Science.gov

Sample records for malignant colorectal disease-a

  1. Palliative Treatment of Malignant Colorectal Strictures with Metallic Stents

    SciTech Connect

    Paul Diaz, Laura; Pinto Pabon, Isabel; Fernandez Lobato, Rosa; Montes Lopez, Carmen

    1999-01-15

    Purpose: To assess the effectiveness and safety of self-expanding metallic stents as a primary palliative treatment for inoperable malignant colorectal strictures. Methods: Under radiological guidance 20 self-expanding metallic Wallstents were implanted in 16 consecutive patients with colorectal stenoses caused by malignant neoplasms, when surgical treatment of the condition had been ruled out. The patients were followed up clinically for 1-44 months, until death or termination of this study. Results: The stents were successfully implanted in all cases and resolved the clinical obstruction in all the patients except one, who underwent subsequent colostomy. During follow-up of the remaining 15 patients, clinical complications arising from the procedure were pain (two patients), minor rectal bleeding (one patient), and severe rectal bleeding (one patient) (26%). There were three cases of stent migration and three cases of stent occlusion, and reintervention by us was necessary in 20% of cases (3/15). The mean life span following the procedure was 130 days, and none of the patients exhibited clinical symptoms of obstruction at the time of death (12 patients) or termination of the study (3 patients). Conclusion: Deployment of metallic stents under radiologic guidance is an effective alternative as a primary palliative measure in malignant colorectal obstruction, though the possible clinical complications and need for repeat intervention during follow-up should be taken into account.

  2. Colorectal villous adenoma: transrectal US in screening for invasive malignancy.

    PubMed

    Hulsmans, F H; Tio, T L; Mathus-Vliegen, E M; Bosma, A; Tytgat, G N

    1992-10-01

    Exclusion of focal infiltrating malignancy in colorectal villous adenoma is a prerequisite when nonsurgical treatment is considered. In a study of 81 patients with endoscopically identified colorectal villous adenoma screened for malignancy with transrectal ultrasonography (US), 15 patients were excluded because of incomplete follow-up. Twelve carcinomas were present, confirmed with either histopathologic examination after surgical resection (n = 9) or biopsies during laser treatment (n = 3). Nine of them were detected with transrectal US on the basis of disruption of the anatomic wall layers (sensitivity, 75%). In 46 of the 54 adenomas transrectal US helped confirm the benign nature of the lesion (specificity, 85%). Seven of the eight false-positive cases happened to be previously treated with surgery or coagulation. Treatment-associated inflammatory changes in the wall layers seemed responsible for this misinterpretation. Because of the high predictive value for a negative result (benign adenoma, 94%), transrectal US is recommended for the evaluation of villous adenomas to detect malignancy, especially when nonsurgical treatment is considered. Transrectal US should be performed before diagnostic polypectomy.

  3. Disparity Expression of Notch1 in Benign and Malignant Colorectal Diseases

    PubMed Central

    Huang, Rui; Tang, Qingchao; You, Qi; Liu, Zheng; Wang, Guiyu; Chen, Yinggang; Sun, Yuwen; Muhammad, Shan; Wang, Xishan

    2013-01-01

    Background and Objectives Although there was growing evidence supporting the hypothesis that Notch1 was one of the few candidate genes linked with colorectal cancer (CRC) susceptibility, the precise level of Notch1 protein expression in benign and malignant colorectal diseases was still unknown. Our study has investigated the Notch1 expression in benign and malignant colorectal diseases as well as to investigate the role and clinicopathological significance of aberrant expression of Notch1 in CRC. Methods The protein expression of Notch1 was examined by immunohistochemistry in 901 clinical specimens with colorectal diseases, including 220 patients with ulcerative colitis, 232 patients with colorectal adenoma and 449 patients with colorectal cancer. Associations between the expression of Notch1 and various clinicopathological features, as well as survival status, were studied. Results Cytoplasmic Notch1 was expressed in 7.7% of patients with ulcerative colitis, 14.7% of patients with colorectal adenoma and 58.0% of patients with colorectal cancer, respectively. Colorectal cancer patients with high expression levels of Notch1 showed lower overall survival (OS) and disease-free survival (DFS) rates than those patients with low Notch1 expression. Conclusions Expression level of Notch1 was gradually increased from precancerous lesions to cancer. It might play as an oncogene in the CRC development, and might be potentially used as a biomarker for prognosis of CRCs. PMID:24312514

  4. Primary-to-secondary care referral experience of suspected colorectal malignancy in young adults

    PubMed Central

    Patel, K; Doulias, T; Hoad, T; Lee, C; Alberts, JC

    2016-01-01

    Introduction Colorectal cancer in patients younger than 50 years of age is increasing steadily in the UK with limited guidelines available indicating need for secondary care referral. The aims of this study were to report the cancer incidence in those aged under 50 years referred to secondary care with suspected colorectal malignancy and also to analyse the quality of those referrals. Methods A total of 197 primary care referrals made between 2008 and 2014 to a UK district general hospital for suspected colorectal malignancy were analysed. All confirmed cancers were further evaluated regarding presenting symptoms, tumour characteristics and clinical outcomes. Each referral was given a referral performance score (out of 9) dependant on relevant information documented. Results The overall malignancy rate was 9.1% (11 male and 7 female patients). The median age in this cohort was 41.5 years (interquartile range [IQR]: 37–49 years). Abdominal pain was the only presenting symptom to differ significantly when comparing malignant with non-malignant patients (44.4% vs 21.8% respectively, p=0.042). The median time period between referral date and colorectal specialist consultation was 11 days (IQR: 7–13 days) and the median referral performance score was 5 (range: 3–9). Conclusions Malignancy is prevalent in patients under 50 years of age who are referred to secondary care for suspected colorectal cancer. Those referred with abdominal pain in the presence of other high risk lower gastrointestinal symptoms are at significant risk of having a malignancy. Major deficiencies are apparent in urgent primary care referrals, highlighting the need for further national guidance to aid early diagnosis of colorectal cancer in the young. PMID:27023637

  5. Venous thromboembolism following colorectal surgery for suspected or confirmed malignancy.

    PubMed

    Sanderson, Brenton; Hitos, Kerry; Fletcher, John P

    2011-01-01

    Surgery for colorectal cancer conveys a high risk of venous thromboembolism (VTE). The effect of thromboprophylactic regimens of varying duration on the incidence of VTE was assessed in 417 patients undergoing surgery between 2005 and 2009 for colorectal cancer. Low-dose unfractionated heparin (LDUH) was used in 52.7% of patients, low-molecular-weight heparin (LMWH) in 35.3%, and 10.7% received LDUH followed by LMWH. Pharmacological prophylaxis was continued after hospitalisation in 31.6%. Major bleeding occurred in 4% of patients. The 30-day mortality rate was 1.9%. The incidence of symptomatic VTE from hospital admission for surgery to 12 months after was 2.4%. There were no in-hospital VTE events. The majority of events occurred in the three-month period after discharge, but there were VTE events up to 12 months, especially in patients with more advanced cancer and multiple comorbidities.

  6. Systematic review of emergent laparoscopic colorectal surgery for benign and malignant disease

    PubMed Central

    Chand, Manish; Siddiqui, Muhammed RS; Gupta, Ashish; Rasheed, Shahnawaz; Tekkis, Paris; Parvaiz, Amjad; Mirnezami, Alex H; Qureshi, Tahseen

    2014-01-01

    Laparoscopic surgery has become well established in the management of both and malignant colorectal disease. The last decade has seen increasing numbers of surgeons trained to a high standard in minimally-invasive surgery. However there has not been the same enthusiasm for the use of laparoscopy in emergency colorectal surgery. There is a perception that emergent surgery is technically more difficult and may lead to worse outcomes. The present review aims to provide a comprehensive and critical appraisal of the available literature on the use of laparoscopic colorectal surgery (LCS) in the emergency setting. The literature is broadly divided by the underlying pathology; that is, inflammatory bowel disease, diverticulitis and malignant obstruction. There were no randomized trials and the majority of the studies were case-matched series or comparative studies. The overall trend was that LCS is associated with shorter hospital stay, par or fewer complications but an increased operating time.Emergency LCS can be safely undertaken for both benign and malignant disease providing there is appropriate patient selection, the surgeon is adequately experienced and there are sufficient resources to allow for a potentially more complex operation. PMID:25493008

  7. Malignancies in autoimmune rheumatic diseases - a mini-review.

    PubMed

    Szekanecz, Zoltán; Szekanecz, Eva; Bakó, Gyula; Shoenfeld, Yehuda

    2011-01-01

    Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases, are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Systemic inflammatory rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma or dermatomyositis, may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. Immunosuppressive drugs and biological agents may also be carcinogenic. However, sustained inflammatory activity seems to be the primary risk factor for malignancies in autoimmune diseases. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in rheumatoid arthritis and other autoimmune diseases.

  8. Immunohistochemical assessment of mitochondrial superoxide dismutase (MnSOD) in colorectal premalignant and malignant lesions

    PubMed Central

    Piecuch, Adam; Dziewit, Bartosz; Segiet, Oliwia; Kurek, Józef; Kowalczyk-Ziomek, Grażyna; Wojnicz, Romuald; Helewski, Krzysztof

    2016-01-01

    Introduction It is generally accepted that mitochondria are a primary source of intracellular reactive oxygen species (ROS). Under physiological circumstances they are permanently formed as by-products of aerobic metabolism in the mitochondria. To counter the harmful effect of ROS, cells possess an antioxidant defence system to detoxify ROS and avert them from accumulation at high concentrations. Mitochondria-located manganese superoxide dismutase (MnSOD, SOD2) successfully converts superoxide to the less reactive hydrogen peroxide (H2O2). To the best of our knowledge, there are no available data regarding immunohistochemical expression of MnSOD in colorectal neoplastic tissues. Aim To investigate the immunohistochemical expression status of MnSOD in colorectal premalignant and malignant lesions. Material and methods This study was performed on resected specimens obtained from 126 patients who had undergone surgical resection for primary sporadic colorectal cancer, and from 114 patients who had undergone colonoscopy at the Municipal Hospital in Jaworzno (Poland). Paraffin-embedded, 4-µm-thick tissue sections were stained for rabbit polyclonal anti SOD2 antibody obtained from GeneTex (clone TF9-10-H10 from America Diagnostica). Results Results of our study demonstrated that the development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Samples of adenocarcinoma with G2 and G3 grade showed significantly higher levels of immunohistochemical expression of this antioxidant enzyme. Moreover, patients with the presence of lymphovascular invasion and higher degree of regional lymph node status have been also characterised by higher levels of MnSOD expression. The samples of adenoma have been characterised by higher levels of MnSOD expression in comparison to normal mucosa as well. Interestingly, there was no significant correlation between expression and histological type of adenoma. Conclusions Development

  9. Detection of APC gene deletions in colorectal malignancies using quantitative PCR in a Chinese population.

    PubMed

    Fang, Zhengyu; Xiong, Yi; Li, Jiana; Liu, Li; Li, Manhui; Zhang, Wei; Shi, Lei; Wan, Jun

    2011-09-01

    The adenomatous polyposis coli (APC) gene has been shown to be involved in genetic instability and to be downregluated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in colorectal cancers (CRCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of CRC and adjacent normal epithelium (n = 134) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in colorectal malignancies. Our results showed that copy number deletions of APC were present in a relatively high percentage of colorectal cancer samples (26.1%, 35 out of 134). There was a positive correlation between copy number decrease of APC and tumor progression in CRCs. Furthermore, copy number loss of APC was correlated with decreased mRNA expression. However, mRNA levels of APC were also impaired in CRC samples with unaltered copy numbers, indicating that sporadic CRCs exhibit different mechanisms of APC regulation.

  10. Myofibroblasts of the muscle layer stimulate the malignant potential of colorectal cancer

    PubMed Central

    Takatsuna, Masafumi; Morohashi, Satoko; Yoshizawa, Tadashi; Hirai, Hideaki; Haga, Toshihiro; Ota, Rie; Wu, Yunyan; Morohashi, Hajime; Hakamada, Kenichi; Terai, Shuji; Kijima, Hiroshi

    2016-01-01

    Myofibroblasts of colorectal cancer (CRC) have been associated with histopathological factors such as lymph node metastasis, liver metastasis and local recurrence. However, few studies have assessed the association between these malignant potentials and the myofibroblast distribution in CRC. We aimed to evaluate the relationship between clinical factors and myofibroblast distribution around CRC invasive lesions. The study included 121 cases of pT3 CRC that were diagnosed at stage II or III. Myofibroblast density of the following three histological layers was measured: the submucosa (SM), muscularis propria (MP) and subserosa (SS). We analyzed the relationship between the clinicopathological factors and myofibroblast density by studying the histopathological features of the three layers. The myofibroblast density of the MP layer was significantly higher in the groups with high-frequency lymphatic and venous invasion than the groups with low-frequency lymphatic (P<0.001) and venous (P<0.01) invasion, respectively. In the positive lymph node metastasis group, the myofibroblast density at the MP layer was significantly higher than that in the negative lymph node metastasis group (P<0.001). The high myofibroblast density group at the MP layer was significantly associated with poor overall survival (P<0.003). Our study indicated that myofibroblasts are a type of cancer-associated fibroblasts and that the myofibroblast distribution contributes to the malignant potential of CRC. Furthermore, we demonstrated that myofibroblasts present at the MP layer play an important role in the malignant potential and poor prognosis of patients with CRC. PMID:27431808

  11. Time Lapse to Colorectal Cancer: Telomere Dynamics Define the Malignant Potential of Polyps

    PubMed Central

    Druliner, Brooke R; Ruan, Xiaoyang; Johnson, Ruth; Grill, Diane; O'Brien, Daniel; Lai, Tsung-Po; Rashtak, Shahrooz; Felmlee-Devine, Donna; Washechek-Aletto, Jill; Malykh, Andrei; Smyrk, Thomas; Oberg, Ann; Liu, Hongfang; Shay, Jerry W; Ahlquist, David A; Boardman, Lisa A

    2016-01-01

    Objective: Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free. Methods: Tissues were identified as cancer-adjacent polyp (CAP)—residual adenoma contiguous with cancer—and cancer-free polyp (CFP)—adenomas without malignancy. Telomere length, TMM, and expression were measured in 102 tissues including peripheral blood leukocytes (PBLs), normal colon epithelium, adenoma, and cancer (in CAP cases) from 31 patients. Telomere length was measured in a separate cohort of 342 PBL from CAP and CFP patients. Results: The mean differences in telomere length between normal and adenoma were greater in CAP than in CFP cases, P=0.001; telomere length in PBL was 91.7 bp greater in CAP than in CFP, P=0.007. Each 100 bp telomere increase was associated with a 1.14 (1.04–1.26) increased odds of being a CAP, P=0.0063. The polyp tissue from CAP patients had shorter telomeres and higher Telomerase reverse transcriptase (hTERT) expression compared with polyps from CFP patients, P=0.05. There was a greater degree of alternative lengthening of telomere (ALT) level difference in CFP polyps than in CAP polyps. The polyp telomere lengths of aggressive CAPs were significantly different from the polyps of non-aggressive CAPs, P=0.01. Conclusions: Adenomas that progress to cancer exhibit distinct telomere length and TMM profiles. We report for the first time that PBL telomeres differ in patients with polyps that become malignant, and therefore may have clinical value in adenoma risk assessment and management. PMID:27584834

  12. In vivo use of hyperspectral imaging to develop a noncontact endoscopic diagnosis support system for malignant colorectal tumors

    NASA Astrophysics Data System (ADS)

    Han, Zhimin; Zhang, Aoyu; Wang, Xiguang; Sun, Zongxiao; Wang, May D.; Xie, Tianyu

    2016-01-01

    The early detection and diagnosis of malignant colorectal tumors enables the initiation of early-stage therapy and can significantly increase the survival rate and post-treatment quality of life among cancer patients. Hyperspectral imaging (HSI) is recognized as a powerful tool for noninvasive cancer detection. In the gastrointestinal field, most of the studies on HSI have involved ex vivo biopsies or resected tissues. In the present study, we aimed to assess the difference in the in vivo spectral reflectance of malignant colorectal tumors and normal mucosa. A total of 21 colorectal tumors or adenomatous polyps from 12 patients at Shanghai Zhongshan Hospital were examined using a flexible hyperspectral (HS) colonoscopy system that can obtain in vivo HS images of the colorectal mucosa. We determined the optimal wavelengths for differentiating tumors from normal tissue based on these recorded images. The application of the determined wavelengths in spectral imaging in clinical trials indicated that such a clinical support system comprising a flexible HS colonoscopy unit and band selection unit is useful for outlining the tumor region and enhancing the display of the mucosa microvascular pattern in vivo.

  13. P4H9-detected molecule expression on spindle-shaped fibroblasts indicates malignant phenotype of colorectal cancer

    PubMed Central

    Yokoyama, Shozo; Ieda, Junji; Yamamoto, Naoyuki; Yamaguchi, Shunsuke; Mitani, Yasuyuki; Takeuchi, Akihiro; Takifuji, Katsunari; Hotta, Tsukasa; Matsuda, Kenji; Watanabe, Takashi; Shively, John E; Yamaue, Hiroki

    2015-01-01

    Background: Our previous study using a mammary fat pad mouse model showed that P4H9, produced by the β2 integrin epitope, detected a molecule on fibroblasts in response to carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-expressing cancer cells. P4H9-detected molecule (PDM) expression appeared to be associated with myofibroblast differentiation. In this study, we investigated whether PDM is expressed on fibroblasts and cancer cells in clinical tissue samples, and whether the presence of PDM-expressing colorectal cancer cells is correlated with clinicopathological features of patients. Methods: Immunohistochemistry was conducted to detect P4H9 on clinical tissue samples from 156 patients with colorectal cancer. Risk factors for metastases and survival were calculated for clinical implication of PDM-expressing spindle-shaped fibroblasts. Results: Multivariate analysis showed that PDM-expressing spindle-shaped fibroblasts were an independent risk factor for lymph node metastasis, hematogenous metastasis, and poor survival. A Kaplan–Meier survival curve indicated that PDM-expressing spindle-shaped fibroblasts were associated with shorter survival time (P<0.0001). Immunofluorescence showed PDM expression on CCD-18Co fibroblasts and two colorectal cancer cell lines (HCT116 and HCT-15). Conclusions: PDM-expressing spindle-shaped fibroblasts are associated with metastasis and shorter survival in colorectal cancer patients. PDM-expressing spindle-shaped fibroblasts may have a role in eliciting the malignant phenotype of colorectal cancer. PMID:26469833

  14. The "HER2-PI3K/Akt-FASN Axis" regulated malignant phenotype of colorectal cancer cells.

    PubMed

    Li, Nan; Bu, Xiaodong; Wu, Peng; Wu, Pingping; Huang, Peilin

    2012-04-01

    Recent evidence suggests that HER2 (ErbB2; Her-2/neu) and the related PI3K/Akt signaling pathway substantially affect the malignant phenotype of colorectal cancer cells. Moreover, fatty acid synthase (FASN), which mediates de-novo fatty acid synthesis, is crucially important in the carcinogenesis process of a variety of cancers, including colorectal cancer. The purpose of this study was to investigate the malignant phenotype regulation of colorectal cancer cells via the "HER2-PI3K/Akt-FASN axis". Caco-2 cells with high expression of HER2 and FASN and high transfection efficiency were selected for functional characterization. The cells were transfected with either HER2-specific RNAi plasmid or negative control RNAi plasmid, followed by Q-RT-PCR and western blot assays to examine expression of HER2, PI3K, Akt, and FASN. MTT and colony-formation assays were used to assess proliferation. Migration was investigated by use of the transwell assay, and apoptosis and cell cycle were assayed by use of flow cytometry. Expression of HER2, PI3K, Akt, and FASN were downregulated when HER2 was silenced. Proliferation decreased after downregulation of HER2, which was consistent with increased apoptosis. Migration of HER2-silenced cells was also impaired. Loss of HER2 inhibits the activity of the "HER2-PI3K/Akt-FASN axis" of Caco-2 cells, and reduced activity of this axis alters the malignant behavior of Caco-2 cells.

  15. Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells

    PubMed Central

    2013-01-01

    Background Vascular endothelial growth factor-a (VEGF)-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance. One of possible mechanisms for the acquired resistance may be the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGFR). Thus, we investigated here the direct effect of chronic VEGF inhibition on phenotype changes in human colorectal cancer (CRC) cells. Methods To chronically inhibit cancer cell-derived VEGF, human CRC cell lines (HCT116 and RKO) were chronically exposed (2 months) to an anti-VEGF monoclonal antibody (mAb) or were disrupted the Vegf gene (VEGF-KO). Effects of VEGF family members were blocked by treatment with a VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI). Hypoxia-induced apoptosis under VEGF inhibited conditions was measured by TUNEL assay. Spheroid formation ability was assessed using a 3-D spheroid cell culture system. Results Chronic inhibition of secreted/extracellular VEGF by an anti-VEGF mAb redundantly increased VEGF family member (PlGF, VEGFR1 and VEGFR2), induced a resistance to hypoxia-induced apoptosis, and increased spheroid formation ability. This apoptotic resistance was partially abrogated by a VEGFR-TKI, which blocked the compensate pathway consisted of VEGF family members, or by knockdown of Vegf mRNA, which inhibited intracellular function(s) of all Vegf gene products. Interestingly, chronic and complete depletion of all Vegf gene products by Vegf gene knockout further augmented these phenotypes in the compensate pathway-independent manner. These accelerated phenotypes were significantly suppressed by knockdown of hypoxia-inducible factor-1α that was up-regulated in the VEGF-KO cell lines. Conclusions Our findings suggest that chronic

  16. Status and Literature Review of Self-Expandable Metallic Stents for Malignant Colorectal Obstruction

    PubMed Central

    Cheung, Dae Young; Lee, Yong Kook

    2014-01-01

    Use of colorectal stents has increased dramatically over the last decades. Colorectal stents offer an alternative way to relieve fatal intestinal obstruction and can take place of emergency surgery, which associated with significant morbidity and mortality and a high incidence of stoma creation, to elective resection. Although there remain a few concerns regarding the use of stents as a bridge to surgical resection, use of self-expandable metallic stents for palliation in patients with unresectable disease has come to be generally accepted. Advantages of colorectal stents include acute restoration of luminal patency and allowance of time for proper staging and surgical optimization, and the well-known disadvantages are procedure-related complications including perforation, migration, and stent failure. General indications, procedures, and clinical outcomes as well as recent evidences regarding the use of colorectal stents will be discussed in this review. PMID:24570885

  17. Inactivation of the retinoblastoma gene yields a mouse model of malignant colorectal cancer.

    PubMed

    Parisi, T; Bronson, R T; Lees, J A

    2015-11-26

    The retinoblastoma gene (Rb) is mutated at significant frequency in various human epithelial tumors, including colorectal cancer, and is strongly associated with metastatic disease. However, sole inactivation of Rb in the mouse has so far failed to yield epithelial cancers. Here, we specifically inactivate Rb and/or p53 in the urogenital epithelium and the intestine. We find that the loss of both tumor suppressors is unable to yield tumors in the transitional epithelium lining the bladder, kidneys and ureters. Instead, these mice develop highly metastatic tumors of neuroendocrine, not epithelial, origin within the urogenital tract to give prostate cancer in the males and vaginal tumors in the females. Additionally, we discovered that the sole inactivation of Rb in the intestine was sufficient to induce formation of metastatic colorectal adenocarcinomas. These tumors closely mirror the human disease in regard to the age of onset, histological appearance, invasiveness and metastatic potential. Like most human colorectal carcinomas, our murine Rb-deficient tumors demonstrate genomic instability and they show activation of β-catenin. Deregulation of the Wnt/β-catenin pathway is specific to the intestinal tumors, as genomic instability but not activation of β-catenin was observed in the neuroendocrine tumors. To date, attempts to generate genetically engineered mouse models of colorectal cancer tumors have yielded mostly cancer of the small intestine, which rarely occurs in humans. Our system provides the opportunity to accurately model and study colorectal cancer in the mouse via a single gene mutation.

  18. Female Sexual Dysfunction in Women with Non-Malignant Cervical Diseases: A Study from an Urban Chinese Sample

    PubMed Central

    Zhang, Aixia; Lei, Yu; Yang, Bin; Li, Ping; Pan, Lianjun

    2015-01-01

    Non-malignant cervical diseases are common causes of disease among women worldwide. Although many studies have focused on sexual function in women with cervical cancer, little is known about the prevalence of female sexual dysfunction and its risk factors in women with non-malignant cervical diseases. The present study aims to assess sexual function in Chinese women with non-malignant cervical diseases and to identify potential risk factors for these diseases. A cross-sectional hospital-based survey was conducted in Nanjing, China. The Chinese version of the Female Sexual Function Index (CVFSFI) was used to evaluate sexual function. Three hundred three women who had been diagnosed with at least one non-malignant cervical disease and 293 healthy women were recruited from Nanjing Maternity and Child Health Hospital of Nanjing Medical University. We found that women with non-malignant cervical diseases had a significantly higher prevalence of female sexual dysfunction (FSD) (51.8% vs. 34.8%), low desire (43.2% vs. 26.3%), arousal disorder (41.6% vs. 28.3%), and lubrication disorder (51.2% vs. 36.9%) compared with the control group. Cervicitis and cervical intraepithelial neoplasia (CIN) were found to be independent risk factors for FSD. Our study indicates that women with cervicitis and CIN are at a high risk for FSD and deserve focused initial and follow-up management. PMID:26473480

  19. Second malignancies after prostate brachytherapy: Incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up

    SciTech Connect

    Liauw, Stanley L.; Sylvester, John E. . E-mail: johnsylvester@seattleprostateinst.com; Morris, Christopher G.; Blasko, John C.; Grimm, Peter D.

    2006-11-01

    Purpose: To report the incidence of second bladder and colorectal cancers after prostate brachytherapy. Methods and Materials: This review included 125 patients treated with I-125 brachytherapy alone, and 223 patients who received supplemental external beam radiation therapy. Median follow-up was 10.5 years. Patients were followed for the development of lower genitourinary and colorectal cancers. Second malignancies arising five years after radiation therapy were defined as being potentially associated with treatment; observed rates were then compared with age-matched expected rates according to Surveillance, Epidemiology, and End Results data. Results: Five years out of treatment, there were 15 patients with a second solid tumor, including bladder cancer (n = 11), colorectal cancer (n = 3), and prostatic urethra cancer (n = 1). The incidence of second malignancy was no different in patients treated with brachytherapy alone (1.6%) vs. those receiving external beam radiotherapy (5.8%, p = 0.0623). There were more observed bladder cancers compared with those expected (relative risk, 2.34, 95% confidence interval 0.96-3.72; absolute excess risk 35 cancers per 10,000 patients). Relative risk did not significantly change over increasing follow-up intervals up to 20 years after treatment. Conclusions: There may be an increased but small risk of developing a second malignancy after radiation therapy for prostate cancer. This outcome could be related to radiation carcinogenesis, but more vigilant screening and thorough workup as a result of radiation side effects and predisposing conditions (e.g., genetic and environmental factors) in many of the patients found to have second malignancies likely contributed to the higher number of observed malignancies than expected.

  20. Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment

    PubMed Central

    Akimoto, Miho; Maruyama, Riruke; Takamaru, Hiroyuki; Ochiya, Takahiro; Takenaga, Keizo

    2016-01-01

    Interleukin-33 (IL-33) was recently shown to be involved in the inflammatory tumour microenvironment and the progression of colorectal cancer (CRC). We report here that the expression level of sST2, a soluble form of the IL-33 receptor (ST2L), is inversely associated with the malignant growth of CRC. sST2 is downregulated in high-metastatic cells compared with low-metastatic human and mouse CRC cells. Knockdown of sST2 in low-metastatic cells enhances tumour growth, metastasis and tumour angiogenesis, whereas its overexpression in high-metastatic cells suppresses these processes. Circulating and intratumourally administered sST2-Fc fusion protein reduce tumour growth, metastatic spread and tumour angiogenesis in mice bearing high-metastatic CRC. Mechanistically, sST2 suppresses IL-33-induced angiogenesis, Th1- and Th2-responses, macrophage infiltration and macrophage M2a polarization. In conclusion, we show that sST2 negatively regulates tumour growth and the metastatic spread of CRC through modification of the tumour microenvironment. Thus, the IL-33/ST2L axis may be a potential therapeutic target in CRC. PMID:27882929

  1. Risk of subsequent primary malignancies among patients with prior colorectal cancer: a population-based cohort study

    PubMed Central

    Yang, Jiao; Li, Shuting; Lv, Meng; Wu, Yinying; Chen, Zheling; Shen, Yanwei; Wang, Biyuan; Chen, Ling; Yi, Min; Yang, Jin

    2017-01-01

    Background The site-distribution pattern and relative risk of subsequent primary malignancies (SPMs) in colorectal cancer (CRC) patients remains to be determined. Materials and methods A population-based cohort of 288,390 CRC patients diagnosed between 1973 and 2012 from the Surveillance, Epidemiology, and End Results database was retrospectively reviewed. Standardized incidence ratios were calculated to estimate the relative risk for SPMs. Results The overall risk of SPMs increased in CRC patients (standardized incidence ratio 1.02) in the first 5 years after CRC diagnosis compared with that in the general population, and was negatively related to age at diagnosis. Risk increased significantly for cancers of the small intestine, ureter, colorectum, renal pelvis, endocrine system, and stomach, and decreased significantly for cancers of the gallbladder, liver, myeloma, and brain, as well as lymphoma. Patients with different prior CRC subsites showed specific sites at high risk of SPM. Prior right-sided colon cancer was associated with cancers of the small intestine, ureter, renal pelvis, thyroid, stomach, pancreas, and breast and prior left-sided colon cancer associated with secondary CRC, whereas rectal cancer was associated with cancers of the vagina, urinary bladder, and lung. Conclusion Risk of SPMs increases in CRC survivors, especially in the first 5 years after prior diagnosis. Intensive surveillance should be advocated among young patients, with specific attention to the small intestine, colorectum, renal pelvis, and ureter. The common sites at high risk of SPM originate from the embryonic endoderm. Genetic susceptibility may act as the main mechanism underlying the risk of multiple cancers. PMID:28352187

  2. Isolated testicular immunoglobulin G4-related disease: A mimicker of malignancy

    PubMed Central

    Lal, Jithin; Bhat, Suresh; Doddamani, Siddalingeswar; Devi, Lekshmi

    2016-01-01

    ImmunoglobulinG4 related disease (IgG4RD) is a systemic fibroinflammatory disease recognized recently. This usually presents with multiorgan involvement. We are reporting a case of a35-year-old male patient with isolated IgG4RD of the testis. This patient presented with right testis pain which responded to conservative treatment. However, later, he reported with hard swelling in the right testis which on imaging was suggestive of malignancy and hence underwent radical orchiectomy. Histopathology with immunohistochemical staining confirmed IgG4RD of the testis. To the best of our knowledge, this is the first report of purely isolated case of IgG4RD of testis in English literature. PMID:27843221

  3. Decellularized matrices as in vitro models of extracellular matrix in tumor tissues at different malignant levels: Mechanism of 5-fluorouracil resistance in colorectal tumor cells.

    PubMed

    Hoshiba, Takashi; Tanaka, Masaru

    2016-11-01

    Chemoresistance is a major barrier for tumor chemotherapy. It is well-known that chemoresistance increases with tumor progression. Chemoresistance is altered by both genetic mutations and the alteration of extracellular microenvironment. Particularly, the extracellular matrix (ECM) is remodeled during tumor progression. Therefore, ECM remodeling is expected to cause the acquisition of chemoresistance in highly malignant tumor tissue. Here, we prepared cultured cell-derived decellularized matrices that mimic native ECM in tumor tissues at different stages of malignancy, and 5-fluorouracil (5-FU) resistance was compared among these matrices. 5-FU resistance of colorectal tumor cells increased on the matrices derived from highly malignant tumor HT-29 cells, although the resistance did not increase on the matrices derived from low malignant tumor SW480 cells and normal CCD-841-CoN cells. The resistance on HT-29 cell-derived matrices increased through the activation of Akt and the upregulation of ABCB1 and ABCC1 without cell growth promotion, suggesting that ECM remodeling plays important roles in the acquisition of chemoresistance during tumor progression. It is expected that our decellularized matrices, or "staged tumorigenesis-mimicking matrices", will become preferred cell culture substrates for in vitro analysis of comprehensive ECM roles in chemoresistance and the screening and pharmacokinetic analysis of anti-cancer drugs.

  4. Guidelines on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy arising from colorectal or appendiceal neoplasms

    PubMed Central

    Dubé, P.; Sideris, L.; Law, C.; Mack, L.; Haase, E.; Giacomantonio, C.; Govindarajan, A.; Krzyzanowska, M.K.; Major, P.; McConnell, Y.; Temple, W.; Younan, R.; McCart, J.A.

