the association of these polymorphisms and clinical outcome in a large cohort of mCRC patients treated with first-line 5-fluorouracil/folinic acid and oxaliplatin (Nordic FLOX) +/- cetuximab in the NORDIC-VII study (NCT00145314). 504 and 497 mCRC patients were evaluable for the FCGR2A and FCGR3A genotyping, respectively. Genotyping was performed on TaqMan ABI HT 7900 (Applied Biosystems, Foster City, CA, USA) with pre-designed SNP genotyping assays for FCGR2A (rs1801274) and FCGR3A (rs396991). The response rate for patients with the FCGR2A R/R genotype was significantly increased when cetuximab was added to Nordic FLOX (31% versus 53%, interaction P = 0.03), but was not significantly different compared to the response rate of patients with the FCGR2A H/H or H/R genotypes given the same treatment. A larger increase in response rate with the addition of cetuximab to Nordic FLOX in patients with KRAS mutated tumors and the FCGR2A R/R genotype was observed (19% versus 50%, interaction P = 0.04). None of the FCGR3A polymorphisms were associated with altered response when cetuximab was added to Nordic FLOX (interaction P = 0.63). Neither of the FCGR polymorphisms showed any significant associations with progression-free survival or overall survival. Patients with KRAS mutated tumors and the FCGR2A R/R polymorphism responded poorly when treated with chemotherapy only, and experienced the most benefit of the addition of cetuximab in terms of response rate

  14. Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma

    OpenAIRE

    2010-01-01

    Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma. The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm. Immunohistochemical stains that may be useful in the dif...

  15. What Is Colorectal Cancer?

    Science.gov (United States)

    ... Topic Key statistics for colorectal cancer What is colorectal cancer? Colorectal cancer is a cancer that starts in ... and spread, see What Is Cancer? How does colorectal cancer start? Most colorectal cancers begin as a growth ...

  16. Colorectal Cancer Prevention

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Prevention (PDQ®)–Patient Version What is prevention? Cancer ... to keep cancer from starting. General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  17. Asymptomatic uterine fibroids.

    Science.gov (United States)

    Divakar, Hema

    2008-08-01

    It is estimated that at least 50% of fibroids are asymptomatic, but this figure is likely to be an underestimate as it is based on women in whom fibroids are found incidentally during another procedure (e.g. cervical screening), and there is little, if any, data from population studies on the true incidence of fibroids. If a prevalence of 50% by 50 years of age is accepted, a large number of women have asymptomatic fibroids. Working on the cliché, 'if it ain't broken, don't fix it', it may seem surprising that there should be a chapter dedicated to the issue of asymptomatic fibroids, since the simplistic approach might be to leave the asymptomatic fibroids well alone. However, asymptomatic fibroids may become symptomatic in the future, so it may be wiser to treat fibroids before they grow to a size when they become symptomatic, or treatment becomes more challenging, especially in young women who may desire fertility at a later stage, and in view of the fact that many women are starting their families in their mid-thirties when they have a 30% chance of having a fibroid(s). Despite their common occurrence, fibroids are still poorly understood. It is not known why they form in the first place, what determines their number and ultimate size, the best treatment approaches, or the factors that determine which women develop symptoms. Even when women present with disorders such as infertility, pelvic pain and abnormal bleeding, it is not always possible to be certain that a given myoma is not simply an innocent bystander rather than the cause of the symptom. This chapter addresses the challenging issue of what to do when fibroids are diagnosed incidentally. Firstly, there is the need to ascertain that the pelvic mass palpated is indeed a fibroid, and not an early, more sinister tumour, especially if conservative management is adopted. In addition, there is the issue of size, position and potential for becoming symptomatic at a later date. With the availability of uterine

  18. Asymptomatic Microscopic Hematuria

    OpenAIRE

    Livingstone, Verity H; Turner, Bradley

    1987-01-01

    A retrospective chart review was performed in a family-practice office, which looked at the prevalence and significance of asymptomatic microscopic hematuria (AMH). Various methods were used to identify the relevant charts and to define the practice demographics, some of which hitherto had not been described. At least 2% of the men and 5% of the women over 44 years old in the practice were found to have AMH; in none of these patients, however, were any significant urological abnormalities det...

  19. MicroRNA regulation network in colorectal cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Jiao-Jiao; Zhou; Shu; Zheng; Li-Feng; Sun; Lei; Zheng

    2014-01-01

    Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.

  20. Cytomorphology of Circulating Colorectal Tumor Cells: A Small Case Series

    Directory of Open Access Journals (Sweden)

    Dena Marrinucci

    2010-01-01

    Full Text Available Several methodologies exist to enumerate circulating tumor cells (CTCs from the blood of cancer patients; however, most methodologies lack high-resolution imaging, and thus, little is known about the cytomorphologic features of these cells. In this study of metastatic colorectal cancer patients, we used immunofluorescent staining with fiber-optic array scanning technology to identify CTCs, with subsequent Wright-Giemsa and Papanicolau staining. The CTCs were compared to the corresponding primary and metastatic tumors. The colorectal CTCs showed marked intrapatient pleomorphism. In comparison to the corresponding tissue biopsies, cells from all sites showed similar pleomorphism, demonstrating that colorectal CTCs retain the pleomorphism present in regions of solid growth. They also often retain particular cytomorphologic features present in the patient's primary and/or metastatic tumor tissue. This study provides an initial analysis of the cytomorphologic features of circulating colon cancer cells, providing a foundation for further investigation into the significance and metastatic potential of CTCs.

  1. TLR8 Agonist VTX-2337 and Cyclophosphamide in Treating Patients With Metastatic, Persistent, Recurrent, or Progressive Solid Tumors

    Science.gov (United States)

    2016-06-15

    Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Melanoma of the Skin; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer

  2. Asymptomatic ischemic cerebral lesions

    International Nuclear Information System (INIS)

    For the purpose of studying the incidence, pathomorphology and etiology of asymptomatic ischemic cerebral lesions, we carried out a brain MRI study on 65 patients with diabetes mellitus accompanied with hypertension who are thought to belong to a high risk group of ischemic cerebrovascular diseases. Excluding the abnormality of tendon reflex due to diabetic neuropathy, sixty percent of the total patients had some mild neurological signs and symptoms, most of them was discrepancy in tendon reflex. The percentage of the patients in whom MRI disclosed some abnormalities was as high as 70%, they were lacunar stroke, multiple lacunar state, cortical infarct, and patchy high signal lesions visible only in the T2 weighted image. Lacunes or these patchy high signal lesions (considered to be the dilatation of the perivascular space or true lacunes) tended to be found along the border zone or the terminal zone. These results indicate that asymptomatic patients in whom MRI discloses the abnormalities should be considered as candidates for the future onset of multi-infarct. (author)

  3. Thermoradiotherapy for colorectal carcinoma

    International Nuclear Information System (INIS)

    The Japanese Society for Therapeutic Radiology and Oncology conducted a survey of the present state of thermoradiotherapy for colorectal carcinomas in Japan. In this survey, 105 cases at the 9 institutions were registered which had been treated from January 1981 to December 1992. From this data, we analyzed the trend of hyperthermia for the colorectal carcinoma and the treatment parameters which might have an influence on the treatment results. Ninety-four of 105 cases were recurrent or metastatic lesions. Mainly, the RF capacitive heating equipment was applied for the colorectal carcinoma. The number of cases in which hyperthermia were given once or twice a week were almost equal, and there was no significant difference in the treatment response rate. The mean duration of hyperthermia at therapeutic temperature was 42 min. Measurements of temperature in lesions were performed in 86% of sessions, and the mean tumor temperature was 43.1degC. Higher maximum tumor temperature and longer treatment time have brought significantly better response. Responder groups have shown better survival than non-responder groups. Acute reactions associated with hyperthermia were as follows: pain in 35 cases, burn and/or skin erosion in 12 cases, abscess formation in 3 cases and others in 3 cases. Late effects of treatment were ileus in 9 cases, ulcer of intestinal tract in 5 cases, subcutaneous fibrosis in 3 and others in 6. In conclusion, the application of thermoradiotherapy for reflactory colorectal carcinoma may contribute to the improvement of prognosis and quality of life of patients. (author)

  4. Tests for Colorectal Cancer

    Science.gov (United States)

    ... symptoms Next Topic Colorectal cancer stages Tests for colorectal cancer Colorectal cancer is often found after symptoms appear, ... of the cancer . Imaging tests to look for colorectal cancer Imaging tests use sound waves, x-rays, magnetic ...

  5. Bio markers and Anti-EGFR therapies for Krads wild-type tumors in metastatic colorectal cancer patients; Biomarcadores y terapeutica ANTI-EGFR en el cancer colorrectal metastasico en pacientes con K-Ras no mutado

    Energy Technology Data Exchange (ETDEWEB)

    Diaz Rubio Garcia, E.

    2009-07-01

    The natural history of metastasis colorectal cancer has being clearly modified in terms of response rate, time to progression and overall survival, once the anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have emerged in combination with the standard cytotoxic chemotherapy (FOLFOX and FOLFIRI). However, the benefit from cetuximab and panitumumab is only confined to KRAS-wild type (KRAS-wt) colorectal tumors, while KRAS mutated tumors do not respond to these drugs. The 65 % of colorectal tumors are KRAS-wt tumors, but efficacy of antiEGFR therapies is detected only in 60-70 % of these KRAS-wt tumors. Other biomarkers and molecular pathways must be involved in the response of the antiEGFR therapies for the KRAS-wt colorectal tumors, such as the EGFR ligands, the EGFR-phosphorilated levels, the number of EGFR copies, the status of the KRAS effected B-RAF and the alternative intracellular signaling pathways PIK3CA/PTEN/AKT and JAK/STAT. A battery of these biomarkers is needed to select the most sensitive patients to the antiEGFR therapies. This pattern may represent a novel favorable cost-effectiveness tool to develop tailored treatments. A review of these biomarkers and molecular pathways, involved in the antiEGFR therapies response, is performed. (Author) 68 refs.

  6. Liver Metastases in Colorectal Cancer.

    Science.gov (United States)

    Folprecht, Gunnar

    2016-01-01

    Resection of colorectal liver metastases is a treatment standard because patients experience long-term disease-free survival or are even cured after undergoing this procedure. Improved surgical techniques for liver resection in combination with downsizing liver metastases by chemotherapy, interventions to induce liver hypertrophy before resection, and the use of ablative techniques have allowed us to expand the indications for liver surgery and local treatment in situations with limited metastatic colorectal cancer. Resectability and identification of patients who might benefit from liver surgery and local ablative techniques are key factors for the treatment of patients with colorectal cancer. Despite the wide acceptance of liver surgery and ablative techniques, there are many open questions on the management of limited metastatic disease, such as which patients benefit from an aggressive surgical approach, what the indications for ablative and other local techniques are, and what the role of chemotherapy is for patients with resectable or resected disease. Unfortunately, results of randomized trials are only available for a limited number of these questions. PMID:27249722

  7. Colorectal tuberculosis

    International Nuclear Information System (INIS)

    Our objective was to evaluate the incidence of colorectal tuberculosis in our series and to study its radiological spectrum. A total of 684 cases of proven gastrointestinal tuberculosis with positive barium contrast findings seen over a period of more than one decade were evaluated. The study did not include cases where colon was involved in direct contiguity with ileo-caecal tuberculosis. Seventy-four patients (10.8%) had colorectal tuberculosis. Commonest site involved was transverse colon, closely followed by rectum and ascending colon. Radiological findings observed were in the form of strictures (54%), colitis (39%) and polypoid lesions (7%). Complications noted were in the form of perforations and fistulae in 18.9% of cases. Colorectal tuberculosis is a very common site for gastrointestinal tuberculosis. Typical findings of colorectal tuberculosis are strictures, signs of colitis and polypoid lesions. Common complications are perforation and fistulae. (orig.)

  8. Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib

    OpenAIRE

    Wong, Andrea Li Ann; Lim, Joline Si Jing; Sinha, Arvind; Gopinathan, Anil; Lim, Robert; Tan, Chee-Seng; Soh, Thomas; Venkatesh, Sudhakar; Titin, Christina; Sapari, Nur Sabrina; Lee, Soo-Chin; Yong, Wei-Peng; Tan, David Shao Ping; Pang, Brendan; Wang, Ting-Ting

    2015-01-01

    Background Regorafenib, a multi-kinase inhibitor, is used in the treatment of patients with metastatic colorectal cancer refractory to standard therapy. However, this benefit was limited to 1.4 months improvement in overall survival, with more than half of patients experiencing grade 3 to 4 adverse events. We aim to elucidate the pharmacodynamic effects of regorafenib in metastatic colorectal cancer and discover potential biomarkers that may predict clinical benefit. Methods Patients with met...

  9. Metastatic Gas gangrene and Colonic Perforation: a case report

    OpenAIRE

    Sasapu Kishore K; Powell Matthew J; Macklin Christopher

    2008-01-01

    Abstract Clostridium septicum myonecrosis is associated with diabetes, colorectal and haematological malignancies. We present a case of metastatic myonecrosis in a diabetic patient with a perforated caecal tumour. The literature since 1989 is reviewed and 28 cases of Clostridium septicum myonecrosis are discussed.

  10. Metastatic Gas gangrene and Colonic Perforation: a case report

    Directory of Open Access Journals (Sweden)

    Sasapu Kishore K

    2008-03-01

    Full Text Available Abstract Clostridium septicum myonecrosis is associated with diabetes, colorectal and haematological malignancies. We present a case of metastatic myonecrosis in a diabetic patient with a perforated caecal tumour. The literature since 1989 is reviewed and 28 cases of Clostridium septicum myonecrosis are discussed.

  11. Asymptomatic bacteriuria among pregnant women

    OpenAIRE

    Sudha Biradar Kerure; Rajeshwari Surpur; Sheela S. Sagarad; Sneha Hegadi

    2013-01-01

    Background: Urinary tract infections (UTIs) are the most common bacterial infections during pregnancy. Asymptomatic bacteriuria (ASB) is a major risk factor for the development of urinary tract infections during pregnancy and with further risk of preterm birth & pyelonephritis if untreated. Aims & Objectives: This study was carried out to determine the prevalence of asymptomatic bacteriuria (ASB) in pregnant women & to isolate, identify and establish antimicrobial susceptibility of pathogens....

  12. Asymptomatic Bacteriuria Frequency in Pregnancy

    OpenAIRE

    Sarı O et al.

    2011-01-01

    Most of the complications caused by asymptomatic bacteriuria (ABU) in pregnancy can be avoided by early treatment. In our study, we aimed to determine the urinary infection prevalence and the pathogen agent identification in the pregnant women observing in our clinic. 240 asymptomatic pregnant women having no antibiotic treatment history during last 1 week and were enrolled to the study. Urine specimens were collected from 12th and 16th week pregnant women, and were examined by light microsco...

  13. Asymptomatic bacteriuria among pregnant women

    OpenAIRE

    Paul Erhunmwunse Imade; Patience Emiolu Izekor; Nosakhare Odeh Eghafona; Onaiwu Idahosa Enabulele; Endurance Ophori

    2010-01-01

    Background: Asymptomatic bacteriuria is the significant presence of bacteria in the urine of an individual without symptoms. In pregnancy, the apparent reduction in immunity of pregnant women tends to encourage the growth of pathogens. Aim : This study was carried out to determine the prevalence of asymptomatic bacteriuria in pregnant women attending a primary health centre in Benin City, Nigeria. Materials and Methods: A total of 1,228 pregnant women were recruited for this study. All subjec...

  14. Asymptomatic Bacteriuria in Pregnant Women

    OpenAIRE

    Samad Hazhir

    2007-01-01

    Introduction: The aim of this study was to evaluate the frequency of bacteriuria in pregnant women referred to the medical centers of Tabriz, Iran, for prenatal care. Materials and Methods: A total of 1100 healthy pregnant women who were referred to 50 medical centers in Tabriz for a regular prenatal care were evaluated for bacteriuria. Results: The frequency of asymptomatic bacteriuria was 6.1%. Maternal age was lower in the women with a positive urine culture (P = .02). Asymptomatic bact...

  15. Evaluation of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Huanhuan [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Department of Radiology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine (China); Yan, Fuhua; Pan, Zilai; Lin, Xiaozhu; Luo, Xianfu; Shi, Cen [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Chen, Xiaoyan [Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Wang, Baisong [Department of Biomedical Statistics, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Zhang, Huan, E-mail: huanzhangy@126.com [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China)

    2015-02-15

    Highlights: • Colorectal cancer is the third most prevalent cancer and the status of the regional lymph nodes in rectal cancer is considered to be one of the most powerful prognostic factor in the absence of distant metastatic disease. Detecting LNs metastasis is still a challenging problem due to the presence of microscopic metastasis or inflammatory swelling of LNs. • We investigated the value of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Our study demonstrated that the quantitative normalized iodine concentration (nIC) could be useful for differentiating metastatic and non-metastatic lymph nodes. The combination of nIC in portal venous phase and conventional size criterion could improve the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of rectal cancer. - Abstract: Objectives: To investigate the value of dual energy spectral CT (DEsCT) imaging in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Methods: Fifty-five patients with rectal cancer underwent the arterial phase (AP) and portal venous phase (PP) contrast-enhanced DEsCT imaging. The virtual monochromatic images and iodine-based material decomposition images derived from DEsCT imaging were interpreted for lymph nodes (LNs) measurement. The short axis diameter and the normalized iodine concentration (nIC) of metastatic and non-metastatic LNs were measured. The two-sample t test was used to compare the short axis diameters and nIC values of metastatic and non-metastatic LNs. ROC analysis was performed to assess the diagnostic performance. Results: One hundred and fifty two LNs including 92 non-metastatic LNs and 60 metastatic LNs were matched using the radiological-pathological correlation. The mean short axis diameter of metastatic LNs was significantly larger than that of the non-metastatic LNs (7.28 ± 2.28 mm vs. 4.90 ± 1.64 mm, P < 0.001). The mean n

  16. Asymptomatic bacteriuria among pregnant women

    Directory of Open Access Journals (Sweden)

    Paul Erhunmwunse Imade

    2010-06-01

    Full Text Available Background: Asymptomatic bacteriuria is the significant presence of bacteria in the urine of an individual without symptoms. In pregnancy, the apparent reduction in immunity of pregnant women tends to encourage the growth of pathogens. Aim: This study was carried out to determine the prevalence of asymptomatic bacteriuria in pregnant women attending a primary health centre in Benin City, Nigeria. Materials and Methods: A total of 1,228 pregnant women were recruited for this study. All subjects were clinically identified to have no signs and symptoms of UTI. Clean catch midstream urine sample was collected from each patient into sterile universal container. The urine samples were examined microscopically and by cultural method. Identification of isolates was by standard microbiological technique. Result: A total of 556 (45.3% were positive for significant bacteriuria. There was a significant difference in the prevalence of asymptomatic bacteriuria with respect to age (P < 0.0001. Trimester did not show any significant difference (P = 0.2006 in the prevalence of asymptomatic bacteriuria. Escherichia coli was the most predominant organism followed closely by Staphylococcus aureus. Ciprofloxacin, Ceftriaxone and Augmentin were found to be the most effective antibiotics against the urinary isolates. Conclusion: Asymptomatic bacteriuria is not uncommon among antenatal patients in the population studied. Routine urine cultural test should be carried out on all antenatal patients in order to identify any unsuspecting infection. This measure will go a long way in reducing maternal and obstetric complications associated with pregnancy.

  17. Asymptomatic Bacteriuria and Bacterial Interference.

    Science.gov (United States)

    Nicolle, Lindsay E

    2015-10-01

    Asymptomatic bacteriuria is very common. In healthy women, asymptomatic bacteriuria increases with age, from asymptomatic bacteriuria, irrespective of age or gender. The prevalence is very high in residents of long-term-care facilities, from 25% to 50% of women and 15% to 40% of men. Escherichia coli is the most frequent organism isolated, but a wide variety of other organisms may occur. Bacteriuria may be transient or persist for a prolonged period. Pregnant women with asymptomatic bacteriuria identified in early pregnancy and who are untreated have a risk of pyelonephritis later in pregnancy of 20% to 30%. Bacteremia is frequent in bacteriuric subjects following mucosal trauma with bleeding, with 5% to 10% of patients developing severe sepsis or septic shock. These two groups with clear evidence of negative outcomes should be screened for bacteriuria and appropriately treated. Asymptomatic bacteriuria in other populations is benign and screening and treatment are not indicated. Antimicrobial treatment has no benefits but is associated with negative outcomes including reinfection with antimicrobial resistant organisms and a short-term increased frequency of symptomatic infection post-treatment. The observation of increased symptomatic infection post-treatment, however, has led to active investigation of bacterial interference as a strategy to prevent symptomatic episodes in selected high risk patients. PMID:26542046

  18. Asymptomatic bacteriuria among pregnant women

    Directory of Open Access Journals (Sweden)

    Paul Erhunmwunse Imade

    2010-01-01

    Full Text Available Background: Asymptomatic bacteriuria is the significant presence of bacteria in the urine of an individual without symptoms. In pregnancy, the apparent reduction in immunity of pregnant women tends to encourage the growth of pathogens. Aim : This study was carried out to determine the prevalence of asymptomatic bacteriuria in pregnant women attending a primary health centre in Benin City, Nigeria. Materials and Methods: A total of 1,228 pregnant women were recruited for this study. All subjects were clinically identified to have no signs and symptoms of UTI. Clean catch midstream urine sample was collected from each patient into sterile universal container. The urine samples were examined microscopically and by cultural method. Identification of isolates was by standard microbiological technique. Result: A total of 556 (45.3% were positive for significant bacteriuria. There was a significant difference in the prevalence of asymptomatic bacteriuria with respect to age (P < 0.0001. Trimester did not show any significant difference (P = 0.2006 in the prevalence of asymptomatic bacteriuria. Escherichia coli was the most predominant organism followed closely by Staphylococcus aureus. Ciprofloxacin, Ceftriaxone and Augmentin were found to be the most effective antibiotics against the urinary isolates. Conclusion : Asymptomatic bacteriuria is not uncommon among antenatal patients in the population studied. Routine urine cultural test should be carried out on all antenatal patients in order to identify any unsuspecting infection. This measure will go a long way in reducing maternal and obstetric complications associated with pregnancy.

  19. Colorectal Cancer Biomarkers: Where Are We Now?

    Directory of Open Access Journals (Sweden)

    Maria Gonzalez-Pons

    2015-01-01

    Full Text Available Colorectal cancer is one of the major causes of cancer-related death in the Western world. Patient survival is highly dependent on the tumor stage at the time of diagnosis. Reduced sensitivity to chemotherapy is still a major obstacle in effective treatment of advanced disease. Due to the fact that colorectal cancer is mostly asymptomatic until it progresses to advanced stages, the implementation of screening programs aimed at early detection is essential to reduce incidence and mortality rates. Current screening and diagnostic methods range from semi-invasive procedures such as colonoscopy to noninvasive stool-based tests. The combination of the absence of symptoms, the semi-invasive nature of currently used methods, and the suboptimal accuracy of fecal blood tests results in colorectal cancer diagnosis at advanced stages in a significant number of individuals. Alterations in gene expression leading to colorectal carcinogenesis are reflected in dysregulated levels of nucleic acids and proteins, which can be used for the development of novel, minimally invasive molecular biomarkers. The purpose of this review is to discuss the commercially available colorectal cancer molecular diagnostic methods as well as to highlight some of the new candidate predictive and prognostic molecular markers for tumor, stool, and blood samples.

  20. Beclin 1 Expression is Closely Linked to Colorectal Carcinogenesis and Distant Metastasis of Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Mei-Ying Zhang

    2014-08-01

    Full Text Available Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05. According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM than adenoma and carcinoma (p < 0.05. Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05. Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05, but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM staging, differentiation or serum carcinoembryonic antigen (CEA concentration (p > 0.05. Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05. Cox’s model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05. It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

  1. Breast cancer (metastatic)

    OpenAIRE

    Stebbing, Justin; Slater, Sarah; Slevin, Maurice

    2007-01-01

    Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered very unusual.

