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Sample records for metastatic colorectal carcinoma

  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. Downregulation of osteoprotegerin expression in metastatic colorectal carcinoma predicts recurrent metastasis and poor prognosis.

    Science.gov (United States)

    Moon, Ahrim; Do, Sung-Im; Kim, Hyun-Soo; Kim, Youn-Wha

    2016-11-29

    We recently reported the downregulation of osteoprotegerin expression in primary colorectal carcinoma and its significant association with aggressive oncogenic behavior, which suggest that this process contributes to colorectal carcinoma development and progression. In this study, we used immunohistochemical staining to evaluate osteoprotegerin expression in 81 colorectal liver metastasis tissue samples and investigated its possible association with the clinicopathological characteristics and outcomes of patients with colorectal liver metastasis. These tissues exhibited significantly reduced expression of osteoprotegerin compared to primary colorectal carcinomas and normal colorectal mucosa. This reduced expression was significantly associated with the extent of colorectal liver metastasis, including multiplicity of metastatic tumors, involvement of the bilateral hepatic lobes, and higher histological grade. In addition, reduced osteoprotegerin expression was an independent significant predictor of recurrent liver metastasis and prognostic factor for reduced patient survival. These findings suggest that osteoprotegerin expression may be a novel predictor of recurrent liver metastasis and a prognostic biomarker in patients with colorectal liver metastasis. Patients harboring colorectal liver metastasis with reduced osteoprotegerin expression should be carefully monitored after hepatic resection for colorectal liver metastasis to enable early detection of potentially resectable metastatic recurrences.

  3. A comprehensive review of 5-fluorouracil and leucovorin in patients with metastatic colorectal carcinoma.

    Science.gov (United States)

    Machover, D

    1997-10-01

    Colorectal carcinoma is the third leading cause of cancer-related death. The primary treatment for patients with metastatic colorectal carcinoma is systemic chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV), a biomodulator of 5-FU that has been shown to enhance its activity. Optimal dosing and administration strategies remain to be determined. This article is a review of recent studies reporting on the use of high dose and low dose LV as a biomodulator of 5-FU in patients with advanced colorectal carcinoma. Studies of LV plus 5-FU demonstrated response rates of 7-58% in patients who had not received prior chemotherapy. A survival advantage was recorded in some trials. LV plus 5-FU produces mild and transient hematologic toxicity. The most common toxicities from LV plus 5-FU were gastrointestinal and schedule-dependent, but generally resolved within a few days. The combination of LV and 5-FU provides a favorable treatment regimen for patients with metastatic colorectal carcinoma. Growing evidence suggests that altering the dose and schedule of both LV and 5-FU can impact positively on the response rate. However, controversy remains regarding the optimal dosing regimen. Therefore, continued study of LV plus 5-FU is urged and a favorable impact on survival is requisite before definitive conclusions are drawn, particularly in relation to LV dosage.

  4. Distinct claudin expression profiles of hepatocellular carcinoma and metastatic colorectal and pancreatic carcinomas.

    Science.gov (United States)

    Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Szijártó, Attila; Kupcsulik, Péter; Schaff, Zsuzsa; Kiss, András

    2013-04-01

    Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 colorectal adenocarcinomas (CRLMs) and 15 pancreatic adenocarcinomas (PLMs) were studied together with paired surrounding non-tumorous liver samples and 5 normal liver samples. Strong claudin-3 and -7 immunohistochemical positivities were detected in CRLM samples, each with significantly stronger staining when compared with HCC and PLM groups. Claudin-1 protein was found highly expressed in CRLM, in contrast to lower expression in PLM and HCC. CRLMs and PLMs also were strongly positive for claudin-4, while being virtually undetectable in HCC. Claudin-2 showed strong positivity in non-tumorous liver tissue, whereas significantly weaker positivity was observed in all tumors. Differences in mRNA expression were mostly similar to those found by immunohistochemistry. In conclusion, HCC and both CRLM and PLM display distinct claudin expression profiles, which might provide better understanding of the pathobiology of these lesions and might be used for differential diagnosis.

  5. Meeting An Unmet Need in Metastatic Colorectal Carcinoma with Regorafenib

    Directory of Open Access Journals (Sweden)

    Barbara Melosky

    2016-01-01

    Full Text Available Colorectal cancer is a global issue, affecting men and women equally. Over the last 25 years, advances in therapy and multidisciplinary care have led to improvements in survival for those with colorectal cancer. Despite these advances, more therapeutic options are needed for those being treated for this disease.Regorafenib is an oral drug that is a new therapeutic option for our patients. The CORRECT and CONCUR trials demonstrate the efficacy of regorafenib in the last line setting. This article summarizes some of the regorafenib clinical trial data and discusses the strategies to help manage the side effects of this drug including patient education, dose reductions and interruptions, and monitoring hypertension and liver function.

  6. Distinct Claudin Expression Profiles of Hepatocellular Carcinoma and Metastatic Colorectal and Pancreatic Carcinomas

    OpenAIRE

    Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Szijártó, Attila; Kupcsulik, Péter; Schaff, Zsuzsa; Kiss, András

    2013-01-01

    Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 col...

  7. 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.

  8. Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells.

    Science.gov (United States)

    Lin, Yuan-Na; Izbicki, Jakob R; König, Alexandra; Habermann, Jens K; Blechner, Christine; Lange, Tobias; Schumacher, Udo; Windhorst, Sabine

    2014-04-01

    In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably down-regulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy. © 2013 UICC.

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

    OpenAIRE

    Kir, Gozde; Gurbuz, Ayse; Karateke, Ates; Kir, Mustafa

    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...

  10. Dasatinib, a Src inhibitor, sensitizes liver metastatic colorectal carcinoma to oxaliplatin in tumors with high levels of phospho-Src

    Science.gov (United States)

    Perez, Marco; Lucena-Cacace, Antonio; Marín-Gómez, Luis Miguel; Padillo-Ruiz, Javier; Robles-Frias, Maria Jose; Saez, Carmen; Garcia-Carbonero, Rocio; Carnero, Amancio

    2016-01-01

    Despite the development of new antineoplastic agents for the treatment of colorectal cancer (CRC), oxaliplatin and fluoropyrimidines remain the most commonly employed drugs for the treatment of both early and advanced disease. Intrinsic or acquired resistance is, however, an important limitation to pharmacological therapy, and the development of chemosensitization strategies constitute a major goal with important clinical implications. In the present work, we determined that high levels of activated Src kinase, measured as phospho-Src at the Tyr419 residue in CRC cell lines, can promote colorectal carcinoma cell resistance to oxaliplatin, but not to 5-fluorouracil (5FU), and that inhibition of this protein restores sensitivity to oxaliplatin. Similar results were observed with in vivo patient-derived xenograft (PDX) models that were orthotopically grown in murine livers. In PDX tumor lines derived from human CRC liver metastasis, dasatinib, a Src inhibitor, increases sensitivity to oxaliplatin only in tumors with high p-Src. However, dasatinib did not modify sensitivity to 5FU in any of the models. Our data suggest that chemoresistance induced by p-Src is specific to oxaliplatin, and that p-Src levels can be used to identify patients who may benefit from this combination therapy. These results are relevant for clinicians as they identify a novel biomarker of drug resistance that is suitable to pharmacological manipulation. PMID:27105527

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

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    Mesti, Tanja; Boshkoska, Biljana Mileva; Kos, Mitja; Tekavčič, Metka; Ocvirk, Janja

    2015-06-01

    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

  12. 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.

  13. Cetuximab in treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Guren, Tormod Kyrre; Thomsen, Maria Morandi; Kure, Elin H

    2017-01-01

    BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival...

  14. 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

  15. Long-Lasting Tumor Response in Patients with Panitumumab Monotherapy for Chemorefractory Metastatic Colorectal Carcinoma – A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    G. Ramadori

    2010-05-01

    Full Text Available Background: Second as well as higher-line therapies have a significant influence on progression-free and overall survival of metastatic colorectal cancer patients. However, treatment of late-stage disease remains suboptimal. Therefore, the introduction of new, effective and well-tolerated agents is of major importance. Case Reports: Here we describe the cases of 2 patients with metastatic KRAS wild-type colorectal cancer who received a fourth-line monotherapy with panitumumab after failure of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab. Results: Both patients achieved a partial remission, and for 11.5 and 18 months, respectively, they had a stable disease with initial reduction in the tumor marker carcinoembryonic antigen. Both patients reported a good tolerability of the treatment with improved quality of life (compared to receiving combined chemotherapy. Conclusion: Panitumumab monotherapy is an effective and well tolerated treatment of metastatic colorectal cancer in extensively pretreated KRAS wild-type patients. Our data have shown a response to panitumumab monotherapy for more than 11 months.

  16. Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial.

    Science.gov (United States)

    Yoshino, Takayuki; Obermannová, Radka; Bodoky, György; Garcia-Carbonero, Rocio; Ciuleanu, Tudor; Portnoy, David C; Kim, Tae Won; Hsu, Yanzhi; Ferry, David; Nasroulah, Federico; Tabernero, Josep

    2017-06-01

    The RAISE phase III clinical trial demonstrated that ramucirumab + (folinic acid plus 5-fluorouracil plus irinotecan) FOLFIRI significantly improved overall survival (OS) versus placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients failing bevacizumab- and oxaliplatin-based chemotherapy (hazard ratio [HR] = 0.84, 95% CI = 0.73-0.98, P = 0.022). Post hoc analyses of RAISE patient data examined the association of carcinoembryonic antigen (CEA) subgroups with efficacy parameters. CEA subgroups (≤10 versus >10 ng/ml) were based on 2X upper limit of normal (ULN) (5 ng/ml). The Kaplan-Meier method estimated the median OS and the progression-free survival (PFS). Log-rank test compared the survival distributions within the subgroups. Hazard ratio (HR) (95% confidence interval [CI]) and treatment-by-subgroup interaction p-values were calculated by Cox proportional hazards model. Ramucirumab treatment prolonged survival for the CEA ≤10 subgroup (HR = 0.68; 95% CI = 0.50-0.92; P = 0.013) and CEA >10 subgroup (HR = 0.90; 95% CI = 0.76-1.07; P = 0.233). However, the ramucirumab OS benefit over placebo was greater for the CEA ≤10 subgroup than for the CEA >10 subgroup (median OS: 3.6 versus 0.8 months greater, respectively). The interaction P-value between CEA level and treatment effect on OS was 0.088. This trend was observed across randomisation strata and to a lesser extent for PFS (P = 0.594). Although patients in both high- and low-CEA subgroups derive OS and PFS benefits from ramucirumab treatment, the low baseline CEA level may identify a subgroup of patients with mCRC who obtain greater benefit from ramucirumab. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  17. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2012-01-01

    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 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...

  18. 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.

  19. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  20. Basal Cell Carcinoma Metastatic to Parotid Gland

    OpenAIRE

    Kurian, Rinsey Rose; Di Palma, Silvana; Barrett, A. W.

    2013-01-01

    Metastasis from basal cell carcinoma of the skin is very rare with cases being documented in the lymph nodes, lung, bone and parotid gland. The main histopathological differential diagnosis is the locally arising basal cell adenocarcinoma from which it is difficult to distinguish by morphology and routine immunohistochemistry. Approximately 85 % of all reported metastatic basal cell carcinomas arise in the head and neck region. Here we present a case of basal cell carcinoma of the skin of the...

  1. Molecularly targeted drugs for metastatic colorectal cancer

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    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

  2. Radiotherapy for metastatic fibrolamellar hepatocellular carcinoma

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    Justin G. Peacock

    2013-07-01

    Full Text Available Fibrolamellar hepatocellular carcinoma (FLHCC is a rare variant of hepatocellular carcinoma (HCC that commonly affects young individuals without a prior history of liver disease. FLHCC commonly results in a better prognosis than HCC; however, the risk of recurrence and metastatic disease is high. FLHCC is typically treated by primary resection of the tumor with 50-75% cure rates. The use of radiation therapy in FLHCC has not been assessed on its own, and may show some success in a very few reported combination therapy cases. We report on the successful use of radiation therapy in a case of metastatic FLHCC to the lung following primary and secondary resections. Our treatment of the large, metastatic, pulmonary FLHCC tumor with 40 Gy in 10 fractions resulted in an 85.9% tumor volume decrease over six months. This suggests FLHCC may be a radiosensitive tumor and radiotherapy may be valuable in unresectable or metastatic tumors.

  3. Metastatic follicular thyroid carcinoma to the mandible

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    Ajay Prakash Pasupula

    2012-01-01

    Full Text Available Metastatic tumors are of great significance since few cases may represent the only symptom of an undiscovered underlying malignancy. Metastatic tumors rarely metastasize to the oral region despite the fact that many common primary neoplasms frequently metastasize to bone. The true incidence of metastatic tumors in the bones of the jaw is unknown, as jaws are not always included in radiographic skeletal surveys for metastasis. Sometimes oral metastasis may be the first evidence of metastasis from its primary site. A case of metastatic follicular thyroid carcinoma to the mandible is presented here, along with the discussion of clinical and histological features. The present case not only emphasizes the importance of considering metastasis in the differential diagnosis of a radiolucent lesion in the mandible, but also emphasizes in the improvement of the overall survival rate and treatment results by an early detection of metastatic disease.

  4. Preoperative hypoxyradiotherapy of colorectal carcinoma

    International Nuclear Information System (INIS)

    Tacev, T.; Skricka, T.; Zaloudik, J.; Pacovsky, Z.

    2002-01-01

    Aim: The article focuses on the radioprotective effect of acute hypoxia on healthy tissues during preoperative accelerated hypoxyradiotherapy of colorectal carcinoma performed as locoregional irradiation including the common iliac lymph nodes. Analysis of early and late side effects and complications. Patients and Methods: In this prospective study, early and late complications were assessed in 50 patients as a function of hypoxyradiotherapeutic dose increase. The preliminary treatment results of this radiotherapeutic modification were evaluated after a median follow-up of 48 months using Kaplan-Meier analysis. Between April 1991 and February 1997, 50 patients (36 men and 14 women) with colorectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated hypoxyradiotherapy. The extent of disease was classified according to Dukes' criteria (A: four patients, B: 28 patients, C: 18 patients). We used a 20-MeV linear accelerator with two parallel opposed fields. Hypoxyradiotherapy was performed extending from the perineum to the L4 region. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen. Total doses of 24 Gy/8 days, 28 Gy/9 days, and 32 Gy/10 days were applied in five, 20, and 25 patients, respectively. Low anterior resection or abdominoperineal amputation of the rectum was performed the day after completion of preoperative hypoxyradiotherapy. The early reactions after irradiation were evaluated according to the Common Toxicity Criteria of the National Cancer Institute (CTC-NCI). Results: Early postirradiation proctitis was documented in three and early radiation-induced cystitis in two patients only. Neither early nor late radiation-associated complications were observed in any of the three hypoxyradiotherapy schedules during the follow-uper period of 6-105 months. Based on Kaplan-Meier analysis (median 48 months), a 5-year overall survival rate of 61.5% and a local relapse

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

    International Nuclear Information System (INIS)

    Erkasap, N.; Ozkurt, M.; Erkasap, S.; Yasar, F.; Uzuner, K.; Ihtiyar, E.; Uslu, S.; Kara, M.; Bolluk, O.

    2013-01-01

    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. Basal cell carcinoma metastatic to parotid gland.

    Science.gov (United States)

    Kurian, Rinsey Rose; Di Palma, Silvana; Barrett, A W

    2014-01-01

    Metastasis from basal cell carcinoma of the skin is very rare with cases being documented in the lymph nodes, lung, bone and parotid gland. The main histopathological differential diagnosis is the locally arising basal cell adenocarcinoma from which it is difficult to distinguish by morphology and routine immunohistochemistry. Approximately 85 % of all reported metastatic basal cell carcinomas arise in the head and neck region. Here we present a case of basal cell carcinoma of the skin of the left lateral canthus of the eye which metastasized to the intraparotid lymph nodes with infiltration of the adjacent parotid parenchyma. More awareness and vigilance is required on the part of the reporting pathologist to consider metastasis in the presence of a parotid tumour. Features favouring metastasis include history of primary cutaneous basal cell carcinoma, histological similarity to the primary lesion and absence of any demonstrable direct extension from the skin lesion. We also review the literature on metastatic basal cell carcinoma and discuss the need for adequate follow up in high risk patients.

  7. Metastatic follicular carcinoma of thyroid in maxilla

    OpenAIRE

    Kumar, Caliaperoumal Santhosh; Shanmugam, Devakumari; Venkatapathy, Ramesh; Munshi, Meer Ahmed Ibrahim

    2013-01-01

    Metastasis to the oral region is very rare and accounts for less than 1% of oral malignant tumors. Breast, lung, kidney, adrenal, gastro intestinal tract and prostates are most common primary tumors from which metastasis to oral region occur frequently. Metastasis from thyroid gland is extremely rare to oral region. We present an unusual case of metastatic follicular carcinoma of thyroid in maxilla. The significance of this report is that the secondary lesion was the only symptom of the prima...

  8. FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer

    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...

  9. Cost-Effectiveness Analysis of Regorafenib for Metastatic Colorectal Cancer.

    Science.gov (United States)

    Goldstein, Daniel A; Ahmad, Bilal B; Chen, Qiushi; Ayer, Turgay; Howard, David H; Lipscomb, Joseph; El-Rayes, Bassel F; Flowers, Christopher R

    2015-11-10

    Regorafenib is a standard-care option for treatment-refractory metastatic colorectal cancer that increases median overall survival by 6 weeks compared with placebo. Given this small incremental clinical benefit, we evaluated the cost-effectiveness of regorafenib in the third-line setting for patients with metastatic colorectal cancer from the US payer perspective. We developed a Markov model to compare the cost and effectiveness of regorafenib with those of placebo in the third-line treatment of metastatic colorectal cancer. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2014. Model robustness was addressed in univariable and probabilistic sensitivity analyses. Regorafenib provided an additional 0.04 QALYs (0.13 life-years) at a cost of $40,000, resulting in an incremental cost-effectiveness ratio of $900,000 per QALY. The incremental cost-effectiveness ratio for regorafenib was > $550,000 per QALY in all of our univariable and probabilistic sensitivity analyses. Regorafenib provides minimal incremental benefit at high incremental cost per QALY in the third-line management of metastatic colorectal cancer. The cost-effectiveness of regorafenib could be improved by the use of value-based pricing. © 2015 by American Society of Clinical Oncology.

  10. Optimal duration of systemic treatment in metastatic colorectal cancer

    NARCIS (Netherlands)

    Simkens, Lieke H. J.; Koopman, Miriam; Punt, Cornelis J. A.

    2014-01-01

    With the currently available cytotoxic and targeted drugs, metastatic colorectal cancer (mCRC) may be controlled by systemic treatment for a significant period of time. However, many questions remain about the optimal use of drugs and duration of treatment. We reviewed the data from clinical trials

  11. Cell-Free DNA in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Boysen, Anders K; Pallisgård, Niels

    2017-01-01

    -analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection. MATERIALS AND METHODS: A systematic literature search of PubMed and Embase was performed by two...... therapy. Small fragments of circulating cell-free DNA (cfDNA) can be measured in a simple blood sample. This report presents the first meta-analysis of the prognostic value of total cfDNA measurement in patients with metastatic colorectal cancer. Data from 1,076 patients confirmed that patients...... with the lowest pre-treatment levels of cfDNA had a significantly higher chance of longer survival than those with higher levels. Cell-free DNA analysis can also be used for detection of tumor-specific mutations, and hold potential as a valuable tool in colorectal cancer treatment....

  12. [The colorectal carcinoma; pathological remarks (author's transl)].

    Science.gov (United States)

    Simon, H

    1980-01-01

    A survey is presented on the incidence of colorectal carcinomas in the GDR, exogenous causes possibly being responsible for the increase in incidence, common screening methods, macro-anatomy and micro-anatomy of colorectal carcinoma, staging, prognosis, and pathways of metastases. The correlation between intestinal polypi and colorectal carcinoma as well as the frequency of their degeneration are also referred to. Adenomatous polypi (polypous adenoma), villous polypi (villous adenoma), and certain rare intestinal polypi, such as familial polyposis coli, multiple polyposis of the entire gastro-intestinal tract, as well as the Gardner- and Turcot-syndromes, are some of those polypi which depending on their size tend to malignant degeneration. Histological information provided by the pathologist is discussed in its value and importance for surgical practice.

  13. Metastatic follicular carcinoma of thyroid in maxilla

    Directory of Open Access Journals (Sweden)

    Caliaperoumal Santhosh Kumar

    2013-01-01

    Full Text Available Metastasis to the oral region is very rare and accounts for less than 1% of oral malignant tumors. Breast, lung, kidney, adrenal, gastro intestinal tract and prostates are most common primary tumors from which metastasis to oral region occur frequently. Metastasis from thyroid gland is extremely rare to oral region. We present an unusual case of metastatic follicular carcinoma of thyroid in maxilla. The significance of this report is that the secondary lesion was the only symptom of the primary tumor and helped us in diagnosis and treatment of disease.

  14. Metastatic follicular carcinoma of thyroid in maxilla.

    Science.gov (United States)

    Kumar, Caliaperoumal Santhosh; Shanmugam, Devakumari; Venkatapathy, Ramesh; Munshi, Meer Ahmed Ibrahim

    2013-11-01

    Metastasis to the oral region is very rare and accounts for less than 1% of oral malignant tumors. Breast, lung, kidney, adrenal, gastro intestinal tract and prostates are most common primary tumors from which metastasis to oral region occur frequently. Metastasis from thyroid gland is extremely rare to oral region. We present an unusual case of metastatic follicular carcinoma of thyroid in maxilla. The significance of this report is that the secondary lesion was the only symptom of the primary tumor and helped us in diagnosis and treatment of disease.

  15. Metastatic mammary carcinoma in a cow

    Directory of Open Access Journals (Sweden)

    Manoela Marchezan Piva

    Full Text Available ABSTRACT: Mammary gland neoplasms in cattle are rarely observed in the field veterinary diagnostics routine. Therefore, the objective of this study is to report a metastatic mammary carcinoma in a fourteen-year-old Holstein cow in the state of Santa Catarina, Brazil. The animal was diagnosed by the field veterinarian with clinical mastitis that was unresponsive to treatment, and was euthanized due to the poor prognosis. At the necropsy, multiple yellow, firm, and sometimes friable nodules, ranging from 0.1 to 20cm were observed in all mammary glands, lymph nodes, kidneys, spleen, liver, pancreas, mediastinal lymph nodes, heart, and lungs. The final diagnosis of mammary carcinoma was established through the association of clinical, necropsy, histopathological, and immunohistochemical findings. Differential diagnoses included diseases such as bovine tuberculosis and chronic fungal or bacterial mastitis.

  16. Australian contemporary management of synchronous metastatic colorectal cancer.

    Science.gov (United States)

    Malouf, Phillip; Gibbs, Peter; Shapiro, Jeremy; Sockler, Jim; Bell, Stephen

    2018-01-01

    This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice. © 2016 Royal Australasian College of Surgeons.

  17. Metastatic renal cell carcinoma to the thyroid gland.

    Science.gov (United States)

    Duggal, Neal Murari; Horattas, Mark C

    2008-11-01

    To examine the presentation, diagnosis, and appropriate management of renal clear cell carcinoma metastasis to the thyroid gland. We describe a clinical case of solitary thyroid metastasis from renal clear cell carcinoma and present a comprehensive review of the related English-language literature. Common patterns of presentation and generalized overall management recommendations are evaluated and summarized. Eight years after nephrectomy for renal carcinoma at age 61 years, a man presented with a thyroid mass. Cytology and histopathologic surgical findings were consistent with a solitary metastasis most compatible with metastatic clear cell carcinoma from his previous renal carcinoma. After left thyroid lobectomy and isthmusectomy, the patient remains disease-free 5 years later. Although uncommon, nearly 150 cases of clinically recognized metastatic renal cell carcinoma to the thyroid have been reported in the English-language literature. Metastatic disease from the kidney to the thyroid gland can occur more than 20 years after nephrectomy with the average time interval being 7.5 years. Obtaining a full clinical history in any patient who presents with a thyroid nodule is essential to allow consideration of possible metastatic disease from previous primary tumor. Metastatic disease to the thyroid gland can be correctly diagnosed preoperatively. If metastatic renal cancer is limited to the thyroid gland only, prompt, appropriate surgical intervention can be curative. Metastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of renal cell carcinoma.

  18. Visualising and quantifying angiogenesis in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Jakobsen, Anders

    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 ch...... of chemotherapy response. Here, we evaluated whether more general approaches to determine vessel density in primary tumours are equally predictive of chemotherapy response....

  19. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2008-01-01

    , panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). MATERIALS AND METHODS: We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data......BACKGROUND: The past years' therapy for colorectal cancer has evolved rapidly with the introduction of novel cytotoxic agents such as irinotecan, capecitabine and oxaliplatin. Further advances have been achieved with the integration of targeted agents such as bevacizumab, cetuximab and recently......OS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. CONCLUSION: Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted...

  20. METASTATIC PENILE CARCINOMA: A STUDY OF NINE CASES AND

    African Journals Online (AJOL)

    9 55 bladder TCC total penectomy 21. TCC = transitional cell carcinoma, SCC = squamous cell carcinoma. The rarity of the event prompted this study which describes 9 metastatic penile carcinoma cases including 7 originating from the bladder and one each from the lung and the bone mar- row. PATIENTS AND METHODS.

  1. Sequential Therapy in Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bradford R Hirsch

    2016-04-01

    Full Text Available The treatment of metastatic renal cell carcinoma (mRCC has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network's Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future.

  2. Intraventricular metastatic clear cell renal carcinoma.

    Science.gov (United States)

    Sava, I; Sava, Anca; Şapte, Elena; Mihailov, Claudia; Dumitrescu, Gabriela; Poeată, I; Sava, Florina; Haba, Danisia

    2013-01-01

    Intraventricular tumors represent a diagnostic problem, due to a wide range of differential diagnosis, with an important variability of tumoral histological types in adult and pediatric population. Patient, Our case is represented by a patient, aged 48 years, without any history of significant personal pathology, accusing nausea, vomiting, and intensive headache. In the morning, he became confused, having hallucinations for a short period of time, and has accused drowsiness for several weeks. Imaging (CT and MRI) shows a neoformation in the third ventricle, accompanied by bilateral lateral ventricles dilatation, with predominantly annular enhancement. During surgery, through the middle third transcallosal interhemispheric approach, it was revealed a reddish, well-demarcated intraventricular mass, well vascularized and with a firm consistency. Final pathologic diagnosis was metastatic clear cell renal carcinoma. Initial postoperative evolution was good, and then neurological and respiratory condition worsened as a bronchopneumonia lead to patient's death in 12 days after surgery. Clear cell carcinoma metastasis located in the third ventricle should be taken into consideration for patients presenting a single intraventricular lesion even they have no documented primary malignancy.

  3. Unusual Metastatic Patterns of Invasive Lobular Carcinoma of the Breast

    OpenAIRE

    Sobinsky, Justin D.; Willson, Thomas D.; Podbielski, Francis J.; Connolly, Mark M.

    2013-01-01

    Invasive lobular carcinoma of the breast has similar patterns of metastatic disease when compared to invasive ductal carcinoma; however, lobular carcinoma metastasizes to unusual sites more frequently. We present a 65-year-old female with a history of invasive lobular breast carcinoma (T3N3M0) treated with modified radical mastectomy and aromatase-inhibitor therapy who underwent a surveillance PET scan, which showed possible sigmoid cancer. Colonoscopy with biopsy revealed a 3?cm sigmoid aden...

  4. A case of metastatic renal cell carcinoma to thyroid gland.

    Science.gov (United States)

    Lee, Jae-Geun; Yang, Youngro; Kim, Kwang Sik; Hyun, Chang Lim; Lee, Ji Shin; Koh, Gwanpyo; Lee, Daeho

    2011-08-01

    Metastasis to the thyroid gland from distant cancer is rare, and, in some cases, is a diagnostic challenge. Here, we report a case of metastatic renal cell carcinoma of the thyroid gland. A 77-year-old man presented with a neck mass detected about 1 month previously. He had undergone a right nephrectomy owing to renal cell carcinoma 14 years previously. Fine needle aspiration cytology showed a few atypical follicular cells with nuclear atypia. Under a tentative diagnosis of papillary thyroid carcinoma, a total thyroidectomy was performed. The histologic and immunohistochemical studies of the surgical specimens indicated that the thyroid masses were metastatic renal cell carcinoma to the thyroid.

  5. Basal cell carcinoma metastatic to cervical lymph nodes and lungs.

    Science.gov (United States)

    Boswell, J Scott; Flam, Marshall S; Tashjian, David N; Tschang, Tai-Po

    2006-10-31

    Metastatic basal cell carcinoma (MBCC) of the skin is rare in occurrence and may initially elude proper diagnosis and management. We describe a case of MBCC to cervical lymph nodes, originally evaluated and treated surgically as metastatic thyroid carcinoma. After definitive diagnosis of MBCC was made, chemotherapy and concomitant radiation treatment were initiated; however, despite these measures, the patient then developed MBCC to the lung. Risk factors and current therapeutic modalities for MBCC are also discussed. In addition to the more commonly metastasizing carcinomas, metastases from a cutaneous basal cell carcinoma primary tumor should be considered when evaluating cervical lymph node metastases of an uncertain head and neck primary.

  6. Breast carcinoma metastatic to the orbit: an unusually late presentation.

    Science.gov (United States)

    Milman, Tatyana; Pliner, Lillian; Langer, Paul D

    2008-01-01

    An 83-year-old woman, diagnosed with breast carcinoma 28 years earlier, presented with left hyperglobus and limitation of extraocular motility. CT and MRI showed bilateral nodular thickening of extraocular muscles. Left orbital biopsy disclosed metastatic breast carcinoma. Subsequent positron-emission tomography/CT revealed diffuse metastatic disease. To the authors' knowledge, this case represents the longest reported interval from the diagnosis of primary breast cancer to the presentation of orbital metastasis.

  7. PROGNOSTIC FACTORS FOR SURVIVAL IN PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED WITH FIRST - LINE CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2017-05-01

    Full Text Available Objective: The aim of this study was to investigate the prognostic significance for survival of certain clinical and pathological factors in patients with advanced or metastatic colorectal carcinoma (CRC treated with first- line chemotherapy. Methods: From 2002 to 2011 seventy- four consecutive patients with advanced or metastatic CRC, treated in UMHAT- Dr. G. Stranski, Department of Medical Oncology entered the study. Some patient’s characteristics, hematological and pathological parameters, were evaluated for their role as predictors of overall survival. The therapeutic regimens included FOLFOX or FOlFIRI. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment characteristics as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: In multivariate analysis a significant correlation was exhibited between survival, poor performance status and multiple sites of metastasis. Variables significantly associated with overall survival in univariate analysis were performance status>1, thrombocytosis, anemia and number of metastatic sites >1. Conclusion: These results indicated that poor performance status, anemia, thrombocytosis as well as multiple site of metastasis could be useful prognostic factors in patients with metastatic CRC.

  8. 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

  9. 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.

  10. Treatment of metastatic colorectal cancer: focus on panitumumab

    International Nuclear Information System (INIS)

    Tay, Rebecca Y; Wong, Rachel; Hawkes, Eliza A

    2015-01-01

    Targeted agents are an important therapeutic option in the treatment of metastatic colorectal cancer (mCRC). Panitumumab is a recombinant, fully humanized, immunoglobulin G2 monoclonal antibody that targets the epidermal growth factor receptor (EGFR) with efficacy in mCRC as monotherapy and in combination with chemotherapy. Kirsten rat sarcoma (KRAS) mutation status has emerged as an important biomarker to predict response to anti-EGFR therapy. Optimal timing for panitumumab use in the mCRC treatment algorithm has not been established. This review discusses the mechanism of action, predictive biomarkers, and role of panitumumab in the treatment of mCRC

  11. miR-345 in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Schou, Jakob V; Rossi, Simona; Jensen, Benny V

    2014-01-01

    for 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...

  12. Ultrasonic imaging of metastatic carcinoma in thyroid gland

    International Nuclear Information System (INIS)

    Bai Ling; Yang Tao; Tang Ying; Mao Jingning; Chen Wei; Wang Wei

    2008-01-01

    Objectives: To explore the ultrasonic findings of metastatic thyroid carcinoma and to evaluate the diagnostic value of the ultrasonic imaging for patients with metastatic thyroid neoplasm. Methods: The ultrasonic imaging characteristics of ten patients who were diagnosed with metastatic thyroid carcinoma were retrospectively analyzed. In all the cases, fine-needle aspiration cytology (FNAC) of the thyroid was performed during the clinical diagnosis. Results: The ultrasonic images of the ten patients fell into four types: multiple nodules in the thyroid, single nodule in the thyroid, diffuse calcification and heterogeneous echo. Seven cases showed speckled calcific foci. Abnormal blood flow signal was found in 9 cases. Conclusion: The ultrasonic findings of metastatic carcinoma in the thyroid gland are various and non-specific. Color Doppler ultrasound may provide ample evidence. The diagnosis depends on FNAC. (authors)

  13. Colorectal carcinoma with dome-like phenotype: an under-recognised subset of colorectal carcinoma?

    DEFF Research Database (Denmark)

    Asmussen, L; Pachler, J; Holck, S

    2008-01-01

    The term dome carcinoma has been applied to a variant of colorectal carcinoma, thought to derive from M-cells of the gut-associated lymphoid tissue. Its distinguishing morphological features include a non-polypoid plaque-like lesion composed of closely apposed cystically dilated glands lined...... by a single layer of non-mucinous cells, intensely PAS-positive intraluminal material, and a close spatial relation to lymphoid stroma. Aims and...

  14. Tailored treatment of metastatic colorectal cancer: clinical and pre-clinical developments

    NARCIS (Netherlands)

    Kuijpers, A.M.J.

    2015-01-01

    Colorectal cancer is the third leading cause of cancer-related death in males and females in developed countries. Metastases in distant organs, which develop in 50% of colorectal cancer patients, are responsible for the majority of colorectal cancer deaths. Treatment of metastatic disease should

  15. Metastatic Merkel Cell Carcinoma (MCC) of Pancreas.

    Science.gov (United States)

    Kartal, K; Hamaloğlu, E

    2015-01-01

    Merkel cell carcinoma (MCC) is a rare, agressive, neurocutaneous malignancy with a high potential to metastasize. We present a 59 year-old woman referred to general surgery department with a complaint of epigastric pain. The abdominal computed tomography (CT) performed and revealed amass of 3 cm in the head of the pancreas. The significant debate in the patient's medical history was that she had a MCC in size of 5 cm removed from the left gluteal region 7 months ago. Following preoperative preparation a pancreatic oduodenectomy with Whipple procedure was performed fort hepancreatic head mass. As the tumor showed morphologically similar properties with the patient's primary neoplasm, it was accepted as a metastatic MCC. Following the operation the patient received adjuvant chemotherapy and at a 30 months follow-up it was observed that the patient is disease free and has no complications related to the disease progression or recurrence. Although MCC is an aggresive and poor prognostic tumor, good results can be obtained with correct diagnosis and proper surgical treatment. Celsius.

  16. Colorectal Carcinoma in Children and Young Adults in Ilorin, Nigeria ...

    African Journals Online (AJOL)

    Conclusion: Colorectal carcinoma is not rare among young Nigerians and it should be suspected when young patients present with chronic bloody diarrhoea. Digital rectal examination should be encouraged as part of clinical examination in this age group too since a large percentage of colorectal carcinomas is within the ...

  17. Pulmonar collision tumor: Metastatic adenoid cystic carcinoma and lung adenocarcinoma

    OpenAIRE

    M. Blanco; E. García-Fontán; J. Ríos; J.E. Rivo; R. Fernández-Martín; M.A. Cañizares

    2012-01-01

    Summary: We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen. Resumo: Descreve...

  18. Anti-CEA monoclonal antibody in the diagnosis of colorectal, lung and ovarian carcinoma

    International Nuclear Information System (INIS)

    Jiang, N.; Lu, B.; Lu, X.; Sha, X.; Yue, D.

    2000-01-01

    This study evaluated the diagnostic value of radioimmnoimaging (RII) with 99 Tc labeled monoclonal antibody C50, raised originally against carcinoembryonic antigen (anti-CEA) in various tumors. 152 pathologically confirmed patients with a tumor were imaged prior to surgery with an anti-CEA monoclonal antibody labeled with 99 Tc. There were 115 patients with ovarian carcinoma, 26 patients with colorectal carcinoma and 11 patients with lung carcinoma. Images were acquired at 3-6 h post injection and were analyzed by the double blind method. Images of patients with ovarian cancer were compared with B-ultrasound images. Immunohistochemical staining was performed on all cases of colorectal cancer. All RII images demonstrated excellent contrast, clear lesions, and no serious toxic or other side reactions occurred. Transient chills and fever were observed in 3 cases. This study showed a sensitivity=88.2%, specificity=83.2%, and an accuracy=4.0%. The smallest lesion size detected was 2 x 2 cm. The total combined lesion detection rate for primary, metastatic, and recurrence lesions was 84.4%. We conclude that 99 Tc labeled anti-CEA MoAb C50 can be used in the diagnosis of colorectal carcinoma, ovarian carcinoma, and lung carcinoma

  19. Immunohistochemistry expression of TCF4 protein on carcinoma, adenoma and non neoplastic colorectal mucosa

    OpenAIRE

    Tauil, Leonardo Huber; Mader, Ana Maria Amaral; Tauil, Thamires Huber; Pires, Andrea; Rezende, Lidia Maria Magalhães; Waisberg, Jaques

    2014-01-01

    PURPOSE: To detect and quantify the immunoreactivity of TCF4 protein in colorectal carcinoma, colorectal adenoma and non-neoplasic colorectal epithelium.METHODS: We studied 129 individuals: 40 with colorectal cancer, 52 with colorectal adenoma and 37 with non-neoplastic colorectal epithelium. The colorectal adenoma and carcinoma samples were obtained from patients who underwent surgical procedures, and colonoscopies and samples of non-neoplastic colorectal epithelium were taken from patients ...

  20. Immunohistochemical assay for detection of K-ras protein expression in metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Tag Elsabah, M.; Iman Adel, I.

    2013-01-01

    Background: The monoclonal antibodies (mAbs) that target the epidermal growth factor receptor (EGFR) had expanded the range of treatment options for metastatic colorectal cancer. However, such type of treatment was shown to be ineffective if there is K-ras mutation. In most previous studies K-ras gene mutation was mainly assessed by PCR. Aim: Our work is designed to detect K-ras protein expression by immunohistochemistry (IHC) aiming to reach a preliminary method that could be confirmed by PCR and considered an alternative way for the detection of K-ras aberration. We are also aiming to find a relation between K-ras protein expression and K-ras gene mutation. Materials and methods: Paraffin embedded tissue samples from 26 metastatic colorectal cancer (mCRC) patients were analyzed for K-ras protein expression by IHC using RaplA polyclonal antibody. Staining patterns were subjectively assessed and correlated with clinicopathological features. The results were statistically evaluated using the Chi-square test. Results: K-ras cytoplasmic positivity was observed in 42.3% of cases. The positivity was either strong in 26.9% or moderate in 15.4%. With respect to adenocarcinoma variants, 50% of cases were positive for K-ras protein expression while all mucinous and signet ring types were negative. The positivity was noted in 50% of moderately differentiated GII colorectal carcinomas as compared with 38.9% in poorly differentiated GIII. Positive staining was observed in 40% of cases with positive lymph node metastasis while in the absence of nodal metastasis the positivity was 45.5%. No significant correlation was found between clinicopathological parameters and K-ras staining results. Conclusion: IHC may compliment PCR in the detection of K-ras mutation.

  1. Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells.

    Science.gov (United States)

    David, Muriel; Naudin, Cécile; Letourneur, Martine; Polrot, Mélanie; Renoir, Jack-Michel; Lazar, Vladimir; Dessen, Philippe; Roche, Serge; Bertoglio, Jacques; Pierre, Josiane

    2014-07-01

    Suppressor of cytokine signaling (SOCS) 1 is an inducible negative regulator of cytokine signaling but its role in human cancer is not completely established. Here we report that, while SOCS1 is expressed in normal colonic epithelium and colon adenocarcinomas, its level decreases during progression of colon adenocarcinomas, the lowest level being found in the most aggressive stage and least differentiated carcinomas. Forced expression of SOCS1 in metastatic colorectal SW620 cells reverses many characteristics of Epithelial-Mesenchymal Transition (EMT), as highlighted by the disappearance of the transcription factor ZEB1 and the mesenchymal form of p120ctn and the re-expression of E-cadherin. Furthermore, miRNA profiling indicated that SOCS1 also up-regulates the expression of the mir-200 family of miRNAs, which can promote the mesenchymal-epithelial transition and reduce tumor cell migration. Accordingly, overexpression of SOCS1 induced cell morphology changes and dramatically reduced tumor cell invasion in vitro. When injected in nude mice, SOCS1-expressing SW620 cells induced metastases in a smaller number of animals than parental SW620 cells, and did not generate any adrenal gland or bone metastasis. Overall, our results suggest that SOCS1 controls metastatic progression of colorectal tumors by preventing the mesenchymal-epithelial transition (MET), including E-cadherin expression. This pathway may be associated with survival to colorectal cancer by reducing the capacity of generating metastases. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. Trastuzumab therapy in metastatic bladder carcinoma: The proof of concept

    Directory of Open Access Journals (Sweden)

    Moussaid Y

    2014-08-01

    Full Text Available About 10% of metastatic urothelial carcinoma overexpress oncogenic HER2/neu receptor. Recent preliminary data suggest that patients with this particular molecular subset could benefit from trastuzumab therapy, which specifically targets the receptor and thus inhibits downstream activation pathway. Here we report a case illustrating this clinical benefit, with complete response reported as third line therapy in a heavily pretreated patient with diffuse metastatic urothelial carcinoma of the bladder. It also highlights the usefulness of 18-Fluorodeoxyglucose Positron Emission Tomography (18-FDG PET as a biomarker for response to trastuzumab.

  3. Diffuse metastatic infiltration of a carcinoma into skeletal muscle

    International Nuclear Information System (INIS)

    Hundt, W.; Braunschweig, R.; Reiser, M.

    1999-01-01

    Skeletal muscle is one of the most unusual sites of metastasis from any malignancy. We report a patient with rapidly progressive contractures due to metastatic infiltration of a carcinoma of unknown origin into the skeletal muscle. This 61-year-old man presented with a 1-month history of rapidly evolving, painful restriction of mobility of his right arm and his legs. Computed tomography showed diffuse metastatic nodules in all muscles, particularly in the hip abductors. Muscle biopsy revealed extensive infiltration of the muscle with carcinoma cells. (orig.)

  4. Diffuse metastatic infiltration of a carcinoma into skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Hundt, W.; Braunschweig, R.; Reiser, M. [Dept. of Diagnostic Radiology, Ludwig-Maximilians-Univ., Muenchen (Germany)

    1999-03-01

    Skeletal muscle is one of the most unusual sites of metastasis from any malignancy. We report a patient with rapidly progressive contractures due to metastatic infiltration of a carcinoma of unknown origin into the skeletal muscle. This 61-year-old man presented with a 1-month history of rapidly evolving, painful restriction of mobility of his right arm and his legs. Computed tomography showed diffuse metastatic nodules in all muscles, particularly in the hip abductors. Muscle biopsy revealed extensive infiltration of the muscle with carcinoma cells. (orig.) With 4 figs., 21 refs.

  5. Metastatic transitional cell carcinoma of the tibia radiologically mimicking osteosarcoma.

    LENUS (Irish Health Repository)

    Cunningham, Laurence Patrick

    2013-01-01

    We report a case of a 73-year-old lady with transitional cell carcinoma and no evidence of metastatic disease presenting with gradual weight loss, pretibial swelling and painful weightbearing. Investigations revealed a lesion of the right tibial diaphysis. The radiological and clinical appearance was that of primary osteosarcoma. Biopsy results revealed metastatic transitional cell carcinoma of the tibia. Intramedullary nailing was performed which relieved pain on weightbearing. The patient declined radiotherapy and was started on a palliative care regimen. This case illustrates the importance of histological diagnosis in the treatment of diaphyseal lesions.

  6. Characterizing the outcomes of metastatic papillary renal cell carcinoma

    DEFF Research Database (Denmark)

    Connor Wells, John; Donskov, Frede; Fraccon, Anna P

    2017-01-01

    Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were...... compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer...

  7. Bevacizumab increases the incidence of cardiovascular events in patients with metastatic breast or colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ioannis Kapelakis

    2017-05-01

    Conclusions: The addition of bevacizumab to conventional chemotherapy for metastatic breast or colorectal cancer increases the incidence of cardiovascular events, which is mainly due to the increased prevalence of myocardial infarction and thromboembolic events.

  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...... with metastatic disease, but the prognostic role of CTC in non-metastatic colorectal cancer is less clear. The aim of this review is to examine the possible clinical significance of circulating tumor cells in non-metastatic colorectal cancer (TNM-stage I-III) with the primary focus on detection methods...... 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...

  9. Patient considerations in metastatic colorectal cancer – role of panitumumab

    Directory of Open Access Journals (Sweden)

    Rogers JE

    2017-04-01

    Full Text Available Jane E Rogers Pharmacy Clinical Programs, University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Epidermal growth factor receptor (EGFR is overexpressed in many malignancies, including colorectal cancer (CRC, making EGFR an attractive treatment option. Panitumumab and cetuximab, monoclonal antibodies (mAbs directed at EGFR, are both currently utilized in the management of metastatic CRC (mCRC. Through the development of these agents in mCRC, key issues surrounding each mAbs use have been revealed. These key issues include negative patient outcome avoidance when determining use, the economic burden with high-cost medication, predictive biomarkers, tumor location, patient geographic location, patient quality of life, and the prevention of debilitating adverse effects. CRC remains a common malignancy, with many of these patients expected to receive targeted therapy, including EGFR mAb therapy. Oncologists must recognize these EGFR mAb factors in order to improve outcomes. This review aims to provide a chronological timeline on the development of panitumumab, clinical pearls, and guidance on the current use of panitumumab in mCRC. Keywords: receptor, epidermal growth factor, antineoplastic agent, antibodies, monoclonal, colorectal neoplasms

  10. Options for Second-Line Treatment in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Lee, James J; Sun, Weijing

    2016-01-01

    Colorectal cancer (CRC) remains a major public health problem in the United States and worldwide. The majority of patients who have CRC eventually present with metastatic disease. The overall therapeutic goals for most patients with metastatic CRC (mCRC) are to control the disease, prolong life span, and maximize quality of life. Therefore, the ratio of efficacy to toxicity is one of the most important factors in choosing among treatment options and sequencing regimens. In addition, the choice of first-line systemic therapy will affect the options for second-line treatment. Several newer cytotoxic agents for the treatment of mCRC have been approved during the past 2 decades by the US Food and Drug Administration (FDA), including irinotecan, oxaliplatin, and capecitabine. The combination of a fluoropyrimidine (5-fluorouracil or capecitabine) with either oxaliplatin or irinotecan has been widely accepted as standard cytotoxic chemotherapy for either the first- or second-line treatment of mCRC. The FDA has approved several pathway-targeting agents for the treatment of mCRC; these include agents that target the vascular endothelial growth factor receptor pathway (bevacizumab, ziv-aflibercept, and ramucirumab) and those that target the epidermal growth factor receptor pathway (cetuximab and panitumumab). Here, we review the current clinical options for the second-line treatment of mCRC and the rationales for their use.

  11. Updated options for liver-limited metastatic colorectal cancer.

    Science.gov (United States)

    Alberts, Steven R

    2008-12-01

    Liver metastases from colorectal cancer (CRC) are common in patients presenting with an initial diagnosis of metastatic disease or at the time of recurrence. Without treatment, patients with metastatic disease have a poor prognosis. Surgical resection of the metastases might provide long-term benefit.; however, the size, number, or location of the metastases can limit the ability to perform a resection. The use of chemotherapy, both systemic and via hepatic artery infusion, in patients undergoing surgery for liver metastases from CRC has augmented the long-term survival benefits and even the cure obtained in some patients with surgery. Chemotherapy might also convert a portion of patients with initially unresectable liver metastases to resectable. A growing body of literature is helping to define the role of chemotherapy for potentially resectable liver metastases and for initially unresectable liver metastases. The introduction of newer agents such as oxaliplatin and irinotecan, and targeted agents such as cetuximab and bevacizumab, has led to meaningful improvements in response rates and survival over those previously achieved with 5-fluorouracil. Further trials are needed to refine the use of chemotherapy and targeted agents in the management of patients with liver metastases.

  12. A Case of Metastatic Renal Cell Carcinoma to Thyroid Gland

    OpenAIRE

    Lee, Jae-Geun; Yang, Youngro; Kim, Kwang Sik; Hyun, Chang Lim; Lee, Ji Shin; Koh, Gwanpyo; Lee, Daeho

    2011-01-01

    Metastasis to the thyroid gland from distant cancer is rare, and, in some cases, is a diagnostic challenge. Here, we report a case of metastatic renal cell carcinoma of the thyroid gland. A 77-year-old man presented with a neck mass detected about 1 month previously. He had undergone a right nephrectomy owing to renal cell carcinoma 14 years previously. Fine needle aspiration cytology showed a few atypical follicular cells with nuclear atypia. Under a tentative diagnosis of papillary thyroid ...

  13. Third-line Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Wells, J Connor; Stukalin, Igor; Norton, Craig

    2017-01-01

    BACKGROUND: The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in a large international population. OBJECTIVE...... between OS and the six factors included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. Subgroup analysis was performed on patients stratified by their IMDC prognostic risk status. RESULTS AND LIMITATIONS: Everolimus was the most prevalent third...

  14. Immunotherapy for metastatic renal cell carcinoma.

    Science.gov (United States)

    Unverzagt, Susanne; Moldenhauer, Ines; Nothacker, Monika; Roßmeißl, Dorothea; Hadjinicolaou, Andreas V; Peinemann, Frank; Greco, Francesco; Seliger, Barbara

    2017-05-15

    Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients.In November 2015, nivolumab, a checkpoint inhibitor directed against programmed death-1 (PD-1), was approved as the first specific immunotherapeutic agent as second-line therapy in previously treated mRCC patients. To assess the effects of immunotherapies either alone or in combination with standard targeted therapies for the treatment of metastatic renal cell carcinoma and their efficacy to maximize patient benefit. We searched the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science and registers of ongoing clinical trials in November 2016 without language restrictions. We scanned reference lists and contacted experts in the field to obtain further information. We included randomized controlled trials (RCTs) and quasi-RCTs with or without blinding involving people with mRCC. We collected and analyzed studies according to the published protocol. Summary statistics for the primary endpoints were risk ratios (RRs) and mean differences (MD) with their 95% confidence intervals (CIs). We rated the quality of evidence using GRADE methodology and summarized the quality and magnitude of relative and absolute effects for each primary outcome in our 'Summary of findings' tables. We identified eight studies with 4732 eligible participants and an additional 13 ongoing studies. We categorized studies into comparisons, all against standard therapy accordingly as first-line (five comparisons) or second-line therapy (one comparison

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

    Directory of Open Access Journals (Sweden)

    Ocvirk Janja

    2016-06-01

    Full Text Available 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.

  16. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  17. Development of a metastatic fluorescent Lewis Lung carcinoma mouse model

    DEFF Research Database (Denmark)

    Rask, Lene; Fregil, Marianne; Høgdall, Estrid

    2013-01-01

    ) and spleen tyrosine kinase (SYK). A modest decrease in Drosha and Dicer mRNA levels was accompanied by significant downregulation of ten microRNAs, including miR-9 and miR-203, in the lung metastatic Lewis Lung carcinoma cell culture. Thus, a tool for cancer metastasis studies has been established...

  18. Metastatic papillary carcinoma of the thyroid in a patient previously ...

    African Journals Online (AJOL)

    She had an 123I diagnostic whole body scan that showed 123I avid areas in the thyroid bed as well as left cervical lymph nodes, which later turned out to be metastatic papillary carcinoma of the thyroid on histology. She was treated with therapeutic doses of 131I. Follow-up radioactive iodine scans and serum thyroglobulin ...

  19. Durable control of metastatic nasopharyngeal carcinoma with metronomic chemotherapy

    Directory of Open Access Journals (Sweden)

    Po-Hsiang Huang

    2017-03-01

    Full Text Available Metronomic chemotherapy has shown encouraging efficacy and low toxicity in various tumor types and is one of the best treatment options for heavily pretreated patients or patients with advanced age and/or poor performance status. We demonstrated a patient with metastatic nasopharyngeal carcinoma who experienced durable disease control under etoposide-based combination metronomic chemotherapy.

  20. Metastatic Carcinoma of Unknown Primary Presenting as Jugular Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Prince Cheriyan Modayil

    2009-01-01

    Full Text Available Jugular venous thrombosis is unusual and is associated with central venous catheterisation, intravenous drug abuse and head and neck sepsis. It is rarely associated with malignancy. We report a case of metastatic carcinoma of unknown primary in a forty year old female which presented with jugular venous thrombosis. The discussion includes investigation and treatment options for this condition.

  1. Pulmonar collision tumor: metastatic adenoid cystic carcinoma and lung adenocarcinoma.

    Science.gov (United States)

    Blanco, M; García-Fontán, E; Ríos, J; Rivo, J E; Fernández-Martín, R; Cañizares, M A

    2012-01-01

    We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen. Copyright © 2010 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  2. Colorectal carcinoma in Port Harcourt | Adotey | Port Harcourt ...

    African Journals Online (AJOL)

    Aim: To report experience with colorectal carcinoma in the University of Port Harcourt Teaching Hospital (UPTH). Methodology: Patients treated for colorectal cancer at the UPTH over a 19- year period (1987-2006) and had complete information, were studied. Data were collected from patients\\' case notes, ward registers, ...

  3. p53 expression in colorectal carcinoma in relation to ...

    African Journals Online (AJOL)

    p53 expression in colorectal carcinoma in relation to histopathological features in Ugandan patients. ... Molecular pathogenesis of colorectal cancer commonly involves mutation in p53 gene which leads to expression of p53 protein in tumor cells. Expression of p53 protein has been associated with poor clinical outcome and ...

  4. Studies on recurrence of colorectal carcinoma

    International Nuclear Information System (INIS)

    Kobayashi, Masayuki; Nosaki, Tadaharu; Murai, Tomoya; Ooshita, Ikuo; Kobayashi, Suzuo

    1989-01-01

    Recurrence patterns of colorectal carcinoma were studied in 402 patients followed up for 5 years or more after surgery. Recurrence was observed in 23% for colon cancer and 38% for rectal canccer. The most frequent site of recurrence or relapse in cases of colon cancer was the liver, followed by multiple organs and a local region; and in the case of rectal cancer, it was multiple organs, followed by a local region, the liver, lung, and bone. The rate of recurrence or relapse tended to be higher in patients with lymph node metastases or more advanced clinical stage. Liver relapse was seen in 13% for colon cancer and 12% for rectal cancer, occurring within 48 months after surgery. Since CT can detect liver relapse within 24 months, abdominal CT and chest plain roentgenography should be performed in the first 6 months, 12 months, and 24 months after surgery. (Namekawa, K)

  5. Pulmonar collision tumor: Metastatic adenoid cystic carcinoma and lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    M. Blanco

    2012-01-01

    Full Text Available Summary: We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen. Resumo: Descrevemos um caso único de tumor de colisão constituído por um adenocarcinoma de pulmão e uma metástase dum carcinoma adenóide cístico em um homem de 56 anos de idade. Ao doente foi diagnosticado um nódulo pulmonar 11 anos após o tratamento de um carcinoma adenóide cístico do seio maxilar direito. O carcinoma de pulmão de não pequenas células foi observado no momento da realização de uma biópsia transbrônquica. O outro componente do nódulo foi diagnosticado depois do exame histológico do material ressecado. Keywords: Bronchogenic carcinoma, Collision tumor, Adenoid cystic carcinoma, Palavras-chave: Carcinoma broncogénico, Tumor de colisão, Carcinoma adenóide cístico

  6. Mutational analysis and clinical correlation of metastatic colorectal cancer.

    Science.gov (United States)

    Russo, Andrea L; Borger, Darrell R; Szymonifka, Jackie; Ryan, David P; Wo, Jennifer Y; Blaszkowsky, Lawrence S; Kwak, Eunice L; Allen, Jill N; Wadlow, Raymond C; Zhu, Andrew X; Murphy, Janet E; Faris, Jason E; Dias-Santagata, Dora; Haigis, Kevin M; Ellisen, Leif W; Iafrate, Anthony J; Hong, Theodore S

    2014-05-15

    Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes. Under Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for >150 mutations across 15 commonly mutated cancer genes. The chi-square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival. Broad-based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with rectal cancer versus colon cancer (12.5% vs 0.6%; P colon cancer (13% vs 3%; P = .024) and older age (15.8% vs 4.6%; P = .006). TP53 mutations were associated with rectal cancer (30% vs 18%; P = .048), younger age (14% vs 28.7%; P = .007), and men (26.4% vs 14%; P = .03). Lung metastases were associated with PIK3CA mutations (23% vs 8.7%; P = .004). Only mutations in BRAF were independently associated with decreased overall survival (hazard ratio, 2.4; 95% confidence interval, 1.09-5.27; P = .029). The current study suggests that underlying molecular profiles can differ between colon and rectal cancers. Further investigation is warranted to assess whether the differences identified are important in determining the optimal treatment course for these patients. © 2014 American Cancer Society.