    2015-01-01

    To meet the needs of patients, Canadian surgical and medical oncology leaders in the treatment of peritoneal surface malignancies (psms), together with patient representatives, formed the Canadian HIPEC Collaborative Group (chicg). The group is dedicated to standardizing and improving the treatment of psm in Canada so that access to treatment and, ultimately, the prognosis of Canadian patients with psm are improved. Patients with resectable psm arising from colorectal or appendiceal neoplasms should be reviewed by a multidisciplinary team including surgeons and medical oncologists with experience in treating patients with psm. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should be offered to appropriately selected patients and performed at experienced centres. The aim of this publication is to present guidelines that we recommend be applied across the country for the treatment of psm. PMID:25908915

  5. Reocclusion after Self-Expandable Metallic Stent Placement for Relieving Malignant Colorectal Obstruction as a Palliative Treatment

    PubMed Central

    Nitta, Toshikatsu; Fujii, Kensuke; Hirata, Yoshimasa; Tominaga, Tomo; Inoue, Yoshihiro; Kawasaki, Hiroshi; Kawakami, Ken; Ishibashi, Takashi

    2016-01-01

    Self-expandable metallic stent (SEMS) placement has been practiced in several hospitals in Japan, including ours, since January 2012. Here, we report the case of an 82-year-old Japanese man who presented to the hospital with a 1-week history of right hypochondrial pain. Computed tomography (CT) findings indicated colorectal cancer. The laboratory findings on admission indicated severe anemia (red blood cell count, 426 × 104/μL; hemoglobin, 7.9 g/dL). We performed SEMS placement because the patient refused to undergo surgery. He did not attend any of the scheduled follow-up visits after SEMS placement. However, a year and a half after the SEMS placement, the patient attended the hospital because of difficulty in passing stool. A plain abdominal CT scan showed bowel reobstruction due to the ascending colon cancer after SEMS placement. We performed an emergency operation, ascending colostomy, on the same day. Colorectal stent placement may be a good treatment option for patients who refuse to undergo conventional therapeutic treatments or in those with unresectable colorectal cancer. Patients should be carefully followed up every few months after SEMS placement because of the risk of reocclusion. PMID:28100994

  6. Colorectal Stents: Current Status

    PubMed Central

    Lee, Jeong-Mi

    2015-01-01

    A self-expandable metal stent (SEMS) is an effective and safe method for the decompression of colon obstruction. Based on recent evidence, colorectal SEMS is now recommended for the palliation of patients with colonic obstruction from incurable colorectal cancer or extracolonic malignancy and also as a bridge to surgery in those who are a high surgical risk. Prophylactic SEMS insertion in patients with no obstruction symptoms is not recommended. Most colorectal SEMS are inserted endoscopically under fluoroscopic guidance. The technical and clinical success rates of colorectal SEMS are high, and the complication rate is acceptable. Advances in this technology will make the insertion of colorectal SEMS better and may expand the indications of colorectal SEMS in the future. PMID:26064818

  7. A novel mixed integer programming for multi-biomarker panel identification by distinguishing malignant from benign colorectal tumors.

    PubMed

    Zou, Meng; Zhang, Peng-Jun; Wen, Xin-Yu; Chen, Luonan; Tian, Ya-Ping; Wang, Yong

    2015-07-15

    Multi-biomarker panels can capture the nonlinear synergy among biomarkers and they are important to aid in the early diagnosis and ultimately battle complex diseases. However, identification of these multi-biomarker panels from case and control data is challenging. For example, the exhaustive search method is computationally infeasible when the data dimension is high. Here, we propose a novel method, MILP_k, to identify serum-based multi-biomarker panel to distinguish colorectal cancers (CRC) from benign colorectal tumors. Specifically, the multi-biomarker panel detection problem is modeled by a mixed integer programming to maximize the classification accuracy. Then we measured the serum profiling data for 101 CRC patients and 95 benign patients. The 61 biomarkers were analyzed individually and further their combinations by our method. We discovered 4 biomarkers as the optimal small multi-biomarker panel, including known CRC biomarkers CEA and IL-10 as well as novel biomarkers IMA and NSE. This multi-biomarker panel obtains leave-one-out cross-validation (LOOCV) accuracy to 0.7857 by nearest centroid classifier. An independent test of this panel by support vector machine (SVM) with threefold cross validation gets an AUC 0.8438. This greatly improves the predictive accuracy by 20% over the single best biomarker. Further extension of this 4-biomarker panel to a larger 13-biomarker panel improves the LOOCV to 0.8673 with independent AUC 0.8437. Comparison with the exhaustive search method shows that our method dramatically reduces the searching time by 1000-fold. Experiments on the early cancer stage samples reveal two panel of biomarkers and show promising accuracy. The proposed method allows us to select the subset of biomarkers with best accuracy to distinguish case and control samples given the number of selected biomarkers. Both receiver operating characteristic curve and precision-recall curve show our method's consistent performance gain in accuracy. Our method

  8. Smad2 and Smad3 phosphorylated at both linker and COOH-terminal regions transmit malignant TGF-beta signal in later stages of human colorectal cancer.

    PubMed

    Matsuzaki, Koichi; Kitano, Chiaki; Murata, Miki; Sekimoto, Go; Yoshida, Katsunori; Uemura, Yoshiko; Seki, Toshihito; Taketani, Shigeru; Fujisawa, Jun-ichi; Okazaki, Kazuichi

    2009-07-01

    Transforming growth factor (TGF)-beta initially inhibits growth of mature epithelial cells. Later, however, autocrine TGF-beta signaling acts in concert with the Ras pathway to induce a proliferative and invasive phenotype. TGF-beta activates not only TGF-beta type I receptor (TbetaRI) but also Ras-associated kinases, which differentially phosphorylate the mediators Smad2 and Smad3 to create distinct phosphorylated forms: COOH-terminally phosphorylated Smad2/3 (pSmad2C and pSmad3C) and both linker and COOH-terminally phosphorylated Smad2/3 (pSmad2L/C and pSmad3L/C). In this study, we investigated actions of pSmad2L/C and pSmad3L/C in cancer progression. TGF-beta inhibited cell growth by down-regulating c-Myc oncoprotein through the pSmad2C and pSmad3C pathway; TGF-beta signaling, in turn, enhanced cell growth by up-regulating c-Myc through the cyclin-dependent kinase (CDK) 4-dependent pSmad2L/C and pSmad3L/C pathways in cell nuclei. Alternatively, TbetaRI and c-Jun NH2-terminal kinase (JNK) together created cytoplasmic pSmad2L/C, which entered the nucleus and stimulated cell invasion, partly by up-regulating matrix metalloproteinase-9. In 20 clinical samples, pSmad2L/C and pSmad3L/C showed nuclear localization at invasion fronts of all TGF-beta-producing human metastatic colorectal cancers. In vitro kinase assay confirmed that nuclear CDK4 and cytoplasmic JNK obtained from the tumor tissue could phosphorylate Smad2 or Smad3 at their linker regions. We suggest that CDK4, together with JNK, alters tumor-suppressive TGF-beta signaling to malignant characteristics in later stages of human colorectal cancer. The linker phosphorylation of Smad2 and Smad3 may represent a target for intervention in human metastatic cancer.

  9. Elastic Deformation Properties of Implanted Endobronchial Wire Stents in Benign and Malignant Bronchial Disease: A Radiographic In Vivo Evaluation

    SciTech Connect

    Hautmann, Hubert; Rieger, Johannes; Huber, Rudolf M.; Pfeifer, Klaus J.

    1999-03-15

    Purpose: To evaluate the long-term mechanical behavior in vivo of expandable endobronchial wire stents, we imaged three different prostheses in the treatment of tracheobronchial disease. Methods: Six patients with bronchial stenoses (three benign, three malignant) underwent insertion of metallic stents. Two self-expandable Wallstents, two balloon-expandable tantalum Strecker stents and two self-expandable nitinol Accuflex stents were used. Measurements of deformation properties were performed during voluntary cough by means of fluoroscopy, at 1 month and 7-10 months after implantation. The procedures were videotaped, their images digitized and the narrowing of stent diameters calculated at intervals of 20 msec. Results: After stent implantation all patients improved with respect to ventilatory function. Radial stent narrowing during cough reached 53% (Wallstent), 59% (tantalum Strecker stent), and 52% (nitinol Accuflex stent) of the relaxed post-implantation diameter. Stent compression was more marked in benign compared with malignant stenoses. In the long term permanent deformation occurred with the tantalum Strecker stents; the other stents were unchanged. Conclusion: Endobronchial wire stents can be helpful in the treatment of major airway collapse and obstructing bronchial lesions. However, evidence of material fatigue as a possible effect of exposure to recurrent mechanical stress on the flexible mesh tube may limit their long-term use. This seems to be predominantly important in benign bronchial collapse.

  10. Adiponectin and colorectal cancer.

    PubMed

    Otani, Kensuke; Ishihara, Soichiro; Yamaguchi, Hironori; Murono, Koji; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-02-01

    Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.

  11. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies.

    PubMed

    Zheng, Han-Han; Jiang, Xue-Liang

    2016-04-01

    Ulcerative colitis (UC) patients with concomitant primary sclerosing cholangitis (PSC) carry an increased risk of colorectal neoplasia (dysplasia and cancer), whereas the association between PSC and the development of colorectal neoplasia in Crohn's disease (CD) is controversial. A meta-analysis was carried out to compare the risk of this neoplasia in patients with inflammatory bowel disease (IBD) with and without PSC. A systematic research of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials was performed to identify studies that compared the risk of colorectal neoplasia (dysplasia and cancer) in patients with IBD with and without PSC. Quality assessment was performed using the Newcastle-Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model by STATA 12.0. A total of 16 studies (four cohort studies, 12 case-control studies; nine prospective studies and seven retrospective studies) were selected for further study. These studies included 13 379 IBD patients, of whom 1022 also had PSC. Patients with IBD and PSC were at an increased risk of colorectal dysplasia and cancer compared with patients with IBD alone [OR 3.24; 95% confidence interval (CI): 2.14-4.90]. This increased risk was present even when the risk of colorectal cancer alone was analysed (OR 3.41; 95% CI: 2.13-5.48). Data only from patients with UC showed that PSC was associated with an increased risk for the development of colorectal neoplasia and cancer in patients with UC (OR 2.98; 95% CI: 1.54-5.76) (OR 3.01; 95% CI: 1.44-6.29), but there were high heterogeneity among studies (I=76.9 and 62.8%, respectively). Heterogeneity of the studies was affected by the study design (prospective or retrospective). The OR of colorectal neoplasia was 2.32 (95% CI: 0.70-7.70, P=0.133) and that of cancer was 2.91 (95% CI: 0.84-10.16, P=0.388) for patients with CD and concurrent PSC. Patients with IBD and PSC have a markedly higher risk for the development of colorectal

  12. Locoregional immunotherapy of malignant effusion from colorectal cancer using the streptococcal preparation OK-432 plus interleukin-2: induction of autologous tumor-reactive CD4+ Th1 killer lymphocytes.

    PubMed

    Yamaguchi, Y; Miyahara, E; Ohshita, A; Kawabuchi, Y; Ohta, K; Shimizu, K; Minami, K; Hihara, J; Sawamura, A; Toge, T

    2003-11-17

    In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation OK-432 alone or OK-432 plus the T-cell growth factor interleukin (IL)-2, and the action mechanism of the treatment was studied. A positive clinical response, showing a cytologic disappearance of cancer cells and decrease of effusion, was observed in nine of 11 (82%) patients treated with OK-432 alone and in all five patients treated with OK-432 plus IL-2. Flow cytometric analysis revealed that OK-432 plus IL-2 locally induced acute inflammation-like responses, including serial cellular infiltrations of granulocyte migration within a matter of hours, and activation of macrophages and T lymphocyte involvement within the following days, and that a predominant expansion of CD3+CD4+ lymphocytes (CD: cluster of differentiation) was induced by in vitro stimulation with IL-2 of locoregional cells after the OK-432 administration (OK/IL-2AK cells). The OK/IL-2AK cells produced tumour necrosis factor-alpha and interferon-gamma, but these cells did not produce IL-4 and IL-6. The OK/IL-2AK cells expressed potent killing activity against autologous tumour cells. This activity was abrogated by treatment of the lymphocytes with anti-CD3, -CD4, -TCRalphabeta antibody, and by the treatment of target cells with anti-human leukocyte antigen (HLA)-DR antibody. The OK/IL-2AK cells expressed Fas-L gene, and flow cytometric analysis demonstrated HLA-DR expression in approximately 75% of CEA+ or cytokeratin+ effusion cells. TCRVbeta gene analysis of the OK/IL-2AK cells showed an oligoclonal usage of TCRbeta20, which was also involved in the cytotoxic mechanism of the OK/IL-2AK cells. Single-strand conformational polymorphism analysis demonstrated the clonotypes for the TCRVbeta20 gene, and the CDR3s of the gene were sequenced. The clonotypic PCR using the TCRVbeta20-CDR3 sequences could detect the CDR3-identical TCRs in

  13. [Colorectal cancer screening].

    PubMed

    Castells, Antoni

    2015-09-01

    Colorectal cancer is one of malignancies showing the greatest benefit from preventive measures, especially screening or secondary prevention. Several screening strategies are available with demonstrated efficacy and efficiency. The most widely used are the faecal occult blood test in countries with population-based screening programmes, and colonoscopy in those conducting opportunistic screening. The present article reviews the most important presentations on colorectal cancer screening at the annual congress of the American Gastroenterological Association held in Washington in 2015, with special emphasis on the medium-term results of faecal occult blood testing strategies and determining factors and on strategies to reduce the development of interval cancer after colonoscopy.

  14. Diagnostic Utility of Pleural Fluid Cell Block versus Pleural Biopsy Collected by Flex-Rigid Pleuroscopy for Malignant Pleural Disease: A Single Center Retrospective Analysis

    PubMed Central

    Sasada, Shinji; Izumo, Takehiro; Matsumoto, Yuji; Tsuchida, Takaaki

    2016-01-01

    Background Some trials recently demonstrated the benefit of targeted treatment for malignant disease; therefore, adequate tissues are needed to detect the targeted gene. Pleural biopsy using flex-rigid pleuroscopy and pleural effusion cell block analysis are both useful for diagnosis of malignancy and obtaining adequate samples. The purpose of our study was to compare the diagnostic utility between the two methods among patients with malignant pleural disease with effusion. Methods Data from patients who underwent flex-rigid pleuroscopy for diagnosis of pleural effusion suspicious for malignancy at the National Cancer Center Hospital, Japan between April 2011 and June 2014 were retrospectively reviewed. All procedures were performed under local anesthesia. At least 150 mL of pleural fluid was collected by pleuroscopy, followed by pleural biopsies from the abnormal site. Results Thirty-five patients who were finally diagnosed as malignant pleural disease were included in this study. Final diagnoses of malignancy were 24 adenocarcinoma, 1 combined adeno-small cell carcinoma, and 7 malignant pleural mesothelioma (MPM), and 3 metastatic breast cancer. The diagnostic yield was significantly higher by pleural biopsy than by cell block [94.2% (33/35) vs. 71.4% (25/35); p = 0.008]. All patients with positive results on cell block also had positive results on pleural biopsy. Eight patients with negative results on cell block had positive results on pleural biopsy (lung adenocarcinoma in 4, sarcomatoid MPM in 3, and metastatic breast cancer in 1). Two patients with negative results on both cell block and pleural biopsy were diagnosed was sarcomatoid MPM by computed tomography-guided needle biopsy and epithelioid MPM by autopsy. Conclusion Pleural biopsy using flex-rigid pleuroscopy was efficient in the diagnosis of malignant pleural diseases. Flex-rigid pleuroscopy with pleural biopsy and pleural effusion cell block analysis should be considered as the initial diagnostic

  15. Colorectal Cancer

    MedlinePlus

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

  16. Colorectal Cancer Metastasis to the Thymus Gland: Rare Presentation of Colorectal Cancer as Anterior Mediastinal Mass.

    PubMed

    Peters, H Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A; Tan, Sanda A

    2017-01-01

    Despite improved screening modalities, 15-25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to the thymus gland presenting as a symptomatic mediastinal mass.

  17. High expression of fibronectin is associated with poor prognosis, cell proliferation and malignancy via the NF-κB/p53-apoptosis signaling pathway in colorectal cancer

    PubMed Central

    Yi, Wenzhong; Xiao, Enhua; Ding, Ru; Luo, Ping; Yang, Yi

    2016-01-01

    Fibronectin is a glycoprotein of the extracellular matrix, and regulates the processes of self-renewal and cell cycle progression. This study aimed to investigate fibronectin expression in colorectal cancer (CRC) and elucidate the effects of fibronectin on CRC by using a knockdown approach. Immunohistochemistry was used to evaluate the expression of fibronectin in 107 CRC patient tissues and gene expression was detected by real-time quantitative PCR (qPCR) and western blot analysis. Based on the above findings, the association among fibronectin expression, clinicopathological features and prognosis was analyzed. Next, fibronectin expression was silenced by small-interfering RNAs (siRNAs) and the effects of fibronectin siRNA transfection on CRC cells and tumor growth in nude mice were assessed. Expression of genes in the NF-κB/p53-apoptosis signaling pathway were analyzed after fibronectin siRNA transfection both in vitro and in vivo. Based on the results, high expression of fibronectin was observed both in the CRC tissues and CRC cell lines. The expression level was positively correlated with TNM stage (P=0.0025) and distant metastasis (P=0.0013). By Kaplan-Meier analysis, the patients with low fibronectin expression had a longer survival time comparing to those with relatively high expression. Knockdown of fibronectin suppressed SW480 cell proliferation, migration and invasion. In addition, knockdown of fibronectin led to S phase cell cycle arrest. The following study showed that the NF-κB/p53-apoptosis signaling pathway in CRC was affected by fibronectin knockdown. Tumor formation was also depressed by fibronectin siRNA transfection of CRC cells. These results showed the significant role of fibronectin in CRC tissues and cell lines. Therefore, fibronectin may be regarded as a potential target for CRC treatment. PMID:27748871

  18. The Risk of Infection and Malignancy with Tumor Necrosis Factor Antagonists in Adult Patients with Psoriatic Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

    PubMed Central

    Dommasch, E. D.; Abuabara, K.; Shin, D.B.; Nguyen, J.; Troxel, A. B.; Gelfand, J.M.

    2010-01-01

    Background There is a need to better understand the safety of TNF inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy. Objective Examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease. Methods Systematic search for trials of TNF antagonists for adults with plaque psoriasis (PsO) and psoriatic arthritis (PsA). We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, and certolizumab for the treatment of PsO and PsA. 20 out of 820 identified studies with a total of 6,810 patients were included. Results were calculated using fixed effects models and reported as pooled odds ratios (OR). Results ORs for overall infection and serious infection over a mean of 17.8 weeks were 1.18 (95% CI: 1.05, 1.33) and 0.70 (95% CI: 0.40, 1.21), respectively. When adjusting for patient-years, the incidence rate ratio for overall infection was 1.01 (95% CI: 0.92, 1.11). The OR for malignancy was 1.48 (95% CI: 0.71, 3.09), and 1.26 (95% CI: 0.39, 4.15) when non-melanoma skin cancer was excluded. Limitations Short duration of follow-up and rarity of malignancies and serious infections. Conclusions There is a small increased risk of overall infection with the short-term use of TNF antagonists for psoriasis that may be attributable to differences in follow-up time between treatment and placebo groups. There was no evidence of an increased risk of serious infection and a statistically significant increased risk in cancer was not observed with short-term use of TNF inhibitors. PMID:21315483

  19. Solitary intracranial tuberculoma mimicking a malignant tumor in a patient without tubercular lesions or a history of disease: a case report

    PubMed Central

    Bustamante-Rengifo, Javier A.; Sua, Luz F.; Astudillo, Miryam; Bravo, Luis E.

    2013-01-01

    Cerebral tuberculoma is a rare cause of intracranial mass. In Latin America and Colombia where tuberculosis is endemic, it represents between 5 and 30% of brain tumours. A 53-year-old Colombian woman was admitted to a third-level hospital in Cali, Colombia, after reporting loss of consciousness, headache, paresthesia, and flight of ideas for a two-week period. Imaging studies showed a left frontal mass of malignant appearance whose first possible diagnosis was metastatic neoplasia or glioma. With the initial results, absence of history of chronic infectious diseases and a history of thyroidectomy, a surgical procedure was carried out and a histopathological and molecular evaluation was conducted. The pathology report noted necrotizing granulomatous inflammation and tissue staining and molecular tests for detection of M. tuberculosis were positive and the patient was managed with anti-tubercular treatment. Intracranial masses are frequently targeted as a malignant neoplastic disease for surgical treatment. Considering an infectious etiology must be a diagnostic option. PMID:23725511

  20. Incidence of Second Primary Malignancies Following Colorectal Cancer: A Distinct Pattern of Occurrence Between Colon and Rectal Cancers and Association of Co-Morbidity with Second Primary Malignancies in a Population-Based Cohort of 98,876 Patients in Taiwan.

    PubMed

    Lee, Yu-Ting; Liu, Chia-Jen; Hu, Yu-Wen; Teng, Chung-Jen; Tzeng, Cheng-Hwai; Yeh, Chiu-Mei; Chen, Tzeng-Ji; Lin, Jen-Kou; Lin, Chun-Chi; Lan, Yuan-Tzu; Wang, Huann-Sheng; Yang, Shung-Haur; Jiang, Jeng-Kai; Chen, Wei-Shone; Lin, Tzu-Chen; Chang, Shih-Ching; Chen, Ming-Huang; Teng, Hao-Wei; Liu, Jin-Hwang; Yen, Chueh-Chuan

    2015-07-01

    The purpose of this study is to determine the features of second primary malignancies (SPMs) among patients with prior colorectal cancer (CRC) using a nationwide population-based dataset.Patients with CRC newly diagnosed between 1996 and 2011, and >1 year of follow-up were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of SPMs in patients with CRC were calculated.During the 16-year study period, 4259 SPMs developed among 98,876 CRC patients. The median duration of follow-up was 4.03 years. The SIR for all SPMs was 1.13 (95% confidence interval = 1.10-1.17). Compared with the general population, a higher incidence of thyroid, prostate, ovarian, and hematologic malignancies developed among patients with colon cancer, whereas the risk for bone and soft tissue cancers increased among patients with rectal cancer. The risk for breast, bladder, kidney, lung, and uterine cancers was significantly higher in patients with colon and rectal cancers than the general population. The risk for liver and biliary tract cancers declined in patients with rectal cancer. Based on multivariate analysis among patients with CRC, age ≥70 years, men, chronic obstructive pulmonary disease (COPD), cirrhosis, and dyslipidemia were independent predictors of an SPM.In conclusion, patients with CRC were at increased risk for a second cancer. The pattern of SPMs was distinct between patients with colon and rectal cancer. Age, men, COPD, cirrhosis, and dyslipidemia were independent risk factors for SPMs. Surveillance and education should be provided for survivors with respect to risk for SPMs.

  1. The role of estrogen receptor {beta} (ER{beta}) in malignant diseases-A new potential target for antiproliferative drugs in prevention and treatment of cancer

    SciTech Connect

    Warner, Margaret; Gustafsson, Jan-Ake

    2010-05-21

    The discovery of ER{beta} in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ER{alpha}, but by two balancing factors, ER{alpha} and ER{beta}, which are often antagonistic to one another. Excitingly, ER{beta} has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ER{beta} by drugs against various diseases. In this review, focus is on the role of ER{beta} in malignant diseases where the anti proliferative activity of ER{beta} gives hope of new therapeutic approaches.

  2. Second Cancers After Colorectal Cancer

    MedlinePlus

    ... After Colorectal Cancer Colorectal Cancer After Treatment Second Cancers After Colorectal Cancer Colorectal cancer survivors can be affected by a ... many of these cancers. Follow-up after colorectal cancer treatment After completing treatment for colorectal cancer, you ...

  3. APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-03-16

    Metastatic Malignant Neoplasm in the Brain; Metastatic Solid Neoplasm; Recurrent Colorectal Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Solid Neoplasm; Stage IV Colorectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer; Unresectable Solid Neoplasm

  4. Biology of colorectal cancer

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2015-01-01

    Colorectal cancer is a serious health problem, a challenge for research, and a model for studying the molecular mechanisms involved in its development. According to its incidence, this pathology manifests itself in three forms: family, hereditary, and most commonly sporadic, apparently not associated with any hereditary or familial factor. For the types having inheritance patterns and a family predisposition, the tumours develop through defined stages ranging from adenomatous lesions to the manifestation of a malignant tumour. It has been established that environmental and hereditary factors contribute to the development of colorectal cancer, as indicated by the accumulation of mutations in oncogenes, genes which suppress and repair DNA, signaling the existence of various pathways through which the appearance of tumours may occur. In the case of the suppressive and mutating tracks, these are characterised by genetic disorders related to the phenotypical changes of the morphological progression sequence in the adenoma/carcinoma. Moreover, alternate pathways through mutation in BRAF and KRAS genes are associated with the progression of polyps to cancer. This review surveys the research done at the cellular and molecular level aimed at finding specific alternative therapeutic targets for fighting colorectal cancer. PMID:25932044

  5. Colorectal polyps

    MedlinePlus

    ... Your provider can order a colonoscopy or other screening tests : These tests help prevent colon cancer by ... on Colorectal Cancer. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US ...

  6. COLORECTAL CANCER

    PubMed Central

    Kuipers, Ernst J.; Grady, William M.; Lieberman, David; Seufferlein, Thomas; Sung, Joseph J.; Boelens, Petra G.; van de Velde, Cornelis J. H.; Watanabe, Toshiaki

    2016-01-01

    Colorectal cancer had a low incidence several decades ago. However, it has become a predominant cancer and now accounts for approximately 10% of cancer-related mortality in western countries. The ‘rise’ of colorectal cancer in developed countries can be attributed to the increasingly ageing population, unfavourable modern dietary habits and an increase in risk factors such as smoking, low physical exercise and obesity. New treatments for primary and metastatic colorectal cancer have emerged, providing additional options for patients; these treatments include laparoscopic surgery for primary disease, more-aggressive resection of metastatic disease (such as liver and pulmonary metastases), radiotherapy for rectal cancer and neoadjuvant and palliative chemotherapies. However, these new treatment options have had limited impact on cure rates and long-term survival. For these reasons, and the recognition that colorectal cancer is long preceded by a polypoid precursor, screening programmes have gained momentum. This Primer provides an overview of the current state of art knowledge on the epidemiology and mechanisms of colorectal cancer, as well as on diagnosis and treatment. PMID:27189416

  7. Colorectal Cancer Metastasis to the Thymus Gland: Rare Presentation of Colorectal Cancer as Anterior Mediastinal Mass

    PubMed Central

    Peters, H. Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A.

    2017-01-01

    Despite improved screening modalities, 15–25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to the thymus gland presenting as a symptomatic mediastinal mass. PMID:28116210

  8. Five Myths about Colorectal Cancer

    MedlinePlus

    ... them. Myth: Colorectal cancer is a man’s disease. Truth: Colorectal cancer is almost as common among women ... colorectal cancer. Myth: Colorectal cancer cannot be prevented. Truth: In many cases, colorectal cancer can be prevented. ...

  9. KISS1 expression in colorectal cancer.

    PubMed

    Kostakis, Ioannis D; Agrogiannis, George; Vaiopoulos, Aristeidis G; Mylona, Eleni; Patsouris, Efstratios; Kouraklis, Gregory; Koutsilieris, Michael

    2013-10-01

    Kisspeptins, the products of the KISS1 gene, are involved in cancer invasion, migration, metastasis and angiogenesis, while they induce apoptosis in various cancers. Herein, we studied KISS1 expression in colorectal cancer. We analyzed KISS1 expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 60 patients with colorectal adenocarcinoma. The results correlated with various clinicopathological parameters. The expression of KISS1 was much higher in normal than in malignant colonic mucosa. However, among malignant tissues, KISS1 expression was higher in larger tumors (>4 cm) than in smaller ones (≤4 cm) and in stages III and IV than in stages I and II. In addition, it was higher in patients with lymph node metastases. Moreover, KISS1 levels in the normal mucosa and their difference from those in the malignant mucosa were higher in the right part of the large intestine than in the left one. KISS1 expression is reduced during the malignant transformation of the colonic mucosa and there is a difference in the expression pattern between the right and the left part of the large intestine. However, larger and advanced colorectal tumors express higher KISS1 levels than smaller and localized ones.

  10. Colorectal Cancer

    MedlinePlus

    ... malignant tumor and enter the bloodstream or the lymphatic system where they travel to other organs in the body. Among other things, the lymphatic system transports white blood cells that fight infection. When ...

  11. [New advances in hereditary colorectal cancer].

    PubMed

    Moreira, Leticia

    2015-09-01

    Colorectal cancer is the most frequent malignancy in both sexes in Spain. Between 20% and 25% of affected individuals have a family history of the disease, and 5% to 6% have a germ mutation, i.e. the disease develops in the context of a hereditary syndrome. The importance of identifying patients with hereditary syndromes predisposing them to colorectal cancer lies in the possibility of applying preventive measures, screening, and more appropriate management of both patients and their families. The present article outlines the most important studies presented at the congress of the American Gastroenterological Association.

  12. Canine olfactory detection of malignant melanoma

    PubMed Central

    Campbell, Leon Frederick; Farmery, Luke; George, Susannah Mary Creighton; Farrant, Paul B J

    2013-01-01

    Our patient is a 75-year-old man who presented after his pet dog licked persistently at an asymptomatic lesion behind his right ear. Examination revealed a nodular lesion in the postauricular sulcus. Histology confirmed malignant melanoma, which was subsequently excised. Canine olfactory detection of human malignancy is a well-documented phenomenon. Advanced olfaction is hypothesised to explain canine detection of bladder, breast, colorectal, lung, ovarian, prostate and skin cancers. Further research in this area may facilitate the development of a highly accurate aid to diagnosis for many malignancies, including melanoma. PMID:24127369

  13. Evaluation of FTIR spectroscopy as diagnostic tool for colorectal cancer using spectral analysis

    NASA Astrophysics Data System (ADS)

    Dong, Liu; Sun, Xuejun; Chao, Zhang; Zhang, Shiyun; Zheng, Jianbao; Gurung, Rajendra; Du, Junkai; Shi, Jingsen; Xu, Yizhuang; Zhang, Yuanfu; Wu, Jinguang

    2014-03-01

    The aim of this study is to confirm FTIR spectroscopy as a diagnostic tool for colorectal cancer. 180 freshly removed colorectal samples were collected from 90 patients for spectrum analysis. The ratios of spectral intensity and relative intensity (/I1460) were calculated. Principal component analysis (PCA) and Fisher's discriminant analysis (FDA) were applied to distinguish the malignant from normal. The FTIR parameters of colorectal cancer and normal tissues were distinguished due to the contents or configurations of nucleic acids, proteins, lipids and carbohydrates. Related to nitrogen containing, water, protein and nucleic acid were increased significantly in the malignant group. Six parameters were selected as independent factors to perform discriminant functions. The sensitivity for FTIR in diagnosing colorectal cancer was 96.6% by discriminant analysis. Our study demonstrates that FTIR can be a useful technique for detection of colorectal cancer and may be applied in clinical colorectal cancer diagnosis.

  14. Pleural malignancies.

    PubMed

    Friedberg, Joseph S; Cengel, Keith A

    2010-07-01

    Pleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent.

  15. MicroRNAs: Clinical Relevance in Colorectal Cancer.

    PubMed

    Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, Hui

    2015-11-25

    Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer.

  16. Self-renewal molecular mechanisms of colorectal cancer stem cells

    PubMed Central

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2017-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal. The elucidation of the molecular mechanisms behind self-renewal may lead to the development of novel targeted interventions for the treatment of colorectal cancer. PMID:27909729

  17. Colorectal Adenomas Contain Multiple Somatic Mutations That Do Not Coincide with Synchronous Adenocarcinoma Specimens

    PubMed Central

    Vaqué, José P.; Martínez, Nerea; Varela, Ignacio; Fernández, Fidel; Mayorga, Marta; Derdak, Sophia; Beltrán, Sergi; Moreno, Thaidy; Almaraz, Carmen; De las Heras, Gonzalo; Bayés, Mónica; Gut, Ivo; Crespo, Javier; Piris, Miguel A.

    2015-01-01

    We have performed a comparative ultrasequencing study of multiple colorectal lesions obtained simultaneously from four patients. Our data show that benign lesions (adenomatous or hyperplastic polyps) contain a high mutational load. Additionally multiple synchronous colorectal lesions show non overlapping mutational signatures highlighting the degree of heterogeneity between multiple specimens in the same patient. Observations in these cases imply that considering not only the number of mutations but an effective oncogenic combination of mutations can determine the malignant progression of colorectal lesions. PMID:25775023

  18. Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

    PubMed

    Di Valentin, T; Asmis, T; Asselah, J; Aubin, F; Aucoin, N; Berry, S; Biagi, J; Booth, C M; Burkes, R; Coburn, N; Colwell, B; Cripps, C; Dawson, L A; Dorreen, M; Frechette, D; Goel, R; Gray, S; Hammad, N; Jonker, D; Kavan, P; Maroun, J; Nanji, S; Roberge, D; Samson, B; Seal, M; Shabana, W; Simunovic, M; Snow, S; Tehfe, M; Thirlwell, M; Tsvetkova, E; Vickers, M; Vuong, T; Goodwin, R

    2016-02-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

  19. Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers

    PubMed Central

    Di Valentin, T.; Asmis, T.; Asselah, J.; Aubin, F.; Aucoin, N.; Berry, S.; Biagi, J.; Booth, C.M.; Burkes, R.; Coburn, N.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Frechette, D.; Goel, R.; Gray, S.; Hammad, N.; Jonker, D.; Kavan, P.; Maroun, J.; Nanji, S.; Roberge, D.; Samson, B.; Seal, M.; Shabana, W.; Simunovic, M.; Snow, S.; Tehfe, M.; Thirlwell, M.; Tsvetkova, E.; Vickers, M.; Vuong, T.; Goodwin, R.

    2016-01-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17–19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer. PMID:26966404

  20. Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis

    PubMed Central

    Brozek, Wolfgang; Manhardt, Teresa; Kállay, Enikö; Peterlik, Meinrad; Cross, Heide S.