  2. Asymptomatic bacteriuria among pregnant women

    Directory of Open Access Journals (Sweden)

    Sudha Biradar Kerure

    2013-04-01

    Full Text Available Background: Urinary tract infections (UTIs are the most common bacterial infections during pregnancy. Asymptomatic bacteriuria (ASB is a major risk factor for the development of urinary tract infections during pregnancy and with further risk of preterm birth & pyelonephritis if untreated. Aims & Objectives: This study was carried out to determine the prevalence of asymptomatic bacteriuria (ASB in pregnant women & to isolate, identify and establish antimicrobial susceptibility of pathogens. Methods: A total of 500 pregnant women were studied over a period of one year. Clean catch midstream urine sample was collected into a sterile container & then subjected to culture method. Results: Significant bacteriuria was noted in 45 patients (9%. 3% patients had insignificant bacteriuria. Growth of contaminants was noted in 8%. 80% samples were sterile with no growth. E. coli was the most common etiological agent, followed by Staphylococcus aureus. Conclusions: Asymptomatic bacteriuria is not uncommon in antenatal patients. All pregnant women should be screened by urine culture to detect asymptomatic bacteriuria at their first visit to prevent overt UTI & other complications in both mother & fetus. [Int J Reprod Contracept Obstet Gynecol 2013; 2(2.000: 213-216

  3. Vaginal flora in asymptomatic women.

    Science.gov (United States)

    Tashjian, J H; Coulam, C B; Washington, J A

    1976-09-01

    Four groups of 25 asymptomatic women--pregnant, premenopausal and taking oral contraceptives, premenopausal and not taking oral contraceptives, and postmenopausal--were studied for the presence in vaginal specimens of aerobic bacteria, anaerobic bacteria, fungi, Mycoplasma, Chlamydia, herpes simplex virus, mycobacteria, and Trichomonas. No significant differences in microbial flora were found among the groups. PMID:957791

  4. DWI in diagnosis of regional lymph node metastasis of colorectal cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the efficacy of diffusion-weighted imaging (DWI) for diagnosing regional lymph nodes metastasis in patients with colorectal cancer. Methods: 75 patients with colorectal cancer underwent preoperative routine MRI and DWI examination, and tumor dissection. Metastatic and non-metastatic lymph nodes were confirmed by pathology after operation. ADC values of lymph nodes and primary tumor were measured and statistically analyzed. Diagnostic efficacies of ADC values and rADC (lymph node/tumor) values in differentiating metastatic lymph nodes from non-metastatic lymph nodes were assessed by comparing area under curve (AUC) of receiver operating characteristic-curve. Results: Metastatic lymph nodes and non-metastatic lymph nodes were identified. The ADC value of metastatic lymph nodes and non-metastatic lymph nodes were (0.79±0.12) x10-3 mm2/s vs. (0.98±0.23) x 10-3 mm2/s, and showed significant difference (P<0.01). The rADC values of metastatic lymph nodes are significantly lower than that of non-metastatic lymph nodes (P<0.01). AUC of ADC and rADC were 0.776 vs. 0.883. The threshold, sensitivity, and specificity for differentiating metastatic lymph nodes from non-metastatic lymph nodes were 1.11x10-3 mm2/s vs. 1.03x10-3 mm2/s, 61.9% vs. 78.6%, and 88% vs.90% respectively. Conclusion: DWI has distinct advantages in detecting metastatic lymph nodes of colorectal cancer. rADC value is more accurate than ADC value. (authors)

  5. Asymptomatic Bacteriuria Frequency in Pregnancy

    Directory of Open Access Journals (Sweden)

    Sarı O et al.

    2011-02-01

    Full Text Available Most of the complications caused by asymptomatic bacteriuria (ABU in pregnancy can be avoided by early treatment. In our study, we aimed to determine the urinary infection prevalence and the pathogen agent identification in the pregnant women observing in our clinic. 240 asymptomatic pregnant women having no antibiotic treatment history during last 1 week and were enrolled to the study. Urine specimens were collected from 12th and 16th week pregnant women, and were examined by light microscope and cultured at the mediums. Demographic data belonging to the patients (age, birth number, abortion number were recorded. Mean age was assigned as 24, 49±2, 74 (20-31 years. 104 patients (43,3% were primipara, 94 patients (39.2% had previous pregnancy and 42 patients (17,5% were multipara. 19,2% of the patients (n=46 had an abortion history. Mean value of leucocyte levels among pregnant women was assigned as 10045 / mm3 (6750-15200. Although positive urine culture ratio was 12,5% (n=30 at first visit, it was 10% (n=30 in the 12th week. Urine culture in 16th week was determined as negative in all pregnant women. When agent pathogen was analyzed from urine culture, the most common isolated microorganism that causes asymptomatic bacteriuria (ABU was Escherichia coli with ratio of 83%(n=200. Asymptomatic bacteriuria (ABU is common in pregnancy and can cause serious maternal and fetal complications if it’s not treated on time and properly. Therefore; all pregnant women should be screened at first antenatal visit for asymptomatic bacteriuria (ABU as a routine program and medical treatment should be required at the positive cases.

  6. Randomized Controlled Trial of Pulmonary Metastasectomy in Colorectal Cancer: PulMiCC International Is Open in Italy

    OpenAIRE

    Migliore, Marcello; Lees, Belinda; Treasure, Tom; Fallowfield, Lesley J

    2013-01-01

    Advocates of the Pulmonary Metastasectomy in Colorectal Cancer trial describe trial design and goals, in agreement with others that such a trial is necessary to solve the question of whether or not surgery is beneficial in patients with metastatic colorectal cancer and, ultimately, to assist patients and clinical teams in deciding for or against pulmonary metastectomy.

  7. Inflammation-based prognostic scores and nutritional prognostic index in patients with locally-advanced unresectable colorectal cancer

    OpenAIRE

    Ikeguchi, Masahide; Urushibara, Sho-ichi; Shimoda, Ryugo; Yamamoto, Manabu; MAETA, YOSHIHIKO; Ashida, Keigo

    2014-01-01

    Background Unresectable colorectal cancer has a poor prognosis. However, some patients survive intensive chemotherapy, and complete resection of primary and metastatic tumors may even be possible. In the present study, we examined the prognostic factors associated with survival after intensive chemotherapy in patients with unresectable colorectal cancer. Methods This retrospective study enrolled 61 patients diagnosed with unresectable locally advanced colorectal cancer between January 2004 an...

  8. Tiam1 gene expression and its significance in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li Liu; De-Hua Wu; Yan-Qing Ding

    2005-01-01

    AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis.METHODS: Expressions of Tiam1 gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptasepolymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiam1 expression with the invasive ability was also analyzed.RESULTS: Tiam1 gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116,LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiam1 gene was highly related to the metastatic potential of colorectal carcinoma cells.CONCLUSION: Tiam1 gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.

  9. Asymptomatic bacteriuria in antenatal women

    OpenAIRE

    Lavanya S; Jogalakshmi D

    2002-01-01

    A total of 500 antenatal women in their first or second trimesters were screened over a period of 2 years for asymptomatic bacteriuria. Out of them, 8.4% (42) were culture positive. A control group of 100 non-pregnant women, both married and unmarried, was also simultaneously screened. The control group yielded an overall culture positivity of 3% (4% in the married non-pregnant women and 2% in the unmarried women). Primigravida had highest percent culture positivit...

  10. Five Myths about Colorectal Cancer

    Science.gov (United States)

    ... ACS » Your Local Offices Close + - Text Size Five Myths About Colorectal Cancer In many cases, colorectal cancer ... screening tests you need, when you need them. Myth: Colorectal cancer is a man’s disease. Truth: Colorectal ...

  11. Get Tested for Colorectal Cancer

    Science.gov (United States)

    ... Print This Topic En español Get Tested for Colorectal Cancer Browse Sections The Basics Overview What to Expect ... section Overview 2 of 6 sections The Basics: Colorectal Cancer What is colorectal cancer? Colorectal cancer is a ...

  12. Early dissemination of bevacizumab for advanced colorectal cancer: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Fouad Mona N

    2011-08-01

    Full Text Available Abstract Background We describe early dissemination patterns for first-line bevacizumab given for metastatic colorectal cancer treatment. Methods We analyzed patient surveys and medical records for a population-based cohort with metastatic colorectal cancer treated in multiple regions and health systems in the United States (US. Eligible patients were diagnosed with metastatic colorectal cancer and initiated first-line chemotherapy after US Food & Drug Administration (FDA bevacizumab approval in February 2004. First-line bevacizumab therapy was defined as receiving bevacizumab within 8 weeks of starting chemotherapy for metastatic colorectal cancer. We evaluated factors associated with first-line bevacizumab treatment using logistic regression. Results Among 355 patients, 31% received first-line bevacizumab in the two years after FDA approval, including 26% of men, 41% of women, and 16% of those ≥ 75 years. Use rose sharply within 6 months after FDA approval, then plateaued. 20% of patients received bevacizumab in combination with irinotecan; 53% received it with oxaliplatin. Men were less likely than women to receive bevacizumab (adjusted OR 0.55; 95% CI 0.32-0.93; p = 0.026. Patients ≥ 75 years were less likely to receive bevacizumab than patients Conclusions One-third of eligible metastatic colorectal cancer patients received first-line bevacizumab shortly after FDA approval. Most patients did not receive bevacizumab as part of the regimen used in the pivotal study leading to FDA approval.

  13. Liver resection in metastatic colorectal cancer: a multidisciplinary approach Resección hepática por metástasis de cáncer colorrectal: una visión multidisciplinar

    Directory of Open Access Journals (Sweden)

    J. F. Noguera Aguilar

    2005-11-01

    Full Text Available Aim: to analyze qualitative short-time results of a new program for multidisciplinary liver evaluation in complex cases of liver metastasis from colorectal cancer. Patients and methods: 40 clinical consecutive evaluations with liver metastasis assessed for major liver resection by a multidisplinary specialist committee. Complementary explorations performed included CT and ultrasounds, and MRI or PET for doubtful cases. Liver resection was made in a single operation or two-stage hepatectomy, or combined with other techniques. Results: postoperative mortality at 30 days was 4%. Complications occurred in 28%, with surgical wound infection being most frequent (20%; 16.6% of resections were transfused, with a mean volume of 1000 ml. Two patients needed reoperation -one for an intraperitoneal abscess and one for bile-duct stenosis. Percentage of global relapse was 36%, with 26% of relapses out of the liver. Actuarial survival at one year follow-up was 90%, and 82% at two years; 64% of patients remain free of disease two years after the operation. Conclusions: programs for liver resection for colorectal cancer metastasis may be implemented by multidisciplinary teams of recent setup. There is a need to evaluate own results and then compare them with a standard of quality previously reported.Objetivo: valorar los resultados cualitativos a corto y medio plazo de un programa de reciente implantación de evaluación hepática multidisciplinar de casos complejos de metástasis hepáticas de cáncer colorrectal. Pacientes y métodos: cuarenta evaluaciones clínicas consecutivas de pacientes con metástasis hepáticas de cáncer colorrectal valorados para resección hepática mayor, realizadas por un comité multidisciplinar de especialistas. Las exploraciones complementarias practicadas fueron TAC trifásica y ecografía intraoperatoria, junto a RMN y/o PET en casos de dudas. La resección hepática se podía realizar como gesto único o bien en dos tiempos y

  14. Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer

    OpenAIRE

    Thérèse H Franco; Ahmed Khan; Vishal Joshi; Beje Thomas

    2008-01-01

    Thérèse H Franco, Ahmed Khan, Vishal Joshi, Beje ThomasDepartment of Internal Medicine, University of Connecticut, Farmington, CT, USAAbstract: Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007). Arte...

  15. Asymptomatic bacteriuria Escherichia coli strains

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Nielsen, E.M.; Klemm, Per

    2006-01-01

    Urinary tract infections (UTIs) affect millions of people each year. Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU) in humans. Persons affected by ABU may carry a particular E. coli strain for extended periods of time without any symptoms. In contrast to...... uropathogenic E. coli (UPEC) that cause symptomatic UTI, very little is known about the mechanisms by which these strains colonize the urinary tract. Here, we have investigated the growth characteristics in human urine as well as adhesin repertoire of nine ABU strains; the ability of ABU strains to compete...

  16. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    OpenAIRE

    David Qualtrough; Phil Rees; Beverley Speight; Williams, Ann C.; Christos Paraskeva

    2015-01-01

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling path...

  17. Papillary thyroid carcinoma presenting as an asymptomatic pelvic bone metastases

    Directory of Open Access Journals (Sweden)

    Siddiq S

    2010-05-01

    Full Text Available Thyroid carcinoma is rare comprising 1% of all malignancies and commonly presents as a neck lump. Papillary thyroid carcinoma unlike follicular thyroid carcinoma tends not to metastasise to distant sites.We present a case of papillary thyroid carcinoma presenting as a solitary asymptomatic pelvic bone metastases and highlight current management of bone metastases. A 59-year old female was found on abdominal computerised tomography to have an incidental finding of a 4.5 cm soft tissue mass in the right iliac bone. Biopsy of the lesion confirmed metastatic thyroid carcinoma. There was no history of a neck lump, head and neck examination was normal. Further imaging confirmed focal activity in the right lobe of the thyroid. A total thyroidectomy and level VI neck dissection was performed and histology confirmed follicular variant of papillary carcinoma.Early detection of bone metastases have been shown to improve prognosis and thyroid carcinoma should be considered as a potential primary malignancy.

  18. Incidence of Asymptomatic Bacteriuria During Pregnancy

    OpenAIRE

    M.H. Shirazi; Sadeghifard, N; R Ranjbar; E. Daneshyar; A Ghasemi

    2006-01-01

    Incidence of asymptomatic bacteriuria during pregnancy among Iranian women was examined. Midstream urine was collected from 380 pregnant women and streaked on blood agar and incubated for 24 to 48 h. Growth was considered significant if 105 mL-1 bacteria were present. Among the pregnant women, 10.1% had asymptomatic bacteriuria. Age, past history of abortion, proteinuria, level of education, number of fertility had no significant association with asymptomatic bacteriuria occurrence. But lower...

  19. Computed tomography evaluation of colorectal carcinoma.

    Science.gov (United States)

    Scharling, E S; Wolfman, N T; Bechtold, R E

    1996-04-01

    Knowledge of the extent of primary colorectal carcinoma at initial diagnosis is critical for proper management of disease. Currently, CT does not have a role in screening for colorectal carcinoma, though promising work on virtual colonoscopy is on the horizon. In patients with proven colorectal carcinoma, accurate prospective noninvasive assessment can identify those who may benefit from preoperative local radiotherapy, hepatic resection or cryoablation, or intra-arterial chemotherapy. CT should be considered complementary to the clinical assessment of colorectal carcinoma and to other modalities, such as barium enema, endorectal ultrasonography, MRI, and immunoscintigraphy. Although limited in evaluation of the primary tumor and local spread, CT has proven useful in assessing patients thought to harbor extensive local or metastatic disease. CT is generally the modality of choice for imaging the postoperative patient. The cross-sectional display of CT clearly depicts the operative bed, particularly after abdominoperineal resection. Baseline examinations should be obtained 2 to 4 months after surgery, with follow-up examinations every 6 to 9 months for 2 years, and yearly studies thereafter. CT-guided biopsies should be performed when findings suggest recurrent carcinoma. PMID:8848730

  20. Immunotherapy and immunoescape in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNy in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma.

  1. Intracranial tumors: Metastatic

    International Nuclear Information System (INIS)

    CT in metastatic disease has resulted in the following benefits: (1) earlier evaluation of patients suspected of having interacranial metastases; (2) better determination of the number, size, and location of metastatic foci; (3) noninvasive follow-up of the various treatment modalities; and (4) occasional suggestion of possible primary site or sites when not already known

  2. Colorectal cancer implant in an external hemorrhoidal skin tag

    Science.gov (United States)

    Liasis, Lampros

    2016-01-01

    External hemorrhoidal skin tags are generally benign. Colorectal cancer metastases to the squamous epithelium of perianal skin tags without other evidence of disseminated disease is a very rare finding. We present the case of a 61-year-old man with metastasis to an external hemorrhoidal skin tag from a midrectal primary adenocarcinoma. This case report highlights the importance of close examination of the anus during surgical planning for colorectal cancers. Abnormal findings of the perianal skin suggesting an implant or metastatic disease warrant biopsy, as distal spread and seeding can occur. In our patient, this finding appropriately changed surgical management. PMID:27034567

  3. Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer

    OpenAIRE

    Sastre, J.; Argilés, G.; M. Benavides; Feliú, J.; García-Alfonso, P.; García-Carbonero, R.; Grávalos, C.; Guillén-Ponce, C; Martínez-Villacampa, M.; Pericay, C

    2014-01-01

    Colorectal cancer is one of the most common tumors worldwide and at least 50 % of patients with this disease develop metastases. In this setting, additional treatment options are needed for patients presenting disease progression after exhausting all standard therapies. Regorafenib is an orally administered multikinase inhibitor which has been shown to provide survival benefits to patients with metastatic colorectal cancer (mCRC). Although most adverse events (AEs) associated with regorafenib...

  4. Metastatic pituitary carcinoma in a patient with acromegaly: a case report.

    LENUS (Irish Health Repository)

    Sreenan, Seamus

    2012-01-01

    Asymptomatic pituitary abnormalities occur in about 10% of cranial magnetic resonance imaging scans, but metastatic carcinoma of the pituitary gland is rare: 133 cases have been reported. Two thirds secreted either prolactin or adrenocorticotropic hormone, and another 24% were non-secreting.

  5. Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer

    Science.gov (United States)

    Lee, Sung Hwan; Kim, Sung Hyun; Lim, Jin Hong; Kim, Sung Hoon; Lee, Jin Gu; Kim, Dae Joon; Choi, Gi Hong; Choi, Jin Sub

    2016-01-01

    Backgrounds/Aims Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. Methods Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. Results Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). Conclusions Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases.

  6. Asymptomatic bacteriuria Escherichia coli strains

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Nielsen, E.M.; Klemm, Per

    2006-01-01

    Urinary tract infections (UTIs) affect millions of people each year. Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU) in humans. Persons affected by ABU may carry a particular E. coli strain for extended periods of time without any symptoms. In contrast to...... uropathogenic E. coli (UPEC) that cause symptomatic UTI, very little is known about the mechanisms by which these strains colonize the urinary tract. Here, we have investigated the growth characteristics in human urine as well as adhesin repertoire of nine ABU strains; the ability of ABU strains to compete...... against the UPEC strain CFT073 was also studied. The different ABU strains displayed a wide variety of the measured characteristics. Half of the ABU strains displayed functional type 1 fimbriae while only one expressed functional P fimbriae. A good correlation between the growth rate of a particular...

  7. The Risk of Colorectal Neoplasia in Patients with Gallbladder Diseases.

    Science.gov (United States)

    Hong, Sung Noh; Lee, Tae Yoon; Yun, Sung-Cheol

    2015-09-01

    Cholecystectomy is associated with an increased risk of colorectal cancer, but little is known about the relationship between gallbladder disease and colorectal adenoma. Gallbladder polyps and colorectal neoplasia (CRN) share several risk factors such as obesity, diabetes and metabolic syndrome, which might account for their association. In this study, we investigated whether asymptomatic patients with gallbladder disease are at increased risk of CRN and identified the factors to their association. The study population consisted of 4,626 consecutive, asymptomatic individuals drawn from a prospective health check-up cohort who underwent both ultrasonography and colonoscopy screening. The prevalence of CRNs in patients with gallbladder polyps or gallstones was significantly higher than that in the control group (32.1% vs. 26.8%; P = 0.032, 35.8% vs. 26.9%; P = 0.020). A multivariate regression analysis showed that gallbladder polyps were an independent risk factor for CRN [adjusted odds ratio (OR): 1.29; 95% confidence interval (CI); 1.03-1.62] whereas gallstones were not (adjusted OR: 1.14; 95% CI: 0.79-1.63). The adjusted OR for the risk of CRN was 1.12 for gallbladder polyps CRN increased with increasing polyp size (P trend = 0.022). Our results suggest that colorectal neoplasia is significantly related to gallbladder polyps, especially those ≥ 5 mm. PMID:26339169

  8. Get Tested for Colorectal Cancer

    Science.gov (United States)

    ... Colorectal Cancer Print This Topic En español Get Tested for Colorectal Cancer Browse Sections The Basics Overview ... cancer screening tests . Does it hurt to get tested? Some people find the tests for colorectal cancer ...

  9. Nodal staging of colorectal carcinomas and sentinel nodes

    OpenAIRE

    Cserni, G.

    2003-01-01

    This review surveys the staging systems used for the classification of colorectal carcinomas, including the TNM system, and focuses on the assessment of the nodal stage of the disease. It reviews the quantitative requirements for a regional metastatic work up, and some qualitative features of lymph nodes that may help in the selection of positive and negative lymph nodes. Identification of the sentinel lymph nodes (those lymph nodes that have direct drainage from the primary tumour site) is o...

  10. Lenalidomide normalizes tumor vessels in colorectal cancer improving chemotherapy activity

    OpenAIRE

    Leuci, V.; Maione, F.; Rotolo, R.; Giraudo, E; Sassi, F.; Migliardi, G.; Todorovic, M.; Gammaitoni, L.; Mesiano, G.; Giraudo, L.; Luraghi, P.; Leone, F.; Bussolino, F.; Grignani, G.; Aglietta, M.

    2016-01-01

    Background Angiogenesis inhibition is a promising approach for treating metastatic colorectal cancer (mCRC). Recent evidences support the seemingly counterintuitive ability of certain antiangiogenic drugs to promote normalization of residual tumor vessels with important clinical implications. Lenalidomide is an oral drug with immune-modulatory and anti-angiogenic activity against selected hematologic malignancies but as yet little is known regarding its effectiveness for solid tumors. The aim...

  11. Dendritic cell-based cancer immunotherapy for colorectal cancer

    OpenAIRE

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are curr...

  12. New approaches in angiogenic targeting for colorectal cancer

    OpenAIRE

    Prat, Aleix; Casado, Esther; Cortés, Javier

    2007-01-01

    Colorectal carcinoma (CRC) is one of the leading causes of cancer death worldwide. In the last decade, the addition of irinotecan and oxaliplatin to standard fluorouracil-based chemotherapy regimens have set the new benchmark of survival for patients with metastatic CRC at approximately 20 mo. Despite these advances in the management of CRC, there is a strong medical need for more effective and well-tolerated therapies. The dependence of tumor growth and metastasis on blood vessels makes angi...

  13. Asymptomatic bacteriuria in antenatal women

    Directory of Open Access Journals (Sweden)

    Lavanya S

    2002-01-01

    Full Text Available A total of 500 antenatal women in their first or second trimesters were screened over a period of 2 years for asymptomatic bacteriuria. Out of them, 8.4% (42 were culture positive. A control group of 100 non-pregnant women, both married and unmarried, was also simultaneously screened. The control group yielded an overall culture positivity of 3% (4% in the married non-pregnant women and 2% in the unmarried women. Primigravida had highest percent culture positivity of 66.6%. The incidence was higher in less than 20 years age group i.e. 71.42%. Of the screening tests, Gram stained smear when compared with the standard loop method, showed the highest sensitivity of 95.2%. The specificity of the screening tests was high [Gram stained smear (98.6%, catalase test (97.1% and pus cell count(96.5%]. Escherichia coli was the most common organism isolated in the test and control groups. The organisms were sensitive to cephalexin, nitrofurantoin, amoxycillin and norfloxacin in decreasing order. Incidence of prematurity was 75% and that of low birth weight was 50% in untreated patients.

  14. Underpinning the repurposing of anthracyclines towards colorectal cancer

    DEFF Research Database (Denmark)

    Nygård, Sune Boris; Christensen, Ib Jarle; Smith, David Hersi;

    2013-01-01

    breast cancer. No prognostic characteristic of TOP2A was identified. Conclusion. TOP2A gene gain is present in numbers relevant to identify a subgroup of patients who may benefit from anthracycline therapy. Based on the present findings, we will initiate a prospective clinical trial designed to evaluate......Abstract Objective. We propose a repurposing strategy where anthracyclines are reintroduced to a subgroup of patients with metastatic colorectal cancer with the highest likelihood of response. In breast cancer, DNA topoisomerase II alpha gene (TOP2A) alterations predict incremental benefit of...... anthracyclines, but this association has not been investigated in colorectal cancer. Frequency analysis of TOP2A gene alterations in colorectal cancer and the association with prognosis are evaluated and the challenges of using a TOP2A/CEN-17 FISH probe combination are addressed. Material and methods. Formalin...

  15. Metastatic renal cell carcinoma presenting as a breast mass in a woman with history of primary breast cancer

    OpenAIRE

    Balliauw, C; Termote, B; Steen, A.; Moerman, P; M. R. Christiaens; Van Ongeval, C

    2011-01-01

    Metastatic extramammary breast tumours are uncommon and differential diagnosis with primary breast carcinoma may prove to be difficult. We report a case of a metastasis of a renal cell cancer in the breast in a woman with a history of primary breast cancer. On follow-up of her breast carcinoma, a lump was detected via mammography and ultrasound. Core needle biopsy revealed a metastatic extramammary lesion originating from an asymptomatic renal cell carcinoma. We conclude that the diagnosis of...

  16. Metachronous colorectal carcinoma

    DEFF Research Database (Denmark)

    Bülow, Steffen; Svendsen, L B; Mellemgaard, A

    1990-01-01

    During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

  17. Role of MGMT as biomarker in colorectal cancer

    Science.gov (United States)

    Inno, Alessandro; Fanetti, Giuseppe; Di Bartolomeo, Maria; Gori, Stefania; Maggi, Claudia; Cirillo, Massimo; Iacovelli, Roberto; Nichetti, Federico; Martinetti, Antonia; de Braud, Filippo; Bossi, Ilaria; Pietrantonio, Filippo

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients. PMID:25516857

  18. A Patient With an Asymptomatic Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Ewa Majos, MD; Rafal Dabrowski MD, PhD

    2015-02-01

    Full Text Available Atrial fibrillation (AF is a common and refractory arrhythmia. Prevalence of AF increases with age. Asymptomatic AF is a state of asymptomatic episodes of arrhythmia and its exact prevalence remains unknown. Ablation and therapy with antiarrhythmic agents may predispose to asymptomatic AF. Detection of silent AF is crucial for prevention of ischaemic stroke. Progress in continuous ECG monitoring by Holter ECG, telemetry methods or implantable devices can provide a useful tools for identifying silent AF. Simple screening procedures like pulse examination and ambulatory ECG may be helpful in arrhythmia detection and logically – ischemic stroke prevention.

  19. Genome-Wide Screening of Genes Showing Altered Expression in Liver Metastases of Human Colorectal Cancers by cDNA Microarray

    Directory of Open Access Journals (Sweden)

    Rempei Yanagawa

    2001-01-01

    Full Text Available In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions.