  7. Merkel cell carcinoma metastatic to the small bowel mesentery

    Directory of Open Access Journals (Sweden)

    Guang-Yu Yang

    2011-03-01

    Full Text Available Merkel cell carcinoma (MCC is an uncommon cutaneous malignant tumor that presents as a rapidly growing skin nodule on sun-exposed areas of the body. MCC is aggressive with regional nodal and distant metastases to the skin, lung, and bones. There have been no reports of metastatic MCC to the mesentery and 6 reports describing metastasis to the small intestine. We present a case of metastatic MCC to the mesentery with infiltration to the small bowel, 8 years after original tumor resection. This is the 5th metastasis and it encased the small bowel resulting in a hair-pin loop contributing to the unusual clinical presentation. Although MCC metastatic to the bowel is uncommon, it is not rare. It is important to recognize the unusual manifestations of this disease as they are becoming more common in the future. Routine radiologic surveillance and thorough review of systems are important to patient follow-up.

  8. Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Pfeiffer, Per; Nielsen, Dorte

    2011-01-01

    The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated.......The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated....

  9. Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Kyriakopoulos, Christos E; Chittoria, Namita; Choueiri, Toni K

    2015-01-01

    BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology......%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P

  10. Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC

    Directory of Open Access Journals (Sweden)

    Rossi L

    2013-11-01

    Full Text Available Luigi Rossi, Foteini Vakiarou, Federica Zoratto, Loredana Bianchi, Anselmo Papa, Enrico Basso, Monica Verrico, Giuseppe Lo Russo, Salvatore Evangelista, Guilia Rinaldi, Francesca Perrone-Congedi, Gian Paolo Spinelli, Valeria Stati, Davide Caruso, Alessandra Prete, Silverio TomaoDepartment of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Rome, Italy; Oncology Unit, ICOT, Latina, ItalyAbstract: Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features.Keywords: metastatic colorectal cancer, patient clinical features, tumor biology, multidisciplinary approach

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

    Science.gov (United States)

    Han, Yo-Han; Kee, Ji-Ye; Kim, Dae-Seung; Mun, Jeong-Geon; Jeong, Mi-Young; Park, Sang-Hyun; Choi, Byung-Min; Park, Sung-Joo; Kim, Hyun-Jung; Um, Jae-Young; Hong, Seung-Heon

    2016-08-27

    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.

  12. 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.

  13. Metastatic Breast Carcinoma to the Prostate Gland

    Directory of Open Access Journals (Sweden)

    Meghan E. Kapp

    2016-01-01

    Full Text Available Cancer of the male breast is an uncommon event with metastases to the breast occurring even less frequently. Prostate carcinoma has been reported as the most frequent primary to metastasize to the breast; however, the reverse has not been previously reported. Herein, we present, for the first time, a case of breast carcinoma metastasizing to the prostate gland. Prostate needle core biopsy revealed infiltrative nests of neoplastic epithelioid cells, demonstrated by immunohistochemistry (IHC to be positive for GATA3 and ER and negative for PSA and P501S. A prostate cocktail by IHC study demonstrated lack of basal cells (p63 and CK903 and no expression of P501S. The patient’s previous breast needle core biopsy showed strong ER positivity and negative staining for PR and HER2. Similar to the prostate, the breast was negative for CK5/6, p63, and p40. This case demonstrates the importance of considering a broad differential diagnosis and comparing histology and IHC to prior known malignancies in the setting of atypical presentation or rare tumors.

  14. Prognostic value of DNA image cytometry in colorectal carcinoma.

    Science.gov (United States)

    Sampedro, A; Urdiales, G; Martínez-Nistal, A; Riera, J; Hardisson, D

    1996-06-01

    To investigate the diagnostic sensitivity and prognosis predicting of DNA image cytometry in colorectal carcinoma. We studied the ploidy status and other DNA cytometric parameters in 68 patients with colorectal carcinoma. In addition, clinical-histologic and follow-up information was collected for at least five years. DNA histograms were available in all cases, showing a diploid DNA distribution pattern in 6 (8.8%), tetraploid in 21 (30.9%), hyperdiploid in 20 (29.4%) and hypertetraploid in 21 (30.9%). The differences in the correlation study between cytometric parameters and pathologic features were not statistically significant. Ploidy status and DNA malignancy grade were individually related to five-year survival (P < .005 and P < .05). The data show that DNA image cytometry can provide valuable prognostic information on colorectal carcinomas and may prove useful in guiding adjuvant therapy in these patients.

  15. Primary and metastatic lobular carcinoma of the breast

    International Nuclear Information System (INIS)

    Harake, Marie D.J.; Maxwell, Anthony J.; Sukumar, Sathi A.

    2001-01-01

    Invasive lobular carcinoma of the breast is the second most common type of primary breast cancer, accounting for 8-14% of cases, but is often difficult to diagnose early. It typically shows a diffuse pattern of infiltration within the breast, resulting in a variety of often subtle radiological appearances. A similar infiltrative pattern is seen in its metastatic form, with involvement of the gastrointestinal tract, peritoneum, retroperitoneum, bone marrow, meninges and uterus occurring more frequently than with the more common infiltrating ductal carcinoma of the breast. This pictorial essay illustrates the spectrum of radiological appearances which may be encountered with both primary and secondary lobular carcinoma. Harake, M.D.J., Maxwell, A.J. and Sukumar, S.A. (2001). Clinical Radiology 56, 621-630

  16. Primary and metastatic lobular carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Harake, Marie D.J.; Maxwell, Anthony J.; Sukumar, Sathi A

    2001-08-01

    Invasive lobular carcinoma of the breast is the second most common type of primary breast cancer, accounting for 8-14% of cases, but is often difficult to diagnose early. It typically shows a diffuse pattern of infiltration within the breast, resulting in a variety of often subtle radiological appearances. A similar infiltrative pattern is seen in its metastatic form, with involvement of the gastrointestinal tract, peritoneum, retroperitoneum, bone marrow, meninges and uterus occurring more frequently than with the more common infiltrating ductal carcinoma of the breast. This pictorial essay illustrates the spectrum of radiological appearances which may be encountered with both primary and secondary lobular carcinoma. Harake, M.D.J., Maxwell, A.J. and Sukumar, S.A. (2001). Clinical Radiology 56, 621-630.

  17. Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC)

    International Nuclear Information System (INIS)

    Rossi, Luigi; Vakiarou, Foteini; Zoratto, Federica; Bianchi, Loredana; Papa, Anselmo; Basso, Enrico; Verrico, Monica; Lo Russo, Giuseppe; Evangelista, Salvatore; Rinaldi, Guilia; Perrone-Congedi, Francesca; Spinelli, Gian Paolo; Stati, Valeria; Caruso, Davide; Prete, Alessandra; Tomao, Silverio

    2013-01-01

    Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features

  18. 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

  19. Axillary node metastatic carcinoma without definitive primary: a case report

    Directory of Open Access Journals (Sweden)

    Spencer R. Anderson

    2016-01-01

    Full Text Available Cancer of unknown primary (CUP is the finding of a metastatic cancerous lesion without an established primary source localized within the body. CUP can be of any cancer cell type, however, adenocarcinoma is most often identified by histology. Up to 5% of all malignant diagnoses are classified as CUP. PET is an imaging modality often utilized to distinguish a primary source in the setting of CUP, yet often a primary is never identified. CUP can be further stratified using specific qualifiers as favorable and unfavorable, indicating the potential therapeutic response to treatment regimens. Treatment approach to CUP relies heavily on the cell type identified by histology, the location of the lesion, and the amount of spread within the body. In the typical setting and presentation, per current literature, CUP arises in the 7th decade of life in patients with multiple comorbidities, and often has a poor prognostic value. This case report identifies an atypical presentation of CUP, a 38-year-old Caucasian female with an axillary mobile mass, and no associated systemic symptoms. Biopsy of the node and immunohistochemical staining showed histology consistent with metastatic carcinoma. Mammography, MRI, and PET scan found no evidence of tumor primary or distant metastasis. Further staining confirmed metastatic carcinoma consistent with breast origin, without an established breast primary. As in this case, CUP may present in an atypical manner, warranting a thorough investigation aiming to identify the tumor primary to aid in identification of a proper treatment regimen and approach.

  20. Metastatic renal cell carcinoma without evidence of a renal primary

    Science.gov (United States)

    Costantino, Corey; Thomas, George V.; Ryan, Christopher; Coakley, Fergus V.; Troxell, Megan L.

    2016-01-01

    Purpose Metastatic renal cell carcinoma (RCC), without an identified kidney primary, has been reported rarely. We report a patient with RCC metastatic to bilateral adrenal glands and liver, without an apparent renal primary. We detail the immunohistochemical and molecular studies employed to substantiate the diagnosis of RCC and direct therapy. Methods Histopathologic findings were correlated with imaging data and supplemented by a panel of immunohistochemical stains, as well as tumor sequence analysis. Results Despite the presence of bilateral adrenal masses and lack of tumor within kidney parenchyma, the diagnosis of RCC was substantiated by immunohistochemistry (RCC+/PAX2+/PAX8+/Melan-A−/SF-1− among others) and molecular genetic analysis, harboring mutations in VHL, TP53, KDM5C, and PBRM1. After debulking surgery, based on the diagnosis of RCC and the molecular profile, the patient was treated with a tyrosine kinase inhibitor (sunitinib), resulting in stablilization of disease. Conclusions This case illustrates the role of mutational analysis in carcinomas with rare or unusual presentations, such as metastatic RCC without a renal primary. PMID:26527083

  1. Results of CT in the diagnosis of recurrence of colorectal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Majewski, A.; Haubitz, B.; Laprell, H.

    1983-06-01

    Postoperative CT was performed in 179 colo-rectal carcinoma patients who had undergone abdominoperineal extirpation (n = 71), resection and rectosigmoid anastomosis (n = 37), hemicolectomy (n = 32), resection of sigma (n = 31), and others (n = 8). Normal CT-findings were found in 25% only, in more than 75% of all cases pathological CT-findings were seen. CT detected loxal recurrence in 87 patients. Based on CT findings local recurrent colo-rectal carcinoma was classified as Stage 0, or intraluminal mass, in 2 patients (2%). Stage 1, or extraluminal mass without invasion of adjacent organs, was found in 38 (44%) patients; Stage 2a, tumor mass with direct invasions of adjacent organs but not the pelvic side walls could be demonstrated in 13 (15%) of the cases; Stage 2b, for extension of mass to pelvic side walls, and Stage 3, or distant metastatic disease, was found in 14 (16%) and 20 (23%) patients. CT was negative in 2 patients with local recurrence (beside Stage 0), an incorrect diagnosis of recurrence due postoperative scarring was found in 4 patients. CT detected exclusive also metastatic disease of the liver in 23 patients and intraabdominal lymph node involvement in 8 patients.

  2. Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Rachna Raman

    2015-01-01

    Full Text Available Localized renal cell carcinoma (RCC is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

  3. 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...

  4. Decoy receptor 1 (DCR1) promoter hypermethylation and response to irinotecan in metastatic colorectal cancer

    NARCIS (Netherlands)

    Bosch, Linda J W; Trooskens, Geert; Snaebjornsson, Petur; Coupe, Veerle M. H.; Mongera, Sandra; Haan, Josien C.; Richman, Susan D.; Koopman, Miriam|info:eu-repo/dai/nl/298209640; Tol, Jolien; Meyer, Tim; Louwagie, Joost; Dehaspe, Luc; van Grieken, Nicole C. T.; Ylstra, Bauke; Verheul, Henk M. W.; van Engeland, Manon; Nagtegaal, Iris D; Herman, James G; Quirke, Philip; Seymour, Matthew T; Punt, Cornelis J A; van Criekinge, Wim; Carvalho, Beatriz; Meijer, Gerrit A.

    2017-01-01

    Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate genes were selected from 389 genes involved in

  5. Metastatic Renal Cell Carcinoma to the Thyroid 23 Years After Nephrectomy

    Directory of Open Access Journals (Sweden)

    Carrie Valdez

    2014-07-01

    Full Text Available Thyroid carcinoma is an uncommon form of human cancer, with an outstanding overall cure rate. This excellent prognosis is based on the fact that well over 99% of thyroid cancers are primary tumors. Metastatic cancer to the thyroid remains very rare. We report a case of clear cell renal carcinoma metastatic to the thyroid gland 23 years after nephrectomy.

  6. Metastatic Renal Cell Carcinoma to the Thyroid 23 Years After Nephrectomy ?

    OpenAIRE

    Valdez, Carrie; Rezaei, M. Katayoon; Hendricks, Fredrick; Knoll, Stanley M.

    2014-01-01

    Thyroid carcinoma is an uncommon form of human cancer, with an outstanding overall cure rate. This excellent prognosis is based on the fact that well over 99% of thyroid cancers are primary tumors. Metastatic cancer to the thyroid remains very rare. We report a case of clear cell renal carcinoma metastatic to the thyroid gland 23 years after nephrectomy.

  7. Metastatic basal cell carcinoma presenting with unilateral upper extremity edema and lymphatic spread.

    Science.gov (United States)

    Soleymani, A David; Scheinfeld, Noah; Vasil, Katherine; Bechtel, Mark A

    2008-08-01

    Basal cell carcinoma (BCC), the most common human malignancy, metastasizes in 0.0028% to 0.5% of cases, usually to the lymph nodes, lungs, bones, and skin. After metastatic spread of BCC, survival averages 1 to 2 years. Chemotherapy, radiotherapy, and surgery are treatment options. We describe metastatic basal cell carcinoma to the skin presenting with unilateral upper extremity edema.

  8. Management of Liver Metastasis from Colo-Rectal Carcinoma with ...

    African Journals Online (AJOL)

    Background: Worldwide, colo-rectal carcinoma is the second most common cancer with liver metastases as its major cause of mortality.This malignant condition is now seen more frequently in our environment typically at a late stage with distant metastasis especially to the liver. This study aims at highlighting the current use ...

  9. Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma

    Czech Academy of Sciences Publication Activity Database

    Kunická, T.; Procházka, Pavel; Krus, I.; Bendová, Petra; Protivová, M.; Susová, S.; Hlaváč, V.; Liška, V.; Novák, P.; Schneiderová, M.; Pitule, P.; Bruha, J.; Vyčítal, O.; Vodička, Pavel; Souček, P.

    2017-01-01

    Roč. 16, oct (2017), s. 795 ISSN 1471-2407 R&D Projects: GA MZd(CZ) NT14329; GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 Keywords : colorectal carcinoma * 5-fluorouracil * methylation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.288, year: 2016

  10. Childhood colorectal carcinoma: A case series | Sharma | African ...

    African Journals Online (AJOL)

    Colorectal carcinoma (CRC) is rare in children, except for a few sporadic reports there is not much information about it in the literature. It is important for pediatricians and paediatric surgeons to be aware that CRC does occur in children, and it should not be excluded only on the basis of the patient\\'s age. Its rarity in children ...

  11. Metastatic Colorectal Cancer in Young Adults: A Study From the South Australian Population-Based Registry.

    Science.gov (United States)

    Vatandoust, Sina; Price, Timothy J; Ullah, Shahid; Roy, Amitesh C; Beeke, Carole; Young, Joanne P; Townsend, Amanda; Padbury, Robert; Roder, David; Karapetis, Christos S

    2016-03-01

    Colorectal cancer (CRC) is a common malignancy. There is growing evidence that CRC incidence is increasing in the younger population. There is controversy surrounding the prognosis of young patients with CRC. In this study we reviewed Australian patients with metastatic CRC (mCRC) who were younger than 40 years of age at the time of diagnosis of metastatic disease. To our knowledge this is the first study to focus on this age group with mCRC. This was a retrospective study using data from the South Australian Metastatic Colorectal Cancer database. We compared patient and disease characteristics, management approaches, and outcomes for age groups Young-onset mCRC patients, when defined as aged younger than 40 years, have equivalent survival compared with their older counterparts. This is despite differences in disease characteristics and management approach between the 2 groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Orbital Cellulitis: A Rare Presentation of Metastatic Bronchial Carcinoma

    Directory of Open Access Journals (Sweden)

    Rohit Kumar

    2011-01-01

    Full Text Available Objective. We report a rare and unusual case of bronchial carcinoma presenting with symptoms of complications of sinonasal disease. Case Report. A 66-year-old lady was referred with a 1-week history of progressive ocular pain, chemosis, and visual disturbance. Computed tomography of the paranasal sinuses revealed frontal and ethmoidal sinus opacification with orbital involvement consistent with a diagnosis of orbital cellulitis secondary to sinusitis. Surgical exploration revealed that the sinuses and right orbit were filled with soft tissue and subsequent histopathological examination of the biopsies indicating metastases from an adenosquamous bronchial carcinoma. Further imaging revealed a large, asymptomatic, bronchial primary with deposits in the brain and liver. The advanced presentation of the disease limited treatment to best supportive care. Conclusion. Orbital cellulitis and sinonasal malignancies have a similar pattern of clinical presentation, posing a potential diagnostic pitfall. There are only two previously reported cases of metastatic lung carcinoma in the frontal sinus with 15 cases of sinonasal tract involvement reported overall. There are no reported cases of adenosquamous carcinoma in the sinonasal tract.

  13. Metastatic pituitary carcinoma: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    ZHANG Shang-fu

    2013-02-01

    Full Text Available Background As a kind of rare tumor, metastatic pituitary carcinoma is very difficult to diagnose clinically and is easy to be misdiagnosed. This article aims to discuss the clinical manifestations and histopathological features of this tumor. Methods The clinical presentations, histopathological features and immunophenotype were studied in one case of poorly differentiated lung adenocarcinoma metastatic to pituitary gland, and related literature was reviewed. Results A 47-year-old woman mainly presented with faint, headache and blurred vision. CT scan demonstrated abnormal signals in suprasellar cistern. During the resection, the tumor could be seen locating in sellar region, the size of which was about 2 cm × 1 cm × 1 cm. Histopathological examination revealed that the structure of pituitary gland was damaged and the tumor was composed of atypical round or oval cells arranged in nest or glandular patterns, in which a number of enlarged plump tumor cells contained abundant eosinophilic cytoplasm with eccentrical caryogenesis. The immunohistochemistry showed that epithelial membrane antigen (EMA, pan cytokeratin (PCK, thyroid transcription factor-1 (TTF-1 and cytokeratin 7 (CK7 were positive in tumor cells with Ki-67 labeling index being 15%, but chromogranin (CgA, cancer embryo antigen (CEA, human chorionic gonadotropin (hCG, placental alkaline phosphatase (PLAP, CD117, leukocyte common antigen (LCA, CD30, anaplastic lymphoma kinase-1 (ALK-1 were negative in tumor cells. After operation the patient received treatment with levothyroxine sodium and γ knife, but died 4 months later. Conclusion Histopathological examination and immunohistochemistry can confirm the diagnosis of metastatic pituitary carcinoma and locate the primary lesion. Postoperative comprehensive therapy is necessary.

  14. Long survival in a patient with metastatic colorrectal carcinoma: reality or utopia?

    Science.gov (United States)

    Illán, Andrea; Aires, Jonathan; Quintana, Laura

    2017-09-01

    We report the case of a 42-year-old male patient with mucinous-type metastatic colorectal carcinoma of eight years of evolution. He has received multiple lines of cytostatic treatment with acceptable tolerance and without significant impairment in his quality of life. At present, it is estimated that the overall survival of metastatic colon cancer in cytostatic treatment is around 24 months. However, a small subset of patients may present prolonged survivals of 5 to 10 years after diagnosis, revealing heterogeneity of tumor behavior and response to treatment. Our clinical case represents a long survivor patient despite the advanced stage of his oncological mucinous-colorrectal disease, endorsed in the scientific literature as having worse rates of objective response and less survival. There are different therapeutic approaches that can achieve a significant overall survival. It is essential in clinical practice to use all drugs available to achieve increase of progression-free survival and overall survival, with maintenance of an adequate quality of life.

  15. Orbitofacial Metastatic Basal Cell Carcinoma: Report of 10 Cases.

    Science.gov (United States)

    Branson, Sara V; McClintic, Elysa; Ozgur, Omar; Esmaeli, Bita; Yeatts, R Patrick

    To explore the clinical features, management, and prognosis of metastatic basal cell carcinoma originating in the orbitofacial region. Ten cases of orbitofacial metastatic basal cell carcinoma were identified by searching databases at 2 institutions from 1995 to 2015. A retrospective chart review was performed. Main outcome measures included patient demographics, lesion size, location of metastases, histologic subtype, recurrence rate, time between primary tumor diagnosis and metastasis, perineural invasion, treatment modalities, and survival from time of metastasis. The median tumor size at largest dimension was 3.3 cm (range, 1.9-11.5 cm), and 6 of 10 patients had at least 1 local recurrence before metastasis (range, 0-2 recurrences). The most common sites of metastasis included the ipsilateral parotid gland (n = 6) and cervical lymph nodes (n = 5). Histologic subtypes included infiltrative (n = 5), basosquamous (n = 2), nodular (n = 1), and mixed (n = 1). The median time from primary tumor diagnosis to metastasis was 7.5 years (range, 0-13). The median survival time from diagnosis of metastasis to last documented encounter or death was 5.3 years (range, 7 months-22.8 years). Treatment regimens included surgical excision, radiotherapy, and hedgehog inhibitors. Based on our findings, the following features may be markers of high risk orbitofacial basal cell carcinoma: 1) increasing tumor size, 2) local recurrence of the primary tumor, 3) aggressive histologic subtype, and 4) perineural invasion. Screening should include close observation of the primary site and tissues in the distribution of regional lymphatics, particularly the parotid gland and cervical lymph nodes.

  16. Collision tumours, squamous cell carcinoma of larynx, papillary thyroid carcinoma, metastatic lymphatic node. Clinical Presentation

    International Nuclear Information System (INIS)

    Villalba, V; Gomez, R; Yoffe, I.; Liu, T.; Arias, J.; Quiroz, J.; Gonzalez, M; Ayala, E.

    2010-01-01

    the opening of the stoma. Papillary carcinoma compromises peritiroideo deep surgical limits and mucous upper right margin. Squamous cell carcinoma committed focally vocal cord left. Foci of vascular and perineural invasion papillary carcinoma. Two papillary carcinoma metastatic lymph nodes perilaringeos. Right middle yugulocarotidea 2-Chain: papillary carcinoma metastatic lymph node conglomerate (9.3 cm.) And tissue extension adipose periganglionar and metastatic squamous cell carcinoma of two lymph nodes (macro metastasis with capsule intact). 3-Chain yugulocarotidea middle and lower left: papillary carcinoma metastatic lymph node conglomerate in (7.2 cm.) And metastatic squamous cell carcinoma four lymph nodes (macro metastases with capsule intact). In two of said nodes simultaneously both tumor metastases is observed. Starts radiation therapy (65Gy) weekly concurrent CDDP, after which there is no evidence of tumor. Six months later, treatment is performed with ablative doses of iodine 131 scintigraphy showed that the remaining thyroid nodular captante in glandular bed. The patient progresses with lung and liver metastases died at 10 months after surgery. Although the literature we found other cases of tumors in collision, we have not found a case with two metastatic tumors in a single node with these histologist

  17. Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases.

    Science.gov (United States)

    Lee, Ja-Rang; Kwon, Chae Hwa; Choi, Yuri; Park, Hye Ji; Kim, Hyun Sung; Jo, Hong-Jae; Oh, Nahmgun; Park, Do Youn

    2016-07-26

    Despite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood. In order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver). The gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells. The present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma.

  18. Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases

    International Nuclear Information System (INIS)

    Lee, Ja-Rang; Kwon, Chae Hwa; Choi, Yuri; Park, Hye Ji; Kim, Hyun Sung; Jo, Hong-Jae; Oh, Nahmgun; Park, Do Youn

    2016-01-01

    Despite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood. In order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver). The gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells. The present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma. The online version of this article (doi:10.1186/s12885-016-2596-3) contains supplementary material, which is available to authorized users

  19. Fusobacterium nucleatum and T-cells in Colorectal Carcinoma

    Science.gov (United States)

    Mima, Kosuke; Sukawa, Yasutaka; Nishihara, Reiko; Qian, Zhi Rong; Yamauchi, Mai; Inamura, Kentaro; Kim, Sun A; Masuda, Atsuhiro; Nowak, Jonathan A.; Nosho, Katsuhiko; Kostic, Alecsandar D.; Giannakis, Marios; Watanabe, Hideo; Bullman, Susan; Milner, Danny A.; Harris, Curtis C.; Giovannucci, Edward; Garraway, Levi A.; Freeman, Gordon J.; Dranoff, Glenn; Chan, Andrew T.; Garrett, Wendy S.; Huttenhower, Curtis; Fuchs, Charles S.; Ogino, Shuji

    2015-01-01

    Importance Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by down-regulating antitumor T-cell-mediated adaptive immunity. Objective To test the hypothesis that higher amount of Fusobacterium nucleatum in colorectal carcinoma tissue is associated with lower density of T-cells in tumor tissue. Design A cross-sectional analysis was conducted on colorectal carcinoma cases in two U.S. nationwide prospective cohort studies. The amount of Fusobacterium nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high versus low). Multivariable ordinal logistic regression analysis was conducted to assess associations of the amount of Fusobacterium nucleatum with densities (quartiles) of T-cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted two-sided α level to 0.013 for multiple hypothesis testing. Setting The Nurses’ Health Study and the Health Professionals Follow-up Study. Participants 598 colon and rectal carcinoma cases. Main outcomes and measures Densities of CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ T-cells in tumor tissue, determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Results Fusobacterium nucleatum was detected in colorectal carcinoma tissue in 76 (13%) of 598 cases. Compared with Fusobacterium nucleatum-negative cases, Fusobacterium nucleatum-high cases were inversely associated with the density of CD3+ T

  20. CD44v6 down-regulation is an independent prognostic factor for poor outcome of colorectal carcinoma.

    Science.gov (United States)

    Wang, Lili; Liu, Qin; Lin, Dongliang; Lai, Maode

    2015-01-01

    We aim to investigate the variation of CD44v6 expression in the normal-adenoma-primary carcinoma-liver metastasis sequence and its prognostic impact on colorectal carcinomas. The difference in CD44v6 expression between the tumor center and invasive front was also assessed. Immunohistochemistry was performed for CD44v6 on two cohorts. The first was tissue microarrays including 402 primary CRCs sampled from the tumor center and the invasive margin. The second was whole-tissue sections, consisting of 217 adenomas, 72 primary carcinomas, and the corresponding metastatic carcinomas. In the first cohort, we found that CD44v6 down-regulation was inclined to lymph node metastasis and perineural invasion, and had an unfavorable prognosis compared with CD44v6 up-regulation. In the second cohort, CD44v6 expression was predominant in adenoma over primary carcinoma and liver metastasis in multiple steps (normal primary carcinoma and liver metastasis). In addition, our analysis showed that CD44v6 expression was decreased at the invasion front of the CRC compared with the center of the tumor. In conclusion, the maximal expression of CD44v6 in adenoma plays a crucial role in colorectal carcinogenesis, while loss of CD44v6 expression on the cell surface of the tumor edge enhances the progression of metastasis. CD44v6 down-regulation is an independent prognostic factor for strikingly worse disease-specific survival.

  1. hereditary non-polyposis colorectal carcinoma (hnpcc)

    African Journals Online (AJOL)

    2011-08-08

    Aug 8, 2011 ... eight siblings had developed colorectal cancer, with incidence in three consecutive generations. This family satisfied Amsterdam criteria (I and II) for Lynch syndrome: three generations affected, six of them below age 50, with proximal colon tumours. Genetic testing showed loss of mismatched repair protein ...

  2. Decline in peripheral blood NKG2D+CD3+CD56+ NKT cells in metastatic colorectal cancer patients.

    Science.gov (United States)

    Gharagozloo, M; Rezaei, A; Kalantari, H; Bahador, A; Hassannejad, N; Maracy, M; Nouri, N; Sedghi, M; Ghazanfari, H; Bayat, B

    2018-01-01

    Colorectal cancer (CRC) is one of the main causes of cancer deaths in the world. This cancer can be divided into non-metastatic and metastatic CRC stages. CD3+CD56+ NKT cell subsets are a minor T cell subset in peripheral blood and conduct the killing of tumor cells in direct manner. Little is obvious about levels and surface markers of these cells such as NKG2D in different cancers, especially in CRC. We included 15 non-metastatic (low-grade), 11 non-metastatic (high-grade), 10 metastatic colorectal cancer patients and 18 healthy controls. The percentages of CD3+CD56+ NKT cells and NKG2D+CD56+ NKT cells from samples were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs) of samples. We found that there was a significantly lower number of NKG2D+CD3+CD56+ cells in peripheral blood of patients with metastatic colorectal cancer compared with normal controls (77.53 ± 5.79 % vs 90.74 ± 9.84 %; pNKT cells was significantly lower in patients with metastatic colorectal cancer compared to healthy controls strengthens the hypothesis that NKT cells can play a substantial role in the protection against human colorectal cancer, and this opens up avenues for novel studies about elucidating the other aspects of tumor surveillance in CRC progression and immunotherapy (Tab. 2, Fig. 2, Ref. 46).

  3. Colorectal cancer: prevention and management of metastatic disease.

    Science.gov (United States)

    Sugarbaker, Paul H

    2014-01-01

    This paper compared the similarities and differences of the two most common types of colorectal cancer metastases. The treatment of liver metastases by surgery combined with systemic chemotherapy was explained. The different natural history of liver metastases as compared to peritoneal metastases and the possibility for prevention of peritoneal metastases were emphasized. Perioperative cancer chemotherapy or second-look surgery must be considered as individualized treatments of selected patients who have small volume peritoneal metastases or who are known to be at risk for subsequent disease progression on peritoneal surfaces. However, the fact that peritoneal metastases, when diagnosed in the follow-up of colorectal cancer patients, can be cured with a combination of cytoreductive surgery and hyperthermic perioperative chemotherapy cannot be ignored. Careful follow-up and timely intervention in colorectal cancer patients with progressive disease are a necessary part of the management strategies recommended by the multidisciplinary team. After a critical evaluation of the data currently available, these strategies for prevention and management of colorectal metastases are presented as the author's recommendations for a high standard of care. As more information becomes available, modifications may be necessary.

  4. 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

  5. Concordant DNA Methylation in Synchronous Colorectal Carcinomas

    Science.gov (United States)

    Konishi, Kazuo; Shen, Lanlan; Jelinek, Jaroslav; Watanabe, Yoshiyuki; Ahmed, Saira; Kaneko, Kazuhiro; Kogo, Mari; Takano, Toshihumi; Imawari, Michio; Hamilton, Stanley R.; Issa, Jean-Pierre J.

    2012-01-01

    Epigenetic changes have been proposed as mediators of the field defect in colorectal carcinogenesis, which has implications for risk assessment and cancer prevention. As a test of this hypothesis, we evaluated the methylation status of eight genes (MINT1, 2, 31, MLH1, p16, p14, MGMT, and ESR1), as well as BRAF and KRAS mutations, in 57 multiple colorectal neoplasias (M-CRN) and compared these to 69 solitary colorectal cancers (S-CRC). There were no significant differences in methylation between M-CRNs and S-CRCs except for p14 and MGMT that was significantly higher in M-CRNs than S-CRCs (16.1% versus 9.3%; 26.5% versus 17.3%, respectively; P < 0.05). We found significant (P < 0.05) correlations for MINT1 (r = 0.8), p16 (r = 0.8), MLH1 (r = 0.9), and MGMT (r = 0.6) methylation between tumors pairs of the same site (proximal/proximal and distal/distal). KRAS showed no concordance in mutations. BRAF mutation showed concordance in proximal site pairs but was discordant in different site pairs. Histologically, eight of 10 paired cancers with similar locations were concordant for a cribriform glandular configuration. We conclude that synchronous colorectal tumors of the same site are highly concordant for methylation of multiple genes, BRAF mutations, and a cribriform glandular configuration, all consistent with a patient-specific predisposition to particular subtypes of colorectal cancers. Screening for and secondary prevention of colon cancer should take this fact into account. PMID:19737982

  6. Axitinib in metastatic renal cell carcinoma: single center experience

    Directory of Open Access Journals (Sweden)

    Agnieszka Buraczewska

    2017-01-01

    Full Text Available Aim of the study : Due to the emergence of new therapeutic opportunities in the second-line treatment of metastatic renal cell carcinoma, the choice of the appropriate medication requires consideration. Making the selection one should take into account the likelihood of response, the probability of toxicity, properties of the drug and the clinical characteristics of the patient. Aim of the work was to confirm antitumor efficacy of axitinib in patients with metastatic clear-cell renal-cell carcinoma in the second line treatment remaining under the care of our institution. The primary objective was to determine antitumor activity, secondary – to evaluate progression free survival, safety of the treatment and to analyse clinical characteristics of treated population. Results: Treatment records of 27 patients (9 females, 18 males treated from October 2014 to the present (July 2016 were reviewed. The median duration of treatment which corresponds to the time to disease progression in observed population was 6 months (range: under 1 month – 16 months. 1 patient (3.7% had got objective response (PR, partial remission. Clinical benefit rate (PR + SD (stable disease was 66%. 9 patients (33.33% experienced treatment toxicity only in the first degree of CTCAE (common toxicity criteria for adverse events, 11 patients (40.74% presented the second degree toxicity and 5 patients (18.5% – third degree. The most commonly reported treatment related adverse events were diarrhea (47%, fatigue (26%, hand-foot syndrome (26%, deterioration of blood pressure control (22.2%, abnormal liver function tests (18.5%, mucositis (11.1%.We observed 3 cases of unacceptable toxicity. Conclusions : Axitinib confirms its effectiveness also in situ ation outside clinical trials, however, it is characterized by significant toxicity. Therefore, qualification for treatment should take into account the clinical patient characteristics. Effective diagnosis and treatment of side

  7. Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pacella, Claudio M. [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)], E-mail: claudiomaurizio.pacella@fastwebnet.it; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)

    2008-04-15

    Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival.

  8. Role of surgery in advanced/metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Suresh Bhat

    2010-01-01

    Full Text Available Metastatic renal cell cancer (RCC is a malignant disease without curative treatment. These patients are usually symptomatic and desperate for effective palliative treatment. Radiotherapy, chemotherapy, and hormonal therapy are not effective in these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (which includes cytokines or targeted molecules, and metastasectomy have been shown to be useful in prolonging the survival and improving the quality of life in a select group of patients with metastatic renal cancer. Patients with oligometastatic disease, good performance status, and delayed presentation of the secondaries have better results following this integrated approach. Although there is some controversy regarding the order in which nephrectomy and systemic therapy are to be instituted, well-controlled studies like the South West Oncology Group and European organization research and treatment of cancer have shown that upfront nephrectomy gives better survival compared to neoadjuvant systemic therapy followed by nephrectomy. This order is the standard presently. Of late, with better understanding of the genetic basis and the biology of the various subtypes of renal cell carcinoma, targeted molecular therapies have emerged as an equally effective alternative therapy to cytokines. Recent reports have proven that targeted therapy is more effective with comparable side effects. Metastasectomy in a subgroup of patients improves survival and quality of life specifically in those with lung secondaries and painful bone metastases.

  9. Detection of metastatic thyroid carcinoma through whole body counting

    International Nuclear Information System (INIS)

    Novenario, H.S.; Pascacio, F.M.; Cruz, Benjamin de la; Anden, A.B.

    Whole body counters are not only used in measuring radioactivity in the body for radiation protection purposes but also in the measurement of iron absorption, body potassium and cesium, chronic blood loss, and also in the determination of the effectiveness of surgery, thyroid hormone and radioactive iodine therapy in thyroid carcinoma. This report deals with our experience in the use of a shadow-shield whole body counter in the determination of I-131 uptake by metastatic lesions of cancer of thyroid after total thyroidectomy and ablation therapy with I-131. This study was undertaken jointly by the Department of Nuclear Medicine, Veterans Memorial Hospital and the Biomedical Research Division of the Philippine Atomic Energy Commission. Preliminary results indicate that the 22 patients who underwent whole body counting after total thyroidectomy I-131 ablation therapy, 9 patients had elevated percentage retention of I-131, 10 patients with normal values and 3 patients with rising values. Foci of I-131 concentration in those with elevated and rising percentage concentration values were seen in the thyroidal bed scintiscans, while the 10 patients with normal values had negative scintiscans. The results of our observations confirm the results obtained by other workers abroad. Our preliminary results indicate that with the use of whole body counters a sensitive method of assessing whether functioning metastatic lesion of cancer of the thyroid still exist after total thyroidectomy and I-131 ablation therapy can be provided. (author)

  10. Renal Cell Carcinoma Metastatic to Thyroid Gland, Presenting Like Anaplastic Carcinoma of Thyroid

    Directory of Open Access Journals (Sweden)

    Khalid Riaz

    2013-01-01

    Full Text Available Background. Renal cell carcinoma (RCC has unpredictable and diverse behavior. The classic triad of hematuria, loin pain, and abdominal mass is uncommon. At time of diagnosis, 25%–30% of patients are found to have metastases. Bones, lungs, liver, and brain are the frequent sites of metastases. RCC with metastasis to the head and neck region and thyroid gland is the rarest manifestation and anaplastic carcinoma behaving metastatic thyroid mass is an extremely rare presentation of RCC. Case Presentation. A 56-year-old Saudi man with past history of right radical nephrectomy 5 years back presented with 3 months history of rapid increasing neck mass with dysphagia, presenting like anaplastic thyroid carcinoma. Tru-cut biopsy turned out to be metastatic renal cell carcinoma. Patient was treated with radiation therapy 30 Gy in 10 fractions to mass. Patient died 4 months after the discovery of anaplastic thyroid looking metastasis. Conclusion. Rapidly progressing thyroid metastases secondary to RCC are rare and found often unresectable which are not amenable to surgery. Palliative radiotherapy can be considered for such patients.

  11. Intestinal obstruction: predictor of poor prognosis in colorectal carcinoma?

    Directory of Open Access Journals (Sweden)

    Mohd Azri Mohd Suan

    2015-03-01

    Full Text Available OBJECTIVES: The goal of this study was to assess the relationship between intestinal obstruction and the prognosis of colorectal carcinoma. METHODS: Data pertaining to 4,501 colorectal carcinoma patients were extracted from the national colorectal registry and analysed. Survival analysis was performed using the Kaplan-Meier method. The log-rank test was used to compare the survival rate between patients with intestinal obstruction and those without intestinal obstruction. The p-values<0.05 were considered to indicate statistical significance. Simple Cox proportional hazards regression analysis was used to estimate the crude hazard ratio of mortality from colorectal cancer. RESULTS: Intestinal obstruction was reported in more than 13% of patients. The 3-year survival rate after treatment was 48.3% (95% confidence interval [CI], 43.9 to 52.8 for patients with intestinal obstruction (n=593 and 54.9% (95% CI, 53.1 to 56.6 for patients without intestinal obstruction (n=3,908. The 5-year survival rate for patients with intestinal obstruction was 37.3% (95% CI, 31.9 to 42.8, which was lower than that of patients without intestinal obstruction (45.6%; 95% CI, 43.5 to 47.7. After adjusting the hazard ratio for other prognostic variables, intestinal obstruction had a statistically significant negative correlation with the survival rate of colorectal cancer patients, with an adjusted hazard ratio of 1.22 (p=0.008. CONCLUSIONS: The presence of intestinal obstruction is associated with a lower survival rate among colorectal cancer patients.

  12. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis.

    Science.gov (United States)

    Mima, Kosuke; Nishihara, Reiko; Qian, Zhi Rong; Cao, Yin; Sukawa, Yasutaka; Nowak, Jonathan A; Yang, Juhong; Dou, Ruoxu; Masugi, Yohei; Song, Mingyang; Kostic, Aleksandar D; Giannakis, Marios; Bullman, Susan; Milner, Danny A; Baba, Hideo; Giovannucci, Edward L; Garraway, Levi A; Freeman, Gordon J; Dranoff, Glenn; Garrett, Wendy S; Huttenhower, Curtis; Meyerson, Matthew; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Ogino, Shuji

    2016-12-01

    Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. Fusobacterium nucleatum may promote colorectal tumour growth and inhibit T cell-mediated immune responses against colorectal tumours. Thus, we hypothesised that the amount of F. nucleatum in colorectal carcinoma might be associated with worse clinical outcome. We used molecular pathological epidemiology database of 1069 rectal and colon cancer cases in the Nurses' Health Study and the Health Professionals Follow-up Study, and measured F. nucleatum DNA in carcinoma tissue. Cox proportional hazards model was used to compute hazard ratio (HR), controlling for potential confounders, including microsatellite instability (MSI, mismatch repair deficiency), CpG island methylator phenotype (CIMP), KRAS, BRAF, and PIK3CA mutations, and LINE-1 hypomethylation (low-level methylation). Compared with F. nucleatum-negative cases, multivariable HRs (95% CI) for colorectal cancer-specific mortality in F. nucleatum-low cases and F. nucleatum-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39), respectively, (p for trend=0.020). The amount of F. nucleatum was associated with MSI-high (multivariable odd ratio (OR), 5.22; 95% CI 2.86 to 9.55) independent of CIMP and BRAF mutation status, whereas CIMP and BRAF mutation were associated with F. nucleatum only in univariate analyses (pnucleatum DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker. Our data may have implications in developing cancer prevention and treatment strategies through targeting GI microflora by diet, probiotics and antibiotics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Palshof, Jesper Andreas; Hogdall, Estrid Vilma Solyom; Poulsen, Tim Svenstrup

    2017-01-01

    Background No biomarker exists to guide the optimal choice of chemotherapy for patients with metastatic colorectal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients...... with metastatic colorectal cancer. Methods From a national cohort, we identified 163 patients treated every third week with irinotecan 350 mg/m2 as second-line therapy. Among these 108 were eligible for analyses and thus entered the study. Primary tumors samples were collected and tissue microarray (TMA) blocks...... of the markers TOP1 CN, TOP1/CEN-20-ratio or TOP1/CEN-2-ratio were associated with progression free survival, overall survival or baseline characteristics. Yet, we observed a borderline association for a stepwise increase of the TOP1 CN in relation to objective response as hazard ratio were 1.35 (95% CI 0...

  14. 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

  15. Dual Inhibition of EGFR and VEGF in Heavily Pretreated Patients with Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Markussen, Alice; Nielsen, Dorte

    2017-01-01

    Objective: The aim of this study was to evaluate the efficacy and safety of combining irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment in patients with metastatic colorectal cancer. Methods: All patients had KRAS wild-type metastatic colorectal cancer and had previously...... received fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab/panitumumab in a 1st, 2nd, and 3rd line setting. Most patients had previously received bevacizumab as well. All patients had progressed within 3 months after the last given treatment before starting the triple combination therapy every...... second week. Results: Sixty-three patients were evaluated. The triple combination therapy was well tolerated. The median progression-free survival was 6.1 months, and the median overall survival was 11.9 months. Four patients (6%) obtained a partial response, and 40 (63%) had stable disease. Conclusion...

  16. KRAS mutational status analysis of peripheral blood isolated circulating tumor cells in metastatic colorectal patients

    OpenAIRE

    GUTI?RREZ, CRISTINA; RODRIGUEZ, JAVIER; PATI?O-GARC?A, ANA; GARC?A-FONCILLAS, JES?S; SALGADO, JOSEFA

    2013-01-01

    The present study describes an optimized method for isolating peripheral blood circulating tumor cells (CTCs) and performing KRAS mutation analysis. The approach combines isolation of peripheral blood mononuclear cells and immunomagnetic labeling with CD45 and CD326 human microbeads with KRAS analysis performed with a Therascreen KRAS kit by quantitative PCR. KRAS mutations were detected in the CTCs of patients with metastatic colorectal cancer (mCRC). CTCs may represent an alternative to inv...

  17. Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.

    Science.gov (United States)

    Del Rio, M; Mollevi, C; Bibeau, F; Vie, N; Selves, J; Emile, J-F; Roger, P; Gongora, C; Robert, J; Tubiana-Mathieu, N; Ychou, M; Martineau, P

    2017-05-01

    Currently, metastatic colorectal cancer is treated as a homogeneous disease and only RAS mutational status has been approved as a negative predictive factor in patients treated with cetuximab. The aim of this study was to evaluate if recently identified molecular subtypes of colon cancer are associated with response of metastatic patients to first-line therapy. We collected and analysed 143 samples of human colorectal tumours with complete clinical annotations, including the response to treatment. Gene expression profiling was used to classify patients in three to six classes using four different molecular classifications. Correlations between molecular subtypes, response to treatment, progression-free and overall survival were analysed. We first demonstrated that the four previously described molecular classifications of colorectal cancer defined in non-metastatic patients also correctly classify stage IV patients. One of the classifications is strongly associated with response to FOLFIRI (P=0.003), but not to FOLFOX (P=0.911) and FOLFIRI + Bevacizumab (P=0.190). In particular, we identify a molecular subtype representing 28% of the patients that shows an exceptionally high response rate to FOLFIRI (87.5%). These patients have a two-fold longer overall survival (40.1 months) when treated with FOLFIRI, as first-line regimen, instead of FOLFOX (18.6 months). Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer and a strong impact of the first-line regimen on the overall survival of some patients. This however remains to be confirmed in a large prospective clinical trial. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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    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.

  19. 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.

  20. Current and Emerging Therapeutic Targets for Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Zarrabi, Kevin; Wu, Shenhong

    2018-04-02

    The treatment of advanced renal cell carcinoma has evolved dramatically over recent years. In this review, we will summarize current and emerging therapies based on molecular targets and provide insight into treatment strategy for metastatic renal cell carcinoma. We have witnessed a paradigm shift in the therapeutic landscape as treatment was formerly reliant on cytokine-based agents which have now been replaced with therapies targeting angiogenesis, mammalian target of rapamycin pathways, and immune responses. These dramatic changes are primarily due to our improved understanding of the underlying mutations and molecular mechanisms leading to tumorigenesis and progression. We now have targeted agents in the form of small-molecule tyrosine kinase inhibitors, monoclonal antibodies, and mTOR inhibitors. Moreover, immunotherapy-targeting checkpoints of T-lymphocyte activity has provided increased overall survival and a new class of agents with potential to radically change the treatment options. With these agents and their combination, durable responses are increasingly seen even though treatment resistance remains a huge challenge. New treatment strategies are rapidly developing and the therapeutic landscape is expected for further evolution.

  1. Axitinib in sequential therapy in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Agata Kuchar

    2015-05-01

    Full Text Available Efficacy of new molecularly targeted drugs in the treatment of renal cell carcinoma (RCC, confirmed in clinical studies in relation to survival and prolongation of time to progression, has became a big chance for patients with metastatic renal cell cancer. Axitinib is a potent and selective receptor tyrosine kinase for vascular endothelial growth factor (VEGFR-1, -2, -3, platelet-derived growth factor  (PDGRF- and c-KIT. This is a case report of a 57-year old female patient with a history of left nephrectomy due to clear cell renal cell carcinoma. The patient had received three prior systemic treatments (interferon – sorafenib – everolimus. After consecutive progression the patient was qualified to 4th line therapy – axitinib at a dose of 5 mg twice daily. Partial response to treatment was achieved. After 6 months therapy was stopped due to the disease progression. The total time to progression was 37.5 months. The total survival time from the disease diagnosis was 45 months. Based on literature date and own experience we showed that sequential treatment RCC is associated with improved survival. In summary, axitinib may be an effective drug after failure of tyrosine-kinase inhibitor (TKI therapy in previous lines of therapy.

  2. Metastatic basal cell carcinoma to the bone and bone marrow.

    Science.gov (United States)

    Elghissassi, Ibrahim; Mikou, Asmaa; Inrhaoun, Hanane; Ennouhi, Amine; Gamra, Lamiae; Errihani, Hassan

    2009-05-01

    Basal cell carcinoma (BCC) is the most common carcinoma in the community, but the incidence of metastatic events is exceedingly low. The few reported cases most often appear in regional nodes or the lungs, and patients usually exhibit multiple concurrent organs of spread at the time of diagnosis. We report a case of primary BCC located on the left forehead of a 48-year-old man, which metastasized exclusively to the bone and bone marrow, associated with hematologic disorders. A short review of the literature is included. Pathologic examination of the tumor located on the left forehead showed BCC. The patient underwent two surgical excisions because of local recurrence. Three years later, the patient developed a bicytopenia (anemia and thrombocytopenia). The bone marrow biopsy revealed metastasis of BCC. There were no abnormal findings in the other routine laboratory tests and radiologic investigations, except for the bone scan which showed multifocal skeletal metastases. The patient received two cycles of chemotherapy with cisplatin 75 mg/m(2) before he died as a result of hemorrhagic complications and progressive disease. Metastasis of BCC is a very rare condition that should not be overlooked. The prognosis remains very poor. We emphasize the importance of long-term follow-up of such patients.

  3. Usefulness of analytical CEA doubling time and half-life time for overlooked synchronous metastases in colorectal carcinoma.

    Science.gov (United States)

    Ito, Katsuki; Hibi, Kenji; Ando, Hideyuki; Hidemura, Kazuhiko; Yamazaki, Taiji; Akiyama, Seiji; Nakao, Akimasa

    2002-02-01

    Measurement of carcinoembryonic antigen (CEA) has been widely applied to detect recurrence, especially of colorectal carcinoma. The validity however, is still controversial. We investigated serial changes in CEA values to calculate whether the CEA doubling time and half-life time could predict metastatic progression or prognosis in colorectal carcinoma. Pre- and post-operative serial serum CEA contents were determined in 22 cases of colorectal cancer with or without metastasis. CEA values were determined by enzyme immunoassay (EIA). Patients were assigned depending upon survival time (within vs. more than 18 months after primary resection) for assessment of CEA doubling time. From the gradient of the semi-logarithmic CEA graph, the preoperative doubling time was calculated and the postoperative half-life time was estimated according to the diagnosis of metastases within 2 years after primary resection [metastasis (+) or (-)]. In spite of the effect of curative re-operation of metastatic lesions or of postoperative adjuvant chemotherapy, the CEA doubling time of the groups showed a relation with prognosis (p = 0.045, Student's t-test) when the patients were divided into >18 and time. The CEA half-life time of the groups without overlooked metastases was statistically longer than those with (mean +/- SD 8.01 +/- 2.07 and 4.33 +/- 1.11, respectively, p Clearance (k) showed a significant difference between the groups (p time appeared to be a less independent prognostic factor, whereas prolongation of the CEA half-life time might potentially suggest the existence of overlooked synchronous metastases from colorectal carcinoma.

  4. Biopsy-Proven Metastatic Merkel Cell Carcinoma to the Orbit: Case Report and Review of Literature.

    Science.gov (United States)

    Cugley, Dean R; Roberts-Thomson, Samuel J; McNab, Alan A; Pick, Zelda

    2018-03-02

    Merkel cell carcinoma is a rare neuroendocrine tumor of subspecialized dermal mechanoreceptors, associated with immunosuppression. The usual ophthalmic presentation is an eyelid lesion. The authors present a case of biopsy-proven orbital metastatic Merkel cell carcinoma in the absence of any eyelid lesion, in an immunosuppressed patient with a history of multiple cancers. There are to the authors' knowledge only 2 other case reports of presumed metastatic Merkel cell carcinoma to the orbit, though neither were biopsied. Despite its rarity, metastatic Merkel cell carcinoma should be included in the differential of a metastatic orbital lesion, in the patient with a known or suspected cutaneous primary. The patient has had an excellent response to combined radiotherapy and programmed death-1 inhibitor pembrolizumab, and this case highlights the potential benefit of an exciting new biologic therapy.

  5. Fusobacterium nucleatum and T Cells in Colorectal Carcinoma.

    Science.gov (United States)

    Mima, Kosuke; Sukawa, Yasutaka; Nishihara, Reiko; Qian, Zhi Rong; Yamauchi, Mai; Inamura, Kentaro; Kim, Sun A; Masuda, Atsuhiro; Nowak, Jonathan A; Nosho, Katsuhiko; Kostic, Aleksandar D; Giannakis, Marios; Watanabe, Hideo; Bullman, Susan; Milner, Danny A; Harris, Curtis C; Giovannucci, Edward; Garraway, Levi A; Freeman, Gordon J; Dranoff, Glenn; Chan, Andrew T; Garrett, Wendy S; Huttenhower, Curtis; Fuchs, Charles S; Ogino, Shuji

    2015-08-01

    Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by downregulating antitumor T cell-mediated adaptive immunity. To test the hypothesis that a greater amount of F nucleatum in colorectal carcinoma tissue is associated with a lower density of T cells in tumor tissue. A cross-sectional analysis was conducted on 598 rectal and colon carcinoma cases in 2 US nationwide prospective cohort studies with follow-up through 2006, the Nurses' Health Study (participants enrolled in 1976) and the Health Professionals Follow-up Study (participants enrolled in 1986). Tissue collection and processing were performed from 2002 through 2008, and immunity assessment, 2008 through 2009. From 2013 through 2014, the amount of F nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high vs low). Multivariable ordinal logistic regression analysis was conducted in 2014 to assess associations of the amount of F nucleatum with densities (quartiles) of T cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted the 2-sided α level to .013 for multiple hypothesis testing. Densities of CD3+, CD8+, CD45RO (protein tyrosine phosphatase receptor type C [PTPRC])+, and FOXP3+ T cells in tumor tissue, determined by means of tissue microarray immunohistochemical analysis and computer-assisted image analysis. F nucleatum was detected in colorectal carcinoma

  6. Induction of trismus by sunitinib and pazopanib in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ridhima Iyer

    2017-01-01

    Full Text Available Tyrosine kinase inhibitors sunitinib and pazopanib are used as first-line agents in the treatment of metastatic renal cell carcinoma. Treatment-related toxicities have been described with both these drugs. This report describes a patient with metastatic renal carcinoma who developed trismus while being treated with these agents and is, to the best of our knowledge, the first such case to be reported.

  7. 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.

  8. Immunohistochemical distinction of primary sweat gland carcinoma and metastatic breast carcinoma: can it always be accomplished reliably?