    2012-01-01

    Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e., CYP27B1-encoded 25-hydroxyvitamin D-1α-hydroxylase and CYP24A1-encoded 25-hydroxyvitamin D-24-hydroxylase, and inflammation-induced cyclooxygenase-2 (COX-2). Data from 105 cancer patients on CYP27B1, VDR, CYP24A1, and COX-2 mRNA expression in relation to tumor grade, anatomical location, gender and age were fit into a multivariate model of exploratory factor analysis. Nearly identical results were obtained by the principal factor and the maximum likelihood method, and these were confirmed by hierarchical cluster analysis: Within the eight mutually dependent variables studied four independent constellations were found that identify different features of colorectal cancer pathogenesis: (i) Escape of COX-2 activity from restraints by the CYP27B1/VDR system can initiate cancer growth anywhere in the colorectum regardless of age and gender; (ii) variations in COX-2 expression are mainly responsible for differences in cancer incidence in relation to tumor location; (iii) advancing age has a strong gender-specific influence on cancer incidence; (iv) progression from well differentiated to undifferentiated cancer is solely associated with a rise in CYP24A1 expression. PMID:24213465

  1. Epigenetics in diagnosis of colorectal cancer.

    PubMed

    Sameer, Aga Syed; Nissar, Saniya

    2016-03-01

    Colorectal cancer (CRC) is a third most common epithelial carcinoma. CRC is known to develop from the early precancerous lesion to full blown malignancy via definite phases due to cumulative mutations and aberrant methylation of number of genes. The use of serum biomarkers that is non-invasive to discriminate cancer patients from healthy persons will prove to be an important tool to improve the early diagnosis of CRC. This will serve as the boon to the clinical management of the disease.

  2. Label-free visualization of collagen in submucosa as a potential diagnostic marker for early detection of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Qiu, Jingting; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Guan, Guoxian; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2014-09-01

    The collagen signature in colorectal submucosa is changed due to remodeling of the extracellular matrix during the malignant process and plays an important role in noninvasive early detection of human colorectal cancer. In this work, multiphoton microscopy (MPM) was used to monitor the changes of collagen in normal colorectal submucosa (NCS) and cancerous colorectal submucosa (CCS). What's more, the collagen content was quantitatively measured. It was found that in CCS the morphology of collagen becomes much looser and the collagen content is significantly reduced compared to NCS. These results suggest that MPM has the ability to provide collagen signature as a potential diagnostic marker for early detection of colorectal cancer.

  3. Endobronchial metastases from extrathoracic malignancies.

    PubMed

    Akoglu, Sebahat; Uçan, Eyüp S; Celik, Gülperi; Sener, Gülper; Sevinç, Can; Kilinç, Oğuz; Itil, Oya

    2005-01-01

    Endobronchial metastases (EBM) from extrapulmonary malignant tumors are rare. The most common extrathoracic malignancies associated with EBM are breast, renal and colorectal carcinomas. In this study, we aimed to evaluate the clinical, radiographic and bronchoscopic aspects of patients with EBM who were diagnosed between 1992 and 2002. Data about patients' clinical conditions, symptoms, radiographic and endoscopic findings, and histopathological examination results were investigated. EBM was defined as bronchoscopically visible lesions histopathologically identical to the primary tumor in patients with extrapulmonary malignancies. We found 15 cases with EBM. Primary tumors included breast (3), colorectal (3), and renal (2) carcinomas; Malignant Melanoma (2); synovial sarcoma (1), ampulla of Vater adenocarcinoma (1), pheochromocytoma (1), hypernephroma (1), and Hodgkin's Disease (1). The most common symptoms were dyspnea (80%), cough (66.6%) and hemoptysis (33.3%). Multiple (40%) or single (13.3%) pulmonary nodules, mediastinal or hilar lymphadenopathy (40%), and effusion (40%) were the most common radiographic findings. The mean interval from initial diagnosis to diagnosis of EBM was 32.8 months (range, 0-96 months) and median survival time was 18 months (range, 4-84). As a conclusion, various extrapulmonary tumors can metastasize to the bronchus. Symptoms and radiographic findings are similar with those in primary lung cancer. Therefore, EBM should be discriminated from primary lung cancer histopathologically. Although mean survival time is usually short, long-term survivors were reported. Consequently, treatment must be planned according to the histology of the primary tumor, evidence of metastasis to other sites and medical status of the patient.

  4. Malignancies after mitoxantrone for multiple sclerosis

    PubMed Central

    Seuffert, Linda; Mäder, Uwe; Toyka, Klaus V.

    2016-01-01

    Objective: To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis. Methods: This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. Malignancy rates were compared to the German national cancer registry matched for sex, age, and year of occurrence. Results: Follow-up was completed in 676 of 677 identified patients. Median follow-up time was 8.7 years (interquartile range 6.8–11.2), corresponding to 6,220 person-years. Median cumulative mitoxantrone dose was 79.0 mg/m2 (interquartile range 50.8–102.4). Thirty-seven patients (5.5%) were diagnosed with a malignancy after mitoxantrone initiation, revealing a standardized incidence ratio of 1.50 (95% confidence interval [CI] 1.05–2.08). Entities included breast cancer (n = 9), colorectal cancer (n = 7), acute myeloid leukemia (n = 4, 0.6%), and others (each entity n = 1 or 2). The standardized incidence ratio of colorectal cancer was 2.98 (95% CI 1.20–6.14) and of acute myeloid leukemia 10.44 (95% CI 3.39–24.36). It was not increased for other entities including breast cancer. Multivariate Cox regression identified higher age at treatment initiation but neither cumulative mitoxantrone dose (>75 vs ≤75 mg/m2) nor treatment with other immunosuppressive drugs or sex as a risk factor. Fifty-five patients had died, among them 12 of a malignancy and 43 reportedly of other causes. Conclusions: While the overall incidence of malignancies was only mildly increased, the risk of leukemia and colorectal cancer was heightened. If confirmed, posttherapy colonoscopy could become advisable. PMID:27170571

  5. Malignant mesothelioma

    PubMed Central

    Moore, Alastair J; Parker, Robert J; Wiggins, John

    2008-01-01

    Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. PMID:19099560

  6. Thymus vulgaris (thyme) inhibits proliferation, adhesion, migration, and invasion of human colorectal cancer cells.

    PubMed

    Al-Menhali, Afnan; Al-Rumaihi, Aisha; Al-Mohammed, Hana; Al-Mazrooey, Hana; Al-Shamlan, Maryam; AlJassim, Meaad; Al-Korbi, Noof; Eid, Ali Hussein

    2015-01-01

    Colorectal cancer (CRC) remains one of the most common malignancies and a leading cause of cancer-related deaths. Its prognosis remains poor for patients with several grades of this disease. This underscores the need for alternative modalities, such as herbal medicines, to treat this disease. A commonly used plant that appears to be of high medicinal value is Thymus vulgaris L. However, the effects of this plant on the malignant behavior of human CRC cells remains poorly investigated. This study was undertaken to determine the anticancer efficacy of T. vulgaris extract (TVE) in CRC cells. Our results show that TVE inhibits proliferation in a concentration- and time-dependent fashion. This decreased proliferation was concomitant with increased apoptotic cell death as evidenced by increased caspase3/7 activity. Moreover, TVE also decreased adhesion to fibronectin in a concentration-dependent manner. The migratory and invasive capacities of HCT116 cells were significantly inhibited by TVE. Taken together, these data suggest that the TVE inhibits malignant phenotype of colon cancer cells. Therefore, T. vulgaris could have an anticancer effect and that some of its bioactive compounds may prove to be effective treatment modalities for human CRC.

  7. Hematologic malignancies

    SciTech Connect

    Hoogstraten, B.

    1986-01-01

    The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

  8. [Pathologic characteristics of malignant neoplasms occurring in the elderly].

    PubMed

    Arai, Tomio; Matsuda, Yoko; Aida, Junko; Takubo, Kaiyo

    2015-08-01

    Malignant neoplasm preferentially occurs in the elderly. Common cancers in the elderly are gastric, colorectal, lung and prostate cancers in men whereas colorectal, lung, gastric and pancreatic cancers in women. There are several characteristic features such as tumor location, histology, biological behavior and pathway of carcinogenesis in malignant neoplasms occurring in the elderly. Multiple cancers increase with aging. Although it is generally believed that carcinoma in the elderly shows well differentiation, slow growth, low incidence of metastasis and favorable prognosis, the tumor does not always show such features. Regarding biological behavior of malignant tumor in the elderly, age-related alterations of the host such as stromal weakness and decreased immune response against cancer cell invasion should be considered as well as characteristics of tumor cell itself. Thus, we need a specific strategy for treatment for malignant neoplasms in the elderly.

  9. Gastrins, iron and colorectal cancer.

    PubMed

    Baldwin, Graham S

    2009-09-01

    This minireview explores the connections between circulating gastrins, iron status and colorectal cancer. The peptide hormone gastrin is a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. Gastrins bind two ferric ions with μM affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity. The ferric ion ligands have been identified as glutamates 7, 8 and 9 in the 18 amino acid peptide glycine-extended gastrin. An interaction between gastrin and transferrin was first demonstrated by covalent crosslinking techniques, and has been recently confirmed by surface plasmon resonance. We have therefore proposed that gastrins act as catalysts in the loading of transferrin with iron. Several recent lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease haemochromatosis, and that transferrin saturation positively correlates with circulating gastrin concentrations, suggest that gastrins may be involved in iron homeostasis. In addition the recognition that ferric ions may play an unexpected role in the biological activity of non-amidated gastrins may assist in the development of new therapies for colorectal carcinoma.

  10. Synchronous trifocal colorectal cancer

    PubMed Central

    Charalampoudis, Petros; Kykalos, Stylianos; Stamopoulos, Paraskevas; Kouraklis, Gregory

    2016-01-01

    Synchronous colorectal cancers (SCRCs) have been increasingly diagnosed due to emerging diagnostic modalities. The presence of three or more synchronous colorectal cancers has, however, only rarely been reported. A 76-year-old white man presented for management of two concurrent colorectal adenocarcinomas in the left colon evidenced on total colonoscopy. Preoperative abdominal ultrasonography and thoracoabdominal computed tomography were negative for metastatic disease. The patient underwent an elective left hemicolectomy. The pathology report ultimately showed the presence of three moderately differentiated, distinct colorectal cancers. The patient experienced an uneventful recovery. PMID:27695171

  11. Primary prevention of colorectal cancer: lifestyle, nutrition, exercise.

    PubMed

    Martínez, María Elena

    2005-01-01

    The past two decades have provided a vast amount of literature related to the primary prevention of colorectal cancer. Large international variation in colorectal cancer incidence and mortality rates and the prominent increases in the incidence of colorectal cancer in groups that migrated from low- to high-incidence areas provided important evidence that lifestyle factors influence the development of this malignancy. Moreover, there is convincing evidence from epidemiological and experimental studies that dietary intake is an important etiological factor in colorectal neoplasia. Although the precise mechanisms have not been clarified, several lifestyle factors are likely to have a major impact on colorectal cancer development. Physical inactivity and to a lesser extent, excess body weight, are consistent risk factors for colon cancer. Exposure to tobacco products early in life is associated with a higher risk of developing colorectal neoplasia. Diet and nutritional factors are also clearly important. Diets high in red and processed meat increase risk. Excess alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, appear to increase risk. There is also recent evidence supporting a protective effect of calcium and vitamin D in the etiology of colorectal neoplasia. The relationship between intake of dietary fiber and risk of colon cancer has been studied for three decades but the results are still inconclusive. However, some micronutrients or phytochemicals in fiber-rich foods may be important; folic acid is one such micronutrient that has been shown to protect against the development of colorectal neoplasia and is currently being studied in intervention trials of adenoma recurrence. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. Continued focus on primary prevention of colorectal cancer, in combination with efforts aimed at screening and surveillance, will be vital in

  12. Malignant hyperthermia.

    PubMed

    Cantin, R Y; Poole, A; Ryan, J F

    1986-10-01

    The increasing use of intravenous and inhalation sedation in the dental office has the potential of increasing the incidence of malignant hyperthermia (MH) in susceptible subjects. The object of this article is to present two cases of MH and to discuss its pathophysiology, its clinical picture, and its management in the light of the current literature. Stringent screening procedures should be adopted and maintained in order to channel suspected cases to appropriate centers for expert consultation and management. It is further advocated that a program of education for patients and their families be instituted, as it is an essential prerequisite of effective prophylaxis.

  13. Venous thromboembolic disease in colorectal patients.

    PubMed

    McNally, Michael P; Burns, Christopher J

    2009-02-01

    Venous thromboembolic disease, which includes deep vein thromboses as well as pulmonary emboli, can be a significant complication in the postoperative patient. In particular, colorectal patients often carry a higher risk for venous thromboembolism when compared with patients undergoing other operative procedures. Features unique to colorectal patients are the high incidence of inflammatory bowel disease or malignancy. Typically, these patients will undergo lengthy pelvic procedures, which also contribute to a cumulative risk of venous thrombosis. It is critical that all patients and the proposed operative procedure are appropriately risk stratified. Risk stratification allows for easier implementation of an appropriate prophylactic strategy. There are a wide range of safe and effective mechanical and pharmacologic measures available. The authors provide very specific recommendations, but note that clinical judgment plays a significant role.

  14. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies.

    PubMed

    Gambhir, Sahil; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

    2015-03-21

    Nuclear factor kappa B (NF-κB) has an established role in the regulation of innate immunity and inflammation. NF-κB is also involved in critical mechanisms connecting inflammation and cancer development. Recent investigations suggest that the NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers. This review will explore NF-κB's function in inflammation-associated gastrointestinal malignancies, highlighting its oncogenic contribution to each step of carcinogenesis. NF-κB's role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy.

  15. Temporal relationship between prostate brachytherapy and the diagnosis of colorectal cancer

    SciTech Connect

    Gutman, Sarah A.; Merrick, Gregory S. . E-mail: gmerrick@urologicresearchinstitute.org; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Galbreath, Robert W.; Adamovich, Edward

    2006-09-01

    Purpose: To identify the location of pretreatment and posttreatment colorectal malignancies and posttreatment colorectal polyps in patients with clinically localized prostate cancer managed with brachytherapy. Methods and Materials: From April 1995 through July 2004, 1,351 consecutive patients underwent brachytherapy for clinical stage T1b-T3a (American Joint Committee on Cancer, 2002) prostate cancer. Supplemental external beam radiotherapy (XRT) was administered to 699 patients. The median follow-up was 4.6 years. Operative and pathology reports were reviewed for all patients with pretreatment and posttreatment colorectal cancer and posttreatment colorectal polyps. Multiple parameters were evaluated for the development of colorectal cancer or colorectal polyps. Results: Colorectal cancer was diagnosed in 23 and 25 patients before and after prostate brachytherapy, respectively. No differences were identified in the distribution of colorectal cancers either before or after treatment (3 and 4 rectal cancers in the pre- and postbrachytherapy cohorts). Thirty-five of the 48 colorectal cancers (73%) were diagnosed within 5 years of brachytherapy with a peak incidence 1 year after brachytherapy. One hundred ninety-two colorectal polyps were diagnosed after brachytherapy, 160 (83%) occurred within 4 years of brachytherapy, and only 27 (14%) were located in the rectum. In multivariate Cox regression analysis, prostate D{sub 9} (minimum percentage of the dose covering 90% of the target volume) predicted for posttreatment colorectal cancer. Rectal polyps were most closely related to patient age and percent positive biopsies, whereas sigmoid/colon polyps were best predicted by patient age, planning volume, and supplemental XRT. Conclusions: Colorectal cancer was diagnosed with equal frequency before and after brachytherapy with comparable geographic distributions. In addition, the vast majority of postbrachytherapy colorectal polyps were located beyond the confines of the

  16. Aetiology of colorectal cancer and relevance of monogenic inheritance

    PubMed Central

    Ponz de Leon, M; Benatti, P; Borghi, F; Pedroni, M; Scarselli, A; Di Gregorio, C; Losi, L; Viel, A; Genuardi, M; Abbati, G; Rossi, G; Menigatti, M; Lamberti, I; Ponti, G; Roncucci, L

    2004-01-01

    Background and aims: Although diet and lifestyle are associated with the development of colorectal malignancies, the only clearly identified aetiological factors in colorectal cancer are inheritance (hereditary non-polyposis colorectal cancer (HNPCC) and familial polyposis), inflammatory bowel diseases, papillomavirus, and acquired immunodeficiency syndrome (AIDS). Our aim was to determine what proportion of colorectal neoplasms could be attributed to these specific factors. Patients and methods: Data from a colorectal cancer registry were analysed over a 15 year period, during which nearly 2500 cases were recorded. In patients with suspected HNPCC, microsatellite instability and immunohistochemical expression of proteins encoded by the main DNA mismatch repair genes were assessed. In families with unstable neoplasms, constitutional mutations of the mismatch repair genes hMSH2, hMLH1, and hMSH6 were evaluated by single strand conformation polymorphism analysis and sequencing. Results: Inflammatory bowel diseases, familial polyposis, and AIDS were rare causes of colorectal cancer (three, three, and one case, respectively). Anal squamous carcinoma developed in 27 patients (1.0%) and could be attributed to papillomavirus infection. In 58 patients (from 34 families) a clinical diagnosis of HNPCC was established (2.4%). In total, cases with a known aetiology were 92 (3.7% of all patients). Microsatellite instability was detected in 15 cancers from HNPCC families, and germline mutations in six families (12 patients, 0.5% of the total). Families with unstable tumours, with or without mutations, were clinically similar, suggesting the involvement of the mismatch repair system even when mutations were not detected. Conclusions: The study suggests that the aetiology of colorectal malignancies remains elusive in the large majority of cases. Among specific causes, HNPCC represents the most frequent. However, with a population based approach, constitutional mutations of the

  17. Review of single incision laparoscopic surgery in colorectal surgery

    PubMed Central

    Madhoun, Nisreen; Keller, Deborah S; Haas, Eric M

    2015-01-01

    As surgical techniques continue to move towards less invasive techniques, single incision laparoscopic surgery (SILS), a hybrid between traditional multiport laparoscopy and natural orifice transluminal endoscopic surgery, was introduced to further the enhanced outcomes of multiport laparoscopy. The safety and feasibility of SILS for both benign and malignant colorectal disease has been proven. SILS provides the potential for improved cosmesis, postoperative pain, recovery time, and quality of life at the drawback of higher technical skill required. In this article, we review the history, describe the available technology and techniques, and evaluate the benefits and limitations of SILS for colorectal surgery in the published literature. PMID:26478673

  18. Colorectal Cancer Screening: Stool DNA and Other Noninvasive Modalities.

    PubMed

    Bailey, James R; Aggarwal, Ashish; Imperiale, Thomas F

    2016-03-01

    Colorectal cancer screening dates to the discovery of precancerous adenomatous tissue. Screening modalities and guidelines directed at prevention and early detection have evolved and resulted in a significant decrease in the prevalence and mortality of colorectal cancer via direct visualization or using specific markers. Despite continued efforts and an overall reduction in deaths attributed to colorectal cancer over the last 25 years, colorectal cancer remains one of the most common causes of malignancy-associated deaths. In attempt to further reduce the prevalence of colorectal cancer and associated deaths, continued improvement in screening quality and adherence remains key. Noninvasive screening modalities are actively being explored. Identification of specific genetic alterations in the adenoma-cancer sequence allow for the study and development of noninvasive screening modalities beyond guaiac-based fecal occult blood testing which target specific alterations or a panel of alterations. The stool DNA test is the first noninvasive screening tool that targets both human hemoglobin and specific genetic alterations. In this review we discuss stool DNA and other commercially available noninvasive colorectal cancer screening modalities in addition to other targets which previously have been or are currently under study.

  19. Biomechanical investigation of colorectal cancer cells

    NASA Astrophysics Data System (ADS)

    Palmieri, Valentina; Lucchetti, Donatella; Maiorana, Alessandro; Papi, Massimiliano; Maulucci, Giuseppe; Ciasca, Gabriele; Svelto, Maria; De Spirito, Marco; Sgambato, Alessandro

    2014-09-01

    The nanomechanical properties of SW480 colon cancer cells were investigated using Atomic Force Microscopy. SW480 cells are composed of two sub-populations with different shape and invasiveness. These two cells populations showed similar adhesion properties while appeared significantly different in term of cells stiffness. Since cell stiffness is related to invasiveness and growth, we suggest elasticity as a useful parameter to distinguish invasive cells inside the colorectal tumor bulk and the high-resolution mechanical mapping as a promising diagnostic tool for the identification of malignant cells.

  20. Epigenetics in diagnosis of colorectal cancer

    PubMed Central

    Sameer, Aga Syed; Nissar, Saniya

    2016-01-01

    Colorectal cancer (CRC) is a third most common epithelial carcinoma. CRC is known to develop from the early precancerous lesion to full blown malignancy via definite phases due to cumulative mutations and aberrant methylation of number of genes. The use of serum biomarkers that is non-invasive to discriminate cancer patients from healthy persons will prove to be an important tool to improve the early diagnosis of CRC. This will serve as the boon to the clinical management of the disease. PMID:27844020

  1. Colorectal cancer screening

    PubMed Central

    Chan, Pak Wo Webber; Ngu, Jing Hieng; Poh, Zhongxian; Soetikno, Roy

    2017-01-01

    Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should work in partnership to improve uptake of colorectal cancer screening to reduce the morbidity and mortality from colorectal cancer. PMID:28111691

  2. Expression Status of UBE2Q2 in Colorectal Primary Tumors and Cell Lines

    PubMed Central

    Shafiee, Sayed Mohammad; Seghatoleslam, Atefeh; Nikseresht, Mohsen; Hosseini, Seyed Vahid; Alizadeh-Naeeni, Mahvash; Safaei, Akbar; Owji, Ali Akbar

    2014-01-01

    Background: Activation of the ubiquitin-proteasome pathway in various malignancies, including colorectal cancer, is established. This pathway mediates the degradation of damaged proteins and regulates growth and stress response. The novel human gene, UBE2Q2, with a putative ubiquitin-conjugating enzyme activity, is reported to be overexpressed in some malignancies. We sought to investigate the expression levels of the UBE2Q2 gene in colorectal cell lines as well as in cancerous and normal tissues from patients with colorectal cancer. Methods: Levels of UBE2Q2 mRNA in cell lines were assessed by Real-Time PCR. Western blotting was employed to investigate the levels of the UBE2Q2 protein in 8 colorectal cell lines and 43 colorectal tumor samples. Results: Expression of UBE2Q2 was observed at the level of both mRNA and protein in colorectal cell lines, HT29/219, LS180, SW742, Caco2, HTC116, SW48, SW480, and SW1116. Increased levels of UBE2Q2 immunoreactivity was observed in the 65.11% (28 out of 43) of the colorectal carcinoma tissues when compared with their corresponding normal tissues. Difference between the mean intensities of UBE2Q2 bands from cancerous and normal tissues was statistically significant at P<0.001 (paired t test). Conclusion: We showed the expression pattern of the novel human gene, UBE2Q2, in 8 colorectal cell lines. Overexpression of UBE2Q2 in the majority of the colorectal carcinoma samples denotes that it may have implications for the pathogenesis of colorectal cancer. PMID:24753643

  3. Targeting Angiogenesis in Colorectal Cancer: Tyrosine Kinase Inhibitors.

    PubMed

    Kircher, Sheetal Mehta; Nimeiri, Halla S; Benson, Al B

    2016-01-01

    Colorectal cancer is commonly diagnosed throughout the world, and treatment options have greatly expanded over the last 2 decades. Targeting angiogenesis has been a major focus of study in a variety of malignancy types. Targeting angiogenesis has been achieved by several mechanisms in colorectal cancer, including use of antiangiogenic small molecule tyrosine kinase inhibitors (TKIs). There have been many attempts and failures to prove efficacy of TKIs in the treatment of colorectal cancer including sorafenib, sunitinib, vatalanib, and tivozanib. Regorafenib was the first TKI to demonstrate efficacy and is an orally active inhibitor of angiogenic (including the vascular endothelial growth factor receptors 1, 2, and 3), stromal, and oncogenic receptor tyrosine kinases. There are ongoing investigations of both regorafenib and ninetanib; however, there remains a critical need to better understand novel combinations with TKIs that could prove more efficacious than available options.

  4. Colorectal Cancer Associated with Streptococcus anginosus Bacteremia and Liver Abscesses

    PubMed Central

    Masood, Umair; Sharma, Anuj; Lowe, Dhruv; Khan, Rashad; Manocha, Divey

    2016-01-01

    Streptococcus anginosus is part of the normal flora of the human gastrointestinal tract. Their ability to cause abscesses is very unique and sets them apart from the rest of the streptococci groups. While an association of group D streptococcus bacteremia and endocarditis with colorectal carcinoma is well established, S. anginosus infections are rarely implicated with colonic malignancy. We present a case of a 62-year-old male who presented to the hospital with fatigue and generalized abdominal pain. Computed tomography of the abdomen revealed multiple liver abscesses and rectal thickening. Blood cultures were found to grow S. anginosus bacteria. Colonoscopy revealed a rectal mass which was later confirmed to be rectal adenocarcinoma. This case presents an association between S. anginosus bacteremia and presence of colorectal cancer which has been highlighted in only a few case reports in literature. This should prompt clinicians to screen for colorectal cancer in patients with S. anginosus bacteremia. PMID:28100999

  5. Colorectal Cancer Coalition

    MedlinePlus

    ... inspire those touched by colorectal cancer. Watch Videos Join us on the hill Attend our annual advocacy ... We always need volunteers. Browse our opportunities. Volunteer Join the Movement We have many ways to fight ...

  6. Epidemiology of colorectal cancer

    PubMed Central

    Marley, Andrew R; Nan, Hongmei

    2016-01-01

    Colorectal cancer is currently the third deadliest cancer in the United States and will claim an estimated 49,190 U.S. lives in 2016. The purpose of this review is to summarize our current understanding of this disease, based on nationally published statistics and information presented in peer-reviewed journal articles. Specifically, this review will cover the following topics: descriptive epidemiology (including time and disease trends both in the United States and abroad), risk factors (environmental, genetic, and gene-environment interactions), screening, prevention and control, and treatment. Landmark discoveries in colorectal cancer risk factor research will also be presented. Based on the information reviewed for this report, we suggest that future U.S. public health efforts aim to increase colorectal cancer screening among African American communities, and that future worldwide colorectal cancer epidemiology studies should focus on researching nutrient-gene interactions towards the goal of improving personalized treatment and prevention strategies. PMID:27766137

  7. Role of colonic stents in the management of colorectal cancers

    PubMed Central

    Sagar, Jayesh

    2016-01-01

    Colorectal cancer is one of the commonly encountered cancers across the Western World. In United Kingdom, this constitutes third most common ranked cancer and second most common ranked cause of cancer related deaths. Its acute presentation as a malignant colonic obstruction imposes challenges in its management. Colonic stent has been used for many years to alleviate acute obstruction in such cases allowing optimisation of patient’s physiological status and adequate staging of cancer. In this review, current literature evidence regarding use of colonic stent in acute malignant colonic obstruction is critically appraised and recommendations on the use of colonic stent are advocated. PMID:26962401

  8. Out of the blue finger ischaemia and occult colorectal cancer.

    PubMed

    Schattner, Ami

    2017-03-08

    A woman aged 66 years with a history of unprovoked deep venous thrombosis (DVT) presented with persistent digital ischaemic changes of 2 of her right hand fingers. Physical examination was otherwise normal and extensive laboratory and imaging studies were unremarkable. A history of unprovoked DVT and the current episode of digital ischaemia prompted concern for underlying occult malignancy. Repeated history-taking revealed a strongly positive family history suggesting an occult colorectal cancer. Colonoscopy with biopsy revealed adenocarcinoma. Adenocarcinoma of the colon has rarely been associated with paraneoplastic acral vascular syndrome. This report suggests that occult malignancy needs to be considered in patients with focal digital ischaemia as this association is poorly unrecognised.

  9. Malignant hyperthermia

    PubMed Central

    Rosenberg, Henry; Davis, Mark; James, Danielle; Pollock, Neil; Stowell, Kathryn

    2007-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene

  10. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

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

  11. Colorectal Cancer: Symptoms, Diagnosis, Treatment

    MedlinePlus

    ... Past Issues Special Section: Colorectal Cancer Colorectal Cancer: Symptoms, Diagnosis and Treatment Past Issues / Spring 2009 Table of ... version of this page please turn Javascript on. Symptoms Check with your healthcare provider if you have ...

  12. Maspin, a Marker of Serrated Colorectal Polyps.

    PubMed

    Rubio, Carlos A; Kaufeldt, Ann; Björk, Jan; Jaramillo, Edgar

    2015-07-01

    The serine proteinase inhibitor maspin is a tumor-suppressor protein that stimulates apoptosis and inhibits motility, invasion and cancer metastasis. Mutant maspin galvanises partial loss of tumor-suppressor function, reducing susceptibility to apoptosis and facilitating malignant progression. Mutant maspin has been reported in many tumor types. We recently analyzed maspin expression in 128 colorectal lesions: 39 hyperplastic polyps (HPs), 29 sessile serrated adenoma/polyps (SSA/Ps), three traditional serrated adenomas (TSAs), 20 conventional colorectal adenomas (CCRAs), 5 carcinomas evolving from CCRA, 12 active inflammatory bowel disease (IBD), 2 ulcerative colitis (UC) in remission, 4 solitary ulcers (rectum) and 12 normal colorectal mucosa. The topographic distribution of maspin in the cytoplasm was classified into i) extensive, ii) focal, or iii) negative. The intensity of maspin expression in the cytoplasm was classified into i) unquestionable or ii) negative. Cases with faint (questionable) maspin expression were also recorded as negative. Extensive maspin expression was recorded in 95% (39/41) of the HPs, in 100% (29/29) of the SSA/Ps (including one carcinoma arising in a SSA/P), in 66% (2/3) of the TSAs, but only in 10% (2/20) of the CCRAs. None of the specimens with carcinoma arising in CCRA, with UC in remission or with solitary ulcer exhibited extensive maspin expression. Importantly, maspin was not expressed in the normal mucosa (including that adjacent to HP, SSA/P, TSA and CCRA). It is submitted that extensive maspin expression might be a manifestation of mutant maspin in lesions central to the serrated pathway of colorectal carcinogenesis.

  13. MicroRNAs: Clinical Relevance in Colorectal Cancer

    PubMed Central

    Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, Hui

    2015-01-01

    Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer. PMID:26602923

  14. Obesity and colorectal cancer.

    PubMed

    Aleksandrova, Krasimira; Nimptsch, Katharina; Pischon, Tobias

    2013-01-01

    This review outlines the association of obesity with risk of colorectal cancer and the potential underlying mechanisms from an epidemiological perspective. Current research indicates that there is a moderate but consistently reported association between general obesity (as determined by BMI) and colorectal cancer incidence and mortality. The relative risk associated with obesity is higher for cancer of the colon than for cancer of the rectum and it is higher in men than in women. By contrast, abdominal adiposity (as determined by waist circumference or waist-to-hip ratio) is similarly strongly associated with colon cancer in men and women, suggesting that abdominal adiposity is a more important risk factor for colon cancer than general adiposity, at least in women. Putative mechanisms that may account for the link between adiposity and colorectal cancer risk include hyperinsulinemia, insulin resistance, inflammation, altered immune response, oxidative stress, as well as disturbances in insulin-like growth factors, adipokines, and sex steroids. Understanding the link between obesity and colorectal cancer may pave the way for targeted prevention of colorectal cancer morbidity and mortality.

  15. Colorectal cancer screening.

    PubMed

    Bessa Caserras, Xavier

    2016-09-01

    In the latest meeting of the American Gastroenterological Association, several clinical studies were presented that aimed to evaluate the various colorectal cancer screening strategies, although most assessed the various aspects of faecal immunochemical testing (FIT) and colonoscopy. Data were presented from consecutive FIT-based screening rounds, confirming the importance of adherence to consecutive screening rounds, achieving a similar or superior diagnostic yield to endoscopic studies. There was confirmation of the importance of not delaying endoscopic study after a positive result. Participants with a negative FIT (score of 0) had a low risk for colorectal cancer. Several studies seemed to confirm the importance of high-quality colonoscopy in colorectal cancer screening programmes. The implementation of high-quality colonoscopies has reduced mortality from proximal lesions and reduced interval cancers in various studies. Finally, participants with a normal colonoscopy result or with a small adenoma are at low risk for developing advanced neoplasms during follow-up.

  16. A clinicopathological analysis of KISS1 and KISS1R expression in colorectal cancer.

    PubMed

    Kostakis, Ioannis D; Agrogiannis, George; Vaiopoulos, Aristeidis G; Mylona, Eleni; Patsouris, Efstratios; Kouraklis, Gregory; Koutsilieris, Michael

    2015-07-01

    Kisspeptins, the products of the KISS1 gene have tumor suppressing and antimetastatic properties. We aimed to study KISS1 and KISS1R expression in colorectal cancer. We analyzed KISS1 and KISS1R expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 111 patients with colorectal adenocarcinoma. KISS1 expression was much higher in the normal than in the malignant colonic mucosa. Regarding malignant tissues, KISS1 levels were higher in larger tumors, in stage III and IV cancers, in cancers with lymph node metastasis and in tumors located in the distal part of the large intestine. Patients with greater KISS1 levels had worse prognosis. No KISS1R expression was detected in normal or malignant tissues or in liver metastases. KISS1 expression is reduced during the malignant transformation of the colonic mucosa. However, larger and advanced colorectal cancers express more KISS1, without reaching the former normal levels, and increased KISS1 levels are associated with worse prognosis. Finally, neither the normal nor the malignant colonic epithelial cells produce KISS1R.