  20. Capecitabine in the management of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Hirsch BR

    2011-03-01

    Full Text Available Bradford R Hirsch, S Yousuf ZafarDivision of Medical Oncology, Duke University Medical Center, Durham, NC, USAAbstract: 5-Fluorouracil has been a mainstay in the treatment of colorectal cancer for nearly five decades; however, the use of oral formulations of the medication has been gaining increasing traction since capecitabine was approved for use in adjuvant settings by the US Food and Drug Administration in 2005. The use of capecitabine has since spread to a number of off-label indications, including the treatment of advanced or metastatic colorectal cancer and the neoadjuvant treatment of rectal cancer. In light of increasing utilization, it is critical that clinicians have a firm understanding of the literature supporting capecitabine across various settings as well as the attributes of the drug, such as its dosing recommendations, side-effect profile, and use in the elderly. The purpose of this review is to synthesize the literature in a fashion that can be used to help guide decisions. In a setting of increasing focus on cost, the pharmacoeconomic literature is also briefly reviewed.Keywords: colon cancer, colorectal cancer, rectal cancer, capecitabine, Xeloda

  1. Tissue inhibitor of matrix metalloproteinase-1 expression in colorectal cancer liver metastases is associated with vascular structures

    DEFF Research Database (Denmark)

    Illemann, Martin; Eefsen, Rikke Løvendahl; Bird, Nigel Charles;

    2016-01-01

    Metastatic growth by colorectal cancer cells in the liver requires the ability of the cancer cells to interact with the new microenvironment. This interaction results in three histological growth patterns of liver metastases: desmoplastic, pushing, and replacement. In primary colorectal cancer...... several proteases, involved in the degradation of extracellular matrix components, are up-regulated. In liver metastases, their expression is growth pattern dependent. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is a strong prognostic marker in plasma from colorectal cancer patients......, with significant higher levels in patients with metastatic disease. We therefore wanted to determine the expression pattern of TIMP-1 in primary colorectal cancers and their matching liver metastases. TIMP-1 mRNA was primarily seen in α-smooth-muscle actin (α-SMA)-positive cells. In all primary tumors and liver...

  2. ASYMPTOMATIC BACTERIURIA AND PYURIA IN PREGNANCY

    OpenAIRE

    M Rahimkhani; H Khavari-Daneshvar; Sharifian, R.

    2008-01-01

    "nPregnant women are at increased risk for urinary tract infection (UTI) but in many cases infection is asymptomatic. This study was performed to determine the incidence of asymptomatic bacteriuria and pyuria in pregnant women. A total of 86 pregnant women during first trimester and 56 nonpregnant women were evaluated. All subjects were clinically identified to have no signs and symptoms of UTI. Clean catch midstream urine samples were collected for both groups. Urine samples were examin...

  3. Asymptomatic bacteriuria and antibacterial susceptibility during pregnancy

    OpenAIRE

    Anjana Verma; Anamika Vyas; Lalit Shrimali; Medhavi Sharma

    2016-01-01

    Background: Urinary tract infections are more common in women than in men and still more in pregnant women because of anatomical and physiological changes during pregnancy. Incidence of asymptomatic bacteriuria is 2-10% globally and it is still more in developing countries. Untreated asymptomatic bacteriuria can lead to many prenatal and maternal complications; hence early detection and treatment is of considerable importance. Methods: Total 220 pregnant women at their first visit were scr...

  4. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Gundgaard, M.G.; Ehrnrooth, E.; Sørensen, Jens Benn

    2008-01-01

    median overall survival (mOS), median time to progression (mTTP) and response rate were recorded. RESULTS: We found 27 articles and 22 abstracts to fulfil the criteria. Patients who received regimens containing oxaliplatin and infusional 5-fluorouracil (5-FU) demonstrated mTTP up to 7 months and a mOS of...

  5. Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression

    International Nuclear Information System (INIS)

    Hypoxia-inducible factor 1 alpha (HIF-1α) is involved in processes promoting carcinogenesis of many tumors. However, its role in the development of colorectal cancer is unknown. To investigate the significance of HIF-1α during colorectal carcinogenesis and progression we examined its expression in precursor lesions constituting the conventional and serrated pathways, as well as in non-metastatic and metastatic adenocarcinomas. Immunohistochemistry and Western blot is used to analyse HIF-1α expression in normal colonic mucosa, hyperplastic polyps (HPP), sessile serrated adenomas (SSA), low-grade (TA-LGD) and high-grade (TA-HGD) traditional adenomas as well as in non-metastatic and metastatic colorectal adenocarcinomas. Eight colorectal carcinoma cell lines are tested for their HIF-1α inducibility after lipopolysaccharide (LPS) stimulation using western blot and immunocytochemistry. In normal mucosa, HPP and TA-LGD HIF-1α was not expressed. In contast, perinuclear protein accumulation and nuclear expression of HIF-1α were shown in half of the examined SSA and TA-HGD. In all investigated colorectal carcinomas a significant nuclear HIF-1α overexpression compared to the premalignant lesions was observed but a significant correlation with the metastatic status was not found. Nuclear HIF-1α expression was strongly accumulated in perinecrotic regions. In these cases HIF-1α activation was seen in viable cohesive tumor epithelia surrounding necrosis and in dissociated tumor cells, which subsequently die. Enhanced distribution of HIF-1α was also seen in periiflammatory regions. In additional in vitro studies, treatment of diverse colorectal carcinoma cell lines with the potent pro-inflammatory factor lipopolysaccharide (LPS) led to HIF-1α expression and nuclear translocation. We conclude that HIF-1α expression occurs in early stages of colorectal carcinogenesis and achieves a maximum in the invasive stage independent of the metastatic status. Perinecrotic

  6. 希罗达联合奥沙利铂治疗转移性结直肠癌的疗效系统评价%A Meta-analysis of Xeloda Combined with Oxaliplatin for Elderly Patients with Metastatic Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    江小梅; 彭杰文; 萧剑军

    2014-01-01

    Objective To assess the clinical efficacy of xeloda combined with oxaliplatin for elderly patients with meta -static colorectal cancer .Methods Literature search were performed by key words such asoxaliplatin ,xeloda,capecitabine ,meta-static colorectal cancer .Relevant literature with RCT from 2000-2012 associated with xeloda combined with oxaliplatin therapy were selected .The source of literature and manual searches were used for reducing undetected literature .2 researchers drew the details of research design ,characteristics of patients and outcomes from the studies included .Data analysis was performed by Stata 12.0.Results 125 articles were retrieved,7 of which met the criteria.Meta-analysis showed that the overall response rate was 17.60%(161/915) in the study group,and compared with 18.65%(169/906) in the control group,the difference was not sta-tistically significant [RR=0.90,95%CI (0.77,1.05),P=0.174].Of 6 studies (n=885),the standardized mean difference (SMD) of median survival was -0.065 [95%CI (-0.158,0.028),P=0.173];and of 7 studies (n=915),the SMD of me-dian progress-free survival was-0.046 [95%CI (-0.136,0.045),P=0.323].The differences were not statistically signifi-cant .Conclusion Xeloda combined with oxaliplatin therapy is effective ,which is similar with the therapy of 5-Fu combined with oxaliplatin,and should be recommended as first-line therapy.%目的:对希罗达联合奥沙利铂治疗转移性结直肠癌的临床疗效作系统评价。方法采用奥沙利铂、希罗达、卡培他滨、转移性结肠癌等检索词,查阅2000年至2012年国内外希罗达联合奥沙利铂治疗转移性结直肠癌随机对照试验的相关文献,并进行文献索源和手工检索,降低文献漏检。由2名人员按照预先制定的数据表筛选并摘录文献中试验设计、研究对象特征和研究结果。采用stata12.0统计软件处理数据。结果共检索文献125篇,按照筛选标准,共7篇纳入研究。meta

  7. Process of distant lymph node metastasis in colorectal carcinoma: Implication of extracapsular invasion of lymph node metastasis

    OpenAIRE

    Asao Takayuki; Tsutsumi Soichi; Yamaguchi Satoru; Yajima Reina; Tabe Yuichi; Fujii Takaaki; Kuwano Hiroyuki

    2011-01-01

    Abstract Background We previously demonstrated that extracapsular invasion (ECI) at a metastatic sentinel node was significantly associated with the presence of positive non-sentinel nodes in patients with breast cancer. However, the mechanism of metastatic spreading of tumor cells to distant lymph nodes in patients with colorectal carcinoma is not fully understood. In this study, we investigated the factors that may determine the likelihood of additional regional lymph node metastasis when m...

  8. Metastatic Crohn's disease

    Science.gov (United States)

    Lanka, Padmavathy; Lanka, Lakshmana Rao; Sylvester, N.; Lakshmi, M. Dhana; Ethirajan, N.

    2014-01-01

    Crohn's disease, first described in 1922, is characterized by segmental granulomatous inflammation of the intestinal tract and frequently involves the cutaneous tissues as well. Cutaneous Crohn's disease (CCD) is synonymous with metastatic Crohn's disease (MSD). A case of CCD, without any gastrointestinal involvement is reported for its rarity. PMID:24616854

  9. Metastatic Crohn's disease

    OpenAIRE

    Padmavathy Lanka; Lakshmana Rao Lanka; Sylvester, N.; M Dhana Lakshmi; Ethirajan, N.

    2014-01-01

    Crohn′s disease, first described in 1922, is characterized by segmental granulomatous inflammation of the intestinal tract and frequently involves the cutaneous tissues as well. Cutaneous Crohn′s disease (CCD) is synonymous with metastatic Crohn′s disease (MSD). A case of CCD, without any gastrointestinal involvement is reported for its rarity.

  10. Asymptomatic cerebral hemorrhage detected by MRI

    International Nuclear Information System (INIS)

    Detection of previous cerebral infarction on CT films of patients with no history of stroke is a common occurrence. The incidence of silent cerebral infarction was reported to be about 10 to 11 percent, but very few reports concerning asymptomatic cerebral hemorrhage available. However, recent clinical application of MRI has resulted in the detection of old asymptomatic hemorrhage in patients with no history known stroke-like episodes. The purpose of this study was to elucidate the incidence, the cause and the character of the asymptomatic cerebral hemorrhage among patients who had undergone MRI examinations. From September 1987 through June 1990, 2757 patients have undergone 3474 MR scans of the brain with 1.0 Tesla Siemens Magneton unit in our hospital. Seventeen patients showed no clinical signs or symptoms suggesting a stroke episode corresponding to the detected hemorrhagic lesion. The 17 patients corresponded to 0.6% of the patients who underwent MRI, 1.5% of the patients with cerebrovascular disease and 9.5% of the patients with intracerebral hemorrhage(ICH), which was rather higher than expected. Among the 17 patients, 12 were diagnosed as primary ICH and 5 as secondary ICH. Most of the primary asymptomatic hemorrhage were hypertensive ones and slit-like curvilinear lesions between the putamen and claustrum or external capsule. The secondary asymptomatic hemorrhage were due to AVM and angiomas in the frontal cortex, thalamus and pons. (author)

  11. Asymptomatic cerebral hemorrhage detected by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Yumi; Ohsuga, Hitoshi; Yamamoto, Masahiro; Shinohara, Yukito (Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine)

    1991-03-01

    Detection of previous cerebral infarction on CT films of patients with no history of stroke is a common occurrence. The incidence of silent cerebral infarction was reported to be about 10 to 11 percent, but very few reports concerning asymptomatic cerebral hemorrhage available. However, recent clinical application of MRI has resulted in the detection of old asymptomatic hemorrhage in patients with no history known stroke-like episodes. The purpose of this study was to elucidate the incidence, the cause and the character of the asymptomatic cerebral hemorrhage among patients who had undergone MRI examinations. From September 1987 through June 1990, 2757 patients have undergone 3474 MR scans of the brain with 1.0 Tesla Siemens Magneton unit in our hospital. Seventeen patients showed no clinical signs or symptoms suggesting a stroke episode corresponding to the detected hemorrhagic lesion. The 17 patients corresponded to 0.6% of the patients who underwent MRI, 1.5% of the patients with cerebrovascular disease and 9.5% of the patients with intracerebral hemorrhage(ICH), which was rather higher than expected. Among the 17 patients, 12 were diagnosed as primary ICH and 5 as secondary ICH. Most of the primary asymptomatic hemorrhage were hypertensive ones and slit-like curvilinear lesions between the putamen and claustrum or external capsule. The secondary asymptomatic hemorrhage were due to AVM and angiomas in the frontal cortex, thalamus and pons. (author).

  12. The role of selective Cox-2 inhibitors on HIF-1 alpha gene in colorectal cancer: an in-vitro study

    Directory of Open Access Journals (Sweden)

    Sanaz Rismanchi

    2014-10-01

    Conclusion: Angiogenesis is a key factor in the carcinogenesis process and FDA today approved bevacizumab as a first-line treatment for patients with metastatic colorectal cancer. The results of this study showed one of the causes of angiogenesis reduction in celecoxib-treated colorectal cancer. According to clinical findings and basic studies, celecoxib will be hopefully used as a first-line therapy along with chemotherapy in the near future in colorectal cancer. The advantages of this treatment method include its low cost and low side effects.

  13. Clinicopathological features and the value of differential Cytokeratin 7 and 20 expression in resolving diagnostic dilemmas of ovarian involvement by colorectal adenocarcinoma and vice-versa

    Directory of Open Access Journals (Sweden)

    Dikshit Rajesh

    2008-09-01

    Full Text Available Abstract The distinction between metastasis from a colorectal adenocarcinoma into the ovary and an ovarian adenocarcinoma is vital, but challenging at times, due to overlapping morphological features. Similarly, a distinction between an ovarian metastasis into the colorectum and a colorectal adenocarcinoma, although rare; is important and can be daunting. We report an analysis of 20 cases of ovarian involvement by metastatic colorectal adenocarcinomas and colorectal involvement by metastatic ovarian adenocarcinomas, including the value of differential expression of cytokeratins 7 & 20 by immunohistochemistry (IHC, in these cases. Nine cases (45% were identified as colorectal adenocarcinomas metastatic to the ovary. On biopsy, all these cases showed a 'garland-like' tumor necrosis, with desmoplasia and predominantly exhibited a tubuloalveolar pattern (67% cases. On IHC, all 8 of 9 such cases, where staining for cytokeratin 20 was performed, displayed strong positivity and 7 cases, where staining for carcinoembryogenic antigen (CEA was performed, revealed positivity for this marker (100%. Other 11 cases (55% were ovarian adenocarcinomas, metastatic to the colorectum. These showed metachronous presentations, with the ovarian tumor preceding the colorectal tumor deposits. Morphologically, psammomatous calcification was noted in 73% of these cases, whereas 'garland-like' necrosis was absent in all. The chief morphological subtype was serous papillary cystadenocarcinoma (55% cases. On IHC, CK7 and CA 125 were positive in all 6 of 11 such cases, whereas CK 20 was negative in all these cases. In cases of complex presentations like an ovarian involvement by a metastatic colorectal adenocarcinoma and vice-versa, certain clinicopathological features are useful. Differential expression of CK 7 and CK20 is vital in resolving these dilemmas. CK20 positivity and CK7 negativity is associated with a colorectal adenocarcinoma. Markers like CEA and CA-125 have an

  14. DIFFERENTIAL DIAGNOSIS OF PRIMARY AND METASTATIC OVARIAN TUMORS IN PATIENTS WITH COLONIC CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Komarov

    2013-01-01

    Full Text Available This report summarizes existing data on differential diagnosis between primary and metastatic ovarian cancer in patients with colorectal cancer (CRC. The results obtained in N.N. Blokhin Russian Cancer Research Center on the management of this malignancy are also presented. The evidence in favour of the need of genetic counseling and monitoring of the patients with aggravated familial history for early diagnosis of synchronous and metachronous ovarian cancer in patients with CRC is produced. A number of clinical, laboratory and diagnostic methods in addition to immunohistology and molecular genetics should be used for differential diagnosis of primary and metastatic ovarian cancer in patients with CRC.

  15. Screening for colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans J; Jakobsen, Karen V; Christensen, Ib J;

    2011-01-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....

  16. ASYMPTOMATIC BACTERIURIA AND PYURIA IN PREGNANCY

    Directory of Open Access Journals (Sweden)

    M Rahimkhani

    2008-11-01

    Full Text Available "nPregnant women are at increased risk for urinary tract infection (UTI but in many cases infection is asymptomatic. This study was performed to determine the incidence of asymptomatic bacteriuria and pyuria in pregnant women. A total of 86 pregnant women during first trimester and 56 nonpregnant women were evaluated. All subjects were clinically identified to have no signs and symptoms of UTI. Clean catch midstream urine samples were collected for both groups. Urine samples were examined microscopically and were cultured. Bacteriological examination revealed asymptomatic bacteriuria in 25 (29.1% and 3 (5.4% of the study group and controls, respectively (P < 0.05. Microscopic analysis of urine revealed pyuria in 18 (20.9% and 3 (5.4% of the study group and controls, respectively (P < 0.05. In study group, Escherichia coli were found in 20%, Staphylococcus epidermidis in 36%, Staphylococcus haemolyticus in 12%, streptococcus group D in 12%, Staphylococcus saprophyticus in 12% and Proteus mirabilis in 8%. In control group, E. coli were found in 33.3% and S. epidermidis in 66.7%. Our results show that the incidence of asymptomatic bacteriuria is significantly higher in pregnant women than nonpregnant women. The main finding in the present study was that 29.1% of the pregnant women who were in first trimester had asymptomatic bacteriuria which is much higher than figures reported from other countries. The use of microscopic urinanalysis was not an effective method of detecting asymptomatic bacteriuria and urine culture is necessary for screening these pregnant women.

  17. Evolving role of cetuximab in the treatment of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Gunter Schuch

    2009-07-01

    Full Text Available Gunter Schuch, Sebastian Kobold, Carsten BokemeyerDepartment of Oncology, Hematology, and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyAbstract: In recent years, the monoclonal epidermal growth factor receptor (EGFR-targeting antibody cetuximab was introduced into systemic therapy of colorectal cancer and gained an established role in the treatment of this disease. Cetuximab was shown to be active as a single agent in chemorefractory metastatic disease as well as in combination with varying chemotherapies. Recently, randomized trials demonstrated the activity of cetuximab combinations in the first-line setting of metastatic colorectal cancer. Interestingly, the activity of cetuximab was restricted to patients with KRAS wildtype tumors, as was seen with panitumumab, another EGFR antibody. While 60%–70% of tumors harbor KRAS wildtype genes, 30%–40% of tumors express oncogenic KRAS with mutations in codons 12 and 13 causing constitutive activation of signaling cascades downstream of EGFR and resistance to EGFR blockade. Since proof of KRAS wildtype status became a prerequisite for cetuximab treatment, KRAS testing is being established throughout the world. Future trials will address the question which part of the KRAS wildtype cohort will benefit from EGFR inhibition and how to identify those patients. Additionally, new strategies for treatment of KRAS mutated tumors are strongly needed. Recent developments and future strategies will be summarized.Keywords: cetuximab, colorectal cancer, KRAS

  18. Colorectal Cancer Coalition

    Science.gov (United States)

    ... disease. Sahar Wali, board member We're The Real Deal Telephone: (703) 548-1225 | 1414 Prince Street, Suite 204, Alexandria, VA 22314 © 2016 Fight Colorectal Cancer. All rights reserved. privacy policy | disclaimers | sponsors | linking policy Shares

  19. Prophylaxis against colorectal cancer

    DEFF Research Database (Denmark)

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing with a...... well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials for...... colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  20. Prophylaxis against colorectal cancer

    DEFF Research Database (Denmark)

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  1. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge;

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid in...... the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated...

  2. Gallstones and colorectal cancer

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Rafaelsen, Søren Rafael

    1992-01-01

    The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1.......59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give...... substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship....

  3. Adenocarcinoma of the caecum metastatic to the bladder: an unusual cause of haematuria

    Directory of Open Access Journals (Sweden)

    Hunt Roger

    2006-10-01

    Full Text Available Abstract Background Primary malignancies of colorectal origin can metastasise to the bladder. Reports are however extremely rare, particularly from the caecum. Case report The report describes the case of a 45-year old male with Duke's B caecal carcinoma treated with a laparoscopically-assisted right hemicolectomy and adjuvant 5-Fluorouracil chemotherapy. Subsequently, a metastatic lesion to the bladder was demonstrated and successfully excised by partial cystectomy. Conclusion In order that optimal therapeutic options can be determined, it is important for clinicians to distinguish between primary disease of the bladder and other causes of haematuria. Various immunohistochemical techniques attempt to differentiate primary adenocarcinoma of the bladder from secondary colorectal adenocarcinoma. Suspicion of metastatic disease must be raised when histologically unusual bladder tumours are identified.

  4. Cost benefit of early diagnosis of colorectal cancer.

    Science.gov (United States)

    Bolin, T D

    1996-01-01

    In most Western countries, colorectal cancer is an important disease in terms of morbidity and mortality. As it has a premalignant asymptomatic stage in the form of benign adenomas that might be detected by screening, and as screening leads to detection of colorectal cancer at an earlier stage, there is potential for improved and better quality survival. Most cost-effective analyses rank the various screening strategies at less than an accepted benchmark value of approximately $40,000 per added year of life. Periodic colorectal screening is therefore a cost-effective intervention and the Office of Technology Assessment of the Congress of the United States has concluded that colorectal cancer screening in average-risk adults beginning at age 50 is a relatively good investment for society. Flexible sigmoidoscopy and double contrast barium enema are the most cost-effective strategies but they both require colonoscopy if a lesion is identified. Colonoscopy at 10-yearly intervals is of comparable cost to flexible sigmoidoscopy every 5 years and less costly than FSIG every 3 years. Combination strategies, using faecal occult blood testing with periodic flexible sigmoidoscopy or double contrast barium enema are as costly as colonoscopy. The choice of screening strategies needs to be tailored to the individual, and a process of community education is an essential prerequisite to the success of any programme. PMID:8898453

  5. Screening for colorectal cancer.

    Science.gov (United States)

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test. PMID:21954677

  6. Techniques for colorectal anastomosis

    OpenAIRE

    Ho, Yik-Hong; Ashour, Mohamed Ahmed Tawfik

    2010-01-01

    Colorectal anastomotic leak remains one of the most feared post-operative complications, particularly after anterior resection of the rectum with, the shift from abdomino-peritoneal resections to total mesorectal excision and primary anastomosis. The literature fails to demonstrate superiority of stapled over hand-sewn techniques in colorectal anastomosis, regardless of the level of anastomosis, although a high stricture rate was noted in the former technique. Thus, improvements in safety asp...

  7. Malignant colorectal polyps

    Institute of Scientific and Technical Information of China (English)

    Luis; Bujanda; Angel; Cosme; Ines; Gil; Juan; I; Arenas-Mirave

    2010-01-01

    Nowadays, the number of cases in which malignant colorectal polyps are removed is increasing due to colorectal cancer screening programmes. Cancerous polyps are classified into non-invasive high grade neoplasia (NHGN), when the cancer has not reached the muscularis mucosa, and malignant polyps, classed as T1, when they have invaded the submucosa. NHGN is considered cured with polypectomy, while the prognosis for malignant polyps depends on various morphological and histological factors. The prognostic facto...

  8. [Colorectal foreign bodies].

    Science.gov (United States)

    Thim, Troels; Laurberg, Søren

    2006-09-25

    A patient with a retained anally introduced colorectal foreign body or complications hereof needs appropriate treatment. The patient may be in danger and is certainly in discomfort. The problem is relatively rare; however, its incidence may be expected to increase. Guidelines for handling of the situation are lacking in many textbooks. Here, a suggestion for handling of a patient with a retained colorectal foreign body or complications hereof is presented. PMID:17032594

  9. Asymptomatic body packers should be treated conservatively

    DEFF Research Database (Denmark)

    Glovinski, Peter V; Lauritsen, Morten L; Bay-Nielsen, Morten;

    2013-01-01

    Body packing takes advantage of the human storage capacity within the alimentary tract. Body packing is used for the smuggling of drugs such as heroin, cocaine, amphetamine, hashish and ecstasy. Most body packers are asymptomatic. However, packets may rupture or obstruct the alimentary tract...

  10. Multiseptate Gallbladder in an Asymptomatic Child

    Directory of Open Access Journals (Sweden)

    Dylan Wanaguru

    2011-01-01

    Full Text Available A one-year-old child being investigated for urinary tract infection was diagnosed with a multiseptate gallbladder. The patient remains asymptomatic, and investigations demonstrate no associated anomalies. Forty-three cases, including 13 cases in children were identified in the literature. Their presentation and management were reviewed.

  11. Asymptomatic Graves' disease during lithium therapy.

    OpenAIRE

    Thompson, C J; Baylis, P. H.

    1986-01-01

    Lithium salts are widely recognized to cause biochemical hypothyroidism and have been used to treat thyrotoxicosis. We present a case of Graves' disease which developed during lithium therapy. The patient was asymptomatic until the lithium was discontinued; she subsequently developed florid symptoms of thyrotoxicosis.

  12. Asymptomatic Pulmonary Hypertension in Systemic Lupus Erythematosus

    OpenAIRE

    Kamel, Shereen R.; Omar, Gihan M.; Darwish, Ayman F.; Asklany, Hany T.; Abdou S. Ellabban

    2011-01-01

    Introduction: Pulmonary arterial hypertension (PAH) is a serious and often fatal complication of systemic lupus erythematosus (SLE). Because the diagnosis of PAH often is made years after symptom onset, early diagnostic strategies are essential. Doppler echocardiography currently is considered the noninvasive screening test of choice for evaluating pulmonary hypertension. Aim: Screening for asymptomatic pulmonary hypertension in systemic lupus erythematosus patients using Doppler echocardiogr...