    Science.gov (United States)

    Mentrikoski, Mark J; Wick, Mark R

    2015-03-01

    Even with adequate history, the distinction of cutaneous metastatic breast carcinoma from primary sweat gland carcinoma can be difficult. Although previous studies have attempted to separate these tumors with various immunohistochemical panels, those series have been limited by small numbers of patients as well as the inclusion of benign sweat gland tumors. In this analysis, stains for p63, CK5/6, and D2-40 were included, as well as GATA3 and mammaglobin, in an evaluation of 21 primary sweat gland carcinomas and 33 examples of cutaneous metastatic breast carcinoma. Immunoreactivity for p63, CK5/6, D2-40, GATA3, and mammaglobin was respectively observed in 81%, 71%, 52%, 71%, and 5% of sweat gland carcinomas compared with 6%, 6%, 6%, 91%, and 45% of metastatic breast carcinomas. These differences were statistically significant for p63, CK5/6, and D2-40. For the diagnosis of metastatic breast carcinoma, GATA3 was the most sensitive marker (91%), but its sensitivity was substantially lower. Mammaglobin was 95% specific for breast carcinoma but again suffered from limited sensitivity (45%) in this context. These data suggest that p63 and CK5/6 are specific determinants for sweat gland carcinoma in the stated setting. In the absence of those analytes, metastatic breast carcinoma cannot always be identified to the exclusion of a primary tumor. This diagnostic scenario continues to require the procurement of a detailed clinical history regarding the number and duration of skin lesions in any given case. Copyright© by the American Society for Clinical Pathology.

  9. MR imaging of colorectal carcinomas using an MR endoscopic coil

    International Nuclear Information System (INIS)

    Murano, Akihiko; Kido, Choichiro; Sasaki, Fumio; Nakamura, Tsuneya; Kobayashi, Semi; Katoh, Tomoyuki; Hirai, Takashi

    1994-01-01

    Diagnosis of the depth of wall invasion by rectal carcinoma using MR endoscopy was performed in ten resected specimens, including five rectal carcinomas, three colon carcinomas, two normal gastric wall. In addition, the gastric wall of a pig was examined. MR imaging was done with a 1.5-T Signa Advantage (GE Medical System) system, with the surface coil of the MR endoscope acting as the receiver coil. Five layers could be distinguished in the bowel wall: mucosa, submucosa and muscularis propria divided into circular muscle, longitudinal muscle and intervening connective tissue. Tumors had almost the same signal intensity as muscle. The MR images of colon carcinomas, rectal carcinomas, and extrinsically metastatic involvement of the sigmoid colon by rectal carcinoma all correlated well with the pathological findings. The normal structure of the gastric wall was similar to that of the colon. 3D-fast Spoiled Grass (SPGR) sequence has a fairly short scanning time. Thus, the possibility of precise clinical diagnosis by this method was suggested. (author)

  10. A rare case of metastatic basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Dai Wee Lee

    2017-12-01

    Full Text Available Background: Basal cell carcinoma (BCC is relatively uncommon in Malaysia with non-melanomatous skin cancer being the 12th most common malignancy in Malaysia.Metastatic basal cell carcinoma (MBCC is extremely rare and the incidence is estimated to be 0.0028% to 0.55% among all BCC. We report a case of MBCC with a summary of clinical and histopathology findings; and the management. Case presentation: A 69-year-old Chinese man, presented with a left wrist mass for 4 years. The mass was on the dorsal surface of the wrist, ulcerated, and measured 15 x 10cm. The tumour size was 2.5 × 8.6 × 10cm on MRI, extending into the extensor digitorum tendons and possible invasion into the lumbricals. He underwent wide excision of the mass, decorticotomy of left 3rd to 5th metacarpal bones and amputation of 2nd metacarpal bone. Histopathological examination showed BCC involving whole skin thickness invading the subcutaneous fat but sparing the underlying tissues, resections margins were clear, maximal diameter was 11.5 cm. The tumour was staged as pT2N0M0. After 18 months, he developed an 8 × 10cm left axillary mass which was fungating and bleeding. CT scan also showed multiple lung metastases. Repeat biopsy of the left axillary mass showed BCC with similar appearance as the previous histopathology examination. Radiotherapy to the left axilla was given (65 Gray in 30 fractions for local control as the tumour was bleeding profusely. Discussion: A review by Wysong et al. for 194 cases of MBCC suggests that its prognosis remains poor over the past 30 years, with the median overall survival of 10 months from diagnosis despite the introduction of systemic chemotherapy and radiotherapy. Most common metastatic sites are the regional lymph nodes, lungs and bone. Large lesions (particularly those over 10 cm2 and tumours that invade deep structures, such as cartilage, skeletal muscle, or bone, are most likely to metastasize. Perineural invasion, aggressive histologic

  11. ITF-2B protein levels are correlated with favorable prognosis in patients with colorectal carcinomas

    Science.gov (United States)

    Brandl, Lydia; Horst, David; de Toni, Enrico; Kirchner, Thomas; Herbst, Andreas; Kolligs, Frank T

    2015-01-01

    The majority of sporadic forms of colorectal carcinomas is characterized by deregulation of Wnt/β-catenin signaling early in colorectal carcinogenesis. As a consequence, ITF-2B protein levels are increased in adenomas of these patients. However, ITF-2B protein levels are strongly reduced with increasing carcinoma stages, suggesting that reduction of ITF-2B protein is required for progression of adenomas to colorectal carcinomas. To find out if ITF-2B protein levels are correlated with the survival of patients with colorectal carcinomas, a tissue microarray containing samples from 213 colorectal carcinomas (T-categories T2 and T3) with corresponding survival information was stained with an ITF-2B antibody. In addition, we analyzed if detection of ITF-2B in microsatellite instable and microsatellite stable carcinomas as well as in colorectal carcinomas with KRAS mutations is correlated with survival. Detection of cytoplasmic ITF-2B protein was associated with better overall and progression free survival of patients with colorectal carcinomas (P=0.033 and 0.024, respectively). Multivariate Cox regression analysis revealed an increased risk to suffer from poor overall survival and recurrent disease if no cytoplasmic ITF-2B was detectable (HR=1.91; P=0.033 and HR=1.75; P=0.033, respectively). Similarly, patients with MSS carcinomas had a better overall survival, if they showed cytoplasmic positivity for ITF-2B (P=0.013). Remarkably, patients with colorectal carcinomas carrying KRAS mutations had a better overall and progression free survival rate if the carcinomas were positive for cytoplasmic ITF-2B (HR=4.71; P=0.002 and HR=2.57; P=0.024, respectively). These data suggest that cytoplasmic protein levels of ITF-2B could be used as a prognostic marker for patients with colorectal carcinomas. PMID:26328254

  12. Combination hyperthermia and intraarterial 5-FU for metastatic colon carcinoma to liver

    International Nuclear Information System (INIS)

    Moseley, H.S.; Palmquist, M.

    1984-01-01

    Metastatic colorectal carcinoma to the liver remains a formidable challenge. Responses to chemotherapy are brief and the number of effective drugs is very limited. A phase II trial of hepatic hyperthermia and intraarterial chemotherapy was undertaken to attempt to improve response rates and duration. Patients were given a 10 day course of IA 5-FU at 15 mg/kg. During the infusion hyperthermia was given five times using the BSD Annular Phased Array (APA). Thermistors were placed percutaneously into normal liver and tumor using ultrasound or CT scan guidance. Six patients have been treated. Significant problems in positioning ill patients in the APA were encountered, and there was difficulty also in preventing heating throughout the abdominal cavity. Four patients, all with poor performance status, failed to benefit. One patient had improvement in liver function studies for two months and failed to respond on a repeat course. One patient had a complete response which is continuing over 18 months with a liver scan reverting to normal and CEA returning to normal. These preliminary results are promising and warrant further trials

  13. Metastatic Penile Carcinomas: A Study of Nine Cases and Review of ...

    African Journals Online (AJOL)

    Objective: Primary penile carcinoma is one of the rarest male genital tract tumors in Turkey, because circumcision is performed routinely. In general, metastatic carcinoma of the penis is the second most common penile tumor. Despite the fact that the penis is rarely affected by metastases, there have been 319 cases reported ...

  14. 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

  15. Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

    Science.gov (United States)

    Schofield, Penelope E; Stockler, M R; Zannino, D; Tebbutt, N C; Price, T J; Simes, R J; Wong, N; Pavlakis, N; Ransom, D; Moylan, E; Underhill, C; Wyld, D; Burns, I; Ward, R; Wilcken, N; Jefford, M

    2016-01-01

    Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.

  16. 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.

  17. STK31 as novel biomarker of metastatic potential and tumorigenicity of colorectal cancer.

    Science.gov (United States)

    Zhong, Lan; Liu, Jing; Hu, Yedong; Wang, Wei; Xu, Fei; Xu, Wen; Han, Junyi; Biskup, Ewelina

    2017-04-11

    Colorectal cancer (CRC) is the fifth most common cause of cancer deaths in China and fourth worldwide. Metastatic dissemination of primary tumors is considered main cause for CRC related mortality. The serine-threonine kinase 31 (STK31) gene is a novel cancer testis (CT) antigen. It was found significantly highly expressed in gastrointestinal cancers. In our study we aimed to analyze the correlation between STK31 expression patterns and metastasization, tumor stage and grade in CRC patients. Relative STK31 expression level was significantly higher in patients with lymph node metastasis. STK31 expression levels in primary tumorous tissues of metastatic patients were significantly higher than in ANCTs and in lymph nodes samples, both at the RNA level and the protein level. Surgical specimens of cancerous tissues, paired with adjacent noncancerous tissues, and lymph nodes from 44 CRC cases with different clinicopathological features were collected. Expression of STK31 was detected and measured by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). Our data suggest that STK31 might be a potential biomarker in detecting, monitoring and predicting the metastatic risk of colorectal cancer.

  18. Clinical Pharmacokinetics and Pharmacodynamics of Atezolizumab in Metastatic Urothelial Carcinoma.

    Science.gov (United States)

    Stroh, M; Winter, H; Marchand, M; Claret, L; Eppler, S; Ruppel, J; Abidoye, O; Teng, S L; Lin, W T; Dayog, S; Bruno, R; Jin, J; Girish, S

    2017-08-01

    Atezolizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human programmed death-ligand 1 (PD-L1), is US Food and Drug Administration (FDA) approved in metastatic urothelial carcinoma (MUC) and is being investigated in various malignancies. This analysis based upon 906 patients from two phase I and one phase II MUC studies, is the first report of the clinical pharmacokinetics (PK) and pharmacodynamics (PD) of atezolizumab. Atezolizumab exhibited linear PK over a dose range of 1-20 mg/kg, including the labeled 1,200 mg dose. The clearance, volume of distribution, and terminal half-life estimates from population pharmacokinetic (PopPK) analysis of 0.200 L/day, 6.91 L, and 27 days, respectively, were as expected for an IgG1. Exposure-response analyses did not identify statistically significant relationships with either objective response rate or adverse events of grades 3-5 or of special interest. None of the statistically significant covariates from PopPK (body weight, gender, antitherapeutic antibody, albumin, and tumor burden) would require dose adjustment. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  19. [Monitoring of metastatic renal cell carcinoma--standards and challenges].

    Science.gov (United States)

    Jäger, Elke

    2010-01-01

    The introduction of targeted therapies has led to a novel situation regarding monitoring of metastatic renal cell carcinoma (mRCC): patients treated with these new drugs have a significantly longer life expectancy than just a few years ago. In order to maximize the treatment benefit, new demands have come up on the assessment of tumor progression: timing and interpretation of imaging studies are crucial for optimal therapeutic management. Detailed knowledge of the new compounds' mode of action is important as it is different from that of classic cytotoxic drugs. The RECIST criteria constitute the standard for evaluation. Following recommendations made by the German Cancer Society's (DKG) interdisciplinary task force, targeted therapies should strive for a sufficient treatment duration in each line of therapy in order to achieve the best therapeutic outcome. Treatment is continued until clinical progression occurs. Assessing therapeutic efficacy with adequate imaging techniques 6-9 weeks after the beginning of therapy is recommended. Subsequent follow-up examinations should be repeated using identical imaging modalities every 2-3 months. For cyclically applied drugs such as Sunitinib, examinations should be carried out at identical time points within the treatment cycle. Copyright 2010 S. Karger AG, Basel.

  20. First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Ruiz-Morales, Jose Manuel; Swierkowski, Marcin; Wells, J Connor

    2016-01-01

    BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. PATIENTS AND METHODS: We used the International m...

  1. Postoperative adjuvant therapy of colorectal carcinoma

    International Nuclear Information System (INIS)

    Scheithauer, W.

    1989-01-01

    Evaluating the results of controlled clinical trials, an attempt has been made to summarize the current status of adjuvant therapy in colorectal cancer. Several different adjuvant treatment approaches including immunotherapy, postoperative fibrinolysis, anticoagulation, pre- and postoperative radiotherapy when used as a single modality, have not resulted in any long-term survival benefit. Rather in contrast to previous experiences, recent prospective randomized trials have provided evidence for the efficacy of chemotherapy in the adjuvant treatment of colon and rectal cancer. Whereas its definitive role in the former disease remains somewhat controversial, for rectal cancer, it seems clear that combined modality therapy including polychemotherapy with or without radiation prolongs the disease-free interval, lowers the local recurrence rate, and may improve survival compared to surgery alone. Questions which remain to be answered by future clinical trials are related to the optimal duration and sequence of combined modality, to the role of different radiation sensitizers, and in both colon and rectal cancer, to the choice of the most effective systemtic chemotherapeutic drugs. (orig./MG) [de

  2. Metastatic Clear Cell Renal Cell Carcinoma Presenting with a Gingival Metastasis

    OpenAIRE

    Ali, Rusha A.E.; Mohamed, Kamal E.H.

    2016-01-01

    Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation...

  3. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J. (Veterans Administration Medical Center, Buffalo, NY (USA))

    1990-07-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

  4. Colorectal carcinoma metastases: detection with In-111-labeled monoclonal antibody CCR 086.

    Science.gov (United States)

    Abdel-Nabi, H H; Levine, G; Lamki, L M; Murray, J L; Tauxe, W N; Shah, A N; Patt, Y Z; Doerr, R J; Klein, H A; Gona, J

    1990-07-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

  5. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    International Nuclear Information System (INIS)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J.

    1990-01-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer

  6. TNFα cooperates with IFN-γ to repress Bcl-xL expression to sensitize metastatic colon carcinoma cells to TRAIL-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Feiyan Liu

    Full Text Available BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL is an immune effector molecule that functions as a selective anti-tumor agent. However, tumor cells, especially metastatic tumor cells often exhibit a TRAIL-resistant phenotype, which is currently a major impediment in TRAIL therapy. The aim of this study is to investigate the synergistic effect of TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The efficacy and underlying molecular mechanism of cooperation between TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis were examined. The functional significance of TNFα- and IFN-γ-producing T lymphocyte immunotherapy in combination with TRAIL therapy in suppression of colon carcinoma metastasis was determined in an experimental metastasis mouse model. We observed that TNFα or IFN-γ alone exhibits minimal sensitization effects, but effectively sensitized metastatic colon carcinoma cells to TRAIL-induced apoptosis when used in combination. TNFα and IFN-γ cooperate to repress Bcl-xL expression, whereas TNFα represses Survivin expression in the metastatic colon carcinoma cells. Silencing Bcl-xL expression significantly increased the metastatic colon carcinoma cell sensitivity to TRAIL-induced apoptosis. Conversely, overexpression of Bcl-xL significantly decreased the tumor cell sensitivity to TRAIL-induced apoptosis. Furthermore, TNFα and IFN-γ also synergistically enhanced TRAIL-induced caspase-8 activation. TNFα and IFN-γ was up-regulated in activated primary and tumor-specific T cells. TRAIL was expressed in tumor-infiltrating immune cells in vivo, and in tumor-specific cytotoxic T lymphocytes (CTL ex vivo. Consequently, TRAIL therapy in combination with TNFα/IFN-γ-producing CTL adoptive transfer immunotherapy effectively suppressed colon carcinoma metastasis in vivo. CONCLUSIONS/SIGNIFICANCE: TNFα and IFN

  7. 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.

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

    International Nuclear Information System (INIS)

    Bae, Sun Hyun; Yun, Seong Hyeon; Kim, Hee Cheol; Park, Won; Choi, Doo Ho; Nam, Heerim; Kang, Won Ki; Park, Young Suk; Park, Joon Oh; Chun, Ho Kyung; Lee, Woo Yong

    2011-01-01

    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 Gy 10 (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 Gy 10 (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 Gy 10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status

  9. A cost comparison of biologic treatment regimens for metastatic colorectal cancer in Italy

    Directory of Open Access Journals (Sweden)

    Sergio Iannazzo

    2017-10-01

    Full Text Available IntroductionBevacizumab is a monoclonal antibody, which, in association with combination chemotherapy regimens, has been shown to be active in metastatic colorectal cancer. Other biologic agents active in the same setting are cetuximab and panitumumab, both of which are monoclonal antibodies directed against the antiepidermal growth factor receptor. The objective of this study was to compare treatment costs of first-line regimens for metastatic colorectal cancer in Italy.MethodsA set of first-line regimens was considered, according to the Italian Association of Medical Oncology and the European Society for Medical Oncology guidelines. A targeted review of the literature was undertaken to identify clinical study references for treatment regimens. The total cost of a regimen was calculated in the perspective of the Italian healthcare system summing up drugs, administration, and adverse event costs, based on year 2016 prices and tariffs.ResultsBevacizumab 7.5 mg + capecitabine was the least expensive regimen, with a total cost of €16,754 per patient. When we consider regimens based on FOLFOX, bevacizumab 5 mg + FOLFOX4 was the least expensive (€32,709 per patient, compared to panitumumab + FOLFOX4 (€42,815, cetuximab + FOLFOX4 (€42,725, and cetuximab + FOLFOX (€37,995. If we consider combination regimens based on FOLFIRI, the association of FOLFIRI and bevacizumab was less expensive than regimens that included cetuximab (€28,389 for bevacizumab 5 mg + FOLFIRI and €35,310 for cetuximab + FOLFIRI.ConclusionsFrom the perspective of the Italian health care system, bevacizumab appears to be a convenient option among the first-line regimens for metastatic colorectal cancer. Further study, based on real-world evidence, would be necessary to confirm this result.

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

    DEFF Research Database (Denmark)

    Van Cutsem, E; Cervantes, A; Adam, R

    2016-01-01

    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. This reflects the increase in the number of patients that are being managed within a multidisciplinary team...... based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.......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...

  11. Fournier gangrene as a manifestation of undiagnosed metastatic perforated colorectal cancer.

    Science.gov (United States)

    Chan, Cyrus C; Williams, Mallory

    2013-01-01

    Abstract Fournier gangrene is a necrotizing soft tissue infection involving the perineum. We present a case of Fournier gangrene as the clinical presentation of perforated metastatic rectal cancer. The patient is a 78-year-old man in a nursing home who presented to our institution with necrosis and ischemia of the scrotum. After wide debridement of necrotic tissue and bilateral orchiectomy, computed tomography was carried out to investigate abnormal findings seen on his chest X-ray, which revealed multiple pulmonary metastases as well as a mass highly suspicious for a perforated rectal mass. Once stable, a diverting colostomy and biopsies of the rectal mass were performed, confirming the presence of a metastatic, poorly differentiated rectal adenocarcinoma. Albeit an unusual etiology of Fournier gangrene, this case highlights the rare but important causes of this deadly condition and teaches us to be cognizant of the variations in the presentation of colorectal cancer.

  12. Treatment options for metastatic colorectal cancer in patients with liver dysfunction due to malignancy.

    Science.gov (United States)

    Faugeras, L; Dili, A; Druez, A; Krug, B; Decoster, C; D'Hondt, L

    2017-07-01

    The survival of colorectal cancer patients is frequently determined by the extent of metastatic invasion to the liver; in cases of major involvement, therapeutic strategies are limited because the liver is necessary for drug metabolism. We have reviewed articles about the pharmacokinetic profiles of each drug used in colorectal cancer patients with hepatic dysfunction to determine which of these treatments are most feasible. Some drugs appear to be feasible options for patients with hepatic insufficiency. Agents such as 5-fluorouracil and oxaliplatin, as well as monoclonal antibodies such as bevacizumab, cetuximab, and panitumumab, can potentially be used in these cases. On the other hand, irinotecan and regorafenib cannot be recommended because of the risk of increased toxicity. Treatment of patients with colorectal cancer and liver dysfunction represents a major challenge because the prognosis is usually very poor and alteration of liver function is normally an exclusion criterion in clinical trials. In this review, we present evidence regarding the use of each drug in patients with colorectal cancer and hepatic impairment. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  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...... histopathologically-verified mCRC refractory to standard chemotherapy, adequate organ function and performance status. Treatment included capecitabine (2,000 mg/m(2) day on days 1-7 q2w) and gemcitabine (1,000 mg/m(2) on day 1). The number of DNA alleles was measured in pre-treatment plasma samples using an in...

  14. Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Thomsen, Maria; Kersten, Christian; Sorbye, Halfdan

    2016-01-01

    Objectives: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. Results...... 24.3 months to 12.3 months, (P treatment serum samples...... from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progressionfree survival (PFS) and overall survival (OS) was estimated. Conclusions: High baseline serum consentrations of IL-6 or CRP were associated...

  15. Limited effect of lymph node status on the metastatic pattern in colorectal cancer

    Science.gov (United States)

    Knijn, Nikki; van Erning, Felice N.; Overbeek, Lucy I.H.; Punt, Cornelis J.A.; Lemmens, Valery E.P.P.; Hugen, Niek; Nagtegaal, Iris D.

    2016-01-01

    Regional lymph node metastases in colorectal cancer (CRC) decrease outcome. Whether nodal metastases function as a biomarker, i.e. as a sign of advanced disease, or are in fact involved in the metastatic process is unclear. We evaluated metastatic patterns of CRC according to the lymph node status of the primary tumor. A retrospective review of 1393 patients with metastatic CRC who underwent autopsy in the Netherlands was performed. Metastatic patterns of regional lymph node positive and negative CRC were compared and validated by population-based data from the Eindhoven Cancer Registry (ECR). Patients with regional lymph node positive CRC more often developed peritoneal metastases (28% vs. 21%, p=0.003) and distant lymph node metastases (25% vs. 15%, p <0.001). Incidences of liver and lung metastases were comparable. Data from the ECR confirmed our findings regarding peritoneal (22.4% vs. 17.0%, p=0.003) and distant lymph node metastases (15.8% vs. 9.7%, p <0.001). Regional lymph node positive CRC show a slightly different dissemination pattern, with higher rates of peritoneal and distant lymph nodes metastases. Comparable incidences of liver and lung metastases support the hypothesis that dissemination to distant organs occurs independently of lymphatic spread. PMID:27145371

  16. Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report.

    Science.gov (United States)

    Yoshino, Kenji; Manaka, Dai; Kudo, Ryo; Kanai, Shunpei; Mitsuoka, Eisei; Kanto, Satoshi; Hamasu, Shinya; Konishi, Sayuri; Nishitai, Ryuta

    2017-08-18

    Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years. A 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression. To the

  17. Cryopreservation of human colorectal carcinomas prior to xenografting

    International Nuclear Information System (INIS)

    Linnebacher, Michael; Maletzki, Claudia; Ostwald, Christiane; Klier, Ulrike; Krohn, Mathias; Klar, Ernst; Prall, Friedrich

    2010-01-01

    Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days). Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research

  18. Liposome encapsulated luteolin showed enhanced antitumor efficacy to colorectal carcinoma

    Science.gov (United States)

    Wu, Guixia; Li, Jing; Yue, Jinqiao; Zhang, Shuying; Yunusi, Kurexi

    2018-01-01

    Luteolin is a falconoid compound that is present in various types of plants and possesses remarkable potential as a chemopreventive agent. However, the poor aqueous solubility of luteolin limits its clinical application. In the present study, an approach towards chemoprevention was explored using liposomes to deliver luteolin, and the antitumor efficacy was investigated in colorectal carcinoma. The present findings demonstrated that luteolin was efficiently encapsulated into liposomes with an encapsulation efficiency as high as 90%. The particle size of the liposomal luteolin (Lipo-Lut) and ζ-potential were optimized. In vitro studies demonstrated that, Lipo-Lut had a significant inhibitory effect on the growth on the CT26 colorectal carcinoma cell line compared with free luteolin (Free-Lut). The in vivo study indicated that Lipo-Lut could achieve superior antitumor effects against CT26 tumor compared with luteolin alone. The present results suggested that liposome delivery of luteolin improved solubility, bioavailability and may have potential applications in chemoprevention in clinical settings. PMID:29207088

  19. Metastatic Basal cell carcinoma: a biological continuum of Basal cell carcinoma?

    Science.gov (United States)

    Mehta, Karaninder S; Mahajan, Vikram K; Chauhan, Pushpinder S; Sharma, Anju Lath; Sharma, Vikas; Abhinav, C; Khatri, Gayatri; Prabha, Neel; Sharma, Saurabh; Negi, Muninder

    2012-01-01

    Basal cell carcinoma (BCC) accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide surgical excision of a pathologically diagnosed basal cell carcinoma. The recurrence was diagnosed as infiltrative BCC and found metastasizing to skin, soft tissue and muscles, and pretracheal and axillary lymph nodes. Three cycles of chemotherapy comprising intravenous cisplatin (50 mg) and 5-florouracil (5-FU, 750 mg) on 2 consecutive days and repeated at every 21 days were effective. As it remains unclear whether metastatic BCC is itself a separate subset of basal cell carcinoma, we feel that early BCC localized at any site perhaps constitutes a biological continuum that may ultimately manifest with metastasis in some individuals and should be evaluated as such. Long-standing BCC is itself potentially at risk of recurrence/dissemination; it is imperative to diagnose and appropriately treat all BCC lesions at the earliest.

  20. Metastatic Basal Cell Carcinoma: A Biological Continuum of Basal Cell Carcinoma?

    Directory of Open Access Journals (Sweden)

    Karaninder S. Mehta

    2012-01-01

    Full Text Available Basal cell carcinoma (BCC accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide surgical excision of a pathologically diagnosed basal cell carcinoma. The recurrence was diagnosed as infiltrative BCC and found metastasizing to skin, soft tissue and muscles, and pretracheal and axillary lymph nodes. Three cycles of chemotherapy comprising intravenous cisplatin (50 mg and 5-florouracil (5-FU, 750 mg on 2 consecutive days and repeated at every 21 days were effective. As it remains unclear whether metastatic BCC is itself a separate subset of basal cell carcinoma, we feel that early BCC localized at any site perhaps constitutes a biological continuum that may ultimately manifest with metastasis in some individuals and should be evaluated as such. Long-standing BCC is itself potentially at risk of recurrence/dissemination; it is imperative to diagnose and appropriately treat all BCC lesions at the earliest.

  1. Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer

    OpenAIRE

    Lee, Myung-Ah; Byun, Jae-Ho; Shim, Byoung-Young; Woo, In-Sook; Kang, Jin-Hyung; Hong, Young Seon; Lee, Kyung Shik; Choi, Myung Gyu; Chang, Suk Kyun; Oh, Seong Taek; Choi, Sung Il; Lee, Doo Suk

    2005-01-01

    Background Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of therapy for patients with relapsed or metastatic colorectal cancer. Methods Between January 2002 and October 2004, 44 patients with histologically confirmed recurrent or metastat...

  2. Patterns of care for metastatic renal cell carcinoma in Australia.

    Science.gov (United States)

    Day, Daphne; Kanjanapan, Yada; Kwan, Edmond; Yip, Desmond; Lawrentschuk, Nathan; Andrews, Miles; Davis, Ian D; Azad, Arun A; Rosenthal, Mark; Wong, Shirley; Johnstone, Alice; Gibbs, Peter; Tran, Ben

    2015-10-01

    To examine the patterns of care and outcomes for metastatic renal cell carcinoma (mRCC) in Australia, where there are limited reimbursed treatment options. In particular, we aim to explore prescribing patterns for first-line systemic treatment, the practice of an initial watchful-waiting approach, and the use of systemic treatments in elderly patients. Patients with mRCC undergoing treatment between 2006 and 2012 were identified from four academic hospitals in Victoria and Australian Capital Territory. Demographic, clinicopathological, treatment, and survival data were recorded by chart review. Descriptive statistics were used to report findings. Survival was estimated by the Kaplan-Meier method and compared using the log-rank test. The study was supported by a grant from Pfizer Australia. Our study identified 212 patients with mRCC for analysis. Patients were predominantly of clear cell histology (75%), Eastern Cooperative Oncology Group performance status 90 days before initiating treatment; these patients had a median OS of 56.3 months. Elderly patients (50 patients aged ≥70 years) were more likely to receive BSC alone than younger patients (46% vs 16%, P < 0.001). Of those who received systemic therapy, elderly patients were also more likely to have upfront dose reductions (30% vs 8%, P = 0.03). Our study of patients with mRCC treated in Australian centres showed that sunitinib was the most commonly prescribed systemic treatment between 2006 and 2012, associated with survival outcomes similar to pivotal studies. We also found that an initial watchful-waiting approach is commonly adopted without apparent detriment to survival. And finally, we found that age has an impact on the prescribing of systemic therapy. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  3. Incidence of capecitabine-related cardiotoxicity in different treatment schedules of metastatic colorectal cancer: A retrospective analysis of the CAIRO studies of the Dutch Colorectal Cancer Group

    NARCIS (Netherlands)

    Kwakman, Johannes J. M.; Simkens, Lieke H. J.; Mol, Linda; Kok, Wouter E. M.; Koopman, Miriam; Punt, Cornelis J. A.

    2017-01-01

    The frequency of capecitabine-related cardiotoxicity has been reported to be low but includes serious adverse events. We conducted a retrospective analysis of the incidence and severity of capecitabine-related cardiotoxicity in different regimens in the treatment of metastatic colorectal cancer in

  4. Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma

    International Nuclear Information System (INIS)

    Kunicka, T.; Prochazka, P.; Krus, I.; Bendova, P.; Protivova, M.; Susova, S.; Hlavac, V.; Liska, V.; Novak, P.; Schneiderova, M.; Pitule, P.; Bruha, J.; Vycital, O.; Vodicka, P.; Soucek, P.

    2016-01-01

    This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients. Testing set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients. Protein levels of two most relevant candidate markers were assessed by immunoblotting. Downregulation of DPYD and upregulation of PPAT, UMPS, RRM2, and SLC29A1 transcripts were found in tumors compared to adjacent mucosa in testing and validation sets of patients. Low RRM2 transcript level significantly associated with poor response to the first-line palliative 5-FU-based chemotherapy in the testing set and with poor disease-free interval of patients in the validation set irrespective of 5-FU treatment. UPP2 was strongly methylated while its transcript absent in both tumors and adjacent mucosa. DPYS methylation level was significantly higher in tumor tissues compared to adjacent mucosa samples. Low intratumoral level of UPB1 methylation was prognostic for poor disease-free interval of the patients (P = 0.0002). The rest of the studied 5-FU genes were not methylated in tumors or adjacent mucosa. The observed overexpression of several 5-FU activating genes and DPYD downregulation deduce that chemotherapy naïve colorectal tumors share favorable gene expression profile for 5-FU therapy. Low RRM2 transcript and UPB1 methylation levels present separate poor prognosis factors for colorectal carcinoma patients and should be further investigated. The online version of this article (doi:10.1186/s12885-016-2826-8) contains supplementary material, which is available to authorized users

  5. Low Grade Lymphoma Mimicking Metastatic Urothelial Carcinoma: When Do We Need Further Histologic Staging?

    Directory of Open Access Journals (Sweden)

    Azka Ali

    2016-01-01

    Full Text Available Introduction. Patients with urothelial carcinoma of the bladder often present with metastases to regional lymph nodes, with lymphadenopathy on physical examination or radiographic imaging. Case Presentation. We present the case of a 73-year-old Caucasian man with presumed metastatic urothelial carcinoma of the bladder to regional pelvic and retroperitoneal lymph nodes. He underwent systemic chemotherapy for treatment of urothelial carcinoma and was discovered on restaging to have findings suggestive of disease progression but ultimately was found to have a concurrent secondary malignancy. Conclusion. Our case suggests that in patients with urothelial carcinoma, the concurrent presentation of regional lymphadenopathy may not be metastatic urothelial carcinoma and may warrant further investigation.

  6. Case report of gastric outlet obstruction from metastatic lobular breast carcinoma.

    Science.gov (United States)

    Kim, Alexander H; Shellenberger, M Joshua; Chen, Zong Ming; Li, Jinhong

    2015-09-25

    The most common malignancy to cause gastric outlet obstruction is primary gastric adenocarcinoma and it is followed by carcinoma of the pancreas and gallbladder. Herein, we report a case of gastric outlet obstruction secondary to metastatic lobular breast carcinoma. Fifty-seven year old Caucasian female with recently diagnosed metastatic lobular breast carcinoma to skin was referred to gastroenterology for evaluation of dyspepsia and dysphagia. She has past medical history significant for acid reflux and Clostridium difficile colitis. Computed tomography of her abdomen showed diffused bowel wall thickening without evidence of bowel obstruction. Due to persistent abdominal pain, an upper endoscopy was performed. The upper endoscopy showed gastritis and gastric stenosis in the gastric antrum. These lesions were biopsied and dilated with a balloon dilator. The biopsy of the gastric antrum later showed a metastatic carcinoma of breast origin with typical tumor morphology and immune-phenotype. Differentiating metastatic breast carcinoma from primary gastric adenocarcinoma cannot be done using histological examination alone. Immunohistochemistry is needed to differentiate the two based on staining for estrogen and progesterone receptors. The presence of gross cystic disease fluid protein 15 is also suggestive of metastatic breast carcinoma. The stomach has a significant capacity to distend (up to 2-4 L of food) and malignant gastric outlet obstruction is often undetected clinically until a high-grade obstruction develops. Our case demonstrates valuable teaching point in terms of broadening our differentials for gastric outlet obstruction. When patients present with gastric outlet obstruction, both non-malignant and malignant causes of gastric outlet obstruction should be considered. Once adenocarcinoma has been determined to be the cause of gastric outlet obstruction, further immunohistochemistry is needed to differentiate breast carcinoma from other carcinomas.

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

    International Nuclear Information System (INIS)

    Khan, Gazala; Moss, Rebecca A; Braiteh, Fadi; Saltzman, Marc

    2014-01-01

    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

  8. Emerging combination therapies for metastatic colorectal cancer – impact of trifluridine/tipiracil

    Directory of Open Access Journals (Sweden)

    Puthiamadathil JM

    2017-10-01

    Full Text Available Jeevan M Puthiamadathil,1 Benjamin A Weinberg1,2 1Department of Medicine, 2Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA Abstract: Patients with metastatic colorectal cancer (mCRC are surviving longer now than ever before, but mortality rates are still high and more effective therapies are clearly needed. For patients with disease that is refractory to fluoropyrimidines, oxaliplatin, irinotecan, and biologic agents targeting the vascular endothelial growth factor and epidermal growth factor receptor pathways, novel treatment options trifluridine/tipiracil (TAS-102 and regorafenib can be effective disease stabilizers. However, objective clinical responses are rare and toxicities are manageable but common. In order to tackle poor clinical responses to TAS-102, there is an ongoing effort to effectively combine this drug with other agents, particularly those targeting angiogenesis. Certain subpopulations appear to benefit more than others from TAS-102; those that benefit often have underlying genetic defects in DNA repair pathways and/or develop neutropenia. In this review, we focus on the role of TAS-102 in the treatment of mCRC, including its use in combination with other agents, potential predictive biomarkers of response to TAS-102, and possible future directions. Keywords: metastatic colorectal cancer, trifluridine, tipiracil, TAS-102, regorafenib

  9. Evaluation of KRAS Gene Mutations in Metastatic Colorectal Cancer Patients in Kermanshah Province.

    Science.gov (United States)

    Amirifard, Nasrin; Sadeghi, Edris; Farshchian, Negin; Haghparast, Abbas; Choubsaz, Mansour

    2016-01-01

    Worldwide, colorectal cancer (CRC) is reported to be the fourth most common cancer in men and the third most common in women. KRAS is a protooncogene located on the short arm of chromosome 12. The aim of this study was to evaluate the KRAS oncogene and its relationship it with clinicopathologic features in 33 Kurdish patients. Metastatic CRC between 2012 and 2016 that came to Imam Reza hospital, Kermanshah province, Iran, were analysed for KRAS mutations using allele specific PCR primers and pyrosequencing. Correlations between variables was analyzed in PASW SPSS and overall survival curves were plotted in Graph Pad prism 5. The mean age for them at diagnosis was 51.5±12.6 years (range, 2276 years). Among the 33 patients that were sequenced, 12 samples in the KRAS gene had a nucleotide change, 11 in codon 12 and 1 in codon 13.There was no significant relationship between the mutation and clinical and pathological aspects of the disease. Knowledge of the KRAS status can help in decisionmaking to treat metastatic colorectal cancer patients more efficiently and increase survival. However, many Kurdish people due to economic problems are not able to do this valuable genetic test. In addition, we need more careful research of KRAS oncogene at the molecular level in young populations with more patients.

  10. [Expression characteristics of PTEN and NDRG1 in colorectal carcinoma and their prognostic value].

    Science.gov (United States)

    Zhang, G X; Qian, Z Y; Yang, L J; Wang, F; Shen, H

    2017-04-08

    Objective: To study the expression status and clinical significance of PTEN and NDRG1 in colorectal carcinoma. Methods: Tissue samples of 91 colorectal cancers, 30 colorectal adenomas and 21 colorectal normal mucosa tissues were collected. Postoperative specimens were examined by immunohistochemistry for PTEN and NDRG1 expression. The expression of PTEN and NDRG1 was correlated with clinicopathological feature. Results: The expression of PTEN and NDRG1 in the studied cases was detected in 55.0%(50/91) and 76.9%(70/91), respectively. Their expression was significantly different from that of colorectal adenomas and normal colorectal mucosa tissues( P PTEN and over expression of NDRG1 were significantly related to the lymph node metastasis ( P PTEN was negatively related to that of NDRG1 in colorectal carcinoma( r s '=-0.251, P =0.016). The patients with negative expression of PTEN showed a lower disease free survival and overall survival( P PTEN protein may be an important molecular marker in predicting the occurrence and PTEN may be useful as a prognostic marker of colorectal carcinoma. NDRG1 plays a role in the development of colorectal carcinoma, although not a prognostic indicator.The ancillary study with combined detection of PTEN and NDRG1 may be useful in difficult cases.

  11. Metastatic giant basal cell carcinoma: a case report.

    Science.gov (United States)

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  12. Expression of AQP5 and AQP8 in human colorectal carcinoma and their clinical significance

    Directory of Open Access Journals (Sweden)

    Wang Wei

    2012-11-01

    Full Text Available Abstract Background The aquaporins (AQPs are a family of small membrane transport proteins whose overexpression has been implicated in tumorigenesis. However, the expression of AQP5 and AQP8 in colorectal cancer and the clinical significance remain unexplored. This study aimed to detect the expression of AQP5 and AQP8 in clinical samples of colorectal cancer and analyze the correlations of their expression with the clinicopathological features of colorectal cancer. Methods Forty pairs of colorectal cancer tissue and paraneoplastic normal tissue were obtained at the time of surgery from patients with colorectal cancer. The expression of AQP5 and AQP8 was detected by immunohistochemical staining and reverse transcriptase polymerase chain reaction. Results AQP5 was mainly expressed in colorectal carcinoma cells and barely expressed in paraneoplastic normal tissues. By contrast, AQP8 was mainly expressed in paraneoplastic normal tissues and barely expressed in colorectal carcinoma cells. AQP5 expression was not significantly associated with the sex or age of the patient with colorectal cancer (P>0.05, but was closely associated with the differentiation, tumor-nodes-metastasis stage and distant lymph node metastasis of colorectal carcinoma (P Conclusions AQP5 might be a novel prognostic biomarker for patients with colorectal cancer.

  13. Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review.

    Science.gov (United States)

    Røed Skårderud, Maria; Polk, Anne; Kjeldgaard Vistisen, Kirsten; Larsen, Finn Ole; Nielsen, Dorte Lisbet

    2018-01-01

    Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib. We systematically searched the PubMed and Embase databases, as well as ASCO and ESMO conference abstracts, for studies in English including ≥30 patients, evaluating the efficacy and safety of regorafenib in patients with metastatic colorectal cancer. A meta-analysis was conducted on the published, randomized phase III trials. 24 eligible studies were included. In two phase III trials, regorafenib significantly increased overall survival (OS), progression free survival (PFS), and disease control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months were presented. The meta-analysis indicated a significant greater treatment effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to placebo. The non-randomized studies mostly supported these results. The most frequently reported adverse events were hand-foot-skin reaction (25%-86%), hypertension (11%-47%) and fatigue (2%-73%). Large phase III randomized trials indicate that regorafenib provides a benefit in OS and PFS when compared to placebo. Adverse events were common, but manageable and typical of multi-target tyrosine kinase inhibitors. Further research is needed to investigate alternative approaches to the dosing of regorafenib and to explore clinical and molecular biomarkers that can guide patient selection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy

    Directory of Open Access Journals (Sweden)

    Paola Ulivi

    2017-06-01

    Full Text Available There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided in patients with metastatic colorectal cancer (mCRC. We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter “Italian Trial in Advanced Colorectal Cancer (ITACa”, randomized to receive first-line chemotherapy (CT or CT plus bevacizumab (CT + B. RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF, endothelial nitric oxide synthase (eNOS, cyclooxygenase-2 (COX2, ephrin type-B receptor 4 (EPHB4, hypoxia-inducible factor 1-alpha (HIF-1α, lactate dehydrogenase (LDH, and high-sensitivity C reactive protein (hs-CRP; and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017. Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.

  15. Metastatic basal cell carcinoma of the posterior neck: case report and review of the literature.

    Science.gov (United States)

    Gropper, Adrienne B; Girouard, Sasha D; Hojman, Lia P; Huang, Susan J; Qian, Xiaohua; Murphy, George F; Vleugels, Ruth Ann

    2012-05-01

    Although primary basal cell carcinoma (BCC) represents an extremely common malignancy, metastases derived from BCC are exceedingly rare. The prognosis for metastatic BCC is poor, and little consensus exists regarding predictive factors or optimal treatment strategies. Here, we present the case of a 63-year-old man with BCC of the neck who subsequently developed multiple metastases to subcutaneous tissue, lymph nodes, and the parotid gland. Risk factors and clinical features of metastatic BCC are reviewed, as is the relationship of histopathologic subtype to metastatic behavior. Current chemotherapeutic and targeted therapies also are discussed in the context of recent advances in molecular biology. Copyright © 2012 John Wiley & Sons A/S.

  16. Evaluation of liquid biopsies for detection of emerging mutated genes in metastatic colorectal cancer.

    Science.gov (United States)

    Furuki, Hiroyasu; Yamada, Takeshi; Takahashi, Goro; Iwai, Takuma; Koizumi, Michihiro; Shinji, Seiichi; Yokoyama, Yasuyuki; Takeda, Kohki; Taniai, Nobuhiko; Uchida, Eiji

    2018-02-02

    Detection of gene mutations is important for planning molecular targeted therapy. Although most gene mutations are concordant between primary colon cancers and their liver metastases, new mutations can emerge in metastases. The liquid biopsy is a newly developed, gene analytic method to detect mutations in metastatic tumors. In this prospective study, we evaluated the applicability of liquid biopsies in the detection of mutations in primary and metastatic tumors. We included 22 patients with liver metastases from colorectal cancer and extracted DNA from primary colorectal tumors, metastatic liver tumors, and peripheral blood (liquid biopsy). Next-generation sequencing (NGS) and digital PCR were performed to detect mutations in these three sample types. We found a total of 36 different mutations in samples from primary tumors, liver metastases, and liquid biopsies using NGS. Twenty-eight of these mutations were found in all three types of samples, whereas liquid biopsy did not identify four mutations that had been found in both primary tumors and liver metastases, but did identify four mutations that were found in liver tumors but not in primary tumors. The sensitivity of liquid biopsies for detecting mutations in liver metastases was 64% (23/36) using NGS and 89% (32/36, P = 0.02) using dPCR. The specificities of NGS and dPCR were 100% (23/23) and 100% (32/32), respectively. Emerging mutations, which are not found in primary tumors, can be detected in their metastases and liquid biopsies. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  17. [Metastatic breast cancer to the stomach: An uncommon evolution of breast carcinoma].

    Science.gov (United States)

    Hild, C; Talha-Vautravers, A; Hoefler, P; Zirabe, S; Bellocq, J-P; Mathelin, C

    2014-01-01

    Breast carcinoma exceptionally leads to metastatic linitis plastica. Distinguishing a breast cancer metastasis to the stomach from a primary gastric cancer on the basis of clinical and radiological signs is very challenging. Thanks to being cognizant of the previous history of invasive lobular carcinoma and the gastric biopsy followed by immunohistochemical analysis, gastric metastasis can be diagnosed. Despite the use of chemotherapy and hormonal therapy, gastric metastasis remains often associated with poor prognosis. We present a case where gastric biopsy allowed a metastatic breast cancer to the stomach to be diagnosed and we discuss its clinical, diagnostic, pathological and therapeutic particularities. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer.

    Science.gov (United States)

    Codony-Servat, Jordi; Cuatrecasas, Miriam; Asensio, Elena; Montironi, Carla; Martínez-Cardús, Anna; Marín-Aguilera, Mercedes; Horndler, Carlos; Martínez-Balibrea, Eva; Rubini, Michele; Jares, Pedro; Reig, Oscar; Victoria, Iván; Gaba, Lydia; Martín-Richard, Marta; Alonso, Vicente; Escudero, Pilar; Fernández-Martos, Carlos; Feliu, Jaime; Méndez, Jose Carlos; Méndez, Miguel; Gallego, Javier; Salud, Antonieta; Rojo, Federico; Castells, Antoni; Prat, Aleix; Rosell, Rafael; García-Albéniz, Xabier; Camps, Jordi; Maurel, Joan

    2017-12-05

    Although chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving. We analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients. The effect of IGF-1R activation and distribution was also assessed using cellular models of CRC and RNAi for functional validation. Nuclear IGF-1R increased in metastatic tumours compared to paired untreated primary tumours, and significantly correlated with poor overall survival in mCRC patients. In vitro, chemo-resistant cell lines presented significantly higher levels of IGF-1R expression within the nuclear compartment, and PIAS3, a protein implicated also in the sumoylation process of intranuclear proteins, contributed to IGF-1R nuclear sequestration, highlighting the essential role of PIAS3 in this process. Intriguingly, we observed that ganitumab, an IGF-1R blocking-antibody used in several clinical trials, and dasatinib, an SRC inhibitor, increased the nuclear localisation of IGF-1R. Our study demonstrates that IGF-1R nuclear location might lead to chemotherapy and targeted agent resistance.

  20. Clinical Usefulness of Tools to Support Decision-making for Palliative Treatment of Metastatic Colorectal Cancer: A Systematic Review

    NARCIS (Netherlands)

    Engelhardt, Ellen G.; Révész, Dóra; Tamminga, Hans J.; Punt, Cornelis J. A.; Koopman, Mirjam; Onwuteaka-Philipsen, Bregje D.; Steyerberg, Ewout W.; Jansma, Ilse P.; de Vet, Henrica C. W.; Coupé, Veerle M. H.

    2018-01-01

    Decision-making regarding palliative treatment for patients with metastatic colorectal cancer (mCRC) is complex and comprises numerous decisions. Decision-making should be guided by the premise of maintaining and/or improving patients' quality of life, by patient preference, and by the trade-off

  1. Phase I Study of Everolimus, Cetuximab and Irinotecan as Second-line Therapy in Metastatic Colorectal Cancer

    NARCIS (Netherlands)

    Hecht, J.R.; Reid, T.R.; Garrett, C.R.; Beck, J.T.; Davidson, S.J.; Mackenzie, M.J.; Brandt, U.; Rizvi, S.; Sharma, S.

    2015-01-01

    AIM: To evaluate feasible doses of weekly everolimus and irinotecan given with cetuximab for previously treated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Adults with mCRC that progressed after 5-fluorouracil or capecitabine-plus-oxaliplatin were treated using a sequential dose

  2. Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer

    NARCIS (Netherlands)

    Blauwhoff-Buskermolen, Susanne; Versteeg, Kathelijn S.; de van der Schueren, Marian A. E.; den Braver, Nicole R.; Berkhof, Johannes; Langius, Jacqueline A. E.; Verheul, Henk M. W.

    2016-01-01

    Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall

  3. CD44-positive cancer stem cells expressing cellular prion protein contribute to metastatic capacity in colorectal cancer.

    Science.gov (United States)

    Du, Lei; Rao, Guanhua; Wang, Hongyi; Li, Baowei; Tian, Weili; Cui, Jiantao; He, Leya; Laffin, Brian; Tian, Xiuyun; Hao, Chunyi; Liu, Hongmin; Sun, Xin; Zhu, Yushan; Tang, Dean G; Mehrpour, Maryam; Lu, Youyong; Chen, Quan

    2013-04-15

    Cancer stem cells are implicated in tumor progression, metastasis, and recurrence, although the exact mechanisms remain poorly understood. Here, we show that the expression of cellular prion protein (PrPc, PRNP) is positively correlated with an increased risk of metastasis in colorectal cancer. PrPc defines a subpopulation of CD44-positive cancer stem cells that contributes to metastatic capacity. PrPc(+)CD44(+) colorectal cancer stem cells displayed high liver metastatic capability, unlike PrPc(-)CD44(+) stem cells, that was inhibited by RNAi-mediated attenuation of PrPc. Notably, administration of PrPc monoclonal antibodies significantly inhibited tumorigenicity and metastasis of colorectal cancer stem cells in mouse models of orthotopic metastasis. PrPc promoted epithelial to mesenchymal transition (EMT) via the ERK2 (MAPK1) pathway, thereby conferring high metastatic capacity. Our findings reveal the function of PrPc in regulating EMT in cancer stem cells, and they identify PrPc as candidate therapeutic target in metastatic colorectal cancer. ©2013 AACR.

  4. Detection of liver metastases from colorectal carcinoma: Is there a place for routine computed tomography arteriography?

    NARCIS (Netherlands)

    B. van Ooijen (B.); M. Oudkerk (Matthijs); P.I.M. Schmitz (Paul); T. Wiggers (Theo)

    1996-01-01

    textabstractBackground. A prospective evaluation of the liver by preoperative ultrasonography, conventional computed tomography (CT), and continuous CT angiography (CCTA) was performed in 60 patients with primary or secondary colorectal carcinoma. Methods. The standards of reference were palpation

  5. Metastatic anal sac carcinoma with hypercalcaemia and associated ...

    African Journals Online (AJOL)

    Tulyasys

    2015-05-07

    May 7, 2015 ... carcinoma, prostatic carcinoma, renal carcinoma, renal ... Radiotherapy of the sublumbar lymph nodes and later concurrent carboplatin chemotherapy ... treatment. Two months later, the patient again developed hypercalcaemia with severe increase in size of the sublumbar lymph nodes. On physical ...

  6. Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer

    Science.gov (United States)

    2018-03-22

    Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  7. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  8. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma.

    Science.gov (United States)

    Castellarin, Mauro; Warren, René L; Freeman, J Douglas; Dreolini, Lisa; Krzywinski, Martin; Strauss, Jaclyn; Barnes, Rebecca; Watson, Peter; Allen-Vercoe, Emma; Moore, Richard A; Holt, Robert A

    2012-02-01

    An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors relative to control specimens. F. nucleatum is an invasive anaerobe that has been linked previously to periodontitis and appendicitis, but not to cancer. Fusobacteria are rare constituents of the fecal microbiota, but have been cultured previously from biopsies of inflamed gut mucosa. We obtained a Fusobacterium isolate from a frozen tumor specimen; this showed highest sequence similarity to a known gut mucosa isolate and was confirmed to be invasive. We verified overabundance of Fusobacterium sequences in tumor versus matched normal control tissue by quantitative PCR analysis from a total of 99 subjects (p = 2.5 × 10(-6)), and we observed a positive association with lymph node metastasis.

  9. Prognostic factors and risk classifications for patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Shinohara, Nobuo; Abe, Takashige

    2015-10-01

    The introduction of molecular-targeted therapy has made dramatical changes to treatment for metastatic renal cell carcinoma. Currently, there are four vascular endothelial growth factor receptor-tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors in Japan. For the appropriate clinical use of these molecular-targeted drugs, the identification of prognostic and/or predictive factors in patients who received these drugs is required. Although molecular biological and genetic factors that determine the prognosis of patients with metastatic renal cell carcinoma have been reported, most of these factors are problematic in that the number of patients analyzed was small. In contrast, clinicopathological prognostic factors, including the practice of cytoreductive nephrectomy, pathological findings, metastatic sites and metastasectomy, and abnormal inflammatory response, have been identified by analyzing a relatively large number of patients. Several prognostic classification models that were developed by combining these clinicopathological factors are widely used in not only clinical trials, but also routine clinical practice. However, the quality of these prognostic models is considered to be insufficient regarding prognostic prediction of metastatic renal cell carcinoma patients and, thus, requires further improvements. Recently, basic and clinical studies have been extensively carried out for the identification of promising informative markers and for understanding molecular mechanisms of resistance to molecular-targeted drugs in metastatic renal cell carcinoma patients. The present review considers ongoing translational research efforts on clinicopathological, molecular biological, and genetic prognostic and/or predictive factors for metastatic renal cell carcinoma patients in the era of molecular-targeted therapy, and discusses the clinical implications of these findings. © 2015 The Japanese Urological Association.

  10. The molecular biology of colorectal carcinoma and its implications: a review.

    Science.gov (United States)

    Harrison, Sanjay; Benziger, Harrison

    2011-08-01

    Colorectal carcinoma is one of the most common cancers encountered in the western world and increasingly in the developing world as well. This conditions results in considerable morbidity and mortality. As a result of the impact colorectal carcinoma has on society, a considerable amount of research has gone into elucidating the molecular mechanisms of this disease. This has led to a proliferation in the understanding of the molecular aetiology of the disease. Such research has revealed the underlying mechanisms to be complex and diverse, with no single molecular cause for the development of colorectal cancer. In this review, we look at the basic underlying molecular mechanisms of colorectal cancer and also briefly explore its implications with regards to clinical applications. We look at how this information relates to the prognosis and also its potential use in screening. A medline and pubmed search was conducted using the keywords colorectal carcinoma, molecular biology of colorectal carcinoma, mutations, and the relevant articles were used for this review. Bibliographies of these articles were also searched for relevant articles. There is considerable information available on the pathogenesis of colorectal carcinoma and such knowledge is beginning to impact on clinical practice. Copyright © 2011 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  11. T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of Metastatic Colorectal Cancer but Induce Severe Transient Colitis

    Science.gov (United States)

    Parkhurst, Maria R; Yang, James C; Langan, Russell C; Dudley, Mark E; Nathan, Debbie-Ann N; Feldman, Steven A; Davis, Jeremy L; Morgan, Richard A; Merino, Maria J; Sherry, Richard M; Hughes, Marybeth S; Kammula, Udai S; Phan, Giao Q; Lim, Ramona M; Wank, Stephen A; Restifo, Nicholas P; Robbins, Paul F; Laurencot, Carolyn M; Rosenberg, Steven A

    2011-01-01

    Autologous T lymphocytes genetically engineered to express a murine T cell receptor (TCR) against human carcinoembryonic antigen (CEA) were administered to three patients with metastatic colorectal cancer refractory to standard treatments. All patients experienced profound decreases in serum CEA levels (74–99%), and one patient had an objective regression of cancer metastatic to the lung and liver. However, a severe transient inflammatory colitis that represented a dose limiting toxicity was induced in all three patients. This report represents the first example of objective regression of metastatic colorectal cancer mediated by adoptive T cell transfer and illustrates the successful use of a TCR, raised in human leukocyte antigen (HLA) transgenic mice, against a human tumor associated antigen. It also emphasizes the destructive power of small numbers of highly avid T cells and the limitations of using CEA as a target for cancer immunotherapy. PMID:21157437

  12. FIRST LINE 5-FU-BASED CHEMOTHERAPY WITH/WITHOUT BEVACIZUMAB FOR METASTATIC COLORECTAL CANCER: TISSUE BIOMARKER CANDIDATES

    Directory of Open Access Journals (Sweden)

    Assia Konsoulova

    2016-03-01

    Full Text Available Purpose: Colorectal cancer is the second leading cause of cancer mortality in the USA. According to Bulgarian National Statistics Institute, 2370 colon and 1664 rectal cancer cases were diagnosed in 2012 with total number of patients 29995. Adding bevacizumab to chemotherapy in patients with metastatic disease improves progression-free survival (PFS but no predictive markers have been proven in the clinical practice. In our study we examined two tissue biomarkers that may correlate with response to bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer. Patients and Methods: 54 patients with metastatic colorectal cancer were assigned to first line 5-Fu-based chemotherapy with/without bevacizumab. The primary end point was PFS, with additional determination of response and toxicity. Paraffin-embedded samples from primary tumors were collected from all 54 patients. Expression levels of two tumor biomarkers VEGFR-2 and Neuropilin 1 (NP-1 were evaluated with immunohistochemistry. Results: The median PFS for the group treated with CT/Bev was 8.8 months, compared with 5.4 months for the group with chemotherapy alone (95% CI, log-rank test P =0.003. The corresponding overall response rates were 19.3% and 10.2% respectively (P < 0.05 for CT/Bev vs CT. Patients with low NP-1 had statistically significant prolongation of PFS as compared to those with high NP-1 (95% CI, log rank test p= 0.017. Patients with low NP-1 appeared to experience a larger bevacizumab treatment effect in terms of PFS (p=0,049,HR 0.333, 95% CI, 0.111 to 0.995 than patients with high NP-1. Conclusion: The addition of bevacizumab to 5-Fu based chemotherapy improves PFS for patients with metastatic colorectal cancer. Expression of tumor NP-1 is a potential biomarker candidate for prediction of clinical outcome in patients with metastatic colorectal cancer, treated with first line chemotherapy plus bevacizumab.