  17. Evolution of laparoscopy in colorectal surgery: An evidence-based review

    PubMed Central

    Blackmore, Alexander Emmanuel; Wong, Mark Te Ching; Tang, Choong Leong

    2014-01-01

    Open surgery for colorectal disease has progressed significantly over the past century from humble beginnings to form the mainstay of treatment for colorectal cancer and a number of benign conditions. Following the introduction of laparoscopic abdominal surgery, the next stage in the evolution of the specialty began in the 1990s with the first laparoscopic colonic resection. Following some early concerns regarding its safety and oncological efficacy during the latter part of that decade, laparoscopic colorectal surgery rapidly came into mainstream use in the early part of the current century with evidence supporting its use being made available from large scale randomised controlled trials. This article provides an evidence-based summary of this evolutionary process as it relates to both benign and malignant colorectal disease, as well as discussion of the next phase of new technologies such as robotic surgery. PMID:24803804

  18. Prevalence of colorectal adenomatous polyps in patients with chronic obstructive pulmonary disease

    PubMed Central

    Chun, Eun Mi; Kim, Seo Woo; Lim, So Yeon

    2015-01-01

    Background Colorectal adenomatous polyps are precancerous lesions of colorectal cancer. The aim of this study was to assess the prevalence of colorectal adenomatous polyps in chronic obstructive pulmonary disease (COPD) patients and determine whether COPD is associated with colorectal malignant potential. Methods Subjects who had undergone post-bronchodilator spirometry and colonoscopy and were 40 years or older were selected from the hospital database. COPD was defined as a spirometry in which the ratio of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) is <0.7 in post-bronchodilator spirometry. The non-COPD group was matched for both age and sex, and were defined as having an FEV1, FVC, and FEV1/FVC ≥0.7 in spirometry. Finally, 333 patients were retrospectively reviewed; of this group, 82 patients had COPD. Results Among the subjects, 201 patients (60%) were nonsmokers, while 78 (23%) were current smokers. The prevalence of colorectal adenomatous polyps was 39% (98/251) in the non-COPD group and 66% (54/82) in the COPD group. Among 54 patients with adenomatous polyps in the COPD group, 47 had tubular adenoma and seven had villous adenoma. Multiple logistic regression analyses revealed that only COPD patients whom matched to the criteria of COPD by pulmonary function test (odds ratio 2.1, 95% confidence interval: 1.1–3.8; P=0.019) were independently associated with colorectal malignant potential. Conclusion The risk of colorectal malignant potential in the COPD group was higher than in the non-COPD group. We may suggest that COPD patients should consider regular colonoscopic evaluation to screen for premalignant colon polyps regardless of smoking. PMID:26028968

  19. Localization of human BRCA1 and BRCA2 in non-inherited colorectal carcinomas and matched normal mucosas.

    PubMed

    Bernard-Gallon, D J; Peffault de Latour, M; Hizel, C; Vissac, C; Cure, H; Pezet, D; Dechelotte, P J; Chipponi, J; Chassagne, J; Bignon, Y J

    2001-01-01

    We characterized the expression of BRCA1 and BRCA2 in 38 sporadic colorectal carcinomas and matched normal mucosas with 9 anti-BRCA1 antibodies and 4 anti-BRCA2 antibodies, raised against several different epitopes, using immunohistochemical technique. We demonstrated an increased BRCA1 and BRCA2 staining in the apical cell pole of epithelial malignant cells and we also revealed a significant increase in BRCA1 and BRCA2 nuclear foci in tumor colorectal specimens in comparison with corresponding normal tissues. These increases in BRCA1 and BRCA2 expression may be explained by the fact that colorectal tissue is subject to very active proliferation and differentiation.

  20. Expression of Wntless in colorectal carcinomas is associated with invasion, metastasis, and poor survival.

    PubMed

    Xu, Hanfeng; Jiang, Wen; Zhu, Fang; Zhu, Chuandong; Wei, Juan; Wang, Jiandong

    2016-06-01

    Wntless also known as WLS, GPR177, or Evi, is a key modulator of Wnt protein secretion. Its overexpression is found in certain types of human cancers such as malignant astrocytoma and breast cancers. We hypothesized that this protein may be aberrantly expressed in colorectal carcinoma which also possesses aberrant Wnt signaling. To investigate the association between the expression of Wnt and clinicopathological parameters in colorectal carcinomas, a set of colorectal carcinoma tissue samples was analyzed for the expression of WLS using an anti-GPR177 monoclonal antibody specific for the WLS protein. High expression of WLS protein was observed in most colorectal carcinoma samples compared with nontumor mucosa in the same patients (117/201, 58.2%). High expression of WLS was associated with sex (p = 0.005), age (p = 0.009), depth of invasion (p < 0.001), lymph node metastasis (p = 0.026), and tumor-node-metastasis (TNM) stage (p = 0.003). No significant relationship between the expression of WLS and tumor location, size, and differentiation was found. The survival analyses showed WLS was an independent prognostic marker and that patients whose carcinoma exhibited high expression of WLS had a poorer outcome (p = 0.033). Our results indicate that WLS may play a role in invasion and metastasis of colorectal carcinoma. The WLS protein expression level may be used as a potential prognostic marker in colorectal carcinoma. Furthermore, the WLS gene may provide a novel target for therapy of colorectal carcinoma.

  1. Cellular and humoral inflammatory response after laparoscopic and conventional colorectal surgery. Preliminary report.

    PubMed

    Laforgia, Rita; D'Elia, Giovanna; Lattarulo, Serafina; Mestice, Anna; Volpi, Annalisa

    Our aim is to compare the immune response after colorectal surgery performed laparoscopically and via traditional technique. This response seems to be proportional to the level of the surgical trauma and presumably is directed to improve host defence. This is a prospective reported study based on patients' randomisation. Fourteen patients with colorectal diseases undergoing laparoscopic or open surgery were enrolled. After both laparoscopic and open colorectal surgery, we observed a significant increase of circulating C-Reactive Protein (CRP) levels. The count of lymphocytes subpopulations did not show significant differences after both procedures. IL-6 serum levels increased immediately after laparoscopic approach. IL-6 production was preserved only in the laparoscopic group, while its plasma levels were significantly higher in conventional group. Postoperative cell-mediated immunity was better preserved after laparoscopic than after conventional colorectal resection. Laparoscopy became a popular approach to treat surgically benign and malignant colorectal diseases and several authors reported a better immune response in patients performing laparoscopic surgery after comparing to conventional colorectal surgery. These findings may have important implications in performing a laparoscopic colorectal resection.

  2. Anticancer effects of fucoxanthin and fucoxanthinol on colorectal cancer cell lines and colorectal cancer tissues.

    PubMed

    Takahashi, Kazuto; Hosokawa, Masashi; Kasajima, Hiroyuki; Hatanaka, Kazuteru; Kudo, Kazuhiro; Shimoyama, Norihiko; Miyashita, Kazuo

    2015-09-01

    Colorectal cancer is one of the most malignant neoplasms worldwide. Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. In the present study, the anticancer effects of fucoxanthin and its metabolite, fucoxanthinol, on 6 colorectal cancer cell lines and 20 tissue samples from surgically resected clinical colorectal cancer specimens were examined using a collagen-gel droplet embedded culture drug sensitivity test (CD-DST). The in vitro sensitivity to fucoxanthin, fucoxanthinol and the anticancer drugs is expressed as T/C (%), where T is the absorbance of cells which stained by neutral red treated with carotenoids and C is the absorbance of non-staining cells. Fucoxanthin and fucoxanthinol decreased the T/C (%) of Caco-2, WiDr, HCT116, and DLD-1 cell lines at doses of 20 µM. Fucoxanthinol also decreased the T/C (%) of SW620 cells, while the T/C (%) of Colo205 cells was not reduced by treatment with either carotenoid. Specifically, the T/C (%) of Caco-2 and WiDr cells, which were incubated in carotenoid-free medium for 6 days following treatment with 20 µM fucoxanthinol for 24 h, was markedly decreased to 1.4±0.2 and 12.0±0.3%, respectively. Furthermore, fucoxanthin and fucoxanthinol decreased the T/C (%) in colorectal cancer tissue samples. Notably, 20 µM fucoxanthinol treatment resulted in a higher proportion of colorectal cancer samples with a T/C (%) of <50% (13/20, 65%) compared with samples treated with 20 µM fucoxanthin (2/20, 10%). The median T/C (%) value of 35.1% for the 20 cancers specimens treated with 20 µM fucoxanthinol was lower than the median T/C (%) values of 86.3% and 75.8% for those treated with fluorouracil and paclitaxel, respectively. These results suggested that fucoxanthin and fucoxanthinol may be of use as chemotherapeutic agents in colorectal cancer.

  3. Radioimmunodetection of colorectal cancer

    SciTech Connect

    Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.

    1980-03-15

    This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with /sup 131/I at a total dose of at least 1.0 ..mu..Ci. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the /sup 131/I-labeled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with /sup 131/I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the apparent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures.

  4. Precursors to Lymphoproliferative Malignancies

    PubMed Central

    Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.

    2013-01-01

    We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy. PMID:23549397

  5. Association Between Coeliac Disease and Risk of Any Malignancy and Gastrointestinal Malignancy

    PubMed Central

    Han, Yuehua; Chen, Wuzhen; Li, Peiwei; Ye, Jun

    2015-01-01

    Abstract Coeliac disease (CD) is reported to be associated with risk of malignancy; however, this association remains unclear. We aimed to systematically evaluate the association between CD and risk of all malignancies as well as gastrointestinal (GI) malignancy specifically. The PUBMED and EMBASE databases were searched to identify eligible studies from 1960 to March 2015, without restriction. Two reviewers independently performed the study inclusion and data extraction methods. Odds ratios (ORs), risk ratios, or standardized incidence ratios were pooled using either a fixed- or a random-effects model. Sensitivity and subgroup analyses were used to explore sources of heterogeneity. A total of 17 studies were included in this meta-analysis. The pooled OR for risk of all malignancies was 1.25 (95% confidence interval [CI] 1.09–1.44), whereas the pooled OR for risk of GI malignancy was 1.60 (95% CI 1.39–1.84) and suggested an inverse association with CD. Moreover, patients with CD were at a higher risk of esophageal cancer (pooled OR = 3.72, 95% CI 1.90–7.28) and small intestinal carcinoma (pooled OR = 14.41, 95% CI 5.53–37.60), whereas no significant associations were observed for other GI cancers, including gastric, colorectal, liver, and pancreatic cancers. Subgroup analyses also indicated that the results were influenced by the CD diagnostic method, as well as the follow-up time after CD diagnosis. CD was associated with increased risk of all malignancies as well as GI malignancies, including esophageal cancer and small intestinal carcinoma. PMID:26402826

  6. Pinworm infection masquerading as colorectal liver metastasis

    PubMed Central

    Roberts, KJ; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

    2012-01-01

    Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur. PMID:22943320

  7. Genetic inactivation of ADAMTS15 metalloprotease in human colorectal cancer.

    PubMed

    Viloria, Cristina G; Obaya, Alvaro J; Moncada-Pazos, Angela; Llamazares, María; Astudillo, Aurora; Capellá, Gabriel; Cal, Santiago; López-Otín, Carlos

    2009-06-01

    Matrix metalloproteinases have been traditionally linked to cancer dissemination through their ability to degrade most extracellular matrix components, thus facilitating invasion and metastasis of tumor cells. However, recent functional studies have revealed that some metalloproteases, including several members of the ADAMTS family, also exhibit tumor suppressor properties. In particular, ADAMTS1, ADAMTS9, and ADAMTS18 have been found to be epigenetically silenced in malignant tumors of different sources, suggesting that they may function as tumor suppressor genes. Herein, we show that ADAMTS15 is genetically inactivated in colon cancer. We have performed a mutational analysis of the ADAMTS15 gene in human colorectal carcinomas, with the finding of four mutations in 50 primary tumors and 6 colorectal cancer cell lines. Moreover, functional in vitro and in vivo studies using HCT-116 and SW-620 colorectal cancer cells and severe combined immunodeficient mice have revealed that ADAMTS15 restrains tumor growth and invasion. Furthermore, the presence of ADAMTS15 in human colorectal cancer samples showed a negative correlation with the histopathologic differentiation grade of the corresponding tumors. Collectively, these results provide evidence that extracellular proteases, including ADAMTS15, may be targets of inactivating mutations in human cancer and further validate the concept that secreted metalloproteases may show tumor suppressor properties.

  8. The expression of cytoskeleton regulatory protein Mena in colorectal lesions.

    PubMed

    Gurzu, Simona; Jung, I; Prantner, I; Ember, I; Pávai, Z; Mezei, T

    2008-01-01

    The actin regulatory proteins Ena/VASP (Enabled/Vasodilator stimulated phosphoprotein) family is involved in the control of cell motility and adhesion. They are important in the actin-dependent processes where dynamic actin reorganization it is necessary. The deregulation of actin cycle could have an important role in the cells' malignant transformation, tumor invasion or metastasis. Recently studies revealed that the human orthologue of murine Mena is modulated during the breast carcinogenesis. In our study, we tried to observe the immunohistochemical expression of mammalian Ena (Mena) in the colorectal polyps and carcinomas. We analyzed 10 adenomatous polyps (five with dysplasia) and 36 adenocarcinomas. We used the indirect immunoperoxidase staining. BD Biosciences have provided the Mena antibody. We observed that Mena was not expressed in the normal colorectal mucosa neither in polyps without dysplasia, but its expression was very high in polyps with high dysplasia. In colorectal carcinomas, Mena marked the tumoral cells in 80% of cases. In 25% of positive cases, the intensity was 3+, in 60% 2+ and in the other 15% 1+. The Mena intensity was higher in the microsatellite stable tumors (MSS) and was correlated with vascular invasion, with intensity of angiogenesis marked with CD31 and CD105 and with c-erbB-2 and p53 expression. This is the first study in the literature about Mena expression in colorectal lesions.

  9. Gastrins, iron homeostasis and colorectal cancer.

    PubMed

    Kovac, Suzana; Anderson, Gregory J; Baldwin, Graham S

    2011-05-01

    The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron deficiency anemia was recognized as a long-term consequence of partial gastrectomy. This review summarizes the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyze the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

  10. Gastrins, Iron Homeostasis and Colorectal Cancer

    PubMed Central

    Kovac, Suzana; Anderson, Gregory J.; Baldwin, Graham S.

    2011-01-01

    The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron-deficiency anemia was recognised as a long-term consequence of partial gastrectomy. This review summarises the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron-binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyse the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron-overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. PMID:21320535

  11. Colorectal tumors: the histology report.

    PubMed

    Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

    2011-03-01

    Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed.

  12. Region-specific differences in colorectal cancer: Slovakia and Hungary have highest incidence in Europe.

    PubMed

    Simko, V; Ginter, E

    2016-01-01

    Epidemiological data on colorectal cancer (CRC) exhibit high incidence in Central East Europe. Hungary, Slovakia and Croatia represent the lead. For decades it was the Czech Republic but it attained the fourth rank after the mid-2000. Remarkably, the Ashkenazi Jews who imigrated to the USA from Central Europe have the highest incidence of CRC among US minorities. They also have high incidence of inflammatory bowel disease, a risk for CRC. Notably, countries surrounding the Central European focus of CRC, Austria, Germany, Poland, Romania, Ukraine and Russia have substantially lower incidence. CRC in Central Europe has higher incidence than CRC among the highest at-risk cohort in the USA, the elderly blacks. Research and the genome wide screening identified genetic mutations associated with CRC in Ashkenazis from Central Europe. Some risk factors for CRC are non genotypic as evidenced by wide variation in CRC incidence in the course of only a few decades. Recent trends offer hope that identification of the non-innate pathogenic mechanisms would potentially reduce the burden of this third most lethal malignancy (Tab. 1, Fig. 4, Ref. 40).

  13. [Colorectal cancer screening].

    PubMed

    Castells, Antoni

    2013-10-01

    Colorectal cancer is the paradigm of tumoral growth that is susceptible to preventive measures, especially screening. Various screening strategies with demonstrated efficacy and efficiency are currently available, notable examples being the fecal occult blood test and endoscopic tests. In addition, new modalities have appeared in the last few years that could become viable alternatives in the near future. The present article reviews the most important presentations on colorectal screening at the annual congress of the American Gastroenterological Association held in Orlando in May 2013, with special emphasis on the medium- and long-term results of strategies using the fecal occult blood test and flexible sigmoidoscopy, as well as initial experiences with the use of new biomarkers.

  14. Liver resection for metastatic colorectal leiomyosarcoma: a single center experience

    PubMed Central

    El-Kehdy, Jessica; Nounou, Ghina El; Deeba, Samer; Fakih, Hawraa; Jabbour, Mark; Haydar, Ali; El Naaj, Abdallah Abou; Abou-Alfa, Ghassan K.; O’Reilly, Eileen M.; Shamseddine, Ali; Khalife, Mohamad; Mukherji, Deborah

    2015-01-01

    Background Leiomyosarcoma arising in the colorectum is a rare malignancy of the smooth muscles accounting for less than 1% of gastrointestinal tumors. Surgery remains the most accepted modality for the treatment of this entity however management of liver metastases remains controversial. Methods & results From 1998 to 2009, five patients diagnosed with primary leiomyosarcoma of colorectal origin with metastatic liver disease, underwent liver resections at the American University of Beirut Medical Center. The median overall survival was 47 months (range, 7-135 months). Conclusions Leiomyosarcoma of colorectal origin with liver metastasis is a very rare entity. Long-term survival can be achieved after surgical resection and should be considered for all patients. PMID:26487954

  15. Mouse models for the discovery of colorectal cancer driver genes

    PubMed Central

    Clark, Christopher R; Starr, Timothy K

    2016-01-01

    Colorectal cancer (CRC) constitutes a major public health problem as the third most commonly diagnosed and third most lethal malignancy worldwide. The prevalence and the physical accessibility to colorectal tumors have made CRC an ideal model for the study of tumor genetics. Early research efforts using patient derived CRC samples led to the discovery of several highly penetrant mutations (e.g., APC, KRAS, MMR genes) in both hereditary and sporadic CRC tumors. This knowledge has enabled researchers to develop genetically engineered and chemically induced tumor models of CRC, both of which have had a substantial impact on our understanding of the molecular basis of CRC. Despite these advances, the morbidity and mortality of CRC remains a cause for concern and highlight the need to uncover novel genetic drivers of CRC. This review focuses on mouse models of CRC with particular emphasis on a newly developed cancer gene discovery tool, the Sleeping Beauty transposon-based mutagenesis model of CRC. PMID:26811627

  16. Mouse models for the discovery of colorectal cancer driver genes.

    PubMed

    Clark, Christopher R; Starr, Timothy K

    2016-01-14

    Colorectal cancer (CRC) constitutes a major public health problem as the third most commonly diagnosed and third most lethal malignancy worldwide. The prevalence and the physical accessibility to colorectal tumors have made CRC an ideal model for the study of tumor genetics. Early research efforts using patient derived CRC samples led to the discovery of several highly penetrant mutations (e.g., APC, KRAS, MMR genes) in both hereditary and sporadic CRC tumors. This knowledge has enabled researchers to develop genetically engineered and chemically induced tumor models of CRC, both of which have had a substantial impact on our understanding of the molecular basis of CRC. Despite these advances, the morbidity and mortality of CRC remains a cause for concern and highlight the need to uncover novel genetic drivers of CRC. This review focuses on mouse models of CRC with particular emphasis on a newly developed cancer gene discovery tool, the Sleeping Beauty transposon-based mutagenesis model of CRC.

  17. Vasculitis associated with malignancy.

    PubMed

    Mertz, L E; Conn, D L

    1992-02-01

    A large variety of vasculopathic syndromes are uncommonly associated with malignancies. Vasculitis is usually manifested by skin lesions and is generally associated with hematologic malignancies rather than solid tumors. Evidence of autoantibodies, immune complexes, and complement consumption is typically absent. Myelodysplastic syndromes can be confidently linked to vasculitis on the basis of recent literature. The temporal relationship of malignancy to vasculitis development is variable except that vasculitis generally follows the discovery of hairy cell leukemia and splenectomy. Vasculitis may occasionally be a complication of chemotherapy, radiation therapy, and bone marrow transplantation. Occasionally, malignant disorders may mimic vasculitic syndromes. The etiopathogenesis of vasculitis in patients with malignant disorders is unknown. The recent literature on vasculitis and malignancy addresses predominantly case reports and small patient cohorts and identifies clinical characteristics rather than pathogenic mechanisms.

  18. Malignant Vagal Paraganglioma.

    PubMed

    Hamersley, Erin R S; Barrows, Amy; Perez, Angel; Schroeder, Ashley; Castle, James T

    2016-06-01

    Paragangliomas are rare, typically benign neuroendocrine tumors that represent a small portion of head and neck tumors. A small percentage of these are known to have malignant potential. They arise from the carotid body, jugular bulb or vagus nerves. There is limited literature discussing the management of malignant vagal paragangliomas. We present a case of a 25 year old female with a left malignant vagal paraganglioma. The following case presentation will describe the presentation, classic radiologic findings, and management of a malignant vagal paraganglioma along with a review of the literature.

  19. Rheumatic Diseases and Malignancies

    PubMed Central

    BOJINCA, Violeta; JANTA, Iustina

    2012-01-01

    ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments. PMID:23482881

  20. [Sporadic colorectal polyps. Updated guidelines for endoscopic surveillance].

    PubMed

    Björk, Jan; Börjesson, Lars; Hertervig, Erik; Lindmark, Gudrun; Ost, Ake

    2003-08-21

    No surveillance is recommended after radical excision of low-risk adenomas (pedunculated adenoma irrespective of size, sessile adenoma < or = 10 mm, number < or = 2. An endoscopic check-up is recommended 3-6 months after radical excision of high-risk adenomas (sessile adenoma > 10 mm, number > or = 3), as well as after excision of a pedunculated or a sessile adenoma with an unclear resection margin. All above is irrespective of histopathological adenoma classification. An endoscopic check-up is recommended 3 months after radical excision of a highly or moderately differentiated malignant polyp with no sign of invasion into blood or lymph vessels and with a maximum invasion depth stage T1-sm1. Surgical resection is necessary if the malignant polyp is poorly differentiated, and/or invades into blood or lymph vessels, and/or is stage T1-sm3, or is excised with unclear resection margins. Treatment for stage T1-sm2 polyps may be individualized. Individuals with low-risk adenomas and a first degree relative with colorectal cancer, individuals having high-risk adenomas or malignant polyps removed, as well as individuals operated on for colorectal cancer should be subjected to colonoscopy after three years and then every fifth year when < or = 75 years of age.

  1. [Colorectal cancer screening with colonoscopy].

    PubMed

    Pereyra, Lisandro; Gómez, Estanislao J; Mella, José M; Cimmino, Daniel G; Boerr, Luis A

    2013-01-01

    Colorectal cancer is one of the leading causes of cancer death worldwide and also in Argentina. In the past few years colorectal cancer screening has become more popular and colonoscopy has been postulated as the gold standard. In this review we analyzed the evidence supporting this method in contrast with its complications and disadvantages.

  2. Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis

    PubMed Central

    Fugazza, Alessandro; Gaiani, Federica; Carra, Maria Clotilde; Brunetti, Francesco; Lévy, Michaël; Sobhani, Iradj; Azoulay, Daniel; Catena, Fausto; de'Angelis, Gian Luigi; de'Angelis, Nicola

    2016-01-01

    Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett's esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. Although CLE has several promising applications, its use has been limited by its low availability, high cost, and need of specific operator training. Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice. PMID:26989684

  3. Evaluation of Cysteinyl Leukotriene Signaling as a Therapeutic Target for Colorectal Cancer

    PubMed Central

    Burke, Lorraine; Butler, Clare T.; Murphy, Adrian; Moran, Bruce; Gallagher, William M.; O'Sullivan, Jacintha; Kennedy, Breandán N.

    2016-01-01

    Colorectal cancer is the third most common cancer worldwide and is associated with significant morbidity and mortality. Current pharmacotherapy options include cytotoxic chemotherapy, anti-VEGF, and anti-EGFR targeting drugs, but these are limited by toxic side effects, limited responses and ultimately resistance. Cysteinyl leukotriene (CysLT) signaling regulates intestinal homeostasis with mounting evidence suggesting that CysLT signaling also plays a role in the pathogenesis of colorectal cancer. Therefore, CysLT signaling represents a novel target for this malignancy. This review evaluates reported links between CysLT signaling and established hallmarks of cancer in addition to its pharmacological potential as a new therapeutic target. PMID:27709113

  4. Role of laparoscopy in hepatobiliary malignancies

    PubMed Central

    Arumugam, Prabhu; Balarajah, Vickna; Watt, Jennifer; Abraham, Ajit T.; Bhattacharya, Satyajit; Kocher, Hemant M.

    2016-01-01

    The many benefits of laparoscopy, including smaller incision, reduced length of hospital stay and more rapid return to normal function, have seen its popularity grow in recent years. With concurrent improvements in non-surgical cancer management the importance of accurate staging is becoming increasingly important. There are two main applications of laparoscopic surgery in managing hepato-pancreatico-biliary (HPB) malignancy: accurate staging of disease and resection. We aim to summarize the use of laparoscopy in these contexts. The role of staging laparoscopy has become routine in certain cancers, in particular T2 staged, locally advanced gastric cancer, hilar cholangiocarcinoma and non-Hodgkin's lymphoma. For other cancers, in particular colorectal, laparoscopy has now become the gold standard management for resection such that there is no role for stand-alone staging laparoscopy. In HPB cancers, although staging laparoscopy may play a role, with ever improving radiology, its role remains controversial. PMID:27377496

  5. [Phase-II-study with vindesine (desacetyl-vinblastine-amide-sulfate) in advanced malignant diseases].

    PubMed

    Goldhirsch, A; Beer, M; Sonntag, R W; Tschopp, L; Cavalli, F; Ryssel, H J; Brunner, K W

    1980-07-08

    53 patients with advanced and measurable cancerr were treated with vindesine in doses of 3 mg/m2 (pretreated) and 4 mg/m2 (non pretreated) i.v. once weekly. 48 patients are evaluable for response: of 14 patients with squamous cell carcinoma of the lung, 1 partial remission (PR), 1 minor response (MR) and 1 no change (NC) were observed. In 5 patients with large cell carcinoma of the lung: 1 NC. In 3 with adenocarcinoma of the lung: 1 MR. One patient with nasopharyngeal carcinoma had progressive disease. Stable disease was observed in a patient with carcinoma of the tongue and in a patient with adenocarcinoma of the esophagus. Four patients with colorectal carcinoma had progressive disease. One MR was observed in a patient with breast cancer, while all of the other 3 patients had progressive disease. One carcinoma of the penis was stable. One MR was observed in a patient with Hodgkin's disease. One PR was observed in a case with no-Hodgkin's lymphoma. A patient with acute leukemia had progressive disease. Among 9 patients with malignant melanoma, 3 had an MR and 1 patient had stable disease. A patient with fibrosarcoma had progressive disease. Observed toxicity included leukopenia, thrombocytopenia, anemia, paresthesias, constipation, jaw pain, nausea, stomatitis, alopecia, loss of taste, pruritus and skin rash, weakness and fatigue.

  6. CDKL1 promotes tumor proliferation and invasion in colorectal cancer

    PubMed Central

    Qin, Chunzhi; Ren, Li; Ji, Meiling; Lv, Shixu; Wei, Ye; Zhu, Dexiang; Lin, Qi; Xu, Pingping; Chang, Wenju; Xu, Jianmin

    2017-01-01

    Background CDKL1 is a member of the cell division cycle 2 (CDC2)-related serine threonine protein kinase family and is overexpressed in malignant tumors such as melanoma, breast cancer, and gastric cancer. Objective This study aimed to evaluate whether CDKL1 can serve as a potential molecular target for colorectal cancer therapy. Materials and methods Expression of CDKL1 in colorectal cancer tissues and cell lines was measured by immunohistochemistry and Western blot, respectively. To investigate the role of CDKL1 in colorectal cancer, CDKL1-small hairpin RNA-expressing lentivirus was constructed and infected into HCT116 and Caco2 cells. The effects of RNA interference (RNAi)-mediated CDKL1 downregulation on cell proliferation and invasion were assessed by CCK-8, colony formation, transwell, and tumorigenicity assays in nude mice. The effects of CDKL1 downregulation on cell cycle and apoptosis were analyzed by flow cytometry. Furthermore, microarray method and data analysis elucidated the molecular mechanisms underlying the phenomenon. Results CDKL1 protein was overexpressed in colorectal cancer tissues compared with paired normal tissues. Knockdown of CDKL1 in HCT116 and Caco2 significantly inhibited cell growth, colony formation ability, tumor invasion, and G1–S phase transition of the cell cycle. The knockdown of CDKL1 stimulated the upregulation of p15 and retinoblastoma protein. Conclusion CDKL1 plays a vital role in tumor proliferation and invasion in colorectal cancer in vitro and in vivo and, thus, may be considered as a valuable target for therapeutic intervention. PMID:28352193

  7. Differential Measurements of Oxidatively Modified Proteins in Colorectal Adenopolyps

    PubMed Central

    Mehrabi, Sharifeh; Wallace, Lashanale; Cohen, Shakeria; Yao, Xuebiao; Aikhionbare, Felix O.

    2015-01-01

    Introduction Adenopolyps patients have a three-fold higher risk of colon cancer over the general population, which increases to six-fold if the polyps are multiple and with lower survival among African American population. Currently, 6% of CRC can be ascribed to mutations in particular genes. Moreover, the optimal management of patients with colorectal adenopolyps depends on the accuracy of appropriate staging strategies because patients with similar colorectal adenocarcinoma architecture display heterogeneity in the course and outcome of the disease. Oxidative stress, due to an imbalance between reactive oxygen species (ROS) and antioxidant capacities as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids which promote tumor formation. Objective/Method This study applied spectrophotometric, dinitrophenylhydrazone (DNPH) assay, two-dimensional gel electrophoresis, and western blot analyses to assess the levels of oxidatively modified proteins in 41 pairs of primary colorectal tissues including normal/surrounding, adenopolyps (tubular, tubulovillous, villous, polypvillous) and carcinoma. Analysis of variance (ANOVA) and Student’s t-tests were utilized for the resulting data set. Results Our data showed that the levels of reactive protein carbonyl groups significantly increased as colorectal adenopolyps progresses to malignancy. No significant differences were found in the levels of carbonyl proteins between gender samples analyzed. For African American patients, there were, relative to Caucasians, 10% higher levels of reactive carbonyls in proteins of tubulovillous tissue samples (P < 0.05) and over 36% higher in levels in adenocarcinomas (P < 0.05). In normal tissues and tubular, there were no significant differences between the two groups in levels of protein carbonyls. Differences in the levels of protein carbonyl expression within individual patient samples with different number of tumor cells were notably

  8. Musashi2 as a novel predictive biomarker for liver metastasis and poor prognosis in colorectal cancer.

    PubMed

    Zong, Zhen; Zhou, Taicheng; Rao, Liangjun; Jiang, Zhipeng; Li, Yingru; Hou, Zehui; Yang, Bin; Han, Fanghai; Chen, Shuang

    2016-04-01

    Aberrant expression of musashi2 (MSI-2) has been detected in several malignancies. However, its role in the progression of colorectal cancer (CRC) remains unknown. Our study was designed to investigate the expression and prognostic significance of MSI-2 protein in patients with colorectal cancer. The expression of MSI-2 was detected in 164 patients' colorectal cancer and control specimens by the tissue microarray technique and immunohistochemical staining. The correlations between MSI-2 expression and clinicopathological variables including overall survival were analyzed. The prognostic value of liver metastasis is evaluated by logistic regression and receiver operating characteristic (ROC) analysis. MSI-2 was highly expressed in 32.9% (54/164) of the colorectal cancer. Overexpression of MSI-2 was associated with depth of invasion, lymph node metastasis, distant metastasis, liver metastasis, Tumor Node Metastasis (TNM) clinical stage, and Carcinoembryonicantigen (CEA) level (P = 0.040, 0.014, <0.001, <0.001, 0.003, and 0.002, respectively). In the Cox multivariate test, MSI-2 overexpression, lymph node metastasis, and distant metastasis were found to be the independent prognostic factors (P = 0.027, 0.010, and 0.001, respectively). Further logistic regression suggested that TNM stage and MSI-2 high expression were related to liver metastasis in colorectal cancer patients. Conclusively, our study indicates that MSI-2 overexpression is associated with an unfavorable prognosis and may be a potential biomarker for liver metastasis in colorectal cancer patients.

  9. Occupational exposures and colorectal cancers: A quantitative overview of epidemiological evidence

    PubMed Central

    Oddone, Enrico; Modonesi, Carlo; Gatta, Gemma

    2014-01-01

    A traditional belief widespread across the biomedical community was that dietary habits and genetic predisposition were the basic factors causing colorectal cancer. In more recent times, however, a growing evidence has shown that other determinants can be very important in increasing (or reducing) incidence of this malignancy. The hypothesis that environmental and occupational risk factors are associated with colorectal cancer is gaining ground, and high risks of colorectal cancer have been reported among workers in some industrial branches. The aim of this study was to investigate the epidemiologic relationship between colorectal cancer and occupational exposures to several industrial activities, by means of a scientific literature review and meta-analysis. This work pointed out increased risks of colorectal cancer for labourers occupied in industries with a wide use of chemical compounds, such as leather (RR = 1.70, 95%CI: 1.24-2.34), basic metals (RR = 1.32, 95%CI: 1.07-1.65), plastic and rubber manufacturing (RR = 1.30, 95%CI: 0.98-1.71 and RR = 1.27, 95%CI: 0.92-1.76, respectively), besides workers in the sector of repair and installation of machinery exposed to asbestos (RR = 1.40, 95%CI: 1.07-1.84). Based on our results, the estimated crude excess risk fraction attributable to occupational exposure ranged from about 11% to about 15%. However, homogeneous pattern of association between colorectal cancer and industrial branches did not emerge from this review. PMID:25253943

  10. Occupational exposures and colorectal cancers: a quantitative overview of epidemiological evidence.

    PubMed

    Oddone, Enrico; Modonesi, Carlo; Gatta, Gemma

    2014-09-21

    A traditional belief widespread across the biomedical community was that dietary habits and genetic predisposition were the basic factors causing colorectal cancer. In more recent times, however, a growing evidence has shown that other determinants can be very important in increasing (or reducing) incidence of this malignancy. The hypothesis that environmental and occupational risk factors are associated with colorectal cancer is gaining ground, and high risks of colorectal cancer have been reported among workers in some industrial branches. The aim of this study was to investigate the epidemiologic relationship between colorectal cancer and occupational exposures to several industrial activities, by means of a scientific literature review and meta-analysis. This work pointed out increased risks of colorectal cancer for labourers occupied in industries with a wide use of chemical compounds, such as leather (RR = 1.70, 95%CI: 1.24-2.34), basic metals (RR = 1.32, 95%CI: 1.07-1.65), plastic and rubber manufacturing (RR = 1.30, 95%CI: 0.98-1.71 and RR = 1.27, 95%CI: 0.92-1.76, respectively), besides workers in the sector of repair and installation of machinery exposed to asbestos (RR = 1.40, 95%CI: 1.07-1.84). Based on our results, the estimated crude excess risk fraction attributable to occupational exposure ranged from about 11% to about 15%. However, homogeneous pattern of association between colorectal cancer and industrial branches did not emerge from this review.