  13. Computed tomography in brain metastases of colorectal cancer

    International Nuclear Information System (INIS)

    Metastatic brain tumors from colorectal cancers are relatively rare. In previous reports, the incidence ranged from 3 to 5 percent of all metastatic brain tumors. We report 7 cases of metastatic brain tumors from colorectal cancers. The time interval from the diagnosis of the primary tumors to the brain metastasis was 3 years on the average. Metastasis to the lung and liver were also found in 6 cases at the time of the diagnosis of the brain metastasis. The CEA levels in the serum were highly elevated in all cases. Solitary metastasis was found in all cases; cancers tend to metastasize in the deep area of the cerebrum or cerebellum. On a plain CT scan, tumors were demonstrated as ring-type, with a high-density mass, and ring-like enhancement was seen in 6 cases. Prognosis was very poor in most cases. The median survival time from diagnosis of brain metastasis was 4.5 months in the 2 cases with surgery and 3.5 months in the 4 cases without surgery. (author)

  14. Contemporary methods of treatment of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Monika Kozłowska

    2016-01-01

    Full Text Available Today, colorectal cancer (CRC is the third most frequently diagnosed worldwide malignant cancer in males, and the second in females, with more than 1,200,000 new cases and more than 600,000 deaths, annually. Screening tests in oncology allow the detection of cancerous disease at an early, asymptomatic stage. The procedures most frequently performed in the case of colorectal cancer include: low anterior resection by the Dixon method (manual suture or staplers; abdominoperineal resection of the rectum by the Miles method; surgical procedure by the Hartmann method; local resection. Various techniques of preoperative radiotherapy are applied, aimed at tumour mass reduction (scheme I and/or obtaining local sterilisation (schemes I and II, which results in the reduction of local metastases (by approximately 50%, as well as an improvement with respect to long-term survival (by approximately 10%. At present, the following drugs for treatment of various forms of colorectal cancer have been registered by the Food and Drug Administration (FDA: fluorouracil capecitabine irinotecan, oxaliplatin, cetuximab, and bevacizumab. The combination of complete cytoreductive surgery (CCS, the goal of which is the removal of all visible (macroscopically cancer foci, with a simultaneous intraperitoneal chemotherapy in hyperthermia – HIPEC, destroying microscopic remains of the disease, allows the curing of some patients with peritoneal cancer. The effect of the action of monoclonal antibodies – cetuximab and panitumumab – is the inhibition of proliferation of cancer cells, intensification of their apoptosis, as well as reduction of synthesis and secretion of pro-angiogenic factors, such as interleukin 8 (IL-8 and vascular endothelial growth factor. In addition, antibodies targeted against EGFR impair the repair of DNA damage caused by chemotherapy and radiotherapy in the cells of the malignant tumour.

  15. Anaplastic transformation of metastatic papillary thyroid carcinoma at shoulder mimicking soft tissue sarcoma

    OpenAIRE

    Seema Kaushal; Mehar Chand Sharma; Mathur, Sandeep R.; Shishir Rastogi; Chander Shekhar Bal; Sunil Chumber

    2011-01-01

    A 52-year-old woman presented with fracture upper end of the left humerus after trivial trauma and aspiration cytology from the lytic lesion in the upper humerus seen on X-ray revealed a metastatic papillary carcinoma from the thyroid. Total thyroidectomy confirmed the papillary carcinoma thyroid. Post-operatively, she was given radioactive iodine (I-131) ablation therapy for 8 years and was asymptomatic during this period; however, for the last 1 year, she has been complaining of swelling in...

  16. PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis.

    Science.gov (United States)

    Nguyen, Alexander; Loo, Jia Min; Mital, Rohit; Weinberg, Ethan M; Man, Fung Ying; Zeng, Zhaoshi; Paty, Philip B; Saltz, Leonard; Janjigian, Yelena Y; de Stanchina, Elisa; Tavazoie, Sohail F

    2016-02-01

    Colorectal cancer metastasis to the liver is a major cause of cancer-related death; however, the genes and pathways that govern this metastatic colonization event remain poorly characterized. Here, using a large-scale in vivo RNAi screen, we identified liver and red blood cell pyruvate kinase (PKLR) as a driver of metastatic liver colonization. PKLR expression was increased in liver metastases as well as in primary colorectal tumors of patients with metastatic disease. Evaluation of a murine liver colonization model revealed that PKLR promotes cell survival in the tumor core during conditions of high cell density and oxygen deprivation by increasing glutathione, the primary endogenous antioxidant. PKLR negatively regulated the glycolytic activity of PKM2, the major pyruvate kinase isoenzyme known to regulate cellular glutathione levels. Glutathione is critical for metastasis, and we determined that the rate-limiting enzyme of glutathione synthesis, GCLC, becomes overexpressed in patient liver metastases, promotes cell survival under hypoxic and cell-dense conditions, and mediates metastatic liver colonization. RNAi-mediated inhibition of glutathione synthesis impaired survival of multiple colon cancer cell lines, and pharmacological targeting of this metabolic pathway reduced colonization in a primary patient-derived xenograft model. Our findings highlight the impact of metabolic reprogramming within the niche as metastases progress and suggest clinical potential for targeting this pathway in colorectal cancer. PMID:26784545

  17. p53 Mutations and Protein Overexpression in Primary Colorectal Cancer and its Liver Metastasis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To compare p53 status in primary and hepatic metastatic colorectal cancer in 34 patients. Methods: p53 gene status (exons 5- 9) was examined by PCR, denaturing gradient gel electrophoresis (DGGE) and automated sequencing. P53 protein was detected by immunohistochemistry using monoclonal antibody DO-7. Results: p53 mutations were found in exons 5 through 9 in 21 of 34 patients (61.8%). Among them, 5 patients had mutation in liver metastasis but not in their primary tumors while in the other patients the same mutations were found in both primary and metastatic colorectal cancers. In no patients was p53 mutation exclusively found in the primary colorectal tumors. Moreover, additional mutation was detected in the metastatic lesions in two cases. Of the 37 mutations within the exons examined, 73% was missense mutation and 16% was nonsense mutation. There were 4 microinsertions. P53 protein was overexpressed in both primary and metastatic colorectal cancers with p53 gene mutations. The presence of p53 mutation significantly correlated with p53 protein accumulation (r=0.96, p< 0.001). However, in 4 patients with p53 nonsense mutation, immunohistochemical staining was negative. In three patients who showed no p53 mutation of the primary tumor, p53 protein was consistently overexpressed. Conclusion: In colorectal cancers, p53 gene mutation usually appears first in the primary tumor and maintains as such but is more prominent when metastasized to the liver. However, p53 gene mutation may occur only after being metastasized.Although p53 gene mutation and p53 protein overexpression correlate with each other, either parameter examined alone may lead to false positive or negative results.

  18. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Summer 2016 Table of Contents Dr. Asad Umar, ... know to help determine the best colon cancer screening test for them? Colonoscopy is considered the gold ...

  19. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... of colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  20. Microflora of urogenital tract in pregnancy with asymptomatic bacterium

    International Nuclear Information System (INIS)

    The article contains results of research interrelationship from colonization of vagina and urinary tract diseases. E.coli one of the main factors in development asymptomatic bacterium. Presented high effects of penicillin medicaments and nitrofurans in treatment of asymptomatic bacterium

  1. Cysteine peptidase and its inhibitor activity levels and vitamin E concentration in normal human serum and colorectal carcinomas

    Institute of Scientific and Technical Information of China (English)

    Robert Szwed; Zygmunt Grzebieniak; Yousif Saleh; Godwin Bwire Ekonjo; Maciej Siewinski

    2005-01-01

    AIM: Cysteine peptidase (CP) and its inhibitor (CPI) are a matrix protease that may be associated with colorectal carcinoma invasion and progression, and vitamin E is also a stimulator of the immunological system. Our purpose was to determine the correlation between the expression of cysteine peptidases and their endogenous inhibitors,and the level of vitamin E in sera of patients with colorectal cancer in comparison with healthy individuals.METHODS: The levels of cysteine peptidases and their inhibitors were determined in the sera of patients with primary and metastatic colorectal carcinoma and healthy individuals using fluorogenic substrate, and the level of vitamin E was determined by HPLC.RESULTS: The levels of cysteine peptidases and their inhibitors were significantly higher in the metastatic colorectal cancer patients than that in the healthy controls (P<0.05).The activity of CP increased 2.2-fold, CPI 2.8-fold and vitamin E decreased 3.4-fold in sera of patients with metastasis in comparison with controls. The level of vitamin E in healthy individuals was higher, whereas the activity of cysteine peptidases and their inhibitors associated with complexes was lower than that in patients with cancer of the digestive tract.CONCLUSION: These results suggest that the serum levels of CP and their inhibitors could be an indicator of the prognosis for patients with metastatic colorectal cancer. Vitamin E can be administered prophylactically to prevent digestive tract neoplasmas.

  2. Mouse models of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yunguang Tong; Wancai Yang; H. Phillip Koeffler

    2011-01-01

    Colorectal cancer is one of the most common malignancies in the world. Many mouse models have been developed to evaluate features of colorectal cancer in humans. These can be grouped into genetically-engineered, chemically-induced, and inoculated models. However, none recapitulates all of the characteristics of human colorectal cancer. It is critical to use a specific mouse model to address a particular research question. Here, we review commonly used mouse models for human colorectal cancer.

  3. Esophageal Squamous Cell Carcinoma Patients Have an Increased Risk of Coexisting Colorectal Neoplasms

    OpenAIRE

    Baeg, Myong Ki; Choi, Myung-Gyu; Jung, Yun Duk; Ko, Sun-Hye; Lim, Chul-Hyun; Kim, Hyung Hun; Kim, Jin Su; Cho, Yu Kyung; Park, Jae Myung; Lee, In Seok; Kim, Sang-Woo

    2016-01-01

    Background/Aims Esophageal squamous cell carcinoma (ESCC) and colorectal neoplasms (CRNs) share risk factors. We aimed to investigate whether the CRN risk is increased in ESCC patients. Methods ESCC patients who underwent a colonoscopy within 1 year of diagnosis were retrospectively analyzed. Patients were matched 1:3 by age, gender, and body mass index to asymptomatic controls. CRN was defined as the histological confirmation of adenoma or adenocarcinoma. Advanced CRN was defined as any of t...

  4. Correlation of the ratio of metastatic to non-metastatic cancer cases with the degree of socioeconomic deprivation among Texas counties

    Directory of Open Access Journals (Sweden)

    Belasco Eric

    2011-02-01

    Full Text Available Abstract Background Previous studies have demonstrated that cancer registrations and hospital discharge rate are closely correlated with census data-based socioeconomic deprivation indices. We hypothesized that communities with higher degrees of socioeconomic deprivation tend to have a higher ratio of metastatic to non-metastatic cancer cases (lung, breast, prostate, female genital system, colorectal cancers or all types of cancers combined. In this study, we investigate the potential link between this ratio and the Wellbeing Index (WI among Texas counties. Results Cancer data in 2000 were provided by the Texas Cancer Registry, while data on the ten socioeconomic variables among the 254 Texas counties in 2000 for building the WI were obtained from U.S. Census Bureau. The ten socioeconomic status variables were subjected to the principal component analysis, and the first principal component scores were grouped into deciles for the WI (1 to 10 and the 254 Texas counties were classified into 10 corresponding groups. Weighted linear regression analyses and a Cochran-Armitage trend test were performed to determine the relationship between the ratio of age-adjusted metastatic to non-metastatic cancer incidence cases and WI. The ratios of metastatic to non-metastatic cases of female genital system cancer (r2 = 0.84, p = 0.0002, all-type cancers (r2= 0.73, p = 0.0017 and lung cancer (r2= 0.54, p = 0.0156 at diagnosis were positively correlated with WI. Conclusions The ratios of metastatic to non-metastatic cases of all-type, female genital system and lung cancers at diagnosis were statistically correlated with socioeconomic deprivation. Potential mediators for the correlation warrant further investigation in order to reduce health disparities associated with socioeconomic inequality.

  5. Tissue detection of natural killer cells in colorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Patsouris Efstratios S

    2004-09-01

    Full Text Available Abstract Background Natural killer (NK cells represent a first line of defence against a developing cancer; however, their exact role in colorectal cancer remains undetermined. The aim of the present study was to evaluate the expression of CD16 and CD57 [immunohistochemical markers of natural NK cells] in colorectal adenocarcinoma. Methods Presence of NK cells was investigated in 82 colorectal adenocarcinomas. Immunohistochemical analysis was performed, using 2 monoclonal antibodies (anti-Fc Gamma Receptor II, CD16 and an equivalent to Leu-7, specific for CD-57. The number of immunopositive cells (% was evaluated by image analysis. The cases were characterized according to: patient gender and age, tumor location, size, grade, bowel wall invasion, lymph node metastases and Dukes' stage. Results NK cells were detected in 79/82 cases at the primary tumor site, 27/33 metastatic lymph nodes and 3/4 hepatic metastases; they were detected in levels similar to those reported in the literature, but their presence was not correlated to the clinical or pathological characteristics of the series, except for a negative association with the patients' age (p = 0.031. Conclusions Our data do not support an association of NK cell tissue presence with clinical or pathological variables of colorectal adenocarcinoma, except for a negative association with the patients' age; this might possibly be attributed to decreased adhesion molecule expression in older ages.

  6. Immunotherapy in colorectal cancer: What have we learned so far?

    Science.gov (United States)

    Sanchez-Castañón, María; Er, Tze-Kiong; Bujanda, Luis; Herreros-Villanueva, Marta

    2016-09-01

    After decades of progress based on chemotherapy and targeted agents, patients with metastatic colorectal cancer still have low long-term survival, with more than 500,000 deaths occurring worldwide every year. Recent results showing clinical evidence of efficacy using immunotherapy in other types of tumors, such as melanoma and lung cancer, have also made this a viable therapy for evaluation in colorectal cancer in clinical trials. The development of cancer immunotherapies is progressing quickly, with a variety of technological approaches. This review summarizes the current status of clinical trials testing immunotherapy in colorectal cancer and discusses what has been learned based on previous results. Immunotherapy strategies, such as various models of vaccines, effector-cell therapy and checkpoint inhibitor antibodies, provide protection against progression for a limited subset of patients diagnosed with colorectal cancer. A better understanding of particular immune cell types and pathways in each patient is still needed. These findings will enable the development of novel biomarkers to select the appropriate subset of patients to be treated with a particular immunotherapy, and the tendencies determined from recent results can guide clinical practice for oncologists in this new therapeutic area and in the design of the next round of clinical trials. PMID:27350293

  7. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... know before using this tool: The Colorectal Cancer Risk Assessment Tool was designed for use by doctors and other health providers with their patients. If you are not a health ... your personal risk of colorectal cancer. (Colorectal cancer is another way ...

  8. Genetic evidence that intratumoral T-cell proliferation and activation is associated with recurrence and survival in patients with resected colorectal liver metastases

    OpenAIRE

    Maker, Ajay V; Ito, Hiromichi; Mo, Qianxing; Weisenberg, Elliot; Qin, Li-Xuan; Turcotte, Simon; Maithel, Shishir; Shia, Jinru; Blumgart, Leslie; Fong, Yuman; Jarnagin, William R; DeMatteo, Ronald P.; D'Angelica, Michael I.

    2015-01-01

    Though immune responses correlate with prognosis in primary colorectal cancer, the role of tumor immunity in metastatic disease is less clear. We hypothesized that patient survival and tumor recurrence correlate with transcriptional evidence of lymphocyte proliferation/activation in resected colorectal cancer liver metastases (CRLM). Microarray gene analysis was performed on liver tumor specimens from 96 patients who underwent resection for CRLM. A Cox proportional hazards model identified ge...

  9. Treatment approaches to asymptomatic follicular lymphoma.

    Science.gov (United States)

    Sarkozy, Clémentine; Salles, Gilles

    2013-12-01

    Follicular lymphoma is a heterogeneous disease in which some patients present an indolent evolution for decades and others, a rather aggressive form of the disease requiring immediate therapy. While immunochemotherapy has emerged as a standard of care for symptomatic patients, treatment of the asymptomatic population remains controversial. Since the disease is still considered incurable, delayed initiation of therapy is an acceptable option. However, four single injections of rituximab can result in an acceptable clinical response and can improve the duration of the interval without cytotoxic therapy. With recent therapeutic approaches that enable substantial improvements in life expectancy for follicular lymphoma patients, limiting short- or long-term treatment toxicities appears as a new concern in the asymptomatic population. Based on these options, the challenge is to preserve patient quality of life and prolong survival: from the patient's perspective, his/her opinion is therefore of significant importance. PMID:24219551

  10. Cerebral blood flow in asymptomatic individuals

    International Nuclear Information System (INIS)

    We studied the relationship between cortical grey matter flow (CBF) and age, cerebrovascular risk factors and the severity of subcortical hypersignals (HS, hyperintensity score in MRI) in 47 asymptomatic subjects with cerebrovascular risk factors. Multiple regression analysis revealed that HS was most strongly related to CBF, and that hematocrit, age and evidence of ischemic change detected in the electrocardiogram also appeared to be independent determinants of CBF. Both the severity and location of hypersignals were correlated with CBF. The most significant negative correlation observed was that between CBF and HS in the basal ganglia-thalamic region, where the degree of signal abnormality was modest. Decreased CBF in asymptomatic subjects with cerebrovascular risk factors may be related to microcirculatory disturbance associated with elevated hematocrit and an increase in the number of risk factors, and functional suppression of cerebral cortex due to the neuronal disconnection associated with subcortical lesions. In addition, impaired cerebral circulation may be related to MRI signal abnormalities. (author)

  11. Asymptomatic carotid disease and cardiac surgery consensus

    OpenAIRE

    Stansby, G.; MacDonald, S.; Allison, R; de Belder, M; Brown, MM; Dark, J; Featherstone, R; Flather, M; Ford, GA; Halliday, A.; Malik, I; R. Naylor; Pepper, J.; Rothwell, PM

    2011-01-01

    The Carotid Disease and Cardiac Surgery Consensus Meeting was convened as a multidisciplinary gathering to consider the management of patients undergoing cardiac surgery who are found to have asymptomatic carotid artery disease. There are no randomized trials concerning whether carotid interventions are of value in this situation and the natural history is unclear. Bilateral carotid artery disease (≥70% stenosis) should be regarded clinically relevant when considering hemodynamic and short-te...

  12. Asymptomatic torsion of intra-abdominal testis

    OpenAIRE

    M. Amin El-Gohary

    2015-01-01

    We report a case of intra-abdominal testicular torsion, of eight years old boy who presented with asymptomatic left impalpable testis. Diagnostic laparoscopy revealed a twisted small intra-abdominal testis in which the spermatic cord twisted 3 times over a band attached to the internal ring. The cord was long enough to bring the small testis into the scrotal sac. This case highlights the pole of laparoscopy in the management of impalpable testes.

  13. Dendritic cell-based cancer immunotherapy for colorectal cancer

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  14. Asymptomatic bacteriuria among HIV positive pregnant women.

    Science.gov (United States)

    Awolude, Olutosin A; Adesina, Olubukola A; Oladokun, Adesina; Mutiu, W B; Adewole, Isaac F

    2010-01-01

    The prognostic significance of asymptomatic bacteriuria resides in the observation that the prevalence is, relatively, high in persons with certain medical conditions, such as diabetes mellitus and pregnancy. This prevalence might, even, be higher in patients with human immunodeficiency virus infection. Hence, this study set out to determine the prevalence of asymptomatic bacteriuria among symptom free and newly enrolled HIV infected pregnant women attending PMTCT unit of Antiretroviral Clinic of University College Hospital, Ibadan, Nigeria between 1st May and 30th September 2007.Information was obtained on the socio-demographic characteristics of the subjects, CD4 count and viral load. Microbial culture was carried out on aseptically collected urines from the patients. Statistical analysis was done with SPSS 12 package. There were 161 analyzable samples from the participants. The mean age and gestational age at presentation of participants was 30.49 ± 4.3 years and 27.3 ± 3.2 weeks, respectively with modal parity of 2. Twenty-five (15.5%) of the urine samples significantly grew bacteria. The CD4 cells were significantly lower and the viral loads significantly higher(250.52 vs. 355.57 cells/mm3; 88,731 vs. 55,384 copies/ml; p = asymptomatic bacteriuria among PLWHAs is high. The microbial isolate from the urine samples were not different from those of HIV-negative patients. PMID:21178431

  15. Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer

    Directory of Open Access Journals (Sweden)

    Thérèse H Franco

    2008-10-01

    Full Text Available Thérèse H Franco, Ahmed Khan, Vishal Joshi, Beje ThomasDepartment of Internal Medicine, University of Connecticut, Farmington, CT, USAAbstract: Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF. It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007. Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab (Genetech, Inc. 2008. This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.Keywords: vascular endothelial growth factor, bevacizumab, metastatic cancer, chemotherapy, takotsubo, cardiomyopathy

  16. Perforation of metastatic melanoma to the small bowel with simultaneous gastrointestinal stromal tumor

    Institute of Scientific and Technical Information of China (English)

    Nathan Brummel; Ziad Awad; Shellaine Frazier; Jiafan Liu; Nitin Rangnekar

    2005-01-01

    The gastrointestinal tract (GIT) is a common site of metastases for malignant melanoma. These metastatic tumors are often asymptomatic. We describe a case of a 58-year-old male who presented with a sudden onset of generalized abdominal pain. The patient's past medical history was significant for lentigo melanoma of the right cheek. Laparotomy was performed and two segments ofsmall bowel, one with a perforated tumor, the other with a non-perforated tumor, were removed. Histology and immunohistochemical staining revealed the perforated tumor to be a metastatic malignant melanoma and the non-perforated tumor was found to be a gastrointestinal stromal tumor (GIST). The patient was discharged 7 d postoperatively. To the best of our knowledge, this is the first reported case in the literature of a simultaneous metastatic malignant melanoma and a GIST. Surgical intervention is warranted in patients with symptomatic GIT metastases to improve the quality of life or in those patients with surgical emergencies.

  17. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma

    Science.gov (United States)

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  18. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma.

    Science.gov (United States)

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  19. Colorectal liver metastases.

    OpenAIRE

    Burke, D; Allen-Mersh, T G

    1996-01-01

    Each year in the UK, between 12-14,000 people develop liver metastases from colorectal cancer. These metastases will contribute to the death of the patient in about 80% of cases. Treatments aimed at these tumours are best administered when the tumour is small. Current investigative methods allow tumours as small as 0.5 mm to be detected, and should be offered to all colorectal cancer patients at risk of developing liver metastases. Surgery remains the only curative treatment for these tumours...

  20. Colorectal cancer screening

    Institute of Scientific and Technical Information of China (English)

    Ramona M McLoughlin; Colm A O'Morain

    2006-01-01

    Colorectal cancer is a major public health burden worldwide.There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use.Most evidence points towards screening with fecal occult blood testing.The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests.In addition,their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can be accommodated within individual health care systems.

  1. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria.

    Science.gov (United States)

    Nicolle, Lindsay E

    2016-01-01

    Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients. PMID:27104571

  2. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria

    Directory of Open Access Journals (Sweden)

    Lindsay E. Nicolle

    2016-04-01

    Full Text Available Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients.

  3. Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Bogusław Kedra

    2009-01-01

    Full Text Available Colorectal cancer growth and spread is absolutely dependent on angiogenesis with vascular endothelial growth factor (VEGF being the most important cytokine involved in the process. Endoglin, a membrane co-receptor for TGF-beta, has recently emerged as a sensitive index of cancer stage. There is now sufficient evidence indicating that microvessel density assessed by endoglin-immunostaining correlates with stage of colorectal cancer and patient survival. An association of a soluble form of endoglin with lymph node and distant metastases has recently been reported in two studies. Both of them used local elaborated immunoassays for endoglin assessment. The aim of our study was to determine the efficacy of plasma endoglin, assessed using a commercial kit, as a marker of tumor spread and distant metastases in colorectal cancer patients. We studied 48 colorectal cancer patients, compared with 22 healthy subjects, using ELISA. We observed that colorectal cancer patients had increased plasma VEGF-A, but not endoglin levels. However, we found an association of plasma endoglin with the stage of malignancy. Endoglin levels were increased in metastasis-positive patients when compared to both metastasis-negative patients and healthy volunteers. Plasma endoglin correlated with VEGF-A, CEA and CA19.9. Endoglin assessment in plasma does not seem useful as a maker of colorectal cancer. Our observations indicate however that it might be helpful in selecting patients with metastatic disease.

  4. Combined perioperative plasma endoglin and VEGF--a assessment in colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Krystyna Pawlak

    2009-12-01

    Full Text Available Colorectal cancer growth and spread is absolutely dependent on angiogenesis with vascular endothelial growth factor (VEGF being the most important cytokine involved in the process. Endoglin, a membrane co-receptor for TGF-beta, has recently emerged as a sensitive index of cancer stage. There is now sufficient evidence indicating that microvessel density assessed by endoglin-immunostaining can correlate with stage of colorectal cancer and patient survival. An association of a soluble form of endoglin with lymph node and distant metastases has recently been reported in two studies. Both of them used local elaborated immunoassays for endoglin assessment. The aim of our study was to determine the efficacy of plasma endoglin, assessed using a commercial kit, as a marker of tumor spread and distant metastases in colorectal cancer patients. We studied 48 colorectal cancer patients, compared with 22 healthy subjects, using ELISA. We observed that colorectal cancer patients had increased plasma VEGF-A, but not endoglin levels. However, we found an association of plasma endoglin with the stage of malignancy. Endoglin levels were increased in metastasis-positive patients when compared to both metastasis-negative patients and healthy volunteers. Plasma endoglin correlated with VEGF-A, CEA and CA19.9. Endoglin assessment in plasma does not seem useful as a maker of colorectal cancer. Our observations indicate however that it might be helpful in selecting patients with metastatic disease.