  13. [Surgical treatment of colorectal carcinoma in the elderly].

    Science.gov (United States)

    Schuld, J; Glanemann, M

    2017-02-01

    Colorectal carcinoma is one of the most frequent tumor entities worldwide. The treatment of elderly and mostly polymorbid patients is an outstanding challenge in view of the demographic change with a continuously aging community. Due to the demographic changes the numbers of elderly (>65 years) and very old (≥80 years) patients are steadily increasing in surgical cohorts. This has resulted in higher morbidity and mortality rates in comparison to younger patients, with increased wound healing and cardiovascular complications but with comparable numbers of anastomotic insufficiency. Multivariate analysis revealed age ≥80 years, higher ASA status and emergency operations as independent risk factors for increased in-hospital mortality. With respect to the localization of colorectal cancer a shift to the right has been observed with increasing patient age. Whether minimally invasive surgical techniques can reduce postoperative morbidity and mortality rates in elderly patients requires further evaluation. Nevertheless, a reduction of both was reported without compromising the oncological result. Elderly patients require individualized treatment modalities, which take the extent of comorbidities and personal environment into consideration. So far, the cohort of octogenarians has not been adequately considered in current guidelines; therefore, geriatric expertise is recommended to be able to make a better assessment of benefit-risk ratios, as age itself has no impact on the decision for therapy.

  14. An Evaluation of Algorithms for Identifying Metastatic Breast, Lung, or Colorectal Cancer in Administrative Claims Data.

    Science.gov (United States)

    Whyte, Joanna L; Engel-Nitz, Nicole M; Teitelbaum, April; Gomez Rey, Gabriel; Kallich, Joel D

    2015-07-01

    Administrative health care claims data are used for epidemiologic, health services, and outcomes cancer research and thus play a significant role in policy. Cancer stage, which is often a major driver of cost and clinical outcomes, is not typically included in claims data. Evaluate algorithms used in a dataset of cancer patients to identify patients with metastatic breast (BC), lung (LC), or colorectal (CRC) cancer using claims data. Clinical data on BC, LC, or CRC patients (between January 1, 2007 and March 31, 2010) were linked to a health care claims database. Inclusion required health plan enrollment ≥3 months before initial cancer diagnosis date. Algorithms were used in the claims database to identify patients' disease status, which was compared with physician-reported metastases. Generic and tumor-specific algorithms were evaluated using ICD-9 codes, varying diagnosis time frames, and including/excluding other tumors. Positive and negative predictive values, sensitivity, and specificity were assessed. The linked databases included 14,480 patients; of whom, 32%, 17%, and 14.2% had metastatic BC, LC, and CRC, respectively, at diagnosis and met inclusion criteria. Nontumor-specific algorithms had lower specificity than tumor-specific algorithms. Tumor-specific algorithms' sensitivity and specificity were 53% and 99% for BC, 55% and 85% for LC, and 59% and 98% for CRC, respectively. Algorithms to distinguish metastatic BC, LC, and CRC from locally advanced disease should use tumor-specific primary cancer codes with 2 claims for the specific primary cancer >30-42 days apart to reduce misclassification. These performed best overall in specificity, positive predictive values, and overall accuracy to identify metastatic cancer in a health care claims database.

  15. Metastatic Carcinoma Occurring in a Gastric Hyperplastic Polyp Mimicking Primary Gastric Cancer: The First Reported Case

    Directory of Open Access Journals (Sweden)

    Gabriel M. Groisman

    2014-01-01

    Full Text Available Hyperplastic polyps of the stomach are regarded as benign. However, in rare cases they may contain incipient primary carcinomas. To our knowledge, breast carcinoma metastatic to a gastric hyperplastic polyp has not yet been reported. We describe the case of a 69-year-old woman to whom a gastric polyp was endoscopically excised. The patient had previously undergone a right mastectomy for mixed, invasive ductal and lobular carcinoma 5 years earlier. Histological sections from the gastric lesion showed typical features of hyperplastic polyp with foci of poorly differentiated adenocarcinoma including signet ring cells infiltrating the lamina propria. The histologic findings were consistent with a primary gastric cancer. However, the carcinoma cells were immunopositive for estrogen and progesterone receptors and GATA3 and negative for CDX2, Hep Par 1, and MUC5AC. E-cadherin showed membranous reactivity in some of the carcinoma cells while in others it was negative. Accordingly, metastatic mixed, lobular and ductal breast carcinoma was diagnosed. We conclude that metastatic adenocarcinoma mimicking primary gastric cancer can be rarely encountered in hyperplastic gastric polyps.

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

    International Nuclear Information System (INIS)

    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. The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1 st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1 st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (≥ 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7–16.2) and 11.3 (95% CI, 10.2–12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4–28.9) and 27.4 (95% CI, 22.7–31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21

  17. Metallic stent placement for the management of acute colorectal obstruction caused by colorectal carcinomas: its effect on scheduled surgery

    International Nuclear Information System (INIS)

    Cao Yan; Liu Bingyan; Mao Aiwu; Yin Xiang; Gao Zhongdu

    2011-01-01

    Objective: To prospectively evaluate the safety and clinical efficacy of a newly designed self-expandable metallic stent (SEMS) placement in the treatment of patients with acute malignant colorectal obstruction due to colorectal carcinomas. Methods: During the period from April 2001 to October 2007, a total of 52 patients with acute malignant colorectal obstruction were treated with stent placement by using a new designed SEMS, which was employed as a preoperative transit means. All the patients were followed up and the relevant data, including technical success rate, clinical efficacy, complications and overall survival rate, were documented. The results were analyzed. Results: Stent placement was successfully carried out in all patients except for two patients who showed complete colorectal obstruction. No procedure-related complications occurred. Technical success rate was 96% (50/52). Two days after the treatment, the relief rate of colorectal obstruction was 98% (49/50). Postoperative complications included stent migration (n=4), anal pain (n=2) and stool impaction (n=1). The stool impaction seen in one patient was successfully removed away with endoscopic manipulation two days after stent placement. An elective one-stage surgical procedure was performed in all 50 patients who successfully received a SEMS placement within a mean interval of (8±2) days (ranged 4-11 days) after stent placement. Mean follow-up time was (36±12) months with a range of (3-70) months. All patients remained alive at the time of this report. Conclusion: The newly designed SEMS placement used as a preoperative transit means is a safe and effective intervention for colonic decompression in patients with acute malignant colorectal obstruction due to colorectal carcinomas. It can reliably ensure most of patients with colorectal carcinomas to successfully accomplish an elective surgery. (authors)

  18. Metastatic nonpalpable invasive lobular breast carcinoma presenting as rectal stenosis: a case report.

    Science.gov (United States)

    Osaku, Tadatoshi; Ogata, Hideaki; Magoshi, Shunsuke; Kubota, Yorichika; Saito, Fumi; Kanazawa, Shinsaku; Kaneko, Hironori

    2015-04-24

    Invasive lobular carcinomas have an increased propensity for distant metastases, particularly to the peritoneum, ovaries, and uterus. In contrast, distant metastases of nonpalpable lobular carcinomas are extremely rare, and the causes of underlying symptoms of primary carcinomas remain unclear. We report a case of an asymptomatic invasive lobular carcinoma with a primary mammary lesion in a patient with rectal stenosis. A 69-year-old Japanese woman presented to our hospital for treatment of constipation. Although rectal stenosis was confirmed, thorough testing of her lower digestive tract did not identify its cause. Thus, an exploratory laparotomy and tissue biopsy was performed, and the presence of an invasive lobular carcinoma was confirmed. Subsequent breast examinations showed that the invasive lobular carcinoma that led to the rectal stenosis was a metastatic lesion from a primary lesion of the breast duct. As the present breast lobular carcinoma was asymptomatic and nonpalpable, we did not initially consider metastatic breast cancer as a cause of her symptoms, and the final diagnosis was delayed. Peritoneal metastasis from nonpalpable invasive lobular carcinomas is very rare. However, breast cancer metastasis should be considered when carcinomatous peritonitis is present in a patient with an unknown primary cancer.

  19. Novel treatment strategies in clear-cell metastatic renal cell carcinoma.

    NARCIS (Netherlands)

    Spronsen, D.J. van; Weijer, K.J.M. de; Mulders, P.F.A.; Mulder, P.H.M. de

    2005-01-01

    Metastatic renal-cell carcinoma (mRCC) is highly resistant to cytotoxic agents or hormones and is currently mainly treated with cytokine-based therapy. Transient responses and moderate survival advantages have been achieved in a subset of patients with these aspecific biological response modifiers.

  20. 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.

  1. Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Penttilä, P; Donskov, F; Rautiola, J

    2017-01-01

    BACKGROUND: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. PATIENTS AND METHODS: Eighty-five mRCC patients received everolimus at Helsinki University...

  2. Treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2

    DEFF Research Database (Denmark)

    Geertsen, P F; Hermann, G G; von der Maase, H

    1992-01-01

    PURPOSE: A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-one patients with RCC were entered onto the study. rIL-2...

  3. 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

    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...... 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...

  4. KRAS-mutated plasma DNA as predictor of outcome from irinotecan monotherapy in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, K G; Appelt, A L; Pallisgaard, N

    2013-01-01

    Background:We investigated the clinical implications of KRAS and BRAF mutations detected in both archival tumor tissue and plasma cell-free DNA in metastatic colorectal cancer patients treated with irinotecan monotherapy.Methods:Two hundred and eleven patients receiving second-line irinotecan (350...... mg m(-2) q3w) were included in two independent cohorts. Plasma was obtained from pretreatment EDTA blood-samples. Mutations were detected in archival tumour and plasma with qPCR methods.Results:Mutation status in tumor did not correlate to efficacy in either cohort, whereas none of the patients...... with mutations detectable in plasma responded to therapy. Response rate and disease control rate in plasma KRAS wt patients were 19 and 66% compared with 0 and 37%, in patients with pKRAS mutations, (P=0.04 and 0.01). Tumor KRAS status was not associated with PFS but with OS in the validation cohort. Plasma BRAF...

  5. Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction

    Science.gov (United States)

    Tsuchihashi, Kenji; Shimokawa, Hozumi; Takayoshi, Kotoe; Nio, Kenta; Aikawa, Tomomi; Matsushita, Yuzo; Wada, Iori; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Sonoda, Koh-Hei; Akashi, Koichi; Baba, Eishi

    2017-01-01

    Abstract Rationale: Regorafenib is effective for metastatic colorectal cancer but its toxicity such as hemorrhage should be considered. The safety of regorafenib for the patient with the liver disease is not known. Patient concerns: Seventy-one-year old man of colon cancer had myodesopsia and blood stool after 14 days from the initiation of regorafenib administration with 50% dose reduction due to liver dysfunction. Diagnoses: Fundus examination revealed hemorrhage of the retinal vein. Interventions: Regorafenib treatment was discontinued and observational therapy was pursued. Outcomes: Retinal and gastrointestinal hemorrhage resolved in 1 week. Lessons: Retinal hemorrhage should be considered as the differential diagnosis of myodesopsia in the patient treated by regorafenib. Safety and pharmacokinetic of continuous regorafenib administration for patients with liver dysfunction remains to be clarified. PMID:29049226

  6. 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 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...... dosing regimen of 250 mg/m(2) (following an initial dose of 400 mg/m(2)) in the treatment of mCRC....

  7. Bevacizumab-Based Therapies in the First-Line Treatment of Metastatic Colorectal Cancer

    Science.gov (United States)

    Hurwitz, Herbert I.

    2012-01-01

    Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a number of different backbone chemotherapy regimens, and its widespread use has introduced several important questions regarding the selection and optimization of bevacizumab-based treatment regimens, its use in various patient populations, and the identification of associated adverse events. This review discusses the results of several phase II and phase III clinical trials, as well as large observational studies, to address the use of bevacizumab in the treatment of patients with mCRC in the first-line setting. PMID:22477726

  8. Circulating free DNA as biomarker and source for mutation detection in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen Lise Garm; Pallisgaard, Niels; Andersen, Rikke Fredslund

    2015-01-01

    this with four cohorts of metastatic colorectal cancer (mCRC) patients. We also investigated the prognostic value of cfDNA and analysed the tumour-specific KRAS mutations in the plasma. METHODS: The study was a prospective biomarker evaluation in four consecutive Phase II trials, including 229 patients.......6-5.9) months, respectively, HR 1.78, p = 0.0006). Multivariate analysis confirmed an independent prognostic value of cfDNA (HR 1.5 (95% CI 1.3-1.7) for each increase in the cfDNA quartile). The overall concordance of KRAS mutations in plasma and tissue was high (85%). CONCLUSIONS: These data confirm...... the prognostic value of cfDNA measurement in plasma and utility for mutation detection with the method presented....

  9. 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

    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 BRAF in plasma and report the changes during third line treatment with cetuximab and irinotecan. One-hundred-and-eight patients received irinotecan 350 mg/m2 q3w and weekly cetuximab (250 mg/m2) until progression (RECIST) or unacceptable toxicity. cfDNA and number of mutated KRAS/BRAF alleles in plasma...... appeared in plasma before radiological evidence of progression. Loss of mutations may explain observed benefit of treatment in primary mutant disease, whereas appearance of mutations during therapy may be responsible for acquired resistance in primary wt disease. Benefit from EGFR MoAbs may be influenced...

  10. 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

    . 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......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......) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44...

  11. Metastatic breast carcinoma in the mandible presenting as a periodontal abscess: a case report

    Directory of Open Access Journals (Sweden)

    Tosios Konstantinos

    2011-07-01

    Full Text Available Abstract Introduction Tumors can metastasize to the oral cavity and affect the jaws, soft tissue and salivary glands. Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Because of their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. The purpose of this report is to present a rare case of a metastatic breast carcinoma mimicking a periodontal abscess in the mandible. Case presentation A 55-year-old Caucasian woman was referred to our clinic for evaluation of bisphosphonate-induced jaw osteonecrosis. She had undergone modified radical mastectomy with axillary lymph node dissection for invasive ductal carcinoma of the left breast. Her clinical examination showed diffuse swelling and a periodontal pocket of 6 mm exhibiting suppuration in the posterior right mandible. Moreover, paresthesia of the lower right lip and chin was noted. There were no significant radiographic findings other than alveolar bone loss due to her periodontal disease. Although the lesion resembled a periodontal abscess, metastatic carcinoma of the breast was suspected on the basis of the patient's medical history. The area was biopsied, and histological analysis confirmed the final diagnosis of metastatic breast carcinoma. Conclusion The general dentist or dental specialist should maintain a high level of suspicion while evaluating patients with a history of cancer. Paresthesias of the lower lip and the chin should be considered ominous signs of metastatic disease. This case highlights the importance of the value of a detailed medical history and thorough clinical examination for the early detection of metastatic tumors in the oral cavity.

  12. Metastatic Clear Cell Renal Cell Carcinoma Presenting with a Gingival Metastasis.

    Science.gov (United States)

    Ali, Rusha A E; Mohamed, Kamal E H

    2016-04-26

    Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation in a clinical trial, should be discussed with the patient despite the poor overall prognosis.

  13. Metastatic clear cell renal cell carcinoma presenting with a gingival metastasis

    Directory of Open Access Journals (Sweden)

    Rusha A.E. Ali

    2016-06-01

    Full Text Available Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation in a clinical trial, should be discussed with the patient despite the poor overall prognosis.

  14. Sunitinib efficacy in the treatment of metastatic skin adnexal carcinomas: report of two patients with hidradenocarcinoma and trichoblastic carcinoma.

    Science.gov (United States)

    Battistella, M; Mateus, C; Lassau, N; Chami, L; Boukoucha, M; Duvillard, P; Cribier, B; Robert, C

    2010-02-01

    Adnexal carcinomas are rare and diverse cutaneous tumours. They are locally aggressive and have the potential for distant metastasis. Metastatic adnexal carcinomas are very resistant to conventional chemotherapies. Sunitinib, an oral tyrosine kinase inhibitor, is reportedly effective for the treatment of various solid cancers. Its use in adnexal carcinomas has never been reported. The first patient had metastatic clear cell hidradenocarcinoma and was stabilized over 8 months with sunitinib, before she relapsed. The second patient had a metastatic malignant hair follicle tumour (trichoblastic carcinoma) and achieved a partial remission with sunitinib, and disease stabilized after 10 months. Dynamic contrast-enhanced ultrasound (DCE-US) performed to evaluate tumour vascularization during treatment depicted a dramatic and early decrease in the tumour blood volume. Sunitinib was effective in controlling the disease in our two patients. DCE-US using linear raw data may have an early predictive value for tumour response to sunitinib. Further studies involving larger cohorts of patients are warranted in order to confirm the efficacy of sunitinib in these rare tumours.

  15. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda Plovmand

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  16. Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer

    Science.gov (United States)

    Prager, Gerald W; Braemswig, Kira H; Martel, Alexandra; Unseld, Matthias; Heinze, Georg; Brodowicz, Thomas; Scheithauer, Werner; Kornek, Gabriela; Zielinski, Christoph C

    2014-01-01

    Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab-based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression-free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab-based treatment cohort was analyzed for specificity assessment of CEA to predict the anti-vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy in patients with mCRC. Previously, we found that CEA induces angiogenesis independent of VEGF. The data presented here now give first evidence that baseline serum CEA levels in patients might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy for metastatic colorectal cancer. PMID:24850362

  17. 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

  18. Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study.

    Directory of Open Access Journals (Sweden)

    Chun-Yu Lin

    Full Text Available Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC patients.We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival.Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015. The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%], fatigue(6[17.6%] vs 7[25.9%], gastrointestinal discomfort (7[20.6%] vs 6[22.2%], neutropenia (4[11.8%] vs 1[3.7%], diarrhea(4[11.8%] vs 1[3.7%], and mucositis(5[14.7%] vs 1[3.7%].The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies.

  19. Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study.

    Science.gov (United States)

    Lin, Chun-Yu; Lin, Tseng-Hsi; Chen, Chou-Chen; Chen, Ming-Cheng; Chen, Chou-Pin

    2018-01-01

    Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC) patients. We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival. Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015). The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%]), fatigue(6[17.6%] vs 7[25.9%]), gastrointestinal discomfort (7[20.6%] vs 6[22.2%]), neutropenia (4[11.8%] vs 1[3.7%]), diarrhea(4[11.8%] vs 1[3.7%]), and mucositis(5[14.7%] vs 1[3.7%]). The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies.

  20. 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

  1. Effectiveness of bevacizumab and cetuximab in metastatic colorectal cancer across selected public hospitals in Queensland.

    Science.gov (United States)

    Chapman, Suzannah J; McKavanagh, Daniel; Burge, Matthew E; McPherson, Ian; Walpole, Euan; Hollingworth, Samantha A

    2017-10-01

    Metastatic colorectal cancer has a large burden of disease in Australia. Medical therapy is fundamental to extending survival and improving quality of life. The benefits of two costly medicines, bevacizumab and cetuximab, used in Australia remain unclear. The aim of this study was to retrospectively examine the use of these two medicines in metastatic colorectal cancer across five public hospitals in south east Queensland and to compare clinical outcomes to those of published clinical trials. We extracted data from the chemotherapy prescribing database for patients planned for bevacizumab or cetuximab therapy between 2009 and 2013. Median overall survival was estimated using Kaplan-Meier methods. There were 490 bevacizumab-containing protocols planned and 292 patients received at least one dose of bevacizumab. Median overall survival was 17.2 months (95% confidence interval [CI], 15.4-19.3). Of 208 planned cetuximab-containing protocols, 134 patients received at least one dose of cetuximab. Median overall survival was 9.1 months (95% CI, 7.6-12.0). Thirty-day mortality rates from date of first dose were 0.7% for bevacizumab and 7.5% for cetuximab. Overall survival of patients receiving bevacizumab and cetuximab was consistent with clinical trials, providing some assurance that benefits seen in trials are observed in usual practice. This study provides a methodology of using routinely collected health data for clinical monitoring and research. Because of the high cost of these medicines and the lack of toxicity data in this study, further analysis in the postmarketing setting should be explored. © 2016 John Wiley & Sons Australia, Ltd.

  2. metastatic carcinoma of the breast with inguinal lymph node

    African Journals Online (AJOL)

    ZINOX

    The University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria. Two Nigerian women, one aged 40 years with an invasive lobular carcinoma of the right breast, and the other aged 48 years with an infiltrating ductal carcinoma of the left breast, presented with metastases to their corresponding inguinal lymph nodes ...

  3. Metastatic Carcinoma Of The BreastWith Inguinal Lymph Node ...

    African Journals Online (AJOL)

    To report two cases of advanced breast carcinoma with metastases to the inguinal lymph nodes in two Nigerian women. The University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria. Two Nigerian women, one aged 40 years with an invasive lobular carcinoma of the right breast, and the other aged 48 yearswith ...

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

    Directory of Open Access Journals (Sweden)

    Seema Kaushal

    2011-01-01

    Full Text Available 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 the shoulder, which did not respond to palliative radiotherapy and rapidly increased in size. Disarticulation of the shoulder joint was performed, which showed anaplastic carcinoma on histopathological examination. Anaplastic transformation of papillary carcinoma at the metastatic sites is well documented in the literature and is rare. However, the same has not been reported at the shoulder and from India before. Although soft tissue sarcomas are most common at this site, however, the possibility of anaplastic transformation should be kept in the differential diagnosis of rapidly enlarging painful mass in a known case of metastatic thyroid carcinoma to prevent misdiagnosis.

  5. Rapidly metastatic carcinoma in lupo in a patient with lupus vulgaris for more than 50 years.

    Science.gov (United States)

    Wulff-Woesten, Andrea; Hildebrandt, Uwe; Leverkus, Martin; Ulrich, Jens

    2010-07-01

    According to current statistics of the WHO, tuberculosis is the infectious disease that causes the most deaths worldwide. Its most common cutaneous manifestation is lupus vulgaris which is seldom diagnosed today. A 69-year old immunocompetent woman complained of a partly elevated, partly sclerotic plaque on her left thigh which had been present for more than 55 years before slowly becoming ulcerated. After biopsy and subsequent excision of the 13 cm ulcer, the diagnosis of carcinoma in lupo with lymph node metastasis was made. Cutaneous and additional nodal metastases appeared rapidly. Tuberculostatic therapy was initiated. Despite systemic chemotherapy the tumor subsequently progressed and the patient died of metastatic carcinoma in lupo 15 months after the initial diagnosis. Early diagnosis and treatment of lupus vulgaris might have prevented the development of carcinoma in lupo and ensuing metastatic death of the patient.

  6. Targeting Angiogenesis and Tumor Microenvironment in Metastatic Colorectal Cancer: Role of Aflibercept

    Directory of Open Access Journals (Sweden)

    Guido Giordano

    2014-01-01

    Full Text Available In the last decades, we have progressively observed an improvement in therapeutic options for metastatic colorectal cancer (mCRC treatment with a progressive prolongation of survival. mCRC prognosis still remains poor with low percentage of 5-year survival. Targeted agents have improved results obtained with standard chemotherapy. Angiogenesis plays a crucial role in colorectal cancer growth, proliferation, and metastasization and it has been investigated as a potential target for mCRC treatment. Accordingly, novel antiangiogenic targeted agents bevacizumab, regorafenib, and aflibercept have been approved for mCRC treatment as the result of several phase III randomized trials. The development of a tumor permissive microenvironment via the aberrant expression by tumor cells of paracrine factors alters the tumor-stroma interactions inducing an expansion of proangiogenic signals. Recently, the VELOUR study showed that addition of aflibercept to FOLFIRI regimen as a second-line therapy for mCRC improved significantly OS, PFS, and RR. This molecule represents a valid second-line therapeutic option and its peculiar ability to interfere with placental growth factor (PlGF/vascular endothelial growth factor receptor 1 (VEGFR1 axis makes it effective in targeting angiogenesis, inflammatory cells and in overcoming resistances to anti-angiogenic first-line treatment. Here, we discuss about Aflibercept peculiar ability to interfere with tumor microenvironment and angiogenic pathway.

  7. Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Yoojoo Lim

    Full Text Available Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear.Tumor attenuation as measured by Hounsfield units (HU in contrast-enhanced computed tomography (CT and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80 treated with regorafenib in a prospective study.141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5%-20.7%. Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson's r = 0.37, p = 0.002. Among 53 patients with lung metastases, 17 (32.1% developed cavitary changes. There were no differences in disease control rate, progression-free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50 and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13.Regorafenib showed prominent anti-angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies.

  8. Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer

    Science.gov (United States)

    Yoon, Jeong Hee; Lee, Jeong Min; Lee, Jung Min; Paeng, Jin Chul; Won, Jae-Kyung; Kang, Gyeong Hoon; Jeong, Seung-Yong; Park, Kyu Joo; Lee, Kyung-Hun; Kim, Jee Hyun; Kim, Tae-You

    2015-01-01

    Background Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear. Methods Tumor attenuation as measured by Hounsfield units (HU) in contrast-enhanced computed tomography (CT) and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80) treated with regorafenib in a prospective study. Results 141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5%–20.7%). Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson’s r = 0.37, p = 0.002). Among 53 patients with lung metastases, 17 (32.1%) developed cavitary changes. There were no differences in disease control rate, progression-free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD) according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50) and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13). Conclusion Regorafenib showed prominent anti-angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies. PMID:26671465

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

    Directory of Open Access Journals (Sweden)

    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

  10. Deficient Mismatch Repair and the Role of Immunotherapy in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Quiroga, Dionisia; Lyerly, H Kim; Morse, Michael A

    2016-08-01

    Division of colorectal cancers (CRCs) into molecular subsets yields important consequences for prognosis and therapeutic response. The microsatellite instability (MSI) immune subgroup, accounting for 15 % of early-stage and 3 % of metastatic CRCs, are a result of deficient cellular DNA mismatch repair (dMMR) mechanisms. dMMR CRCs are notable for greater survivability, yet lack of benefit from fluoropyrimidine-based therapy in early-stage disease as compared to proficient DNA mismatch repair (pMMR) CRCs but are substantially lethal when metastatic. The surging interest in cancer immunotherapy, particularly checkpoint blockade, has further led to a focus on MSI tumors, which are notable for their substantial T cell infiltrate. In this review, we will discuss the biologic underpinnings for the immunogenicity of dMMR CRC and the preclinical development of therapies intended to modulate this immune response. Next, we will discuss the previous and ongoing clinical trials specifically designed to evaluate immunotherapeutic treatment of dMMR CRCs. Building on the success of the early immune checkpoint inhibitor clinical trials for dMMR CRC, combinations with other anti-tumor immunotherapies may provide an even more robust response, thereby, creating an alternative treatment regimen for those who have failed standard therapies or possibly resulting in prophylactic therapies for patients with highly oncogenic hereditary mismatch repair deficiencies.

  11. Risk factors for brain metastases in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Troels Dreier; Palshof, Jesper Andreas; Larsen, Finn Ole

    2017-01-01

    BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict......, the risk of developing BM was significantly increased in patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2; 95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases were significantly...... associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the investigated mutations were associated with BM. CONCLUSION: The incidence of BM was 8.8% in patients with mCRC who received third-line therapy. The most important risk factor for developing BM was lung metastases. Furthermore, rectal cancer...

  12. Prognostic values of matrix metalloproteinase family expression in human colorectal carcinoma.

    Science.gov (United States)

    Asano, Toshimichi; Tada, Mitsuhiro; Cheng, Shaoqiang; Takemoto, Norihiro; Kuramae, Taro; Abe, Motoki; Takahashi, Osamu; Miyamoto, Masaki; Hamada, Jun-Ichi; Moriuchi, Tetsuya; Kondo, Satoshi

    2008-05-01

    We examined expression patterns of matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in colorectal cancer tissues to assess their prognostic significance. mRNA expressions of 17 MMPs, 4 TIMPs, and RECK were measured in 112 colorectal cancerous tissues, 20 normal mucosa tissues, and 11 metastatic liver lesions by real-time reverse-transcriptional-polymerase chain reaction. The protein level expressions were confirmed with immunohistochemistry. Cancers and normal mucosa displayed highly significant differences (P matrix degrading (which is characteristic of colorectal cancers) and its role in metastasis.

  13. Metastatic papillary carcinoma of the thyroid in a patient previously ...

    African Journals Online (AJOL)

    ... the patient was referred to our nuclear medicine department with a clinical diagnosis of suspected metastatic lymph nodes presumably from a thyroid malignancy.She had an 123I diagnostic whole body scan that showed 123I avid areas in the thyroid bed as well as left cervical lymph nodes, which later turned out to be.

  14. Breast carcinoma following radiotherapy of metastatic Wilms' tumor

    International Nuclear Information System (INIS)

    Reimer, R.R.; Fraumeni, J.F. Jr.; Reddick, R.; Moorhead, E.L. II.

    1977-01-01

    A 22-year-old woman developed breast cancer 15 years after radiotherapy to the lung for metastatic Wilms' tumor. Her 32-year-old mother died of bilateral breast cancer, suggesting a genetic predisposition to radiogenic cancer. Recent improvements in the survival of children with certain cancers necessitate long-term surveillance for iatrogenic neoplasia, particularly when familial susceptibility is evident

  15. 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).......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)....

  16. Colorectal liver metastases are more often super wild type. Toward treatment based on metastatic site genotyping?

    Science.gov (United States)

    Allard, M A; Saffroy, R; de la Maisonneuve, P Bouvet; Ricca, L; Bosselut, N; Hamelin, J; Lecorche, E; Bejarano, M A; Innominato, P; Sebagh, M; Adam, R; Morère, J F; Lemoine, A

    2015-09-01

    Recent data showed that metastatic colorectal (mCRC) tumors exhibiting extended RAS-BRAF mutations were resistant to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, making these drugs suitable for the so-called "super" wild-type (WT) patients only. This study aimed to compare the extended RAS-BRAF mutation frequency and characteristics according to location of tumor sampling. All consecutive mCRC specimens (N = 1659) referred to our institution from January 2008 till June 2014 were included in the analysis. Tumor genotyping (first for KRAS exon 2, then for BRAF exon 15, and later for KRAS exons 2, 3, and 4 and NRAS exons 2, 3, and 4) was performed with high-resolution melting analysis or allelic discrimination. The factors predicting for the presence of mutation were explored using multivariate binary logistic regression. Overall, the prevalence of KRAS exon 2 was 36.8%, and it was lower in liver metastases (N = 138/490; 28.2%) in comparison with primary tumors (N = 442/1086; 40.7%), lung metastases (16/32; 50%), or other metastatic sites (15/51; 29.4%; P < 0.0001). Similarly, in the 1428 samples analyzed, BRAF mutations were less often found in liver metastases (N = 9/396; 2.3%) as compared to primary tumors (N = 79/959; 8.2%), lung metastases (N = 2/29; 6.9%), or other metastatic locations (N = 2/44; 4.5%; P < 0.0002). Overall occurrence of extended RAS mutation was 51.7%. Of the 503 samples tested, the prevalence of extended RAS-BRAF mutations was twice as low in liver metastases (N = 53/151; 34.2 %) as compared to primary tumors (N = 191/322; 59.3%, P < 0.0001). Univariate analysis identified age ≤65 years, male gender, and liver localization as predictors of super WT status. At multivariate analysis, only liver metastases were retained (RR 2.85 [95% CI 1.91-4.30]). Colorectal liver metastases are twice as likely to exhibit a super WT genotype as compared to other tumor locations

  17. A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Glimelius, B; Lahn, M; Gawande, S

    2010-01-01

    BACKGROUND: Preclinically, protein kinase C and AKT activation can be inhibited by enzastaurin and reduce tumor growth of colorectal cancer cells. In asymptomatic patients with metastatic colorectal cancer (mCRC), enzastaurin activity was evaluated by measuring the 6-month progression-free survival...... cycles. Progression was assessed on the basis of radiographic imaging, rise in carcinoembryonic antigen or lactate dehydrogenase (LDH) levels or by appearance of clinical symptoms. RESULTS: Twenty-eight patients received daily enzastaurin. The 6-month PFS rate was 28% [95% confidence interval (CI) 13...

  18. Malignant Mesothelioma Versus Metastatic Carcinoma of the Pleura: A CT Challenge

    International Nuclear Information System (INIS)

    Bakhshayesh Karam, Mehrdad; Karimi, Shirin; Mosadegh, Leila; Chaibakhsh, Samira

    2016-01-01

    Malignant pleural mesothelioma (MPM) is a rare malignant neoplasm of the pleura that typically affects individuals occupationally exposed to asbestos through a variety of industries. MPM presents with several CT features similar to more common pleural diseases such as metastatic pleural malignancy. The aim of this study is to differentiate malignant pleural mesothelioma from metastatic carcinoma of the pleura by pathological and radiological assessment in order to investigate accuracy of CT scan in this regard and to compare CT features of these two malignancies. Chest CT scans of 55 pleural malignancy patients including MPM and metastatic pleural malignancy were evaluated in this retrospective study. The pathologist made the definite diagnosis based on immunohistochemistry. A chest radiologist unaware of the pathology diagnosis observed all CT scans. Several parameters including pleural thickening, pleural effusion, thickening of inter lobar fissure, contralateral extension, contraction of involved hemithorax, parenchymal involvement (infiltration, nodules, fibrosis), pleural mediastinal involvement, lymphadenopathy, extrapleural invasion (hepatic, chest wall, diaphragm, intraperitoneal), and pericardial involvement were checked. Data analysis was carried out using SPSS version 16, and the ability of CT scan to differentiate malignant pleural mesothelioma and metastatic pleural diseases was investigated. Totally 29 males and 26 females were assessed in this study. Based on pathology, 17 MPM and 38 metastatic pleural malignancies were diagnosed. According to CT study, about 82% of the patients with MPM and about 79% of the patients with metastatic pleural diseases were correctly diagnosed by a radiologist. The most common findings suggestive of MPM were pleural thickening (88.2%), loculated effusion (58.8%), and thickening of the interlobar fissure (47.1%). Whereas free pleural effusion (71.7%), parenchymal infiltration (65.8%) and pleural thickening (63.2%) were

  19. Diagnostic value of carcinoembryonic antigen and carcinoma antigen 19-9 for colorectal carcinoma.

    Science.gov (United States)

    Zhang, Shi-Yan; Lin, Min; Zhang, Hui-Bing

    2015-01-01

    The purpose of this study was to evaluate the diagnostic efficiency of colorectal carcinoma (CRC) with the tumor markers Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA 19-9), in addition to investigating whether CA 19-9 can be used to screen the disease process in patients with CRC who had no elevation of CEA levels. Serum levels of CEA and CA 19-9 were measured in: 138 patients with CRC; 111 patients with benign colorectal diseases. The diagnostic value was performed using the logistic regression equation and receiver operating characteristic curves (ROC). The serum levels of CEA and CA 19-9 in the patients with CRC were significantly higher than those in the patients with benign colorectal diseases (P < 0.001). Receiver operating characteristic curves (ROC) in the patients with CRC versus those with benign colorectal disease yielded the optimal cut-off value of 3.36 ng/ml for CEA and 23.9 U/ml for CA 19-9, respectively. The area under ROC curve (AUC) was 0.789 for CEA, 0.690 for CA 19-9 and 0.900 for the combination of the two tumor markers. The combination resulted in a higher Youden index and a sensitivity of 85.3%. The combined detection of serum CEA and CA 19-9 could play a pivotal role in the diagnosis of CRC, and could drastically improve the sensitivity for the diagnosis of CRC. CA 19-9 might be a tumor biomarker in addition to CEA for CRC.

  20. A Favorable Response to Levetiracetam in a Patient with Metastatic Adenoid Cystic Carcinoma.

    Science.gov (United States)

    Sakata, Shinya; Saeki, Sho; Terasaki, Yasuhiro; Natori, Yoshihiro; Fujii, Kazuhiko

    2018-03-01

    Adenoid cystic carcinoma (ACC) is a rare cancer, and there are no standard-of-care treatments for patients with metastatic ACC. We herein report a patient with lung metastasis of ACC who achieved a favorable response to levetiracetam. A 52-year-old Japanese man was admitted to our hospital because of multiple lung metastases of ACC. We performed first-line chemotherapy with cisplatin plus gemcitabine, and subsequently oral S-1 as second-line chemotherapy, which resulted in disease progression. The patient developed symptomatic epilepsy and received levetiracetam (250 mg twice daily). At five months after the initiation of levetiracetam, chest computed tomography showed regression of the metastatic lung lesions.

  1. Radiation therapy of a metastatic tumour of the orbit caused by prostatic carcinoma

    International Nuclear Information System (INIS)

    Daniel, F.; Langmann, G.; Faulborn, J.; Poschauko, J.

    1994-01-01

    We report a case of metastatic carcinoma to the apex of the orbit in a 66-year old patient. Orbital metastasis occurred while the patient suffered from another metastatic activity especially in his bony structures. The orbital tumour caused rapid visual impairment because of compression of the optic nerve. The metastasis was treated by radiation therapy. With CT-scan, electrophysiological examination, visual field examination, and visual function we demonstrate the regression of the tumour. One year after therapy the tumor was no longer detectable. Visual function had recovered and visual fields were normally. Radiation therapy prolonged high quality life for our patient due to preservation of visual function. (authors)

  2. 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.

  3. Metastatic cervical carcinoma of the jaw presenting as periapical disease.

    Science.gov (United States)

    Torregrossa, V R; Faria, K M; Bicudo, M M; Vargas, P A; Almeida, O P; Lopes, M A; Santos-Silva, A R

    2016-02-01

    To present a case report of a metastasis from cervical cancer to the maxilla, which was misdiagnosed as periapical disease and to caution clinicians that metastases could have a disguised clinical presentation that must be taken into account in the differential diagnosis of periapical disease in oncologic patients. Although metastatic tumours of the jaws are uncommon, they may mimic benign inflammatory processes and reactive lesions. The ability of metastatic lesions to mimic periapical disease is discussed and a brief review of the literature is presented, emphasizing the importance of correct diagnosis to prevent delay in diagnosing cancer. Attention should therefore be given to the patient's medical history, especially of those with a previous history of cancer, and all dental practitioners should be aware of the possibility of metastases that may be confused with periapical disease. Finally, endodontists are well placed to recognize malignant and metastatic oral lesions during the initial clinical stages, given that their treatments are usually based on frequent dental appointments and long-term follow-ups. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  4. A Systematic Review and Meta-analysis of Retrospective Series of Regorafenib for Treatment of Metastatic Colorectal Cancer.

    Science.gov (United States)

    Mercier, Joey; Voutsadakis, Ioannis A

    2017-11-01

    Metastatic colorectal cancer is a common disease encountered in oncology practice and treatment options beyond fluoropyrimidines, irinotecan, oxaliplatin and monoclonal antibodies against epidermal growth factor receptor and vascular endothelium growth factor (VEGF) are limited. Regorafenib, a new drug that targets tyrosine kinases such as VEGF receptor as well as others, has been added recently to the armamentarium for metastatic colorectal cancer. This report analyzes the published experience with this drug in clinical practice outside of clinical trials. A literature search of major databases was performed for the identification of studies of regorafenib in metastatic colorectal cancer. Studies retained for further analysis were in English or French, describing 20 or more patients treated with regorafenib monotherapy and not part of a phase I, II or III trial. Results of the pooled analysis of retrospective studies were compared with results of the published phase III trials and a phase IIIb prospective study. Twelve publications including a total of 702 patients were included in the meta-analysis. Summary response rate was 2% [95% confidence interval (CI) =0.8-3.2%] and the disease control rate 38.14% (95% CI=32.35-43.93%). Summary survival rates were 3.34 months (95% CI=2.71-3.97 months) for progression-free and 7.27 months (95% CI=6.23-8.3 months) for overall survival. These were similar to the phase III and IIIb studies. Most common adverse effects were also consistent with those of the published phase III experience. This systematic review and meta-analysis confirmed a moderate efficacy of regorafenib in later-stage metastatic colorectal cancer in the everyday clinical practice setting outside of clinical trials. Future identification of biomarkers may aid in further tailoring of this treatment in order to obtain maximum clinical benefit. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Ocoxin oral solution? as a complement to irinotecan chemotherapy in the metastatic progression of colorectal cancer to the liver

    OpenAIRE

    Hernandez-Unzueta, Iera; Benedicto, Aitor; Olaso, Elvira; Sanz, Eduardo; Viera, Cristina; Arteta, Beatriz; M?rquez, Joana

    2017-01-01

    Colorectal cancer (CRC) is an aggressive disease in which patients usually die due to its metastatic progression to the liver. Up to date, irinotecan is one of the most used chemotherapeutic agents to treat CRC metastasis with demonstrated efficacy. However, the severity of the side effects constitute the main limitation to its use in the treatment. Consequently, new complementary therapies are being developed to avoid these adverse effects while maintaining the efficacy of the antitumoral dr...

  6. Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer

    Science.gov (United States)

    2005-07-01

    AD Award Number: DAMD17-03-1-0487 TITLE: Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer... Borras -Cuesta, F., and Lasarte, J. J. CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN- gamma-dependent

  7. 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....

  8. Identification of extracapsular invasion of the metastatic lymph nodes as a useful prognostic sign in patients with resectable colorectal cancer.

    Science.gov (United States)

    Komuta, K; Okudaira, S; Haraguchi, M; Furui, J; Kanematsu, T

    2001-12-01

    The present study was undertaken to evaluate whether the microscopic patterns of distribution and extracapsular invasion of cancer cells in the regional lymph nodes were linked to the survival rates for patients with advanced colorectal cancer who undergo a curative surgical resection. Two hundred ninety-six surgically resected metastatic lymph nodes from 84 patients with node-positive colorectal cancer were microscopically examined. The distribution of cancer cells in the lymph nodes were grouped into two types: type A (> or =50 percent cancer) and type B (cancer). The extracapsular invasion of cancer cells in the nodes were divided into three subgroups: pattern X (no evidence of cancer cell invasion into the adjacent tissue); pattern Y (less than five cancer cells were seen in the adjacent tissue); and pattern Z (more than five cancer cells invaded the adjacent tissue). The patients, based on these microscopic manifestations of metastatic patterns in the nodes, were divided into three groups: Group 1, patients with pattern X nodal metastases only; Group 2, patients with pattern Y and pattern (X + Y) nodal metastases; and Group 3, patients with pattern Z, pattern (X + Z), pattern (Y + Z), and pattern (X + Y + Z) nodal metastases. The survival rates and disease-free survival rates for patients with metastatic lymph nodes showing an extracapsular invasion pattern (Groups 2 and 3) were significantly worse than those for patients with metastatic nodes showing no extracapsular invasion pattern only (Group 1; P thesis of this article that the identification of extracapsular invasion of the metastatic lymph nodes can be taken as a useful prognostic sign in patients with resectable colorectal cancer.

  9. 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.

  10. New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy.

    Science.gov (United States)

    Zarrabi, Kevin; Fang, Chunhui; Wu, Shenhong

    2017-02-02

    Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

  11. New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy

    Directory of Open Access Journals (Sweden)

    Kevin Zarrabi

    2017-02-01

    Full Text Available Abstract Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

  12. Lack of Caudal-Type Homeobox Transcription Factor 2 Expression as a Prognostic Biomarker in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Zhang, Ben Y; Jones, Jeremy C; Briggler, Andrew M; Hubbard, Joleen M; Kipp, Benjamin R; Sargent, Daniel J; Dixon, Jesse G; Grothey, Axel

    2017-06-01

    Although the lack of CDX2 expression has recently been proposed as a potential biomarker for a high risk of relapse in patients with stage II and III colon cancer after complete surgical resection, its prognostic role in metastatic colorectal cancer (CRC) remains unclear and warrants investigation. We identified 145 patients treated at our institution from 2006 to 2016, including 66 patients with CDX2-negative metastatic CRC and a comparison cohort of 79 patients with CDX2-positive metastatic CRC. Overall survival (OS) and progression-free survival (PFS) for first-line systemic therapy were estimated using the Kaplan-Meier method. The associations of CDX2 expression with survival were evaluated using Cox proportional hazards regression models. The prevalence of absent CDX2 expression in our cohort was 5.6%. Patients with CDX2-negative metastatic CRC were significantly more likely to be female, and to have right-sided primary tumors, poorly differentiated histologic features, and distant lymph node metastasis. The median OS for patients with CDX2-negative and -positive metastatic CRC was 8 and 39 months, respectively (hazard ratio [HR], 4.04; 95% confidence interval [CI], 2.49-6.54; P lack of CDX2 expression and OS remained statistically significant (HR, 4.52; 95% CI, 2.50-8.17; P lack of CDX2 expression in metastatic CRC is an adverse prognostic feature and a potential negative predictor of the response to chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer.

    Science.gov (United States)

    Mármol, Inés; Sánchez-de-Diego, Cristina; Pradilla Dieste, Alberto; Cerrada, Elena; Rodriguez Yoldi, María Jesús

    2017-01-19

    Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli . CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%); inherited (5%) and familial (25%). The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53), and mutations; in particular, genes such as c-MYC, KRAS , BRAF , PIK3CA , PTEN , SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined with

  14. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Inés Mármol

    2017-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%–5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli. CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%; inherited (5% and familial (25%. The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN, microsatellite instability (MSI and CpG island methylator phenotype (CIMP. Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53, and mutations; in particular, genes such as c-MYC, KRAS, BRAF, PIK3CA, PTEN, SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined

  15. Immunohistochemistry expression of TCF4 protein on carcinoma, adenoma and non neoplastic colorectal mucosa

    Directory of Open Access Journals (Sweden)

    Leonardo Huber Tauil

    2014-01-01

    Full Text Available Purpose: To detect and quantify the immunoreactivity of TCF4 protein in colorectal carci- noma, colorectal adenoma and non-neoplasic colorectal epithelium. Methods: We studied 129 individuals: 40 with colorectal cancer, 52 with colorectal ad- enoma and 37 with non-neoplastic colorectal epithelium. The colorectal adenoma and carcinoma samples were obtained from patients who underwent surgical procedures, and colonoscopies and samples of non-neoplastic colorectal epithelium were taken from patients who died from cardiovascular diseases, without diseases of the large intestine. Samples of different tissues were included in paraffin blocks, and the immunohistochem- ical expression of protein TCF4 was analyzed using the technique of tissue microarray (TMA with polyclonal antibody TCF4. The immunoreactivity was analyzed and classified as positive and negative. Results: The immunohistochemical expression of TCF4 protein was significantly higher (p < 0.01 in colorectal carcinoma than in the non-neoplastic colorectal epithelium and adenoma. There was no difference (p = 0.76 between TCF4 protein immunohistochemical expression in colorectal adenoma and non-neoplastic colorectal tissue. Conclusions: TCF4 protein showed a more intense expression in colorectal carcinoma than in non-neoplastic colorectal epithelium and adenoma, indicating that this protein is in- volved in colorectal carcinogenesis. Resumo: Objetivos: Detectar e quantificar a imunoexpressão da proteína TCF4 no carcinoma e no adenoma colorretal e no epitélio colorretal não neoplásico. Método: Foram estudados 129 indivíduos: 40 com carcinoma colorretal, 52 com adenoma colorretal e 37 com epitélio colorretal não neoplásico. Os tecidos de adenoma e carcinoma colorretais foram representados por amostras da lesão retirada de doentes submetidos a procedimentos cirúrgicos e colonoscópicos, e as amostras de epitélio colorretal não neo- plásico foram retiradas de doentes falecidos por

  16. Reactive Hypertrophy of an Accessory Spleen Mimicking Tumour Recurrence of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Christin Tjaden

    2011-01-01

    Full Text Available De novo occurrence of an accessory spleen after splenectomy is worth noting for two reasons. First, it is known that splenectomy can cause reactive hypertrophy of initially inactive and macroscopically invisible splenic tissue. Second, it can mimic tumour recurrence in situations in which splenectomy has been performed for oncological reasons. This might cause difficulties in differential diagnosis and the clinical decision for reoperation. We report the case of a patient with suspected recurrence of renal cell carcinoma after total pancreatectomy and splenectomy for metastatic renal cell carcinoma, which finally revealed an accessory spleen as the morphological correlate of the newly diagnosed mass in the left retroperitoneum.

  17. Metastatic Transitional Cell Carcinoma of the Bladder to the Testis: A Case Report

    Directory of Open Access Journals (Sweden)

    Gregory N. Kozak

    2012-01-01

    Full Text Available An 84-year-old gentleman presented with onset of gross hematuria in September 2010. Follow-up investigations revealed T1 superficially invasive, poorly differentiated, papillary urothelial carcinoma. He subsequently had GreenLight laser for BPH and bladder neck contracture on two occasions. He developed a right hydrocele 16 months after initial presentation and during his hydrocelectomy, a rock-hard right epididymis and testicle were discovered. Pathology revealed metastatic urothelial carcinoma replacing nearly the entire testis with lymphovascular invasion.

  18. Oophorectomy versus radiation ablation of ovarian function in patients with metastatic carcinoma of the breast

    International Nuclear Information System (INIS)

    Lees, A.W.; Giuffre, C.; Burns, P.E.; Hurlburt, M.E.; Jenkins, H.J.

    1980-01-01

    A retrospective study of two methods of ovarian ablation as primary therapy for metastatic carcinoma of the breast was carried out using records from this cancer institute. Sixty-one radiation and 97 surgical ovarian ablations, performed from 1972 to 1977, were assessed. Over-all response was similar for the surgical and irradiation groups. Survival from the time of ovarian ablation was greater in both groups in those who responded positively than in those who did not. Factors other than estrogen receptor status can determine the response of patients with metastatic carcinoma of the breast to ovarian ablation. The results indicate that clinical determinates and not the efficiency of one method over the other should be the main criteria for choosing between ovarian ablation by irradiation or by oophorectomy

  19. Rescue chemotherapy using multidrug chronomodulated hepatic arterial infusion for patients with heavily pretreated metastatic colorectal cancer.

    Science.gov (United States)

    Bouchahda, Mohamed; Adam, René; Giacchetti, Sylvie; Castaing, Denis; Brezault-Bonnet, Catherine; Hauteville, Dominique; Innominato, Pasquale F; Focan, Christian; Machover, David; Lévi, Francis

    2009-11-01

    : Hepatic arterial infusion (HAI) chemotherapy delivers a high concentration of drugs both to liver metastases and to healthy liver with specific, limiting, hepatobiliary toxicities. Relevant detoxification and cellular proliferation pathways are controlled by the molecular circadian clock in normal liver but not in advanced tumors. In this article, the authors report their experience with chronomodulated HAI chemotherapy as rescue therapy in heavily pretreated patients who had metastatic colorectal cancer. : Data from all consecutive patients with colorectal cancer liver metastases who received HAI with chronomodulated, multidrug chemotherapy regimens in the authors' center after failure on standard chemotherapy were reviewed for efficacy and safety. : Twenty-nine patients were treated, including 76% with liver metastasis only and 24% with liver and lung metastases. Seventy-five percent of patients had received > or =3 chemotherapy lines, including intravenous, chronomodulated chemotherapy in 59% of patients. Patients received a median of 4 HAI courses (range, 1-9 courses). The most frequent grade (according to National Cancer Institute of Canada Common Toxicity Criteria [version 3]) 3 and 4 nonhematologic toxicities were vomiting, diarrhea, abdominal pain, and fatigue. No severe hematologic or hepatic toxicities and no chemical cholangitis were reported. An objective tumor response was observed in 10 patients (34.5%), including 4 patients who subsequently underwent R0 or R1 hepatic resection. The median progression-free survival and overall survival were 4.5 months (95% confidence limits, 2.4-6.5 months) and 18 months (95% confidence limits, 5.8-30.2 months), respectively. : HAI chronomodulated chemotherapy had well tolerated activity in selected, heavily pretreated patients, and the authors believe it deserves to be assessed prospectively in clinical trials among patients who have less advanced disease. Cancer 2009. (c) 2009 American Cancer Society.

  20. 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

  1. Clinicopathological risk factors of early carcinoma in colorectal neoplasias according to Japanese and Western criteria.

    Science.gov (United States)

    Cha, Jae Myung; Lee, Joung Il; Joo, Kwang Ro; Shin, Hyun Phil; Park, Jae Jun; Jeun, Jung Won; Lim, Jun Uk

    2015-01-01

    There are discrepancies in the classification of early carcinoma in colorectal neoplasia between Japanese and Western criteria. However, no studies have investigated the clinicopathological risk factors associated with early carcinoma according to these criteria. We compared the clinicopathological risk factors of early carcinoma with those of dysplasia, and used multivariate analysis to elucidate the independent risk factors associated with early carcinoma. Lesions with severe cytologic or architectural changes confined to the mucosa are classified as carcinoma in Japanese criteria and as high grade dysplasia (HGD) in Western criteria. Pathologically, 625 total patients were diagnosed with low grade dysplasia (n=321), HGD (n=244), intramucosal carcinoma (n=35) or submucosal carcinoma (n=25). In multivariate analysis, age, large lesion size, and non-polypoid appearance were associated with carcinoma in Japanese criteria; however, only large lesion size was associated with carcinoma in Western criteria. The clinicopathological characteristics of intramucosal carcinoma were similar to those of submucosal carcinoma rather than HGD. The clinicopathological characteristics for early carcinoma were not identical between Japanese and Western criteria. Japanese criteria classifying intramucosal carcinoma as carcinoma rather than HGD may be supported by our findings.

  2. The CEA−/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells

    Science.gov (United States)

    Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

    2016-01-01

    Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA−/lo) levels of CEA. Our findings show that the abundance of CEA−/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA−/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA−/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA−/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA−/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA−/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies. PMID:27813496

  3. Full Length Article Role of glypican-3 immunocytochemistry in differentiating hepatocellular carcinoma from metastatic carcinoma of the liver utilizing fine needle aspiration cytology

    International Nuclear Information System (INIS)

    Zaakook, M.; Abu Sinna, E.; Ayoub, M.; El-Sheikh, S.

    2013-01-01

    Purpose: Evaluation of the sensitivity and specificity of glypican3 (GPC3) in differentiating hepatocellular carcinoma (HCC) from metastatic carcinomas of the liver in cell block material. Patients and methods: Sixty cell blocks were prepared from liver FNAs performed in the radiodiagnosis department, National Cancer Institute, in the period between August 2011 and May 2012. Cases diagnosed as hepatocellular carcinoma, or metastatic carcinoma were included in the study. Cell block sections were stained with anti GPC-3. Sensitivity, specificity, and positive and negative predictive values, of GPC3 were calculated. The final diagnosis was based on the triple approach of clinical data, radiological findings, as well as cytomorphologic features aided by GPC-3 results. Results: 70% of cases were diagnosed as HCC, and 30% as metastatic carcinomas. 95.2% of HCC cases expressed GPC3. Poorly differentiated cases showed the highest GPC3 sensitivity (100%), followed by moderately differentiated cases (96.5%), while well differentiated cases expressed GPC3 in 90% of cases. 83.3% of metastatic carcinomas were negative for GPC3. In this study, sensitivity of GPC-3 in HCC was 95.2%, specificity was 83.3%, positive and negative predictive values were 93% and 88.2% respectively, and total accuracy was 91.7%. Conclusion: Immunocytochemical staining for GPC3 in cell block material is a highly sensitive and specific method capable of distinguishing HCC from the vast majority of metastatic carcinomas of the liver

  4. Histopathological and immunohistochemical findings of primary and metastatic medullary thyroid carcinoma in a young dog.