  11. Practical genetics of colorectal cancer.

    PubMed

    Lynch, Henry T; Shaw, Trudy G

    2013-06-01

    Hereditary colorectal cancer (CRC) is highly heterogeneous, both genotypically and phenotypically. The most frequently occurring hereditary colorectal cancer syndrome is Lynch syndrome, accounting for approximately 3% of the total colorectal cancer burden. Polyposis syndromes, such as familial adenomatous polyposis, account for a lesser percentage. Familial colorectal cancer, defined by family history, occurs in an estimated 20% of all colorectal cancer cases. With a worldwide annual colorectal cancer incidence of over one million, and annual mortality of over 600,000, hereditary and familial forms of colorectal cancer are a major public health problem. Lynch syndrome is attributable to DNA mismatch repair germline mutations, with the MSH2, MLH1, MSH6, and PMS2 genes being implicated. The characteristics of Lynch syndrome-associated colorectal tumors, including early age of onset and predilection to the proximal colon, mandate surveillance by colonoscopy beginning by age 20 to 25 and repeated every other year through age 40 and annually thereafter. Besides colorectal cancer, Lynch syndrome also predisposes to a litany of extracolonic cancers, foremost of which is endometrial cancer, followed by cancer of the ovary, stomach, renal pelvis and ureter, small bowel, hepatobiliary tract, pancreas, glioblastoma multiforme in the Turcot's variant, and sebaceous skin tumors in the Muir-Torre variant and, more recently identified, cancers of the breast and prostate. The most common polyposis syndrome is familial adenomatous polyposis, caused by mutations in the APC gene. Affected individuals have multiple colonic adenomas and, without treatment invariably develop colorectal cancer. Colonic surveillance with polypectomy may be pursued until the appearance of multiple colonic adenomas, at which time prophylactic colectomy should be considered. Extra-intestinal manifestations include desmoid tumor, hepatoblastoma, thyroid carcinoma, and medulloblastoma. Other polyposis

  12. Bronchial malignant melanoma.

    PubMed

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  13. New intracellular and molecular aspects in pathophysiology of colorectal cancer

    PubMed Central

    Ziapour, Payman; Shadifar, Mohammad; Vaillancourt, Cathy; Ahmadi, Ali; Jafari-Sabet, Majid; Ataee, Amin

    2011-01-01

    Colorectal cancer is one of the most common malignancy in the world and the second cancer-related death, many molecular and genetic aspects of this disease have been cleared as chromosomal instability and the role of some key proteins as WNT/β catenin, trypsin and others. Also recently the role of folate turnover and some neurotransmitters as serotonin were also considered. The scope of this review is to describe some details about new molecular pathways suggested for occurrence or progress of this disease. PMID:24834156

  14. Chemoprevention of colorectal cancer

    PubMed Central

    LANGMAN, M; BOYLE, P

    1998-01-01

    Department of Medicine, Queen Elizabeth Hospital, Birmingham B15 2TH, UK P BOYLE Colorectal cancer is the fourth commonest form of cancer in men with 678 000 estimated new cases per year worldwide, representing 8.9% of all new cancers. The disease is most frequent in Occidental countries and particularly so in North America, Australia, New Zealand, and parts of Europe. Prospects for colorectal cancer control are bright and a number of possible approaches could prove fruitful. Among these, pharmaceutical measures seem to be valid and logical approaches to the prevention of colorectal cancer and diminishing its impact. Such approaches could concentrate in primary prevention in at-risk subjects or be applied in altering the course of precursor or established disease. Treatments used must fulfil basic requirements of biological plausibility and safety in continued use in large numbers of subjects. Those available include vitamins and minerals, and other drugs with potential as antioxidants, immune modulators or promoters of cell differentiation or apoptosis. Of the various regimens suggested, vitamin A supplementation may even predispose to adverse outcomes, and antioxidant vitamins in general have no coherent body of evidence to support their use. N-acetylcysteine and ursodeoxycholic acid have promising characteristics but there are as yet no clinical data to support the use of the former in gut epithelial cancer, and formal dose ranging studies must be carried out before the latter is submitted to large scale trial. Folate shows promising characteristics but non-steroidal anti-inflammatory drugs and vitamin D seem the most promising agents. Both seem to reduce the incidence of disease, and to reduce growth rates and/or induce differentiation or apoptosis in gut epithelial cancer cells. Both are also well understood pharmacologically. They may be preferred to newer selective compounds in the same class until these newer compounds are confirmed as safe for widespread

  15. [Genetics of colorectal cancer].

    PubMed

    Balaguer, Francesc

    2013-10-01

    Up to 5% of all cases of colorectal cancer (CRC) are due to a known hereditary syndrome. These hereditary forms often require a high degree of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has important consequences, not only for patients-for whom highly effective preventive measures are available-, but also for their relatives, who may be carriers of the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of these syndromes and in the discovery of new causative genes.

  16. Screening for colorectal cancer.

    PubMed

    Mandel, Jack S

    2008-03-01

    Although there are several methods available for colon cancer screening, none is optimal. This article reviews methods for screening, including fecal occult blood tests, flexible sigmoidoscopy, colonoscopy, CT colonography, capsule endoscopy, and double contrast barium enema. A simple, inexpensive, noninvasive, and relatively sensitive screening test is needed to identify people at risk for developing advanced adenomas or colorectal cancer who would benefit from colonoscopy. It is hoped that new markers will be identified that perform better. Until then we fortunately have a variety of screening strategies that do work.

  17. What's New in Colorectal Cancer Research and Treatment?

    MedlinePlus

    ... Cancer Research? Colorectal Cancer About Colorectal Cancer What’s New in Colorectal Cancer Research? Research is always going ... ways to find colorectal cancer early by studying new types of screening tests and improving the ones ...

  18. Can Colorectal Polyps and Cancer Be Found Early?

    MedlinePlus

    ... Found Early? Why is it important to find colorectal cancer early? Screening is the process of looking for ... Ask Your Doctor About Colorectal Cancer? More In Colorectal Cancer About Colorectal Cancer Causes, Risk Factors, and Prevention ...

  19. Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

    PubMed

    Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

    2014-04-14

    Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

  20. [Hereditary and familial colorectal cancer].

    PubMed

    Balaguer, Francesc

    2014-09-01

    Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes.

  1. [Multidisciplinary therapy of colorectal cancer].

    PubMed

    Balogh, A; Kahán, Z; Maráz, A; Mikó, T; Nagy, F; Palkó, A; Thurzó, L; Tiszlavicz, L

    2001-03-18

    A multidisciplinary program for the treatment of colorectal cancer is described. The main objective of the authors has been to define uniform up to date guidelines based on recent progress in the treatment of colorectal cancer. Preoperative diagnostic procedures are summarized which advance determination of clinical stage and prognosis. These information essentially determine care. Sequences of surgical methods, preoperative and postoperative radiotherapy and medical treatments are discussed according to tumor stages. Guidelines for surveillance following active treatment and recommendation for the screening of population at high risk for colorectal cancer are presented.

  2. A Big Bang model of human colorectal tumor growth.

    PubMed

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

  3. [Colorectal cancer in spouses of colorectal cancer patients].

    PubMed

    Matsumata, T; Shikada, Y; Hasuda, S; Kishihara, F; Suehiro, T; Funahashi, S; Nagamatsu, Y; Iso, Y; Shima, I; Koga, C; Osamura, S; Ueda, M; Furuya, K; Sakino, I

    2000-06-01

    Married couples share home environments and life style for years. In the case of colorectal cancer, an association with insulin resistance was reported. We determined the presence of the insulin-resistance syndrome (IRS, 1 or more of the following: body mass index of > 25 kg/m2, diabetes, or hyperlipidemia) in 84 colorectal cancer patients, of whom 61 patients (73%) had IRS. The incidence of the distal colorectal cancer, which has been declining in the United States, was significantly higher in the IRS group than in the non-IRS group (75.4 vs 52.2%, p = 0.0400). Some mechanisms may promote the progression of mucosal lesions to invasive cancers in the distal colorectum. There were no significant differences with respect to the age (64.6 +/- 9.4 vs 64.3 +/- 11.3 yr, p = 0.8298), height (159 +/- 9 vs 157 +/- 8 cm, p = 0.1375), and body mass index (22.2 +/- 3.6 vs 22.4 +/- 2.7 kg/m2, p = 0.6364) between the patients and their spouses. In 84 couples in whom colorectal cancer develops at least in one may then not illustrate the nursery rhyme: "Jack Sprat could eat no fat, His wife could eat no lean...". The spouses had been married for an average of 38 years, and in 30 spouses who had been followed in a colorectal cancer screening, 5 developed colorectal cancer. To diminish the incidence of colorectal cancer in Japan, we might advise screening colonoscopy to the spouses of colorectal cancer patients, or déjà vu all over again?

  4. Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome

    NASA Astrophysics Data System (ADS)

    Galon, Jérôme; Costes, Anne; Sanchez-Cabo, Fatima; Kirilovsky, Amos; Mlecnik, Bernhard; Lagorce-Pagès, Christine; Tosolini, Marie; Camus, Matthieu; Berger, Anne; Wind, Philippe; Zinzindohoué, Franck; Bruneval, Patrick; Cugnenc, Paul-Henri; Trajanoski, Zlatko; Fridman, Wolf-Herman; Pagès, Franck

    2006-09-01

    The role of the adaptive immune response in controlling the growth and recurrence of human tumors has been controversial. We characterized the tumor-infiltrating immune cells in large cohorts of human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. Collectively, the immunological data (the type, density, and location of immune cells within the tumor samples) were found to be a better predictor of patient survival than the histopathological methods currently used to stage colorectal cancer. The results were validated in two additional patient populations. These data support the hypothesis that the adaptive immune response influences the behavior of human tumors. In situ analysis of tumor-infiltrating immune cells may therefore be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.

  5. Stages of Malignant Mesothelioma

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  6. What Is Malignant Mesothelioma?

    MedlinePlus

    ... you learn about the treatment options and possible side effects, and point you to information and services to help you in your cancer journey. ... free PDFs of our malignant mesothelioma information ...

  7. Asbestos-related malignancy

    SciTech Connect

    Antmann, K.; Aisner, J.

    1986-01-01

    This book contains 20 chapters. Some of the chapter titles are: The Radiology of Asbestosis and Related Neoplasms; Computed Tomography and Malignant Mesothelioma; Radiation Therapy for Pleural Mesothelioma; and Radiation Therapy of Peritoneal Mesothelioma.

  8. Colorectal carcinogenesis-update and perspectives

    PubMed Central

    Raskov, Hans; Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob

    2014-01-01

    Colorectal cancer (CRC) is a very common malignancy in the Western World and despite advances in surgery, chemotherapy and screening, it is still the second leading cause of cancer deaths in this part of the world. Numerous factors are found important in the development of CRC including colonocyte metbolism, high risk luminal environment, inflammation, as well as lifestyle factors such as diet, tobacco, and alchohol consumption. In recent years focus has turned towards the genetics and molecular biology of CRC and several interesting and promising correlations and pathways have been discovered. The major genetic pathways of CRC are the Chromosome Instability Pathway representing the pathway of sporadic CRC through the K-ras, APC, and P53 mutations, and the Microsatellite Instability Pathway representing the pathway of hereditary non-polyposis colon cancer through mutations in mismatch repair genes. To identify early cancers, screening programs have been initiated, and the leading strategy has been the use of faecal occult blood testing followed by colonoscopy in positive cases. Regarding the treatment of colorectal cancer, significant advances have been made in the recent decade. The molecular targets of CRC include at least two important cell surface receptors: the epidermal growth factor receptor and the vascular endothelial growth factor receptor. The genetic and molecular knowledge of CRC has widen the scientific and clinical perspectives of diagnosing and treatment. However, despite significant advances in the understanding and treatment of CRC, results from targeted therapy are still not convincing. Future studies will determine the role for this new treatment modality. PMID:25561783

  9. Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point.

    PubMed

    Arber, Nadir

    2008-08-01

    The limited success of current treatments for most advanced common malignancies highlights the importance of cancer prevention. Clinical trials on cyclooxygenase (COX) inhibitor drugs showed the potential of chemoprevention as a strategy for reducing cancer incidence, although not without associated side effects. The attractiveness of these drugs partly stems from an ability to engage multiple mechanisms of action by their potential to influence multiple components of the carcinogenesis pathway, from initiation to progression. There are two isoforms of the COX enzymes. COX-1 is constitutively expressed in normal tissues and serves as a "housekeeper" of mucosal integrity, whereas COX-2 is an immediate early response gene that is highly inducible by neoplastic and inflammatory stimuli. COX-2 is significantly overexpressed in colorectal neoplasms, making it an attractive therapeutic target. The drug market has been revolutionized by the development of preparations targeted selectively against COX-2, and a proof of concept has been achieved. Chemoprevention of colorectal cancer is already possible with celecoxib, but it is still not the ultimate drug of choice especially because of the cardiovascular risk associated with COX-2 inhibitors. Better patient selection and more effective and safer drugs are needed. Celecoxib is probably best used in a subset of individuals at moderate to high colorectal cancer risk and low risk of cardiovascular disease.

  10. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer.

    PubMed

    Mansilla, Francisco; da Costa, Kerry-Ann; Wang, Shuli; Kruhøffer, Mogens; Lewin, Tal M; Orntoft, Torben F; Coleman, Rosalind A; Birkenkamp-Demtröder, Karin

    2009-01-01

    The alteration of the choline metabolite profile is a well-established characteristic of cancer cells. In colorectal cancer (CRC), phosphatidylcholine is the most prominent phospholipid. In the present study, we report that lysophosphatidylcholine acyltransferase 1 (LPCAT1; NM_024830.3), the enzyme that converts lysophosphatidylcholine into phosphatidylcholine, was highly overexpressed in colorectal adenocarcinomas when compared to normal mucosas. Our microarray transcription profiling study showed a significant (p < 10(-8)) transcript overexpression in 168 colorectal adenocarcinomas when compared to ten normal mucosas. Immunohistochemical analysis of colon tumors with a polyclonal antibody to LPCAT1 confirmed the upregulation of the LPCAT1 protein. Overexpression of LPCAT1 in COS7 cells localized the protein to the endoplasmic reticulum and the mitochondria and increased LPCAT1 specific activity 38-fold. In cultured cells, overexpressed LPCAT1 enhanced the incorporation of [(14)C]palmitate into phosphatidylcholine. COS7 cells transfected with LPCAT1 showed no growth rate alteration, in contrast to the colon cancer cell line SW480, which significantly (p < 10(-5)) increased its growth rate by 17%. We conclude that LPCAT1 may contribute to total choline metabolite accumulation via phosphatidylcholine remodeling, thereby altering the CRC lipid profile, a characteristic of malignancy.

  11. Epigenetic silencing of diacylglycerol kinase gamma in colorectal cancer.

    PubMed

    Kai, Masahiro; Yamamoto, Eiichiro; Sato, Akiko; Yamano, Hiro-O; Niinuma, Takeshi; Kitajima, Hiroshi; Harada, Taku; Aoki, Hironori; Maruyama, Reo; Toyota, Mutsumi; Hatahira, Tomo; Nakase, Hiroshi; Sugai, Tamotsu; Yamashita, Toshiharu; Toyota, Minoru; Suzuki, Hiromu

    2017-02-20

    Diacylglycerol kinases (DGKs) are important regulators of cell signaling and have been implicated in human malignancies. Whether epigenetic alterations are involved in the dysregulation of DGKs in cancer is unknown, however. We therefore analyzed methylation of the promoter CpG islands of DGK genes in colorectal cancer (CRC) cell lines. We found that DGKG, which encodes DGKγ, was hypermethylated in all CRC cell lines tested (n = 9), but was not methylated in normal colonic tissue. Correspondingly, DGKG expression was suppressed in CRC cell lines but not in normal colonic tissue, and was restored in CRC cells by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC). DGKG methylation was frequently observed in primary CRCs (73/141, 51.8%) and was positively associated with KRAS and BRAF mutations and with the CpG island methylator phenotype (CIMP). DGKG methylation was also frequently detected in colorectal adenomas (89 of 177, 50.3%), which suggests it is an early event during colorectal tumorigenesis. Ectopic expression of wild-type DGKγ did not suppress CRC cell proliferation, but did suppress cell migration and invasion. Notably, both constitutively active and kinase-dead DGKγ mutants exerted inhibitory effects on CRC cell proliferation, migration and invasion, and the wild-type and mutant forms of DGKγ all suppressed Rac1 activity in CRC cells. These data suggest DGKG may play a tumor suppressor role in CRC.

  12. Get Tested for Colorectal Cancer

    MedlinePlus

    ... of fiber . Talk with your doctor about taking aspirin every day. Taking aspirin every day can lower your risk of colorectal ... 50 to 59, ask your doctor if daily aspirin is right for you . Previous section Get Tested ...

  13. Lysyl oxidase in colorectal cancer.

    PubMed

    Cox, Thomas R; Erler, Janine T

    2013-11-15

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent advancements in the field of colorectal cancer.

  14. [Surgery in complicated colorectal cancer].

    PubMed

    Kreisler, Esther; Biondo, Sebastiano; Martí-Ragué, Joan

    2006-07-01

    Colorectal cancer continues to have a serious social impact. A large proportion of patients are diagnosed at an advanced stage of the disease. Approximately one-third of patients with colorectal cancer will undergo emergency surgery for a complicated tumor, with a high risk of mortality and poorer long-term prognosis. The most frequent complications are obstruction and perforation, while massive hemorrhage is rare. The curative potential of surgery, whether urgent or elective, depends on how radical the resection is, among other factors. In the literature on the management of urgent colorectal disease, there are few references to the oncological criteria for resection. Uncertainly about the optimal treatment has led to wide variability in the treatment of this entity. The present article aims to provide a critical appraisal of the controversies surrounding the role of surgery and its impact on complicated colorectal cancer.

  15. Tucatinib (ONT-380) and Trastuzumab for Patients With HER2-positive Metastatic Colorectal Cancer (MOUNTAINEER)

    ClinicalTrials.gov

    2017-02-13

    Colorectal Cancer; Colorectal Carcinoma; Colorectal Tumors; Neoplasms, Colorectal; HER-2 Gene Amplification; Metastatic Cancer; Metastatic Colon Cancer; Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum

  16. Lipidome in colorectal cancer

    PubMed Central

    Zhu, Bo; Li, Yongsheng

    2016-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. Understanding its pathophysiology is essential for developing efficient strategies to treat this disease. Lipidome, the sum of total lipids, related enzymes, receptors and signaling pathways, plays crucial roles in multiple cellular processes, such as metabolism, energy storage, proliferation and apoptosis. Dysregulation of lipid metabolism and function contributes to the development of CRC, and can be used towards the evaluation of prognosis. The strategies targeting lipidome have been applied in clinical trails and showed promising results. Here we discuss recent advances in abnormal lipid metabolism in CRC, the mechanisms by which the lipidome regulates tumorigenesis and tumor progression, and suggest potential therapeutic targets for clinical trials. PMID:26967051

  17. Epigenetics of colorectal cancer.

    PubMed

    Goel, Ajay; Boland, C Richard

    2012-12-01

    In the early years of the molecular biology revolution, cancer research was mainly focused on genetic changes (ie, those that altered DNA sequences). Although this has been extremely useful as our understanding of the pathogenesis and biology of cancer has grown and matured, there is another realm in tumor development that does not involve changing the sequence of cellular DNA. This field is called "epigenetics" and broadly encompasses changes in the methylation of cytosines in DNA, changes in histone and chromatin structure, and alterations in the expression of microRNAs, which control the stability of many messenger RNAs and serve as "master regulators" of gene expression. This review focuses on the epigenetics of colorectal cancer and illustrates the impact epigenetics has had on this field.

  18. Robotics in Colorectal Surgery

    PubMed Central

    Weaver, Allison; Steele, Scott

    2016-01-01

    Over the past few decades, robotic surgery has developed from a futuristic dream to a real, widely used technology. Today, robotic platforms are used for a range of procedures and have added a new facet to the development and implementation of minimally invasive surgeries. The potential advantages are enormous, but the current progress is impeded by high costs and limited technology. However, recent advances in haptic feedback systems and single-port surgical techniques demonstrate a clear role for robotics and are likely to improve surgical outcomes. Although robotic surgeries have become the gold standard for a number of procedures, the research in colorectal surgery is not definitive and more work needs to be done to prove its safety and efficacy to both surgeons and patients. PMID:27746895

  19. Colorectal cancer manifesting with metastasis to prolactinoma: report of a case involving symptoms mimicking pituitary apoplexy.

    PubMed

    Thewjitcharoen, Yotsapon; Shuangshoti, Shanop; Lerdlum, Sukalaya; Siwanuwatn, Rungsak; Sunthornyothin, Sarat

    2014-01-01

    Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

  20. [Techniques of thermal ablation in primary hepatic carcinoma and metastatic tumors of colorectal cancer].

    PubMed

    Rudzki, Sławomir; Jamroz, Adam

    2004-01-01

    Liver metastases develop in 30-50 per cent of patients with colorectal cancer. Without treatment, the median survival is approximately 7 months. Recent results from multiple investigations indicate that several minimally invasive treatment techniques are very effective for treating primary and secondary malignant hepatic tumors and they may replace surgical resection in the near future. Thermal ablation techniques for the treatment of primary and secondary malignant hepatic tumors include both freezing (cryoablation) and heating (microwave, laser, and high-intensity focused ultrasound) are characterized in this article.

  1. Wire-guided balloon coloplasty--a new treatment for colorectal strictures?

    PubMed Central

    Banerjee, A K; Walters, T K; Wilkins, R; Burke, M

    1991-01-01

    A new technique for dilatation of colorectal anastomotic strictures--wire-guided balloon coloplasty--is described. It is suitable for high strictures, may be performed without general anaesthetic and is repeatable. It does not require endoscopy and may be used to relieve obstructive symptoms in both benign and malignant strictures so avoiding the need for a defunctioning colostomy. Images Figure 1. Figure 2. Figure 3. PMID:2013892

  2. Primary anorectal malignant melanoma: an uncommon anorectal pathology.

    PubMed

    Juanmartiñena Fernández, José Francisco; Fernández-Urien, Ignacio; Córdoba, Alicia

    2016-09-01

    Anorectal malignant melanoma (AMM) is most common primary melanoma of gastrointestinal tract, accounting for 0.05% and 1% of all colorectal and anal cancers. We reported an 85 year-old woman with no significant past medical history who presented two-month period of rectal bleeding, abdominal pain, tenesmus and 2kg weight-loss. Laboratory markers were unremarkable, although rectal examination revealed two small haemorrhoids and a firm, non-obstructing mass in the lower rectum. Colonoscopy confirmed presence of an ulcerated pigmented neoplasm arising at dental line [A,B]. No distant metastases were found on computed tomography [C] although presented metastatic regional lymph nodes on pelvic MRI [D]. Therefore, abdominoperineal resection was performed, confirming loco-regional disease. Histopathology showed malignant melanoma with positive stains in immunohistochemistry for protein S100, HMB-45 and Melan-A [E,F,G,H] and stained negative for c-Kit.

  3. Colorectal Cancer: The Importance of Early Detection

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer The Importance of Early Detection Past Issues / Summer ... Cancer of the colon or rectum is called colorectal cancer. The colon and the rectum are part of ...

  4. Tests to Detect Colorectal Cancer and Polyps

    MedlinePlus

    ... may trigger unnecessary procedures or follow-up. Does health insurance pay for colorectal cancer screening? The Affordable Care ... other federal laws.) People should check with their health insurance provider to determine their colorectal cancer screening coverage. ...

  5. Genetic Testing for Hereditary Colorectal Cancer

    MedlinePlus

    ... is it Important to Know Your Family Health History? If you have a family health history of colorectal cancer, your doctor may consider your family health history when deciding which colorectal cancer screening might be ...

  6. Identification of a biomarker panel for colorectal cancer diagnosis

    PubMed Central

    2012-01-01

    Background Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955). PMID:22280244

  7. CIRH1A augments the proliferation of RKO colorectal cancer cells.

    PubMed

    Guo, Feng; Chen, Jian-Jun; Tang, Wei-Jun

    2017-03-08

    Accumulating evidence suggests that ribosomal proteins may have extraribosomal functions in various physiological and pathological processes, including cancer. We analyzed the expression of the CIRH1A ribosomal protein in colorectal carcinoma and para-carcinoma samples by bioinformatics analyses of data extracted from The Cancer Genome Atlas and in colorectal cancer cell lines in vitro by qPCR. CIRH1A was highly expressed in carcinoma samples and colorectal cancer cells. We also transduced the RKO colorectal cancer (CRC) cell line with lentivirus-mediated small interfering RNAs (siRNAs) and studied the impact that this knockdown of CIRH1A expression had on cell growth. RNA interference (RNAi)-mediated inhibition of CIRH1A expression significantly suppressed proliferation and increased apoptosis of transduced cells, and tended to arrest them in G1 phase. Our data suggest that CIRH1A plays a critical role in the proliferation, cell cycle distribution, and apoptosis of human malignant colorectal cells, and might therefore be a potential target for therapeutic strategies.

  8. Identification of novel tumor suppressor proteases by degradome profiling of colorectal carcinomas

    PubMed Central

    Fraile, Julia M.; Ordóñez, Gonzalo R.; Quirós, Pedro M.; Astudillo, Aurora; Galván, José A.; Colomer, Dolors; López-Otín, Carlos; Freije, José M.P.; Puente, Xose S.

    2013-01-01

    Proteolytic enzymes play important roles during tumor development and progression through their ability to promote cell growth or by facilitating the invasion of surrounding tissues. The human genome contains more than 570 protease-coding genes, many of them forming functional networks, which has forced the use of global strategies for the analysis of this group of enzymes. In this study, we have designed a new quantitative PCR-based device for profiling the entire degradome in human malignancies. We have used this method to evaluate protease expression levels in colorectal carcinomas with the finding that most proteases with altered expression in these tumors exert their function in the extracellular compartment. In addition, we have found that among genes encoding repressed proteases there was a higher proportion with somatic mutations in colorectal cancer when compared to genes coding for upregulated proteases (14% vs. 4%, p<0.05). One of these genes, MASP3, is consistently repressed in colorectal carcinomas as well as in colorectal cancer cell lines when compared to normal colonic mucosa. Functional analysis of this gene revealed that ectopic expression of MASP3 reduces cell proliferation in vitro and restrains subcutaneous tumor growth, whereas its downregulation induces an increase in the tumorigenic potential of colorectal cancer cells. These results provide new insights into the diversity of proteases associated with cancer and support the utility of degradome profiling to identify novel proteases with tumor-defying functions.

  9. Study on image feature extraction and classification for human colorectal cancer using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Huang, Shu-Wei; Yang, Shan-Yi; Huang, Wei-Cheng; Chiu, Han-Mo; Lu, Chih-Wei

    2011-06-01

    Most of the colorectal cancer has grown from the adenomatous polyp. Adenomatous lesions have a well-documented relationship to colorectal cancer in previous studies. Thus, to detect the morphological changes between polyp and tumor can allow early diagnosis of colorectal cancer and simultaneous removal of lesions. OCT (Optical coherence tomography) has been several advantages including high resolution and non-invasive cross-sectional image in vivo. In this study, we investigated the relationship between the B-scan OCT image features and histology of malignant human colorectal tissues, also en-face OCT image and the endoscopic image pattern. The in-vitro experiments were performed by a swept-source optical coherence tomography (SS-OCT) system; the swept source has a center wavelength at 1310 nm and 160nm in wavelength scanning range which produced 6 um axial resolution. In the study, the en-face images were reconstructed by integrating the axial values in 3D OCT images. The reconstructed en-face images show the same roundish or gyrus-like pattern with endoscopy images. The pattern of en-face images relate to the stages of colon cancer. Endoscopic OCT technique would provide three-dimensional imaging and rapidly reconstruct en-face images which can increase the speed of colon cancer diagnosis. Our results indicate a great potential for early detection of colorectal adenomas by using the OCT imaging.

  10. Combination Therapy of Lactobacillus plantarum Supernatant and 5-Fluouracil Increases Chemosensitivity in Colorectal Cancer Cells.

    PubMed

    An, JaeJin; Ha, Eun-Mi

    2016-08-28

    Colorectal cancer (CRC) is the third most common cancer in the world. Although 5-fluorouracil (5-FU) is the representative chemotherapy drug for colorectal cancer, it has therapeutic limits due to its chemoresistant characteristics. Colorectal cancer cells can develop into cancer stem cells (CSCs) with self-renewal potential, thereby causing malignant tumors. The human gastrointestinal tract contains a complex gut microbiota that is essential for the host's homeostasis. Recently, many studies have reported correlations between gut flora and the onset, progression, and treatment of CRC. The present study confirms that the most representative symbiotic bacteria in humans, Lactobacillus plantarum (LP) supernatant (SN), selectively inhibit the characteristics of 5-FU-resistant colorectal cancer cells (HT-29 and HCT- 116). LP SN inhibited the expression of the specific markers CD44, 133, 166, and ALDH1 of CSCs. The combination therapy of LP SN and 5-FU inhibited the survival of CRCs and led to cell death by inducing caspase-3 activity. The combination therapy of LP SN and 5-FU induced an anticancer mechanism by inactivating the Wnt/β-catenin signaling of chemoresistant CRC cells, and reducing the formation and size of colonospheres. In conclusion, our results show that LP SN can enhance the therapeutic effect of 5-FU for colon cancer, and reduce colorectal cancer stem-like cells by reversing the development of resistance to anticancer drugs. This implies that probiotic substances may be useful therapeutic alternatives as biotherapeutics for chemoresistant CRC.

  11. Identification of novel tumor suppressor proteases by degradome profiling of colorectal carcinomas.

    PubMed

    Fraile, Julia M; Ordóñez, Gonzalo R; Quirós, Pedro M; Astudillo, Aurora; Galván, José A; Colomer, Dolors; López-Otín, Carlos; Freije, José M P; Puente, Xose S

    2013-11-01

    Proteolytic enzymes play important roles during tumor development and progression through their ability to promote cell growth or by facilitating the invasion of surrounding tissues. The human genome contains more than 570 protease-coding genes, many of them forming functional networks, which has forced the use of global strategies for the analysis of this group of enzymes. In this study, we have designed a new quantitative PCR-based device for profiling the entire degradome in human malignancies. We have used this method to evaluate protease expression levels in colorectal carcinomas with the finding that most proteases with altered expression in these tumors exert their function in the extracellular compartment. In addition, we have found that among genes encoding repressed proteases there was a higher proportion with somatic mutations in colorectal cancer when compared to genes coding for upregulated proteases (14% vs. 4%, p<0.05). One of these genes, MASP3, is consistently repressed in colorectal carcinomas as well as in colorectal cancer cell lines when compared to normal colonic mucosa. Functional analysis of this gene revealed that ectopic expression of MASP3 reduces cell proliferation in vitro and restrains subcutaneous tumor growth, whereas its downregulation induces an increase in the tumorigenic potential of colorectal cancer cells. These results provide new insights into the diversity of proteases associated with cancer and support the utility of degradome profiling to identify novel proteases with tumor-defying functions.

  12. Malignant peritoneal mesothelioma

    PubMed Central

    Munkholm-Larsen, Stine; Cao, Christopher Q; Yan, Tristan D

    2009-01-01

    Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. The great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade. PMID:21160794

  13. Malignant Vestibular Schwannoma

    PubMed Central

    Gruber, B.; Petchenik, L.; Williams, M.; Thomas, C.; Luken, M.G.