  5. Colorectal cancer and pollution

    Institute of Scientific and Technical Information of China (English)

    AM; El-Tawil

    2010-01-01

    The incidence of colorectal carcinoma is increasing in young patients, in contrast to the well established wisdom that it is exclusively diagnosed in patients older than 40 years. In this survey, we examined all possible risk factors, and we recommend a number of measures for early detection in young patients who are at risk of developing this malignant tumor.

  6. Colorectal Cancer Screening

    Science.gov (United States)

    ... laxatives to clear the colon, shows polyps clearly. DNA stool test This test checks DNA in stool cells for genetic changes that may be a sign of colorectal cancer. Screening clinical trials are taking place in many parts of the ... Screening tests have risks. False-negative test results can occur. ...

  7. Colorectal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Colorectal Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race ...

  8. JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats

    International Nuclear Information System (INIS)

    Epidemiological studies have shown that individuals who regularly consume NSAIDs have lower rates of mortality associated with colorectal cancer. Because COX-2 inhibitors prevent tumor growth through some mechanisms, we assessed the effect of JTE-522, a selective COX-2 inhibitor, on pulmonary metastases of colon cancer in a rat model. A suspension of 5 × 106 RCN-9 (rat colon cancer cells) was injected into the tail vein of 24 anesthetized male F344/DuCrj rats. Oral JTE-522 (0, 3, 10, or 30 mg/kg/day) was administered from the day before RCN-9 injection until the end of the study. Twenty-four days later, the lungs were removed from sacrificed rats and weighed. Pulmonary metastatic tumors were microscopically evaluated in the largest cross sections. We also performed immunohistochemical staining for both COX-2 and VEGF. JTE-522 dose-dependently decreased lung weight (p = 0.001) and the size of pulmonary metastatic tumors (p = 0.0002). However, the differences in the number of metastatic tumors among 4 groups were insignificant. Significant adverse effects of JTE-522 were undetectable. Immunohistochemical staining showed high levels of both COX-2 and VEGF in pulmonary metastatic tumors. JTE-522 dose-dependently decreased the size, but not the number of pulmonary metastases. COX-2 inhibitors might block metastatic tumor growth, but not actual metastasis. Selective COX-2 inhibitors might be useful as therapeutic agents that inhibit the growth of metastatic tumors, as well as the tumorigenesis of colorectal cancer

  9. Chromosomal Alterations during Lymphatic and Liver Metastasis Formation of Colorectal Cancer1

    OpenAIRE

    Knösel, Thomas; Schlüns, Karsten; Stein, Ulrike; Schwabe, Holger; Schlag, Peter Michael; Dietel, Manfred; Petersen, Iver

    2004-01-01

    Comparative genomic hybridization (CGH) was used to screen colorectal carcinomas for chromosomal aberrations that are associated with metastatic phenotype. In total, 63 tumor specimens from 40 patients were investigated, comprising 30 primary tumors, 22 systemic metastases (12 liver, 6 brain, and 4 abdominal wall metastases) and 11 lymph node tumors. Using statistical analysis and histograms to evaluate the chromosomal imbalances, overrepresentations were detected most frequently at 20q11.2–2...

  10. Which endpoints should we use in evaluating the use of novel fluoropyrimidine regimens in colorectal cancer?

    OpenAIRE

    Twelves, C. J.; Cassidy, J

    2002-01-01

    Although significant advances have been made in the treatment of advanced/metastatic colorectal cancer, 5-fluorouracil (5-FU) still forms the basis of chemotherapy. Recently, new 5-FU schedules and novel fluoropyrimidines have been developed, but there are no trials directly comparing these regimens. The current review describes the mechanisms of action, pre-clinical and phase I/II studies of two oral fluoropyrimidine therapies, capecitabine and uracil with tegafur plus leucovorin. It also co...

  11. COLD-PCR enhanced melting curve analysis improves diagnostic accuracy for KRAS mutations in colorectal carcinoma

    OpenAIRE

    Joseph Loren; Reddy Poluru L; Akagi Laura; Pritchard Colin C; Tait Jonathan F

    2010-01-01

    Abstract Background KRAS mutational analysis is the standard of care prior to initiation of treatments targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer. Sensitive methods are required to reliably detect KRAS mutations in tumor samples due to admixture with non-mutated cells. Many laboratories have implemented sensitive tests for KRAS mutations, but the methods often require expensive instrumentation and reagents, parallel reactions, multiple ...

  12. The Use of Microgravity To Emulate Three-Dimensional Tissue Interactions in Colorectal Cancer Metastasis

    Science.gov (United States)

    Jessup, J. Milburn

    1997-01-01

    The hypothesis of this ground-based project was that simulated microgravity may be used to recreate with high fidelity the in vivo environment in tissue culture. The objectives were to determine whether: (1) simulated microgravity induces differentiation within poorly differentiated human colon carcinoma cells that are similar to that observed in experimental metastases in vivo in nude mice; and (2) the use of simulated microgravity helps define the experimental metastatic potential of human colorectal carcinoma.

  13. Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis

    OpenAIRE

    Brandi, Giovanni; De Lorenzo, Stefania; Nannini, Margherita; Curti, Stefania; Ottone, Marta; Dall’Olio, Filippo Gustavo; Barbera, Maria Aurelia; Pantaleo, Maria Abbondanza; Biasco, Guido

    2016-01-01

    Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role...

  14. Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array

    OpenAIRE

    Abajo, A.; Bitarte, N; Zarate, R; Boni, V; Lopez, I; Gonzalez-Huarriz, M. (Marisol); Rodriguez, J.; Bandres, E; Garcia-Foncillas, J.

    2012-01-01

    AIM: To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer (mCRC) with the aim of identifying prognostic markers. METHODS: The expression of 44 angiogenesis-secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vascular endothelial growth factor (VEGF) and its soluble vascular endothelial growth factor receptor (sVEGFR)-1 protein levels by enzyme immunoassay (EIA) in a panel of 16 CRC...

  15. Prevalence of asymptomatic urinary abnormalities among adolescents

    Directory of Open Access Journals (Sweden)

    Mohamed Fouad

    2016-01-01

    Full Text Available To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1% individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8% at the second screening, (P <0.001. Hematuria was the most common urinary abnormalities detected in 245 (9.8% adolescents who had persistent urine abnormalities; 228 (9.1% individuals had non glomerular hematuria. The hematuria was isolated in 150 (6% individuals, combined with leukocyturia in 83 (3.3% individuals, and combined with proteinuria in 12 (0.5% individuals. Leukocyturia was detected in 150 (6% of all studied adolescents; it was isolated in 39 (1.6% individuals and combined with proteinuria in 28 (1.1% of them. Asymp- tomatic bacteriuria was detected in 23 (0.9% of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6% of all the studied adolescents; 45 (1.8% indivi- duals had <0.5 g/day and twenty (0.8% individuals had 0.5-3 g/day. Asymptomatic urinary abnormalities were more common in males than females and adolescents from rural than urban areas (P <0.01 and (P <0.001, respectively. The present study found a high prevalence of asymptomatic urinary abnormalities among adolescents in our population.

  16. Asymptomatic neonatal colonisation by Clostridium difficile.

    OpenAIRE

    Bolton, R P; Tait, S K; Dear, P R; Losowsky, M. S.

    1984-01-01

    In a prospective survey of infants born in a single maternity unit, asymptomatic faecal colonisation by Clostridium difficile occurred in 31 (47%) of 66 babies who provided a faecal sample during week one of life and at age 14 and 28 days, and in 46 (30.7%) of the total of 150 babies for whom at least one faecal sample was obtained during the month of study. There was no evidence for acquisition of the organism from the mother during delivery and colonisation was unrelated to the means of del...

  17. Asymptomatic Bacteriuria in Clinical Urological Practice

    DEFF Research Database (Denmark)

    Cai, Tommaso; Mazzoli, Sandra; Lanzafame, Paolo;

    2016-01-01

    Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary antimicrobial use. The reduction of antibiotic overuse for ABU is consequently an important issue for antimicrobial stewardship and to reduce the emergence of multidrug resistant strains. There are two...... risk factor, and screening and treatment are not considered necessary. On the other hand, in the case of all procedures entering the urinary tract, ABU should be treated in line with the results of a urine culture obtained before the procedure. In patients affected by rUTIs, ABU can even have a...

  18. Asymptomatic ulcerative colitis and pyoderma gangrenosum

    Directory of Open Access Journals (Sweden)

    Nanda Arti

    1990-01-01

    Full Text Available A Total of 11 patients of pyoderma gangrenosum (PG; 5 males and 6 females were observed over 8 years. The ages ranged between 35-72 years. Nine patients were associated with ulcerative colitis, one with chronic renal failure, and one was labelled idiopathic. Three of the 9 patients of PG, who had ulcerative colitis presented first with skin lesions and had clinically silent, but acute, ulcerative colitis, diagnosed only after colonoscopy and rectal biopsy. This highlights the need for investigation including colonoscopy and biopsy even in asymptomatic patients of PG. Most of the cases benefitted from medical treatment (Corticosteroids + Salazopyrin.

  19. Neurosyphilis Presenting as Asymptomatic Optic Perineuritis

    OpenAIRE

    Parker, Sarah E.; Pula, John H.

    2012-01-01

    Introduction. Syphilis is a sexually transmitted disease that is known as “the great imitator” due to its wide variety of clinical presentations, including ocular disorders. There has been an increase in the rate of syphilis in the United States, especially in persons with HIV. We report a case of optic perineuritis in an asymptomatic male secondary to central nervous system (CNS) syphilis. Case Report. A 41-year-old man was found to have bilateral disc edema on a routine exam. Brain MRI was ...

  20. Carrier molecules and extraction of circulating tumor DNA for next generation sequencing in colorectal cancer.

    Science.gov (United States)

    Beránek, Martin; Sirák, Igor; Vošmik, Milan; Petera, Jiří; Drastíková, Monika; Palička, Vladimír

    2016-01-01

    The aims of the study were: i) to compare circulating tumor DNA (ctDNA) yields obtained by different manual extraction procedures, ii) to evaluate the addition of various carrier molecules into the plasma to improve ctDNA extraction recovery, and iii) to use next generation sequencing (NGS) technology to analyze KRAS, BRAF, and NRAS somatic mutations in ctDNA from patients with metastatic colorectal cancer. Venous blood was obtained from patients who suffered from metastatic colorectal carcinoma. For plasma ctDNA extraction, the following carriers were tested: carrier RNA, polyadenylic acid, glycogen, linear acrylamide, yeast tRNA, salmon sperm DNA, and herring sperm DNA. Each extract was characterized by quantitative real-time PCR and next generation sequencing. The addition of polyadenylic acid had a significant positive effect on the amount of ctDNA eluted. The sequencing data revealed five cases of ctDNA mutated in KRAS and one patient with a BRAF mutation. An agreement of 86% was found between tumor tissues and ctDNA. Testing somatic mutations in ctDNA seems to be a promising tool to monitor dynamically changing genotypes of tumor cells circulating in the body. The optimized process of ctDNA extraction should help to obtain more reliable sequencing data in patients with metastatic colorectal cancer. PMID:27526306

  1. Beyond Histologic Staging: Emerging Imaging Strategies in Colorectal Cancer with Special Focus on Magnetic Resonance Imaging.

    Science.gov (United States)

    Fraum, Tyler J; Owen, Joseph W; Fowler, Kathryn J

    2016-09-01

    Imaging plays an increasingly important role in the staging and management of colorectal cancer. In recent years, magnetic resonance imaging (MRI) has supplanted transrectal ultrasound as the preferred modality for the locoregional staging of rectal cancer. Furthermore, the advent of both diffusion-weighted imaging and hepatobiliary contrast agents has significantly enhanced the ability of MRI to detect colorectal liver metastases. In clinical practice, MRI routinely provides prognostic information, helps to guide surgical strategy, and determines the need for neoadjuvant therapies related to both the primary tumor and metastatic disease. Expanding on these roles for MRI, positron emission tomography (PET)/MRI is the newest clinical hybrid imaging modality and combines the metabolic information of PET with the high soft tissue contrast of MRI. The addition of PET/MRI to the clinical staging armamentarium has the potential to provide comprehensive state-of-the-art colorectal cancer staging in a single examination. PMID:27582645

  2. Monoclonal immunoscintigraphy for detection of metastasis and recurrence of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Vera Artiko; Neboj(s)a Radovanovi(c); Danijel Galun; Aleksandar Milovanovi(c); Jovica Milovanovi(c); Anica Bobi(c)-Radovanovi(c); Zoran Krivokapic; Vladimir Obradovi(c); Ana Koljevic Markovi(c); Dragana (S)obi(c)-(S)aranovi(c); Milorad Petrovi(c); Andrija Anti(c); Mirjana Stojkovi(c); Marinko (Z)uvela; Djordjije (S)aranovi(c); Milica Stojkovi(c)

    2011-01-01

    AIM: To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer. METHODS: Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocarcinomasuspected of local recurrence and metastatic disease. The results were compared with conventional diagnostics. RESULTS: Immunoscintigraphic investigation was done in 53 patients. Tumor recurrence occurred in 38 patients, and was confirmed by other diagnostic modalities in 35. In 15 patients, immunoscintigraphic findings were negative, and confirmed in 14 with other diagnostic methods. Comparative analysis confirmed good correlation of immunoscintigraphic findings and the results of conventional diagnostics and the level of tumor marker carcinoembryonic antigen. Statistical analysis of parameters of radiopharmaceutical groups imacis, indimacis and oncoscint presented homogenous characteristics all of three radiopharmaceuticals. The analysis of immunoscintigraphic target focus was clearly improved using tomography. CONCLUSION: Immunoscintigraphy is highly specific and has a good predictive value in local recurrence of colorectal cancer.

  3. Epigenetic changes in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yan Jia; Mingzhou Guo

    2013-01-01

    Epigenetic changes frequently occur in human colorectal cancer.Genomic global hypomethylation,gene promoter region hypermethylation,histone modifications,and alteration of miRNA patterns are major epigenetic changes in colorectal cancer.Loss of imprinting (LOI) is associated with colorectal neoplasia.Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation.HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment.Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer.This review is mainly focused on DNA methylation,histone modification,and microRNA changes in colorectal cancer.

  4. Differences in toileting habits between children with chronic encopresis, asymptomatic siblings, and asymptomatic nonsiblings.

    Science.gov (United States)

    Borowitz, S M; Cox, D J; Sutphen, J L

    1999-06-01

    No studies have compared toileting-specific behaviors of encopretic children with those of asymptomatic children and have controlled for environmental factors such as parental attitudes, parenting styles, and bathroom facilities. This study prospectively examined the toileting habits of 86 chronically encopretic children compared with those of 27 asymptomatic siblings and 35 asymptomatic nonsiblings. Although encopretic children experienced significantly more soiling than did controls, the total number of daily bowel movements passed in the toilet (+/-SD) was comparable in the three groups (.92 +/- .76 in encopretic children compared with 1.14 +/- .43 and 1.08 +/- .47 in siblings and nonsiblings, respectively). Encopretic children experienced pain with defecation more often than did controls. During the 14-day study period, encopretic children complained of pain on 2.75 +/- 4.03 days compared with .58 +/- 1.84 days among sibling controls and 2.31 +/- 3.21 days among nonsibling controls. The mean pain score in encopretic children was .76 +/- 1.00 compared with .05 +/- .15 and .26 +/- .38 among siblings and nonsiblings, respectively. All three groups of children sat on the toilet without parental prompting the same number of times each day. In summary, children with chronic encopresis do not seem to avoid toileting, and they exhibit toileting behaviors that are very similar to those of asymptomatic siblings as well as to those of nonsibling controls. PMID:10393070

  5. Critical appraisal of the use of regorafenib in the management of colorectal cancer

    International Nuclear Information System (INIS)

    The lack of valid clinical management options for patients affected by metastatic colorectal cancer, which has progressed after all approved standard treatments, has lead to research into new active molecules. Regorafenib is an oral small-molecule multi kinase inhibitor, binding to several intracellular kinases, with powerful inhibitory activity against vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3), platelet-derived growth factor receptor, fibroblast growth factor receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. The antitumor activity of regorafenib has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in several cancer models, particularly colorectal cancer and gastrointestinal stromal tumors. The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation. Only a few Phase I–II trials, and most recently a Phase III trial in pretreated colorectal cancer, have been carried out to date. Several ongoing trials are testing the efficacy of regorafenib in combination with chemotherapy. At this point in time, regorafenib is the first small-molecule tyrosine kinase inhibitor to gain approval by the US Food and Drug Administration for pretreated metastatic colorectal cancer patients

  6. EGFR signaling in colorectal cancer: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Saletti P

    2015-01-01

    Full Text Available Piercarlo Saletti,1 Francesca Molinari,2 Sara De Dosso,1 Milo Frattini2 1Oncology Institute of Southern Switzerland, Bellinzona, 2Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland Abstract: Colorectal cancer (CRC remains a formidable health burden worldwide, with up to 50% of patients developing metastases during the course of their disease. This group of CRC patients, characterized by the worst prognosis, has been extensively investigated to improve their life expectancy. Main efforts, focused on the epidermal growth-factor receptor (EGFR, which plays a pivotal role in CRC pathogenesis, have led to the development and introduction in clinical practice of specific targeted therapies (ie, monoclonal antibodies. Subsequently, the scientific community has tried to identify molecular predictors of the efficacy of such therapies. However, it has become clear that EGFR alterations occurring in CRC are difficult to investigate, and therefore their predictive role is unclear. In contrast, the clinical role of two downstream members (KRAS and NRAS has been clearly demonstrated. Currently, EGFR-targeted therapies can be administered only to patients with wild-type KRAS and NRAS genes. Our review addresses the medical management of metastatic CRC. Specifically, we describe in detail the molecular biology of metastatic CRC, focusing on the EGFR signaling pathway, and we discuss the role of current and emerging related biomarkers and therapies in this field. We also summarize the clinical evidence regarding anti-EGFR monoclonal antibodies and examine potential future perspectives. Keywords: colorectal cancer, EGFR, gene mutations, cetuximab, panitumumab

  7. Sinonasal Metastatic Tumors in Taiwan

    Directory of Open Access Journals (Sweden)

    Po-Hung Chang

    2008-10-01

    Full Text Available Background: To analyze the incidence of the metastatic tumors within sinonasal tract inTaiwan and review the data in the English literature.Methods: Retrospective reviewed of patients from 1990 to 2005 with a histologicallyproven diagnosis of metastatic malignancies in the sinonasal tract.Results: Among seventeen enrolled patients, 9 were men and 8 were women, withages ranging from 24 to 76 years old, with a mean of 50.8 years. In order offrequency, sinonasal metastatic tumors originated from the gastrointestinaltract (30%, liver (18%, kidney (18%, breast (18%, thyroid gland (12%and lung (6%.Conclusion: The incidence and characteristics of metastatic neoplasms in Taiwanesepatients are comparable to other countries in East Asia, except for Japan.However, our data are very different when compared with European andNorth American reports. Different incidences of malignant neoplasms in theprimary site may explain the result of different incidences of sinonasalmetastatic tumor.

  8. Neurosyphilis Presenting as Asymptomatic Optic Perineuritis

    Directory of Open Access Journals (Sweden)

    Sarah E. Parker

    2012-01-01

    Full Text Available Introduction. Syphilis is a sexually transmitted disease that is known as “the great imitator” due to its wide variety of clinical presentations, including ocular disorders. There has been an increase in the rate of syphilis in the United States, especially in persons with HIV. We report a case of optic perineuritis in an asymptomatic male secondary to central nervous system (CNS syphilis. Case Report. A 41-year-old man was found to have bilateral disc edema on a routine exam. Brain MRI was unremarkable, and lumbar puncture revealed a normal opening pressure, with an elevated cerebrospinal fluid white cell count. Orbit MRI showed optic nerve sheath expansion and enhancement, consistent with optic perineuritis. He tested positive for syphilis based on serum RPR and FTA-ABS. Conclusion. Ophthalmologic findings, including disc edema, may be the presenting features of CNS syphilis. Even in asymptomatic persons, perineuritis should be considered early, as diagnosis and treatment are imperative given the progressive nature of the disease.

  9. AC133抗原联合 EpCAM 识别转移性结直肠癌干细胞的研究%The study of combinin g AC133 antigen and E-cadherin in the identifying metastatic colorectal cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    杜航向; 杨治力; 杨逸; 盛能全; 王志刚

    2013-01-01

    目的:利用AC133抗原联合EpCAM检测人结直肠癌组织中结直肠癌干细胞,并初步观察其生物学特性,为后续结直肠癌干细胞研究提供实验基础。方法利用新鲜结直肠癌组织,无血清悬浮成球培养,流式细胞检测AC133、EpCAM 的表达情况,Balb/C小鼠移植观察其成瘤情况。组间比较采用t检验,以P<0.05为差异有统计学意义。结果从人原代结肠腺癌中分离、纯化AC133+EpCAM +结直肠癌干细胞,结直肠癌原代细胞中AC133+EpCAM +细胞比例为1.5%~35%(平均4.8%)。单克隆形成实验证实结直肠癌组织中存在肿瘤干细胞。其比例为2.18±0.15%,分离获得的AC133+EpCAM +细胞能在无血清培养基中“成球”,在血清诱导下能贴壁分化;将AC133+EpCAM+细胞移植在Balb/C裸鼠体内,表现出很强的致瘤性,移植瘤中AC133+EpCAM +细胞比例为4.9%~40.2%(平均17.2%)。结论人结肠腺癌组织中存在AC133+EpCAM +细胞群,具有和普通干细胞相类似的无限增殖、自我更新和分化能力,可为人结直肠癌干细胞的后续研究提供实验基础。%Objective To isolate colorectal cancer stem cells from human fresh carcinoma samples obtained at surgical operation and to study their biological characteristics .Then to provide foundation for the follow-up experiments .Methods Colorectal cancer tissues obtained from surgically resected specimens of colorectal cancer patients were fully chopped ,trypsinized,and filtered to prepare single cell suspensions .The cells were cultured in serum-free DMEM/F12 medium,with LIF,EGF,bFGF and 2% fetal bovine serum weekly.The stem cell-markers AC133 and EpCAM on the isolated cells were detected by using flow cytometry.The tumorigenic potent of the isolated cells was evaluated via the transplantation into Balb /C nude mice.All the variables were tested with T-test.P<0.05 was considered to be

  10. Revaluation on detection of metastatic cancer of the colorectum with barium enema. Comparison with computed tomography and colonoscopy

    International Nuclear Information System (INIS)

    The findings with barium enema were analyzed and compared to those with computed tomography and colonoscopy in 15 patients with metastatic cancer of the colorectum, which were from 8 gastric, 2 colonic, 2 ovarian, 1 pancreatic, 1 prostatic carcinomas and 1 unknown origin. Primary cancers of intra-abdominal cavity origin tended to make multiple colorectal metastases (91.7%). With barium enema colonic and rectal involvement was mostly expressed as the tethered type and the diffuse type by Ishikawa's classification, respectively. Computed tomography detected direct tumor invasion to the colorectum in 4 cases. Of the other 11 cases, 8 patients (72.3%) showed abnormally thickened colorectal wall. Colonoscopy detected only 3 (37.5%) out of 8 lesions seen in 4 patients who had undergone colonoscopy before barium enema. Many of the lesions missed were the tethered type involvement. Barium enema is the most sensitive method to detect metastatic cancer of the colorectum. (author)

  11. Ectopic Prostatic and Seminal Vesicle Tissue Confusing as Metastatic Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Jyotsna Wader

    2014-05-01

    Full Text Available Ectopic prostatic tissue and seminal vesicle at pericolic fat is extremely rare. The nodules in the pericolic fat could raise a dilemma of metastatic deposits in cases of rectal adenocarcinoma. A 61 years old male underwent abdomino-perineal resection for rectal carcinoma. Nodules along with lymph nodes from pericolic fat were sampled to assess the spread. Histopathological and immunohistochemical staining of one nodule confirmed it to be the prostatic tissue while another nodule to be seminal vesicle. Seminal vesicle and prostatic heterotopia is significant in several respects, either symptomatic or asymptomatic, as the ectopic tissue can be endoscopically and histologically confused with malignancy of urinary or lower gastrointestinal system and may reflect divergent differentiation or a malformative process.

  12. A case report on efficacy of Abound™ for anti-EGFR antibody-associated skin disorder in metastatic colon cancer

    OpenAIRE

    Matsuhashi, Nobuhisa; Takahashi, Takao; Nonaka,kenichi; ICHIKAWA, KENGO; Yawata, Kazunori; Tanahashi, Toshiyuki; Imai, Hisashi; Sasaki, Yoshiyuki; Tanaka, Yoshihiro; Okumura, Naoki; Yamaguchi, Kazuya; Osada, Shinji; Yoshida, Kazuhiro

    2014-01-01

    Background Panitumumab is a full human epidermal growth factor receptor (EGFR) monoclonal antibody, an agent for metastatic colorectal cancer therapy. One of the most general adverse events of anti-EGFR monoclonal antibody therapy is skin disorder. At the present time, although prophylaxis of skin disorder is important for continuation of cancer therapy, there are no effective precautionary treatments. Case presentation A 73-year-old male with sigmoid colon cancer and synchronous lung metasta...

  13. Changes in thymidylate synthase mRNA in blood leukocytes from patients with colorectal cancer after bolus administration of 5-fluorouracil

    DEFF Research Database (Denmark)

    Ehrnrooth, E; Sørensen, B; Poulsen, J H;

    2000-01-01

    5-fluorouracil (5-FU) is considered the standard antineoplastic drug of choice for metastatic colorectal cancer. It has been suggested that 5-FU administered as bolus infusion is cytotoxic mainly through an RNA damaging effect. We investigated the effect of i.v. bolus 5-FU 500-600 mg/m2 on the 5-FU...