    Science.gov (United States)

    Piñeyro, Pablo; Vieson, Miranda D; Ramos-Vara, José A; Moon-Larson, Martha; Saunders, Geoffrey

    2014-01-01

    This report describes the gross, histological, and immunohistochemical features of medullary thyroid carcinoma (MTC) with pulmonary metastases in a young dog. Sheets of pleomorphic cells supported by fibrous stroma characterized the primary mass, while metastatic nodules had a neuroendocrine pattern. Despite differing histologic features, all masses showed marked immunoreactivity against calcitonin and multiple neuroendocrine markers consistent with MTC. Although MTC is a well-recognized entity, it may be difficult to distinguish this mass from other thyroid neoplasms, necessitating immunohistochemical characterization.

  5. Histopathological and immunohistochemical findings of primary and metastatic medullary thyroid carcinoma in a young dog

    OpenAIRE

    Piñeyro, Pablo; Vieson, Miranda D.; Ramos-Vara, José A.; Moon-Larson, Martha; Saunders, Geoffrey

    2014-01-01

    This report describes the gross, histological, and immunohistochemical features of medullary thyroid carcinoma (MTC) with pulmonary metastases in a young dog. Sheets of pleomorphic cells supported by fibrous stroma characterized the primary mass, while metastatic nodules had a neuroendocrine pattern. Despite differing histologic features, all masses showed marked immunoreactivity against calcitonin and multiple neuroendocrine markers consistent with MTC. Although MTC is a well-recognized enti...

  6. Metastatic Signet-Ring Cell Gastric Carcinoma Masquerading as Breast Primary

    Directory of Open Access Journals (Sweden)

    Dinesh Chandra Doval

    2009-03-01

    Full Text Available Metastasis to the breast from an extra-mammary primary is a rare phenomenon; metastasis from gastric carcinoma to the breast is extremely so. We report a case who initially presented as mucin-secreting and signet-ring cell tumor of the ovary, and after an interval of 8 months with breast and chest wall metastatic nodules. The covert gastric primary eluded the oncologists at both presentations.

  7. Positive indium-III bone marrow scan in metastatic breast carcinoma. Case report

    International Nuclear Information System (INIS)

    LaManna, M.M.; Hyzinski, M.; Swami, V.K.; Parker, J.A.

    1984-01-01

    Indium is generally presumed to localize in the bone marrow within the erythroid cell line. Fibrosis, inflammation, lymphoma, extended field radiation, chemotherapy, or combinations of both treatment modalities generally depress the uptake of indium by the marrow in a complex fashion. We report a case of metastatic breast carcinoma and pancytopenia in which the In-111 scan appeared qualitatively similar to a Tc-99m MDP bone scan. Findings were confirmed by bone marrow biopsy

  8. New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells

    International Nuclear Information System (INIS)

    Cen, Ling; Hutzen, Brian; Ball, Sarah; DeAngelis, Stephanie; Chen, Chun-Liang; Fuchs, James R; Li, Chenglong; Li, Pui-Kai; Lin, Jiayuh

    2009-01-01

    Colorectal carcinoma is one of the major causes of morbidity and mortality in the Western World. Novel therapeutic approaches are needed for colorectal carcinoma. Curcumin, the active component and yellow pigment of turmeric, has been reported to have several anti-cancer activities including anti-proliferation, anti-invasion, and anti-angiogenesis. Clinical trials have suggested that curcumin may serve as a potential preventive or therapeutic agent for colorectal cancer. We compared the inhibitory effects of curcumin and novel structural analogues, GO-Y030, FLLL-11, and FLLL-12, in three independent human colorectal cancer cell lines, SW480, HT-29, and HCT116. MTT cell viability assay was used to examine the cell viability/proliferation and western blots were used to determine the level of PARP cleavages. Half-Maximal inhibitory concentrations (IC 50 ) were calculated using Sigma Plot 9.0 software. Curcumin inhibited cell viability in all three of the human colorectal cancer cell lines studied with IC 50 values ranging between 10.26 μM and 13.31 μM. GO-Y030, FLLL-11, and FLLL-12 were more potent than curcumin in the inhibition of cell viability in these three human colorectal cancer cell lines with IC 50 values ranging between 0.51 μM and 4.48 μM. In addition, FLLL-11 and FLLL-12 exhibit low toxicity to WI-38 normal human lung fibroblasts with an IC-50 value greater than 1,000 μM. GO-Y030, FLLL-11, and FLLL-12 are also more potent than curcumin in the induction of apoptosis, as evidenced by cleaved PARP and cleaved caspase-3 in all three human colorectal cancer cell lines studied. The results indicate that the three curcumin analogues studied exhibit more potent inhibitory activity than curcumin in human colorectal cancer cells. Thus, they may have translational potential as chemopreventive or therapeutic agents for colorectal carcinoma

  9. Evaluation of MR diffusion-weighted imaging in differentiating endometriosis infiltrating the bowel from colorectal carcinoma

    International Nuclear Information System (INIS)

    Busard, M.P.H.; Pieters-van den Bos, I.C.; Mijatovic, V.; Van Kuijk, C.; Bleeker, M.C.G.; Waesberghe, J.H.T.M. van

    2012-01-01

    Objective: Endometriosis infiltrating the bowel may be difficult to differentiate from colorectal carcinoma in cases that present with non-specific clinical and imaging features. The aim of this study is to assess the value of MR diffusion-weighted imaging (DWI) in differentiating endometriosis infiltrating the bowel from colorectal carcinoma. Methods: In 66 patients, MR DWI was added to the standard imaging protocol in patients visiting our outdoor MR clinic for the analysis of suspected or known deep infiltrating endometriosis (DIE). In patients diagnosed with DIE infiltrating the bowel on MR imaging, high b-value diffusion-weighted images were qualitatively assessed by two readers in consensus and compared to high b-value diffusion weighted images in 15 patients evaluated for colorectal carcinoma. In addition, ADC values of lesions were calculated, using b-values of 50, 400 and 800 s/mm 2 . Results: A total of 15 patients were diagnosed with DIE infiltrating the bowel on MR imaging. Endometriosis infiltrating the bowel showed low signal intensity on high b-value diffusion-weighted images in all patients, whereas colorectal carcinoma showed high signal intensity on high b-value diffusion-weighted images in all patients. Mean ADC value in endometriosis infiltrating the bowel (0.80 ± 0.06 × 10 −3 mm 2 /s) was significantly lower compared to mean ADC value in colorectal carcinoma (0.86 ± 0.06 × 10 −3 mm 2 /s), but with considerable overlap between ADC values. Conclusion: Only qualitative assessment of MR DWI may be valuable to facilitate differentiation between endometriosis infiltrating the bowel and colorectal carcinoma.

  10. A Comparison of Regorafenib and TAS-102 for Metastatic Colorectal Cancer: A Systematic Review and Network Meta-analysis.

    Science.gov (United States)

    Abrahao, Ana B K; Ko, Yoo-Joung; Berry, Scott; Chan, Kelvin K W

    2017-11-21

    Regorafenib and TAS-102 have shown to be superior to placebo in refractory metastatic colorectal cancer. However, no studies have directly compared both drugs. Giving the lack of standard options in this scenario, a systematic review to compare the efficacy and safety of regorafenib and TAS-102 was performed. A systematic review using the PubMed, Medline, Embase, Scopus, and Cochrane databases to identify published and unpublished studies up to November 2015 for randomized controlled trials for patients with metastatic colorectal cancer, involving regorafenib or TAS-102, was performed. Data including overall survival, progression-free survival, and toxicity were extracted. Pairwise direct meta-analyses (regorafenib vs. placebo and TAS-102 vs. placebo) and indirect comparison (regorafenib vs. TAS-102) using network meta-analyses methods to preserve randomization were performed using random effects. Three randomized controlled trials fulfilled eligibility criteria (regorafenib monotherapy for previously treated metastatic colorectal cancer [CORRECT]: an international, multicentre, randomised, pacebo-controlled, phase 3 trial, regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer [CONCUR]: a randomised, double-blind, placebo-controlled, phase 3 trial, and randomized trial of TAS-102 for refractory metastatic colorectal cancer [RECOURSE] trials) involving 1764 patients (regorafenib, 641; TAS-102, 534; placebo, 589). Subgroups of patients (1659) who had not received prior regorafenib or TAS-102 were used to perform meta-analyses for efficacy. In the indirect comparison, no statistically significant differences were observed between regorafenib and TAS-102 in overall survival (hazard ratio, 0.96; 95% confidence interval [CI], 0.57-1.66; P = .91) or progression-free survival (hazard ratio, 0.85; 95% CI, 0.40-1.81; P = .67). However, regorafenib has statistically more all

  11. Metastatic carcinoma of bone in skeleton and a report on one of its rare one in hand bone

    Directory of Open Access Journals (Sweden)

    Farzan M

    1996-06-01

    Full Text Available The primary carcinoma may secondarily invade bone tissue through direct extensions, blood circulation or lymphatic transportation particulary when it is arising from breast, prostate, kidney, thyroid and lung. Metastatics tumors of bone are more common than primary tumor of bone. The most common tumor, which metastasizes into bone, is the breast adenocarcinoma. Some metastatic tumors of bone including the breast cancer, may appear only as a destructive lesion, while prostatic carcinoma is osteoblastoma. The metastasis is mostly appeared in skull, vertebrae, pelvic, femur and humerus bones. The first metastatic syndrome is usually the affected bone pain and pathologic fractures are commonly caused by osteometastasis

  12. Mutational analysis of primary and metastatic colorectal cancer samples underlying the resistance to cetuximab-based therapy

    Directory of Open Access Journals (Sweden)

    Nemecek R

    2016-07-01

    Full Text Available Radim Nemecek,1 Jitka Berkovcova,2 Lenka Radova,3 Tomas Kazda,4 Jitka Mlcochova,3 Petra Vychytilova-Faltejskova,1,3 Ondrej Slaby,1,3 Marek Svoboda1 1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic; 2Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic; 3Central European Institute of Technology, Masaryk University, Brno, Czech Republic; 4Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic Purpose: Although several molecular markers predicting resistance to cetuximab- or panitumumab-based therapy of metastatic colorectal cancer were described, mutations in RAS proto-oncogenes remain the only predictors being used in daily clinical practice. However, 35%–45% of wild-type RAS patients still do not respond to this anti-epidermal growth factor receptor (anti-EGFR monoclonal antibody-based therapy, and therefore the definition of other predictors forms an important clinical need. The aim of the present retrospective single-institutional study was to evaluate potential genes responsible for resistance to anti-EGFR therapy in relation to mutational analysis of primary versus metastatic lesions. Patients and methods: Twenty-four paired primary and corresponding metastatic tissue samples from eight nonresponding and four responding metastatic colorectal cancer patients treated with cetuximab-based therapy were sequenced using a next-generation sequencing panel of 26 genes involved in EGFR signaling pathway and colorectal carcinogenesis. Results: Mutational status of primary tumors and metastatic lesions was highly concordant in TP53, APC, CTNNB1, KRAS, PIK3CA, PTEN, and FBXW7 genes. Metastatic samples harbor significantly more mutations than primary tumors. Potentially negative predictive value of FBXW7 mutations in relationship to anti-EGFR treatment outcomes was confirmed

  13. Metastatic ovarian carcinoma to the brain: an approach to identification and classification for neuropathologists.

    Science.gov (United States)

    Nafisi, Houman; Cesari, Matthew; Karamchandani, Jason; Balasubramaniam, Gayathiri; Keith, Julia Lee

    2015-04-01

    Brain metastasis is an uncommon but increasing manifestation of ovarian epithelial carcinoma and neuropathologists' collective experience with these tumors is limited. We present clinicopathological characteristics of 13 cases of brain metastases from ovarian epithelial carcinoma diagnosed at two academic institutions. The mean ages at diagnosis of the ovarian carcinoma and their subsequent brain metastases were 58.7 and 62.8 years, respectively. At the time of initial diagnosis of ovarian carcinoma the majority of patients had an advanced stage and none had brain metastases as their first manifestation of malignancy. Brain metastases tended to be multiple with ring-enhancing features on neuroimaging. Primary tumors and their brain metastases were all high-grade histologically and the histologic subtypes were: nine high-grade serous carcinoma (HGSC) cases, two clear cell carcinoma (CCC) cases and a single case each of carcinosarcoma and high-grade adenocarcinoma. A recommended histo- and immunopathological approach to these tumours are provided to aid neuropathologists in the recognition and classification of metastatic ovarian carcinoma to the brain. © 2014 Japanese Society of Neuropathology.

  14. FGFR-1 amplification in metastatic lymph-nodal and haematogenous lobular breast carcinoma

    Directory of Open Access Journals (Sweden)

    Brunello Eleonora

    2012-12-01

    Full Text Available Abstract Background Lobular breast carcinoma usually shows poor responsiveness to chemotherapies and often lacks targeted therapies. Since FGFR1 expression has been shown to play pivotal roles in primary breast cancer tumorigenesis, we sought to analyze the status of FGFR1 gene in a metastatic setting of lobular breast carcinoma, since promising FGFR1 inhibitors has been recently developed. Methods Fifteen tissue metastases from lobular breast carcinomas with matched primary infiltrative lobular breast carcinoma were recruited. Eleven cases showed loco-regional lymph-nodal and four haematogenous metastases. FGFR-1 gene (8p12 amplification was evaluated by chromogenic in situ hybridization (CISH analysis. Her-2/neu and topoisomerase-IIα gene status was assessed. E-cadherin and Hercept Test were also performed. We distinguished amplification (>6 or cluster of signals versus gains (3–6 signals of the locus specific FGFR-1 gene. Results Three (20% primary lobular breast carcinomas showed >6 or cluster of FGFR1 signals (amplification, six cases (40% had a mean of three (range 3–6 chromogenic signals (gains whereas in 6 (40% was not observed any abnormality. Three of 15 metastasis (20% were amplified, 2/15 (13,4% did not. The ten remaining cases (66,6% showed three chromogenic signals. The three cases with FGFR-1 amplification matched with those primary breast carcinomas showing FGFR-1 amplification. The six cases showing FGFR-1 gains in the primary tumour again showed FGFR-1 gains in the metastases. Four cases showed gains of FGFR-1 gene signals in the metastases and not in the primary tumours. Her-2/neu gene amplification was not observed in all cases but one (6% case. Topoisomerase-IIα was not amplified in all cases. Conclusions 1 a subset of metastatic lobular breast carcinoma harbors FGFR-1 gene amplification or gains of chromogenic signals; 2 a minor heterogeneity has been observed after matching primary and metastatic carcinomas; 3 in the

  15. Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells.

    Science.gov (United States)

    Hsu, Fei-Ting; Sun, Cho-Chin; Wu, Chia-Hsing; Lee, Yen-Ju; Chiang, Chih-Hung; Wang, Wei-Shu

    2017-09-01

    The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G 1 phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

    2018-02-23

    Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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.

  19. Circulating free DNA as biomarker and source for mutation detection in metastatic colorectal cancer.

    Science.gov (United States)

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

    2015-01-01

    Circulating cell-free DNA (cfDNA) in plasma has shown potential as biomarker in various cancers and could become an importance source for tumour mutation detection. The objectives of our study were to establish a normal range of cfDNA in a cohort of healthy individuals and to compare this with four cohorts of metastatic colorectal cancer (mCRC) patients. We also investigated the prognostic value of cfDNA and analysed the tumour-specific KRAS mutations in the plasma. The study was a prospective biomarker evaluation in four consecutive Phase II trials, including 229 patients with chemotherapy refractory mCRC and 100 healthy individuals. Plasma was obtained from an EDTA blood-sample, and the total number of DNA alleles and KRAS mutated alleles were assessed using an in-house ARMS-qPCR as previously described. Median cfDNA levels were higher in mCRC compared to controls (p mutations in plasma and tissue was high (85%). These data confirm the prognostic value of cfDNA measurement in plasma and utility for mutation detection with the method presented.

  20. Strategies to overcome resistance to epidermal growth factor receptor monoclonal antibody therapy in metastatic colorectal cancer.

    Science.gov (United States)

    Jeong, Woo-Jeong; Cha, Pu-Hyeon; Choi, Kang-Yell

    2014-08-07

    Administration of monoclonal antibodies (mAbs) against epidermal growth factor receptor (EGFR) such as cetuximab and panitumumab in combination with conventional chemotherapy substantially prolongs survival of patients with metastatic colorectal cancer (mCRC). However, the efficacy of these mAbs is limited due to genetic variation among patients, in particular K-ras mutations. The discovery of K-ras mutation as a predictor of non-responsiveness to EGFR mAb therapy has caused a major change in the treatment of mCRC. Drugs that inhibit transformation caused by oncogenic alterations of Ras and its downstream components such as BRAF, MEK and AKT seem to be promising cancer therapeutics as single agents or when given with EGFR inhibitors. Although multiple therapeutic strategies to overcome EGFR mAb-resistance are under investigation, our understanding of their mode of action is limited. Rational drug development based on stringent preclinical data, biomarker validation, and proper selection of patients is of paramount importance in the treatment of mCRC. In this review, we will discuss diverse approaches to overcome the problem of resistance to existing anti-EGFR therapies and potential future directions for cancer therapies related to the mutational status of genes associated with EGFR-Ras-ERK and PI3K signalings.

  1. Reduced dose of salvage-line regorafenib monotherapy for metastatic colorectal cancer in Japan.

    Science.gov (United States)

    Hirano, Gen; Makiyama, Akitaka; Makiyama, Chinatsu; Esaki, Taito; Oda, Hisanobu; Uchino, Keita; Komoda, Masato; Tanaka, Risa; Matsushita, Yuzo; Mitsugi, Kenji; Shibata, Yoshihiro; Kumagai, Hozumi; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Akashi, Koichi; Baba, Eishi

    2015-01-01

    Salvage-line regorafenib monotherapy exhibited a marked survival benefit for metastatic colorectal cancer (mCRC). However, the toxicity of this regimen has resulted in the clinical use of a reduced dose of regorafenib. Thirty-two Japanese mCRC patients (median age=61 years) who had been treated with regorafenib were retrospectively examined. Best objective response rate was 0% and stable disease (SD) was 31%. Median progression-free survival was 81 days and median overall survival was 233 days. Adverse events of any grade were observed in all patients: 17 (53%) patients suffered grade 3 or 4 adverse events including fatigue (13%), anorexia (13%), hand-foot skin reaction (22%) and elevations of alanine aminotransferase/aspartate aminotransferase (19%/16%). One patient with grade 5 liver dysfunction was identified (3%). Twenty-nine (91%) patients required treatment dose reduction or a delay in treatment. The relative dose intensity was 59%. Regorafenib treatments were terminated because of disease progression (59%) or adverse events (34%). Despite a decrease in the intensity of regorafenib treatment, because of severe adverse events, a fairly favorable efficacy was achieved in Japanese patients. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study.

    Science.gov (United States)

    Garcia-Alfonso, Pilar; Chaves, Manuel; Muñoz, Andrés; Salud, Antonieta; García-Gonzalez, Maria; Grávalos, Cristina; Massuti, Bartomeu; González-Flores, Encarna; Queralt, Bernardo; López-Ladrón, Amelia; Losa, Ferran; Gómez, Maria Jose; Oltra, Amparo; Aranda, Enrique

    2015-04-29

    The optimal sequence of chemotherapeutic agents is not firmly established for the treatment of metastatic colorectal cancer (mCRC). This phase II multi-centre study investigated the efficacy and tolerability of a standard capecitabine plus irinotecan (XELIRI) regimen with bevacizumab in previously untreated patients with mCRC. Patients received intravenous irinotecan 175 mg/m(2) on day 1 and oral capecitabine 1000 mg/m(2) (800 mg/m(2) for patients >65 years of age) twice daily on days 2-8, followed by a 1-week rest, and bevacizumab 5 mg/kg as an intravenous infusion on day 1 every 2 weeks. Seventy-seven patients were included in the intention-to-treat and safety populations. Progression-free survival at 9 months was 61%. The overall response and disease control rates were 51% and 84%, respectively. Median progression-free and overall survival times were 11.9 and 24.8 months, respectively. 48 patients (62%) had at least one grade 3/4 adverse event, the most common being asthenia, diarrhoea and neutropenia. Quality of life varied little over the study period with mean visual analogue scale general health scores ranging from 71 to 76 over cycles 1-11. Our study found irinotecan and capecitabine administered fortnightly with bevacizumab in patients with mCRC to be an effective and tolerable regimen. clinicaltrials.gov identifier NCT00875771. Trial registration date: 04/02/2009.

  3. Low Visceral Fat Content Is a Negative Predictive Marker for Bevacizumab in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Miyamoto, Yuji; Oki, Eiji; Emi, Yasunori; Tokunaga, Shoji; Shimokawa, Mototsugu; Ogata, Yutaka; Akagi, Yoshito; Sakamoto, Yasuo; Tanaka, Takaho; Saeki, Hiroshi; Maehara, Yoshihiko; Baba, Hideo

    2018-01-01

    This study aimed to clarify the predictive impact of visceral fat on response to bevacizumab in patients with metastatic colorectal cancer (mCRC). Pretreatment computed tomography was used to measure visceral fat area (VFA) and patients with mCRC receiving first-line chemotherapy with/without bevacizumab were divided by median VFA value into two groups: high VFA and low VFA. In the bevacizumab-treated group, patients with low VFA had significantly shorter overall survival (OS) than patients with high VFA in univariate (median=21.1 vs. 38.9 months; hazard ratio=1.70, 95% confidence interval=1.06-2.70, p=0.03) and multivariate analysis (hazard ratio=1.85, 95% confidence interval=1.15-3.03, p=0.01). No significant differences were seen in OS between groups treated with chemotherapy alone. The VFA had a marginally significant modifying effect on the relationship between bevacizumab and OS (p for interaction=0.07). Our findings provide the first evidence that a low VFA might be a negative predictive marker for response to bevacizumab in patients with mCRC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Resilience and hope during advanced disease: a pilot study with metastatic colorectal cancer patients.

    Science.gov (United States)

    Solano, Joao Paulo Consentino; da Silva, Amanda Gomes; Soares, Ivan Agurtov; Ashmawi, Hazem Adel; Vieira, Joaquim Edson

    2016-08-02

    The balance between hope-hopelessness plays an important role in the way terminally ill patients report quality of life, and personal resilience may be related to hope at the end of life. The objective of this study was to explore associations between personal resilience, hope, and other possible predictors of hope in advanced cancer patients. A cross-sectional pilot study was carried out with metastatic colorectal cancer patients in a tertiary hospital. The patients answered the Connor-Davidson Resilience Scale, Herth Hope Index, Barthel Index, an instrument addressing family and social support, visual-numeric scales for pain and suffering, a two-item screening for depression, socio-demographic and socio-economic information about the family. Forty-four patients were interviewed (mean age 56 years; range 29-86). A strong correlation was noted between resilience and hope (0.63; p resilience (p = 0.005) and hope (p = 0.003), and higher scores of suffering (p resilience and hope kept stable after adjusting for age, gender, and presence of depression (p resilience is a dynamic, changeable path that can improve hope, resilience-fostering interventions should be most valued in palliative care settings and should be commenced as soon as possible with cancer patients. Patients with advanced stages of non-malignant conditions would also probably benefit from such interventions.

  5. Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum.

    Science.gov (United States)

    Liu, Li; Tabung, Fred K; Zhang, Xuehong; Nowak, Jonathan A; Qian, Zhi Rong; Hamada, Tsuyoshi; Nevo, Daniel; Bullman, Susan; Mima, Kosuke; Kosumi, Keisuke; da Silva, Annacarolina; Song, Mingyang; Cao, Yin; Twombly, Tyler S; Shi, Yan; Liu, Hongli; Gu, Mancang; Koh, Hideo; Li, Wanwan; Du, Chunxia; Chen, Yang; Li, Chenxi; Li, Wenbin; Mehta, Raaj S; Wu, Kana; Wang, Molin; Kostic, Aleksander D; Giannakis, Marios; Garrett, Wendy S; Hutthenhower, Curtis; Chan, Andrew T; Fuchs, Charles S; Nishihara, Reiko; Ogino, Shuji; Giovannucci, Edward L

    2018-04-24

    Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and TNF receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on empirical dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment. We calculated EDIP scores based on answers to questionnaires collected from participants in the Nurses' Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a PCR assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status. During 28 years of follow up of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores associated with

  6. Biochemical liver function test parameter levels in relation to treatment response in liver metastatic colorectal patients treated with FOLFOX4 with or without bevacizumab

    Directory of Open Access Journals (Sweden)

    Denić Kristina

    2016-01-01

    Full Text Available Introduction. Combined use of bevacizumab and conventional anticancer drugs leads to a significant improvement of treatment response in patients with metastatic colorectal carcinoma (CRC. Conventional treatment protocols exert undesired effects on the liver tissue. Hepatotoxic effects are manifested as a disturbance of liver function test parameters. The relation between clinical outcome and disorder of biochemical parameters has not been completely evaluated. Objective. The objective of our study was to examine whether clinical outcome in patients with liver metastatic CRC correlates with the level of liver function test parameters. Methods. The study included 96 patients with untreated liver metastatic CRC who received FOLFOX4 protocol with or without bevacizumab. Biochemical liver parameters were performed before and after the treatment completion. Treatment response was evaluated as disease regression, stable disease, and disease progression. The patients were divided into three groups according to the accomplished treatment response. Results. In the group of patients with disease regression the post-treatment levels of aspartate aminotransferase, alanine aminotransferase, and bilirubin were statistically significantly increased. In contrast to this, gamma-glutamyltransferase and protein post-treatment values were significantly lower in relation to initial values. In patients with stable disease, difference was found only in the level of proteins being lower after the treatment. In patients with disease progression, values of aspartate aminotransferase and bilirubin were significantly increased after completed treatment. Conclusion. Treatment responses are not completely associated with the level of liver function test parameters. The only parameter which correlated with treatment response is gamma-glutamyltransferase. Its decrease is accompanied with disease regression.

  7. Radiosensitization of colorectal carcinoma cell lines by histone deacetylase inhibition

    International Nuclear Information System (INIS)

    Flatmark, Kjersti; Nome, Ragnhild V; Folkvord, Sigurd; Bratland, Åse; Rasmussen, Heidi; Ellefsen, Mali Strand; Fodstad, Øystein; Ree, Anne Hansen

    2006-01-01

    The tumor response to preoperative radiotherapy of locally advanced rectal cancer varies greatly, warranting the use of experimental models to assay the efficacy of molecular targeting agents in rectal cancer radiosensitization. Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of histone proteins and thereby remodeling of chromatin structure, may override cell cycle checkpoint responses to DNA damage and amplify radiation-induced tumor cell death. Human colorectal carcinoma cell lines were exposed to ionizing radiation and HDAC inhibitors, and cell cycle profiles and regulatory factors, as well as clonogenicity, were analyzed. In addition to G 2 /M phase arrest following irradiation, the cell lines displayed cell cycle responses typical for either intact or defective p53 function (the presence or absence, respectively, of radiation-induced expression of the cell cycle inhibitor p21 and subsequent accumulation of G 1 phase cells). In contrast, histone acetylation was associated with complete depletion of the G 1 population of cells with functional p53 but accumulation of both G 1 and G 2 /M populations of cells with defective p53. The cellular phenotypes upon HDAC inhibition were consistent with the observed repression of Polo-like kinase-1, a regulatory G 2 /M phase kinase. Following pre-treatment with HDAC inhibitors currently undergoing clinical investigation, the inhibitory effect of ionizing radiation on clonogenicity was significantly amplified. In these experimental models, HDAC inhibition sensitized the tumor cells to ionizing radiation, which is in accordance with the concept of increased probability of tumor cell death when chromatin structure is modified

  8. A genome-wide DNA methylation study in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Dodsworth Charlotte

    2011-06-01

    Full Text Available Abstract Background We performed a genome-wide scan of 27,578 CpG loci covering 14,475 genes to identify differentially methylated loci (DML in colorectal carcinoma (CRC. Methods We used Illumina's Infinium methylation assay in paired DNA samples extracted from 24 fresh frozen CRC tissues and their corresponding normal colon tissues from 24 consecutive diagnosed patients at a tertiary medical center. Results We found a total of 627 DML in CRC covering 513 genes, of which 535 are novel DML covering 465 genes. We also validated the Illumina Infinium methylation data for top-ranking genes by non-bisulfite conversion q-PCR-based methyl profiler assay in a subset of the same samples. We also carried out integration of genome-wide copy number and expression microarray along with methylation profiling to see the functional effect of methylation. Gene Set Enrichment Analysis (GSEA showed that among the major "gene sets" that are hypermethylated in CRC are the sets: "inhibition of adenylate cyclase activity by G-protein signaling", "Rac guanyl-nucleotide exchange factor activity", "regulation of retinoic acid receptor signaling pathway" and "estrogen receptor activity". Two-level nested cross validation showed that DML-based predictive models may offer reasonable sensitivity (around 89%, specificity (around 95%, positive predictive value (around 95% and negative predictive value (around 89%, suggesting that these markers may have potential clinical application. Conclusion Our genome-wide methylation study in CRC clearly supports most of the previous findings; additionally we found a large number of novel DML in CRC tissue. If confirmed in future studies, these findings may lead to identification of genomic markers for potential clinical application.

  9. Aural carcinoma with chondroid metaplasia at metastatic sites in a dog.

    Science.gov (United States)

    Romanucci, Mariarita; Malatesta, Daniela; Marinelli, Alessia; Di Lorenzo, Pierluigi; Della Salda, Leonardo

    2011-08-01

    A case of aural carcinoma with chondroid metaplasia at metastatic foci in an 8-year-old male pug is described. Multiple metastases in both lungs and the right submandibular, parotid, retropharyngeal, cervical and prescapular lymph nodes were detected. Histologically, the skin of the right ear canal appeared to be diffusely infiltrated by cords and nests of neoplastic epithelial cells, showing multifocal contiguity with the overlying hyperplastic squamous epithelium. Most of the carcinomatous cells were arranged in a glandular-like pattern, with formation of lumens containing epithelial cells attached to the peripheral cell layer by elongated intercellular bridges. Scattered foci of keratinization with central accumulations of compact, laminated keratin were also observed, and histochemical stains failed to detect mucinous secretory material. Even though histological and histochemical findings were compatible with a diagnosis of acantholytic squamous cell carcinoma, CAM5.2 immunostaining was detectable in the majority, although not all, neoplastic cells, confirming a diagnosis of poorly differentiated ceruminous gland carcinoma. Pulmonary metastatic nodules revealed multifocal areas of cartilaginous metaplasia with apparent transition of carcinomatous cells to chondroid cells, showing nuclear atypia and focal cytokeratin immunostaining. Carcinomatous cells surrounding chondroid areas also revealed focal vimentin and S100 immunoreactivity. Histological evidence of transition between the two components, as well as the presence of intermediate cells displaying both epithelial and mesenchymal immunohistochemical features, strongly indicated a final diagnosis of carcinosarcoma, in which chondrosarcomatous elements were derived from carcinoma cells. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

  10. A Case of Metastatic Basal Cell Carcinoma Treated with Cisplatin and Adriamycin.

    Science.gov (United States)

    Kanzaki, Akiko; Ansai, Shin-Ichi; Ueno, Takashi; Kawana, Seiji; Shimizu, Akira; Naito, Zenya; Saeki, Hidehisa

    2017-01-01

    A 72-year-old man was referred to our hospital for treatment of an ulcer that had been growing on his back for 10 years. Physical examination showed an ulcerated tumor from the neck to the back and swollen cervical lymph nodes. The tumor size was 12×9 cm. Histology of the biopsy showed a nodular and morpheic basal cell carcinoma (BCC). A chest computed tomography (CT) scan showed multiple lung tumors. CT-guided biopsy of the lung and the cervical lymph node revealed metastatic basal cell carcinoma (MBCC). The primary skin tumor was resected and a total of 10 courses of cisplatin (25 mg/m 2 /day×75%) and adriamycin (50 mg/m 2 ×75%) were administered for metastatic basal cell carcinoma (MBCC). The patient died 5 years and 3 months after his first visit. Autopsy revealed MBCC in the lung, kidney, pancreas, several lymph nodes, liver and bone. A portion of the tumor cells were composed of squamoid cells with eosinophilic cytoplasm, large nuclei, lack of the characteristic peripheral palisading and retraction artifacts, and variable cytoplasmic keratinization. These pathological findings were compatible with basosquamous cell carcinoma. Chemotherapy was effective for MBCC in this patient.

  11. Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

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    D. M. Heijink

    2007-01-01

    Full Text Available Background: TNF-Related Apoptosis Inducing Ligand (TRAIL is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP. Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n = 20, colorectal adenomas (n = 66 and colorectal carcinomas (n = 44 using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome-associated adenomas and carcinomas. Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P = 0.02. Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P < 0.001. A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.

  12. Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2014-06-01

    Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

  13. Identification of Differentially Expressed Genes in Metastatic and Non-Metastatic Nasopharyngeal Carcinoma Cells by Suppression Subtractive Hybridization

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    Xu-Yu Yang

    2005-01-01

    Full Text Available Background & Objective: Nasopharyngeal carcinoma (NPC is an epithelial neoplasm with high occurrence rates in southern China. The disease often metastasizes to regional lymphnodes at a very early stage. Local recurrences and metastasis occur frequently in patients with NPC and are a leading cause of death, despite improvements on treatment modalities. The molecular mechanism underlying the metastasis of nasopharyngeal carcinoma remains poorly understood, however, and requires additional elucidation. The aim of this study was to explore possible NPC gene candidates that may play key roles in NPC metastasis. Methods: Subtractive suppression hybridization (SSH was performed to isolate differentially expressed clones between the metastatic 5-8F and non-metastatic 6-10B nasopharyngeal carcinoma cell lines. Differentially expressed clones were screened and confirmed by reverse Northern blotting. The sequences of cDNA fragments were subsequently analyzed and compared to known sequences in Genbank. Results & Discussion: The SSH library contained thousands of positive clones. Random analysis of 300 clones by PCR demonstrated that 269 clones contained inserted fragments. Reverse Northern blot confirmed that 20 out of 192 clones examined were significantly up-regulated in the 5-8F cell line. Among these 20 clones, 16 were previously identified genes (flotilin-2, ezrin, pim-3, fli-1, mel, neugrin, znf216, ASB1, raly, UBE2A, keratin6A, TMED7, EIF3S9, FTL, two ribosomal proteins RPL21 and RPL16, two were predicted genes (c9orf74 and MDS006, and two sequences shared no homology with known genes listed in GenBank and may represent novel genes. The proposed functions of the genes identified in this study include cell signal transduction, cell survival, transcription regulation, cell mobility, protein synthesis, and DNA damage repair. Flotillin-2, fli-1, pim-3 and ezrin have previously been reported to be associated with tumor metastasis and progression. The

  14. Investigation of acupuncture-point injection combined with intratumor injection of radionuclide phosphorus 32 in treatment of metastatic carcinoma

    International Nuclear Information System (INIS)

    Chou, H.C.

    1986-01-01

    Seventeen patients with carcinoma and three patients with benign lesions of the head were studied by acupuncture-point injection combined with intratumor injection of radionuclide P-32 for treatment of metastatic carcinoma. The metastatic cervical nodules shrank to half their original sizes within 2-3 weeks in five cases of nasopharyngeal carcinoma. The injected dose ranged from 0.222 to 0.421 mCi, approximately 10 times less than that given by the ordinary method. The acupuncture points are selected according to the Theory of Channels and Collaterals of Chinese traditional medicine. The mechanism of therapeutic action of radionuclide P-32 is possibly by the delivery of destructive ionizing radiation from beta emission properties of P-32. This method appears to offer a low-dose means of P-32 treatment of metastatic carcinoma

  15. Alopecia neoplastica: An uncommon presentation of metastatic breast carcinoma

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    Felipe Ladeira de Oliveira

    2016-12-01

    Full Text Available Cutaneous metastasis may correspond to the initial clinical presentation of hidden internal malignancies. In patients presenting said neoplasia, clinical manifestations of breast cancer reaches 23.9%. Considering that neoplastic alopecia appears as an unusual pattern of the said metastasis, this report describes a case of such uncommon neoplastic alopecia which presents itself as a cutaneous metastasis of rapid progression in a patient with prior breast cancer history. We present a 47-year-old female patient reporting lesions at the scalp, and who was asymptomatic with a 1-year evolution. The patient reported prior breast cancer history and presence of lung metastasis, and was undergoing chemotherapy at the time of consultation. A dermatological evaluation showed only a nodular lesion with erythematous surface and a diameter measuring about 4 cm, firm in consistency, and immovable. She was routed to the Department of Dermatological Surgery, and the results from histopathology were consistent with a diagnosis of metastatic breast adenocarcinoma. Neoplastic alopecia appears as an unusual form of cutaneous metastasis which is predominantly described in association with breast cancer. The lesion’s clinical features play a crucial role at the differential diagnosis, as the presence of erythema could distinguish neoplastic alopecia from alopecia areata. The existence of cutaneous metastasis leads to unfavorable outcomes. As a conclusion, cutaneous evaluation of patients is essential for treating visceral metastases, since the forms of cutaneous metastasis are diverse and can also affect the scalp.

  16. Colorectal Carcinoma: An Update of Current Trends in Accra ...

    African Journals Online (AJOL)

    BACKGROUND: Clinical experience and earlier studies indicate that the number of colorectal cancer cases seen annually in the Accra metropolis is increasing. OBJECTIVE: This study was aimed at providing a current update on colorectal cancer in Accra, Ghana. METHODS: A prospective study of confirmed cases of ...

  17. Metastatic primary neuroendocrine carcinoma of the breast (NECB

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    Tsung-Hsien Tsai

    2018-03-01

    Full Text Available Neuroendocrine carcinoma of the breast (NECB is a subtype of breast cancer. The diagnostic criteria of primary NECB were established in 2003 and updated in 2012. It is a rare entity, and few studies have reported the histogenesis, immunohistochemistry for a pathological diagnosis, clinical behavior, therapeutic strategies, and the prognostic factors. Because of the rarity of this disease, consistent diagnostic criteria will remind physicians of this disease when making a differential diagnosis to enable a timely diagnosis and prompt treatment. Herein, we report a case of primary NECB who presented with a history of right hip pain arising from an osteolytic lesion in the right acetabulum and ischium. The course of investigation started with metastasis in the right hip and concluded with a diagnosis of NECB. In addition to the case report, we also conducted a literature review.

  18. Safety and Efficacy of Combined Yttrium 90 Resin Radioembolization with Aflibercept and FOLFIRI in a Patient with Metastatic Colorectal Cancer

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    Andre De Souza

    2015-01-01

    Full Text Available Background. When associated with isolated four or fewer liver foci, metastatic colorectal cancer is amenable to surgical resection. Alternative therapeutic methods for isolated liver metastases include radioembolization with yttrium 90 (Y90 and transarterial chemoembolization (TACE. We present here a case of a patient with two sites of liver metastatic disease from colorectal cancer who underwent Y90 radioembolization combined with aflibercept and FOLFIRI. Case Report. A 56-year-old female with history of bilateral breast cancer and metastatic colon cancer with prior hemicolectomy and 4 previous chemotherapy regimens developed liver metastasis. She was started on aflibercept and FOLFIRI and concurrently underwent two treatments of radioembolization with Y90, initially targeting the largest right lobe tumor, and then a subsequent treatment targeting the smaller left lobe tumor with retreatment of the right lobe tumor. Her liver metastases exhibited partial response on imaging utilizing the modified RECIST criteria. Interestingly, the patient CEA levels decreased after the procedure. Discussion. This is the first reported case of a patient managed with radioembolization with Y90 combined with aflibercept, an anti-VEGF treatment, and FOLFIRI. An ongoing randomized clinical trial aims to define the role of combined targeted therapy and chemotherapy with radioembolization with Y90.

  19. Correlation between spiral CT features of pericolic infiltration and tumor angiogenesis in colorectal carcinoma

    International Nuclear Information System (INIS)

    Zhang Ruiping; Li Jianding

    2007-01-01

    Objective: To investigate the correlation of spiral CT (SCT) features with pathology, microvessel density (MVD), expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2( MMP-2) in colorectal carcinoma. Methods: Forty patients with colorectal carcinoma confirmed by operation were examined by SCT. The resected tumor specimens were immunohistochemically stained for the expression of VEGF, MMP-2 and the calculation of MVD. Results: The accuracy of SCT in depicting the pericolic and wall infiltration was 92.5%. The metastasis rates of colorectal cancer with pericolic infiltration and wall infiltration were 75.0% and 33.3%, respectively, the differences were statistically significant between the two groups (P<0.05). The differences of CT enhancement value, MVD, expressions of VEGF and MMP-2 between the two groups were statistically significant (P<0.05). The enhancement degree of CT had a positive correlation with MVD (P<0.05). Conclusion: SCT is accurate for depicting pericolic and wall infiltration, pericolic infiltration in colorectal carcinoma indicates the tendency of metastasis. The enhancement degree of CT might be used to quantitatively evaluate the tumor angiogenesis, expressions of VEGF and MMP-2 and MVD are closely correlated with the infiltration of colorectal cancer. (authors)

  20. Colorectal carcinomas from Middle East: Molecular and tissue microarray analysis of genomic instability pathways

    International Nuclear Information System (INIS)

    Bavi, P.P.; Abubaker, Jehad A.; Jehan, Zeenath D.; Al-Jomah, Naif A.; Siraj, Abdul K.; Al-Harbi, Sayer R.; Atizado, Valerie L.; Uddin, S.; Al-Kuraya, Khawla S.; Abduljabbar, Alaa S.; Al-Homoud, Samar J.; Ashari, Luai H.; Al-Sanea, Nasser A.; Al-Dayel, Fouad H.

    2008-01-01

    Objective was to evaluate the overall incidence of microsatellite instability (MSI), hereditary non polyposis colorectal cancer and tumor suppressor gene (TP53) mutations in Saudi colorectal carcinomas. We studied the MSI pathway in Saudi colorectal cancers (CRC) from 179 unselected patients using 2 methods: MSI by polymerase chain reaction and immunohistochemistry detection of mutL homologs 1 and mutS homologs 2 proteins. The TP53 mutations were studied by sequencing exons 5, 6, 7 and 8. Of the 150 colorectal carcinomas analyzed for MSI, 16% of the tumors showed high level instability (MSI-H), 19.3% had low level instability (MSI-L) and the remaining 64% tumors were stable. Survival of the MSI-H group was better as compared to the MSI-L or microsatellite stable group (p=0.0217). In the MSI-H group, 48% were familial MSI tumors which could be attributable to the high incidence of consanguinity in the Saudi population. The TP53 mutations were found in 24% of the cases studied. A high production of familial MSI cases and a lower incidence of TP53 mutations are some of the hallmarks of the Saudi colorectal carcinomas which need to be explored further. (author)

  1. High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients.

    Science.gov (United States)

    Fukugaiti, Márcia H; Ignacio, Aline; Fernandes, Miriam R; Ribeiro Júnior, Ulysses; Nakano, Viviane; Avila-Campos, Mario J

    2015-01-01

    Colorectal carcinoma is considered the fourth leading cause of cancer deaths worldwide. Several microorganisms have been associated with carcinogenesis, including Enterococcus spp., Helicobacter pylori, enterotoxigenic Bacteroides fragilis, pathogenic E. coli strains and oral Fusobacterium. Here we qualitatively and quantitatively evaluated the presence of oral and intestinal microorganisms in the fecal microbiota of colorectal cancer patients and healthy controls. Seventeen patients (between 49 and 70 years-old) visiting the Cancer Institute of the Sao Paulo State were selected, 7 of whom were diagnosed with colorectal carcinoma. Bacterial detection was performed by qRT-PCR. Although all of the tested bacteria were detected in the majority of the fecal samples, quantitative differences between the Cancer Group and healthy controls were detected only for F. nucleatum and C. difficile. The three tested oral microorganisms were frequently observed, suggesting a need for furthers studies into a potential role for these bacteria during colorectal carcinoma pathogenesis. Despite the small number of patients included in this study, we were able to detect significantly more F. nucleatum and C. difficile in the Cancer Group patients compared to healthy controls, suggesting a possible role of these bacteria in colon carcinogenesis. This finding should be considered when screening for colorectal cancer.

  2. Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report.

    Science.gov (United States)

    Bezpalko, Kseniya; Mohamed, Mohamed A; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth

    2015-01-01

    At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Analysis of hepatocellular carcinoma and metastatic hepatic carcinoma via functional modules in a protein-protein interaction network

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    Jun Pan

    2014-01-01

    Full Text Available Introduction: This study aims to identify protein clusters with potential functional relevance in the pathogenesis of hepatocellular carcinoma (HCC and metastatic hepatic carcinoma using network analysis. Materials and Methods: We used human protein interaction data to build a protein-protein interaction network with Cytoscape and then derived functional clusters using MCODE. Combining the gene expression profiles, we calculated the functional scores for the clusters and selected statistically significant clusters. Meanwhile, Gene Ontology was used to assess the functionality of these clusters. Finally, a support vector machine was trained on the gold standard data sets. Results: The differentially expressed genes of HCC were mainly involved in metabolic and signaling processes. We acquired 13 significant modules from the gene expression profiles. The area under the curve value based on the differentially expressed modules were 98.31%, which outweighed the classification with DEGs. Conclusions: Differentially expressed modules are valuable to screen biomarkers combined with functional modules.

  4. Surgical Management of Advanced and Metastatic Renal Cell Carcinoma: A Multidisciplinary Approach

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    Brian M. Shinder

    2017-05-01

    Full Text Available The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy (predominantly high-dose interleukin 2 has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoadjuvant systemic therapy may increase the feasibility of resecting the primary tumor, which may be beneficial for patients with locally advanced or metastatic disease. Several prospective trials examining the role of adjuvant therapy are underway. Lastly, the first immune checkpoint inhibitor was approved for metastatic renal cell carcinoma (mRCC in 2015, providing a new treatment mechanism and new opportunities for combining systemic therapy with surgery. This review discusses current and historical literature regarding the surgical management of patients with advanced and mRCC and explores approaches for optimizing patient selection.

  5. Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma

    DEFF Research Database (Denmark)

    Guo, Tianhua; Krzystanek, Marcin; Szallasi, Zoltan Imre

    2014-01-01

    Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 K/μl) in patients with colorectal cancer. We...

  6. Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses

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    Myklebost Ola

    2007-01-01

    Full Text Available Abstract Background Despite the fact that metastases are the leading cause of colorectal cancer deaths, little is known about the underlying molecular changes in these advanced disease stages. Few have studied the overall gene expression levels in metastases from colorectal carcinomas, and so far, none has investigated the peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the present study is to investigate and compare the gene expression patterns of primary carcinomas (n = 18, liver metastases (n = 4, and carcinomatoses (n = 4, relative to normal samples from the large bowel. Results Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622 mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient. Conclusion By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.

  7. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

    International Nuclear Information System (INIS)

    Saelen, Marie Grøn; Ree, Anne Hansen; Kristian, Alexandr; Fleten, Karianne Giller; Furre, Torbjørn; Hektoen, Helga Helseth; Flatmark, Kjersti

    2012-01-01

    The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials

  8. Cytogenetic comparisons of synchronous carcinomas and polyps in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Thirty tumorous lesions from seven patients with colorectal cancer were short-term cultured and cytogenetically analysed: 16 non-adenomatous polyps, six adenomas, seven carcinomas, including one in polyp, and one lymph node metastasis. Clonal chromosome aberrations were found in 20 samples in 100...

  9. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma.

    Science.gov (United States)

    Saelen, Marie Grøn; Ree, Anne Hansen; Kristian, Alexandr; Fleten, Karianne Giller; Furre, Torbjørn; Hektoen, Helga Helseth; Flatmark, Kjersti

    2012-09-27

    The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

  10. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Saelen Marie

    2012-09-01

    Full Text Available Abstract Background The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC. Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Methods Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Results Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Conclusions Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

  11. BVES regulates EMT in human corneal and colon cancer cells and is silenced via promoter methylation in human colorectal carcinoma.

    Science.gov (United States)

    Williams, Christopher S; Zhang, Baolin; Smith, J Joshua; Jayagopal, Ashwath; Barrett, Caitlyn W; Pino, Christopher; Russ, Patricia; Presley, Sai H; Peng, DunFa; Rosenblatt, Daniel O; Haselton, Frederick R; Yang, Jin-Long; Washington, M Kay; Chen, Xi; Eschrich, Steven; Yeatman, Timothy J; El-Rifai, Wael; Beauchamp, R Daniel; Chang, Min S

    2011-10-01

    The acquisition of a mesenchymal phenotype is a critical step in the metastatic progression of epithelial carcinomas. Adherens junctions (AJs) are required for suppressing this epithelial-mesenchymal transition (EMT) but less is known about the role of tight junctions (TJs) in this process. Here, we investigated the functions of blood vessel epicardial substance (BVES, also known as POPDC1 and POP1), an integral membrane protein that regulates TJ formation. BVES was found to be underexpressed in all stages of human colorectal carcinoma (CRC) and in adenomatous polyps, indicating its suppression occurs early in transformation. Similarly, the majority of CRC cell lines tested exhibited decreased BVES expression and promoter DNA hypermethylation, a modification associated with transcriptional silencing. Treatment with a DNA-demethylating agent restored BVES expression in CRC cell lines, indicating that methylation represses BVES expression. Reexpression of BVES in CRC cell lines promoted an epithelial phenotype, featuring decreased proliferation, migration, invasion, and anchorage-independent growth; impaired growth of an orthotopic xenograft; and blocked metastasis. Conversely, interfering with BVES function by expressing a dominant-negative mutant in human corneal epithelial cells induced mesenchymal features. These biological outcomes were associated with changes in AJ and TJ composition and related signaling. Therefore, BVES prevents EMT, and its epigenetic silencing may be an important step in promoting EMT programs during colon carcinogenesis.

  12. Factors associated with the efficiency of maintenance therapy in patients with metastatic colorectal cancer

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    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Objective: to evaluate tolerability and efficacy of maintenance treatment in the absence of progression after 16 weeks of first-line therapy in patients with unresectable metastatic colon cancer.Materials and methods. We have analyzed medical case histories of patients with metastatic colorectal cancer who underwent treatment in the department of clinical pharmacology and chemotherapy of N. N. Blokhin Russian Cancer Research Center from 2007 to 2015 years. Inclusion criteria were the following: 16–24 weeks of first-line chemotherapy with no signs of progression and the inability to perform metastasectomy. Progression-free survival was the main criterion for effectiveness in our study.Results. 160 (44.5 % of 359 treated patients met the inclusion criteria. 102 (63.7 % patients were followed up, while the other 58 (36.3 % – comparison group patients underwent maintenance chemotherapy. Grade I–II toxic reactions and grade III complications associated with first-line chemotherapy were insignificantly more common in the group of patients left on maintenance chemotherapy: 72.4 % and 37.9 % versus 57.8 % and 24.5 % in the comparison group, p = 0.07 and p = 0.07 respectively. The frequency of grade I–II toxic reactions and grade III complications in the second-line treatment did not differ between treatment groups (p = 0.9 and p = 0.8. The median of progression-free survival in observation group and comparison group was 4, and 6 months (odds ratio (OR 0.6; p = 0.009, and life expectancy – 23 and 31 months (OR 0.75; p = 0.1, respectively. Statistically significant differences between groups with respect to achieving the objective response and/or normalization of carcinoembryonic antigen level were revealed: median of progression-free survival was 13 (n = 26 of 57; 45.6 % and 4 months (n = 31 of 57, 54.4 %, respectively (HR 0.38; p = 0.002, median of life expectancy – 34 months versus 26 months (OR 0.37; p = 0.3.

  13. Bevacizumab for Metastatic Colorectal Cancer: A Global Cost-Effectiveness Analysis.

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    Goldstein, Daniel A; Chen, Qiushi; Ayer, Turgay; Chan, Kelvin K W; Virik, Kiran; Hammerman, Ariel; Brenner, Baruch; Flowers, Christopher R; Hall, Peter S

    2017-06-01

    In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties. Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY. The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers. The cost-effectiveness of bevacizumab varies significantly between multiple countries. By conventional thresholds, bevacizumab is not cost-effective in metastatic colon cancer in the U.S., the U.K., Australia, Canada, and Israel. © AlphaMed Press 2017.

  14. Can preoperative CEA and CA19-9 serum concentrations suggest metastatic disease in colorectal cancer patients?

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    Stojkovic Lalosevic, Milica; Stankovic, Sanja; Stojkovic, Mirjana; Markovic, Velimir; Dimitrijevic, Ivan; Lalosevic, Jovan; Petrovic, Jelena; Brankovic, Marija; Pavlovic Markovic, Aleksandra; Krivokapic, Zoran

    2017-01-01

    This study was designed to investigate the efficiency of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate cancer antigen (CA19-9) levels for diagnosing synchronous liver metastases and lymph node in colorectal carcinoma (CRC) patients. A total of 300 patients with histologically diagnosed CRC were included in this study between May 2014 and March 2015. The data were obtained prospectively from patient's medical records: medical history, demographics, tumor location, differentiation (grade), depth of the tumor (T), lymph node metastases (N), distant metastases (M), lymphatics, venous and perineural invasion, and disease stage. Tumor markers were measured with an electrochemiluminescent assay and the reference value was 5ng/ml for CEA and for Ca19-9, 37u/ml. There was A high statistically significant difference in the levels of serum CEA and CA19-9 between different disease stages of CRC (PCEA (stage I 3.76±8.73; II 5.68±17.27, III 7.56±14.81, and IV 70.90±253.23) and CA 19-9 levels (stage I 9.65±11.03, II 9.83±11.09; III 19.58±36.91, and IV 228.9±985.38, respectively). The mean CEA and CA19-9 serum levels were significantly higher in patients with regional lymph nodes involvement (CEA 37.21±177.85 vs 4.79±9.90, CA19-9 119.51±687.71 VS 12.24±17.69, respectively, PCEA 86.56±277.65 vs. 5.98±12.98, and CA19-9 273.27±1073.46 vs. 4.98±3142, respectively, with PCEA and CA 19-9, 3.5 ng/mL and 7.5 U/mL, respectively. While, a cut-off value for the presence of synchronous liver metastases of these two markers was 3.5ng/mL AND 5.5 U/mL. Our study showed that tumor makers, CEA and CA19-9, can be used as diagnostic factors regarding the severity of CRC specifically to suggest metastatic disease in CRC.