    1994-01-01

    A 61-year-old woman underwent a translabyrinthine resection of a right intracanulicular acoustic neuroma, which had been detected in the work-up of sudden hearing loss. At the time of surgery, the tumor was roughly twice as large as indicated by the magnetic resonance scan taken only 2 months previously. The tumor eroded the vertical and transverse crests and extended well into the cerebellopontine angle. It was impossible to distinguish the facial nerve proximal to the geniculate ganglion. All visible tumor was resected, along with the facial nerve. Histological evaluation showed a highly cellular tumor, with many mitoses and areas of necrosis, meeting the criteria for malignant schwannoma. The patient has no stigmata of neurofibromatosis, and has no known relatives with that condition. This case is only the fourth reported of a malignant vestibular schwannoma. The relationships between vestibular schwannoma, neurofibromatosis, and malignancy are discussed. ImagesFigure 2Figure 3Figure 4Figure 5Figure 6 PMID:17171176

  14. Giant malignant insulinoma

    PubMed Central

    Karavias, Dimitrios; Habeos, Ioannis; Maroulis, Ioannis; Kalogeropoulou, Christina; Tsamandas, Athanasios; Chaveles, Ioannis

    2015-01-01

    Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed. PMID:25960993

  15. Crohn's disease and colorectal cancer.

    PubMed Central

    Gillen, C D; Andrews, H A; Prior, P; Allan, R N

    1994-01-01

    The colorectal cancer risk in Crohn's disease eliminating all known biases was assessed in a cohort of 281 patients with Crohn's disease who resided in the West Midlands at the time of diagnosis, and were first seen within five years of onset of symptoms between 1945-1975. All patients were 15 years of age or more at onset and were followed up from 12-35 years (total 5213 person years at risk (PYR)). The colorectal cancer risk in the series compared with the risk in the general population was computed by applying sex and age specific PYRs to the date of death or end of the study period 31 December 1991. There were six colonic and two rectal cancers. Six of the eight colorectal cancers were diagnosed 20 or more years after the onset of Crohn's disease. The relative risk (RR) of colorectal cancer for the series as a whole was 3.4 (p < 0.001), with a fivefold excess in the colon, but no significant excess in the rectum. Patients with extensive colitis showed an 18-fold increase in risk (RR = 18.2, p < 0.001), which decreased with increasing age at onset. This study shows that there is a statistical excess risk of developing colorectal cancer in patients who develop their Crohn's disease at a young age of onset (less than 30 years of age). PMID:8200559

  16. Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV

    PubMed Central

    Miranda, M B; Lauseker, M; Kraus, M-P; Proetel, U; Hanfstein, B; Fabarius, A; Baerlocher, G M; Heim, D; Hossfeld, D K; Kolb, H-J; Krause, S W; Nerl, C; Brümmendorf, T H; Verbeek, W; Fauser, A A; Prümmer, O; Neben, K; Hess, U; Mahlberg, R; Plöger, C; Flasshove, M; Rendenbach, B; Hofmann, W-K; Müller, M C; Pfirrmann, M; Hochhaus, A; Hasford, J; Hehlmann, R; Saußele, S

    2016-01-01

    Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63–1.20)) for men and 1.06 (95% CI 0.69–1.55) for women. SIRs were between 0.49 (95% CI 0.13–1.34) for colorectal cancer in men and 4.29 (95% CI 1.09–11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time. PMID:26859076

  17. Leptomeningeal metastasis as initial manifestation of signet ring colorectal adenocarcinoma: a case report with review of literature

    PubMed Central

    Assi, Rita; Hamieh, Lana; Mukherji, Deborah; Haydar, Ali; Temraz, Sally; El-Dika, Imane

    2015-01-01

    Leptomeningeal carcinomatosis (LMC) is an exceedingly rare event especially as a first manifestation of an occult primary colorectal cancer and even when there is a known history of malignancy. Sensorineural hearing loss is by itself an unusual isolated presentation of LMC with unsolved pathophysiology in this setting. In this paper, we report such a case and review the literature for similar cases, focusing on postulated mechanisms of spread. In view of the poor prognosis they carry, we highly recommend that physicians be aware of the risk of rare metastasis from colorectal adenocarcinoma in order to establish an early confirmative diagnosis. PMID:26697206

  18. Cytokine-Induced Modulation of Colorectal Cancer

    PubMed Central

    Mager, Lukas F.; Wasmer, Marie-Hélène; Rau, Tilman T.; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies. PMID:27148488

  19. Malignant tumors of childhood

    SciTech Connect

    Brooks, B.J.

    1986-01-01

    This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children.

  20. Early malignant syphilis*

    PubMed Central

    Ortigosa, Yara Martins; Bendazzoli, Paulo Salomão; Barbosa, Angela Marques; Ortigosa, Luciena Cegatto Martins

    2016-01-01

    Early malignant syphilis is a rare and severe variant of secondary syphilis. It is clinically characterized by lesions, which can suppurate and be accompanied by systemic symptoms such as high fever, asthenia, myalgia, and torpor state. We report a diabetic patient with characteristic features of the disease showing favorable evolution of the lesions after appropriate treatment. PMID:28300925

  1. Hereditary forms of colorectal cancer.

    PubMed

    Castells, Antoni

    2016-09-01

    Colorectal cancer is one of the most frequent neoplasms in western countries; it is the third most common cancer in men after prostate and lung cancer and the second most common in women after breast cancer. Colorectal cancer is usually sporadic but in a small proportion is hereditary. The genetic cause is well established, allowing pre-symptomatic diagnosis in at-risk relatives. The present article reviews the most novel findings presented at the latest meeting of the American Gastroenterological Association on hereditary forms of colorectal cancer, especially Lynch syndrome and MUTYH-associated polyposis, as well as diverse organisational aspects that can favour the correct management of these patients and their relatives.

  2. Nutrients, foods, and colorectal cancer prevention.

    PubMed

    Song, Mingyang; Garrett, Wendy S; Chan, Andrew T

    2015-05-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence.

  3. Nutrients, Foods, and Colorectal Cancer Prevention

    PubMed Central

    Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.

    2015-01-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits and vegetables. Nutrients and foods may also interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of over-nutrition and obesity—risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. PMID:25575572

  4. [New drugs for colorectal cancer].

    PubMed

    Pestalozzi, B C; Jäger, D; Knuth, A

    2004-09-01

    Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to fluorouracil new anticancer drugs like irinotecan and oxaliplatin have become available. The activity of fluorouracil was optimized by using schedules of prolonged infusion. Capecitabine is an oral pro-drug of fluorouracil. When colorectal metastases are limited to the liver they should be resected if possible. Sometimes they can be reduced in size by primary chemotherapy (downstaging) and resected later. Very new and exciting are reports with the monoclonal antibody bevacizumab in combination with chemotherapy. Bevacizumab blocks angiogenesis. So far it is available only in the USA.

  5. Colorectal cancers and chlorinated water.

    PubMed

    El-Tawil, Ahmed Mahmoud

    2016-04-15

    Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. Oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentrations of calcium, magnesium and iron in the public drinking water and prescribing oestrogen in susceptible individuals. Hypo-methylation of genomic DNA could be used as a biological marker for screening for the potential development of colorectal cancers.

  6. Colorectal cancers and chlorinated water

    PubMed Central

    El-Tawil, Ahmed Mahmoud

    2016-01-01

    Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. Oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentrations of calcium, magnesium and iron in the public drinking water and prescribing oestrogen in susceptible individuals. Hypo-methylation of genomic DNA could be used as a biological marker for screening for the potential development of colorectal cancers. PMID:27096035

  7. Iron, microbiota and colorectal cancer.

    PubMed

    Ng, Oliver

    2016-10-01

    Iron deficiency and anaemia are common in colorectal cancer. Replacement with oral or intravenous iron effectively treats this deficiency. However, mechanistic and population studies suggest that excess iron promotes colorectal carcinogenesis. Growing research into gut microbiota and dysbiosis suggests one explanation for this association. Iron is growth limiting for many pathogenic bacteria and may promote a shift in the ratio of pathogenic to protective bacteria. This may increase the toxic bacterial metabolites, promoting inflammation and carcinogenesis. This has important implications as we seek to correct anaemia in our patients.

  8. Colorectal cancer in aged patients. Toward the routine treatment through laparoscopic surgical approach

    PubMed Central

    VECCHIO, R.; MARCHESE, S.; FAMOSO, F.; LA CORTE, F.; MARLETTA, S.; LEANZA, G.; ZANGHÌ, G.; LEANZA, V.; INTAGLIATA, E.

    2015-01-01

    Aim Colorectal cancer is one of the most common malignancies in general population. The incidence seems to be higher in older age. Surgery remains the treatment of choice and laparoscopic approach offers numerous benefits. We report our personal experience in elderly patients operated on for colorectal cancer with laparoscopic resection. Patients and methods From January 2003 to September 2013, out of 160 patients aged 65 years or older and operated with minimally invasive techniques, 30 cases affected by colorectal cancer and operated on with laparoscopic approach were analyzed in this study. Results Male/female ratio was 1.35 and mean age 72 years. Constipation, weight loss, anemia and rectal bleeding were the most commonly reported symptoms. Lesions involved descending-sigmoid colon in 53% of cases, rectum in 37% and ascending colon in 10%. Among laparoscopic colorectal operations laparoscopic left colectomy was the most frequently performed, followed by right colectomy, abdominoperineal resection and Hartmann procedure. Operative times ranged from 3 to 5 hours depending on surgical procedure performed. Mean hospital stay was 6 days (range 4–9). Conversion to open approach occurred only in a case of laparoscopic right colectomy (3%) for uncontrolled bleeding. A single case of mortality was reported. In two cases (7%) anastomotic leakage was observed, conservatively treated in one patient and requiring reoperation in the other one. Conclusions Laparoscopic colorectal surgery is feasible and effective for malignancies in elderly population offering several advantages including immunologic and oncologic ones. However an experienced surgical team is essential in reducing risks and complications. PMID:25827663

  9. p16 Protein is Upregulated in a Stepwise Fashion in Colorectal Adenoma and Colorectal Carcinoma

    PubMed Central

    Al-Ahwal, Mahmoud; Gomaa, Wafaey; Emam, Eman; Qari, Yousif; Buhmeida, Abdelbaset; Radwi, Salman; Al-Maghrabi, Basim; Al-Qahtani, Mohammad; Al-Maghrabi, Jaudah

    2016-01-01

    Background/Aims: p16 is tumor suppressor gene acting as a cell cycle regulator. The present study was conducted to compare p16 expression in normal, dysplastic, and malignant colonic mucosae, and to explore its relation to clinicopathological variables and follow-up data in colorectal carcinoma (CRC). Patients and Methods: Tissue microarrays were performed from 25 normal colonic mucosae, 41 colonic adenomas, and 191 CRC, with corresponding 50 nodal metastases. Immunohistochemistry was performed using anti-p16 antibody, sections were scored, and statistical analysis was performed. K-ras mutation detection was also performed. Results: Immunoexpression of p16 was significantly higher in CRC than in adenomas (P = 0.033) and normal colonic mucosa (P = 0.005). There was no statistically significant difference between p16 expression in CRC and nodal metastasis. There was no significant association between p16 immunoexpression in CRC and all clinicopathological data and survival probability. K-ras mutations were detected in 34% of CRC. However, there was no correlation between K-ras status and p16 expression (P = 0.325). Conclusion: Absence of p16 expression is correlated to a benign course of CRC adenomas. p16 has a key role in CRC progression and can be used as a marker for colorectal adenoma. On the other hand, it has no role as a predictive and/or prognostic factor in CRC. Further extended studies are required to explore the role of p16 as indicator of premalignant lesions in the colon and to test its relation with CRC histological grade, as well as to test its value as a new therapeutic target. PMID:27976639

  10. Immune escape mechanisms in colorectal cancer pathogenesis and liver metastasis.

    PubMed

    Pancione, Massimo; Giordano, Guido; Remo, Andrea; Febbraro, Antonio; Sabatino, Lina; Manfrin, Erminia; Ceccarelli, Michele; Colantuoni, Vittorio

    2014-01-01

    Over the past decade, growing evidence indicates that the tumor microenvironment (TME) contributes with genomic/epigenomic aberrations of malignant cells to enhance cancer cells survival, invasion, and dissemination. Many factors, produced or de novo synthesized by immune, stromal, or malignant cells, acting in a paracrine and autocrine fashion, remodel TME and the adaptive immune response culminating in metastasis. Taking into account the recent accomplishments in the field of immune oncology and using metastatic colorectal cancer (mCRC) as a model, we propose that the evasion of the immune surveillance and metastatic spread can be achieved through a number of mechanisms that include (a) intrinsic plasticity and adaptability of immune and malignant cells to paracrine and autocrine stimuli or genotoxic stresses; (b) alteration of positional schemes of myeloid-lineage cells, produced by factors controlling the balance between tumour-suppressing and tumour-promoting activities; (c) acquisition by cancer cells of aberrant immune-phenotypic traits (NT5E/CD73, CD68, and CD163) that enhance the interactions among TME components through the production of immune-suppressive mediators. These properties may represent the driving force of metastatic progression and thus clinically exploitable for cancer prevention and therapy. In this review we summarize results and suggest new hypotheses that favour the growing impact of tumor-infiltrating immune cells on tumour progression, metastasis, and therapy resistance.

  11. Managing malignant pericardial effusion.

    PubMed Central

    Buzaid, A C; Garewal, H S; Greenberg, B R

    1989-01-01

    The involvement of the pericardium by metastatic tumors is not uncommon, particularly in patients with lung cancer, breast cancer, lymphomas, leukemias, and melanomas. There are five therapeutic modalities for the treatment of malignant pericardial effusion, including pericardiocentesis, pericardial sclerosis, systemic chemotherapy, radiotherapy, and surgical treatment. The optimal treatment selection is dependent principally on a patient's life expectancy; responsiveness of the tumor to chemotherapy, irradiation, or both; and whether or not cardiac tamponade is present at diagnosis. The overall prognosis of patients with malignant pericardial effusion is primarily influenced by the extent and histologic features of the underlying cancer. Although this condition is usually incurable, a reasonable period of useful palliation can be obtained in most patients. Images PMID:2471362

  12. Lymphoscintigraphy in malignant melanoma

    SciTech Connect

    Berman, C.G.; Norman, J.; Cruse, C.W.; Reintgen, D.S.; Clark, R.A. )

    1992-01-01

    The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

  13. Managing Malignant Cerebral Infarction

    PubMed Central

    Sahuquillo, Juan; Sheth, Kevin N.; Kahle, Kristopher T.; Walcott, Brian P.

    2011-01-01

    Opinion statement Managing patients with malignant cerebral infarction remains one of the foremost challenges in medicine. These patients are at high risk for progressive neurologic deterioration and death due to malignant cerebral edema, and they are best cared for in the intensive care unit of a comprehensive stroke center. Careful initial assessment of neurologic function and of findings on MRI, coupled with frequent reassessment of clinical and radiologic findings using CT or MRI are mandatory to promote the prompt initiation of treatments that will ensure the best outcome in these patients. Significant deterioration in either neurologic function or radiologic findings or both demand timely treatment using the best medical management, which may include osmotherapy (mannitol or hypertonic saline), endotracheal intubation, and mechanical ventilation. Under appropriate circumstances, decompressive craniectomy may be warranted to improve outcome or to prevent death. PMID:21190097

  14. Hyaluronan in human malignancies

    SciTech Connect

    Sironen, R.K.; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Kosma, V-M.

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  15. Asbestos-related malignancy

    SciTech Connect

    Talcott, J.A.; Antman, K.H.

    1988-05-01

    Asbestos-associated malignancies have received significant attention in the lay and medical literature because of the increasing frequency of two asbestos-associated tumors, lung carcinoma and mesothelioma; the wide distribution of asbestos; its status as a prototype environmental carcinogen; and the many recent legal compensation proceedings, for which medical testimony has been required. The understanding of asbestos-associated carcinogenesis has increased through study of animal models, human epidemiology, and, recently, the application of modern molecular biological techniques. However, the detailed mechanisms of carcinogenesis remain unknown. A wide variety of malignancies have been associated with asbestos, although the strongest evidence for a causal association is confined to lung cancer and mesothelioma. Epidemiological studies have provided evidence that both the type of asbestos fiber and the industry in which the exposure occurs may affect the rates of asbestos-associated cancers. It has been shown that asbestos exerts a carcinogenic effect independent of exposure to cigarette smoking that, for lung cancers, is synergistically enhanced by smoking. Other questions remain controversial, such as whether pulmonary fibrosis necessarily precedes asbestos-associated lung cancer and whether some threshold level of exposure to asbestos (including low-dose exposures that may occur in asbestos-associated public buildings) may be safe. Mesothelioma, the most closely asbestos-associated malignancy, has a dismal natural history and has been highly resistant to therapy. However, investigational multi-modality therapy may offer benefit to some patients. 179 references.

  16. Malignant Catatonia Mimicking Pheochromocytoma

    PubMed Central

    Li, Dailin

    2013-01-01

    Malignant catatonia is an unusual and highly fatal neuropsychiatric condition which can present with clinical and biochemical manifestations similar to those of pheochromocytoma. Differentiating between the two diseases is essential as management options greatly diverge. We describe a case of malignant catatonia in a 20-year-old male who presented with concurrent psychotic symptoms and autonomic instability, with markedly increased 24-hour urinary levels of norepinephrine at 1752 nmol/day (normal, 89–470 nmol/day), epinephrine at 1045 nmol/day (normal, <160 nmol/day), and dopamine at 7.9 μmol/day (normal, 0.4–3.3 μmol/day). The patient was treated with multiple sessions of electroconvulsive therapy, which led to complete clinical resolution. Repeat urine collections within weeks of this presenting event revealed normalization or near normalization of his catecholamine and metanephrine levels. Malignant catatonia should be considered in the differential diagnosis of the hypercatecholamine state, particularly in a patient who also exhibits concurrent catatonic features. PMID:24251048

  17. Colorectal Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  18. [Systemic therapy for colorectal cancer].

    PubMed

    Pestalozzi, B C; Jäger, D; Knuth, A

    2005-06-01

    Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to the traditional 5-fluorouracil, newer anticancer drugs are available including irinotecan and oxaliplatin. Monoclonal antibodies like bevacizumab and cetuximab have been integrated into modern treatment regimens. Based on randomized clinical trials we can formulate rational treatment strategies as outlined in this article.

  19. Pembrolizumab in Treating Patients With Malignant Mesothelioma

    ClinicalTrials.gov

    2016-11-14

    Biphasic Mesothelioma; Epithelioid Mesothelioma; Peritoneal Malignant Mesothelioma; Pleural Biphasic Mesothelioma; Pleural Epithelioid Mesothelioma; Pleural Malignant Mesothelioma; Pleural Sarcomatoid Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Sarcomatoid Mesothelioma

  20. Epigenetics in the hematologic malignancies

    PubMed Central

    Fong, Chun Yew; Morison, Jessica; Dawson, Mark A.

    2014-01-01

    A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies requires a thorough understanding of the underlying mechanisms of malignant transformation driven by aberrant epigenetic regulators. In this review we provide an overview of the major protagonists in epigenetic regulation, their aberrant role in myeloid malignancies, prognostic significance and potential for therapeutic targeting. PMID:25472952

  1. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

    SciTech Connect

    Bajenova, Olga; Chaika, Nina; Tolkunova, Elena; Davydov-Sinitsyn, Alexander; Gapon, Svetlana; Thomas, Peter; O’Brien, Stephen

    2014-06-10

    Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.

  2. Lipid phosphatase SHIP2 functions as oncogene in colorectal cancer by regulating PKB activation

    PubMed Central

    Hoekstra, Elmer; Das, Asha M.; Willemsen, Marcella; Swets, Marloes; Kuppen, Peter J.K.; van der Woude, Christien J.; Bruno, Marco J.; Shah, Jigisha P.; Hagen, Timo L.M. ten; Chisholm, John D.; Kerr, William G.; Peppelenbosch, Maikel P.; Fuhler, Gwenny M.

    2016-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related death, encouraging the search for novel therapeutic targets affecting tumor cell proliferation and migration. These cellular processes are under tight control of two opposing groups of enzymes; kinases and phosphatases. Aberrant activity of kinases is observed in many forms of cancer and as phosphatases counteract such “oncogenic” kinases, it is generally assumed that phosphatases function as tumor suppressors. However, emerging evidence suggests that the lipid phosphatase SH2-domain-containing 5 inositol phosphatase (SHIP2), encoded by the INPPL1 gene, may act as an oncogene. Just like the well-known tumor suppressor gene Phosphatase and Tensin Homolog (PTEN) it hydrolyses phosphatidylinositol (3,4,5) triphosphate (PI(3,4,5)P3). However, unlike PTEN, the reaction product is PI(3,4)P2, which is required for full activation of the downstream protein kinase B (PKB/Akt), suggesting that SHIP2, in contrast to PTEN, could have a tumor initiating role through PKB activation. In this work, we investigated the role of SHIP2 in colorectal cancer. We found that SHIP2 and INPPL1 expression is increased in colorectal cancer tissue in comparison to adjacent normal tissue, and this is correlated with decreased patient survival. Moreover, SHIP2 is more active in colorectal cancer tissue, suggesting that SHIP2 can induce oncogenesis in colonic epithelial cells. Furthermore, in vitro experiments performed on colorectal cancer cell lines shows an oncogenic role for SHIP2, by enhancing chemoresistance, cell migration, and cell invasion. Together, these data indicate that SHIP2 expression contributes to the malignant potential of colorectal cancer, providing a possible target in the fight against this devastating disease. PMID:27716613

  3. Use of RNA isolated from feces as a promising tool for the early detection of colorectal cancer.

    PubMed

    Bernal, Giuliano

    2012-07-19

    Colorectal cancer is one of the most common forms of cancer worldwide. Early detection would allow patients to be treated surgically and halt the progression of the disease; however, the current methods of early detection are invasive (colonoscopy and sigmoidoscopy) or have low sensitivity (fecal occult blood test). The altered expression of genes in stool samples of patients with colorectal cancer can be determined by RT-PCR. This is a noninvasive and highly sensitive technique for colorectal cancer screening. According to information gathered in this review and our own experience, the use of fecal RNA to determine early alterations in gene expression due to malignancy appears to be a promising alternative to the current detection methods and owing to its low cost could be implemented in public health services.

  4. Epigenetic silencing of NTSR1 is associated with lateral and noninvasive growth of colorectal tumors

    PubMed Central

    Niinuma, Takeshi; Yamano, Hiro-o; Nojima, Masanori; Yoshikawa, Kennjiro; Kimura, Tomoaki; Takagi, Ryo; Harada, Eiji; Harada, Taku; Maruyama, Reo; Sasaki, Yasushi; Tokino, Takashi; Shinomura, Yasuhisa; Sugai, Tamotsu; Imai, Kohzoh; Suzuki, Hiromu

    2015-01-01

    Our aim was to identify DNA methylation changes associated with the growth pattern and invasiveness of colorectal cancers (CRCs). Comparison of the methylation statuses of large (≥20 mm in diameter along the colonic surface) noninvasive tumors (NTs) and small (<20 mm in diameter along the colonic surface) invasive tumors (ITs) using CpG island microarray analysis showed neurotensin receptor 1 (NTSR1) to be hypermethylated in large NTs. Quantitative bisulfite pyrosequencing revealed that NTSR1 is frequently methylated in colorectal tumors, with large NTs exhibiting the highest methylation levels. The higher NTSR1 methylation levels were associated with better prognoses. By contrast, NTSR1 copy number gains were most frequent among small ITs. Methylation of NTSR1 was associated with the gene's silencing in CRC cell lines, whereas ectopic expression of NTSR1 promoted proliferation and invasion by CRC cells. Analysis of primary tumors composed of adenomatous and malignant portions revealed that NTSR1 is frequently methylated in the adenomatous portion, while methylation levels are generally lower in the cancerous portions. These results suggest that NTSR1 methylation is associated with lateral and noninvasive growth of colorectal tumors, while low levels of methylation may contribute to the malignant potential through activation of NTSR1. Our data also indicate that NTSR1 methylation may be a prognostic biomarker in CRC. PMID:26334593

  5. Immunotherapy in human colorectal cancer: Challenges and prospective

    PubMed Central

    Sun, Xuan; Suo, Jian; Yan, Jun

    2016-01-01

    Human colorectal cancer (CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC. In this review, we will discuss important immunological landscape within the CRC microenvironment and introduce immunoscore system to better describe immunophenotyping in CRC. We will also discuss different immunotherapeutic approaches currently utilized in different phases of clinical trials. Some of those completed or ongoing trials are summarized. Finally, we provide a brief prospective on the future human CRC immunotherapy. PMID:27605872

  6. Combined Endoscopic Laparoscopic Surgery Procedures for Colorectal Surgery.

    PubMed

    Placek, Sarah B; Nelson, Jeffrey

    2017-04-01

    Colonoscopy is the standard of care for screening and surveillance of colorectal cancers. Removal of adenomatous polyps prevents the transformation of adenomas to potential adenocarcinoma. While most polyps are amenable to simple endoscopic polypectomy, difficult polyps that are large, broad-based, or located in haustral folds or in tortuous colon segments can present a challenge for endoscopists. Traditionally, patients with endoscopically unresectable polyps have been referred for oncologic surgical resection due to the underlying risk of malignancy within the polyp; however, the majority of these polyps are benign on final pathology. Combined endoscopic laparoscopic surgery can help facilitate endoscopic removal of difficult lesions, or allow the surgeon to select the correct laparoscopic approach for polyp excision. Current literature suggests that these procedures are safe and effective and can potentially save patients from the morbidity of laparotomy and segmental colectomy.

  7. History of allergy and reduced incidence of colorectal cancer, Iowa Women's Health Study.

    PubMed

    Prizment, Anna E; Folsom, Aaron R; Cerhan, James R; Flood, Andrew; Ross, Julie A; Anderson, Kristin E

    2007-11-01

    Previous epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. We studied the association between allergy history and incident colorectal cancer (n=410) prospectively in 21,292 Iowa women followed for 8 years. Allergy was defined from four self-reported questions about physician-diagnosed asthma (a), hay fever (b), eczema or allergy of the skin (c), and other allergic conditions (d). A history of any allergy was inversely associated with incident colorectal cancer: after multivariate adjustment, the hazard ratio (HR) was 0.74 [95% confidence interval (95% CI), 0.59-0.94]. Compared with women with no allergy, women reporting only one of the four types of allergy and women reporting two or more types had HRs of 0.75 (95% CI, 0.56-1.01) and 0.58 (95% CI, 0.37-0.90), respectively (P trend=0.02). The inverse association persisted in analyses restricted to any type of nonasthmatic allergy (HR, 0.73; 95% CI, 0.56-0.95). HRs were similar for rectal and colon cancers as well as for colon subsites: proximal and distal (HRs for any allergy ranged from 0.63 to 0.78 across these end points). Allergy history, which may reflect enhanced immunosurveillance, is associated with a reduced risk of colorectal cancer.

  8. Morphological and quantitative analysis of BCL6 expression in human colorectal carcinogenesis.

    PubMed

    Sena, Paola; Mariani, Francesco; Benincasa, Marta; De Leon, Maurizio Ponz; Di Gregorio, Carmela; Mancini, Stefano; Cavani, Francesco; Smargiassi, Alberto; Palumbo, Carla; Roncucci, Luca

    2014-01-01

    The aim of the present study was to determine whether BCL6 is expressed during malignant transformation of the large bowel and to assess whether, and to what extent, immunoreactivity is related to the different stages of neoplastic progression. Samples of normal colorectal mucosa (n=22), microadenomas (n=22) and colorectal cancer (n=22), were analyzed by immunohistochemistry, immunofluorescence coupled with confocal microscopy and western blotting. Our results clearly outlined the marked increase occurring in both intensity and density of BCL6 protein expression in the normal mucosa-microadenoma-carcinoma sequence. Immunohistochemistry and immunofluorescence analyses showed that BCL6 is expressed at low levels in normal mucosa and increases in microadenoma and in cancer with statistical significance. These results were confirmed by western blotting data. The increasing expression of BCL6 in human colorectal cancer development suggests the involvement of BCL6 in tumor progression, from the earliest stages of carcinogenesis with significant increase in cancer. The enhanced understanding of the biological role of BCL6, previously shown to exert a key role in lymphomagenesis, may lead to a re-evaluation of this protein and may highlight the importance of performing further studies in order to identify novel therapeutic targets for colorectal cancer.

  9. Cancer stem cells in colorectal cancer from pathogenesis to therapy: controversies and perspectives.

    PubMed

    Fanali, Caterina; Lucchetti, Donatella; Farina, Marisa; Corbi, Maddalena; Cufino, Valerio; Cittadini, Achille; Sgambato, Alessandro

    2014-01-28

    Colorectal cancer remains one of the most common and lethal malignancies worldwide despite the use of various therapeutic strategies. A better understanding of the mechanisms responsible for tumor initiation and progression is essential for the development of novel, more powerful therapies. The traditional, so-called "stochastic model" of tumor development, which assumes that each cancer cell is tumorigenic, has been deeply challenged during the past decade by the identification of cancer stem cells (CSCs), a biologically distinct subset of cells within the bulk of tumor mass. This discovery led to the development of the hierarchical model of tumorigenesis which assumes that only CSCs have the ability to initiate tumor growth, both at primary and metastatic sites. This model implies that the elimination of all CSCs is fundamental to eradicate tumors and that failure to do so might be responsible for the occurrence of relapses and/or metastases frequently observed in the clinical management of colorectal cancer patients. Identification and isolation of CSCs is essential for a better understanding of their role in the tumorigenetic process and for the development of CSC-specific therapies. Several methods have been used for this purpose and many efforts have been focused on the identification of specific CSC-surface markers. This review provides an overview of the proposed roles of CSC in human colorectal tumorigenesis focusing on the most important molecules identified as CSC-specific markers in colorectal cancer and on the potential strategies for the development of CSC-targeted therapy.

  10. Quantitative expression analysis and prognostic significance of L-DOPA decarboxylase in colorectal adenocarcinoma

    PubMed Central

    Kontos, C K; Papadopoulos, I N; Fragoulis, E G; Scorilas, A

    2010-01-01

    Background: L-DOPA decarboxylase (DDC) is an enzyme that catalyses, mainly, the decarboxylation of L-DOPA to dopamine and was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of the DDC gene and to evaluate its clinical utility in tissues with colorectal adenocarcinoma. Methods: Total RNA was isolated from colorectal adenocarcinoma tissues of 95 patients. After having tested RNA quality, we prepared cDNA by reverse transcription. Highly sensitive quantitative real-time PCR method for DDC mRNA quantification was developed using the SYBR Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative CT method (2−ΔΔCT). Results: DDC mRNA expression varied remarkably among colorectal tumours examined in this study. High DDC mRNA expression levels were found in well-differentiated and Dukes' stage A and B tumours. Kaplan–Meier survival curves showed that patients with DDC-positive tumours have significantly longer disease-free survival (P=0.009) and overall survival (P=0.027). In Cox regression analysis of the entire cohort of patients, negative DDC proved to be a significant predictor of reduced disease-free (P=0.021) and overall survival (P=0.047). Conclusions: The results of the study suggest that DDC mRNA expression may be regarded as a novel potential tissue biomarker in colorectal adenocarcinoma. PMID:20424616

  11. Clinic-genomic association mining for colorectal cancer using publicly available datasets.

    PubMed

    Liu, Fang; Feng, Yaning; Li, Zhenye; Pan, Chao; Su, Yuncong; Yang, Rui; Song, Liying; Duan, Huilong; Deng, Ning

    2014-01-01

    In recent years, a growing number of researchers began to focus on how to establish associations between clinical and genomic data. However, up to now, there is lack of research mining clinic-genomic associations by comprehensively analysing available gene expression data for a single disease. Colorectal cancer is one of the malignant tumours. A number of genetic syndromes have been proven to be associated with colorectal cancer. This paper presents our research on mining clinic-genomic associations for colorectal cancer under biomedical big data environment. The proposed method is engineered with multiple technologies, including extracting clinical concepts using the unified medical language system (UMLS), extracting genes through the literature mining, and mining clinic-genomic associations through statistical analysis. We applied this method to datasets extracted from both gene expression omnibus (GEO) and genetic association database (GAD). A total of 23,517 clinic-genomic associations between 139 clinical concepts and 7914 genes were obtained, of which 3474 associations between 31 clinical concepts and 1689 genes were identified as highly reliable ones. Evaluation and interpretation were performed using UMLS, KEGG, and Gephi, and potential new discoveries were explored. The proposed method is effective in mining valuable knowledge from available biomedical big data and achieves a good performance in bridging clinical data with genomic data for colorectal cancer.

  12. 3-D visualization and quantitation of microvessels in transparent human colorectal carcinoma [corrected].

    PubMed

    Liu, Yuan-An; Pan, Shien-Tung; Hou, Yung-Chi; Shen, Ming-Yin; Peng, Shih-Jung; Tang, Shiue-Cheng; Chung, Yuan-Chiang

    2013-01-01

    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.

  13. Proteomics for discovery of candidate colorectal cancer biomarkers

    PubMed Central

    Álvarez-Chaver, Paula; Otero-Estévez, Olalla; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers. PMID:24744574

  14. Surgical treatment of advanced colorectal cancer in the elderly.

    PubMed

    Chiappa, Antonio; Zbar, Andrew P; Bertani, Emilio; Biffi, Roberto; Luca, Fabrizio; Pace, Ugo; Viale, Giuseppe; Pruneri, Giancarlo; Orecchia, Roberto; Lazzari, Roberta; Biella, Francesca; Grassi, Carmine; Zampino, Giulia; Fazio, Nicola; Della Vigna, Paolo; Andreoni, Luca; Andreoni, Bruno

    2005-01-01

    The aim of the study was to compare the short and long-term outcomes of older and younger colorectal cancer patients with advanced disease resected with a curative intent. Six hundred and ninety-two patients were analysed. Four hundred and seventy-nine patients were younger than 70 years (Group 1), and 213 were 70 years of age or above (Group 2). The overall perioperative mortality rate in the younger group was 0.8% (n = 7), as against 1.4% (n = 3) in the elderly group (p = NS). The morbidity rates were 35% and 42%, respectively (p = NS). At univariate analysis, the elderly patients had a worse overall survival compared to the younger group, when only patients undergoing postoperative chemo-radiotherapy were considered (54% vs 67% overall survival at 5 years; p = 0.03). Using logistic regression analysis, tumour stage (p < 0.0001) and radicality of surgery (p < 0.0001) correlated significantly with overall survival rates in the elderly. Colorectal surgery for malignancy can be performed safely in the elderly with acceptable morbidity and mortality rates and long-term survival.

  15. Estrogen Receptors and Their Implications in Colorectal Carcinogenesis

    PubMed Central

    Caiazza, Francesco; Ryan, Elizabeth J.; Doherty, Glen; Winter, Desmond C.; Sheahan, Kieran

    2015-01-01

    Upon binding their cognate receptors, ERα (ESR1) and ERβ (ESR2), estrogens activate intracellular signaling cascades that have important consequences for cellular behavior. Historically linked to carcinogenesis in reproductive organs, estrogens have also been implicated in the pathogenesis of different cancer types of non-reproductive tissues including the colon. ERβ is the predominant estrogen receptor expressed in both normal and malignant colonic epithelium. However, during colon cancer progression, ERβ expression is lost, suggesting that estrogen signaling may play a role in disease progression. Estrogens may in fact exert an anti-tumor effect through selective activation of pro-apoptotic signaling mediated by ERβ, inhibition of inflammatory signals and modulation of the tumor microenvironment. In this review, we analyze the estrogen pathway as a possible therapeutic avenue in colorectal cancer, we report the most recent experimental evidence to explain the cellular and molecular mechanisms of estrogen-mediated protection against colorectal tumorigenesis, and we discuss future challenges and potential avenues for targeted therapy. PMID:25699240

  16. Non-invasive diagnostic imaging of colorectal liver metastases

    PubMed Central

    Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone

    2015-01-01

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs. PMID:26217455

  17. Non-invasive diagnostic imaging of colorectal liver metastases.

    PubMed

    Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone

    2015-07-28

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.