  14. Reproducibility of functional volume and activity concentration in (18)F-FDG PET/CT of liver metastases in colorectal cancer

    NARCIS (Netherlands)

    Heijmen, L.; Geus-Oei, L.F. de; Wilt, J.H. de; Visvikis, D.; Hatt, M.; Visser, E.P.; Bussink, J.; Punt, C.J.A.; Oyen, W.J.G.; Laarhoven, H.W.M. van

    2012-01-01

    PURPOSE: Several studies showed potential for monitoring response to systemic therapy in metastatic colorectal cancer patients with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Before (18)F-FDG PET can be implemented for response evaluation the repeatability should be known. Th

  15. RHOA inactivation enhances Wnt signaling and promotes colorectal cancer

    Science.gov (United States)

    Rodrigues, Paulo; Macaya, Irati; Bazzocco, Sarah; Mazzolini, Rocco; Andretta, Elena; Dopeso, Higinio; Mateo-Lozano, Silvia; Bilić, Josipa; Cartón-García, Fernando; Nieto, Rocio; Suárez-López, Lucia; Afonso, Elsa; Landolfi, Stefania; Hernandez-Losa, Javier; Kobayashi, Kazuto; Cajal, Santiago Ramón y; Tabernero, Josep; Tebbutt, Niall C.; Mariadason, John M.; Schwartz, Simo; Arango, Diego

    2014-01-01

    Activation of the small GTPase RHOA has strong oncogenic effects in many tumor types, although its role in colorectal cancer remains unclear. Here we show that RHOA inactivation contributes to colorectal cancer progression/metastasis, largely through the activation of Wnt/β-catenin signaling. RhoA inactivation in the murine intestine accelerates the tumorigenic process and in human colon cancer cells leads to the redistribution of β-catenin from the membrane to the nucleus and enhanced Wnt/β-catenin signaling, resulting in increased proliferation, invasion and de-differentiation. In mice, RHOA inactivation contributes to colon cancer metastasis and reduced RHOA levels were observed at metastatic sites compared to primary human colon tumors. Therefore, we have identified a new mechanism of activation of Wnt/β-catenin signaling and characterized the role of RHOA as a novel tumor suppressor in colorectal cancer. These results constitute a shift from the current paradigm and demonstrate that RHO GTPases can suppress tumor progression and metastasis. PMID:25413277

  16. Association between measures of obesity and colorectal adenoma

    Institute of Scientific and Technical Information of China (English)

    KIM You Joung; LEE Kang-moon; CHUNG Woo Chul; PAIK Chang Nyol; JUNG Sung Hoon

    2011-01-01

    Background Few studies have used body mass index (BMI),waist-to-hip ratio (WHR) and waist circumference (WC) at the same time to investigate the association between obesity and colorectal adenoma.This study examined the strength of association between colorectal adenoma and obesity using not only BMI,but also WHR and WC.Methods Subjects of this study included 1322 asymptomatic patients who underwent colonoscopy for cancer screening from January 2006 to June 2008.Anthropometric measurements,blood test results,and a self-administered questionnaire from each subject were analyzed.Results Four hundred and fourteen adenoma cases were identified in 1322 subjects.Using univariate analysis,the prevalence of adenoma was associated with BMI and WHR and was higher among the abdominal obesity group using WC guidelines of the Korean Society for the Study of Obesity,but not using WC guidelines of the International Diabetes Federation.In multiple Logistic regression analysis,general obesity (BMI >25 kg/m2) increased the risk of colorectal adenoma (odds ratio (OR),1.43; 95% confidence interval (CI),1.05-1.94).Also,abdominal obesity by the WC cutoffs and the highest WHR percentile group (WHR >0.95) were significantly associated with adenoma.Among three measures of obesity,however,only BMI had a persistent association with adenoma after adjusting reciprocally for BMI,WC,and WHR (OR,1.30; 95% CI,1.02-1.80; and 1.49; 1.06-2.10,adjusted for WC and WHR,respectively).Conclusion The data suggest that general obesity is associated with an increased risk of colorectal adenoma.

  17. Epidemiology of colorectal cancer

    International Nuclear Information System (INIS)

    Colorectal tumors are among the most frequently encountered forms of cancer worldwide. With approximately 57,000 new cases every year, they represent the most frequent type of cancer in Germany, ranking before breast cancer (approximately 46,000) and lung cancer (approximately 37,000). Although global incidence is on the rise, in Germany it is only increasing among men, but not among women. The mortality rate (approximately 26,500 deaths annually) in Germany has declined among men for about the past 10 years and among women for about the past 20 years.The most important risk factors are familial history of colorectal and other tumors as well as lifestyle factors such as nutrition, obesity, inactivity,and smoking.Lifestyle-related risks offer a broad area for implementing primary preventive measures, which have not yet been adequately exhausted. Several proven (fecal occult blood test) and probably effective (endoscopic) methods are available for secondary prevention. Consistent encouragement of these possibilities for prevention could reduce incidence and mortality substantially and render colorectal tumors less frequent. (orig.)

  18. Primary colorectal lymphomas

    Directory of Open Access Journals (Sweden)

    Stanojević Goran

    2009-01-01

    Full Text Available Background/Aim. Colorectal lymphoma is a rare tumor representing 1.4% of human lymphomas, 10-20% of gastrointestinal lymphomas, namely 0.2-0.6% of all malignancies in the colon. The aim of this study was to review clinical characteristics of primary colorectal lymphoma and overall survival. Methods. A detailed analysis of 16 surgically treated patients included patients age, symptoms and signs, tumor site, type of surgery, histopathologic findings, diagnosis of the disease, disease stage, type of surgery related to the degree of emergency (elective or urgent, applied adjuvant therapy, patient follow-up and treatment outcomes. Survival was expressed by the Kaplan-Meier curve, while the difference in survival among the two groups by the Log-rank test. Results. The all patients were on an average followed-up for a median of 29 months (range 2-60 months, while those with chemotherapy 48 months (range 4-60 months. An overall mean survival time was 38.65 months. Conclusion. Primary colorectal lymphoma is a rare malignant tumor of the large bowel. Therapy usually involves resection of the affected colon or rectum and regional lymphovascular structures, followed by adjuvant therapy. Survival period is short and, therefore, timely diagnosis is crucial in early disease stages when the probability of cure is high.

  19. Nuclear legumain activity in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Mads H Haugen

    Full Text Available The cysteine protease legumain is involved in several biological and pathological processes, and the protease has been found over-expressed and associated with an invasive and metastatic phenotype in a number of solid tumors. Consequently, legumain has been proposed as a prognostic marker for certain cancers, and a potential therapeutic target. Nevertheless, details on how legumain advances malignant progression along with regulation of its proteolytic activity are unclear. In the present work, legumain expression was examined in colorectal cancer cell lines. Substantial differences in amounts of pro- and active legumain forms, along with distinct intracellular distribution patterns, were observed in HCT116 and SW620 cells and corresponding subcutaneous xenografts. Legumain is thought to be located and processed towards its active form primarily in the endo-lysosomes; however, the subcellular distribution remains largely unexplored. By analyzing subcellular fractions, a proteolytically active form of legumain was found in the nucleus of both cell lines, in addition to the canonical endo-lysosomal residency. In situ analyses of legumain expression and activity confirmed the endo-lysosomal and nuclear localizations in cultured cells and, importantly, also in sections from xenografts and biopsies from colorectal cancer patients. In the HCT116 and SW620 cell lines nuclear legumain was found to make up approximately 13% and 17% of the total legumain, respectively. In similarity with previous studies on nuclear variants of related cysteine proteases, legumain was shown to process histone H3.1. The discovery of nuclear localized legumain launches an entirely novel arena of legumain biology and functions in cancer.

  20. Colorectal cancer: diagnostic and therapeutic strategies

    International Nuclear Information System (INIS)

    Technical advances that has been achieved during the past two decades have not dramatically improved the 35 % five-year rate observed in patients with colorectal cancer. These tumours remain one of the most challenging problems in public health policies in western countries. Screening applies to some subgroups of high-risk individuals and the general population aged over 50. In order to improve their efficacy, such screening programs imply large-scale information campaigns and a strong cooperation with the general physicians. The diagnosis is strongly suggested by any recent modification of bowel habits ad by rectal bleeding. It has to be confirmed by rectal examination and by colonoscopy which allows sampling to the tumour. Loco-regional and distant metastatic tumour spread must be assessed precisely before any therapeutic strategy is decided. Surgery, which resects the tumour en bloc with the corresponding lymphatic territories, is the only treatment that can achieve long term cure. In localized tumours, surgery alone can provide patients with 5-years survival rates close to 95 %. On the other hand, surgery alone is not sufficient to cure patients with advances cancers. In recent years, several adjuvant therapeutic modalities have been shown to improve the results of surgery in these cases (rectal cancer: pre-operative radiotherapy or post-operative radio-chemotherapy, colon cancer with nodal metastases: post-operative chemotherapy). There is a hope that a better use of our diagnostic and therapeutic armementarium would be able to avoid or to cure up to 75 % of the colorectal cancers we are dealing with. (author)

  1. Liver-first approach of colorectal cancer with synchronoushepatic metastases: A reverse strategy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Recently, there has been a change in the strategy ofhow synchronous colorectal hepatic metastases areattributed to the development of more valuable protocolsof chemotherapy and radiotherapy for neoadjuvanttreatment of colorectal neoplasms and their hepaticmetastases. There is a consensus that patients withsynchronous colorectal hepatic metastases have lowersurvival than those with metachronous colorectal hepaticmetastases. Currently, controversy remains concerningthe best approach is sequence in a patient withcolorectal cancer and synchronous hepatic metastasesresection. To obtain a better patient selection, theauthors have suggested the initial realization of systemicchemotherapy in the circumstance of patients withcolorectal tumor stage Ⅳ, since these patients have asystemic disease. The rationale behind this liver-firststrategy is initially the control of synchronous hepaticmetastases of colorectal carcinoma, which can optimizea potentially curative hepatic resection and longstandingsurvival. The liver-first strategy procedure is indicatedfor patients with colorectal hepatic metastases whorequire downstaging therapy to make a curative liverresection possible. Thus, the liver-first strategy isconsidered an option in cases of rectal carcinoma in theearly stage and with limited or advanced synchronouscolorectal hepatic metastases or in case of patientswith asymptomatic colorectal carcinoma, but withextensive liver metastases. Patients undergoing systemicchemotherapy and with progression of neoplasticdisease should not undergo hepatic resection, becauseit does not change the prognosis and may even makeit worse. To date, there have been no randomizedcontrolled trials on surgical approach of colorectalsynchronous hepatic metastases, despite the relativelyhigh number of available manuscripts on this subject.All of these published studies are observational, usuallyretrospective, and often non-comparative. The patientselection criteria for the liver-first strategy

  2. Hedgehog Wnteraction in colorectal cancer

    OpenAIRE

    Brink, G.R. van den; Hardwick, J C H

    2006-01-01

    The Hedgehog pathway was recently shown to antagonise constitutive activity of the Wnt pathway that drives proliferation of colorectal cancer cells. Studies in this issue of Gut refine our understanding of the underlying mechanism and provide evidence for such antagonism in colorectal cancers in vivo

  3. Hedgehog Wnteraction in colorectal cancer

    NARCIS (Netherlands)

    G.R. van den Brink; J.C.H. Hardwick

    2006-01-01

    The Hedgehog pathway was recently shown to antagonise constitutive activity of the Wnt pathway that drives proliferation of colorectal cancer cells. Studies in this issue of Gut refine our understanding of the underlying mechanism and provide evidence for such antagonism in colorectal cancers in viv

  4. Colorectal cancer risk factors among the population of South-East Siberia: a case-control study.

    Science.gov (United States)

    Zhivotovskiy, Alexey S; Kutikhin, Anton G; Azanov, Artur Z; Yuzhalin, Arseniy E; Magarill, Yuri A; Brusina, Elena B

    2012-01-01

    Colorectal cancer remains one of the most widespread malignancies in the world. However, there is a lack of comprehensive studies considering colorectal cancer risk factors among Russian populations, particularly in Siberia. The aim of this investigation was to determine the impact of various lifestyle, dietary, family, and socioeconomical factors on colorectal cancer risk in South-East Siberia. We recruited 185 Russian colorectal cancer cases and 210 gender-, age-, and ethnicity-matched asymptomatic controls with no history of any malignant tumor, using a specially designed questionnaire to obtain relevant information. After the statistical analysis, we defined several significant factors affecting colorectal cancer risk. Among these were smoking (OR=2.13, 95%CI=1.4- 3.24, P=0.0004), being overweight (BMI between 25-30, OR=2.45, 95%CI=1.49-4.03, P=0.0004), alcohol drinking (OR=8.73, 95%CI=5.49-13.87, Pbeer drinking (OR=9.24, 95%CI=5.14-16.61, Pelaboration of programs of colorectal cancer prevention in Russia, particularly in Siberia. PMID:23244132

  5. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical & Analytical Sciences, University of the West of England, Faculty of Health and Applied Sciences, University of the West of England, Frenchay, Bristol BS16 1QY (United Kingdom); Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos [School of Cellular & Molecular Medicine, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD (United Kingdom)

    2015-09-17

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  6. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    David Qualtrough

    2015-09-01

    Full Text Available Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  7. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer

  8. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells.

    Science.gov (United States)

    Qualtrough, David; Rees, Phil; Speight, Beverley; Williams, Ann C; Paraskeva, Christos

    2015-01-01

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer. PMID:26393651

  9. The relationship between brain atrophy and asymptomatic cerebral lesions

    International Nuclear Information System (INIS)

    In order to clarify the relationship between brain atrophy and asymptomatic cerebral lesions, total of 235 subjects (130 males and 105 females), who had neither neurologic deficits nor organic lesions on cerebral computed tomography, were studied. The subjects' ages ranged from 40 to 86 years (mean 66). They were divided into two groups: 90 controls without hypertension or diabetes mellitus (Group C), and 145 patients with essential hypertension (Group H). Brain atrophy was diagnosed using the caudate head index (CHI). Asymptomatic cerebral lesions on magnetic resonance imaging were defined as asymptomatic lacunae and white matter lesions. Caudate head index was higher in Group H than it was in Group C, and CHI in both groups was significantly correlated with the number of asymptomatic lacunae and the severity of white matter lesions on magnetic resonance imaging. These results indicate that brain atrophy may progress along with asymptomatic cerebral lesions. (author)

  10. Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study

    International Nuclear Information System (INIS)

    Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients

  11. Inositol Hexaphosphate and Inositol Inhibit Colorectal Cancer Metastasis to the Liver in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Min Fu

    2016-05-01

    Full Text Available Inositol hexaphosphate (IP6 and inositol (Ins, naturally occurring carbohydrates present in most mammals and plants, inhibit the growth of numerous cancers both in vitro and in vivo. In this study, we first examined the anti-metastatic effects of IP6 and Ins using a liver metastasis model of colorectal cancer (CRC in BALB/c mice. CT-26 cells were injected into the splenic capsule of 48 BALB/c mice. The mice were then randomly divided into four groups: IP6, Ins, IP6 + Ins and normal saline control (n = 12 per group. IP6 and/or Ins (80 mg/kg each, 0.2 mL/day were injected into the gastrointestinal tracts of the mice on the second day after surgery. All mice were sacrificed after 20 days, and the tumor inhibition rates were determined. The results demonstrated that the tumor weights of liver metastases and the tumor inhibition rates were reduced in the experimental groups compared to the control group and that treatment with the combination of IP6 and Ins resulted in greater inhibition of tumor growth than treatment with either compound alone. These findings suggest that IP6 and Ins prevent the development and metastatic progression of colorectal cancer to the liver in mice by altering expression of the extracellular matrix proteins collagen IV, fibronectin and laminin; the adhesion factor receptor integrin-β1; the proteolytic enzyme matrix metalloproteinase 9; and the angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta in the tumor metastasis microenvironment. In conclusion, IP6 and Ins inhibited the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. This evidence supports further testing of the combined application of IP6 and Ins for the prevention of colorectal cancer metastasis to the liver in clinical studies.

  12. Management of Asymptomatic Renal Stones in Astronauts

    Science.gov (United States)

    Reyes, David; Locke, James

    2016-01-01

    Introduction: Management guidelines were created to screen and manage asymptomatic renal stones in U.S. astronauts. The risks for renal stone formation in astronauts due to bone loss and hypercalcuria are unknown. Astronauts have a stone risk which is about the same as commercial aviation pilots, which is about half that of the general population. However, proper management of this condition is still crucial to mitigate health and mission risks in the spaceflight environment. Methods: An extensive review of the literature and current aeromedical standards for the monitoring and management of renal stones was done. The NASA Flight Medicine Clinic's electronic medical record and Longitudinal Survey of Astronaut Health were also reviewed. Using this work, a screening and management algorithm was created that takes into consideration the unique operational environment of spaceflight. Results: Renal stone screening and management guidelines for astronauts were created based on accepted standards of care, with consideration to the environment of spaceflight. In the proposed algorithm, all astronauts will receive a yearly screening ultrasound for renal calcifications, or mineralized renal material (MRM). Any areas of MRM, 3 millimeters or larger, are considered a positive finding. Three millimeters approaches the detection limit of standard ultrasound, and several studies have shown that any stone that is 3 millimeters or less has an approximately 95 percent chance of spontaneous passage. For mission-assigned astronauts, any positive ultrasound study is followed by low-dose renal computed tomography (CT) scan, and flexible ureteroscopy if CT is positive. Other specific guidelines were also created. Discussion: The term "MRM" is used to account for small areas of calcification that may be outside the renal collecting system, and allows objectivity without otherwise constraining the diagnostic and treatment process for potentially very small calcifications of uncertain

  13. Risk factors for colorectal cancer

    Directory of Open Access Journals (Sweden)

    Mihajlović-Božić Vesna

    2004-01-01

    Full Text Available Colorectal cancer is one of the most common cancers in human population. It causes significant morbidity and mortality in our country. The incidence of colorectal cancer increases in the fifth decade of life. The aim of this study was to evaluate the association between colorectal cancer and potential risk factors. A case-control study of colorectal cancer was carried out between 1998 and 1999 in Clinical Center of Serbia, Center for Digestive Surgery. A total of 100 cases of newly diagnosed patients with colorectal cancer confirmed by histopathology and an equal number of controls, individually matched by gender and age (+/-5 years, were chosen from patients from the same hospital with no history of cancer at all. McNemar test and conditional logistic regression were used in the analysis. According to logistic regression analysis the following risk factors were independently related with the occurrence of colorectal cancer: cigarette smoking, alcohol consumption, and diet rich in red meat and fat promote the carcinogenic process; food rich in vegetables, fruits, grains, vitamin C, physical activity, and oral contraceptive use inhibit the same process. A family history of cancer and long standing inflammatory bowel diseases also have significant role. There is convincing evidence that nutrition affects colorectal carcinogenesis in a complex fashion.

  14. Critical appraisal of the use of regorafenib in the management of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Festino L

    2013-04-01

    Full Text Available Lucia Festino*, Alessio Fabozzi*, Anna Manzo, Valentina Gambardella, Erika Martinelli, Teresa Troiani, Ferdinando De Vita, Michele Orditura, Fortunato Ciardiello, Floriana Morgillo Division of Medical Oncology, Department of clinical and experimental medicine and surgery "F. Magrassi e A. Lanzara", Second University of Naples, Napoli, Italy*These authors contributed equally to this work Abstract: The lack of valid clinical management options for patients affected by metastatic colorectal cancer, which has progressed after all approved standard treatments, has lead to research into new active molecules. Regorafenib is an oral small-molecule multi kinase inhibitor, binding to several intracellular kinases, with powerful inhibitory activity against vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3, platelet-derived growth factor receptor, fibroblast growth factor receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. The antitumor activity of regorafenib has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in several cancer models, particularly colorectal cancer and gastrointestinal stromal tumors. The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation. Only a few Phase I–II trials, and most recently a Phase III trial in pretreated colorectal cancer, have been carried out to date. Several ongoing trials are testing the efficacy of regorafenib in combination with chemotherapy. At this point in time, regorafenib is the first small-molecule tyrosine kinase inhibitor to gain approval by the US Food and Drug Administration for pretreated metastatic colorectal cancer patients. Keywords: colorectal cancer, angiogenesis, regorafenib

  15. Unsuspected urological anomalies in asymptomatic cryptorchid boys

    International Nuclear Information System (INIS)

    In a period of 6 years 144 asymptomatic boys with cryptorchidism, of mean age 7 ± SD 3.5 years, underwent orchiopexy. None of these boys referred to a history of a known urological anomaly, urinary tract infection haematuria, palpable mass in the renal region, bladder extrophy, epispadias, hypospadias or anorectal malformation. On the third day after orchiopexy an intravenous pyelography was done in every boy following testicular protection against irradiation. Ultrasonic investigation was not available at that time. There were minor urological abnormalities in 36 (25%) boys and major ones in 8 (5.5%) boys. A major anomaly is defined as one resulting in significant loss of renal substance (one case of single kidney and three cases of unilateral renal hypoplasia), or requiring surgical correction for conservation of the renal substance (one case of ureterocele, two cases of pelviureteric stenosis and one case of vesicoureteric stenosis with ipsilateral hydronephrosis). The unsuspected major urological abnormalities are usually ipsilateral to the more undescended testis. They may be associated with a hernia and are more frequent in bilateral cryptorchidism. In conclusion we encourage the routine use of IVP, or ultrasonic investigation or dynamic renal scanning (99mTc-DTPA), if it is possible, in all patients undergoing orchiopexy for the detection of an unsuspected major renal anomaly. (orig.)

  16. Asymptomatic cerebral infarction examined by magnetic resonance imaging (MRI)

    International Nuclear Information System (INIS)

    To find the real incidence and risk factors in asymptomatic cerebral infarction, a retrospective review was made on magnetic resonance (MR) images, which were obtained from 713 outpatients seen at the Geriatrics Research Institute Hospital between March and November of 1990. The criteria for asymptomatic cerebral infarction are: high signal intensity areas larger than 3 mm in diameter on T2-weighted image; no history of stroke; no neurological and psychological signs or symptoms with or without subjective symptoms. Symptomatic cerebral stroke was defined as stroke episodes associated with neurological signs and infarction lesions on CT or MR imaging. Of a total of 713 patients, 215 (30.2%) had symtomatic cerebral infarction and 384 (53.9%) had no cerebral lesions. The incidence of asymptomatic cerebral infarction increased with aging. Cerebral risk factors, i.e. hypertension, atrial fibrillation, and diabetes mellitus, were more significantly common in both symptomatic and asymptomatic groups than the normal control group. In the group of asymptomatic patients, T2-weighted images showed hyperintensity in the corona radiata in 60.9%, in the frontal lobe in 32.1%, in the semioval center in 28.8%, and in the basal ganglia in 23.7%. Periventricular hyperintensity was present in 124 of all 713 patients (17.4%). Common complaints in asymptomatic patients were headache (40.0%), dizziness (14.4%), and neck muscle contraction (9.8%). In conclusion, MR imaging may contribute to manage asymptomatic patients. (N.K.)

  17. Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Yifan Wang

    Full Text Available Solid tumors exist in a hypoxic microenvironment, and possess high-glycolytic metabolites. To avoid the acidosis, tumor cells must exhibit a dynamic cytosolic pH regulation mechanism(s. The voltage-gated proton channel Hv1 mediates NADPH oxidase function by compensating cellular loss of electrons with protons. Here, we showed for the first time, that Hv1 expression is increased in colorectal tumor tissues and cell lines, associated with poor prognosis. Immunohistochemistry showed that Hv1 is strongly expressed in adenocarcinomas but not or lowly expressed in normal colorectal or hyperplastic polyps. Hv1 expression in colorectal cancer is significantly associated with the tumor size, tumor classification, lymph node status, clinical stage and p53 status. High Hv1 expression is associated significantly with shorter overall and recurrence-free survival. Furthermore, real-time RT-PCR and immunocytochemistry showed that Hv1 is highly expressed in colorectal cancer cell lines, SW620, HT29, LS174T and Colo205, but not in SW480. Inhibitions of Hv1 expression and activity in the highly metastatic SW620 cells by small interfering RNA (siRNA and Zn(2+ respectively, markedly decrease the cell invasion and migration, restraint proton extrusion and the intracellular pH recovery. Our results suggest that Hv1 may be used as a potential biomarker for diagnosis and prognosis of colorectal carcinoma, and a potential target for anticancer drugs in colorectal cancer therapy.

  18. Metastatic Crohn′s disease

    Directory of Open Access Journals (Sweden)

    Padmavathy Lanka

    2014-01-01

    Full Text Available Crohn′s disease, first described in 1922, is characterized by segmental granulomatous inflammation of the intestinal tract and frequently involves the cutaneous tissues as well. Cutaneous Crohn′s disease (CCD is synonymous with metastatic Crohn′s disease (MSD. A case of CCD, without any gastrointestinal involvement is reported for its rarity.