  15. Lumican and versican protein expression are associated with colorectal adenoma-to-carcinoma progression.

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    Meike de Wit

    Full Text Available One prominent event associated with colorectal adenoma-to-carcinoma progression is genomic instability. Approximately 85% of colorectal cancer cases exhibit chromosomal instability characterized by accumulation of chromosome copy number aberrations (CNAs. Adenomas with gain of chromosome 8q, 13q, and/or 20q are at high risk of progression to cancer. Tumor progression is also associated with expansion of the extracellular matrix (ECM and the activation of non-malignant cells within the tumor stroma. The glycoproteins versican and lumican are overexpressed at the mRNA level in colon carcinomas compared to adenomas, and are associated with the formation of tumor stroma.The aim of this study was to characterize versican and lumican protein expression in tumor progression and investigate their association with CNAs commonly associated with adenoma-to-carcinoma progression.Tissue microarrays were constructed with colon adenomas and carcinomas that were characterized for MSI-status and DNA copy number gains of chromosomes 8q, 13q and 20q. Sections were immunohistochemically stained for lumican and versican. Protein expression levels were evaluated using digitized slides, and scores were finally dichotomized into a positive or negative score per sample.Lumican and versican expression were both observed in neoplastic cells and in the tumor stroma of colon adenomas and carcinomas. Lumican expression was more frequently present in epithelial cells of carcinomas than adenomas (49% versus 18%; P = 0.0001 and in high-risk adenomas and carcinomas combined compared to low-risk adenomas (43% versus 16%; P = 0.005. Versican staining in the tumor stroma was more often present in high-risk adenomas combined with carcinomas compared to low-risk adenomas (57% versus 36%; P = 0.03 and was associated with the presence of gain of 13q (71% versus 44%; P = 0.04.Epithelial lumican and stromal versican protein expression are increased during colorectal adenoma-to-carcinoma

  16. NDRG2 gene copy number is not altered in colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders Blomkild; Mitchelmore, Cathy

    2017-01-01

    AIM To investigate if the down-regulation of N-myc Downstream Regulated Gene 2 (NDRG2) expression in colorectal carcinoma (CRC) is due to loss of the NDRG2 allele(s). METHODS The following were investigated in the human colorectal cancer cell lines DLD-1, LoVo and SW-480: NDRG2 mRNA expression...... levels using quantitative reverse transcription-polymerase chain reaction (qRT-PCR); interaction of the MYC gene-regulatory protein with the NDRG2 promoter using chromatin immunoprecipitation; and NDRG2 promoter methylation using bisulfite sequencing. Furthermore, we performed qPCR to analyse the copy...... numbers of NDRG2 and MYC genes in the above three cell lines, 8 normal colorectal tissue samples and 40 CRC tissue samples. RESULTS As expected, NDRG2 mRNA levels were low in the three colorectal cancer cell lines, compared to normal colon. Endogenous MYC protein interacted with the NDRG2 core promoter...

  17. Two Canine Papillomaviruses Associated With Metastatic Squamous Cell Carcinoma in Two Related Basenji Dogs.

    Science.gov (United States)

    Luff, J; Rowland, P; Mader, M; Orr, C; Yuan, H

    2016-11-01

    Papillomaviruses (PV) are associated with benign mucosal and cutaneous epithelial proliferations. In dogs, PV-associated pigmented plaques and papillomas can undergo malignant transformation, but this is rare, and most cases of canine squamous cell carcinoma do not arise from PV-induced precursor lesions. We describe herein the progression of pigmented plaques to invasive and metastatic squamous cell carcinoma associated with 2 canine papillomaviruses (CPV) in 2 related Basenji dogs. Immunohistochemistry for PV antigen revealed strong nuclear immunoreactivity within keratinocytes from pigmented plaques from both dogs, consistent with a productive viral infection. Polymerase chain reaction (PCR) using degenerate primers for the L1 gene revealed PV DNA sequences from 2 different CPVs. In situ hybridization for CPV revealed strong hybridization signals within the pigmented plaques and neoplastic squamous epithelial cells from both dogs. We report here progression of PV-associated pigmented plaques to metastatic squamous cell carcinoma within 2 Basenji dogs associated with 2 different CPVs. © The Author(s) 2016.

  18. Metastatic pancreatic carcinoma to the orbital apex presenting as a superior divisional third cranial nerve palsy

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    Bhatti MT

    2012-11-01

    Full Text Available Paula E Pecen,1 Nicholas A Ramey,1 Michael J Richard,1 M Tariq Bhatti1,21Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA; 2Department of Medicine (Division of Neurology, Duke University Medical Center, Durham, NC, USAAbstract: Metastatic tumors to the orbit are rare, especially from a primary pancreatic carcinoma. A 59-year-old man presented with 4 weeks of right eye pain and eyelid swelling. There was right upper eyelid ptosis associated with a right supraduction deficit consistent with a superior divisional third cranial nerve (CN III palsy. Magnetic resonance imaging revealed a right orbital apex lesion. A right orbital exenteration was performed for intractable and severe pain. Surgical pathology demonstrated a poorly differentiated carcinoma that was ultimately felt to be derived from the pancreas. In this report, we describe the clinical and neurological imaging findings of a superior divisional CN III palsy as the presenting manifestation of a presumed metastatic pancreatic carcinoma to the orbital apex, and review the neuroanatomy of CN III with particular emphasis on the anatomical bifurcation of the nerve into a superior and inferior division.Keywords: orbital tumor, orbital metastasis, superior division, third cranial nerve palsy

  19. Follicular Thyroid Carcinoma Metastatic to the Kidney: Report of a Case with Cytohistologic Correlation

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    Vikas Nath

    2015-01-01

    Full Text Available Here we report a case of a 45-year-old female who underwent thyroidectomy for thyroid cancer and presented 20 years later with a left renal mass. CT-guided core biopsy was performed, and imprints and histologic sections of the biopsy showed cells resembling thyroid follicular cells with a background containing colloid. Immunohistochemistry revealed positivity for thyroglobulin and thyroid transcription factor 1, consistent with metastatic follicular thyroid carcinoma (FTC. The patient later underwent radical nephrectomy; histologic sections of the resected tumor revealed an encapsulated lesion morphologically similar to the biopsy specimen. Thyroid metastases to the kidney are extremely rare and are often detected during postthyroidectomy surveillance by elevation in thyroid hormone levels, 131I scintigraphy, or 18F-fluorodeoxyglucose uptake in positron emission tomography studies. Treatment involves total thyroidectomy, resection of the metastatic foci, and 131I therapy. The differential diagnoses of renal metastasis of FTC include the encapsulated follicular variant of papillary thyroid carcinoma (PTC, which possesses some of the nuclear features seen in conventional PTC but may occasionally be indistinguishable from FTC in cytologic preparations, and renal lesions such as benign thyroidization of the kidney and thyroid-like follicular carcinoma of the kidney, which mimic FTC in histologic appearance but do not stain with thyroid markers.

  20. Papillary renal cell carcinoma with metastatic laparoscopic port site and vaginal involvement: a case report

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    Fong Kah

    2011-04-01

    Full Text Available Abstract Introduction Laparoscopic port-site metastasis is a rare but well recognized outcome following surgery in urological cancers, with its etiology not clearly understood. Additionally, vaginal metastasis in clear cell renal cell carcinoma is rare, and has not been previously reported in the setting of papillary renal cell carcinoma. Case presentation We present the case of a 71-year-old Chinese woman with metastatic type II papillary renal cell carcinoma with histologically verified vaginal involvement and a concurrent laparoscopic port-site metastasis. This was also associated with a unique constellation of widely disseminated metastatic sites, which include a local relapse, the peritoneum and the urethra. Conclusion Laparoscopic port-site metastases are associated with the presence of advanced cancer with multiple sites of metastasis. We hypothesize from the findings of our report and background data that this phenomenon is more likely to be related to tumor factors rather than operative factors. We also present what is, to the best of our knowledge, the first reported case in the literature of vaginal and urethral metastasis and the second reported case of laparoscopic port-site recurrence.

  1. Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

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    Ronald M Bukowski

    2010-03-01

    Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, CCF Lerner College of Medicine of CWRU Cleveland, OH, USAAbstract: The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC. One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed.Keywords: metastatic renal cell carcinoma, bevacizumab, interferon-α

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

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    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

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

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    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.

  4. Who will benefit more from maintenance therapy of metastatic colorectal cancer?

    Science.gov (United States)

    Zhou, Mingyi; Fu, Lingyu; Zhang, Jingdong

    2018-02-23

    Whether there is a difference in the efficacy of maintenance treatment for metastatic colorectal cancer (mCRC) between patients who achieve complete response (CR)/partial response (PR) and those with stable disease (SD) after induction treatment is controversial. PubMed, Cochrane Systematic Reviews, the Cochrane Collaboration Central Register of Controlled Clinical Trials, ClinicalTrials.gov, and databases of conferences were queried to identify randomized controlled trials evaluating the efficacy of maintenance treatment for mCRC patients. The search included articles dated from the inception of these resources until June 20, 2017. We estimated hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS). Network meta-analysis was performed to compare the efficacy of four regimens as maintenance treatment. Three randomized controlled trials comprising 1,301 patients were included in this network meta-analysis. Patients who achieved CR/PR after induction therapy benefited more from maintenance treatment than patients who achieved SD (PFS: HR [CR/PR] 1.50, 95% CI 1.09-2.08, vs. HR [SD] 1.35, 95% CI 1.04-1.74; OS: HR [CR/PR] 1.04, 95% CI 0.94-1.15, vs. HR [SD] 1.03, 95% CI 0.99-1.07). The results of network meta-analysis suggested that chemotherapy alone and observation were inferior to chemotherapy plus bevacizumab as maintenance treatment. Patients with mCRC who achieve CR/PR after induction therapy might benefit more from maintenance treatment than those with SD. Chemotherapy plus bevacizumab was the most appropriate regimen for maintenance treatment.

  5. Regorafenib Versus Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: A Retrospective Comparison.

    Science.gov (United States)

    Masuishi, Toshiki; Taniguchi, Hiroya; Hamauchi, Satoshi; Komori, Azusa; Kito, Yosuke; Narita, Yukiya; Tsushima, Takahiro; Ishihara, Makoto; Todaka, Akiko; Tanaka, Tsutomu; Yokota, Tomoya; Kadowaki, Shigenori; Machida, Nozomu; Ura, Takashi; Fukutomi, Akira; Ando, Masashi; Onozawa, Yusuke; Tajika, Masahiro; Yasui, Hirofumi; Muro, Kei; Mori, Keita; Yamazaki, Kentaro

    2017-06-01

    Regorafenib and trifluridine/tipiracil (TAS-102) both prolong survival for patients with refractory metastatic colorectal cancer. However, it is unclear which drug should be administered first. We retrospectively evaluated the data from patients who had received regorafenib or TAS-102 at 2 institutions from May 2013 to March 2015. The inclusion criteria were disease refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, anti-vascular endothelial growth factor antibodies, and anti-epidermal growth factor receptor (EGFR) antibodies (if KRAS exon 2 wild-type), and no previous treatment with regorafenib or TAS-102. A total of 146 and 54 patients received regorafenib and TAS-102, respectively. The baseline characteristics were similar between the 2 groups, except for a history of irinotecan and anti-EGFR therapy and high alkaline phosphatase levels. The median progression-free survival and overall survival were 2.1 months and 6.7 months, respectively, with regorafenib and 2.1 months and 6.5 months, respectively, with TAS-102 (progression-free survival hazard ratio 1.20, P = .27; overall survival hazard ratio, 1.01, P = .97). The analysis of overall survival for patients after the approval of TAS-102 in Japan was similar to the overall survival for the entire population. The frequency of hand-foot syndrome and increased aspartate aminotransferase, alanine aminotransferase, and bilirubin levels was higher and the frequency of neutropenia, leukopenia, anemia, nausea, and febrile neutropenia was lower with regorafenib than with TAS-102. No remarkable differences were found in the efficacy and safety of TAS-102 between patients with and without previous regorafenib and vice versa. Regorafenib and TAS-102 had similar efficacy but resulted in different toxicities, which could guide the agent choice. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib

    International Nuclear Information System (INIS)

    Lim, Yoojoo; Lee, Kyung-Hun; Bang, Ji-In; Paeng, Jin Chul; Han, Sae-Won; Kim, Jee Hyun; Kang, Gyeong Hoon; Jeong, Seung-Yong; Park, Kyu Joo; Kim, Tae-You

    2017-01-01

    This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC). Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome. A total of 40 patients were evaluable for PET image analysis. Among various PET parameters, total lesion glycolysis (TLG) measured in the same target lesions for RECIST 1.1 analysis were the most significant in predicting prognosis, with the lowest p-value observed in TLG calculated using the margin threshold of 40 % (TLG 40 % ). Further analysis using TLG 40 % showed significantly longer overall survival (OS) in patients with lower baseline TLG 40 % (<151.8) (p = 0.003, median 14.2 vs. 9.1 months in <151.8 and ≥151.8, respectively). Patients showing higher decrease in TLG 40 % after treatment showed significantly longer progression-free survival (PFS) (p = 0.001, median 8.0 vs. 2.4 months in % ΔTLG 40 % < -9.6 % and ≥ -9.6 %, respectively) and OS (p = 0.002, median 16.4 vs. 9.1 months in % ΔTLG 40 % < -9.6 % and ≥ -9.6 %, respectively). The same cutoff could discriminate patients with longer survival among the patients who were under the stable disease category according to RECIST 1.1 (median PFS 8.4 vs. 6.8 months, p = 0.020; median OS 18.3 vs. 11.5 months, p = 0.049). Measurement of TLG can predict treatment outcome of regorafenib in mCRC. (orig.)

  7. Aflibercept as a second-line therapy in metastatic colorectal cancer: A limited Indian experience

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    Govind Babu

    2016-01-01

    Full Text Available Introduction: Aflibercept in combination with FOLFIRI has been shown to improve overall survival in the pivotal VELOUR study. Aflibercept has not yet been marketed in India. Sanofi has made available this drug for Indian patients under a program called Named Patient Access Program (NPP. We present a limited clinical experience with the use of aflibercept at our center. Materials and Methods: We analyzed the data of the patients who received aflibercept under NPP. Aflibercept was given in combination with FOLFIRI as second-line for patients who progressed on oxaliplatin based therapy. Aflibercept was given at 4 mg/kg intravenous (IV every 15 days. Chemotoxicities were assessed as per CTCAE. Response evaluation was done every four cycles. Results: Five patients were enrolled. The median age was 34 years. The median number of aflibercept cycles administered was 12. Common grade 2/3 toxicities were mucositis, diarrhea, neutropenia thrombocytopenia, and hypertension seen in three (60%, three (60%, two (40%, two (40%, and one patient respectively. After four cycles, the response was assessed as: One complete remission (CR, three partial remissions (PR, and one progressive disease (PD. Three patients completed 12 cycles of chemotherapy and aflibercept. At the end of 12 cycles, one patient still in CR and two patients were in PR. Four patients were alive till date. Conclusion: As we had very less number of patients, it was very difficult to compare it with VELOUR data. It is one of option as second-line in metastatic colorectal cancer (mCRC who progressed on oxaliplatin chemotherapy. Mucositis, diarrhea, and hematological toxicity were the most common toxicity in our patient.

  8. SATB2 is a Promising Biomarker for Identifying a Colorectal Origin for Liver Metastatic Adenocarcinomas

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    Yi-Jun Zhang

    2018-02-01

    Full Text Available SATB2 (Special AT-rich sequence-binding protein 2 has recently been shown to be a specific biomarker of colorectal cancer (CRC. The aim of this study was to investigate the diagnostic potential of SATB2 as a means of detecting a CRC origin for liver metastases. SATB2 expression was examined in a resection cohort of 101 CRC and 273 non-CRC adenocarcinoma samples using immunohistochemistry (IHC. The diagnostic accuracy of CRC origins of liver metastases based on SATB2 and a three marker panel of SATB2, CK20 and CDX2 was evaluated using an independent cohort of 192 liver biopsies. IHC showed 97 of the 101 (96.0% primary CRC samples were SATB2 positive, compared to only 6 of the 273 (2.1% samples of other cancer types. The sensitivity, specificity and AUC values of SATB2 expression in resection samples were 97%, 97.1% and 0.977, respectively. Meanwhile, for the liver biopsy samples, the sensitivity, specificity and AUC values of a CRC liver metastases was 92.2%, 97.8% and 0.948 for SATB2, 95.1%, 91.0% and 0.959 for CK20, and 100%, 85.4% and 0.976 for CDX2, respectively. Further analysis demonstrated that all three-marker positivity was detected in 92/103 (89.3% CRC and 2/89 (2.2% non-CRC liver metastases sampled by biopsy. Our findings suggest that SATB2, as measured by IHC, could serve as a promising diagnostic biomarker of CRC metastases. Combining evaluation of SATB2 with CK20 and CDX2 to form a three marker panel further improved the detection of metastatic CRCs in liver biopsy tissues.

  9. Metastatic Renal Cell Carcinoma Presenting as Gastric Ulcer: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Alhareth Al Juboori

    2017-01-01

    Full Text Available Renal cell carcinoma (RCC accounts for approximately 3% of all adult malignancies. True gastrointestinal metastases, specifically to gastric wall, have been rarely observed. Herein we describe a case of delayed metastasis to gastric wall occurring more than a decade after previously curative nephrectomy for RCC. A 67-year-old male with history of right radical nephrectomy in 2001 for RCC was found to have an asymptomatic right lower lobe solitary lung mass upon routine follow-up in 2011, with final biopsy results showing metastatic RCC for which he was treated accordingly. In 2014, patient was evaluated for dyspepsia with microcytic anemia and underwent an esophagogastroduodenoscopy and colonoscopy. EGD revealed a solitary one-centimeter atypical ulcer in the posterior mid gastric body with biopsy results being consistent with metastatic RCC. Our literature review has yielded thirty-six reported cases of RCC in association with gastric wall metastases.

  10. Late metastatic endometrial carcinoma at the repair site of an abdominal wall incisional hernia.

    Science.gov (United States)

    Meshikhes, Abdul-Wahed N; Al-Badr, Suha H; Sulais, Ehsan A; Al-Qudaihi, Hibba M

    2017-05-01

    The abdominal wall is a very rare site for endometrial cancer metastases. Its appearance generally indicates advanced cancer with poor prognosis. We report a case of a 55-year-old female who presented with an incisional hernia 4 years after abdominal panhysterectomy for endometrioid adenocarcinoma in 2009. Open hernia mesh repair was performed but on follow-up, she complained of pain and a swelling at the repair site. This was radiologically diagnosed as fibromatosis, but tru-cut biopsy confirmed presence of fibromatosis as well as a metastatic endometrial carcinoma. She was started on neoadjuvant chemotherapy, but had poor response, and therefore, radical excision was performed. She remained well with no metastatic recurrence at 12-month follow-up. This case illustrates late appearance of abdominal wall metastasis from abdomino-pelvic malignancies and highlights the need to exclude the presence of recurrence or metastases prior to surgical repair of incisional hernia occurring after the resection of abdominal or pelvic malignancy.

  11. External beam radiotherapy for palliation of pain from metastatic carcinoma of the prostate

    International Nuclear Information System (INIS)

    Benson, R.C. Jr.; Hasan, S.M.; Jones, A.G.; Schlise, S.

    1982-01-01

    Radiotherapy often is used for palliation of bone pain from metastatic cancer of the prostate but an objective evaluation of its efficacy in a large series of patients is unavailable. We report the results of external beam irradiation in 62 patients who had bone pain secondary to stage D carcinoma of the prostate. The variables used to judge pain before and after radiotherapy included subjective evaluation of pain, status of activity and quantitation of analgesic use. Complete relief of pain was achieved in 26 patients (42 per cent), partial relief in 22 (35 per cent) and no relief in 14 (23 per cent). On the basis of our experience external beam irradiation is useful palliative therapy for pain from metastatic cancer of the prostate

  12. Detection of recurrent colorectal carcinoma with 18F-FDG positron emission tomography (PET)

    International Nuclear Information System (INIS)

    Scott, A.M.; Berlangieri, S.U.; Zalcberg, J.; Fox, R.; Cebon, J.; McLeish, A.; Thomas, D.; Chan, G.; Tochon-Danguy, H.; Egan, G.F.; McKay, W.J.

    1998-01-01

    Full text: The appropriate surgical management of recurrent colorectal carcinoma is dependent on the accurate detection of possible primary site recurrence and distant spread of disease. The aim of this study was therefore to evaluate the clinical accuracy of 18 F-FDG PET in detecting recurrent colorectal carcinoma. Over a 12-month period we have performed 21 studies in 17 patients (12 M: 5 F, age range 52-73 y) with known or suspected recurrent colorectal carcinoma. All patients underwent PET imaging of the abdomen and pelvis, or whole body imaging, with a whole body PET scanner (Siemens 951/R) following injection of 400 MBq of 18 F-FDG. All PET studies were interpreted with full knowledge of CT findings, and results were compared to subsequent surgical findings, biopsy or follow-up by conventional imaging methods (e.g. CT scan). Of the 21 studies performed, 18 (86%) had abnormal sites of 18 F-FDG uptake; all sites were subsequently confirmed as recurrent colorectal carcinoma. PET identified a total of 30 sites of disease in the pelvis (n = 4), abdomen (n =10), liver (n = 6), thorax (n = 9) and abdominal surgical scar (n 1), and was false negative in one lung lesion. CT scan correctly identified 14 sites as recurrent tumour; 9/12 patients (pts) with equivocal changes on CT scan had recurrent disease identified by PET. In 10 pts with elevated serum CEA but negative or equivocal CT scans, PET correctly identified 8 pts with proven recurrent disease. Previously unsuspected disease was found at six sites by PET. Lesions as small as 1.2 cm proven at surgery were identified with PET. In conclusion, this study shows 18 F-FDG PET to be a promising method for accurate detection of recurrent colorectal carcinoma

  13. 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

    2015-01-01

    in 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...... was performed with a standardised method. A total of 107 patients were included in the biomarker study. The median baseline plasma TIMP-1 level was 271.1 ng/ml (range 65.9-1432 ng/ml) with no significant associations with baseline clinical characteristics. Median baseline plasma TIMP-1 levels were significantly...... % CI 4.4-13.7) and 12.0 months (95 % CI 10.1-14.3), respectively, p characteristics (except primary tumour...

  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...... at a dose of 500 mg/m(2) for 16 weeks followed by cetuximab as maintenance therapy until disease progression. RESULTS: Between July 2008 and September 2010, 152 KRASwt patients were included. The response rate was 62% (95% confidence interval [CI], 54%-69%), median progression-free survival was 8.0 months...

  15. Intact and cleaved plasma soluble urokinase receptor in patients with metastatic colorectal cancer treated with oxaliplatin with or without cetuximab

    DEFF Research Database (Denmark)

    Tarpgaard, Line Schmidt; Christensen, Ib Jarle; Høyer-Hansen, Gunilla

    2015-01-01

    ) in a ligand-independent manner. The purpose of the study was to evaluate whether plasma soluble intact and cleaved uPAR(I-III)+(II-III) levels could identify a subpopulation of patients with metastatic colorectal cancer (mCRC) where treatment with cetuximab would have a beneficial effect. Plasma samples were...... with FLOX + cetuximab as compared to patients with KRAS wild-type and high levels of suPAR. These results thus support the preclinical findings and should be further tested in an independent clinical data set....

  16. The Effect of Overweight Status on Total and Metastatic Number of Harvested Lymph Nodes During Colorectal Surgery

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    Sezgin Zeren

    2016-03-01

    Full Text Available Objective: The aim of this study is to evaluate the rela­tionship between higher body mass index (BMI and har­vested total or metastatic lymph node numbers in patients who underwent surgery for colorectal cancers. Methods: Between March 2014 and January 2016, totally 71patients who underwent laparoscopic or conventional surgery for colorectal cancer were evaluated retrospec­tively. The data of age, gender, BMI, surgical procedure, tumor localization , postoperative mortality status, total number of harvested and metastatic lymph node were collected. The patients having 24.9 (kg/m2 or lower BMI values were classified as normal (Group 1 and patients having BMI values of 25 or over were overweight (Group 2. Afterwards, the parameters between groups and the effect of higher BMI were analyzed. Results: The mean age of the patients was 64.5 ± 14 years. The average BMI value in group 1 was 22.3 (kg/m2 and 27.0 (kg/m2 in group 2. According to localisation of tumor, transverse colon was the rare region for both groups. The common regions for tumor localisation in group 1 were right colon, sigmoid colon and rectum. In group 2 the common localisation for tumors were rectum, right colon and sigmoid colon. There was no difference between groups about postoperative mortality rates (p > 0.05. The mean of the total number of harvested lymph nodes were 14 in group 1 and 12 in group 2. There were no relationship between BMI and tumor diameter, total or metastatic number of harvested lymph nodes. Conclusion: Higher BMI values does not effect the num­ber of excised total or metastatic lymph nodes and tumor diameters. Therefore, the surgeons should not hesitate in overweight patients cancer surgery for dissecting ad­equate number of lymph nodes.

  17. Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition.

    Science.gov (United States)

    Ma, Yihong R; Siegal, Gene P; Wei, Shi

    2017-06-01

    To examine the expression of E-cadherin in paired primary and metastatic signet-ring cell carcinomas (SRCC) of various organ systems in order to explore the potential role of the molecule in metastatic dissemination of this unique tumour type. Thirty-seven consecutive cases of SRCC from various organs with paired primary and metastatic tumorous tissue available were retrieved. The intensity of membranous E-cadherin expression was semiquantitatively scored on a scale of 0-3+. Reduced E-cadherin expression was a distinct feature of primary SRCC and was observed in 78% of primary tumours. Interestingly, the E-cadherin reduction was less frequently seen in metastatic SRCC when compared with their primary counterparts, and was only found in 57% of tumours in lymph node metastases or at distant sites of relapse. Furthermore, the mean score of E-cadherin expression of primary SRCC was significantly lower than that of their metastatic counterparts (2.3 vs 1.8; p=0.008). When divided by organ systems, the reacquisition of E-cadherin expression in the metastatic deposits was most remarkable in the SRCC of upper gastrointestinal tract origin (2.3 vs 1.4; p=0.003), whereas no significant difference was observed in other organ systems. While the reduction of E-cadherin in primary SRCC supports its pivotal role in epithelial-mesenchymal transition, a process crucial in tumour progression and metastatic dissemination, the re-expression of this molecule in metastatic SRCC cells implies a reversal to their epithelial phenotype (thus mesenchymal-epithelial transition) which, in turn, theoretically helps tumour cells to anchor and form cohesive metastatic deposits. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing.

    Science.gov (United States)

    Estrella, Jeannelyn S; Tetzlaff, Michael T; Bassett, Roland L; Patel, Keyur P; Williams, Michelle D; Curry, Jonathan L; Rashid, Asif; Hamilton, Stanley R; Broaddus, Russell R

    2015-12-01

    Although sequencing provides the gold standard for identifying colorectal carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results with melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in ≥ 20% of tumor cells, VE1 IHC had sensitivity of 75% and specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57 BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining, whereas 6 (11%) had no or weak (colorectal carcinomas, 16 (48%) had no or weak staining, whereas 15 (45%) had heterogeneous staining. In contrast with colorectal carcinoma, Bond and Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results. We conclude that VE1 IHC produces suboptimal results in colorectal carcinoma and should not be used to guide patient management. ©2015 American Association for Cancer Research.

  19. Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

    DEFF Research Database (Denmark)

    Davis, Ian D; Xie, Wanling; Pezaro, Carmel

    2017-01-01

    BACKGROUND: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response. OBJECTIVE: To assess outcomes of 2L according to type...... before each line of therapy (favorable, F; intermediate, I; poor, P). Data were analyzed for 1516 patients, of whom 89% had clear cell histology. INTERVENTION: All included patients received targeted therapy for mRCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), time to treatment....... PATIENT SUMMARY: The pattern of treatment failure might help to predict what the next treatment should be for patients with metastatic renal cell carcinoma....

  20. Papillary carcinoma of thyroid with an unusual coexistence of metastatic deposits and tuberculosis in the cervical lymph nodes

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    Nagarajan Swathanthra

    2014-01-01

    Full Text Available Papillary carcinoma of the thyroid with clinically significant cervical lymphadenopathy is a common presentation (particularly in young patients, and it may be the first manifestation of disease. Occasionally, besides metastatic deposits, the cervical lymph nodes may harbor other diseases, and determining the etiology in such a case becomes critical for the institution of proper treatment and complete cure of the patient. Detection of tuberculous lymphadenitis and metastatic deposits by radiological and/or fine needle aspiration cytology methods may not be always easy and may be missed due to inherent defects of the techniques hence, histopathological examination still remains the final resort. We report a case of papillary carcinoma of the thyroid and its rare association with both metastatic deposits and tuberculosis of the contiguous cervical lymph node groups. We suggest that tuberculosis must always be borne in mind besides metastases while evaluating the enlarged neck nodes in papillary carcinoma of the thyroid.

  1. Increased intratumoral FOXP3-positive regulatory immune cells during interleukin-2 treatment in metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Nordsmark, Marianne

    2009-01-01

    PURPOSE: The administration of interleukin-2 (IL-2) may increase the frequency of peripherally circulating FOXP3-positive regulatory immune cells, thus potentially compromising this treatment option for patients with metastatic renal cell carcinoma. The impact of IL-2-based therapy...... on the accumulation of FOXP3-positive immune cells in the tumor microenvironment in metastatic renal cell carcinoma is unknown. EXPERIMENTAL DESIGN: Baseline (n = 58) and on-treatment (n = 42) tumor core biopsies were prospectively obtained from patients with clear cell metastatic renal cell carcinoma before...... and during IL-2-based immunotherapy. Immunohistochemical expression of FOXP3 was estimated by stereological counting technique and correlated with other immune cell subsets and overall survival. RESULTS: A significant increase in absolute intratumoral FOXP3-positive immune cells was observed comparing...

  2. Metastatic breast carcinoma uncovered in an otherwise unremarkable “random colon biopsy”

    Directory of Open Access Journals (Sweden)

    Mike Black

    2016-06-01

    Full Text Available Breast cancer is one of the most devastating cancers afflicting women, being a main cause of cancer related death. Approximately 50% of these patients have developed regional or distant metastases at the time of diagnosis; hence, an early diagnosis and surgery with indicated neoadjuvant therapy are crucial in eradicating this disease and improving patient survival. A significant percentage of patients, even after initial satisfactory tumor removal, still face the threat of metastatic diseases which could plague a wide spectrum of body sites such as bones, lungs, central nervous system, liver and gastrointestinal tract (mostly upper gastrointestinal locations. Colonic and anorectal involvement by metastatic breast cancer has been less frequently reported in disseminated diseases. Typically, metastatic disease presents as a mass, enteric stenosis, or obstruction. Rare cases, however, may not form an endoscopically or radiologically recognizable lesion, and thus could be overlooked. Here we report a unique case of random colon biopsies in a patient presenting with epigastric pain, whose stomach biopsy showed Helicobacter pylori-associated chronic active gastritis. No colonoscopic lesion was present; however, microscopic examination of the “random biopsy” revealed scattered single and small clusters of tumor cells involving the lamina propria of the colonic mucosa, morphologically and immunophenotypically consistent with metastatic disease from breast carcinoma. The clinical presentation and histopathology of the case were reviewed and compared with limited cases reported in the literature. We conclude that high levels of suspicion and alertness are essential to identify occult microscopic gastrointestinal metastatic breast cancer in the absence of a grossly appreciable lesion.

  3. Non-metastatic squamous cell carcinoma in two Hermann’s tortoises (Testudo hermanni

    Directory of Open Access Journals (Sweden)

    Marie-Charlotte von Deetzen

    2012-02-01

    Full Text Available Squamous cell carcinomas (SCC are malignant tumors of the epidermal cells with varying degrees of keratinocyte differentiation. They are common tumors in mammalian and avian species but there are, however, only two description of SCC in tortoises. In this case report we describe two cases of non-metastatic squamous cell carcinomas of the carapax and the plastron in Hermann’s tortoises with evidence of humoral hypercalcemia of malignancy (HHM in one case. HHM is thought to be associated with SCC in mammals due to de novo secretion of parathyroid hormone-related protein (PTHrP by the tumor cells or tumor induced osteolysis but has not been described in reptiles so far.

  4. Metastatic Small Cell Carcinoma of the Breast from Cancer of the Uterine Cervix: A Case Report

    Directory of Open Access Journals (Sweden)

    Beom Seok Kwak

    2018-01-01

    Full Text Available We report here on a case of 51-year-old woman with metastatic small cell carcinoma of the breast that came from her cancer of the uterine cervix. She underwent radical hysterectomy with bilateral salpingo-oophorectomy due to small cell carcinoma of the uterine cervix, and adjuvant radiotherapy was administered to the pelvis. Breast metastasis with a palpable mass then occurred 3 months after the primary surgery. Simple mastectomy and adjuvant chemotherapy were performed. She initially showed a good response to the therapy, yet she ultimately died of multiple metastases with a fulminating disease course. This is an extremely rare case, and only 1 similar case has been reported earlier, so we report on this case along with a review of the relevant literature.

  5. 3-D visualization and quantitation of microvessels in transparent human colorectal carcinoma [corrected].

    Directory of Open Access Journals (Sweden)

    Yuan-An Liu

    Full Text Available Microscopic analysis of tumor vasculature plays an important role in understanding the progression and malignancy of colorectal carcinoma. However, due to the geometry of blood vessels and their connections, standard microtome-based histology is limited in providing the spatial information of the vascular network with a 3-dimensional (3-D continuum. To facilitate 3-D tissue analysis, we prepared transparent human colorectal biopsies by optical clearing for in-depth confocal microscopy with CD34 immunohistochemistry. Full-depth colons were obtained from colectomies performed for colorectal carcinoma. Specimens were prepared away from (control and at the tumor site. Taking advantage of the transparent specimens, we acquired anatomic information up to 200 μm in depth for qualitative and quantitative analyses of the vasculature. Examples are given to illustrate: (1 the association between the tumor microstructure and vasculature in space, including the perivascular cuffs of tumor outgrowth, and (2 the difference between the 2-D and 3-D quantitation of microvessels. We also demonstrate that the optically cleared mucosa can be retrieved after 3-D microscopy to perform the standard microtome-based histology (H&E staining and immunohistochemistry for systematic integration of the two tissue imaging methods. Overall, we established a new tumor histological approach to integrate 3-D imaging, illustration, and quantitation of human colonic microvessels in normal and cancerous specimens. This approach has significant promise to work with the standard histology to better characterize the tumor microenvironment in colorectal carcinoma.

  6. Genetic dissimilarity between primary colorectal carcinomas and their lymph node metastases: ploidy, p53, bcl-2, and c-myc expression--a pilot study.

    Science.gov (United States)

    Zalata, Khaled Refaat; Elshal, Mohamed Farouk; Foda, Abd AlRahman Mohammad; Shoma, Ashraf

    2015-08-01

    The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. This study investigated the changes in the level of expression of a well-defined panel of cell proliferation, differentiation, and apoptosis markers between the primary colorectal cancer (CRC) and the corresponding synchronous lymph node (LN) metastasis from the same patients. DNA flow cytometry and immunostaining of p53, bcl-2, and c-myc were carried out on 36 cases of CRC radical resection specimens with their corresponding LN metastases. There was very low probability that the histological patterns of primary tumors and LN metastases are independent (p < 0.001). Metastatic tumors were significantly more diffusely positive for p53 than the primary tumors (p < 0.001). Conversely, primary tumors were significantly more diffusely positive for c-myc than metastatic tumors (p = 0.011). No significant difference was found between the LNs and the primary tumors in bcl-2 positivity (p = 0.538) and DNA aneuploidy (p = 0.35), with a tendency towards negative bcl-2 and less aneuploidy in LN metastases than primary tumors. In conclusion, LN metastatic colorectal carcinomas have a tendency of being less differentiated, with a higher incidence of diffuse p53 staining, lower incidence of bcl-2 staining, and less aneuploidy in comparison to their primary counterparts suggesting a more aggressive biological behavior, which could indicate the necessity for more aggressive adjuvant therapy.

  7. Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma.

    Science.gov (United States)

    Kaur, Gurjeet; Masoud, Abdelhafid; Raihan, N; Radzi, M; Khamizar, W; Kam, Lee Suk

    2011-08-01

    DNA mismatch repair gene (MMR) abnormalities are seen in 95 per cent of hereditary nonpolyposis colorectal cancer (HNPCC) and 10-15 per cent of sporadic colorectal cancers. There are no data on MMR abnormalities in Malaysian colorectal cancer patients. This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry. Clinicopathological information was obtained from 148 patients' records who underwent bowel resection for colorectal cancer (CRC) at the three hospitals in Malaysia. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins were performed on paraffin embedded tissue containing carcinoma. A total of 148 subjects and 150 colorectal carcinomas of sporadic and hereditary types were assessed. Three patients had synchronous tumours. Twenty eight cancers (18.6%) from 26 subjects (17.6%) had absent immunohistochemical expression of any one of the MMR gene proteins. This comprised absent MLH1 only - 3 cancers, absent MSH2 only - 3, absent MSH6 only - 2, absent PMS2 only - 3, absent MLH1 and PMS2 - 14, absent MSH2 and MSH6 - 2 and absent MLH1, MSH6 and PMS2 - 1. There was significant association between abnormal MMR gene protein expression and proximal colon cancers, mucinous, signet ring and poorly differentiated morphology. Cancers with abnormal MMR gene expression were associated with microsatellite instability-high (MSI-H) phenotype. About 15 per cent demonstrated absent MSH2, MSH6 and PMS2 protein expression in isolation or in combination with other MMR genes, which often predicts a germline mutation, synonymous with a diagnosis of HNPCC. This appears to be high frequency compared to reported data.

  8. Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

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    Christopher Williams

    2005-01-01

    Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

  9. Gastric and Colorectal Metastases of Lobural Breast Carcinoma: A Case Report

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    David Buka

    2016-04-01

    Full Text Available Background: Occurrence of gastric metastasis as the first symptom of breast carcinoma with a long period of latency before presentation of the primary breast carcinoma is rare. Case Report: A patient with gastric metastasis as the first symptom of lobular breast carcinoma, treated by neoadjuvant preoperative chemoradiotherapy and total gastrectomy, with complete local control. Fourteen months after presentation of the gastric metastasis a primary lobular breast carcinoma was discovered, treated by radiotherapy, chemotherapy and hormonal treatment with complete local response. Twenty-three months after diagnosis of breast cancer multiple colorectal metastases from the breast cancer occurred, which were treated by chemotherapy and hormonal treatment. Eighty-six months after diagnosis of gastric metastasis the patient died due to progression of cancer. Conclusions: Metastases to gastrointestinal or gynaecological tracts are more likely in invasive lobular carcinoma than invasive ductal cancer. The pathologist should determine whether or not they check estrogen and progesterone receptor status not simply by signet ring cell morphology but also by consideration of clinic-pathological correlation of the patient, such as the presence of a past history of breast cancer, or the colorectal localization of poorly differentiated carcinoma, which may occur less frequently than in the stomach.

  10. Basal cell carcinoma with progression to metastatic neuroendocrine carcinoma: Case report and review of the literature

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    Volkan Adsay

    2010-03-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Merkel cell carcinoma (MCC or primary cutaneous neuroendocrine carcinoma is a malignant tumor considered to demonstrate differentiation towards Merkel cells that are present at the base of the epidermis or around the apical end of some hair follicles and are thought to play an yet uncertain role in sensory transduction. Here we present the case of a 54-year-old female with a basal cell carcinoma (BCC of the skin with neuroendocrine features (positivity for chromogranin that has evolved during multiple recurrences and radiotherapy into a high-grade neuroendocrine carcinoma with morphologic and immunohistochemical features of MCC (trabecular and nesting arrangement, positivity for chromogranin, cytokeratin 20, neuron specific enolase, and also neurosecretory granules on electron microscopy. The progression from a chromogranin positive basal cell carcinoma of the skin, to a high grade neuroendocrine carcinoma demonstrates the potential for cross differentiation among skin tumors.

  11. Pulmonary sclerosing hemangioma in a 21-year-old male with metastatic hereditary non-polyposis colorectal cancer: Report of a case

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    Angele Martin K

    2011-06-01

    Full Text Available Abstract Background Pulmonary sclerosing hemangioma (SH is a rare tumor of the lung predominantly affecting Asian women in their fifth decade of life. SH is thought to evolve from primitive respiratory epithelium and mostly shows benign biological behavior; however, cases of lymph node metastases, local recurrence and multiple lesions have been described. Case Presentation We report the case of a 21-year-old Caucasian male with a history of locally advanced and metastatic rectal carcinoma (UICC IV; pT4, pN1, M1(hep that was eventually identified as having hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome. After neoadjuvant chemotherapy followed by low anterior resection, adjuvant chemotherapy and metachronous partial hepatectomy, he was admitted for treatment of newly diagnosed bilateral pulmonary metastases. Thoracic computed tomography showed a homogenous, sharply marked nodule in the left lower lobe. We decided in favor of atypical resection followed by systematic lymphadenectomy. Histopathological analysis revealed the diagnosis of SH. Conclusions Cases have been published with familial adenomatous polyposis (FAP and simultaneous SH. FAP, Gardner syndrome and Li-Fraumeni syndrome, however, had been ruled out in the present case. To the best of our knowledge, this is the first report describing SH associated with Lynch syndrome.

  12. Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer

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    Karthaus, Meinolf; Hofheinz, Ralf-Dieter; Mineur, Laurent; Letocha, Henry; Greil, Richard; Thaler, Josef; Fernebro, Eva; Oliner, Kelly S; Boedigheimer, Michael; Twomey, Brian; Zhang, Ying; Demonty, Gaston; Köhne, Claus-Henning

    2016-01-01

    Background: To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC). Methods: 154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression. Results: Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease. Median response duration was longer in RAS WT (13.0 months) vs RAS MT (5.8 months) (hazard ratio (HR): 0.16). Median progression-free survival was longer in RAS WT vs MT (11.2 vs 7.3 months; HR, 0.37) and was also longer in RAS WT/BRAF WT vs RAS or BRAF MT (13.2 vs 6.9 months; HR, 0.25). Incidence of adverse events was similar regardless of RAS/BRAF status, and no new safety signals were noted. Among patients with RAS WT tumours, ORR was 67% with high AREG expression and 38% with low AREG expression. Conclusions: First-line panitumumab+FOLFIRI was associated with favourable efficacy in patients with RAS WT and RAS WT/BRAF WT vs MT mCRC tumours and was well tolerated. PMID:27764839

  13. Sensitivity of single and double contrast barium enema in the detection of colorectal carcinoma

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    Myllylae, V.; Paeivansalo, M.; Laitinen, S.; Oulu Univ.

    1984-01-01

    The preoperative barium enema of the 188 colorectal carcinoma patients operated at the Oulu University Central Hospital (Finland) during 1977-1982 were examined retrospectively. Altogether 112 single contrast studies and 87 double contrast studies had been made on these patients. The single contrast barium enemas had resulted in a correct diagnosis of colorectal carcinoma in 93 cases (sensitivity 83%). The correct diagnosis in the double contrast studies numbered 71 (sensitivity 82%). Most of the overlooked carcinomas were located in the caecum, in the sigmoid or the rectum. Most of the errors made in the single contrast studies were due to detection errors and poor evacuation. The most common failures in double contrast enemas were detection errors and nonvisualisation of the sigmoid. The authors recommend use of the double contrast technique and suggest that the two methods of barium enema be used to complement each other. A false negative diagnosis delayed the operation of the colorectal carcinoma patients by 2.2 months (median). (orig.) [de

  14. Patterns of somatic alterations between matched primary and metastatic colorectal tumors characterized by whole-genome sequencing.

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    Xie, Tao; Cho, Yong Beom; Wang, Kai; Huang, Donghui; Hong, Hye Kyung; Choi, Yoon-La; Ko, Young Hyeh; Nam, Do-Hyun; Jin, Juyoun; Yang, Heekyoung; Fernandez, Julio; Deng, Shibing; Rejto, Paul A; Lee, Woo Yong; Mao, Mao

    2014-10-01

    Colorectal cancer (CRC) patients have poor prognosis after formation of distant metastasis. Understanding the molecular mechanisms by which genetic changes facilitate metastasis is critical for the development of targeted therapeutic strategies aimed at controlling disease progression while minimizing toxic side effects. A comprehensive portrait of somatic alterations in CRC and the changes between primary and metastatic tumors has yet to be developed. We performed whole genome sequencing of two primary CRC tumors and their matched liver metastases. By comparing to matched germline DNA, we catalogued somatic alterations at multiple scales, including single nucleotide variations, small insertions and deletions, copy number aberrations and structural variations in both the primary and matched metastasis. We found that the majority of these somatic alterations are present in both sites. Despite the overall similarity, several de novo alterations in the metastases were predicted to be deleterious, in genes including FBXW7, DCLK1 and FAT2, which might contribute to the initiation and progression of distant metastasis. Through careful examination of the mutation prevalence among tumor cells at each site, we also proposed distinct clonal evolution patterns between primary and metastatic tumors in the two cases. These results suggest that somatic alterations may play an important role in driving the development of colorectal cancer metastasis and present challenges and opportunities when considering the choice of treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Profile of trifluridine/tipiracil hydrochloride in the treatment of metastatic colorectal cancer: efficacy, safety, and place in therapy

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    Sunakawa Y

    2017-09-01

    Full Text Available Yu Sunakawa, Naoki Izawa, Takuro Mizukami, Yoshiki Horie, Mami Hirakawa, Hiroyuki Arai, Takashi Ogura, Takashi Tsuda, Takako Eguchi Nakajima Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan Abstract: TAS-102, with its robust survival efficacy and feasible toxicity, is one of the standard salvage-line treatments for patients with metastatic colorectal cancer (mCRC. No definitive data are available to determine which drug should be administered first during salvage-line treatment. Therefore, it is imperative that we establish the sequence of administration by considering drug toxicity profiles based on patient characteristics, such as age, performance status, comorbidities, tolerability to previous treatments, and patient preferences. The identification of predictive biomarkers in response to TAS-102 or its toxicity is urgently needed for better patient selection. Moreover, to strengthen efficacy or relieve toxicity, combinations with other agents, which could potentially emerge as standard treatment regimens, have been investigated and compared to existing active regimens for mCRC. Keywords: TAS-102, metastatic colorectal cancer, regorafenib, biomarker

  16. Prophylactic Use of Oral Dexamethasone to Alleviate Fatigue During Regorafenib Treatment for Patients With Metastatic Colorectal Cancer.

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    Fukuoka, Shota; Shitara, Kohei; Noguchi, Masaaki; Kawazoe, Akihito; Kuboki, Yasutoshi; Bando, Hedeaki; Okamoto, Wataru; Kojima, Takashi; Doi, Toshihiko; Ohtsu, Atsushi; Yoshino, Takayuki

    2017-06-01

    Fatigue is the most common toxicity of all grade toxicities with regorafenib, was the second most common toxicity in the CORRECT (regorafenib monotherapy for previously treated metastatic colorectal cancer) study, and is a major reason for early dose modification. The results from a recent randomized study suggested that dexamethasone (DEX) can improve cancer-related fatigue. We retrospectively analyzed the effect of prophylactic use of an oral DEX on fatigue during regorafenib treatment in patients with metastatic colorectal cancer (mCRC). A total of 105 patients who had received regorafenib at our institution from May 2013 to August 2014 were divided into 2 groups according to oral DEX use (2 mg/day; at the physician's discretion). Of the 105 patients, 31 received prophylactic DEX and 74 received regorafenib alone. The time to dose modification was significantly longer in the DEX group than in the no DEX group (15 days vs. 9 days; P = .009). The incidence of fatigue (grade ≥ 1) was significantly lower with DEX than without DEX (25.8% vs. 50.0%; P = .022). Fewer patients experienced a decreased appetite (grade ≥ 1; 3.2% vs. 35.1%; P regorafenib treatment, resulting in prolonging the time to dose modification for regorafenib. The decreased incidence of appetite loss and HFSR also suggest that concurrent DEX administration with regorafenib warrants further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2.

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    Xu, Ke; Liang, Xin; Shen, Ke; Cui, Daling; Zheng, Yuanhong; Xu, Jianhua; Fan, Zhongze; Qiu, Yanyan; Li, Qi; Ni, Lei; Liu, Jianwen

    2012-09-01

    Colorectal carcinoma is a frequent cause of cancer-related death in men and women. miRNAs (microRNAs) are endogenous small non-coding RNAs that regulate gene expression negatively at the post-transcriptional level. In the present study we investigated the possible role of microRNAs in the development of MDR (multidrug resistance) in colorectal carcinoma cells. We analysed miRNA expression levels between MDR colorectal carcinoma cell line HCT116/L-OHP cells and their parent cell line HCT116 using a miRNA microarray. miR-297 showed lower expression in HCT116/L-OHP cells compared with its parental cells. MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells and is a predicted target of miR-297. Additionally miR-297 was down-regulated in a panel of human colorectal carcinoma tissues and negatively correlated with expression levels of MRP-2. Furthermore, we found that ectopic expression of miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. Taken together, our findings suggest that miR-297 could play a role in the development of MDR in colorectal carcinoma cells, at least in part by modulation of MRP-2.

  18. Radiotherapy for Metastatic Merkel Cell Carcinoma: A Review of the Literature

    International Nuclear Information System (INIS)

    Khan, L.; Barnes, E. A.

    2012-01-01

    Merkel cell carcinoma is a rare form of non-melanoma skin cancer of neuroendocrine origin. Optimal management of patients is controversial and the role of radiotherapy is unclear. Purpose. The purpose of this study was to review the efficacy of RT in the treatment of both local and distant metastatic disease from MCC. Methods. A literature search was conducted in MEDLINE (1946-January Week 1 2012) and Embase (1980-2012 Week 2). Articles of interest analyze the efficacy of radiotherapy for treatment of metastatic MCC and did not exclude case reports. Results. All articles except one focusing on the role of radiotherapy were of retrospective origin or case series. Significant limitations applied in all studies due to limited sample sizes and the retrospective nature of these studies. Radiotherapy improves locoregional control in the adjuvant setting, and many series suggest an improvement in overall survival. In cases where surgery is not possible, definitive radiotherapy may be an as-efficacious alternative. The radiosensitive nature of MCC coupled with existing reports suggests that treatment via current protocols for other primary tumors is adequate. Conclusion. Further studies should be conducted prospectively to clarify the true role of radiotherapy in metastatic MCC.

  19. Management of metastatic renal cell carcinoma in patients with poor prognosis

    International Nuclear Information System (INIS)

    Bullock, Andrea; McDermott, David F; Atkins, Michael B

    2010-01-01

    An improved understanding of renal cell carcinoma (RCC) biology has translated into major advances in the treatment of patients with metastatic RCC in recent years. Clinical and pathologic criteria can be used to identify RCC patients with poor prognoses. Such patients, however, are often excluded from the cancer clinical trials that guide treatment recommendations. This article reviews available information on the management of patients with metastatic RCC and poor risk features, focusing on the role of vascular endothelial growth factor (VEGF) pathway and mammalian target of rapamycin (mTOR) inhibitors. While patients with poor risk features have a more guarded outcome, treatment with temsirolimus has produced meaningful improvements in overall survival for this population. Definitive phase III trial data are lacking for the VEGF pathway inhibitors in patients with poor prognostic features. However, available data suggest that such patients tolerate VEGF pathway blockade reasonably well and are likely to achieve some benefit relative to treatment with interferon. Ongoing translational research efforts may help to define novel treatment approaches specific for patients with metastatic RCC and poor prognostic features

  20. Radiotherapy for Metastatic Merkel Cell Carcinoma: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Luluel Khan

    2012-01-01

    Full Text Available Introduction. Merkel cell carcinoma is a rare form of non-melanoma skin cancer of neuroendocrine origin. Optimal management of patients is controversial and the role of radiotherapy is unclear. Purpose. The purpose of this study was to review the efficacy of RT in the treatment of both local and distant metastatic disease from MCC. Methods. A literature search was conducted in MEDLINE (1946—January Week 1 2012 and Embase (1980–2012 Week 2. Articles of interest analyze the efficacy of radiotherapy for treatment of metastatic MCC and did not exclude case reports. Results. All articles except one focusing on the role of radiotherapy were of retrospective origin or case series. Significant limitations applied in all studies due to limited sample sizes and the retrospective nature of these studies. Radiotherapy improves locoregional control in the adjuvant setting, and many series suggest an improvement in overall survival. In cases where surgery is not possible, definitive radiotherapy may be an as-efficacious alternative. The radiosensitive nature of MCC coupled with existing reports suggests that treatment via current protocols for other primary tumors is adequate. Conclusion. Further studies should be conducted prospectively to clarify the true role of radiotherapy in metastatic MCC.

  1. Metastatic Sarcomatoid Squamous Cell Carcinoma of the Cervix Presenting with Chest Mass

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    Lilit Karapetyan

    2017-01-01

    Full Text Available Background. Sarcomatoid squamous cell carcinoma is a rare and aggressive form of cervical cancer. We report a case of metastatic sarcomatoid squamous cell carcinoma (SSCC of cervix that presented with an anterior chest wall mass. Case. A 43-year-old Hispanic female presented with a two-month history of a central chest wall mass. The patient’s only past medical history was SSCC of the cervix, stage IIB, diagnosed two years priorly. She underwent neoadjuvant chemoradiation therapy (CRT with cisplatin followed by radical hysterectomy. Surgical margins were positive which led to adjuvant CRT with carboplatin and paclitaxel. PET scan 4 months after the postoperative treatment was negative for recurrence and metastatic disease. On current presentation, the CT chest revealed anterior mediastinal destructive soft tissue mass involving sternum, and the biopsy showed SSCC. The patient received palliative radiation therapy to her chest with improvement in pain and ability to swallow. After discussing the prognosis she refused further chemotherapy and decided on hospice care. Conclusion. Despite good response to first-line therapy, SSCC tends to recur early and does not respond to second-line therapy. Radiation therapy seems to be the most effective modality for treatment, but randomized controlled trials of therapy are impractical.