  18. Colorectal cancer stem cells.

    PubMed

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  19. Giving AXL the axe: targeting AXL in human malignancy

    PubMed Central

    Gay, Carl M; Balaji, Kavitha; Byers, Lauren Averett

    2017-01-01

    The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers. In the context of malignancy, evidence suggests that AXL overexpression drives wide-ranging processes, including epithelial to mesenchymal transition, tumour angiogenesis, resistance to chemotherapeutic and targeted agents, and decreased antitumor immune response. As a result, AXL is an attractive candidate not only as a prognostic biomarker in malignancy but also as a target for anticancer therapies. Several AXL inhibitors are currently in preclinical and clinical development. This article reviews the structure, regulation, and function of AXL; the role of AXL in the tumour microenvironment; the development of AXL as a therapeutic target; and areas of ongoing and future investigation. PMID:28072762

  20. Oats and bowel disease: a systematic literature review.

    PubMed

    Thies, Frank; Masson, Lindsey F; Boffetta, Paolo; Kris-Etherton, Penny

    2014-10-01

    Whole-grain foods such as oats may protect against colorectal cancer and have benefits on inflammatory bowel disease and coeliac disease. The present study aimed to systematically review the literature describing intervention studies that investigated the effects of oats or oat bran on risk factors for bowel disease. A literature search was conducted using Embase, Medline and the Cochrane library, which identified 654 potential articles. Thirty-eight articles describing twenty-nine studies met the inclusion criteria. Two studies carried out in participants with a history of colorectal adenomas found no effects of increased oat-bran intake on indirect risk makers for colorectal cancer. One of two interventions with oat bran in patients with ulcerative colitis showed small improvements in the patients' conditions. Most of the eleven studies carried out in adults with coeliac disease showed no negative effects of uncontaminated oat consumption. The fourteen studies carried out in volunteers with no history of bowel disease suggest that oats or oat bran can significantly increase stool weight and decrease constipation, but there is a lack of evidence to support a specific effect of oats on bowel function compared with other cereals. A long-term dietary intake of oats or oat bran could benefit inflammatory bowel disorders, but this remains to be proven. A protective effect on colorectal adenoma and cancer incidence has not yet been convincingly shown. The majority of patients with coeliac disease could consume up to 100 g/d of uncontaminated oats, which would increase the acceptability of, and adherence to, a gluten-free diet.

  1. Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

    ClinicalTrials.gov

    2016-08-19

    Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

  2. Prevention of malignant melanoma

    PubMed Central

    Chaidemenos, G; Stratigos, A; Papakonstantinou, M; Tsatsou, F

    2008-01-01

    The results of Primary Prevention programs, aiming at the decrease of melanoma incidence, were less encouraging than those of Secondary prevention which aims at an early diagnosis of malignant melanoma. Australia was the country with the best results obtained in both Prevention strategies, especially in avoiding intense, though intermittent, UV exposure. The success of these programs encouraged health authorities to initiate their application to other disorders. New sunscreens containing substances correcting the UV-damaged DNA may offer a promising result in the decades to come. However, so far no one epidemiological study has proved the prevention of malignant melanoma with the use of sun protecting agents. A meta-analysis verified the connection between melanoma and solarium use. The protective role of vitamin D in the development of prostate, breast and colon cancer was shown in a meta-analysis. The authors, however, suggest that fair-skinned persons should take oral supplementation of vitamin D, instead of exposing themselves to the sun. The Hellenic Society of Dermatology and Venereology published the results of 5-year-prevention programs in Greece. Their favorable results in the early diagnosis of melanoma justify an intense continuation of these efforts. PMID:18923759

  3. General Aspects of Colorectal Cancer

    PubMed Central

    Centelles, Josep J.

    2012-01-01

    Colorectal cancer (CRC) is one of the main causes of death. Cancer is initiated by several DNA damages, affecting proto-oncogenes, tumour suppressor genes, and DNA repairing genes. The molecular origins of CRC are chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). A brief description of types of CRC cancer is presented, including sporadic CRC, hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndromes, familiar adenomatous polyposis (FAP), MYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). Some signalling systems for CRC are also described, including Wnt-β-catenin pathway, tyrosine kinase receptors pathway, TGF-β pathway, and Hedgehog pathway. Finally, this paper describes also some CRC treatments. PMID:23209942

  4. General aspects of colorectal cancer.

    PubMed

    Centelles, Josep J

    2012-01-01

    Colorectal cancer (CRC) is one of the main causes of death. Cancer is initiated by several DNA damages, affecting proto-oncogenes, tumour suppressor genes, and DNA repairing genes. The molecular origins of CRC are chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). A brief description of types of CRC cancer is presented, including sporadic CRC, hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndromes, familiar adenomatous polyposis (FAP), MYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). Some signalling systems for CRC are also described, including Wnt-β-catenin pathway, tyrosine kinase receptors pathway, TGF-β pathway, and Hedgehog pathway. Finally, this paper describes also some CRC treatments.

  5. Stem cells and colorectal carcinogenesis

    PubMed Central

    Stoian, M; Stoica, V; Radulian, G

    2016-01-01

    Abstract Colorectal cancer represents an important cause of mortality and morbidity. Unfortunately, the physiopathology is still under study. There are theories about carcinogenesis and it is known that not only a single factor is responsible for the development of a tumor, but several conditions. Stem cells are a promising target for the treatment of colorectal cancer, along with the environment that has an important role. It has been postulated that mutations within the adult colonic stem cells may induce neoplastic changes. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumor and therefore they are responsible for recurrence. It is important to know that a new way of treatment needs to be found, since these cells are resistant to chemotherapy and radiotherapy. PMID:27713769

  6. Colorectal hepatic metastasis: Evolving therapies

    PubMed Central

    Macedo, Francisco Igor B; Makarawo, Tafadzwa

    2014-01-01

    The approach for colorectal hepatic metastasis has advanced tremendously over the past decade. Multidrug chemotherapy regimens have been successfully introduced with improved outcomes. Concurrently, adjunct multimodal therapies have improved survival rates, and increased the number of patients eligible for curative liver resection. Herein, we described major advancements of surgical and oncologic management of such lesions, thereby discussing modern chemotherapeutic regimens, adjunct therapies and surgical aspects of liver resection. PMID:25067997

  7. The deubiquitinase USP54 is overexpressed in colorectal cancer stem cells and promotes intestinal tumorigenesis.

    PubMed

    Fraile, Julia M; Campos-Iglesias, Diana; Rodríguez, Francisco; Español, Yaiza; Freije, José M P

    2016-11-15

    Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis. In agreement with these results, Usp54 downregulation in mouse melanoma cells inhibits lung metastasis formation. Collectively, this work has uncovered the pro-tumorigenic properties of USP54, highlighting the importance of deubiquitinating enzymes as promising targets for the development of specific anti-cancer therapies.

  8. Lymph node-independent liver metastasis in a model of metastatic colorectal cancer.

    PubMed

    Enquist, Ida B; Good, Zinaida; Jubb, Adrian M; Fuh, Germaine; Wang, Xi; Junttila, Melissa R; Jackson, Erica L; Leong, Kevin G

    2014-03-26

    Deciphering metastatic routes is critically important as metastasis is a primary cause of cancer mortality. In colorectal cancer (CRC), it is unknown whether liver metastases derive from cancer cells that first colonize intestinal lymph nodes, or whether such metastases can form without prior lymph node involvement. A lack of relevant metastatic CRC models has precluded investigations into metastatic routes. Here we describe a metastatic CRC mouse model and show that liver metastases can manifest without a lymph node metastatic intermediary. Colorectal tumours transplanted onto the colonic mucosa invade and metastasize to specific target organs including the intestinal lymph nodes, liver and lungs. Importantly, this metastatic pattern differs from that observed following caecum implantation, which invariably involves peritoneal carcinomatosis. Anti-angiogenesis inhibits liver metastasis, yet anti-lymphangiogenesis does not impact liver metastasis despite abrogating lymph node metastasis. Our data demonstrate direct hematogenous spread as a dissemination route that contributes to CRC liver malignancy.

  9. The deubiquitinase USP54 is overexpressed in colorectal cancer stem cells and promotes intestinal tumorigenesis

    PubMed Central

    Fraile, Julia M.; Campos-Iglesias, Diana; Rodríguez, Francisco; Español, Yaiza; Freije, José M.P.

    2016-01-01

    Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis. In agreement with these results, Usp54 downregulation in mouse melanoma cells inhibits lung metastasis formation. Collectively, this work has uncovered the pro-tumorigenic properties of USP54, highlighting the importance of deubiquitinating enzymes as promising targets for the development of specific anti-cancer therapies. PMID:27769071

  10. The deoxycholic acid targets miRNA-dependent CAC1 gene expression in multidrug resistance of human colorectal cancer.

    PubMed

    Kong, Ying; Bai, Pei-Song; Sun, Hong; Nan, Ke-Jun; Chen, Nan-Zheng; Qi, Xiao-Gai

    2012-12-01

    There is evidence indicating that bile acid is a promoter of colorectal cancer. Deoxycholic acid modifies apoptosis and proliferation by affecting intracellular signaling and gene expression. We are interested in revealing the relationship between deregulated miRNAs and deoxycholic acid in colorectal cancer development. We found that miR-199a-5p was expressed at a low level in human primary colonic epithelial cells treated with deoxycholic acid compared with control, and miR-199a-5p was significantly down-regulated in colorectal cancer tissues. The miR-199a-5p expression in colorectal cancer cells led to the suppression of tumor cell growth, migration and invasion. We further identified CAC1, a cell cycle-related protein expressed in colorectal cancer, as a miR-199a-5p target. We demonstrated that CAC1 is over-expressed in malignant tumors, and cellular CAC1 depletion resulted in cancer growth suppression. HCT-8 cells transfected with a miR-199a-5p mimic or inhibitor had a decrease or increase in CAC1 protein levels, respectively. The results of the luciferase reporter gene analysis demonstrated that CAC1 was a direct miR-199a-5p target. The high miR-199a-5p expression and low CAC1 protein expression reverse the tumor cell drug resistance. We conclude that miR-199a-5p can regulate CAC1 and function as a tumor suppressor in colorectal cancer. Therefore, the potential roles of deoxycholic acid in carcinogenesis are to decrease miR-199a-5p expression and/or increase the expression of CAC1, which contributes to tumorigenesis in patients with CRC. These findings suggest that miR-199a-5p is a useful therapeutic target for colorectal cancer.

  11. The proto-oncogene PBF binds p53 and is associated with prognostic features in colorectal cancer.

    PubMed

    Read, Martin L; Seed, Robert I; Modasia, Bhavika; Kwan, Perkin P K; Sharma, Neil; Smith, Vicki E; Watkins, Rachel J; Bansal, Sukhchain; Gagliano, Teresa; Stratford, Anna L; Ismail, Tariq; Wakelam, Michael J O; Kim, Dae S; Ward, Stephen T; Boelaert, Kristien; Franklyn, Jayne A; Turnell, Andrew S; McCabe, Christopher J

    2016-01-01

    The PTTG1-binding factor (PBF) is a transforming gene capable of eliciting tumor formation in xenograft models. However, the precise role of PBF in tumorigenesis and its prognostic value as a cancer biomarker remain largely uncharacterised, particularly in malignancies outside the thyroid. Here, we provide the first evidence that PBF represents a promising prognostic marker in colorectal cancer. Examination of a total of 39 patients demonstrated higher PBF expression at both the mRNA (P = 0.009) and protein (P < 0.0001) level in colorectal tumors compared to matched normal tissue. Critically, PBF was most abundant in colorectal tumors associated with Extramural Vascular Invasion (EMVI), increased genetic instability (GI) and somatic TP53 mutations, all features linked with recurrence and poorer patient survival. We further demonstrate by glutathione-S-transferase (GST) pull-down and coimmunoprecipitation that PBF binds to the tumor suppressor protein p53, as well as to p53 mutants (Δ126-132, M133K, V197E, G245D, I255F and R273C) identified in the colorectal tumors. Importantly, overexpression of PBF in colorectal HCT116 cells interfered with the transcriptional activity of p53-responsive genes such as mdm2, p21 and sfn. Diminished p53 stability (> 90%; P < 0.01) was also evident with a concurrent increase in ubiquitinated p53. Human colorectal tumors with wild-type TP53 and high PBF expression also had low p53 protein levels (P < 0.05), further emphasizing a putative interaction between these genes in vivo. Overall, these results demonstrate an emerging role for PBF in colorectal tumorigenesis through regulating p53 activity, with implications for PBF as a prognostic indicator for invasive tumors.

  12. National burden of colorectal cancer in Lithuania and the ranking of Lithuania within the 45 European nations.

    PubMed

    Lunevicius, Raimundas; Poskus, Tomas; Samalavicius, Narimantas E

    2015-07-01

    The aim of the present paper was to assess the national burden of colorectal cancer in Lithuania, and to determine the performance of Lithuania for the control of colorectal cancer compared with 45 European nations by ranking. Seven sources of data and information were used. The majority of the findings on disease burden are reported in the present study in the form of the crude and age-standardised incidence, age-specific and age-standardised mortality, disability adjusted life years (DALYs), years lived with disability (YLDs) and years of life lost (YLLs) per 100,000 individuals per year by gender and in the two genders combined between 1990 and 2011. Colorectal cancer was ranked as the 3rd leading cause of disease burden out of all malignancies. Overall, the crude incidence was 35 per 100,000 individuals in 2001 and 51 per 100,000 individuals in 2011 in Lithuania. Incidence and mortality from colorectal cancer varied markedly within Lithuania. The number of DALYs and YLLs slightly declined between 2005 and 2010. YLLs contributed 97% of the total burden due to colorectal cancer in 1990, and 96% in 2010. The mortality rate was 4-5 times higher in males aged 50-54 years than in males aged 45-49. The YLDs per 100,000 individuals per year in Lithuania increased by 61.1% between 1990 and 2010. However, Lithuania was below the average of the Central & Eastern, Southern, Northern and Western regions of Europe. It was concluded that the national colorectal cancer service provision should be amplified and that a programme for the prevention and control of colorectal cancer is required.

  13. Oral potentially malignant disorders: Is malignant transformation predictable and preventable?

    PubMed Central

    van der Waal, Isaäc

    2014-01-01

    Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in regression or even disappearance of the leukoplakia and will diminish the risk of cancer development either at the site of the leukoplakia or elsewhere in the mouth or the upper aerodigestive tract. The debate on the allegedly potentially malignant character of oral lichen planus is going on already for several decades. At present, there is a tendency to accept its potentially malignant behaviour, the annual malignant transformation rate amounting less than 0.5%. As in leukoplakia, there are no reliable predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented either. Follow-up visits, e.g twice a year, may be of some value. It is probably beyond the scope of most dentists to manage patients with these lesions in their own office. Timely referral to a specialist seems most appropriate, indeed. Key words:Oral potentially malignant disorders, oral leukoplakia, oral lichen planus. PMID:24905952

  14. Malignant lymphoma of bone.

    PubMed

    Dürr, Hans Roland; Müller, Peter Ernst; Hiller, Erhard; Maier, Markus; Baur, Andrea; Jansson, Volkmar; Refior, Hans Jürgen

    2002-02-01

    Malignant lymphoma of bone is rare. In many cases, its diagnosis is delayed because of unspecific clinical signs and equivocal radiographs. Therapy in general is multimodal, including surgery and radio- and chemotherapy. Our objective was to demonstrate the clinical and radiological aspects of the lesion to optimize diagnostic approaches and to evaluate treatment and prognostic factors. Thirty-six patients with malignant lymphoma of bone who were surgically treated over a 15-year-period were retrospectively reviewed. Seventeen of them showed a singular bone non-Hodgkin's lymphoma (NHL) which was classified as primary lymphoma of the bone (PLB). In 13 cases, dissemination of the disease with multiple bone or visceral involvement was apparent (dNHL). Six patients suffered from bone involvement due to Hodgkin's disease (HD). Surgical treatment was indicated for diagnostic reasons or complications due to the disease. Radiation and chemotherapy were part of the oncological treatment. The patients' mean age was 57 years. The main symptom in malignant bone lymphoma in 33 patients was pain, with an average duration of 8 months. In the secondary cases, bone involvement appeared on average 57 months after the initial diagnosis. An osteolytic pattern was seen in 58% of the lesions. Soft-tissue involvement was seen in 71% of cases (PLB 80%, dNHL 73%, HD 40%) and was the primary diagnostic sign associated with this disease. The 5-year survival rate was 61% (PLB 88%, dNHL 38%, HD 50%). Multiple vs solitary bone involvement was the most significant factor in the prognosis. Extraskeletal involvement significantly decreased survival. No correlation was found between gender, age, location, or histological subtypes and survival. Bone involvement in NHL appears late in the extraskeletal disease. The clinical appearance is nonspecific, and the delay between the onset of symptoms and diagnosis is often long. One of the major radiologic signs is the existence of a soft-tissue tumor

  15. A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer

    PubMed Central

    Adumeau, Pierre; Carnazza, Kathryn E.; Brand, Christian; Carlin, Sean D.; Reiner, Thomas; Agnew, Brian J.; Lewis, Jason S.; Zeglis, Brian M.

    2016-01-01

    The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans-cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a 64Cu-labeled tetrazine radioligand (64Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful

  16. A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer.

    PubMed

    Adumeau, Pierre; Carnazza, Kathryn E; Brand, Christian; Carlin, Sean D; Reiner, Thomas; Agnew, Brian J; Lewis, Jason S; Zeglis, Brian M

    2016-01-01

    The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as (89)Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans-cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a (64)Cu-labeled tetrazine radioligand ((64)Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful

  17. Malignant Pleural Mesothelioma

    PubMed Central

    Tsao, Anne S.; Wistuba, Ignacio; Roth, Jack A.; Kindler, Hedy Lee

    2009-01-01

    Malignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript. PMID:19255316

  18. Primary pineal malignant melanoma

    PubMed Central

    Cedeño Diaz, Oderay Mabel; Leal, Roberto García; La Cruz Pelea, Cesar

    2011-01-01

    Primary pineal malignant melanoma is a rare entity, with only thirteen cases reported in the world literature to date. We report a case of a 70-year-old man, who consulted with gait disturbance of six months duration, associated in the last month with dizziness, visual abnormalities and diplopia. No other additional melanocytic lesions were found elsewhere. The magnetic resonance showed a 25 mm expansive mass in the pineal gland that was associated with hydrocephaly, ventricular and transependimary oedema. The lesion was partially excised by a supracerebellar infratentorial approach. The histological examination revealed a melanoma. The patient received radiation therapy, but died of disease 16 weeks later. We herein review the literature on this rare tumour and comment on its clinical, radiological and histopathological features and differential diagnosis. PMID:24765293

  19. Tailored Telephone Counseling Increases Colorectal Cancer Screening

    ERIC Educational Resources Information Center

    Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas

    2015-01-01

    To compare the efficacy of two interventions to promote colorectal cancer screening participation and forward stage movement of colorectal cancer screening adoption among first-degree relatives of individuals diagnosed with adenomatous polyps. One hundred fifty-eight first-degree relatives of individuals diagnosed with adenomatous polyps were…

  20. Colorectal cancer in Jordan: prevention and care.

    PubMed

    Ahmad, Muayyad M; Dardas, Latefa; Dardas, Lubna; Ahmad, Huthaifa

    2015-12-01

    The aim of this study was to describe the knowledge, attitudes, and practices toward colorectal cancer prevention and care in Jordan. A survey was designed to produce reliable estimates for the population's knowledge, attitudes, and practices in all 12 governorates of Jordan by using stratified random sampling. A representative sample of the adult population in Jordan completed a comprehensive tool which explored participants' knowledge about the risk factors associated with colorectal cancer, cancer prevention through lifestyle changes, and early cancer diagnosis and screening. According to the participants (n = 3196), colorectal cancer had the second highest percentage of screening recommendation (12.6%) after breast cancer (57.3%). Only 340 individuals (11%) reported ever screening for cancer. About 20% of the participants had heard of one of the screening tests for colorectal cancer. In fact, only 290 (9.1%) participants had performed the colorectal cancer screening tests. This study provides data that will help colorectal cancer prevention and treatment programs and may enhance the efficiency of colorectal cancer-controlling programs. The findings confirm the necessity of starting colorectal screening intervention that targets the most vulnerable individuals.

  1. Best practice in colorectal cancer care.

    PubMed

    Taylor, Claire

    Nurses need up-to-date knowledge of colorectal cancer. This article provides an overview of the aetiology and risk factors for this disease, diagnostic and staging investigations, treatment options and future care. Managing colorectal cancer is complex. Patients can have a range of healthcare needs. Nurses play an increasingly important role in informing, supporting and coordinating care to improve patients' quality of life.

  2. Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway.

    PubMed

    Vasconcelos-Dos-Santos, A; Loponte, H F B R; Mantuano, N R; Oliveira, I A; de Paula, I F; Teixeira, L K; de-Freitas-Junior, J C M; Gondim, K C; Heise, N; Mohana-Borges, R; Morgado-Díaz, J A; Dias, W B; Todeschini, A R

    2017-03-20

    Hyperglycemia is a common feature of diabetes mellitus, considered as a risk factor for cancer. However, its direct effects in cancer cell behavior are relatively unexplored. Herein we show that high glucose concentration induces aberrant glycosylation, increased cell proliferation, invasion and tumor progression of colon cancer. By modulating the activity of the rate-limiting enzyme, glutamine-fructose-6-phosphate amidotransferase (GFAT), we demonstrate that hexosamine biosynthetic pathway (HBP) is involved in those processes. Biopsies from patients with colon carcinoma show increased levels of GFAT and consequently aberrant glycans' expression suggesting an increase of HBP flow in human colon cancer. All together, our results open the possibility that HBP links hyperglycemia, aberrant glycosylation and tumor malignancy, and suggest this pathway as a potential therapeutic target for colorectal cancer.

  3. Primary malignant melanoma of prostate.

    PubMed

    Doublali, M; Chouaib, A; Khallouk, A; Tazi, M F; El Fassi, M J; Farih, My H; Elfatmi, H; Bendahou, M; Benlemlih, A; Lamarti, O

    2010-05-01

    Primary genitourinary melanoma accounts for less than one per cent of all cases of melanoma. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate.

  4. Genetics Home Reference: malignant hyperthermia

    MedlinePlus

    ... 26(5):413-25. Citation on PubMed Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P. Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat. 2006 Oct;27(10):977-89. Review. Citation on PubMed Rosenberg H, Davis M, James D, Pollock N, Stowell K. Malignant ...

  5. Examining the Polymorphisms in the Hypoxia Pathway Genes in Relation to Outcome in Colorectal Cancer

    PubMed Central

    Haja Mohideen, Asan M. S.; Hyde, Angela; Squires, Jessica; Wang, Jing; Dicks, Elizabeth; Younghusband, Ban; Parfrey, Patrick; Green, Roger; Savas, Sevtap

    2014-01-01

    Introduction Colorectal cancer is a common malignancy. Identification of genetic prognostic markers may help prognostic estimations in colorectal cancer. Genes that regulate response to hypoxia and other genes that are regulated under the hypoxic conditions have been shown to play roles in cancer progression. In this study, we hypothesized that genetic variations in the hypoxia pathway genes were associated with the risk of outcome in colorectal cancer patients. Methods This study was performed in two phases. In the first phase, 49 SNPs from six hypoxia pathway genes (HIF1A, HIF1B, HIF2A, LOX, MIF and CXCL12) in 272 colorectal cancer patients were analyzed. In the second phase, 77 SNPs from seven hypoxia pathway genes (HIF1A, HIF1B, HIF2A, HIF2B, HIF3A, LOX and CXCL12) were analyzed in an additional cohort of 535 patients. Kaplan Meier, Cox univariate and multivariable regression analyses were performed to analyze the relationship between the SNPs and overall survival (OS), disease free survival (DFS) or disease specific survival (DSS). Since this was a hypothesis-generating study, no correction for multiple testing was applied. Results In phase I, one SNP (HIF2A rs11125070) was found to be associated with DFS in multivariable analysis; yet association of a proxy polymorphism (HIF2A rs4953342) was not detected in the phase II patient cohort. In phase II, associations of two SNPs (HIF2A rs4953352 and HIF2B rs12593988) were significant in both OS and DFS multivariable analyses. However, association of HIF2A rs4953352 was not replicated in the phase I cohort using a proxy SNP (HIF2A rs6706003). Conclusion Overall, our study did not find a convincing evidence of association of the investigated polymorphisms with the disease outcomes in colorectal cancer. PMID:25405996

  6. Are patients with skin cancer at lower risk of developing colorectal or breast cancer?

    PubMed

    Soerjomataram, I; Louwman, W J; Lemmens, V E P P; Coebergh, J W W; de Vries, E

    2008-06-15

    Ultraviolet exposure may reduce the risk of colorectal and breast cancer as the result of rising vitamin D levels. Because skin cancer is positively related to sun exposure, the authors hypothesized a lower incidence of breast and colorectal cancer after skin cancer diagnosis. They analyzed the incidence of colorectal and breast cancer diagnosed from 1972 to 2002 among 26,916 Netherlands skin cancer patients (4,089 squamous cell carcinoma (SCC), 19,319 basal cell carcinoma (BCC), and 3,508 cutaneous malignant melanoma (CMM)). Standardized incidence ratios were calculated. A markedly decreased risk of colorectal cancer was found for subgroups supposedly associated with the highest accumulated sun exposure: men (standardized incidence ratio (SIR) = 0.83, 95% confidence interval (CI): 0.71, 0.97); patients with SCC (SIR = 0.64, 95% CI: 0.43, 0.93); older patients at SCC diagnosis (SIR = 0.59, 95% CI: 0.37, 0.88); and patients with a SCC or BCC lesion on the head and neck area (SIR = 0.59, 95% CI: 0.36, 0.92 for SCC and SIR = 0.78, 95% CI: 0.63, 0.97 for BCC). Patients with CMM exhibited an increased risk of breast cancer, especially advanced breast cancer (SIR = 2.20, 95% CI: 1.10, 3.94) and older patients at CMM diagnosis (SIR = 1.87, 95% CI: 1.14, 2.89). Study results suggest a beneficial effect of continuous sun exposure against colorectal cancer. The higher risk of breast cancer among CMM patients may be related to socioeconomic class, both being more common in the affluent group.

  7. Identification of carcinoembryonic antigen-producing cells circulating in the blood of patients with colorectal carcinoma by reverse transcriptase polymerase chain reaction.

    PubMed Central

    Jonas, S; Windeatt, S; O-Boateng, A; Fordy, C; Allen-Mersh, T G

    1996-01-01

    BACKGROUND: Application of the reverse transcriptase polymerase chain reaction (RT-PCR) to identification of circulating tumour cells in colorectal cancer. AIMS: To assess whether circulating malignant cells in patients with colorectal liver metastasis could be identified by RT-PCR recognition of mRNA coding for the tumour marker carcinoembryonic antigen (CEA). PATIENTS: A total of 31 with colorectal liver metastases and 22 no-cancer controls. METHODS: Specific cDNA primers for CEA transcripts were used to apply RT-PCR to tissue biopsy specimens, colon carcinoma cell lines, and peripheral blood samples from patients with colorectal liver metastases. A strongly CEA-expressive HT115 colorectal carcinoma cell line was used to spike blood samples from no-cancer control subjects. RESULTS: The limit for detection of CEA cDNA by Southern blotting using HT115 cells was 50 cells per 14 ml of spiked blood. There was a significant difference (p = 0.007) in RT-PCR positive expression between patients with liver metastasis (26/31) compared with controls (5/22). There was no significant relation between the prevalence of CEA cDNA amplification and serum CEA level or metastasis volume in patients with liver metastasis. CONCLUSIONS: This is the first study to suggest that identification of circulating colorectal cancer cells using RT-PCR for detection of CEA cDNA is feasible. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:9014772

  8. Palliation of Obstructing Malignant Colonic Lesions Using Self-Expanding Metal Stents: A Single-Center Experience

    SciTech Connect

    Shrivastava, Vivek; Tariq, Omar; Tiam, ReeNee; Nyhsen, Christiane; Marsh, Ralph

    2008-09-15

    To evaluate the efficacy, risks, and survival after palliative colorectal stenting at a single center, we conducted a retrospective review of consecutive patients who had colorectal self-expanding metal stents (SEMSs) inserted over an 8-year period (September 1998 to September 2006) to relieve an obstructing colorectal tumor. All patients either had proven distant metastases or were unfit for surgical decompression. A single interventional radiologist (R.M.) inserted the stents, which were either Memotherm or WallFlex. Ninety-one patients with a median age of 73 years had a colorectal stent inserted for palliation of an obstructing colorectal malignancy. Technical success was achieved in 81 of 91 (89%) patients, and clinical success in 80 of 81 (99%). At the time of analysis (December 2006), 13 of 91 (14.2%) patients were alive. The patients who died had a median survival of 59 days, IQR 17-181 days. Seven (7/81) patients suffered stent migration, which occurred 10.3 days (IQR, 5-14 days) after the procedure. Three patients (3/81) re-presented with intestinal obstruction secondary to tumor ingrowth and 10 (10.9%) patients suffered bowel perforation. Ten patients (10.9%) had two stents inserted coaxially and overlapping in one procedure. This was performed in cases where the stricture was too long to be easily crossed by a single stent. We conclude that colorectal SEMS is a safe and effective mode of treatment for the palliation of obstructing colorectal cancers, which avoids high-risk surgery.

  9. The New Nitinol Conformable Self-Expandable Metal Stents for Malignant Colonic Obstruction: A Pilot Experience as Bridge to Surgery Treatment

    PubMed Central

    2014-01-01

    Introduction. Self-expandable metal stents (SEMS) are a nonsurgical option for treatment of malignant colorectal obstruction also as a bridge to surgery approach. The new nitinol conformable stent has improved clinical outcomes in these kinds of patients. We report a pilot experience with nitinol conformable SEMS placement as bridge to surgery treatment in patients with colorectal obstruction. Materials and Methods. Between April and August 2012, we collected data on colonic nitinol conformable SEMS placement in a cohort of consecutive symptomatic patients, with malignant colorectal obstruction, who were treated as a bridge to surgery. Technical success, clinical success, and adverse events were recorded. Results. Ten patients (7 male (70%)), with a mean age of 69.2 ± 10.1, were evaluated. The mean length of the stenosis was 3.6 ± 0.6 cm. Five patients (50%) were treated on an emergency basis. The median time from stent placement to surgery was 16 days (interquartile range 7–21). Technical and clinical success was achieved in all patients with a significant early improvement of symptoms. No adverse events due to the SEMS placement were observed. Conclusion. This pilot study confirmed the important role of nitinol conformable SEMS as a bridge to surgery option in the treatment of symptomatic malignant colorectal obstruction. PMID:24526914

  10. Malignant eroticized countertransference.

    PubMed

    Chessick, R D

    1997-01-01

    Gabbard (1994) divided the pathology of therapists, both male and female, who commit sexual boundary violations into those who are psychotic, those who are predatory psychopaths, those engaging in masochistic surrender, and those called "the lovesick therapist." Lovesick therapists are the most common type and manifest crucial narcissistic themes of "a desperate need for validation by their patients, a hunger to be loved and idealized, and a tendency to use patients to regulate their own self-esteem" (p. 127). Among the psychodynamic aspects of this curiously circumscribed area of loss of reality testing that makes it difficult for the therapist to see how self-destructive and harmful such enactment is, are an unconscious reenactment of incestuous longings, a misperception of the patient's wish for maternal nurturance as a sexual overture, enactments of rescue fantasies, a projected idealization of the self of the therapist, a confusion of the therapist's needs with the patient's needs, a fantasy that love is curative, acting out disavowed rage at the patient, or rage at an organization, an institute, or one's training analyst, a manic defense against mourning, a narcissistic fantasy that their sexual affair is an exception, insecurity regarding masculine identity, and assorted primitive preoedipal themes. Gabbard's (1991) erotized countertransference is one variety of what I have termed malignant eroticized countertransference. His variety is a development that occurs under the pressure of the patient's preemptive and compelling expressions of lust and love, the patient's erotic transference. But malignant eroticized countertransference can also occur without the patient having offered any such expressions; it can even occur on first meeting the patient when he or she walks into the office! This is akin to the romantic "love-at-first-sight" theme so favored in the movies and by novelists, but it is always pathological when it occurs in the therapeutic situation

  11. Genotoxicity of Cytolethal Distending Toxin (CDT) on Isogenic Human Colorectal Cell Lines: Potential Promoting Effects for Colorectal Carcinogenesis

    PubMed Central

    Graillot, Vanessa; Dormoy, Inge; Dupuy, Jacques; Shay, Jerry W.; Huc, Laurence; Mirey, Gladys; Vignard, Julien

    2016-01-01

    The composition of the human microbiota influences tumorigenesis, notably in colorectal cancer (CRC). Pathogenic Escherichia coli possesses a variety of virulent factors, among them the Cytolethal Distending Toxin (CDT). CDT displays dual DNase and phosphatase activities and induces DNA double strand breaks, cell cycle arrest and apoptosis in a broad range of mammalian cells. As CDT could promote malignant transformation, we investigated the cellular outcomes induced by acute and chronic exposures to E. coli CDT in normal human colon epithelial cells (HCECs). Moreover, we conducted a comparative study between isogenic derivatives cell lines of the normal HCECs in order to mimic the mutation of three major genes found in CRC genetic models: APC, KRAS, and TP53. Our results demonstrate that APC and p53 deficient cells showed impaired DNA damage response after CDT exposure, whereas HCECs expressing oncogenic KRASV12 were more resistant to CDT. Compared to normal HCECs, the precancerous derivatives exhibit hallmarks of malignant transformation after a chronic exposure to CDT. HCECs defective in APC and p53 showed enhanced anchorage independent growth and genetic instability, assessed by the micronucleus formation assay. In contrast, the ability to grow independently of anchorage was not impacted by CDT chronic exposure in KRASV12 HCECs, but micronucleus formation is dramatically increased. Thus, CDT does not initiate CRC by itself, but may have promoting effects in premalignant HCECs, involving different mechanisms in function of the genetic alterations associated to CRC. PMID:27047802

  12. Unexpected Malignant Diagnosis in Colonic Biopsies: Malignant Transformation of Ovarian Mature Teratomas—Two Case Reports and Review of the Literature

    PubMed Central

    Rojas, Claudia P.; Ganjei-Azar, Parvin; Garcia-Buitrago, Monica T.