  19. Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

    Science.gov (United States)

    Quintero, Enrique; Gargallo, Carla; Lanas, Angel; Bujanda, Luis; Gimeno-García, Antonio Z.; Hernández-Guerra, Manuel; Nicolás-Pérez, David; Alonso-Abreu, Inmaculada; Morillas, Juan Diego; Balaguer, Francesc; Muriel, Alfonso

    2016-01-01

    Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced

  20. Process of distant lymph node metastasis in colorectal carcinoma: Implication of extracapsular invasion of lymph node metastasis

    International Nuclear Information System (INIS)

    We previously demonstrated that extracapsular invasion (ECI) at a metastatic sentinel node was significantly associated with the presence of positive non-sentinel nodes in patients with breast cancer. However, the mechanism of metastatic spreading of tumor cells to distant lymph nodes in patients with colorectal carcinoma is not fully understood. In this study, we investigated the factors that may determine the likelihood of additional regional lymph node metastasis when metastasis is found in nodes at the N1 site in colorectal cancer, especially focusing on the presence of ECI. Two hundred and twenty-eight consecutive patients who underwent colorectal resection were identified for inclusion in this study, of which 37 (16.2%) had positive lymph nodes at the N1 site. Six of these 37 cases had additional metastasis in N2 site lymph nodes. We reviewed the clinicopathological features of these cases and performed statistical analysis of the data. In the univariate analysis ECI at the N1 site was the only factor significantly associated with the presence of cancer cells in the N2 site. Other factors, including number of positive lymph nodes, lymphovascular invasion of the primary tumor, tumor size and tumor depth of invasion, were not associated with metastatic involvement at the N2 site. Our results suggest that the presence of ECI at metastatic lymph nodes at the N1 site is correlated with further metastasis at the N2 site. These findings imply the possibility that ECI might indicate the ability of colorectal tumor cells to disseminate to distant lymph nodes

  1. The Actin-Cytoskeleton Pathway and Its Potential Role in Inflammatory Bowel Disease-Associated Human Colorectal Cancer

    OpenAIRE

    Kanaan, Ziad; Qadan, Motaz; Eichenberger, Maurice Robert; Galandiuk, Susan

    2010-01-01

    Introduction: To improve our understanding of the various clinical phenotypes in inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) and provide potential targets for early diagnosis and future therapy, we sought to identify new candidate genes and molecular pathways involved in the pathogenesis and progression of this disorder. Recent evidence has implicated the actin-cytoskeleton pathway in the development of metastatic sporadic CRC through cytoskeletal proteins such as fasc...

  2. KRAS Mutation Detection in Paired Frozen and Formalin-Fixed Paraffin-Embedded (FFPE) Colorectal Cancer Tissues

    OpenAIRE

    Solassol, Jérome; Ramos, Jeanne; Crapez, Evelyne; SAIFI, MAJDA; Mangé, Alain; Vianès, Evelyne; Lamy, Pierre-Jean; Costes, Valérie; Maudelonde, Thierry

    2011-01-01

    KRAS mutation has been unambiguously identified as a marker of resistance to cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients. However, most studies of KRAS mutation analysis have been performed using homogenously archived CRC specimens, and studies that compare freshly frozen specimens and formalin-fixed paraffin-embedded (FFPE) specimens of CRC are lacking. The aim of the present study was to evaluate the impact of tissue preservation on the determination of KRAS mu...

  3. Circulating Tumor Cells as a Potential Biomarker in Selecting Patients for Pulmonary Metastasectomy from Colorectal Cancer: Report of a Case

    OpenAIRE

    Hashimoto, M.; Tanaka, F; Yoneda, K.; Kondo, N.; Takuwa, T.; Matsumoto, S; Kuroda, A.; Noda, M.; Tomita, N; Hasegawa, S.

    2012-01-01

    Pulmonary metastasectomy is indicated for selected patients with metastatic colorectal cancer. A 43-year-old woman presented with solitary pulmonary metastasis from descending colon cancer and pulmonary metastasectomy was performed because of absence of any other active metastasis as well as normal serum carcinoembryonic antigen value. However, she died due to early development of nodal and bone metastases within 6 months after thoracotomy. The presence of circulating tumor cells (CTCs) in th...

  4. Detection of colonic cells in peripheral blood of colorectal cancer patients by means of reverse transcriptase and polymerase chain reaction.

    OpenAIRE

    Castells, A.; Boix, L.; Bessa, X; Gargallo, L.; Piqué, J M

    1998-01-01

    Circulating tumour cells play a central role in the metastatic process, but little is known about the relationship between this cellular subpopulation and the development of secondary disease. This study was aimed at assessing the presence of colonic cells in peripheral blood of patients with colorectal cancer in different evolutionary stages, by means of reverse transcriptase polymerase chain reaction (RT-PCR) targeted to carcinoembryonic antigen (CEA) mRNA. In vitro sensitivity was establis...

  5. A Cost Comparison of Oral Tegafur Plus Uracil/Folinic Acid and Parenteral Fluorouracil for Colorectal Cancer in Canada

    OpenAIRE

    Jean A. Maroun; Carl Asche; Francoise Romeyer; Jayanti Mukherjee; Christine Cripps; Amit Oza; Jamie R. Skillings; Jacques Letarte

    2003-01-01

    Background: Two randomised, controlled trials (n = 1396) comparing (i) intravenous fluorouracil (FU) plus oral folinic acid (leucovorin) and (ii) oral tegafur plus uracil (UFT) plus folinic acid for the treatment of metastatic colorectal carcinoma found both regimens to have equivalent efficacy in terms of survival, tumour response and time to disease progression. The UFT/folinic acid regimen was associated with a better toxicity profile than FU/folinic acid. Objective: To determine the compa...

  6. Multi-level evidence that circulating CK18 is a biomarker of tumour burden in colorectal cancer

    OpenAIRE

    Greystoke, A; Dean, E; Saunders, M P; Cummings, J; Hughes, A; Ranson, M; Dive, C; Renehan, A G

    2012-01-01

    Background: Circulating total cytokeratin 18 (tCK18) and/or caspase cleaved cytokeratin 18 (cCK18) (measured by M65 and M30 enzyme-linked immunosorbent assays (ELISAs), respectively) are used as pharmacodynamic (PD) biomarkers of epithelial cell death in clinical trials. Having validated these ELISAs, we assessed their utility in colorectal cancer (CRC). Methods: We applied the assays in several settings: 53 controls; 97 patients undergoing surgery and 74 patients with metastatic CRC undergoi...

  7. KRAS Mutations in Primary Colorectal Cancer Tumors and Related Metastases: A Potential Role in Prediction of Lung Metastasis

    Science.gov (United States)

    Cejas, Paloma; López-Gómez, Miriam; Aguayo, Cristina; Madero, Rosario; de Castro Carpeño, Javier; Belda-Iniesta, Cristóbal; Barriuso, Jorge; Moreno García, Víctor; Larrauri, Javier; López, Rocío; Casado, Enrique; Gonzalez-Barón, Manuel; Feliu, Jaime

    2009-01-01

    Background KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status. Methodology/Principal Findings KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006). Conclusions/Significance Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to

  8. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  9. Metastatic pituitary carcinoma in a patient with acromegaly: a case report

    Directory of Open Access Journals (Sweden)

    Sreenan Seamus

    2012-09-01

    Full Text Available Abstract Introduction Asymptomatic pituitary abnormalities occur in about 10% of cranial magnetic resonance imaging scans, but metastatic carcinoma of the pituitary gland is rare: 133 cases have been reported. Two thirds secreted either prolactin or adrenocorticotropic hormone, and another 24% were non-secreting. Case presentation A 42-year-old Caucasian man lived for 30 years after the diagnosis of a pituitary tumor whose clinical and biochemical features were those of acromegaly and hypogonadism. Radiotherapy, totaling 7300 rad, was administered to the sella over two courses. Growth hormone levels normalized, but he developed both thyroid and adrenal insufficiency, and replacement therapy was commenced. Fourteen years later, growth hormone levels again became elevated, and bromocriptine was commenced but led to side effects that could not be tolerated. An attempted surgical intervention failed, and octreotide and pergolide were used in succession. Twenty-seven years after the diagnosis, a mass from an excisional biopsy of below the angle of the mandible proved to be metastatic pituitary carcinoma. Immunohistochemical staining was positive for synaptophysin, growth hormone, and prolactin. One year later, an octreotide scan showed uptake at the sella, neck, and spleen. Our patient declined further active oncology treatment. Conclusions Metastatic pituitary carcinoma associated with acromegaly is particularly rare. To the best of our knowledge, this is the eighth such case and is the first report of growth hormone and prolactin present in the metastatic mass.

  10. A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer

    DEFF Research Database (Denmark)

    Mesher, David; Dove-Edwin, Isis; Sasieni, Peter;

    2014-01-01

    centers. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under 50. The most advanced findings on colonoscopy......Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six...... were analyzed. One thousand five hundred eighty-five individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4,992 colonoscopies with 7,904 patient-years of follow-up. Results for FCC type X and LOFCC were very similar. At baseline, 22 prevalent asymptomatic...

  11. SOX9-regulated cell plasticity in colorectal metastasis is attenuated by rapamycin.

    Science.gov (United States)

    Carrasco-Garcia, Estefania; Lopez, Lidia; Aldaz, Paula; Arevalo, Sara; Aldaregia, Juncal; Egaña, Larraitz; Bujanda, Luis; Cheung, Martin; Sampron, Nicolas; Garcia, Idoia; Matheu, Ander

    2016-01-01

    The cancer stem cell (CSC) hypothesis proposes a hierarchical organization of tumors, in which stem-like cells sustain tumors and drive metastasis. The molecular mechanisms underlying the acquisition of CSCs and metastatic traits are not well understood. SOX9 is a transcription factor linked to stem cell maintenance and commonly overexpressed in solid cancers including colorectal cancer. In this study, we show that SOX9 levels are higher in metastatic (SW620) than in primary colorectal cancer cells (SW480) derived from the same patient. This elevated expression correlated with enhanced self-renewal activity. By gain and loss-of-function studies in SW480 and SW620 cells respectively, we reveal that SOX9 levels modulate tumorsphere formation and self-renewal ability in vitro and tumor initiation in vivo. Moreover, SOX9 regulates migration and invasion and triggers the transition between epithelial and mesenchymal states. These activities are partially dependent on SOX9 post-transcriptional modifications. Importantly, treatment with rapamycin inhibits self-renewal and tumor growth in a SOX9-dependent manner. These results identify a functional role for SOX9 in regulating colorectal cancer cell plasticity and metastasis, and provide a strong rationale for a rapamycin-based therapeutic strategy. PMID:27571710

  12. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... certain people. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 11 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  13. Treatment Individualization in Colorectal Cancer

    NARCIS (Netherlands)

    van Geel, Robin M J M; Beijnen, Jos H; Bernards, René; Schellens, Jan H M

    2015-01-01

    Colorectal cancer has been characterized as a genetically heterogeneous disease, with a large diversity in molecular pathogenesis resulting in differential responses to therapy. However, the currently available validated biomarkers KRAS, BRAF, and microsatellite instability do not sufficiently cover

  14. Obesity and colorectal cancer risk

    International Nuclear Information System (INIS)

    Obesity is a chronic and multifactor disease characterized by presence of excess body fat harmful for health. Several studies have been conducted to assess the possible risk character of different factors for colorectal cancer including the following modifying factors: a diet rich in saturated fats, a diet low in vegetables, physical inactivity, alcohol consumption and obesity. A case-control study was conducted to include 276 adult patients (93 cases and 184 controls) consecutively seen from May, 2008 to May, 2009 in the Institute of Gastroenterology determining a possible association between obesity as risk factor and colorectal cancer. Variables measures included: sex, age, skin color, body mass index, hip-waist circumference and endoscopic location of cancer. We conclude that the colorectal cancer with predominance in female sex and in white people in both groups. Obesity according to a great relation hip-waist had an strong relation with colorectal cancer, which had predominance towards distal colon in both sexes

  15. Asymptomatic myocardial ischemia following cold provocation

    International Nuclear Information System (INIS)

    Cold is thought to provoke angina in patients with coronary disease either by an increase in myocardial demand or an increase in coronary vascular resistance. We investigated and compared the effects of cold pressor stimulation and symptom-limited supine bicycle exercise on regional myocardial perfusion in 35 patients with stable angina and coronary disease and in 10 normal subjects. Regional myocardial perfusion was assessed with positron emission tomography and rubidium-82. Following cold pressor stimulation 24 of 35 patients demonstrated significant abnormalities of regional myocardial perfusion with reduced cation uptake in affected regions of myocardium: 52 +/- 9 to 43 +/- 9 (p less than 0.001 vs normal subjects). Among these 24 patients only nine developed ST depression and only seven had angina. In contrast, 29 of 35 patients underwent supine exercise, and abnormal regional myocardial perfusion occurred in all 29, with a reduction in cation intake from 48 +/- 10 to 43 +/- 14 (p less than 0.001 vs normal subjects). Angina was present in 27 of 29 and ST depression in 25 of 29. Although the absolute decrease in cation uptake was somewhat greater following cold as opposed to exercise, the peak heart rate after cold was significantly lower than that after exercise (82 +/- 12 vs 108 +/- 16 bpm, p less than 0.05). Peak systolic blood pressures after cold and exercise were similar (159 +/- 24 vs 158 +/- 28). Thus, cold produces much more frequent asymptomatic disturbances of regional myocardial perfusion in patients with stable angina and coronary disease than is suggested by pain or ECG changes

  16. Chronic asymptomatic hyperamylasemia unrelated to pancreatic disease

    Directory of Open Access Journals (Sweden)

    Generoso Uomo

    2013-05-01

    Full Text Available BACKGROUND Almost all patients presenting with chronic hyperamylasemia undergo an expensive, long, difficult and often repeated diagnostic workup even if this occurrence is not associated with symptoms or with known pancreatotoxic factors. This is in relationship with the poor knowledge that, beside hyperenzymemia secondary to pancreatic diseases and systemic illnesses, various non-pathological forms of chronic hyperamylasemia can occur in clinical practice. AIM OF THE STUDY This study was addressed to assess the clinical characteristics of patients presenting with chronic hyperamylasemia unrelated to pancreatic diseases (CHUPD. PATIENTS AND METHODS Data of all patients with CHUPD were retrospectively reviewed (June 1997-March 2007. Forty patients were included in the study; median follow- up was 33 months (range 3-84 months. CHUPD was secondary to: a chronic benign pancreatic hyperamylasemia, 16 patients (40%; b macroamylasemia, 15 patients (37.5%; c salivary hyperamylasemia, 9 patients (22.5%. Gilbert’s syndrome was present in 13 patients (32.5%; 8 with macroamylasemia and hyperdyslipidemia in 8 patients (20%; 5 with chronic benign pancreatic hyperamylasemia. Diagnostic exams (all in the normal range performed before our observation were: Ca19-9 serum level in 37/40 (92.5%, ultrasonography and computed tomography-scan in all patients, endoscopic retrograde cholangiopancreatography in 21/40 (52.5%, abdominal magnetic resonance in 14/40 (35%. Previous diagnosis in these asymptomatic subjects were: chronic pancreatitis in 26 cases (65%; recurrent pancreatitis in 10 cases (25%; the remaining 4 patients (10% were addressed without a specific diagnosis. CONCLUSIONS In clinical practice, the occurrence of an unexplained chronic hyperamylasemia very often allows to an unappropriate diagnostic workup due to the poor familiarity with CHUPD conditions.

  17. Nutritional profile of asymptomatic alcoholic patients

    Directory of Open Access Journals (Sweden)

    Maria Beatriz Sobral-Oliveira

    2011-06-01

    Full Text Available CONTEXT: Alcoholism may interfere with nutritional status, but reports are often troubled by uncertainties about ingested diet and organ function, as well as by ongoing abuse and associated conditions. OBJECTIVE: To identify nutritional and body compartment changes in stable alcoholics without confounding clinical and dietetic variables, a prospective observational pilot study was designed. Three well-matched populations were considered: subjects with chronic alcoholic pancreatitis, alcoholics without visceral disease, and healthy never-drinking adults (controls. METHODS: Subjects (n = 60 were asymptomatic males with adequate diet, no superimposed disease or complication, and alcohol-free for at least 6 months. After exclusions, 48 patients were compared. Variables encompassed dietary recall, bioimpedance analysis, biochemical profile and inflammatory markers. Main outcome measures were body fat, lean body mass, serum lipids, C-reactive protein, and selected minerals and vitamins. RESULTS: Both alcoholic populations suffered from reduced lean body mass (P = 0.001, with well-maintained body fat.Magnesium was depleted, and values of vitamin D and B12 correlated with alcohol abuse. LDL and total cholesterol was increased in alcoholics without pancreatitis (P = 0.04, but not in those with visceral damage. C-reactive protein and serum amyloid A correlated with duration of excessive drinking (P = 0.01. CONCLUSIONS: Undernutrition (diminished lean body mass, risk of magnesium and vitamin deficiencies contrasted with dyslipidemia and increased cardiovascular risk. This second danger was masked during chronic pancreatitis but not in alcoholics without visceral disease. Further studies should focus special requirements of this population.

  18. HOSPITAL BASED STUDY FOR ASYMPTOMATIC BACTERIURIA IN PREGNANT WOMEN

    OpenAIRE

    Babital; Sanjeev,; Shankar

    2013-01-01

    Asymptomatic bacteriuria (ASB) is infection in pregnancy which requires medical treatment. If left untreated, may lead to prematurity, intrauteri ne death and pyelonephrit i s. The diagnosis is done by culture and its antibiotic sensitivity helped the women in treatment.

  19. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

    DEFF Research Database (Denmark)

    Nicolaides, Andrew N; Kakkos, Stavros K; Kyriacou, Efthyvoulos;

    2010-01-01

    The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis....

  20. Familial colorectal cancer type X

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina;

    2015-01-01

    Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention....

  1. Prevalence and risk factors of asymptomatic bacteriuria in pregnancy

    OpenAIRE

    Ghafarnezhad M; Shams

    2001-01-01

    Asymptomatic bacteriuria is prevalent during pregnancy. It can lead to pyelonephritis, premature pregnancy and low birth weight. In this prospective study, to determine prevalence and risk factors of asymptomatic bacteriuria, 205 consecutive pregnant women who visited our prenatal care clinic in Mirza-Koochakkhan Hospital and had no urinary symptom were entered. Patients data were recorded using a questionnaire and urine samples were obtained for urinalysis and urine culture. We analysed data...

  2. Prevalence and risk factors of asymptomatic bacteriuria in pregnancy1

    OpenAIRE

    Ghafarnezhad M; Shams

    2000-01-01

    Asymptomatic bacteriuria is prevalent during pregnancy. It can lead to pyelonephritis, premature pregnancy and low birth weight. In this prospective study, to determine prevalence and risk factors of asymptomatic bacteriuria, 205 consecutive pregnant women who visited our prenatal care clinic in Mirza-Koochakkhan Hospital and had no urinary symptom were entered. Patients data were recorded using a questionnaire and urine samples were obtained for urinalysis and urine culture. We analysed data...

  3. Significant Bacteriuria Among Asymptomatic Antenatal Clinic Attendees In Ibadan, Nigeria

    OpenAIRE

    Aderemi O. Kehinde; Adedapo, Kayode S.; Aimaikhu, Christopher O.; Odukogbe, Akin-tunde A.; Olayemi, Oladapo; Salako, Babatunde

    2011-01-01

    Untreated asymptomatic bacteriuria can lead to urinary tract infection (UTI) in pregnancy with devastating maternal and neonatal effects such as prematurity and low birth weight, higher fetal mortality rates and significant maternal morbidity. We carried out a two year (April 2007 to March 2009) cross-sectional epidemiological study to determine the prevalence of significant bacteriuria among asymptomatic antenatal clinic attendees at two antenatal clinics (ANCs) in University College Hospita...

  4. Femoral prosthesis subsidence in asymptomatic patients. A stereophotogrammetric assessment.

    Science.gov (United States)

    Chafetz, N; Baumrind, S; Murray, W R; Genant, H K

    1984-01-01

    A radiographic stereophotogrammetric technique (SPG) was used to evaluate quantitatively the presence of early femoral prosthesis subsidence after total hip arthroplasty (THA). This paper focuses on the measurement of subsidence in 12 patients who remained asymptomatic during the first two years after surgery. Only one of these had SPG estimated subsidence in excess of one millimeter at any timepoint. These findings are consistent with the conclusion that early postoperative subsidence is not a common finding among asymptomatic THA patients. PMID:6469528

  5. Successful Reconstruction of Asymptomatic Bilateral External Carotid Artery Aneurysms.

    Science.gov (United States)

    Loja, Melissa N; Pevec, William C

    2016-04-01

    True aneurysms of the external carotid artery (ECA) are extremely rare with an unknown incidence and natural history. We present the successful operative management of an asymptomatic 65-year-old man found to have bilateral internal carotid artery stenosis and bilateral ECA aneurysms. His bilateral carotid arteries were reconstructed with bifurcated interposition grafts in a staged fashion. The patient recovered without sequelae and continues to be asymptomatic 1 year after reconstruction. We present the operative management of this rare case. PMID:26802292

  6. Psychiatric morbidity in asymptomatic human immunodeficiency virus patients

    OpenAIRE

    Chauhan, V S; Suprakash Chaudhury; Sudarsanan, S.; Kalpana Srivastava

    2013-01-01

    Background: Psychiatric morbidity in human immunodeficiency virus (HIV) patients is being studied all over the world. There is paucity of Indian literature particularly in asymptomatic HIV individuals. Aim: The aim of the following study is to establish the prevalence and the determinants of psychiatric morbidity in asymptomatic HIV patients. Materials and Methods: A cross-sectional study was undertaken to assess psychiatric morbidity as per ICD-10 dacryocystorhinostomy criteria in 100 consec...

  7. Retained Asymptomatic Third Molars and Risk for Second Molar Pathology

    OpenAIRE

    Nunn, M.E.; Fish, M.D.; Garcia, R.I.; Kaye, E.K.; R. Figueroa; Gohel, A.; Ito, M; Lee, H J.; Williams, D E; Miyamoto, T

    2013-01-01

    Prophylactic extraction of unerupted asymptomatic third molars is the most common oral surgery procedure in the United States. However, limited evidence exists to justify its costs and associated morbidity. We analyzed data collected over 25 years from 416 adult men enrolled in the Veterans Affairs Dental Longitudinal Study to evaluate the association of retained asymptomatic third molars with risk of adjacent second molar pathology (caries and/or periodontitis), based on third molar status (...

  8. Molecular genetics of colorectal cancer.

    Science.gov (United States)

    Bogaert, Julie; Prenen, Hans

    2014-01-01

    Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer. PMID:24714764

  9. Asymptomatic rotavirus infections in England: prevalence, characteristics, and risk factors.

    Science.gov (United States)

    Phillips, Gemma; Lopman, Ben; Rodrigues, Laura C; Tam, Clarence C

    2010-05-01

    Rotavirus is a major cause of infectious intestinal disease in young children; a substantial prevalence of asymptomatic infection has been reported across all age groups. In this study, the authors determined characteristics of asymptomatic rotavirus infection and potential risk factors for infection. Healthy persons were recruited at random from the general population of England during the Study of Infectious Intestinal Disease in England (1993-1996). Rotavirus infection was identified using reverse-transcription polymerase chain reaction. Multivariable logistic regression was used to compare exposures reported by participants with rotavirus infection with those of participants who tested negative. Multiple imputation was used to account for missing responses in the data set. The age-adjusted prevalence of asymptomatic rotavirus infection was 11%; prevalence was highest in children under age 18 years. Attendance at day care was a risk factor for asymptomatic rotavirus infection in children under age 5 years; living in a household with a baby that was still in diapers was a risk factor in older adults. The results suggest that asymptomatic rotavirus infection is transmitted through the same route as rotavirus infectious intestinal disease: person-to-person contact. More work is needed to understand the role of asymptomatic infections in transmission leading to rotavirus disease. PMID:20392863

  10. Biomarkers for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Rikako Ishigamori

    2010-09-01

    Full Text Available Colorectal cancer (CRC is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy significantly improves the detection rate of CRC, but the examination is expensive and inconvenient. Therefore, we need novel biomarkers that are non-invasive to enable us to detect CRC quite early. A number of validation studies have been conducted to evaluate genetic, epigenetic or protein markers for identification in the stool and/or serum. Currently, the fecal occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics will lead to the discovery of novel non-invasive biomarkers.

  11. Immunotherapy in human colorectal cancer: Challenges and prospective.

    Science.gov (United States)

    Sun, Xuan; Suo, Jian; Yan, Jun

    2016-07-28

    Human colorectal cancer (CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC. In this review, we will discuss important immunological landscape within the CRC microenvironment and introduce immunoscore system to better describe immunophenotyping in CRC. We will also discuss different immunotherapeutic approaches currently utilized in different phases of clinical trials. Some of those completed or ongoing trials are summarized. Finally, we provide a brief prospective on the future human CRC immunotherapy. PMID:27605872

  12. The microenvironment of liver metastases from Colorectal adenocarcinoma

    DEFF Research Database (Denmark)

    Eefsen, Rikke Løvendahl

    Colorectal adenocarcinoma (CRC) is the third most frequent cancer type worldwide and the third leading cause of cancer related death. During the course of the disease about 50% of patients are diagnosed with metastatic CRC (mCRC). The 5-year survival for patients who undergo a hepatic resection...... is about 40% and up to 58% in selected groups of patients, while the median overall survival for patients who receive palliative treatment has been reported to be from a few months and up to about 24 months, depending on dissemination of the cancer and response to treatment. The initial neo......-adjuvant treatment is crucial for patients with potential resectable liver metastases, allowing a subsequent hepatic resection if treatment have a downsizing effect on metastases.Antineoplastic agents include chemotherapy (e.g. 5-fluorouracil, oxaliplatin and irinotecan) or a combination of chemotherapy and targeted...