  2. Multilevel 3D Printing Implant for Reconstructing Cervical Spine With Metastatic Papillary Thyroid Carcinoma.

    Science.gov (United States)

    Li, Xiucan; Wang, Yiguo; Zhao, Yongfei; Liu, Jianheng; Xiao, Songhua; Mao, Keya

    2017-11-15

    MINI: A 3D printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma. The personalized porous implant printed in Ti6AL4V provided excellent physicochemical properties and biological performance, including biocompatibility, osteogenic activity, and bone ingrowth effect. A unique case report. A three-dimensional (3D) printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma in a middle-age female patient. Papillary thyroid carcinoma is a malignant neoplasm with a relatively favorable prognosis. A metastatic lesion in multilevel cervical spine (C2-C4) destroys neurological functions and causes local instability. Radical excision of the metastasis and reconstruction of the cervical vertebrae sequence conforms with therapeutic principles, whereas the special-shaped multilevel upper-cervical spine requires personalized implants. 3D printing is an additive manufacturing technology that produces personalized products by accurately layering material under digital model control via a computer. Reporting of this recent technology for reconstructing multilevel cervical spine (C2-C4) is rare in the literature. Anterior-posterior surgery was performed in one stage. Radical resection of the metastatic lesion (C2-C4) and thyroid gland, along with insertion of a personalized implant manufactured by 3D printing technology, were performed to rebuild the cervical spine sequences. The porous implant was printed in Ti6AL4V with perfect physicochemical properties and biological performance, such as biocompatibility and osteogenic activity. Finally, lateral mass screw fixation was performed via a posterior approach. Patient neurological function gradually improved after the surgery. The patient received 11/17 on the Japanese Orthopedic Association scale and ambulated with a personalized skull-neck-thorax orthosis on

  3. Clear Cell Renal Cell Carcinoma Metastatic to the Gynecologic Tract: A Clinicopathologic Analysis of 17 Cases.

    Science.gov (United States)

    Fadare, Oluwole; Desouki, Mohamed M; Gwin, Katja; Hanley, Krisztina Z; Jarboe, Elke A; Liang, Sharon X; Quick, Charles M; Rawish, Kojo R; Roma, Andres A; Zheng, Wenxin; Hecht, Jonathan L; Parkash, Vinita; Osunkoya, Adeboye O

    2017-11-14

    Clear cell renal cell carcinomas (CCRCC) rarely metastasizes to the gynecologic tract. In this study, we analyzed a multi-institutional data set to provide insights into the clinical, morphologic, and immunophenotypic features of this phenomenon. Seveteen metastatic CCRCC involving the gynecologic tract [ovary/fallopian tube (n=9), vulva (n=2), uterine corpus (n=3), cervix (n=2), uterine serosa (n=1)] were analyzed. Mean patient age was 62 yr (range: 45-79 yr). Most cases (15/17) presented as a recurrence 6 to 72 mo postnephrectomy, 1 case was concurrently diagnosed, and 1 case (a cervical metastasis) was diagnosed prenephrectomy. In 10 cases, metastases to other locations were identified within 6 wk of the gynecologic tract lesion. The adnexa were the most common site of metastases and the mean tumor size of adnexal metastases was 3.7 cm; in only 2 of 9 cases were metastases bilateral and only 1 had external surface nodules. The morphologic and immunohistochemical features of metastatic CCRCC were compared with those of 102 müllerian clear cell carcinomas (müllerian CCC: 49 endometrial, 53 ovarian). Although CCRCC and müllerian CCC displayed extensive morphologic overlap, a higher mitotic index and a higher frequency of an alveolar pattern were seen in CCRCC, whereas diffuse hobnail cells, hyaline globules, tubulocystic pattern, or any papillary pattern were more frequently seen in müllerian CCC. CA-IX, CD10, and renal cell carcinoma antigen were more frequently expressed in CCRCC than müllerian CCC, whereas Napsin-A, CK7, and p504S showed the reverse. PAX8 and HNF1β did not significantly distinguish between the 2 groups. In summary, gynecologic tract metastases most often occur as a relapse of a previously resected CCRCC, and these relapses may occur many years postnephrectomy. Gynecologic tract metastases are often accompanied by concurrent metastases to other organs. The gross pathology of metastatic CCRCC in the ovary may potentially overlap

  4. Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib

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    Lim, Yoojoo; Lee, Kyung-Hun [Seoul National University Hospital, Department of Internal Medicine, 101 Daehang-ro, Jongno-gu, Seoul (Korea, Republic of); Bang, Ji-In; Paeng, Jin Chul [Seoul National University Hospital, Department of Nuclear Medicine, 101 Daehang-ro, Jongno-gu, Seoul (Korea, Republic of); Han, Sae-Won [Seoul National University Hospital, Department of Internal Medicine, 101 Daehang-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Cancer Research Institute, Seoul (Korea, Republic of); Kim, Jee Hyun [Seoul National University Bundang Hospital, Department of Internal Medicine, Geyonggi-do (Korea, Republic of); Kang, Gyeong Hoon [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Jeong, Seung-Yong; Park, Kyu Joo [Seoul National University Hospital, Department of Surgery, Seoul (Korea, Republic of); Kim, Tae-You [Seoul National University Hospital, Department of Internal Medicine, 101 Daehang-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of)

    2017-05-15

    This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC). Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome. A total of 40 patients were evaluable for PET image analysis. Among various PET parameters, total lesion glycolysis (TLG) measured in the same target lesions for RECIST 1.1 analysis were the most significant in predicting prognosis, with the lowest p-value observed in TLG calculated using the margin threshold of 40 % (TLG{sub 40} {sub %}). Further analysis using TLG{sub 40} {sub %} showed significantly longer overall survival (OS) in patients with lower baseline TLG{sub 40} {sub %} (<151.8) (p = 0.003, median 14.2 vs. 9.1 months in <151.8 and ≥151.8, respectively). Patients showing higher decrease in TLG{sub 40} {sub %} after treatment showed significantly longer progression-free survival (PFS) (p = 0.001, median 8.0 vs. 2.4 months in % ΔTLG{sub 40} {sub %} < -9.6 % and ≥ -9.6 %, respectively) and OS (p = 0.002, median 16.4 vs. 9.1 months in % ΔTLG{sub 40} {sub %} < -9.6 % and ≥ -9.6 %, respectively). The same cutoff could discriminate patients with longer survival among the patients who were under the stable disease category according to RECIST 1.1 (median PFS 8.4 vs. 6.8 months, p = 0.020; median OS 18.3 vs. 11.5 months, p = 0.049). Measurement of TLG can predict treatment outcome of regorafenib in mCRC. (orig.)

  5. Response to Chemotherapy and Prognosis in Metastatic Colorectal Cancer With DNA Deficient Mismatch Repair.

    Science.gov (United States)

    Alex, Alexandra Khichfy; Siqueira, Sheila; Coudry, Renata; Santos, Juliana; Alves, Michel; Hoff, Paulo M; Riechelmann, Rachel P

    2017-09-01

    DNA deficient mismatch repair (dMMR) genes are associated with microsatellite instability and good prognosis in early-stage colorectal cancer (CRC). However dMMR is rare in metastatic CRC (mCRC) and little is known about its influence on treatment response rate (RR). The primary objective of this study was to compare the RR of patients with mCRC according to dMMR status. This was a retrospective study that compared the RR by Response Evaluation Criteria In Solid Tumors 1.1 criteria in patients with mCRC treated with chemotherapy according to dMMR status. All digital images were retrieved for RR evaluation by a single radiologist blinded to dMMR results. dMMR was defined as loss of immunohistochemistry expression of at least 1 of the MMR genes (MLH1, MSH2, MSH6, or PMS2). Cases were dMMR patients, and controls were proficient MMR (pMMR) patients (1:2 fashion). Based on clinical and molecular features, dMMR patients were classified as probable Lynch or sporadic. From January 2009 to January 2013, 762 out of 1270 patients were eligible and screened for dMMR: n = 27 (3.5%) had dMMR mCRC and n = 735 (96.5%) had pMMR mCRC. Given the rarity, 14 dMMR cases outside the inclusion period were included (total 41 dMMR cases) and 84 controls (pMMR). By intention-to-treat analysis, considering all patients who received at least 1 dose of oxaliplatin-based chemotherapy (N dMMR = 34), those with dMMR had lower RR compared with those with pMMR (RR, 11.7% vs. 28.6%; odds ratio, 0.33; 95% confidence interval, 0.08-1.40; P = .088); patients with probable Lynch-related mCRC presented higher RR than subjects with probable sporadic dMMR (22.2% vs. 0%). dMMR was associated with BRAF mutations and poor prognosis, particularly in the sporadic subgroup (median survival, 29.8 vs. 5.9 months; P = .025). This study suggests that the dMMR phenotype is predictive of resistance to oxaliplatin-based chemotherapy. Apparently, such resistance is more pronounced in the sporadic dMMR phenotype

  6. Efficacy, Safety and Cost of Regorafenib in Patients with Metastatic Colorectal Cancer in French Clinical Practice.

    Science.gov (United States)

    Calcagno, Fabien; Lenoble, Sabrina; Lakkis, Zaher; Nguyen, Thierry; Limat, Samuel; Borg, Christophe; Jary, Marine; Kim, Stefano; Nerich, Virginie

    2016-01-01

    Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment-related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice. We retrospectively reviewed patients treated with regorafenib monotherapy for unresectable mCRC in five Franche-Comté cancer hospitals (France). The primary end point was overall survival. Secondary end points were safety and descriptive cost analyses of patients treated with regorafenib in clinical practice. Another aim of this study was to assess the impact of regorafenib prescription on the risk of hospitalization in real-life practice. From January 2014 to August 2014, 29 consecutive patients were enrolled. Patients were heavily pretreated and were refractory to standard chemotherapies. The primary tumor sites were the colon and the rectum for 55% and 45% of patients, respectively. Fifteen patients (51%) harbored an RAS mutation. Eastern Cooperative Oncology Group - Performance Status (PS) was 0-1 for 86% of patients and 2 for 14% of patients. Nineteen patients (66%) initially received reduced doses of 120 or 80 mg/day. The median duration of treatment was 2.5 months (range, 0.13-11.4 months). Treatment-related adverse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital due to drug-related severe adverse events. The mean cost of patient management with regorafenib for the duration of treatment was 9908 ± 8191

  7. Real-life treatment of metastatic colorectal cancer with regorafenib: a single-centre review.

    Science.gov (United States)

    Gotfrit, J; Vickers, M; Sud, S; Asmis, T; Cripps, C; Goel, R; Hsu, T; Jonker, D; Goodwin, R

    2017-08-01

    Various tyrosine kinase signalling pathways affect the development and progression of colorectal cancer (crc). In clinical trials, regorafenib has been associated with a survival benefit in metastatic crc (mcrc). We assessed the safety and efficacy of regorafenib in real-world patients. In a retrospective review of patients with mcrc treated with regorafenib at our institution from 2013 to 2015, patient demographics, treatment, and survival data were collected. Progression-free survival (pfs) and overall survival (os) were estimated using the Kaplan-Meier method. In total, 48 patients were offered regorafenib, and 35 (73%) started treatment. Of the patients who started regorafenib, 57% were men. Median age in the cohort was 61 years, and all patients had a performance status in the range 0-2. Time from diagnosis of mcrc to regorafenib treatment was more than 18 months in 71% of patients. Starting dose was 160 mg in 54% of the patients, 120 mg in 40%, and 80 mg in 6%. Dose reductions occurred in 34% of the patients, and interruptions, in 29%. Best response was progressive disease (60%) and stable disease (17%); response in the rest of the patients was unknown. The most common adverse events on regorafenib (any grade) were fatigue (57%), hyperbilirubinemia (43%), thrombocytopenia (37%), anorexia (31%), and hypertension (31%). The most common grade 3 or 4 adverse events were fatigue (29%), hypophosphatemia (17%), weight loss (11%), and hyperbilirubinemia (9%). Common reasons for discontinuing regorafenib included progressive disease (51%) and toxicity (26%). In patients treated with regorafenib, pfs was 2.4 months (95% confidence interval: 1.8 to 3.3 months) and os was 5.6 months (95% confidence interval: 3.7 to 8.9 months). No factors were associated with survival in univariate or multivariate analysis. In a real-world setting, regorafenib is associated with survival similar to that reported in the randomized controlled trials, but at the expense of toxicity leading

  8. Increased risk of hemorrhage in metastatic colorectal cancer patients treated with bevacizumab

    Science.gov (United States)

    Zhu, Xiaoqiang; Tian, Xianglong; Yu, Chenyang; Hong, Jie; Fang, Jingyuan; Chen, Haoyan

    2016-01-01

    Abstract Background: As an important antivascular endothelial growth factor monoclonal antibody, bevacizumab has been administrated for the treatment of cancer patients. Hemorrhage, one of the common adverse events of angiogenesis inhibitors, sometimes is also fatal and life-threatening. We aimed at determining the incidence and risk of hemorrhage associated with bevacizumab in patients with metastatic colorectal cancer (mCRC). Methods: We searched PubMed, EMBASE, and the Web of Science databases for relevant randomized controlled trials (RCTs). The overall incidence, overall relative risk (RR), and 95% confidence interval (CI) were calculated by using a random-effects or fixed-effects model based on the heterogeneity of selected trials. Results: A total of 10,555 mCRC patients from 12 RCTs were included in our study. The overall incidence of hemorrhage was 5.8% (95% CI 3.9%–7.8%). Bevacizumab significantly increased the overall risk of hemorrhage with an RR of 1.96 (95% CI 1.27–3.02). The RR of all-grade hemorrhage was 2.39 (95% CI 1.09–5.24) and 1.41 (95% CI 1.01–1.97) for high-grade hemorrhage. The risk of hemorrhage associated with bevacizumab was dose-dependent with an RR of 1.73 (95% CI 1.15–2.61) for 2.5 mg/kg/wk and 4.67 (95% CI 2.36–9.23) for 5 mg/kg/wk. More importantly, the RR of hemorrhage for treatment duration ( 6 months) based on subgroup analysis was 4.13 (95% CI 2.58–6.61) and 1.43 (95% CI 0.96–2.14), respectively. Conclusion: The addition of bevacizumab to concurrent antineoplastic in patients with mCRC significantly increased the risk of hemorrhage. The dose of bevacizumab may contribute to the risk of hemorrhage. And the 1st 6 months of treatment may be a crucial period when hemorrhagic events occur. PMID:27559943

  9. Hereditary non-polyposis colorectal carcinoma (HNPCC) in a ...

    African Journals Online (AJOL)

    Colorectal cancer (CRC) is relatively uncommon in sub Saharan Africa because of relative young age of the population, rarity of pre-malignant conditions and favourable dietary factors. The role of heredity in its causation in Africa is, however, unknown. Four first degree relatives were treated for CRC within three years by ...

  10. Leptin regulates proliferation and apoptosis of colorectal carcinoma ...

    Indian Academy of Sciences (India)

    Furthermore, HCT-116 colon cancer cells were used to elucidate the effect of PI3K/Akt/. mTOR signalling pathway on the leptin's regulation on colon cancer. 2. Materials and ... prior knowledge of the patients' clinical data using Olympus. CX42 microscope ..... and clinicopathologic characteristics of colorectal cancer.

  11. Novel Inflammation-Based Prognostic Score for Predicting Survival in Patients with Metastatic Urothelial Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yu-Li Su

    Full Text Available We developed a novel inflammation-based model (NPS, which consisted of a neutrophil to lymphocyte ratio (NLR and platelet count (PC, for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC.We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/μL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS by using Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS.In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001 or PC (P < .0001. The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001. Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20-2.24, P = .002.The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS.

  12. Metastatic Breast Carcinoma Presenting as a Sigmoid Stricture: Report of a Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    A. Nikkar-Esfahani

    2013-03-01

    Full Text Available Metastatic spread of breast carcinoma to the colon and rectum is rare. We report the case of a patient treated for lobular breast carcinoma presenting 17 years later with metastatic breast cancer of the colon. A 63-year-old lady with a past history of right-sided invasive lobular carcinoma of the breast presented with persistent diarrhoea. Colonoscopy with biopsies revealed a benign-looking stricture at the rectosigmoid junction. A CT scan of the abdomen and pelvis revealed a benign-looking stricture in keeping with a probable diverticular stricture. A Hartmann procedure was performed and histology revealed a metastatic lobular carcinoma with oestrogen and progesterone receptor-positive status. Treatment was commenced with letrozole and the patient remains well under clinical surveillance. In a patient with a history of breast carcinoma who presents with gastrointestinal symptoms the possibility of gastrointestinal tract spread should always be considered. Endoscopic diagnosis may be misleading with pathological diagnosis only being made following surgical resection. A history of breast carcinoma must be declared to the histopathologist following surgical resection so that an accurate diagnosis is made and appropriate treatment is commenced.

  13. Prognostic Impact of Modulators of G proteins in Circulating Tumor Cells from Patients with Metastatic Colorectal Cancer.

    Science.gov (United States)

    Barbazan, Jorge; Dunkel, Ying; Li, Hongying; Nitsche, Ulrich; Janssen, Klaus-Peter; Messer, Karen; Ghosh, Pradipta

    2016-02-26

    The consequence of a loss of balance between G-protein activation and deactivation in cancers has been interrogated by studying infrequently occurring mutants of trimeric G-protein α-subunits and GPCRs. Prior studies on members of a newly identified family of non-receptor guanine nucleotide exchange factors (GEFs), GIV/Girdin, Daple, NUCB1 and NUCB2 have revealed that GPCR-independent hyperactivation of trimeric G proteins can fuel metastatic progression in a variety of cancers. Here we report that elevated expression of each GEF in circulating tumor cells (CTCs) isolated from the peripheral circulation of patients with metastatic colorectal cancer is associated with a shorter progression-free survival (PFS). The GEFs were stronger prognostic markers than two other markers of cancer progression, S100A4 and MACC1, and clustering of all GEFs together improved the prognostic accuracy of the individual family members; PFS was significantly lower in the high-GEFs versus the low-GEFs groups [H.R = 5, 20 (95% CI; 2,15-12,57)]. Because nucleotide exchange is the rate-limiting step in cyclical activation of G-proteins, the poor prognosis conferred by these GEFs in CTCs implies that hyperactivation of G-protein signaling by these GEFs is an important event during metastatic progression, and may be more frequently encountered than mutations in G-proteins and/or GPCRs.

  14. TIMP-1 Is Significantly Associated with Objective Response and Survival in Metastatic Colorectal Cancer Patients Receiving Combination of Irinotecan, 5-Fluorouracil, and Folinic Acid

    DEFF Research Database (Denmark)

    Sørensen, Nanna M; Byström, Per; Christensen, Ib Jarle

    2007-01-01

    with metastatic colorectal cancer were included in the study. PlasmaTIMP-1and serum carcinoembryonic antigen (CEA) were measured in samples obtainedbef ore the first cycle of chemotherapy. Results: Analysis of best objective response (complete or partial response versus stable or progressive disease) showed...

  15. 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...

  16. 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...

  17. The effect of individualized nutritional counseling on muscle mass and treatment outcome in patients with metastatic colorectal cancer undergoing chemotherapy: a randomized controlled trial protocol

    NARCIS (Netherlands)

    van der Werf, Anne; Blauwhoff-Buskermolen, Susanne; Langius, Jacqueline A. E.; Berkhof, Johannes; Verheul, Henk M. W.; de van der Schueren, Marian A. E.

    2015-01-01

    A low muscle mass is prevalent in patients with metastatic colorectal cancer (mCRC) and has been associated with poor treatment outcome. Chemotherapeutic treatment has an additional unfavorable effect on muscle mass. Sufficient protein intake and physical activity are known to induce muscle protein

  18. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hagman, H; Frödin, J-E; Berglund, Å

    2016-01-01

    BACKGROUND: Maintenance treatment (mt) with bevacizumab (bev) ± erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies...

  19. 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...

  20. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

    International Nuclear Information System (INIS)

    Nielsen, Maartje; Hes, Frederik J; Morreau, Hans; Miranda, Noel FCC de; Puijenbroek, Marjo van; Jordanova, Ekaterina S; Middeldorp, Anneke; Wezel, Tom van; Eijk, Ronald van; Tops, Carli MJ; Vasen, Hans FA

    2009-01-01

    MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR) of APC, p53, and SMAD4 were analyzed for somatic mutations. MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36) while 64% (23/36) had KRAS2 mutations (22/23 c.34G>T). G>T tranversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development) but not in P53 and SMAD4 (implicated in tumour progression) might indicate a predominant MUTYH effect in early carcinogenesis

  1. Induction of Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma by Litchi Seed Extract

    Directory of Open Access Journals (Sweden)

    Chih-Ping Hsu

    2012-01-01

    Full Text Available The Litchi (Litchi chinensis fruit products possess rich amounts of flavanoids and proanthocyanidins. Its pericarp has been shown to inhibit breast and liver cancer cell growth. However, the anticolorectal cancer effect of Litchi seed extract has not yet been reported. In this study, the effects of polyphenol-rich Litchi seed ethanol extract (LCSP on the proliferation, cell cycle, and apoptosis of two colorectal cancer cell lines Colo320DM and SW480 were examined. The results demonstrated that LCSP significantly induced apoptotic cell death in a dose-dependent manner and arrested cell cycle in G2/M in colorectal carcinoma cells. LCSP also suppressed cyclins and elevated the Bax : Bcl-2 ratio and caspase 3 activity. This study provides in vitro evidence that LCSP serves as a potential chemopreventive agent for colorectal cancer.

  2. Malnutrition In Patients With Colorectal Carcinoma (Oncologist's Point Of View)

    International Nuclear Information System (INIS)

    Zanova, M.

    2008-01-01

    Colorectal cancer is a worldwide health, social and economic problem. The incidence of malnutrition in patients with colorectal cancer is stated as 54 - 60 %. Primary cachexia is caused by hormonal, metabolic and energetic abnormalities; secondary cachexia is a consequence of functional and anatomic damage to digestive apparatus resulting from a tumor itself or its treatment. Colorectal carcinoma treatment is a complex process involving surgery, radiotherapy and cytostatic treatment. Each treatment modality also brings desirable and undesirable effects and influences patient's nutritional status. Malnutrition worsens patient's overall chances of successful treatment; therefore nutritional support aims to increase his/her anti-infection and antitumor immunity by means of mineral and water industry adjustment as well as by energetic stabilization. (author)

  3. Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation.

    LENUS (Irish Health Repository)

    Canney, A

    2012-02-01

    Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.

  4. Expression of circadian clock genes in human colorectal adenoma and carcinoma.

    Science.gov (United States)

    Momma, Tomoyuki; Okayama, Hirokazu; Saitou, Masaru; Sugeno, Hidekazu; Yoshimoto, Nobuhiro; Takebayashi, Yuji; Ohki, Shinji; Takenoshita, Seiichi

    2017-11-01

    Circadian rhythms are fundamental biological systems in most organisms. Epidemiological and animal studies have demonstrated that disruption of circadian rhythms is linked to tumor progression and mammalian tumorigenesis. However, the clinical significance of in situ clock gene expression in precancerous and cancerous colorectal lesions remains unknown. The present study aimed to investigate mRNA transcript levels of circadian clock genes within human colorectal cancer and adenoma tissue sections. Using in situ hybridization, the expression of key clock genes, including period circadian protein homolog ( Per ) 1 and 2, cryptochrome 1 ( Cry1 ), circadian locomoter output cycles protein kaput ( Clock ), brain and muscle ARNT-like protein 1 ( Bmal1 ) and casein kinase 1ε ( CK1 ε) were retrospectively examined in 51 cases of colorectal carcinoma and 10 cases of adenoma. The expression of clock genes was almost undetectable in the majority of adenomas, whereas positive expression of clock genes was observed in 27-47% of carcinomas. Notably, positive Per1 , Per2 and Clock staining in colorectal carcinomas were each significantly associated with a larger tumor size (P=0.012, P=0.011 and P=0.009, respectively). Tumors with positive Per2 and Clock expression tended to exhibit deeper depth of invasion and were generally more advanced than tumors that did not express these genes (P=0.052 and P=0.064, respectively). However, no statistically significant association was observed between clock gene expression and clinicopathological variables, including histopathological differentiation, lymph node metastasis, depth of invasion or disease stage, although Per2 -positive tumors tended to be associated with poorer overall survival (P=0.060). The results of the current study suggest that dysregulated expression of clock genes may be important in human colorectal tumorigenesis.

  5. Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal carcinoma.

    Science.gov (United States)

    Peretti, Thais; Waisberg, Jaques; Mader, Ana Maria A A; de Matos, Leandro L; da Costa, Ricardo B; Conceição, Gleice Margarete de S; Lopes, Antônio Carlos; Nader, Helena B; Pinhal, Maria Aparecida S

    2008-08-01

    To propose a quantitative method to detect heparanase-2 (HPA2) and syndecan-1 (Syn-1) using immunohistochemistry in colorectal (colon and rectal) carcinomas compared with nonneoplastic tissues and evaluate the possible role of these molecules in tumor development and extracellular remodeling. Cytoplasmic staining of HPA2 and Syn-1 was obtained by standard immunohistochemical reactions in 50 colorectal carcinoma and 20 nonneoplastic large bowels tissues. An image system was used to quantify the immunoexpression by digital computer-assisted method (Matos et al. 2006). The cutoff point for the immunohistochemistry variable was defined by sensibility and specificity curves. Statistical analysis was performed using SPSS version 13.0. HPA2 was over-expressed in colorectal cancer (131.1+/-24.9 o.u./microm) when compared with nonneoplastic tissues (27.9+/-12.2 o.u./microm) (P<0.0001). However, an opposite correlation was observed between Syn-1 and tumor presence, where colorectal tissues expressed lower Syn-1 proteoglycan compared with nonneoplastic tissues, respectively (39.2+/-17.8 o.u./microm) and (102.2+/-25.2 o.u./microm) (P<0.0001). A methodology with high sensitivity and specificity is proposed with a cutoff value for HPA2 and Syn-1 in the immunohistochemistry assay to define the presence of tumor. It was demonstrated for the first time in the literature that HPA2 is over-expressed in colorectal carcinoma tissues compared with nonneoplastic tissues. HPA2 over-expression could be possibly related to Syn-1 shedding despite the fact that HPA2 does not present enzymatic activity as HPA1.

  6. Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

    International Nuclear Information System (INIS)

    Skjelbred, Camilla F; Sæbø, Mona; Hjartåker, Anette; Grotmol, Tom; Hansteen, Inger-Lise; Tveit, Kjell M; Hoff, Geir; Kure, Elin H

    2007-01-01

    The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population. We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (GSTM1, GSTT1, GSTP1 Ile 105 Val, EPHX1 Tyr 113 His and EPHX1 His 139 Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression. A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2 nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious. Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma

  7. Deficient mismatch repair andRASmutation in colorectal carcinoma patients: a retrospective study in Eastern China.

    Science.gov (United States)

    Zhang, Xiangyan; Ran, Wenwen; Wu, Jie; Li, Hong; Liu, Huamin; Wang, Lili; Xiao, Yujing; Wang, Xiaonan; Li, Yujun; Xing, Xiaoming

    2018-01-01

    To investigate the frequency and prognostic role of deficient mismatch repair (dMMR) and RAS mutation in Chinese patients with colorectal carcinoma. Clinical and pathological information from 813 patients were reviewed and recorded. Expression of mismatch repair proteins was tested by immunohistochemistry. Mutation analyses for RAS gene were performed by real-time polymerase chain reaction. Correlations of mismatch repair status and RAS mutation status with clinicopathological characteristics and disease survival were determined. The overall percentage of dMMR was 15.18% (121/797). The proportion of dMMR was higher in patients mismatch repair was also associated with mucinous production ( p  mismatch repair status and RAS mutation reflects the specific clinicopathological characteristics of colorectal carcinoma.

  8. Metastase de carcinoma comprometendo a cauda equina Metastatic carcinoma of the cauda equina: a case report

    Directory of Open Access Journals (Sweden)

    Lígia M. B. Coutinho

    1976-09-01

    Full Text Available É relatado um caso de paciente, de 60 anos, que apresentou tumor nos segmentos apical e posterior direitos, cujo diagnóstico histopatológico foi de carcinoma indiferenciado. O paciente foi submetido à cobaltoterapia, tendo melhorado por três meses, quando foi novamente hospitalizado por dor lombar. A mielografia com lipiodol mostrou processo expansivo intrarraqueano. Mediante cirurgia foi encontrado tumor intra-dural, englobando raízes nervosas. O diagnóstico microscópico foi de carcinoma indiferenciado infiltrando os espaços epi e peri-neurais.The case of a 60 year-old man who had an indifferenciated carcinoma in the lung is reported. He had recieved cobaltotherapy and had improved. After 3 months a lumbar pain had begun and the patient was hospitalized. A myelography with lipiodol demonstrated an intra-dural mass. At operation a big intra-dural tumor including the cauda equina was found. The microscopic examination revealed an undifferenciated carcinoma, that infiltrated the epi and peri-neural space.

  9. Evaluation of a Colorectal Carcinoma Screening Program in Kota Setar and Kuala Muda Districts, Malaysia.

    Science.gov (United States)

    Abu Hassan, Muhammad Radzi; Leong, Tan Wei; Othman Andu, Delarina Frimawati; Hat, Habshoh; Nik Mustapha, Nik Raihan

    2016-01-01

    A colorectal cancer screening program was piloted in two districts of Kedah in 2013. There is scarcity of information on colorectal cancer screening in Malaysia. Thus, this research was conducted to evaluate the colorectal cancer screening program in the districts to provide insights intop its efficacy. A cross sectional study was conducted using data on the colorectal cancer screening program in 2013 involving Kota Setar and Kuala Muda districts in Malaysia. We determined the response rate of immunochemical fecal occult blood test (iFOBT), colonoscopy compliance, and detection rates of neoplasia and carcinoma. We also compared the response of FOBT by demographic background. The response rate of FOBT for first iFOBT screening was 94.7% while the second iFOBT screening was 90.7%. Participants from Kuala Muda district were 27 times more likely to default while Indians had a 3 times higher risk of default compared to Malays. The colonoscopy compliance was suboptimal among those with positive iFOBT. The most common finding from colonoscopy was hemorrhoids, followed by tubular adenoma. Detection rate of carcinoma and neoplasia for our program was 1.2%. In summary, the response rate of iFOBT was encouraging but the colonoscopy compliance was suboptimal which led to a considerably low detection rate.

  10. Identifying and quantifying the stromal fibrosis in muscularis propria of colorectal carcinoma by multiphoton microscopy

    Science.gov (United States)

    Chen, Sijia; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2014-10-01

    The examination of stromal fibrosis within colorectal cancer is overlooked, not only because the routine pathological examinations seem to focus more on tumour staging and precise surgical margins, but also because of the lack of efficient diagnostic methods. Multiphoton microscopy (MPM) can be used to study the muscularis stroma of normal and colorectal carcinoma tissue at the molecular level. In this work, we attempt to show the feasibility of MPM for discerning the microstructure of the normal human rectal muscle layer and fibrosis colorectal carcinoma tissue practicably. Three types of muscularis propria stromal fibrosis beneath the colorectal cancer infiltration were first observed through the MPM imaging system by providing intercellular microstructural details in fresh, unstained tissue samples. Our approach also presents the capability of quantifying the extent of stromal fibrosis from both amount and orientation of collagen, which may further characterize the severity of fibrosis. By comparing with the pathology analysis, these results show that the MPM has potential advantages in becoming a histological tool for detecting the stromal fibrosis and collecting prognosis evidence, which may guide subsequent therapy procedures for patients into good prognosis.

  11. CT colonography: Diagnostic role of contrast enhancement of benign polyps and colorectal carcinoma

    International Nuclear Information System (INIS)

    Stoinova, V.; Nedevska, M.

    2006-01-01

    Full text: The aim of this study was to compare pre- and postcontrast CT attenuation values of benign colorectal polyps and carcinoma lesions detected by CT colonography, and to investigate whether contrast enhancement of these lesions can be potentially used for differentiation from residual fluid and feces. We retrospectively reviewed CT colonographic dataset of 120 patients. 35 benign polyps and 22 colorectal carcinomas were included in our study. All lesions were confirmed by colonoscopic biopsy or surgery. The difference in attenuation value between precontrast and postcontrast studies of polyps was statistically significant; the same was true for colorectal cancers. In the precontrast phase no statistically significant difference was observed between stool, polyps and cancers. The mean attenuation value of solid fecal residuals was 37 HU before and after contrast enhancement. Residual fluid do not take up contrast and the density does not change in the contrast-enhanced phase. The difference between postcontrast density of polyps and cancers with respect to density of stools and residual fluid was significant. The use of contrast medium could be helpful in CT colonography for discriminating polypoid benign lesions and colorectal cancer from fecal and fluid residuals

  12. Outcome of first line systemic treatment in elderly compared to younger patients with metastatic colorectal cancer: A retrospective analysis of the CAIRO and CAIRO2 studies of the Dutch Colorectal Cancer Group (DCCG)

    NARCIS (Netherlands)

    Venderbosch, Sabine; Doornebal, Joan; Teerenstra, Steven; Lemmens, Wim; Punt, Cornelis J. A.; Koopman, Miriam

    2012-01-01

    Background. Metastatic colorectal cancer (CRC) is predominantly a disease of the elderly, therefore the current standards should be evaluated in this population. Material and methods. We evaluated in different age groups the outcome in terms of median overall and progression-free survival, response

  13. Metastatic sebaceous cell carcinoma, review of the literature and use of electrochemotherapy as possible new treatment modality

    Directory of Open Access Journals (Sweden)

    Ribero Simone

    2016-09-01

    Full Text Available Metastatic extraorbital sebaceous carcinoma is a rare event that could involve the head and neck. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial.

  14. Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma.

    NARCIS (Netherlands)

    Nutting, C.M.; Herpen, C.M.L. van; Miah, A.B.; Bhide, S.A.; Machiels, J.P.; Buter, J.; Kelly, C.; Raucourt, D. de; Harrington, K.J.

    2009-01-01

    BACKGROUND: Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of approximately 30% and median survival of 6 months. PATIENTS AND METHODS: In a multicentre phase II study, 32 patients with recurrent or

  15. Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma

    NARCIS (Netherlands)

    Kil, P. J. M.; Goldschmidt, H. M. J.; Wieggers, B. J. A.; Kariakine, O. B.; Studer, U. E.; Whelan, P.; Hetherington, J.; de Reijke, Th M.; Hoekstra, J. W.; Collette, L.

    2003-01-01

    To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to

  16. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

    Directory of Open Access Journals (Sweden)

    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

  17. Comparison of the clinical and pathological features between patients with recurrent metastatic breast carcinoma and patients with initially metastatic breast carcinoma

    International Nuclear Information System (INIS)

    Saydam, Birsen K.; Goksel, G.; Sezgin, C.; Uslu, R.; Korkmaz, E.; Kapkac, M.; Ozdemir, N.

    2008-01-01

    Objective was to compare initial metastatic breast carcinoma (MBC) with recurrent MBC and assess their biologic phenotypes and clinical behaviors. A comparison of clinical and biological characteristics and median overall survival times were assessed in the 251 patients with MBC at the Division of Medical Oncology, Ege University School of Medicine and the Division of radiation Oncology, Tepecik Government Hospital, Izmir, Turkey between 1995 and 2004. Hormone receptors, c-erb B-2,ki-67 and p53 expressions were performed by immunohistochemistry. Out of 251 MBC patients, 206 patients had recurrent MBC and 45 had initial MBC. Regarding survival there was no difference between the recurrent MBC group and the initial MBC group. The initial MBC group had a higher proportion of T4 tumors (46% versus 27%), a lower proportion of T-1-2 tumors (31% versus 55%; p=0.01), and higher percentage of patients with high Ki-67 expression (64% versus 49%; p=0.05). Multivariate analysis showed that T stage was an independent prognostic factor (p=0.02). Patients with initial MBC tended to present with larger tumors. This relationship can be explained by delayed diagnosis. The potential for reducing death rates from breast cancer is contingent on educational improvement and increased screening rates. (author)

  18. Metastatic thyroid carcinoma without identifiable primary tumor within the thyroid gland: a retrospective study of a rare phenomenon.

    Science.gov (United States)

    Xu, Bin; Scognamiglio, Theresa; Cohen, Perry R; Prasad, Manju L; Hasanovic, Adnan; Tuttle, Robert Michael; Katabi, Nora; Ghossein, Ronald A

    2017-07-01

    Metastatic papillary thyroid carcinoma (PTC) without an identifiable primary tumor despite extensive microscopic examination of the thyroid gland is a rare but true phenomenon.We retrieved 7 of such cases and described in detail the clinical and pathologic features of these tumors. BRAF V600E immunohistochemistry and Sequenom molecular profile were conducted in selected cases. All patients harbored metastatic disease in the central (n=3), lateral (n=3), or both neck compartments (n=1). The histotype of the metastatic disease was PTC (n=5), poorly differentiated thyroid carcinoma in association with a PTC columnar variant (n=1), and anaplastic thyroid carcinoma in association with a PTC tall cell variant (n=1). Fibrosis was present in the thyroid of 5 patients. All patients with PTC were alive without evidence of recurrence. The 76-year-old patient with poorly differentiated thyroid carcinoma did not recur and died of unknown causes. Finally, the patient with anaplastic thyroid carcinoma was alive with distant metastasis at last follow-up. The median follow-up for this cohort was 2.2years (range, 0.8-17). BRAF V600E was detected in 4 of 6 cases by immunohistochemistry. In conclusion, metastatic nodal disease without identifiable thyroid primary is a rare but real phenomenon of unknown mechanisms. Although most tumors are low grade and well differentiated, aggressive behavior due to poorly differentiated or anaplastic carcinoma can happen. Most cases are BRAF V600E -positive thyroid tumors. A papillary carcinoma phenotype is found in all reported cases. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

    Science.gov (United States)

    Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

    2008-01-07

    To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

  20. Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

    Science.gov (United States)

    Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

    2017-11-17

    Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

  1. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lyu, Qing [School of Life Sciences, Tsinghua University, Beijing, 100084 (China); Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055 (China); Tou, Fangfang [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China); Su, Hong; Wu, Xiaoyong [First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002 (China); Chen, Xinyi [Department of Hematology and Oncology, Beijing University of Chinese Medicine, Beijing, 100029 (China); Zheng, Zhi, E-mail: zheng_sheva@hotmail.com [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China)

    2015-06-19

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway.

  2. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    International Nuclear Information System (INIS)

    Lyu, Qing; Tou, Fangfang; Su, Hong; Wu, Xiaoyong; Chen, Xinyi; Zheng, Zhi

    2015-01-01

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway

  3. Clinical evaluation of preoperative arterial infusion chemotherapy and surgical operation for colorectal carcinoma

    International Nuclear Information System (INIS)

    Yuan Jianhua; Zhao Zhongsheng; Deng Gaoli; Hu Tingyang; Yu Wenqiang; Chen Fanghong; Luo Zuyan; Ru Guoqing; Dong Quanjin; Tu Shiliang

    2003-01-01

    Objective: To investigate the clinical values of preoperative arterial infusion chemotherapy and surgical operation for colorectal carcinoma. Methods: 66 patients with colorectal carcinoma were subjected to percutaneous femoral artery catheterization by Seldinger's technique with infusion of anti-cancer drugs. The resection was performed 5-30 days after the arterial infusion (mean 12 days). In 50 surgical specimens of the 66 cases, histological findings were evaluated including the density and distribution of the apoptosis cells under the observation by DNA nick end labelling technique. Of which 22 specimens before arterial infusion chemotherapy (got from biopsy of preoperation) and 25 normal mucosa (got from normal surgical specimens) were used as controls. Results: The total histological response rate was 100% with grade I in 20 cases, grade II in 21 cases, grade III in 9 cases. The densities of the apoptosis cells were 31.47 ± 5.58 before arterial infusion chemotherapy, 76.69 ± 17.12 after arterial infusion chemotherapy and 8.01 ± 3.39 in normal mucosa. The density of the apoptosis cells after arterial infusion chemotherapy was significantly higher than that before arterial infusion chemotherapy (P 2 =4.696, P>0.30). There were no significant differences in the apoptosis of adenocarcinoma during different pathological stages (F=0.001376, P>0.05). Conclusions: Peroperative transcatheter arterial infusion chemotherapy resulting in apoptosis of adenocarcinoma, can raise the radical operation rate, and prolong survival rate for colorectal carcinoma patients

  4. The incidence of metastatic basal cell carcinoma (mBCC) in Denmark, 1997-2010.

    Science.gov (United States)

    Nguyen-Nielsen, Mary; Wang, Lisa; Pedersen, Lars; Olesen, Anne Braae; Hou, Jeannie; Mackey, Howard; McCusker, Margaret; Basset-Seguin, Nicole; Fryzek, Jon; Vyberg, Mogens

    2015-01-01

    Few data exist on the occurrence of metastatic basal cell carcinoma (mBCC). To identify all cases of mBCC in Denmark over a 14-year period. We searched the Danish National Patient Registry covering all Danish hospitals, the Danish Cancer Registry, the National Pathology Registry and the Causes of Death Registry during the period 1997 to 2010 for potential cases of mBCC registered according to the International classification of diseases ICD-10 and the International Systemized Nomenclature of Medicine (SNOMED). We identified 126,627 patients with a history of primary basal cell carcinoma (BCC) in the registries during the 14-year study period. Using case identifications from the four registries, a total of 170 potential mBCC cases were identified. However, after a pathology review, only five cases could be confirmed, of which three were basosquamous carcinomas. The 14-year cumulative incidence proportion of mBCC was 0.0039% (95% CI 0.0016-0.0083) among individuals with a history of previous BCC (n = 126,627) and 0.0001% (95% CI 0.0000-0.0002) in the general population. MBCC is a rare disease and only a small proportion of potential cases identified in automated clinical databases or registries can be confirmed by pathology and medical record review.

  5. Role of SIRT6 in Metabolic Reprogramming During Colorectal Carcinoma

    Science.gov (United States)

    2015-09-01

    Keystone Symposia: Biology of Sirtuins, Santa Fe, NM (March 8-12, 2015). 6 7. INVENTIONS, PATENTS AND LICENSES Nothing to report 8. REPORTABLE...impairing tumor growth ( Fig. 1 ). However, it also raises several intriguing questions. Which other species of bacteria are important in colorectal car...including SCFA-producing species , have been identifi ed in the human colon ( 8 ). In this context, different species could generate luminal

  6. Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer

    Science.gov (United States)

    2015-05-15

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  7. A possible association of baseline serum IL-17A concentrations with progression-free survival of metastatic colorectal cancer patients treated with a bevacizumab-based regimen.

    Science.gov (United States)

    Lereclus, Emilie; Tout, Mira; Girault, Alban; Baroukh, Nadine; Caulet, Morgane; Borg, Christophe; Bouché, Olivier; Ternant, David; Paintaud, Gilles; Lecomte, Thierry; Raoul, William

    2017-03-27

    Colorectal cancer is a major public health issue worldwide. Interleukin-17 (IL-17) and Th17 (T-helper cell type 17)-related molecules are involved in tumor development and in resistance to bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody used in association with chemotherapy in metastatic colorectal cancer. Some studies have previously shown that IL-17A and IL-17F polymorphisms, respectively rs2275913 and rs763780, are associated with gastric or colorectal cancer risk. Here we aimed at studying the influence of IL-17A-related individual factors on overall survival and progression-free survival in patients with metastatic colorectal cancer treated with a bevacizumab-based chemotherapy. Pre-treatment serum biomarkers were retrospectively evaluated in 122 metastatic colorectal cancer patients treated by bevacizumab in combination with chemotherapy at 2-weeks intervals in a prospective cohort study (NCT00489697). The polymorphisms of IL-17A and IL-17F were analyzed by polymerase chain reaction - restriction fragment length polymorphism. Serum concentrations of Th17-related cytokines were measured by MultiPlex. The impact of individual parameters on overall survival and progression-free survival was assessed using multivariate Cox models. High baseline IL-17A serum concentrations were significantly associated with shorter progression-free survival [p = 0.043]. Other baseline serum Th17-related cytokines and polymorphisms of IL-17 were not associated with overall survival or progression-free survival. In this ancillary study, baseline serum IL-17A concentration is the only Th17/IL-17 related factor that was significantly associated with the response of patients with metastatic colorectal cancer to bevacizumab. But this main significant result is highly dependent on one case which, if left out, weakens the data. Other clinical studies are required to confirm this association. NCT00489697 . June 20, 2007.

  8. The integrin alpha 6 beta 1 promotes the survival of metastatic human breast carcinoma cells in mice

    DEFF Research Database (Denmark)

    Wewer, U M; Shaw, L M; Albrechtsen, R

    1997-01-01

    The role of the integrin alpha 6 beta 1 in breast carcinoma progression was studied by targeted elimination of this integrin in MDA-MB-435 cells, a human breast carcinoma cell line that is highly metastatic in athymic mice. The strategy used is based on the finding that expression of a cytoplasmi...... in the liver after intrahepatic injection because of extensive apoptosis in the beta 4-delta CYT transfectants. These data suggest that a major function of the alpha 6 beta 1 integrin in breast carcinoma is to facilitate tumorigenesis and promote tumor cell survival in distant organs....

  9. p53 and erbB-2 Are Not Associated in Matched Cases of Primary and Metastatic Ovarian Carcinomas

    Directory of Open Access Journals (Sweden)

    Cristina Rodríguez-Burford

    2003-01-01

    Full Text Available Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients were evaluated for nuclear accumulation of p53 (clone BP53-12-1 and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5 by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative and phenotypic expression of p185erbB-2 (cytoplasm or membrane immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent.

  10. Aggressive treatment of metastatic squamous cell carcinoma of the rectum to the liver: a case report and a brief review of the literature

    Directory of Open Access Journals (Sweden)

    Carvounis Eleni E

    2006-08-01

    Full Text Available Abstract Background Rectal squamous cell carcinoma (SCC is a rare tumor. The incidence of this malignancy has been reported to be 0.25 to 1 per 1000 colorectal carcinomas. From a review of the English literature 55 cases of SCC of the rectum have been published. In this study we report a rectal metastatic SCC to the liver, discussing the efficacy of aggressive adjuvant and neo-adjuvant therapies on survival and prognosis. Case presentation A 39-year-old female patient with a pure SCC of the rectum diagnosed endoscopically is presented. The patient underwent initially neoadjuvant chemo-radiotherapy and then abdominoperineal resection with concomitant bilateral oophorectomy and hysterectomy, followed by adjuvant chemo-radiotherapy. Five months after the initial operation liver metastasis was demonstrated and a liver resection was carried out, followed by adjuvant chemotherapy. Eighteen months after the initial operation the patient is alive. Conclusion Although prognosis of rectal SCC is worse than that of adenocarcinoma, an aggressive therapeutic approach with surgery as the primary treatment, followed by combined neo- and adjuvant chemo-radiotherapy, may be necessary in order to improve survival and prognosis.

  11. Metastatic renal cell carcinoma from a native kidney of a renal transplant patient diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA biopsy

    Directory of Open Access Journals (Sweden)

    Yaseen Alastal

    2015-04-01

    Full Text Available Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA biopsy sampling of enlarged lymph nodes is increasingly used to diagnose metastatic tumors, especially of the gastrointestinal tract and the lungs. Herein, we describe the diagnosis of metastatic renal cell carcinoma from a native kidney of a 54 year-old male patient, who had a 5-years history of renal transplant, by EUS-FNA of mediastinal and celiac lymph nodes. Histological and immunohistochemical findings confirmed the origin of metastatic tumor. EUS-FNA with proper cytological evaluation can be useful in the diagnosis of metastatic renal cell carcinoma in renal transplant patients. 

  12. 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.

  13. Lack of retroperitoneal lymphadenopathy predicts survival of patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Vasselli, J R; Yang, J C; Linehan, W M; White, D E; Rosenberg, S A; Walther, M M

    2001-07-01

    Patients with metastatic renal cell carcinoma have a reported 5-year survival of 0% to 20%. The ability to predict which patients would benefit from nephrectomy and interleukin-2 (IL-2) therapy before any treatment is initiated would be useful for maximizing the advantage of therapy and improving the quality of life. A retrospective analysis of the x-rays and charts of patients treated at the National Institutes of Health Surgery Branch between 1985 and 1996, who presented with metastatic renal cancer beyond the locoregional area and the primary tumor in place, was performed. Preoperative computerized tomography or magnetic resonance imaging, or radiological reports if no scans were available, were used to obtain an estimate of the volume of retroperitoneal lymphadenopathy. Operative notes were used to evaluate whether all lymphadenopathy was resected or disease left in situ, or if any extrarenal resection, including venacavotomy, was performed. Mean survival rate was calculated from the time of nephrectomy to the time of death or last clinical followup. If patients received IL-2 therapy, the response to treatment was recorded. Mean survival and response rate for IL-2 were compared among patients in 3 separate analyses. Patients without preoperatively detected lymphadenopathy were compared with those with at least 1 cm.3 retroperitoneal lymphadenopathy. Also, the patients who had detectable lymphadenopathy were divided into subgroups consisting of all resected, incompletely resected, unresectable and unknown if all disease was resected. Each subgroup was compared with patients without detectable preoperative lymphadenopathy. Patients with less than were compared to those with greater than 50 cm.3 retroperitoneal lymphadenopathy. Patients undergoing extrarenal resection at nephrectomy (complex surgery) due to direct invasion of the tumor into another intra-abdominal organ were compared with those undergoing radical nephrectomy alone, regardless of lymph node status

  14. In vitro anticancer activity of ethanolic extracts of Piper nigrum against colorectal carcinoma cell lines

    Science.gov (United States)

    Prashant, Akila; Rangaswamy, Chandini; Yadav, Anshu Kumar; Reddy, Varun; Sowmya, MN; Madhunapantula, Subbarao

    2017-01-01

    Background: Piper nigrum (PN) is well known for its cytotoxic and pharmacological benefits. However, there is minimal documented evidence about its cytotoxic efficacy against colorectal carcinoma. We therefore sought to procure a precisely quantitative and qualitative result, pertaining the efficacy of an ethanolic extract of PN (EEPN) against colorectal carcinoma. Materials and Methods: EEPN was prepared by subjecting dried PN seeds to gradient ethanol fractionation. The total phenol content (TPC), antioxidant activity (AOA), and anti-inflammatory activity (AIA) were determined using Folin–Ciocalteu assay, ferric reducing ability of plasma and 2, 2-diphenyl-1-picrylhydrazyl methods, and human red blood cells membrane stabilizing assay, respectively. Colorectal carcinoma cell lines (HCT-116, HCT-15, and HT-29) were procured from National Centre for Cell Science, Pune, and were cultured in Dulbecco's modified eagle media supplemented with 10% fetal bovine serum and 1 mM L-glutamine. Cells were seeded into a 96-well plate, followed by treatment with increasing concentrations of EEPN. The cytotoxic efficacy was evaluated based on percentage inhibition of cells, using sulforhodamine-B assay. The IC-50 values were calculated using Prism software (Prism from GraphPad software, Inc. CA, USA). Results: Biochemical analysis revealed that 50% EEPN exhibited higher TPC, AOA, and AIA when compared to 70% and 100% EEPN at any given concentration (P = 0.041). Cytotoxic analysis revealed a dose-dependent response with maximum cellular inhibition at TPC of 6 and 3 μg/ml, using 50% EEPN. However, 50% inhibition of cellular growth using 50% EEPN was seen with TPC of 3.2, 2.9, and 1.9 μg/ml at 24, 48, and 72 h, respectively, in HCT-15 cells. Hence, time- and dose-dependent increase in the cytotoxic efficacy of 50% EEPN against colorectal carcinoma cell lines were noted (P < 0.001). Conclusion: Given the significantly positive correlations exhibited between the biochemical and the

  15. Metastatic Renal Cell Carcinoma: The Importance of Immunohistochemistry in Differential Diagnosis

    Directory of Open Access Journals (Sweden)

    Sandra Custódio

    2012-01-01

    Full Text Available Introduction: Clear cell carcinoma accounts for 75% of all types of renal neoplasms. Approximately one third presents with metastatic disease at diagnosis. Immunohistochemical studies play a significant diagnostic role. Case Report: We report the case of a 48-year-old heavy smoker who presented with productive cough and progressive dyspnea. The study revealed a renal mass and lung alterations compatible with primary tumor of the lung. The patient underwent a right complete nephrectomy. The anatomopathological exam showed clear cell renal carcinoma (pT1bN0Mx. After transthoracic needle aspiration biopsy, the clinical diagnosis was stage IV adenocarcinoma of the lung. Initially, the patient received one cycle of chemotherapy (cisplatin/pemetrexed. Two weeks later, the immunohistochemistry tests revealed a secondary lesion with probable renal origin. Chemotherapy was stopped and the patient was started on sunitinib treatment. After two cycles the disease progressed. A second-line treatment with everolimus was proposed; however, the patient died 2 weeks later due to terminal respiratory insufficiency. Discussion: Clear cell renal cell carcinoma remains one of the great mimickers in pathology. Immunohistochemistry is a valuable tool in the differential diagnosis of lung carcinomas. With the help of thyroid transcription factor 1, it is possible to distinguish a primary lung tumor from a metastasis with a reasonable degree of certainty. The present case report illustrates the challenge of making a definitive and adequate diagnosis. The immunohistochemistry added information that changed the whole treatment strategy. For the best treatment approach, it is fundamental that clinicians await all possible test results, before establishing a treatment plan.

  16. CIAPIN1 and ABCA13 are markers of poor survival in metastatic ovarian serous carcinoma.

    Science.gov (United States)

    Nymoen, Dag Andre; Holth, Arild; Hetland Falkenthal, Thea E; Tropé, Claes G; Davidson, Ben

    2015-02-18

    The objective of this study was to investigate the expression and clinical role of 14 genes previously shown to be associated with chemotherapy response and/or progression-free survival in a smaller series of ovarian serous carcinoma effusions. Advanced-stage serous ovarian carcinoma effusions (n = 150) were analyzed for mRNA expression of AKR1C1, ABCA4, ABCA13, ABCB10, BIRC6, CASP9, CIAPIN1, FAS, MGMT, MUTYH, POLH, SRC, TBRKB and XPA using quantitative real-time PCR. mRNA expression was studied for association with clinicopathologic parameters, including chemotherapy response and survival. ABCA4 mRNA expression was significantly related to better (complete) chemotherapy response at diagnosis in the entire cohort (p = 0.018), whereas higher POLH mRNA levels were significantly related to better chemoresponse at diagnosis in analysis to 58 patients with pre-chemotherapy effusions treated with standard chemotherapy (carboplatin + paclitaxel; p = 0.023). In univariate survival analysis for patients with pre-chemotherapy effusions (n = 77), CIAPIN1 mRNA expression was significantly related to shorter overall (p = 0.007) and progression-free (p = 0.038) survival, whereas ABCA13 mRNA expression was significantly related to shorter OS (p = 0.024). Higher CIAPIN1 mRNA expression was an independent marker of poor overall survival in Cox multivariate analysis (p = 0.044). Our data identify ABCA4 and POLH as markers of better chemotherapy response in metastatic serous carcinoma. CIAPIN1 and ABCA13 may be novel markers of poor outcome in pre-chemotherapy serous carcinoma effusions.

  17. Sarcopenia as a predictor of overall survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

    Science.gov (United States)

    Sharma, Pranav; Zargar-Shoshtari, Kamran; Caracciolo, Jamie T; Fishman, Mayer; Poch, Michael A; Pow-Sang, Julio; Sexton, Wade J; Spiess, Philippe E

    2015-08-01

    Cytoreductive nephrectomy (CN) is a therapeutic consideration in patients with metastatic renal cell carcinoma (mRCC). We hypothesized that sarcopenia, a novel marker of nutritional status, is a predictor of survival after CN. Of 105 patients who underwent CN at our institution for mRCC, 93 had preoperative imaging available for analysis. Skeletal muscle index was calculated on axial images at the third lumbar vertebrae, and a threshold skeletal muscle index of25 kg/m(2), and2 (hazard ratio = 2.09, 95% CI: 1.24-3.53; P = 0.006). Sarcopenia can be an important prognostic factor associated with worse OS after CN for mRCC. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Sudden hemorrhage in metastatic thyroid carcinoma of the brain during treatment with 131I

    International Nuclear Information System (INIS)

    Holmquest, D.L.; Lake, P.

    1976-01-01

    A patient with papillary--follicular carcinoma of the thyroid, with metastases to the lungs, skeleton, and brain, was treated 5 weeks after thyroidectomy with 135 mCi of 131 I. Although preliminary studies with 1 mCi had not shown any iodine uptake by the brain metastasis, this lesion showed intense concentration at the time of the larger therapeutic dose. Four days later, acute hemorrhage of the tumor occurred, requiring surgical removal. Although 131 I therapy would seem an unlikely cause of acute necrosis and hemorrhage in these lesions, the association of therapeutic radioiodine and hemorrhage is interesting. Since recent reports suggest that brain metastasis may be somewhat more common than previously suspected, we suggest that brain imaging be included in the workup prior to radioiodine therapy of patients with advanced metastatic disease or neurologic symptoms

  19. Metastatic renal cell carcinoma mimicking diverticulitis in a patient with chronic lymphocytic leukaemia.

    Science.gov (United States)

    Hwang, S M; Kuyava, J M; Grande, J P; Swetz, K M

    2015-01-07

    We present an unusual case of metastatic renal cell carcinoma (RCC) mimicking diverticulitis in a 76-year-old man with a 16-year history of chronic lymphocytic leukaemia (CLL) and a 2 cm left renal mass. The patient presented with severe abdominal pain and lower gastrointestinal bleeding with anticoagulation from recent pulmonary embolism. His clinical course was troubled by recurrent hospitalisations and complications that delayed investigations and potential treatments. Radiographic findings revealed stable CLL, mild sigmoid diverticulitis and a small renal mass. Small renal masses (less than 4 cm) are considered low risk for metastasising and are, thus, often observed or ablated, rather than resected. Furthermore, gastrointestinal metastases from RCC are rare. This case adds new perspective to the unpredictable nature of RCC and how synchronous malignancies may be masked in patients with long-standing CLL. 2015 BMJ Publishing Group Ltd.

  20. Interleukin-2 based immunotherapy in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Donskov, Frede

    2007-01-01

    The present thesis consists of 8 published articles focusing on interleukin-2 based immunotherapy in metastatic renal cell carcinoma (mRCC). This disease represents a significant challenge, as the tumor is resistant to current chemotherapy, hormonal therapy and radiation therapy. However, IL-2...... based immunotherapy may induce dramatic durable tumor regression by manipulating the immune system, however, only in a minority of patients. Two critical questions have driven the present thesis. First, which properties of the immune system are responsible for the dramatic tumor regression seen in some...... patients with mRCC following IL-2 administration? And second, can histamine increase the efficacy of IL-2 based immunotherapy by ending the immune suppression induced by phagocyte-generation of reactive oxygen species? 120 Danish patients, 41 UK patients and 20 Swedish patients were treated with low...