  13. Scrotal metastases from colorectal carcinoma: a case report.

    LENUS (Irish Health Repository)

    McWeeney, Doireann M

    2012-01-31

    ABSTRACT: A 72-year-old man presented with a two month history of rectal bleeding. Colonoscopy demonstrated synchronous lesions at 3 cm and 40 cm with histological analysis confirming synchronous adenocarcinomata. He developed bilobar hepatic metastases while undergoing neoadjuvant chemoradiotherapy. Treatment was complicated by Fournier\\'s gangrene of the right hemiscrotum which required surgical debridement. Eight months later he re-presented with an ulcerating lesion on the right hemiscrotum. An en-bloc resection of the ulcerating scrotal lesion and underlying testis was performed. Immunohistological analysis revealed metastatic adenocarcinoma of large bowel origin. Colorectal metastasis to the urogenital tract is rare and here we report a case of rectal carcinoma metastasizing to scrotal skin.

  14. PET/CT diagnostic of colo-rectal cancers

    International Nuclear Information System (INIS)

    Full text: Objective: Presenting the advantages of Positron Emission Tomography/Computed Tomography (PET/ CT) examination, using the radiotracer fluorure 18-deoxyglucose (FDG) in colo-rectal cancer diagnostic. Basics of the method will be also presented. Introduction: FDG PET/CT is recognized as the most efficient diagnostic imaging weapon in colorectal cancer, enable too comprehend all the 3 targets needed for staging of colo-rectal cancers: 1)Detection and evaluation of primary tumor (T) and recurrence; 2) Lymphadenopathy (N); 3)Metastatic disease (M). Assessment of treatment response during and after therapy, follow up and radiotherapy planning are also indications for PET/CT. There are two essential advantages of the method: 1)The whole body examination; 2)The complementary morphological information offered by CT and functional information offered by PET. Material and methods: Study of a total of 394 patients diagnosed with colo-rectal cancer of the total of 4125 investigated by PET/CT in Diagnosztika Pozitron center of Oradea, between 01.06.2008 - 06.06.2012. All cases had documented preoperative or postoperative histopathologic evaluation. We used a Siemens Biograph 16 device and only FDG as radiotracer, injected intravenously at a dose of 0.1-0.15 mCi /kg. Standard protocol of examination was performed at 60 minutes after FDG injection. CT acquisition consists of 'low dose' from vertex to thighs, followed by PET acquisition in 7 to 8 beds. Results: We followed the performance of PET/CT diagnostic in staging and restaging of colorectal cancer compared with other imaging methods. 141 patients had negative examinations. 107 patients were diagnosed with locally recurrent lesions, lymphadenopathy and/ or metastases. Compared with the results of previous imaging new metabolically active lesions were detected in 87 patients by PET/CT and suspected lesions were denied in 48 patients. Significant clinically cases are presented. Conclusions: The data obtained by PET

  15. Metastatic Thymoma of the Breast

    OpenAIRE

    Kim, Sung Mok; Ko, Eun Young; Han, Boo-Kyung; Shin, Jung Hee; Kang, Seok Seon; Nam, Seok-Jin; Cho, Eun Yoon

    2008-01-01

    Breast metastasis from nonmammary malignant neoplasms is uncommon, and it accounts for approximately 2% of all breast tumors. Distant metastasis of thymoma is very rare, and especially to extrathorcic areas. We report a female who had a metastatic thymoma in her breast 20 years after undergoing resection for a non-invasive thymoma. She presented with a palpable mass in her left breast. Mammography and ultrasonogram showed a lobular mass at the anterior glandular portion. Histological examinat...

  16. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bajenova, Olga, E-mail: o.bazhenova@spbu.ru [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Chaika, Nina [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Tolkunova, Elena; Davydov-Sinitsyn, Alexander [Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064 (Russian Federation); Gapon, Svetlana [Boston Children' s Hospital, Boston, MA 02115 (United States); Thomas, Peter [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); O’Brien, Stephen [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation)

    2014-06-10

    Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.

  17. Synthesis and expression of CDw75 antigen in human colorectal cancer

    International Nuclear Information System (INIS)

    Increased ST6Gal I activity has been associated with the α(2,6)sialylation enhancement of membrane glycoconjugates observed in metastatic colorectal carcinomas (CRC). Siaα(2,6)Galβ(1,4)GlcNAc sequence, known as CDw75, is a sialylated carbohydrate determinant generated by the ST6Gal I. This epitope has been reported to be associated with the progression of gastric and colorectal tumours, hence there are only a few conclusive studies to date. By radioisotopic techniques we evaluated the ST6Gal I activity in healthy, transitional and tumour tissues from 43 patients with CRC. By immunohistochemistry we assessed the CDw75 expression in 25 colorectal adenomas, 43 tumours, 13 transitional and 28 healthy tissues of CRC patients. ST6Gal I activity was likewise found to be statistically higher in tumour tissue respect to healthy tissue from CRC patients. CDw75 expression was positive in 20% of colorectal adenomas. Furthermore, 70% of tumour specimens and 8.3% of transitional specimens were positive for CDw75 expression, whereas none of the healthy ones showed the presence of the epitope. The major contribution of this study is the inclusion of data from transitional tissue and the analysis of CDw75 antigen expression in CRC and in colorectal adenomas, little known so far. ST6Gal I activity and CDw75 antigen expression were increased in CRC. Although their comparison did not reach the statistical significance, a great extent of patients showed both, an enhanced tumour ST6Gal I activity and an increased CDw75 expression in the tumour tissue. So, these two variables may play a role in malignant transformation. The expression of CDw75 in colorectal adenomas suggests that this antigen may be a tumour marker in CRC

  18. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

    International Nuclear Information System (INIS)

    Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein

  19. Colorectal cancer and diet in Scotland

    OpenAIRE

    Theodoratou, Evropi

    2008-01-01

    Introduction Colorectal cancer is a cancer that forms in the tissues of the colon and/ or rectum and more than 95% of colorectal cancers are adenocarcinomas. It is the third most common cancer in incidence and mortality rates, accounting for 9% of all cancer cases and for 8% of all cancer related deaths (2002). The established risk factors of colorectal cancer include personal or family history of previous colorectal cancer or adenomatous polyps, chronic bowel inflammatory d...

  20. Proposal of a new and simple staging system of colorectal liver metastasis

    Institute of Scientific and Technical Information of China (English)

    Ikuo Nagashima; Tadahiro Takada; Hirokazu Nagawa; Tetsuichiro Muto; Kota Okinaga

    2006-01-01

    AIM: To create a new, simple and useful staging system for colorectal liver metastasis analogous to the Tumor Node Metastasis classification system of International Union Against Cancer.MFTHODS: A retrospective review was undertaken of 81 consecutive patients who underwent partial hepatectomy for colorectal liver metastases (group 1). Clinical and pathological features of both primary and metastatic liver cancers were entered into a multivariate analysis to determine independent variables helpful in accurately predicting long-term prognosis after hepatectomy. Using selected variables, we created a new staging system like TNM classification. The usefulness of the new staging system was examined in a series of 92 patients from another hospital (group 2).RESULTS: Multivariate analysis showed that 81 patients in group 1 had significant multiple hepatic tumors with the largest tumor being more than 5 cm in diameter,resectable extrahepatic distant metastases, and independent prognostic factors for poor survival after hepatectomy. Using these three variables, we created a new staging system to classify patients with colorectal liver metastases. Finally, our new staging system classified the patients both in group 1 and in group 2.CONCLUSION: Our new staging system of colorectal liver metastasis is simple and useful for staging patients.

  1. Suggestion of optimal patient characteristics for sentinel lymph node mapping in colorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Claudio A Quadros

    2010-12-01

    Full Text Available CONTEXT: In a previously published study, the variables lower rectal tumor site, preoperative chemoradiotherapy and large tumors were considered as independent risk factors for the inability of sentinel lymph node identification in patients with colorectal adenocarcinoma. OBJECTIVES: To determine if these variables could interfere in the precision and upstaging benefit of sentinel lymph node mapping in colorectal cancer. METHODS: A database composed of 52 patients submitted to lymphatic mapping using technetium-99m-phytate and patent blue was reviewed. Only patients with tumors smaller than 5.0 cm, not submitted to preoperative chemoradiotherapy and without lower rectal cancer were included. RESULTS: With these parameters, 11 patients remained to be studied. The sentinel lymph node identification rate was 100%, with a sensitivity of 100%, negative predictive value of 100%, no false negatives and accuracy of 100%. Sentinel lymph nodes were the only metastatic nodes in 36.4% of the patients, micrometastases (<0.2 cm or only identified by immunohistochemistry provided an upstaging rate of 27.1% and metastases an upstaging rate of 9.1%. CONCLUSION: The parameters proposed in this study for selection of colorectal adenocarcinoma patients to be submitted to sentinel lymph node mapping identified optimal accuracy and good upstaging results. As the number of included patients was low, these results could serve as guidance for proper patient selection in further prospective lymph node mapping studies in colorectal cancer patients.

  2. Clinical efficacy of stereotactic ablative radiotherapy for lung metastases arising from colorectal cancer

    International Nuclear Information System (INIS)

    Limited data describe the prognosis after stereotactic ablative radiotherapy for lung metastases arising from colorectal cancer. Thus, we evaluated treatment outcomes of stereotactic ablative radiotherapy for those patients. The study involved patients received stereotactic ablative radiotherapy for one to three lung metastases arising from colorectal cancer at a single institution. A total dose of 40–60 Gy (median, 48 Gy) in three or four fractions was prescribed. A total of 79 metastatic lung lesions from 50 patients who underwent curative resection for their primary colorectal cancer or salvage treatment at a recurrent site were included. The one- and three-year local control rates were 88.7 % and 70.6 %, respectively. The three-year overall survival and progression-free survival rates were 64.0 % and 24.0 %, respectively. Patients with tumor volume ≤1.5 mL had a significantly better overall survival rate than those with tumor volume >1.5 mL (68.0 % vs. 60.0 % at three-year, p = 0.02). Local control was associated with a trend towards better survival (p = 0.06). No pulmonary complications greater than grade 2 were observed. Stereotactic ablative radiotherapy is a competitive treatment modality for the management of lung metastases arising from colorectal cancer

  3. Five year colorectal cancer outcomes in a large negative CT colonography screening cohort

    Energy Technology Data Exchange (ETDEWEB)

    Kim, David H.; Pooler, B.D.; Pickhardt, Perry J. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States); Weiss, Jennifer M. [University of Wisconsin School of Medicine and Public Health, Section of Gastroenterology, Department of Internal Medicine, Madison, WI (United States)

    2012-07-15

    To assess the 5-year incidence of clinically presenting colorectal cancers following a negative CT colonography (CTC) screening examination, as few patient outcome data regarding a negative CTC screening result exist. Negative CTC screening patients (n = 1,050) in the University of Wisconsin Health system over a 14-month period were included. An electronic medical record (EMR) review was undertaken, encompassing provider, colonoscopy, imaging and histopathology reports. Incident colorectal cancers and other important GI tumours were recorded. Of the 1,050 cohort (mean [{+-}SD] age 56.9 {+-} 7.4 years), 39 (3.7%) patients were excluded owing to lack of follow-up within our system beyond the initial screening CTC. The remaining 1,011 patients were followed for an average of 4.73 {+-} 1.15 years. One incident colorectal adenocarcinoma represented a crude cancer incidence of 0.2 cancers per 1,000 patient years. EMR revealed 14 additional patients with clinically important GI tumours including: advanced adenomas (n = 11), appendiceal goblet cell carcinoid (n = 1), appendiceal mucinous adenoma (n = 1) and metastatic ileocolonic carcinoid (n = 1). All positive patients including the incident carcinoma are alive at the time of review. Clinically presenting colorectal adenocarcinoma is rare in the 5 years following negative screening CTC, suggesting that current strategies, including non-reporting of diminutive lesions, are appropriate. (orig.)

  4. Five year colorectal cancer outcomes in a large negative CT colonography screening cohort

    International Nuclear Information System (INIS)

    To assess the 5-year incidence of clinically presenting colorectal cancers following a negative CT colonography (CTC) screening examination, as few patient outcome data regarding a negative CTC screening result exist. Negative CTC screening patients (n = 1,050) in the University of Wisconsin Health system over a 14-month period were included. An electronic medical record (EMR) review was undertaken, encompassing provider, colonoscopy, imaging and histopathology reports. Incident colorectal cancers and other important GI tumours were recorded. Of the 1,050 cohort (mean [±SD] age 56.9 ± 7.4 years), 39 (3.7%) patients were excluded owing to lack of follow-up within our system beyond the initial screening CTC. The remaining 1,011 patients were followed for an average of 4.73 ± 1.15 years. One incident colorectal adenocarcinoma represented a crude cancer incidence of 0.2 cancers per 1,000 patient years. EMR revealed 14 additional patients with clinically important GI tumours including: advanced adenomas (n = 11), appendiceal goblet cell carcinoid (n = 1), appendiceal mucinous adenoma (n = 1) and metastatic ileocolonic carcinoid (n = 1). All positive patients including the incident carcinoma are alive at the time of review. Clinically presenting colorectal adenocarcinoma is rare in the 5 years following negative screening CTC, suggesting that current strategies, including non-reporting of diminutive lesions, are appropriate. (orig.)

  5. Molecular Classification and Correlates in Colorectal Cancer

    OpenAIRE

    Ogino, Shuji; Goel, Ajay

    2008-01-01

    Molecular classification of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are incorporating new knowledge into the classification system. In particular, global genomic status [microsatellite instability (MSI) status and chromosomal instability (CIN) status] and epigenomic status [CpG island methylator phenotype (CIMP) status] play a significant role in determining clinical, pathological and biological characteristics of colorectal cancer. In thi...

  6. Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding.

    Science.gov (United States)

    Newman, K L; Moe, C L; Kirby, A E; Flanders, W D; Parkos, C A; Leon, J S

    2016-06-01

    Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world-wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription-polymerase chain reaction (RT-qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune-mediated in NoV infection. PMID:26822517

  7. The PREVAIL trial of enzalutamide in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer: Post hoc analysis of Korean patients

    OpenAIRE

    Kim, Choung-Soo; Theeuwes, Ad; Kwon, Dong Deuk; Choi, Young Deuk; Chung, Byung Ha; Lee, Hyun Moo; Lee, Kang Hyun; Lee, Sang Eun

    2016-01-01

    Purpose This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial. Materials and Methods Asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-...

  8. Pancreatic Metastasis from Renal Carcinoma Managed by Whipple Resection. A Case Report and Literature Review of Metastatic Pattern, Surgical Management and Outcome

    OpenAIRE

    Norman Oneil Machado; Pradeep Chopra

    2009-01-01

    Context Metastatic cancer to the pancreas is rare and accounts for less than 2% of all pancreatic malignancies, metastasis from renal cell carcinoma being predominant. While symptomatic patients present with obstructive jaundice, abdominal pain, or GI bleeding, the diagnosis is often made in asymptomatic patients during follow-up for renal cell carcinoma. Hence, a high index of clinical suspicion is required in a patient who presents with a pancreatic tumor following a nephrectomy for renal c...

  9. Update on the optimal management of patients with colorectal liver metastases.

    Science.gov (United States)

    Alberts, Steven R

    2012-10-01

    Patients with colorectal liver metastases represent a distinct subset of metastatic colorectal cancer. Optimal management requires a multidisciplinary approach, local and systemic. Curative hepatic surgery is standard for resectable cases, but unfortunately, the majority of patients are not initially resectable due to the size, location, and/or extent of disease, inadequate remnant liver volume, or comorbidities. Other local approaches may be complementary (such as portal vein embolization) or alternative (such as ablation, hepatic arterial infusion, selective internal radiation therapy, and stereotactic body radiotherapy) to surgery. Systemic therapy can downsize disease, allowing surgical resection and, potentially, long-term survival, but it must be balanced against the potential for hepatotoxicity. Current standard approaches including cytotoxics and biologics, such as bevacizumab and particularly anti-epidermal growth factor receptor therapy, improve response rates and may enhance downsizing and resection rates. Optimization of local therapies and systemic conversion strategies via controlled, randomized trials is still a pending question. PMID:22425016

  10. Exosomes in colorectal carcinoma formation: ALIX under the magnifying glass.

    Science.gov (United States)

    Valcz, Gábor; Galamb, Orsolya; Krenács, Tibor; Spisák, Sándor; Kalmár, Alexandra; Patai, Árpád V; Wichmann, Barna; Dede, Kristóf; Tulassay, Zsolt; Molnár, Béla

    2016-08-01

    Exosomes are small membrane vesicles that have important roles in transporting a great variety of bioactive molecules between epithelial compartment and their microenvironment during tumor formation including colorectal adenoma-carcinoma sequence. We tested the mRNA expression of the top 25 exosome-related markers based on ExoCharta database in healthy (n=49), adenoma (n=49) and colorectal carcinoma (n=49) patients using Affymetrix HGU133 Plus2.0 microarrays. Most related genes showed significantly elevated expression including PGK1, PKM, ANXA5, ENO1, HSP90AB1 and MSN during adenoma-carcinoma sequence. Surprisingly, the expression of ALIX (ALG 2-interacting protein X), involved in multivesicular body (MVB) and exosome formation, was significantly reduced in normal vs adenoma (P=5.02 × 10(-13)) and in normal vs colorectal carcinoma comparisons (P=1.51 × 10(-10)). ALIX also showed significant reduction (Pexosome function. MVB-like structures were also detected in tumor microenvironment including α-smooth muscle actin-positive stromal cells, budding off cancer cells in the tumor front as well as in cancer cells entrapped within lymphoid vessels. In conclusion, we determined the top aberrantly expressed exosome-associated markers and revealed the transition of diffuse ALIX protein signals into a MVB-like pattern during adenoma-carcinoma sequence. These tumor-associated particles seen both in the carcinoma and the surrounding microenvironment can potentially mediate epithelial-stromal interactions involved in the regulation of tumor growth, metastatic invasion and therapy response. PMID:27150162

  11. Association between Asymptomatic Bacteriuria and Pre-Eclampsia.

    Science.gov (United States)

    Rezavand, Negin; Veisi, Firooze; Zangane, Mrayam; Amini, Roghaye; Almasi, Afshin

    2016-01-01

    Asymptomatic bacteriuria is one of the most common and important bacterial infections during pregnancy and can result in progressive infections and endanger maternal as well as fetal health. In this study, we assessed the relationship between asymptomatic bacteriuria and pre-eclampsia. In this case-control study, pregnant women who presented to Imam Reza Hospital in Kermanshah in 2013-14 were studied. The minimum sample size was calculated as 125 pregnant women in each group with a total of 250 subjects. There were 125 women with pre-eclampsia and 125 women without pre-eclampsia (control group). Matching was done for age, gestational age, and parity between case and control groups. Matching was verified by a P value of 0.061 for maternal age and gestational age and 0.77 for parity. The statistical analyses were done by applying the chi-squared test and determining odds ratio (OR) for having bacteriuria in univariate logistic regression as well as multivariate regression with adjusting the effect of maternal age, gestational age, and parity. Pyuria and bacteriuria were significantly more common in pre-eclampsia group than in control group. The results showed that a significant association existed between asymptomatic bacteriuria and pre-eclampsia. The rate of asymptomatic bacteriuria was 6.8 times higher in women with pre-eclampsia compared to those without pre-eclampsia. Further studies are required for better clarification of association between asymptomatic bacteriuria and pre-eclampsia. PMID:26925912

  12. Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy.

    Science.gov (United States)

    Schnarr, J; Smaill, F

    2008-10-01

    Symptomatic and asymptomatic bacteriuria is common in pregnant women. A history of previous urinary tract infections and low socioeconomic status are risk factors for bacteriuria in pregnancy. Escherichia coli is the most common aetiologic agent in both symptomatic and asymptomatic infection and quantitative culture is the gold standard for diagnosis. Treatment of asymptomatic bacteriuria has been shown to reduce the rate of pyelonephritis in pregnancy and therefore screening for and treatment of asymptomatic bacteriuria has become a standard of obstetrical care. Antibiotic treatment of asymptomatic bacteriuria is associated with a decrease in the incidence of low birth weight, but the methodological quality of the studies limits the strength of the conclusions that can be drawn. Debate exists in the literature as to whether treated pyelonephritis is associated with adverse fetal outcomes. There is no clear consensus in the literature on antibiotic choice or duration of therapy for infection. With increasing antibiotic resistance, consideration of local resistance rates is necessary when choosing therapy. PMID:18826482

  13. Asymptomatic severe aortic stenosis: challenges in diagnosis and management.

    Science.gov (United States)

    Izumi, Chisato

    2016-08-01

    Optimal management for asymptomatic severe aortic stenosis (AS) remains controversial. Considering the increase in elderly patients, improved surgical outcomes and the introduction of transcatheter aortic valve implantation, we must reconsider the optimal management of asymptomatic severe AS. In this article, previous studies regarding the natural history of asymptomatic severe AS were reviewed to obtain a clinical perspective of AS in the growing elderly patient population. The incidence of sudden death in asymptomatic severe AS varies among studies from 0.25% to 1.7% per year, with differences related to study design and patient background. Except for very severe AS, sudden death or AS-related cardiac death without preceding symptoms is uncommon if 'watchful' waiting strategy is possible. Therefore, early operation is reasonable in very severe AS, but it is not recommended for all patients with severe AS. Using exercise tests, plasma levels of natriuretic peptides and other parameters, risk stratification of asymptomatic severe AS is needed to select patients who may have greater benefit following early operation. On the other hand, 'watchful' waiting is not always possible in real world of our practice. Patient education and periodic echocardiography are essential in 'watchful' waiting, which is not simply waiting strategy without careful monitoring. Individualised discussion regarding the indication for early operation is necessary, considering age, clinical background, predicted natural history and operative risk in each patient. PMID:27091844

  14. Colorectal Cancer with Synchronous Liver Metastases: Influence of Surgical Strategy on Treatment Results and Costs

    OpenAIRE

    Kolesnik, O. O.; Burlaka, A. A.; Lukashenko, A. V.; Priymak, V. V.; Volk, M. O.

    2015-01-01

    The objective of the research was to improve immediate and long-term results of treatment in patients with synchronous metastatic colorectal cancers (smCRC) developing surgical treatment program with application of simultaneous and staged methods for resection of primary tumor and liver metastases.   Materials and methods. The study was based upon reviewing treatment results for 125 patients with smCRC (рТ1-4N0-2M1 in colon cancer and рТ1-3N0-2M1 in rectal cancer) who underwent either simulta...

  15. In vivo and in vitro invasion in relation to phenotypic characteristics of human colorectal carcinoma cells.

    OpenAIRE

    Vries, J.E. de; Dinjens, W.N.; De Bruyne, G. K.; Verspaget, H. W.; van der Linden, E. P.; de Bruïne, A. P.; Mareel, M. M.; Bosman, F. T.; ten Kate, J.

    1995-01-01

    In this study we investigated the tumorigenicity, growth pattern and spontaneous metastatic ability of a series of nine human colorectal carcinoma cell lines after subcutaneous and intracaecal xenografting in nude mice. CaCo2 cells were found to be poorly tumorigenic to non-tumorigenic in either site; the other cell lines were tumorigenic in both sites. SW1116, SW480 and SW620 did not show local invasive in the NCI-H716 and LS174T cells were both invasive in the caecum, but only NCI-H716 was ...

  16. STUDY DATA OF KRAS- AND RAS-UNMUTATED (WILD TYPE OF COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    V. A. Gorbunova

    2015-05-01

    Full Text Available  Analysis of latest trials, comparing treatment schemes including chemotherapy with anti-EGFR monoclonal antibodies or bevacizumab is presented in this article. The data in these trials is inconsistent, but detailed analysis of FIRE-3 trial allows to distinguish a wild-type RAS patient group that benefits most from chemotherapy with cetuximab or panitumumab as 1st line metastatic colorectal cancer treatment. A final analysis of this patient group in CALGB/SWOG 80 405 trial is pending. The RAS analysis is pivotal for choice of 1st line chemotherapy.

  17. Tumor lysis syndrome following endoscopic radiofrequency interstitial thermal ablation of colorectal liver metastases.

    LENUS (Irish Health Repository)

    Barry, B D

    2012-02-03

    Radiofrequency interstitial thermal ablation (RITA) provides a palliative option for patients suffering from metastatic liver disease. This procedure can be performed using a laparoscopic approach with laparoscopic ultrasound used to position the RITA probe. We describe a case of laparoscopic RITA performed for colorectal liver metastasis that was complicated by tumor lysis syndrome (TLS) following treatment. We consider RITA to be a safe procedure, as supported by the literature, but where intracorporal tumor lysis is the treatment goal we believe that the systemic release of tumor products can overwhelm the excretory capacity; therefore, TLS is an inevitable consequence in some patients.

  18. DPD is a molecular determinant of capecitabine efficacy in colorectal cancer

    DEFF Research Database (Denmark)

    Vallböhmer, Daniel; Yang, Dong Yun; Kuramochi, Hidekazu;

    2007-01-01

    Capecitabine is a fluoropyrimidine-based drug that offers physicians a more convenient treatment for advanced colorectal cancer (CRC), with manageable toxicity and antitumor activity comparable to that of continuous-infusion therapies with 5-fluorouracil (5-FU). However, there are no validated and...... study and treated with single agent capecitabine. The intratumoral mRNA levels of DPD, TP and TS were assessed from paraffin-embedded tissue samples using laser-capture-microdissection methods and quantitative real-time PCR. There were 20 women and 17 men with a median age of 61 years (range 49-74). The...... fluoropyrimidine-based drugs in various tumors. Therefore, we investigated whether intratumoral mRNA expression levels of these genes are also associated with the clinical outcome of patients with metastatic CRC treated with first-line capecitabine. Thirty-seven patients with metastatic CRC were enrolled in this...

  19. Colorectal cancer screening

    Directory of Open Access Journals (Sweden)

    Almeida Frederico Ferreira Novaes de

    2000-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening.

  20. Animal Models of Colorectal Cancer

    Science.gov (United States)

    Johnson, Robert L.; Fleet, James C.

    2012-01-01

    Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650