  1. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    Science.gov (United States)

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  2. Treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2

    DEFF Research Database (Denmark)

    Geertsen, P F; Hermann, G G; von der Maase, H

    1992-01-01

    PURPOSE: A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-one patients with RCC were entered onto the study. rIL-2...... (Proleukin; Eurocetus Corp, Amsterdam, The Netherlands) was administered intravenously in a dose of 18 x 10(6) IU/m2 per 24 hours. A maximum of two induction cycles and four maintenance cycles were given. Each induction cycle consisted of two rIL-2 infusion periods of 120 hours and 108 hours duration......, respectively; these were separated by a 6-day rest period. Each maintenance cycle consisted of a 120 hours rIL-2 infusion period. RESULTS: Six of 30 assessable patients (20%) responded; two (7%) with a complete response (CR) and four (13%) with a partial response (PR). The response duration for patients...

  3. Gastrointestinal imaging with hydrosonography and hydro-CT. Pt. 2. Colorectal carcinoma

    International Nuclear Information System (INIS)

    Duex, M.; Richter, G.M.; Roeren, T.; Heuschen, U.; Kauffmann, G.W.

    1996-01-01

    74 patients in whom colorectal carcinoma was suspected were examined. At HUS the colonic wall ist distended by a methylcellulose/water suspension and the carcinoma is enlarged to perform staging of the tumour. HCT is a spiral-CT optimised for parenchymal and vessel contrast. Before the scan is started, up to two litres of fluid are given rectally and spasmolytics are administered to reduce peristalsis. Colorectal carcinomas were classified according to the TNM system and histopathologic correlation was achieved. Out of 43 (HUS) and 39 (HCT) colonic lesions 33 (77%) and 36 (92%), respectively, were diagnosed. T-stage accuracy was 88% (HUS) and 66% (HCT), N-stage accuracy 33% and 46% and M-stage accuracy 88% and 85%, respectively. The T-stage of sonographically visible tumours of the colon is determined precisely by HUS. In contrast to predicting lymph node involvement distant metastases are reliably detected by both methods. If performed together, HUS and HCT achieve high diagnostic accuracy for staging carcinoma of the colon. (orig./MG) [de

  4. Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction: A case report.

    Science.gov (United States)

    Tsuchihashi, Kenji; Shimokawa, Hozumi; Takayoshi, Kotoe; Nio, Kenta; Aikawa, Tomomi; Matsushita, Yuzo; Wada, Iori; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Sonoda, Koh-Hei; Akashi, Koichi; Baba, Eishi

    2017-10-01

    Regorafenib is effective for metastatic colorectal cancer but its toxicity such as hemorrhage should be considered. The safety of regorafenib for the patient with the liver disease is not known. Seventy-one-year old man of colon cancer had myodesopsia and blood stool after 14 days from the initiation of regorafenib administration with 50% dose reduction due to liver dysfunction. Fundus examination revealed hemorrhage of the retinal vein. Regorafenib treatment was discontinued and observational therapy was pursued. Retinal and gastrointestinal hemorrhage resolved in 1 week. Retinal hemorrhage should be considered as the differential diagnosis of myodesopsia in the patient treated by regorafenib. Safety and pharmacokinetic of continuous regorafenib administration for patients with liver dysfunction remains to be clarified.

  5. HER2/HER3-positive metastatic salivary duct carcinoma in the pleural effusion: A case report.

    Science.gov (United States)

    Murata, Kazuya; Kawahara, Akihiko; Ono, Takeharu; Takase, Yorihiko; Abe, Hideyuki; Naito, Yoshiki; Akiba, Jun

    2017-12-04

    Salivary duct carcinoma (SDC) is an aggressive form of salivary gland tumor, and SDC patients tend to be older men, more commonly in advanced stage with a poorer prognosis. Although the cytological characteristics of SDC on fine-needle aspiration cytology have been well-described at the primary site, they have not been explored in metastasis. Here we reported a case of HER2/HER3-positive metastatic SDC in the lung and pleural effusion. The patient was a man in his 50s who had undergone extended total parotidectomy in 2008. He was originally diagnosed as having HER2-positive left parotid SDC. Six years later a mass was discovered in the left lung by chest computed tomography (CT) and was diagnosed as metastatic SDC by both bronchial biopsy and cytology. Subsequently he had a recurrent SDC in the left pleural effusion and died of respiratory failure. Cytological findings from bronchial brushing smear showed small sheet clusters in a slightly necrotic background. In the pleural effusion cytology, tumor cells appeared as ball-like clusters of epithelioid cells with apocrine-like findings. In immunocytochemistry, HER3 of SDC cells in pleural effusion was significantly overexpressed relative to the matched primary tumor, even though HER2 amplification did not change. Cytological findings and HER family receptors differed between the primary and metastatic SDC. Therefore, molecular tests, such as protein expression and gene amplification using cytological specimens, may become important in future when determining therapy strategies in patients with distant metastasis. © 2017 Wiley Periodicals, Inc.

  6. Transarterial Yttrium-90 Radioembolization Treatment of Patients with Liver-Dominant Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Kis, Bela; Shah, Jehan; Choi, Junsung; El-Haddad, Ghassan; Sweeney, Jennifer; Biebel, Benjamin; Mellon, Eric; Frakes, Jessica M; Hoffe, Sarah E; Fishman, Mayer N; Shridhar, Ravi

    2017-02-01

    To evaluate safety and efficacy of transarterial hepatic radioembolization treatment of patients with liver-dominant metastatic renal cell carcinoma (RCC). From July 2010 to December 2014, 18 patients with liver-dominant metastatic RCC were treated with yttrium-90 glass microsphere radioembolization. Retrospective review of medical records and imaging studies was performed to evaluate toxicities, treatment response, and overall survival. The median follow-up period from radioembolization treatment was 17.8 months (range, 3-54.4 months). Median overall survival from RCC diagnosis was 64 months (95% confidence interval [CI], 0-144.1 months), from diagnosis of liver metastasis was 29 months (95% CI, 7.2-50.8 months), and from radioembolization treatment was 22.8 months (95% CI, 13.2-32.3 months). After treatment, 10 patients reported grade 1 clinical toxicities, and 8 patients had grade 1 or 2 biochemical toxicities. The best radiographic responses of 17 patients who underwent contrast-enhanced cross-sectional imaging showed complete response in 16 patients and partial response in 1 patient evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The last available imaging of these 17 patients demonstrated complete response in 14 patients, partial response in 1 patient, and progression of disease in 2 patients. Images of a patient who underwent noncontrast CT showed stable disease as best response and stable disease on the last available imaging evaluated by RECIST. Radioembolization is safe and effective and led to improved hepatic disease control and overall survival in patients with liver-dominant metastatic RCC. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  7. Inherent characteristics of metachronous metastatic renal cell carcinoma in the era of targeted agents.

    Science.gov (United States)

    Han, Jang Hee; Lee, Seung Hwan; Ham, Won Sik; Han, Woong Kyu; Rha, Koon Ho; Choi, Young Deuk; Hong, Sung Joon; Yoon, Young Eun

    2017-10-03

    To assess the prognostic and predictive factors of time to treatment failure (TTF) and overall survival (OS), respectively, in patients with metachronous metastatic renal cell carcinoma (mRCC) who were treated with targeted agents. We retrospectively reviewed metachronous mRCC patients, defined as individuals diagnosed with metastatic disease >3 months after initial nephrectomy, treated at an institute since 2005. Cox proportional hazard regression analysis was performed to discover the most determinant variables associated with TTF and OS. Sarcomatoid features, absence of metastasectomy, multiple site metastasis, time to metastasis risk group (0-1 risk factors) did not reach the median OS, whereas the OS for the intermediate (2 risk factors) and high risk groups (3-5 risk factors) were 58.6 and 23.6 months, respectively (prisk criteria models. Initial tumor size or T stage did not affect TTF or OS. Patients who could not undergo metastasectomy and rapidly developed multiple metastases with higher corrected calcium and initial tumors with sarcomatoid features were less likely to benefit from targeted therapy; thus, the new agents under development or clinical trials could be more helpful than the use of standard targeted agents.

  8. Thoracic high-resolution computed tomography in the diagnosis of metastatic carcinoma.

    Science.gov (United States)

    Johnson, V S; Ramsey, I K; Thompson, H; Cave, T A; Barr, F J; Rudorf, H; Williams, A; Sullivan, M

    2004-03-01

    Three dogs were presented for investigation of recurrent pyrexia of unknown origin, chronic vomiting and respiratory distress, respectively. One dog was markedly underweight and the other two were cachexic. Physical examination and initial diagnostic tests failed to establish the underlying cause of the presenting signs. Thoracic radiographs were within normal limits for the age of the dog. In each case there was a high index of suspicion for an occult neoplastic process in view of the profound unexplained weight loss present. High-resolution computed tomography (HRCT) of the thorax was performed. The lung fields were divided into three zones for analysis and a novel classification scheme was used to describe the HRCT findings in each zone. Postmortem examination and histopathology confirmed the presence of an infiltrating metastatic carcinoma in all three cases. The HRCT changes correlated closely with the pathological findings. The authors conclude that HRCT of the lung should be considered for pulmonary metastatic screening in the dog and introduce a classification system for HRCT findings, based on terminology used in human medicine.

  9. Systemic chemotherapy with doxorubicin, cisplatin and capecitabine for metastatic hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Bang Soo-Mee

    2006-01-01

    Full Text Available Abstract Background Although numerous chemotherapeutic agents have been tested, the role of systemic chemotherapy for hepatocellular carcinoma (HCC has not been clarified. New therapeutic strategies are thus needed to improve outcomes, and we designed this study with new effective drug combination. Methods Twenty-nine patients with histologically-confirmed, metastatic HCC received a combination chemotherapy with doxorubicin 60 mg/m2 and cisplatin 60 mg/m2 on day 1, plus capecitabine 2000 mg/m2/day as an intermittent regimen of 2 weeks of treatment followed by a 1-week rest. Results The median age was 49 years (range, 32–64 and 19 patients were hepatitis B virus seropositive. Child-Pugh class was A in all patients and 4 had Zubrod performance status of 2. The objective response rate was 24% (95% CI 9–40 with 6 stable diseases. The chemotherapy was generally well tolerated despite one treatment-related death. Conclusion Combination chemotherapy with doxorubicin, cisplatin and capecitabine produced modest antitumor activity with tolerable adverse effects in patients with metastatic HCC.

  10. Prolonged Survival following Repetitive Stereotactic Radiosurgery in a Patient with Intracranial Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ethan A. Ferrel

    2015-01-01

    Full Text Available Patients with metastatic renal cell carcinoma (RCC to the brain have a very poor prognosis of three months if left untreated. SRS is an effective treatment modality in numerous patients. This case exemplifies the utility of stereotactic radiosurgery (SRS in prolonging survival and maintaining quality of life in a patient with RCC. This 64-year-old female patient initially presented to her primary care physician 22 months after a left nephrectomy for RCC with complaints of mild, intermittent headaches and difficulty with balance. An MRI revealed five cerebellar lesions suspicious for intracranial metastasis. The patient’s first GKRS treatment targeted four lesions with 22 Gy at the 50% isodose line. She underwent a total of seven GKRS treatments over the next 60 months for recurrent metastases to the brain. 72 months and 12 months have now passed since her brain metastases were first discovered and since her last GKRS treatment, respectively, and this woman is alive with considerable quality of life and no evidence of metastatic reoccurrence. This case shows that repeated GKRS treatments, with minimal surgical intervention, can effectively treat multiple intracranial lesions in select patients, prolonging survival and avoiding iatrogenic neurocognitive decline while maintaining a high quality of life.

  11. Late metastatic endometrial carcinoma at the repair site of an abdominal wall incisional hernia

    Directory of Open Access Journals (Sweden)

    Abdul-Wahed N. Meshikhes

    2017-05-01

    Full Text Available The abdominal wall is a very rare site for endometrial cancer metastases. Its appearance generally indicates advanced cancer with poor prognosis. We report a case of a 55-year-old female who presented with an incisional hernia 4 years after abdominal panhysterectomy for endometrioid adenocarcinoma in 2009. Open hernia mesh repair was performed but on follow-up, she complained of pain and a swelling at the repair site. This was radiologically diagnosed as fibromatosis, but tru-cut biopsy confirmed presence of fibromatosis as well as a metastatic endometrial carcinoma. She was started on neoadjuvant chemotherapy, but had poor response, and therefore, radical excision was performed. She remained well with no metastatic recurrence at 12-month follow-up. This case illustrates late appearance of abdominal wall metastasis from abdomino-pelvic malignancies and highlights the need to exclude the presence of recurrence or metastases prior to surgical repair of incisional hernia occurring after the resection of abdominal or pelvic malignancy.

  12. Case of metastatic basal cell carcinoma to bone marrow, resulting in myelophthisic anemia.

    Science.gov (United States)

    Pham, Catherine M; Syed, Almas A; Siddiqui, Huma A; Keller, Richard A; Kowalewski, Catherine

    2013-04-01

    While basal cell carcinoma (BCC) remains the most common skin cancer, the incidence of metastasis is rare. Most cases of metastatic BCC have been to regional lymph nodes. Metastasis to bone marrow with myelophthisic anemia is especially rare. To our knowledge, there have been only 5 reported cases in literature. We report a sixth case. A 46-year-old male patient presented with an 8 × 7-cm ulcerated plaque on his chest, found to be morpheaform basal cell on pathology. Laboratory findings were notable for normocytic anemia, thrombocytopenia, and elevated LDH. Further work up with bone marrow biopsy revealed tumor cells staining positive for CK AE1/AE3, BerEP4, CK7, CD56, and PIN-4. This confirmed the diagnosis of metastatic BCC (MBCC) to bone marrow. Although the rate of metastasis for BCC is rare, once it occurs, prognosis is poor. MBCC remains a challenge to treat. Therefore, it is critical to resolve the primary BCC and obtain vigilant follow-up, especially in patients with multiple risk factors for MBCC.

  13. Metastatic Basal Cell Carcinoma: A Biological Continuum of Basal Cell Carcinoma?

    OpenAIRE

    Karaninder S. Mehta; Vikram K. Mahajan; Pushpinder S. Chauhan; Anju Lath Sharma; Vikas Sharma; C. Abhinav; Gayatri Khatri; Neel Prabha; Saurabh Sharma; Muninder Negi

    2012-01-01

    Basal cell carcinoma (BCC) accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide s...

  14. Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas.

    Science.gov (United States)

    McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas

    2017-03-01

    Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Comparison of quantitative methods on FDG PET/CT for treatment response evaluation of metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Ji In; Paeng, Jin Chul; Park, So Hyun [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of); and others

    2017-06-15

    FDG PET is effective in treatment response evaluation of cancer. However, there is no standard method for quantitative evaluation of FDG PET, particularly regarding cytostatic drugs. We compared various FDG PET quantitative methods in terms of response determination. A total of 39 refractory metastatic colorectal cancer patients who received a multikinase inhibitor treatment were included. Baseline and posttreatment FDG PET/CT scans were performed before and two cycles after treatment. Standardized uptake value (SUV) and total lesion glycolysis (TLG) values using various margin thresholds (30–70 % of maximum SUV with increment 10 %, twice mean SUV of blood pool, SUV 3.0, and SUV 4.0) were measured, with measurement target of the hottest lesion or a maximum of five hottest lesions. Treatment response by the PERCIST criteria was also determined. Predictive values of the PET indexes were evaluated in terms of the treatment response determined by the RECIST 1.1 criteria. The agreement rate was 38 % between response determined by the PERCIST and the RECIST criteria (κ = 0.381). When patients were classified into disease control group (PR, SD) and non-control group (PD) by the RECIST criteria, percent changes of TLG with various margin thresholds (particularly, 30–50 % of maximum SUV) exhibited significant differences between the two groups, and high diagnostic power for the response by the RECIST criteria. TLG-based criteria, which used a margin threshold of 50 % of maximum SUV, exhibited a high agreement with the RECIST criteria compared with the PERCIST criteria (κ = 0.606). In metastatic colorectal cancer, FDG PET/CT could be effective for treatment response evaluation by using TLG measured by margin thresholds of 30–50 % of maximum SUV. Further studies are warranted regarding the optimal cutoff values for this method.

  16. Regorafenib in combination with silybin as a novel potential strategy for the treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Belli, Valentina; Sforza, Vincenzo; Cardone, Claudia; Martinelli, Erika; Barra, Giusi; Matrone, Nunzia; Napolitano, Stefania; Morgillo, Floriana; Tuccillo, Concetta; Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina; Gravina, Antonietta Gerarda; De Palma, Raffaele; Ciardiello, Fortunato; Troiani, Teresa

    2017-09-15

    Regorafenib, an oral multikinase inhibitor, has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients that have progressed after all standard therapies. However, novel strategies to improve tolerability and enhance anti-cancer efficacy are needed. We have evaluated in vitro the effects of regorafenib in combination with silybin, a biologically active component extracted from the seeds of Silybum marianum, in a panel of human colon cancer cells. Furthermore, we have prospectively treated a cohort of 22 refractory mCRC patients with regorafenib plus silybin. Treatment with regorafenib determined a dose-dependent growth inhibition whereas treatment with silybin had no anti-proliferative effects among all cancer cells tested. The combined treatment with regorafenib and silybin induced synergistic anti-proliferative and apoptotic effects by blocking PI3K/AKT/mTOR intracellular pathway. Moreover, combined treatment with regorafenib and silybin increased the production of reactive oxygen species levels within cells. In an exploratory proof of concept clinical study in a cohort of 22 mCRC patients after failure of all standard therapies, the clinical activity of regorafenib in combination with silybin was assessed. A median progression-free survival of 10.0 months and a median overall survival of 17.6 months were observed in these patients. These results suggest that the combined treatment potentially increases the clinical efficacy of regorafenib. Moreover, due to its anti-oxidative properties, silybin could protect patients from drug-induced liver damages, allowing to continue an effective anti-cancer therapy. The present study suggests that silybin in combination with regorafenib is a promising strategy for treatment of metastatic colorectal patients.

  17. Pathophysiological mechanisms of death resistance in colorectal carcinoma.

    Science.gov (United States)

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-11-07

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

  18. Soluble vascular endothelial growth factor levels in patients with primary colorectal carcinoma. The Danish RANX05 Colorectal Cancer Study Group

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Brünner, N

    2000-01-01

    INTRODUCTION: Angiogenesis is decisive in tumour progression and metastasis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, and increased VEGF levels in patients with carcinomas may facilitate growth of both primary and secondary tumours. METHODS: Soluble (s) VEGF levels...... were determined in serum from 91 volunteer healthy blood donors and from 614 patients scheduled to undergo resection for primary colorectal cancer. None of the patients received pre- and/or post-operative chemo- and/or radiotherapy. The results of sVEGF were analysed with respect to Dukes>> stage...... disease, who had comparable values. Patients with the primary tumour localized in the colon had significantly (Pprimary tumour localized in the rectum. By classifying the patients into two groups, based on the upper limit of the 95(th)percentile of s...

  19. Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2013-08-01

    Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma.

    Directory of Open Access Journals (Sweden)

    Fabian Feiersinger

    Full Text Available Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01. MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01. No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01.In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.

  1. INTEGRATION OF BEVACIZUMAB IN METASTATIC COLORECTAL CANCER CHEMOTHERAPY REGIMENS IN 2 CLINICAL CENTERS IN MOSCOW AND SAINT PETERSBURG

    Directory of Open Access Journals (Sweden)

    N. V. Dobrova

    2013-01-01

    Full Text Available The aim of this study was to estimate efficacy of first line chemotherapy with bevacizumab in metastatic colorectal cancer patients and investigate the impact of different prognostic factors on treatment outcome.Methods.During 2004–2008 48 colorectal cancer patients were included (29 in Russian N.N. Blokhin Cancer Research Center, 19 in St. Petersburg, who had unresectable distant metastases. Primary tumor was resected in 93.8 % patients. 52.1 % had rectal cancer. 87.5 % had liver metastases, 43.8 % had more than 1 organ affected. 66.7 % received chemotherapy with bevacizumab 5 mg/kg biweekly, 33.3 % received bevacizumab 7,5 mg/kg every 3 weeks. 62.5 % patients had oxaliplatin-based regimens, 35.4 % – only fluorpyrimidines, 2.1 % – chemotherapy with irinotecan.Results.Median time of bevacizumab use was 7.8 months. 60.3 % had objective response, 87.4 % had stable diseases during more than 6 months. Median progression-free survival (PFS was 11.5 months. Median overall survival (OS was 24.1 months.Conclusions.Survival and efficacy results are comparable to international experience. Combination of fluorpyrimidines with bevacizumab had comparable efficacy to combined chemotherapy regimens with no impact on quality of life. Integration of bevacizumab in combined treatment regimens reduced the impact of negative prognostic factors on PFS and OS. 

  2. Adipo-R1 and adipo-R2 expression in colorectal adenomas and carcinomas.

    Science.gov (United States)

    Ayyildiz, Talat; Dolar, Enver; Ugras, Nesrin; Eminler, Ahmet Tarik; Erturk, Banu; Adim, Saduman Balaban; Yerci, Omer

    2015-01-01

    Human adiponectin (ApN), a 30 kDa glycoprotein of 244-amino acids which is predominantly produced by adipocytes, exerts its effects via two receptors, namely adiponectin receptor-1 (adipo-R1) and adiponectin receptor-2 (adipo-R2) with differential binding affinity to globular adiponectin. Adiponectin receptor expression has been studied in several cancer tissues. However, there are no studies of colorectal adenomas which are considered to be precursors for colorectal carcinoma (CRC). In the present study, the expression of adipo-R1 and adipo-R2 was investigated immunohistochemically in colorectal adenomas and colorectal carcinoma tissues in an attempt to determine associations with these tumors. The study enrolled 50 CRC patients with tumor resection and 82 patients who were diagnosed with adenomatous polyps, classified as negative for neoplasia, low-grade dysplasia (L-GD) or high- grade dysplasia (H-GD). Expression of both adipo-R1 and adipo-R2 was found to be significantly lower in the CRCs than in colorectal adenomas (tubular and tubulovillous, p=0.009 and p<0.001, respectively). Adipo-R1 and adipo-R2 expression was also significantly lower in the CRC group when compared with the groups of patients with low grade dysplasia, high-grade dysplasia or no neoplasia (p=0.012 and p<0.001, respectively). In addition, it was observed that adipo-R2 expression was generally positive in the non-neoplastic group irrespective of the adipo-R2 expression. In the L-GD, H-GD and CRC groups, the adipo-R2 result was positive whenever adipo-R1 result was positive but some patients with negative adipo-R1 had positive adipo-R2 (p<0.001, p=0.004, p<0.001, respectively). This study indicated that ApN may play a role in the progression of colorectal adenomatous polyps to carcinoma through actions on adipo-R1 and adipo-R2 receptors.

  3. Treatment monitoring in metastatic colorectal cancer patients by quantification and KRAS genotyping of circulating cell-free DNA.

    Directory of Open Access Journals (Sweden)

    Andreas W Berger

    Full Text Available Treatment of metastatic colorectal cancer (CRC has continuously improved over the last decade. However, disease monitoring remains underdeveloped and mostly dependent on imaging e.g. RECIST 1.1 criteria. The genetic landscape of individual cancers and subsequently occurring treatment-induced evolution remain neglected in current surveillance strategies. Novel biomarkers demand minimally invasive and repetitive tracking of the cancer mutagenome for therapy stratification and to make prognostic predictions. Carcinoembryonic antigen (CEA, a routinely used tumor marker for CRC, does not meet these goals and thus prevents its use as a reliable monitoring tool. A tumor-derived fraction of circulating cell-free DNA (cfDNA, isolated from blood samples, may bypass the limitations of currently available biomarkers and could be a tool for noninvasive disease monitoring. Here, total cfDNA levels differentiated a cohort of metastatic CRC patients from healthy controls. Furthermore, we correlated cfDNA during chemotherapy of 27 stage IV patients with clinical parameters to establish its prognostic and predictive value. Indeed, cfDNA levels in chemotherapy naive patients correlate with the tumor burden and CEA values at diagnosis and increase upon disease progression during 1st and 2nd line treatment. Moreover, we confirm the possibility of cfDNA-based genotyping of KRAS to early detect the emergence of resistance during chemotherapy. These data indicate that repetitive quantitative and mutational analysis of cfDNA might complement current treatment standards but may have also limited value in some patients.

  4. Molecular profiling of 6,892 colorectal cancer samples suggests different possible treatment options specific to metastatic sites.

    Science.gov (United States)

    El-Deiry, Wafik S; Vijayvergia, Namrata; Xiu, Joanne; Scicchitano, Angelique; Lim, Bora; Yee, Nelson S; Harvey, Harold A; Gatalica, Zoran; Reddy, Sandeep

    2015-01-01

    Metastatic colorectal cancer (mCRC) carries a poor prognosis with an overall 5-year survival of 13.1%. Therapies guided by tumor profiling have suggested benefit in advanced cancer. We used a multiplatform molecular profiling (MP) approach to identify key molecular changes that may provide therapeutic options not typically considered in mCRC. We evaluated 6892 mCRC referred to Caris Life Sciences by MP including sequencing (Sanger/NGS), immunohistochemistry (IHC) and in-situ hybridization (ISH). mCRC metastases to liver, brain, ovary or lung (n = 1507) showed differential expression of markers including high protein expression of TOPO1 (52%) and/or low RRM1 (57%), TS (71%) and MGMT (39%), suggesting possible benefit from irinotecan, gemcitabine, 5FU/capecitabine and temozolomide, respectively. Lung metastases harbored a higher Her2 protein expression than the primary colon tumors (4% vs. 1.8%, p = 0.028). Brain and lung metastases had higher KRAS mutations than other sites (65% vs 59% vs 47%, respectively, p = 0.07, cancer versus colon cancer (10% and 3.3%, respectively). MP of 6892 CRCs identified significant differences between primary and metastatic sites and among BRAF/KRAS sub-types. Our findings are hypothesis generating and need to be examined in prospective studies. Specific therapies may be considered for different actionable targets in mCRC as revealed by MP.

  5. Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma.

    Science.gov (United States)

    Karabulut, M; Gunaldi, M; Alis, H; Afsar, C U; Karabulut, S; Serilmez, M; Akarsu, C; Seyit, H; Aykan, N F

    2016-02-01

    Nectins are a family of integral protein and immunoglobulin-like cell adhesion molecules involved in the formation of functioning adherence and tight junctions. Aberrant expression is associated with cancer progression, apoptosis and cell proliferation but little is known how these effects change in cell behavior. The objective of this study was to evaluate the serum levels of nectin-2 with regard to diagnostic, predictive and prognostic value in colorectal cancer (CRC) patients. One-hundred and forty CRC patients were enrolled in this study. Serum nectin-2 levels were determined by enzyme-linked immunosorbent assay method. Age- and sex-matched 40 healthy controls were included in the analysis. Median age of patients was 60 years old, range 24-84 years. The localization of tumor in majority of the patients was colon (n = 81, 58 %). Non-metastatic (stage II and III) and metastatic patients' baseline serum nectin-2 levels were significantly higher than those in the healthy control group (p 0.05). While non-metastatic group patients with elevated serum nectin-2 levels showed significant adverse effect on PFS, metastatic group patients with elevated serum nectin-2 levels showed no significant adverse effect on PFS (p = 0.05 and p = 0.29, respectively). On the other hand, our study results did not show statistically significant serum nectin-2 concentrations regarding overall survival rates. Serum levels of nectin-2 may have diagnostic roles for CRC patients. Moreover, our study results show the prognostic role of nectin-2 in non-metastatic group patients.

  6. DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis.

    Directory of Open Access Journals (Sweden)

    Kazuo Konishi

    Full Text Available BACKGROUND: The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs is unclear. METHODS: We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM in three paired primary and metastatic cancers. RESULTS: Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively (P<.05. When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013, and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency. CONCLUSIONS: Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis.

  7. Apoptosis and histological response of preoperative intraarterial chemotherapy infusion for colorectal carcinoma

    International Nuclear Information System (INIS)

    Yuan Jianhua; Hu Tingyang; Yu Wenqiang; Chen Fanghong; Luo Zuyan; Mao Yinmin; Zhao Zhongsheng; Ru Guoqing; Deng Gaoli; Dong Quanjin; Tu Shiliang

    2003-01-01

    Objective: To investigate apoptosis and histological response of preoperative intraarterial chemotherapy infusion for colorectal carcinoma. Methods: Fifty patients with colorectal carcinoma were treated by intraarterial infusion of anti-cancer drugs. Surgical resection of the tumor was performed 5-30 days after the intraarterial infusion (mean 12 days). The histological response was evaluated. The density and distribution of the apoptosis cells were observed by DNA nick end labelling technique. 22 biopsy specimens before the intraarterial chemotherapy and 25 normal mucosa (obtained from surgery specimen) were used as controls. Results: The total histological response rate was 100% with grade I in 20 cases, grade II in 21 cases, and grade III in 9 cases. The density of the apoptosis cells was 31.47±5.58 before and 76.69±17.12 after the intraarterial chemotherapy infusion, and 8.01±3.39 in normal mucosa, respectively. The density of the apoptosis cells after the intraarterial chemotherapy was significantly higher than that before the intraarterial chemotherapy (t=13.701, P 2 =4.696, P>0.30). The apoptosis of adenocarcinoma was significantly different with different histological response (F=7.73, P 0.05) and for adenocarcinoma with different pathological stages (F=0.001376, P>0.05). Conclusion: As an effective and safe procedure, preoperative transcatheter intraarterial chemotherapy infusion achieves a significant histological response and apoptosis in colorectal adenocarcinoma

  8. Metastatic pattern of invasive lobular carcinoma of the breast-Emphasis on gastric metastases.

    Science.gov (United States)

    El-Hage, Ali; Ruel, Carolanne; Afif, Wahiba; Wissanji, Hussein; Hogue, Jean-Charles; Desbiens, Christine; Leblanc, Guy; Poirier, Éric

    2016-10-01

    Breast invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have different metastatic patterns, but the exact pattern of metastases from ILC is poorly known. This study aimed to determine the frequency of ILC metastases in atypical locations, with an emphasis on gastric metastases. Patients with ILC treated at the Saint-Sacrement Hospital (Quebec City, Canada) and the Maisonneuve-Rosemont Hospital (Montreal, Canada) between January 2003 and December 2009 were retrospectively reviewed. Demographic, clinical, and follow-up data were retrieved from the medical charts. Metastases that were diagnosed during follow-up were recorded. Among the 481 patients with ILC, 74 (15.4%) were diagnosed with metastases after a median follow-up of 46 months. Among these 74 patients, 41.9% had metastases in atypical sites. Five patients were diagnosed with histologically confirmed gastric metastases of ILC. Metastases of breast ILC to atypical sites might be more frequent than previously reported. Clinicians should keep a high level of suspicion when a patient with a history of ILC develops digestive symptoms. It is important to differentiate metastases from a primary GI tumor by using immunohistochemical markers. J. Surg. Oncol. 2016;114:543-547. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Immunotherapy with dendritic cells in an animal model of early pulmonary metastatic squamous cell carcinoma.

    Science.gov (United States)

    Moon, Jeong Hwan; Chung, Man Ki; Son, Young-Ik

    2012-11-01

    Distant metastases is becoming a more frequently recognized pattern of treatment failure in patients with squamous cell carcinoma of the head and neck (SCCHN). In this study, we evaluated the effect of a dendritic cell (DC)-based vaccine in an early pulmonary metastatic murine model with the aim of providing an effective treatment for SCCHN patients presenting with occult pulmonary metastasis. In vivo animal experiments were conducted in C3H/He immunocompetent mice using the SCCVII syngeneic squamous carcinoma cell line. SCCVII cells were injected through the tail vein to establish early pulmonary metastases. Bone marrow-derived DCs were cultured and educated with ultraviolet B-irradiated apoptotic SCCVII cells before adoptive transfer into the inguinal area. Control groups were vaccinated with normal saline, naïve DCs, or apoptotic tumor cells. In the apoptotic SCCVII-pulsed DC group, the number of pulmonary tumor nodules was reduced, extirpated lung weight was less, and survival was longer than in control groups. Differences were statistically significant (P cells. We hope this study will help improve overall survival of patients with SCCHN, especially when they have early or occult pulmonary metastasis. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  10. An Unusual Metastatic Renal Cell Carcinoma with Maintained Complete Response to Sunitinib Treatment

    Directory of Open Access Journals (Sweden)

    Luis Chara

    2011-12-01

    Full Text Available Recently, metastatic renal cell carcinoma (mRCC treatment has changed dramatically with the onset of new therapies against molecular targets replacing immunotherapy as standard treatment. We report the case of a 49-year-old patient with a moderately differentiated renal clear cell carcinoma without extracapsular extension who underwent radical nephrectomy. Eight months after surgery, he developed a thyroid metastasis which was also treated surgically with a hemithyroidectomy. Seventy-five months after nephrectomy, the patient presented an upper gastrointestinal bleeding due to a duodenal metastasis that infiltrates the head of the pancreas. The treatment applied was surgery by duodenopancreatectomy, with positive surgical margins in the pathologic study. In addition to this, the extension study showed lung metastases requiring initiation of systemic treatment with sunitinib. The patient presented an excellent response to treatment, showing complete clinical and radiological response at 5 months of treatment (RECIST criteria and a disease-free survival of 48 months until now, without evidence of toxicity. RCC has the potential to metastasize to almost any location, but thyroid and duodenal metastases in RCC are extremely rare. Moreover, this case also highlights the good responses that can be achieved in terms of disease-free survival, low toxicity and quality of life in this new era of therapies against molecular targets.

  11. A case of acute adrenal insufficiency unmasked during sunitinib treatment for metastatic renal cell carcinoma.

    Science.gov (United States)

    Yoshino, Takayuki; Kawai, Koji; Miyazaki, Jun; Kimura, Tomokazu; Ikeda, Atsushi; Takaoka, Ei-ichiro; Suetomi, Takahiro; Oikawa, Takehiro; Kojima, Takahiro; Iwasaki, Hitoshi; Shimano, Hitoshi; Nishiyama, Hiroyuki

    2012-08-01

    Sunitinib has recently become a standard treatment for metastatic renal cell carcinoma. However, various adverse events have been reported. We present the first case of clinically evident adrenal insufficiency during sunitinib therapy. A 72-year-old man began sunitinib therapy for bilateral lung and adrenal metastases of renal cell carcinoma. His adrenocorticotrophic hormone level was 93.6 pg/ml (7.2-63.3 pg/ml) before sunitinib treatment, indicating that subclinical adrenal insufficiency already existed. Fatigue, which is a frequently seen adverse effect of sunitinib treatment, emerged acutely on Day 24 of the second cycle. Adrenocorticotrophic hormone and free T4 were high and thyroid-stimulating hormone was suppressed. Under the clinical diagnosis of acute adrenal insufficiency with thyrotoxicosis, a low dose of steroid was administered. Fatigue was completely ameliorated by the following morning, although free T4 was still high and thyroid-stimulating hormone was still low. Therefore, hypermetabolism due to thyrotoxicosis unmasked adrenal insufficiency in our case. Physicians should be aware of this rare but potentially fatal complication when severe acute fatigue develops in patients with subclinical adrenal insufficiency.

  12. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial.

    Science.gov (United States)

    Argilés, Guillem; Saunders, Mark P; Rivera, Fernando; Sobrero, Alberto; Benson, Al; Guillén Ponce, Carmen; Cascinu, Stefano; Van Cutsem, Eric; Macpherson, Iain R; Strumberg, Dirk; Köhne, Claus-Henning; Zalcberg, John; Wagner, Andrea; Luigi Garosi, Vittorio; Grunert, Julia; Tabernero, Josep; Ciardiello, Fortunato

    2015-05-01

    The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Regorafenib+mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. Copyright © 2015. Published by Elsevier Ltd.

  13. Regorafenib with a fluoropyrimidine for metastatic colorectal cancer after progression on multiple 5-FU-containing combination therapies and regorafenib monotherapy.

    Science.gov (United States)

    Marks, Eric I; Tan, Carlyn; Zhang, Jun; Zhou, Lanlan; Yang, Zhaohai; Scicchitano, Angelique; El-Deiry, Wafik S

    2015-01-01

    We present 2 patients with metastatic colorectal cancer who had progressed despite treatment with first-line FOLFOX and second-line FOLFIRI combination chemotherapy regimens. After failing these fluoropyrimidine-based regimens, both patients received additional cytotoxic and targeted therapies with eventual disease progression. These therapies included capecitabine plus dabrafenib and trametinib, regorafenib monotherapy, and regorafenib with panitumumab. After exhausting available options, both patients were offered regorafenib with either 5-fluorouracil (5-FU) or capecitabine. These therapies are individually approved for the treatment of colorectal cancer but have not yet been studied in combination. This regimen produced stable disease in both patients with acceptable toxicity. One patient continued therapy for 17 months. Although these patients previously progressed during treatment with regorafenib, capecitabine or 5-FU, the combination had some activity in both cases of refractory metastatic colorectal cancer and may be considered in the palliative setting. In bedside-to-bench cell culture experiments performed after the clinical observations, we observed sensitivity of human colorectal cancer cell lines (N = 4) to single agent regorafenib or 5-FU and evidence of synergy with the combination therapy. Synergistic effects were noted in colorectal cancer cells with KRAS mutation, BRAF mutation, and p53 mutation, as well as mismatch repair deficient cells. Regorafenib suppressed Mcl-1 and Bcl-XL in treated cancer cells that may have contributed to the anticancer efficacy including in combination with 5-FU. The safety and efficacy of regorafenib with 5-FU or capecitabine in combination should be further investigated as a therapy for patients with refractory metastatic colorectal cancer, including individuals who had progressed on regorafenib monotherapy.

  14. Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy

    DEFF Research Database (Denmark)

    Templeton, Arnoud J; Knox, Jennifer J; Lin, Xun

    2016-01-01

    BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), if elevated, is associated with worse outcomes in several malignancies. OBJECTIVE: Investigation of NLR at baseline and during therapy for metastatic renal cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 1199 patients ...

  15. Colorectal Carcinoma: Why Is There a Lower Incidence in Nigerians When Compared to Caucasians?

    Directory of Open Access Journals (Sweden)

    David Omoareghan Irabor

    2011-01-01

    Full Text Available Carcinoma of the colon and rectum is the 2nd commonest cancer in the United States; the leading cancer being lung cancer. It has been estimated that 130,200 new cases of colorectal cancer will be diagnosed annually while 56,300 sufferers will die from the disease (Murphy et al., 2000. In developing countries especially West Africa, the rate has not yet reached such magnitude. This suggests that there may be factors either anthropomorphic or environmental which may be responsible for this. The paper acknowledges the reduced incidence of colorectal cancer in native West Africans living in Africa and endeavours to highlight the various factors that produce this observation in medical literature. A diligent search through available literature on the aetiology, epidemiology and comparative anthropology of colorectal cancer was done. Internet search using Pubmed, British library online and Google scholar was also utilized. The rarity of adenomatous polyposis syndromes in the native West African contributes to the reduced incidence of colorectal cancer. Cancer prevention and cancer-protective factors are deemed to lie in the starchy, high-fiber, spicy, peppery foodstuff low in animal protein which many West African nations consume.

  16. Colorectal Carcinoma: Why Is There a Lower Incidence in Nigerians When Compared to Caucasians?

    International Nuclear Information System (INIS)

    Irabor, D. O.

    2011-01-01

    Carcinoma of the colon and rectum is the 2nd commonest cancer in the United States; the leading cancer being lung cancer. It has been estimated that 130,200 new cases of colorectal cancer will be diagnosed annually while 56,300 sufferers will die from the disease (Murphy et al., 2000). In developing countries especially West Africa, the rate has not yet reached such magnitude. This suggests that there may be factors either anthropomorphic or environmental which may be responsible for this. The paper acknowledges the reduced incidence of colorectal cancer in native West Africans living in Africa and endeavours to highlight the various factors that produce this observation in medical literature. A diligent search through available literature on the aetiology, epidemiology and comparative anthropology of colorectal cancer was done. Internet search using Pub med, British library online and Google scholar was also utilized. The rarity of adenomatous polyposis syndromes in the native West African contributes to the reduced incidence of colorectal cancer. Cancer prevention and cancer-protective factors are deemed to lie in the starchy, high-fiber, spicy, peppery foodstuff low in animal protein which many West African nations consume.

  17. Metastatic renal cell carcinoma in the thyroid gland: ultrasonographic features and the diagnostic role of core needle biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ok Kyu; Koo, Ja Seung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Eun Kyung [Severance Hospital, Yonsei University College of Medicine, Seoul(Korea, Republic of)

    2017-07-15

    The aims of this study were to present the ultrasonographic (US) features of metastatic renal cell carcinoma (RCC) in the thyroid gland and to evaluate the diagnostic utility of fine needle aspiration (FNA) and core needle biopsy (CNB). Eight patients with nine metastatic RCC nodules in the thyroid glands who were treated from January 2002 to March 2015 in a single tertiary hospital were consecutively selected and retrospectively reviewed. US features and clinical history were obtained from the institution’s medical database. FNA was performed nine times on eight nodules and CNB was performed six times on six nodules. The diagnostic utility of FNA and CNB was evaluated. All nine nodules showed mass formation without diffuse thyroid involvement. On ultrasonography, metastatic RCC nodules were solid (100%), hypoechoic (100%), and ovalshaped nodules with a well-defined smooth margin (88.9%) and increased vascularity (100%, with 55% showing extensive vascularity). No calcifications were noted in any nodules. Lymph node metastasis and direct extension to nearby structures beyond the thyroid gland were not found. One FNA (11%) was able to confirm metastatic RCC, whereas all six CNBs confirmed metastatic RCC. Metastatic RCC appears as oval-shaped hypoechoic solid nodules with well-defined smooth margins, no calcifications, and increased vascularity on ultrasonography. Characteristic US features along with a previous history of RCC should raise clinical suspicion, and CNB should be performed to make an accurate diagnosis.

  18. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  19. Variation in the staging of colorectal carcinomas: a survey of current practice.

    Science.gov (United States)

    Raraty, M G; Winstanley, J H

    1998-05-01

    Dukes' staging is the most common means of staging and grouping colorectal carcinomas and is also used to determine which patients will be offered adjuvant therapies or entered into clinical trials. This study was performed to assess the degree of variation in the staging of colorectal carcinomas in normal clinical practice. Seven consultant surgeons and two consultant pathologists returned questionnaires asking them to stage 14 carcinomas on the basis of their pathology reports alone. The results show agreement among all nine in only six out of the 14 cases. In two cases there was a close to 50:50 split in perceived stage. Between them, the nine consultants produced eight different sets of staging results. These results indicate difficulties in the application of Dukes' staging system for several possible reasons. There may be misinterpretation of the written report, misapplication of the staging system because of unfamiliarity or confusion between the various modifications of Dukes' system which have been published. A more precisely defined staging system based on a standard proforma may be more appropriate in modern clinical practice.

  20. Colorectal carcinoma in a patient with prior breast cancer: Is there a causal link?

    Energy Technology Data Exchange (ETDEWEB)

    Scarles, Elaine [Blackpool Victoria Hospital, Blackpool, Lancashire FY3 8NR (United Kingdom); Nightingale, Julie [Department of Radiography, School of Health Care Professions, University of Salford, Salford, Greater Manchester, M6 6PU (United Kingdom)], E-mail: j.nightingale@salford.ac.uk

    2008-02-15

    A 70-year-old female patient with prior breast cancer was diagnosed with colorectal carcinoma six years following the original breast referral. The cancers were both discovered at an early stage enabling potentially curative surgery to be performed, with an associated good long-term prognosis. This article explores a range of cancer risk factors associated with lifestyle, genetics and medication to ascertain whether the two primary cancers were independent oncological events, or whether they were related. Factors such as smoking, alcohol consumption, genetic predisposition and the use of contraceptives and Tamoxifen may increase the relative risk for both cancers. Various studies have offered conflicting data regarding the relative risk for developing the second cancer, but long-term cohort studies will continue to add to the evidence base. It is possible that the outcomes of these studies may have implications for the follow up of breast cancer patients within the colorectal cancer screening service.

  1. Colorectal carcinoma in a patient with prior breast cancer: Is there a causal link?

    International Nuclear Information System (INIS)

    Scarles, Elaine; Nightingale, Julie

    2008-01-01

    A 70-year-old female patient with prior breast cancer was diagnosed with colorectal carcinoma six years following the original breast referral. The cancers were both discovered at an early stage enabling potentially curative surgery to be performed, with an associated good long-term prognosis. This article explores a range of cancer risk factors associated with lifestyle, genetics and medication to ascertain whether the two primary cancers were independent oncological events, or whether they were related. Factors such as smoking, alcohol consumption, genetic predisposition and the use of contraceptives and Tamoxifen may increase the relative risk for both cancers. Various studies have offered conflicting data regarding the relative risk for developing the second cancer, but long-term cohort studies will continue to add to the evidence base. It is possible that the outcomes of these studies may have implications for the follow up of breast cancer patients within the colorectal cancer screening service

  2. OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer.

    NARCIS (Netherlands)

    Poston, G.J.; Adam, R.; Alberts, S.; Curley, S.; Figueras, J.; Haller, D.; Kunstlinger, F.; Mentha, G.; Nordlinger, B.; Patt, Y.; Primrose, J.; Roh, M.; Rougier, P.; Ruers, T.J.M.; Schmoll, H.J.; Valls, C.; Vauthey, N.J.; Cornelis, M.; Kahan, J.P.

    2005-01-01

    PURPOSE: Most patients with colorectal liver metastases present to general surgeons and oncologists without a specialist interest in their management. Since treatment strategy is frequently dependent on the response to earlier treatments, our aim was to create a therapeutic decision model

  3. Study of Alpha Tocopherol, Celecoxib Induced Apoptosis in Human Colorectal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Solgui R

    2010-03-01

    Full Text Available Background and Objectives: Chronic, unbridled oxidative damages have been known as the culprits behind many chronic diseases, including cancers, atherosclerosis, diabetes and Alzheimer’s. Cyclooxygenase-2 (COX-2-the main enzyme involved in inducing these processes- plays an important role in tumor development and progression. COX-2 inhibitors should be used at high doses for a long time in order to bring about chemoprevention and induction of anti-tumor effects. For example, celecoxib prevents colorectal tumor growth and induces apoptosis in both in vitro and in vivo models. Disregulation of COX-2 expression coincides with the development of gastrointestinal malignancy in humans and in animal models of colorectal cancer. Increased COX-2 expression in human colorectal adeno-carcinomas has been elucidated when compared with normal adjacent colonic mucosa. The capacity of vitamin E, particularly in α form, to quench free radical damage, induces apoptosis and impact expression of oncogenes makes it an appropriate choice for chemotherapeutic strategies. Studies have shown that carcinogenesis and DNA damage due to UV are inhibited by vitamin E. The goal of this study was to investigate alpha tocopherol and celecoxib induced apoptosis in human colorectal carcinoma cell line.Methods: In this study, HT29 cells were exposed to different concentrations of tocopherol (5, 10, and 20µM and celecoxib (25, 50, 75, 100µM followed by DNA extraction and fragmentation for demonstrating cell death process. Results: The results indicated that celecoxib at lower doses (25, and 50µM could not induce cell death, but at higher doses (75, and 100 µM, DNA fragmentation results typically resembled programmed cell death.Conclusion: ocopherol (5, 10, and 20µM in combination with celecoxib improved the impact of celecoxib on cell death induction and made it the rational notion to be combined with vitamin E in clinical practice.

  4. Gut-associated Lymphoid Tissue (GALT) Carcinoma or Dome Carcinoma?

    Science.gov (United States)

    Rubio, Carlos A; Schmidt, Peter T

    2016-10-01

    The vast majority of colorectal carcinomas (CRCs) evolve from mucosa not associated to lymphoid tissues aggregates via the adenoma-carcinoma sequence or via the serrated pathway. Rarely CRCs evolve from gut mucosa associated to lymphoid tissue (GALT). Based on the presence of a circumscribed elevation in the colorectal mucosa, GALT carcinomas are also referred to as dome carcinomas (DC). Descriptions of the surface mucosa covering 21 GALT-CRCs appearing in pathological reports were reviewed. Three of the 21 GALT-CRCs fulfilled the criteria of dome carcinoma. Of the remaining 18 GALT-CRCs, nine were described as polypoid lesions, five as plaque-like lesions, two as sessile elevated lesions or mass, one as ulcerated and one as histological finding. Hence, only 14.3% (n=3) of the 21 GALT-CRCs displayed a dome configuration, whereas the majority, 85.7% (n=18), exhibited structures other than dome shapes at gross or at histologic examination. It becomes apparent that by using "dome" in addressing carcinomas in the colorectal mucosa, many cases of GALT carcinomas might be overlooked. Another drawback of using the "dome" nomenclature is that dome-like outlines may be detected in small metastatic tumors in the submucosa or in small colorectal carcinomas not arising from GALT mucosa. Instead, by using "GALT carcinoma", that is the histologic diagnosis in addressing these neoplasias, all cases of GALT-CRCs will be included. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma - A clinical, phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, A.; Trepiakas, R.; Wenandy, L.

    2008-01-01

    Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC- based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype......, and low-dose IL-2 was administered concomitantly. Tumor response, immune response, and serum IL-6 and YKL-40 were measured during treatment. Vaccine generation was Successful in all patients and no serious adverse events were observed. None of the patients had an objective response but 13/27 patients...

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

    International Nuclear Information System (INIS)

    Arndt, Greg M; Retzlaff, Kathy; Bittner, Anton; Raponi, Mitch; Dossey, Lesley; Cullen, Lara M; Lai, Angela; Druker, Riki; Eisbacher, Michael; Zhang, Chunyan; Tran, Nham; Fan, Hongtao

    2009-01-01

    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

  7. KRAS testing on colo-rectal carcinoma cytological imprints.

    Science.gov (United States)

    Malapelle, Umberto; Bellevicine, Claudio; Russo, Anna; Salatiello, Maria; Palombini, Lucio; Troncone, Giancarlo

    2011-04-01

    Anti-EGFR monoclonal antibodies, cetuximab, and panitumumab, are administrated under the condition that advanced colo-rectal cancer (CRC) carries a wild-type KRAS gene. Thus, clinicians request pathologists to genotype KRAS before treatment. In the near future routine mutation testing at the same time of the surgery may be implemented. The reliability of a rapid KRAS testing on ex vivo cytological samples obtained by direct scraping of the colon tumour tissue is here evaluated. A consecutive series of 20 surgically resected, primary CRC specimens was analysed. Fresh tissue from CRC was scraped with a scalpel blade, smeared on uncoated glass slides, air-dried and Diff-Quik stained to ensure malignant cell presence. The same tissue area was also histologically processed. Exon 2 KRAS gene mutations were evaluated on both cytological and histological specimens by dideoxy sequencing and by the DxS KRAS Mutation Test Kit (DxS, Manchester, England). Data obtained on on imprint cytology and matched histological samples showed full concordance; however, the mutation frequency was slightly higher (35%) by the DxS KRAS Mutation Test Kit than by the dideoxy sequencing (30%). Thus, colon cancer imprint cytology sample is a reliable biospecimen for both dideoxy-sequencing and DxS KRAS Mutation Test Kit analysis and it may be useful to abbreviate the KRAS assay turnaround time. Copyright © 2010 Wiley-Liss, Inc.

  8. The effect of biological effective dose on time to symptom progression in metastatic renal cell carcinoma.

    Science.gov (United States)

    Wilson, D; Hiller, L; Gray, L; Grainger, M; Stirling, A; James, N

    2003-10-01

    Renal cell carcinoma is commonly thought to be a radioresistant malignancy. Retrospective studies report conflicting results on the effect of radiotherapy dose escalation on response and time to progression in symptomatic metastatic disease; studies using the linear quadratic model have used alpha/beta ratios that are inappropriate for slow growing tumours. We aim to describe our experience with palliative radiotherapy in this context, relating Biological Effective Dose to outcome. From December 1995 to April 2001, 143 independent palliative radiotherapy treatments were delivered to 78 patients in a single institution. Retrospective data was obtained on the radiotherapy schedule used, symptom response and time to symptom progression. The biological effective dose (BED) was calculated using alpha/beta ratios of 3 and 7 Gy (BED3 and BED7). The Log-Rank test was used to assess any differences in time to progression, and the Cox Proportional Hazards analysis to determine prognostic factors of time to progression. Overall symptomatic response rate was 73%, with most responses being partial (67%). Forty-three (38%) patients had symptomatic progression after a median follow-up of 425 days. BED (BED3 or BED7) was not significantly different across response types (complete, partial or no response; P=0.90 and 0.88, respectively) and was not predictive for time to symptomatic progression (P=0.99 for BED3 and P=0.70 for BED7). Patients with bone metastases received less total dose (P=0.001), less BED (BED3, P=0.0013, and BED7, P=0.0005) and had a significantly longer time to progression than other sites of metastases (hazard ratio (HR) 0.4; 95% confidence interval (CI) 0.2-0.7; P=0.004). Initial treatment with interferon-alpha alone in patients presenting with metastatic disease, before palliative radiotherapy, was also associated with a shorter time to symptom progression (HR 4.6; 95% CI 1.5-14.1; P=0.007). On removal of these criteria, brain metastases became a significant

  9. Mutation of the p53 gene precedes aneuploid clonal divergence in colorectal carcinoma.

    OpenAIRE

    Carder, P. J.; Cripps, K. J.; Morris, R.; Collins, S.; White, S.; Bird, C. C.; Wyllie, A. H.

    1995-01-01

    To establish whether p53 mutation precedes or follows clonal divergence in human colorectal carcinomas, 17 tumours were analysed at multiple sites (2-5 each) for single-strand conformation polymorphisms (SSCP) within exons 5-8 of the p53 gene. A previous study had demonstrated subclones of differing DNA ploidy in these tumours, but all showed immunocytochemical evidence for p53 stabilisation, using the monoclonal antibody PAb 1801. Mutations within exons 5-8 of p53 were identified by the pres...

  10. Colorectal carcinoma in a ten-year-old girl: A case report

    Directory of Open Access Journals (Sweden)

    Sarbani Chattopadhyay

    2012-01-01

    Full Text Available Colorectal carcinoma is very rare in childhood. In this case report, we depict a ten-year-old girl who presented with features of intestinal obstruction which turned out to be due to poorly differentiated mucin secreting adenocarcinoma of descending colon. Only increased awareness of this malignancy in this age-group and a high index of suspicion can help when a child complains of persistent pain of abdomen, altered bowel habits or rectal bleeding, and may provide diagnosis at an earlier stage, thereby improving the prognosis.

  11. CD44 splice variants as prognostic markers in colorectal cancer

    NARCIS (Netherlands)

    Wielenga, V. J.; van der Voort, R.; Mulder, J. W.; Kruyt, P. M.; Weidema, W. F.; Oosting, J.; Seldenrijk, C. A.; van Krimpen, C.; Offerhaus, G. J.; Pals, S. T.

    1998-01-01

    BACKGROUND: Splice variants of CD44 play a causal role in the metastatic spread of pancreatic carcinoma in the rat. In previous studies we have shown that homologues of these CD44 isoforms (CD44v6) are overexpressed during colorectal tumorigenesis in man and that CD44v6 overexpression is associated

  12. Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T F; Carlsen, A L; Heegaard, N H H

    2015-01-01

    BACKGROUND: This study investigated the predictive value of circulating microRNA-126 (cir-miRNA-126) in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy combined with bevacizumab.METHODS: The study included 68 patients. Blood samples (plasma) were collected...... and bevacizumab in patients with mCRC, thus representing a possible biomarker for the resistance to anti-angiogenic containing treatments....

  13. Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T F; Carlsen, A L; Heegaard, N H H

    2015-01-01

    BACKGROUND: This study investigated the predictive value of circulating microRNA-126 (cir-miRNA-126) in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy combined with bevacizumab. METHODS: The study included 68 patients. Blood samples (plasma) were collected...... and bevacizumab in patients with mCRC, thus representing a possible biomarker for the resistance to anti-angiogenic containing treatments....

  14. Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.

    Science.gov (United States)

    Inoue, Masayuki; Nakagomi, Hiroshi; Nakada, Haruka; Furuya, Kazushige; Ikegame, Kou; Watanabe, Hideki; Omata, Masao; Oyama, Toshio

    2017-09-01

    Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial. We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor-node-metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) e