    2015-01-01

    Colorectal adenocarcinoma is the second cause of cancer-related deaths in the United States. The occurrence of squamous cell carcinoma in the colorectum is extremely unusual. Malignant transformation from mature cystic teratoma of the ovary is a rare event. The most common transformation is squamous cell carcinoma, followed by adenocarcinoma. It occurs more often in elderly patients, who usually present with advance disease. We report two unusual cases of postmenopausal women diagnosed with squamous cell carcinoma in colon biopsies. After surgical resections, the carcinoma was proven to be the result of malignant transformation of ovarian mature cystic teratomas. Since squamous cell carcinoma of the colorectum is extremely rare, the presence of squamous cell carcinoma in a colonic biopsy in a female patient should alert the clinicians to other possible primary sites, as seen in these cases. PMID:26881165

  13. Malignancy and chronic renal failure.

    PubMed

    Peces, Ramon

    2003-01-01

    Increased incidence of cancer at various sites is observed in patients with end-stage renal disease (ESRD). Certain malignant diseases, such as lymphomas and carcinomas of the kidney, prostate, liver and uterus, show an enhanced prevalence compared with the general population. In particular, renal cell carcinoma (RCC) shows an excess incidence in ESRD patients. A multitude of factors, directly or indirectly associated with the renal disease and the treatment regimens, may contribute to the increased tumor formation in these patients. Patients undergoing renal replacement therapy (RRT) are prone to develop acquired cystic kidney disease (ACKD), which may subsequently lead to the development of RCC. In pre-dialysis patients with coexistent renal disease, as in dialysis and transplant patients, the presence of ACKD may predispose to RCC. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse, are additional risk factors for malignancy. Malignancy following renal transplantation is an important medical problem during the follow-up. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. The type of malignancy is different in various countries and dependent on genetic and environmental factors. Finally, previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and post-malignancy screening.

  14. Danish Colorectal Cancer Group Database

    PubMed Central

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    Aim of database The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. Study population All Danish patients with newly diagnosed colorectal cancer who are either diagnosed or treated in a surgical department of a public Danish hospital. Main variables The database comprises an array of surgical, radiological, oncological, and pathological variables. The surgeons record data such as diagnostics performed, including type and results of radiological examinations, lifestyle factors, comorbidity and performance, treatment including the surgical procedure, urgency of surgery, and intra- and postoperative complications within 30 days after surgery. The pathologists record data such as tumor type, number of lymph nodes and metastatic lymph nodes, surgical margin status, and other pathological risk factors. Descriptive data The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001–2003 to <2% since 2013. Conclusion The database is a national population-based clinical database with high patient and data completeness for the perioperative period. The resolution of data is high for description of the patient at the time of diagnosis, including comorbidities, and for characterizing diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish

  15. Red Meat and Colorectal Cancer.

    PubMed

    Aykan, Nuri Faruk

    2015-02-10

    Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented.

  16. Red Meat and Colorectal Cancer

    PubMed Central

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton) is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented. PMID:26779313

  17. Primary cerebral malignant melanoma

    PubMed Central

    Tang, Kai; Kong, Xiangyi; Mao, Gengsheng; Qiu, Ming; Zhu, Haibo; Zhou, Lei; Nie, Qingbin; Xu, Yi; Du, Shiwei

    2017-01-01

    Abstract Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs. We report an uncommon case of primary cerebral malignant melanoma—a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions. We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers’ reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy. It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors. PMID:28121927

  18. Tailored telephone counseling increases colorectal cancer screening

    PubMed Central

    Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas

    2015-01-01

    To compare the efficacy of two interventions to promote colorectal cancer screening participation and forward stage movement of colorectal cancer screening adoption among first-degree relatives of individuals diagnosed with adenomatous polyps. One hundred fifty-eight first-degree relatives of individuals diagnosed with adenomatous polyps were randomly assigned to receive one of two interventions to promote colorectal cancer screening. Participants received either a tailored telephone counseling plus brochures intervention or a non-tailored print brochures intervention. Data were collected at baseline and 3 months post-baseline. Group differences and the effect of the interventions on adherence and stage movement for colorectal cancer screening were examined using t-tests, chi-square tests, and logistic regression. Individuals in the tailored telephone counseling plus brochures group were significantly more likely to complete colorectal cancer screening and to move forward on stage of change for fecal occult blood test, any colorectal cancer test stage and stage of the risk-appropriate test compared with individuals in the non-tailored brochure group at 3 months post-baseline. A tailored telephone counseling plus brochures intervention successfully promoted forward stage movement and colorectal cancer screening adherence among first-degree relatives of individuals diagnosed with adenomatous polyps. PMID:26025212

  19. Knowledge of colorectal cancer among older persons.

    PubMed

    Weinrich, S P; Weinrich, M C; Boyd, M D; Johnson, E; Frank-Stromborg, M

    1992-10-01

    Cancer screening is a national health priority, especially for colorectal cancer, the second leading cause of death due to cancer in the United States. The researchers measured colorectal cancer knowledge among 211 older Americans. A quasiexperimental pretest-posttest two-by-two factorial design was used to test the effect of knowledge on participation in fecal occult blood screening. The American Cancer Society's colorectal cancer educational slide-tape presentation served as the basis for all of the educational programs. Hemoccult II kits were distributed at no cost to the participants. Descriptive statistics, chi 2, and logistic regressions were used to analyze data. One-half of the participants had incomes below the poverty level. Almost one-half the subjects in the study sample stated that they had not received any information about colorectal cancer within the past year. Caucasians had more knowledge of colorectal cancer than African Americans [F(1, 78) = 7.92, p < 0.01] and persons with higher income had more knowledge than persons with less income [F(2, 76) = 3.01, p = 0.05]. Subjects showed significant increases in colorectal cancer knowledge 6 days after the colorectal cancer education program [t(79) = 2.59, p = 0.01] and this increased knowledge was a predictor of participation in free fecal occult blood screening [chi 2(1, n = 164) = 5.34, p = 0.02].

  20. Familial aggregation of colorectal cancer in Egypt.

    PubMed

    Soliman, A S; Bondy, M L; Levin, B; El-Badawy, S; Khaled, H; Hablas, A; Ismail, S; Adly, M; Mahgoub, K G; McPherson, R S; Beasley, R P

    1998-09-11

    We have investigated the familial aggregation of colorectal cancer and hereditary nonpolyposis colorectal cancer (HNPCC) in Egypt because of the high incidence of colorectal cancer in Egyptian children and young adults and the prevalence of consanguinity there. In a pilot study, we conducted detailed interviews with 111 Egyptian colorectal cancer patients and 111 healthy Egyptian controls about their family histories of colorectal cancer, and other cancers, consanguinity, age at diagnosis, symptoms and recurrence. Eight patients (7.2%) had one or more first- or second-degree relatives under age 40 with colorectal cancer, suggestive of HNPCC by the Amsterdam criteria. One of these families had a typical history of HNPCC, with 4 relatives having colorectal cancer in 3 generations; 3 of these relatives were younger than age 45 at colon cancer diagnosis, and other relatives had extracolonic tumors. Another 14 patients (12.6%) had a first- or second-degree relative with a family history of other neoplasms such as endometrial, urinary and hepatobiliary cancers that could also be related to HNPCC. Four patients with early-onset colon cancer and a family history of other HNPCC-related cancers reported that their parents were first-degree cousins.

  1. Malignant renal tumors in children

    PubMed Central

    Sanchez, Thomas Ray; Wootton-Gorges, Sandra

    2015-01-01

    Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. PMID:28326263

  2. Management of colorectal cancer and diabetes

    PubMed Central

    Yao, Caroline; Nash, Guy F; Hickish, Tamas

    2014-01-01

    Colorectal cancer is associated with diabetes mellitus and both of these common conditions are often managed together by a surgeon. The surgical focus is usually upon cancer treatment rather than diabetes management. The relationship between colorectal cancer and diabetes is a complex one and can raise problems in both diagnosis and the management of patients with both conditions. This literature review explores the relationship between diabetes, diabetic treatment and colorectal cancer and addresses the issues that arise in diagnosing and treating this patient group. By highlighting these difficulties, this review aims to improve understanding and to provide clearer insight into both surgical and non-surgical management. PMID:24334910

  3. Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

    PubMed Central

    Lemoine, Lieselotte; Sugarbaker, Paul; Van der Speeten, Kurt

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Besides the lymphatic and haematogenous routes of dissemination, CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity, which ultimately leads to peritoneal carcinomatosis (PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco-regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However, this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements, involving several well-defined steps, together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor, gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum, subsequently invade the subperitoneal space, where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript, we review current data regarding the molecular mechanisms underlying the development of colorectal PC, with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread. PMID:27678351

  4. [Colonoscopies for colorectal cancer screening].

    PubMed

    Bessa Caserras, Xavier

    2014-09-01

    Colonoscopies play a vital role in population screening programs, either for initial examinations or as a test carried out after a positive result from a fecal occult blood test or sigmoidoscopy. Colonoscopies, and ancillary techniques such as polipectomies, must comply with basic quality criteria that must be reflected in the quality standards of screening programs. A quality colonoscopy is absolutely vital to avoid the occurrence of interval cancers. It is extremely important to detect any proximal lesions during a colonoscopy, especially those which are serrated, because they are difficult to identify and due to the increased risk of colorectal cancer. Regarding follow-up programs for resected colorectal polyps, current evidence of the relationship between the risk of neoplasia and certain variables (age, sex, smoker, BMI, diabetes, etc.) must allow for individualized risk and algorithms for screening and follow-up frequency to be developed for these patients. However, initial endoscopic exploration in a screening colonoscopy is essential to establishing the optimum interval and ensuring follow-up. Despite poor adherence to follow-up programs, mostly due to their overuse, follow-up colonoscopies 3 years after resection of all polypoid lesions detect clinically significant lesions as effectively as colonoscopies at one year.

  5. General Information about Malignant Mesothelioma

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  6. Treatment Option Overview (Malignant Mesothelioma)

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  7. Treatment Options for Malignant Mesothelioma

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  8. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  9. Malignant external otitis: CT evaluation

    SciTech Connect

    Curtin, H.D.; Wolfe, P.; May, M.

    1982-11-01

    Malignant external otitis is an aggressive infection caused by Pseudomonas aeruginosa that most often occurs in elderly diabetics. Malignant external otitis often spreads inferiorly from the external canal to involve the subtemporal area and progresses medially towards the petrous apex leading to multiple cranial nerve palsies. The computed tomographic (CT) findings in malignant external otitis include obliteration of the normal fat planes in the subtemporal area as well as patchy destruction of the bony cortex of the mastoid. The point of exit of the various cranial nerves can be identified on CT scans, and the extent of the inflammatory mass correlates well with the clinical findings. Four cases of malignant external otitis are presented. In each case CT provided a good demonstration of involvement of the soft tissues at the base of the skull.

  10. Predictive Value of POSSUM and ACPGBI Scoring in Mortality and Morbidity of Colorectal Resection: A Case–Control Study

    PubMed Central

    Bremers, A. J. A.; Groenewoud, J. M. M.; van Laarhoven, C. J. H. M.; Bleichrodt, R. P.

    2010-01-01

    Background Preoperative risk prediction to assess mortality and morbidity may be helpful to surgical decision making. The aim of this study was to compare mortality and morbidity of colorectal resections performed in a tertiary referral center with mortality and morbidity as predicted with physiological and operative score for enumeration of mortality and morbidity (POSSUM), Portsmouth POSSUM (P-POSSUM), and colorectal POSSUM (CR-POSSUM). The second aim of this study was to analyze the accuracy of different POSSUM scores in surgery performed for malignancy, inflammatory bowel diseases, and diverticulitis. POSSUM scoring was also evaluated in colorectal resection in acute vs. elective setting. In procedures performed for malignancy, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) score was assessed in the same way for comparison. Methods POSSUM, P-POSSUM, and CR-POSSUM predictor equations for mortality were applied in a retrospective case–control study to 734 patients who had undergone colorectal resection. The total group was assessed first. Second, the predictive value of outcome after surgery was assessed for malignancy (n = 386), inflammatory bowel diseases (n = 113), diverticulitis (n = 91), and other indications, e.g., trauma, endometriosis, volvulus, or ischemia (n = 144). Third, all subgroups were assessed in relation to the setting in which surgery was performed: acute or elective. In patients with malignancy, the ACPGBI score was calculated as well. In all groups, receiver operating characteristic (ROC) curves were constructed. Results POSSUM, P-POSSUM, and CR-POSSUM have a significant predictive value for outcome after colorectal surgery. Within the total population as well as in all four subgroups, there is no difference in the area under the curve between the POSSUM, P-POSSUM, and CR-POSSUM scores. In the subgroup analysis, smallest areas under the ROC curve are seen in operations performed for malignancy, which

  11. The novel colorectal cancer biomarkers CDO1, ZSCAN18 and ZNF331 are frequently methylated across gastrointestinal cancers.

    PubMed

    Vedeld, Hege Marie; Andresen, Kim; Eilertsen, Ina Andrassy; Nesbakken, Arild; Seruca, Raquel; Gladhaug, Ivar P; Thiis-Evensen, Espen; Rognum, Torleiv O; Boberg, Kirsten Muri; Lind, Guro E

    2015-02-15

    We have previously shown that gastrointestinal cancers display similar epigenetic aberrations. In a recent study, we identified frequently methylated genes for cholangiocarcinoma (CDO1, DCLK1, SFRP1 and ZSCAN18), where one of these genes, DCLK1, was also confirmed to be highly methylated in colorectal cancer. The aim of the present study was to determine whether these four genes, in addition to one gene found to be methylated in colon cancer cell lines (ZNF331), are commonly methylated across gastrointestinal malignancies, as well as explore their role as potential biomarkers. Quantitative methylation specific PCR (qMSP) of colorectal cancer (n=164) and normal colorectal mucosa (n=106) samples showed that all genes were frequently methylated in colorectal cancer (71-92%) with little or no methylation in normal mucosa (0-3%). Methylation of minimum two of these five genes identified 95% of the tumors with a specificity of 98%, and an area under the receiver operating characteristics curve (AUC) of 0.98. For gastric (n=25) and pancreatic (n=20) cancer, the same panel detected 92% and 90% of the tumors, respectively. Seventy-four cancer cell lines were further analyzed by qMSP and real time RT-PCR. In addition to the previously reported DCLK1, a high negative correlation between promoter DNA methylation and gene expression was observed for CDO1, ZNF331 and ZSCAN18. In conclusion, the high methylation frequency of these genes in colorectal- as well as in gastric-, pancreatic- and bile duct cancer confirmed an epigenetic similarity between gastrointestinal cancer types, and simultaneously demonstrated their potential as biomarkers, particularly for colorectal cancer detection.

  12. An apple a day may hold colorectal cancer at bay: recent evidence from a case-control study.

    PubMed

    Jedrychowski, Wieslaw; Maugeri, Umberto

    2009-01-01

    Environmental factors play an important role in the etiology of colorectal cancer, the second-most common malignancy in both genders in developed countries. Evidence has shown that potential cancer-inducing oxidative damage might be prevented or restricted largely by the presence of dietary antioxidants of plant origin, such as fruits or vegetables. The protective antioxidant effect of fruits and vegetables has been attributed to flavonoids, a major class of phytochemicals naturally occurring in fruits, vegetables, and various foods of plant origin. Yet, epidemiologic cohort studies relating flavonoid intake to risk of colorectal cancer have been sparse and inconclusive. Apples are a rich source of flavonoids and have the second highest level of antioxidant power among all fruits, with peels having a stronger antioxidant activity than apple flesh. A recent reanalysis of several case-control studies in Italy demonstrated a consistent inverse association between apple consumption and the risk of various cancers, and among them ofcolorectal cancer. Here we assessed the potential protective impact of apples on risk of colorectal cancer in the course of a recently performed hospital-based case-control study in a country with dietary habits very different from those of Mediterranean region. The results showed that highest risk of colorectal cancer was among older persons and those who were residents of villages or small towns. The risk of colorectal cancer was inversely correlated with daily number of apple servings, but the most significant reductions of OR estimates were observed for an intake one or more apple servings daily (OR = 0.37, 95% CI: 0.15-0.91). No other fruit was significantly associated with altering the risk of colorectal cancer.

  13. Telomerase Activation in Hematological Malignancies

    PubMed Central

    Ropio, Joana; Merlio, Jean-Philippe; Soares, Paula; Chevret, Edith

    2016-01-01

    Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT) is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies. PMID:27618103

  14. Primary malignant melanoma of prostate

    PubMed Central

    Doublali, M.; Chouaib, A.; Khallouk, A.; Tazi, M. F.; El Fassi, M. J.; Farih, My. H.; Elfatmi, H.; Bendahou, M.; Benlemlih, A.; Lamarti, O.

    2010-01-01

    Primary genitourinary melanoma accounts for less than one per cent of all cases of melanoma. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate. PMID:20882159

  15. Molecular Diagnosis for Breast Malignancy

    DTIC Science & Technology

    1997-07-01

    AD GRANT NUMBER DAMD17-94-J-4033 TITLE: Molecular Diagnosis for Breast Malignancy PRINCIPAL INVESTIGATOR: Wen-Tien Chen, Ph.D. CONTRACTING...Biomedical Laboratories. - Signature -^yjgf Wen-Tien Chen, Ph.D. Page 4 Molecular diagnosis for breast malignancy (1) FRONT COVER: (2) SF 298...June 8-9, 1995 (abstract). Chen, W.-T, Goldstein LA, Pineiro-Sänchez M, Howard L, Ghersi G, Salamone M, Flessate D, Yeh Y. 1977. " Molecular Diagnosis for

  16. Malignant tumours after renal transplantation.

    PubMed

    Fahlenkamp, D; Reinke, P; Kirchner, S; Schnorr, D; Lindeke, A; Loening, S A

    1996-10-01

    In 1243 patients after renal transplantation, 39 malignant tumours were detected in 37 patients. The average latency period between transplantation and tumour disease was 72 months. Tumours included 8 malignant lymphomas, 7 dermatomas and 24 visceral tumours. The patients who developed a tumour had received fewer blood transfusions before transplantation than a tumour-free control group of 60 patients with renal transplants. Rejection crises occurred in a significantly smaller number of tumour patients compared with the control group.

  17. Multiple malignancies in a female patient with common variable immunodeficiency syndrome.

    PubMed

    Todorovic, Milena; Balint, Bela; Andjelic, Bosko; Mihaljevic, Biljana

    2014-10-01

    We herein present the case of a 55-year-old woman with a previous history of malignancies--uterine adenocarcinoma, basal cell carcinoma (which occurred twice consecutively), recurrent respiratory infections due to common variable immunodeficiency (CVID), and systemic granulomatous disease diagnosed at a later age. The patient suffered from diffuse large B cell lymphoma (DLBCL), which was successfully treated with R-CHOP chemotherapy, and continued with immunoglobulin supplementation. The patient was free of lymphoma and infectious complications for over 20 months despite her persistent immunodeficiency, but eventually developed colorectal adenocarcinoma. To the best of our knowledge, this is the first reported case of CVID associated with multiple solid tumours and DLBCL.

  18. Analysis of risk factors associated with complications of colonic stenting for malignant obstruction.

    PubMed

    Dindar, Gokhan; Ustundag, Yucel; Karakan, Tarkan

    2014-07-21

    Self expanding metalic stent (SEMS) application can cause serious problems up to one third of the patients and some studies reported negative effect of SEMSs on survival in patients with malignancy. The SEMS type especially the rigid one like Wall-stent rather than more flexible type Ultraflex was also reported to have bad impact on the risk of perforation we believe that stent based management protocol for patients with non-perforating left sided obstructing colorectal cancer is a complex method that needs qualified medical and technical team.

  19. Analysis of risk factors associated with complications of colonic stenting for malignant obstruction

    PubMed Central

    Dindar, Gokhan; Ustundag, Yucel; Karakan, Tarkan

    2014-01-01

    Self expanding metalic stent (SEMS) application can cause serious problems up to one third of the patients and some studies reported negative effect of SEMSs on survival in patients with malignancy. The SEMS type especially the rigid one like Wall-stent rather than more flexible type Ultraflex was also reported to have bad impact on the risk of perforation we believe that stent based management protocol for patients with non-perforating left sided obstructing colorectal cancer is a complex method that needs qualified medical and technical team. PMID:25083098

  20. Selective internal radiation therapy (SIRT) for liver metastases secondary to colorectal adenocarcinoma

    SciTech Connect

    Welsh, James S. . E-mail: welsh@humonc.wisc.edu; Kennedy, Andrew S.; Thomadsen, Bruce

    2006-10-01

    Introduction: Selective internal radiation therapy (SIRT) is a relatively new commercially available microbrachytherapy technique for treatment of malignant hepatic lesions using {sup 9}Y embedded in resin microspheres, which are infused directly into the hepatic arterial circulation. It is FDA approved for liver metastases secondary to colorectal carcinoma and is under investigation for treatment of other liver malignancies, such as hepatocellular carcinoma and neuroendocrine malignancies. Materials/Methods: A modest number of clinical trials, preclinical animal studies, and dosimetric studies have been reported. Here we review several of the more important results. Results: High doses of beta radiation can be selectively delivered to tumors, resulting in impressive local control and survival rates. Ex vivo analyses have shown that microspheres preferentially cluster around the periphery of tumor nodules with a high tumor:normal tissue ratio of up to 200:1. Toxicity is usually mild, featuring fatigue, anorexia, nausea, abdominal discomfort, and slight elevations of liver function tests. Conclusions: Selective internal radiation therapy represents an effective means of controlling liver metastases from colorectal adenocarcinoma. Clinical trials have demonstrated improved local control of disease and survival with relatively low toxicity. Investigations of SIRT for other hepatic malignancies and in combination with newer chemotherapy agents and targeted biologic therapies are under way or in planning. A well-integrated team involving interventional radiology, nuclear medicine, medical oncology, surgical oncology, medical physics, and radiation oncology is essential for a successful program. Careful selection of patients through the combined expertise of the team can maximize therapeutic efficacy and reduce the potential for adverse effects.

  1. Immune Modulation in Hematologic Malignancies

    PubMed Central

    Dhodapkar, Madhav V.; Dhodapkar, Kavita M.

    2015-01-01

    The therapeutic potential of the immune system in the context of hematologic malignancies has long been appreciated particularly due to the curative impact of allogeneic hematopoietic stem cell transplantation. The role of immune system in shaping the biology and evolution of these tumors is now well recognized. While the contribution of the immune system in anti-tumor effects of certain therapies such as immune-modulatory drugs and monoclonal antibodies active in hematologic malignancies is quite evident, the immune system has also been implicated in anti-tumor effects of other targeted therapies. The horizon of immune-based therapies in hematologic malignancies is rapidly expanding with promising results from immune-modulatory drugs, immune-checkpoint blockade and adoptive cellular therapies, including genetically-modified T cells. Hematologic malignancies present distinct issues (relative to solid tumors) for the application of immune therapies due to differences in cell of origin/developmental niche of tumor cells, and patterns of involvement such as common systemic involvement of secondary lymphoid tissues. This article discusses the rapidly changing landscape of immune modulation in hematologic malignancies and emphasizes areas wherein hematologic malignancies present distinct opportunities for immunologic approaches to prevent or treat cancer. PMID:26320065

  2. Pulmonary nodules and metastases in colorectal cancer.

    PubMed

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i.e. synchronous metastases. Most common are hepatic metastases followed by pulmonary involvement. The optimal staging modality for detecting synchronous pulmonary metastases is debated. It has been argued, that synchronous pulmonary metastases (SPCM) are rare in CRC and that the consequence of detecting SPCM is minimal. Furthermore, the current staging practice is complicated by a high number of incidental findings on the thoracic CT, so-called indeterminate pulmonary nodules (IPN). IPN can potentially represent SPCM. The purpose of this thesis was to estimate the prevalence, characteristics and clinical significance of IPN and SPCM detected at the primary staging in CRC. Study I was a systematic review of published studies on IPN in CRC focusing on the prevalence and radiological characteristics of IPN proving to be malignant. This knowledge would be of value in management strategies for IPN. On average 9% of all patients staged with a thoracic CT had IPN, however, the prevalence varied significantly between patients series. This was mainly attributed to varying/lacking definitions on IPN and variable radiological expertise in the assessment of the scans. Data were too inconsistently reported in the case series for a robust statement to be made on potential radiological characteristics suggestive of malignancy in IPN. Lymph node metastasis was the most common clinicopathological finding associated with malignancy of IPN. In conclusion, one patient of every 100 scanned patients had an IPN proving to a SPCM at follow-up, but we found no evidence that IPN should result in intensified diagnostic work-up besides routine follow-up for CRC. Study II was an analysis of the

  3. Human Blood Autoantibodies in the Detection of Colorectal Cancer

    PubMed Central

    Negm, Ola H.; Hamed, Mohamed R.; Schoen, Robert E.; Whelan, Richard L.; Steele, Robert J.; Scholefield, John; Dilnot, Elizabeth M.; Shantha Kumara, H. M. C.; Robertson, John F. R.; Sewell, Herbert F.

    2016-01-01

    Colorectal cancer (CRC) is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls) from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls) and 20 sera from Dundee, UK (10 CRC and 10 controls) were tested against a panel of multiple tumour-associated antigens (TAAs) using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19), stage II (n = 40), stage III (n = 34) and stage IV (n = 6) was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively), with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice. PMID:27383396

  4. Meat intake and the recurrence of colorectal adenomas.

    PubMed

    Mathew, A; Sinha, R; Burt, R; Caan, B; Paskett, E; Iber, F; Kikendall, W; Lance, P; Shike, M; Weissfeld, J; Schatzkin, A; Lanza, E

    2004-06-01

    A large multicenter randomized controlled trial was re-assessed to check whether meat intake and a reduction in its consumption are associated with recurrence of adenomatous polyps of the large bowel, which are precursors of most colorectal malignancies. All subjects (n = 1905; 958 interventions and 947 controls) had one or more histologically confirmed colorectal adenomas removed during a colonoscopy within 6 months before randomization. The subjects were followed-up for approximately 4 years after randomization and a colonoscopy for detecting adenomas was conducted at the 1st and 4th year after randomization. Dietary variables were assessed at baseline (T0) and in conjunction with annual visits at the end of the 1st (T1), 2nd (T2), 3rd (T3) and 4th (T4) years. Odds ratios using logistic regression models for meat variables were estimated based on the average intake at T0, T1, T2, T3 and T4 (prior to the T4 colonoscopy) as well as change (T0-T4) in intake. In the intervention group, the total reduction in median intake of red meat from T0 to T4 was observed by the end of 1st year itself (30 and 31% for men and women, respectively). The analysis provide no evidence to suggest that lower intake or reduction in total and in red meat consumption during a period of 4 years reduces the risk of adenoma recurrence (including multiple or advanced adenoma), whereas the data suggest that high intake of fish is associated with lower risk of adenoma recurrence.

  5. Clinical impact of PAI 1 4G/5G gene polymorphism in colorectal carcinoma patients.

    PubMed

    Halamkova, J; Kiss, I; Pavlovsky, Z; Tomasek, J; Jarkovsky, J; Cech, Z; Bednarova, D; Tucek, S; Hanakova, L; Moulis, M; Zavrelova, J; Man, M; Benda, P; Robek, O; Kala, Z; Penka, M

    2013-01-01

    Plasminogen activator ihnibitor (PAI 1) belongs to the plasminogen activator system, which is part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumors. Its plasma level is normally low but 4G/4G homozygotes have higher concentrations of PAI 1. This genotype may be associated with worse prognosis and proximal location of colorectal cancer than 5G/5G homozygotes. In our prospective evaluation we examined plasma level PAI 1 (using photometric microplate method ELISA) pre-surgery and, subsequently, 6-8 weeks later, from 80 patients. For the PAI 1 rs1799889 -675 4G/5G polymorphism test the PCR amplification was used.Analysis of collected data was confirmed that significantly higher plasma levels of PAI 1 were found in patients before starting therapy, which decreased (p=0.004) after initiation of treatment. Patients with higher plasma level PAI 1 before (p=0.013) and after therapy (p=0.004) had significantly shorter survival. We found no relationship between polymorphisms of PAI 1 (-675 4G/5G) in relation to stage, survival or tumor location. PAI 1 is useful as a negative marker of prognosis and could be advantageous when planning adjuvant treatment of patients with colorectal carcinoma. Although opinions on the importance of polymorphisms of PAI 1 in relation to the prognosis are not uniform, it does seem that their role in the prognosis of patients with colorectal cancer is not essential.

  6. Colorectal cancer screening programme by faecal occult blood test in Tuscany: first round results.

    PubMed

    Grazzini, G; Castiglione, G; Ciabattoni, C; Franceschini, F; Giorgi, D; Gozzi, S; Mantellini, P; Lopane, P; Perco, M; Rubeca, T; Salvadori, P; Visioli, C B; Zappa, M

    2004-02-01

    Screening with faecal occult blood test (FOBT) has been shown to be effective in reducing mortality from colorectal cancer. Tuscany was the first region in Italy in which a screening programme for colorectal cancer by FOBT was initiated region-wide. The aim of the paper was to describe organizational aspects, a quality control model and the results of this experience. From June 2000 to December 2001, 192583 subjects aged 50-70 were invited to undergo a 1-day immunochemical test without any dietary restriction. A total of 78505 subjects (41%) performed the screening test, of whom 4537 responders had a positive test result (5.8%). Among them, 1122 refused any form of assessment or underwent a colonoscopy outside the screening referral centres, with an overall assessment compliance of 75.3%. Malignancies were found in 193 patients and at least a high-risk adenomatous polyp in 692 patients. In about a quarter of the positive subjects who underwent assessment, cancer or high-risk adenoma was detected. In conclusion, data from this experience supported the feasibility of biennial colorectal screening programme by FOBT, particularly regarding invitation compliance and positivity rate. Further efforts are necessary to implement screening extension and to improve data collection.

  7. Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology.

    PubMed

    Lin, Mao Song; Huang, Jun Xing; Chen, Wei Chang; Zhang, Bao Feng; Fang, Jing; Zhou, Qiong; Hu, Ying; Gao, Heng Jun

    2011-11-01

    Although aberrations of peroxisome proliferator-activated receptor γ (PPARγ) and phosphatase and tensin homolog (PTEN) expression have been identified in several other cancer types, certain previous studies have revealed that PPARγ is abundant in normal and malignant tissue in the colon. The question of whether aberrant PTEN is involved in the initial stage or is a later event during colorectal carcinogenesis remains controversial. Relatively few studies have focused on the correlation of expression of PPARγ and PTEN in various tissues. In the present study, paraffin-embedded blocks from 139 patients with CRC, 18 adenomatous polyps and 50 paired paracancerous benign mucosas were selected and analysed in 4 tissue microarray (TMA) blocks comprising 104, 72, 130 and 54 cores, respectively. Expression of PPARγ and PTEN was examined using immunohistochemical staining on TMAs. There were no significant differences in the expression of PPARγ (P=0.055) and PTEN (P=0.100) between the colorectal cancers, adenomas and paracancerous mucosas. However, correlations of PPARγ expression with clinical stage (P=0.004) and PTEN expression with histological grade (P=0.006) and distant metastasis (P=0.015) were demonstrated in the CRC specimens. Although the differences in PPARγ and PTEN protein expression in human colorectal cancer may not be considered as early diagnostic markers, our results indicate that CRCs with a low expression or deletion of PTEN may progress towards invasion and even metastasis; thus, PTEN may have potential as a prognostic marker in human CRC.

  8. Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association.

    PubMed

    Hammerling, Ulf; Bergman Laurila, Jonas; Grafström, Roland; Ilbäck, Nils-Gunnar

    2016-01-01

    Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.

  9. Quantitative Diagnosis of Colorectal Polyps by Spectral Domain Optical Coherence Tomography

    PubMed Central

    Wang, Chen; Zhang, Qinqin; Wu, Xiaojing; Tang, Tao; Liu, Hong; Zhu, S. W.; Gao, Bruce Z.; Yuan, X.-C.

    2014-01-01

    The principal aim of this study is to investigate the scattering coefficient of colorectal polyp tissues using an optical coherence tomography (OCT) technique. It combines the existing scattering coefficient model and spectral domain OCT to achieve method of early diagnosis of colorectal polyp in hospitals. Seventeen patients were studied, and a total of 1456 data points were extracted by curve-fitting the OCT signals into a confocal single-backscattering model. The results show that the mean scattering coefficient value for colorectal polyps is 1.91 mm−1 (std: ±0.54 mm−1), which is between the values for normal and malignant tissues. In addition, we studied the difference between adenomatous polyps (n = 15) and inflammatory polyps (n = 2) quantitatively and found that the adenomatous tissues had lower scattering coefficients than the inflammatory ones. The quantitative measurements confirmed that OCT can be used in primary diagnosis to compensate for the deficiencies in methods of pathological diagnosis, with a great potential for early diagnosis of tissues. PMID:24818145

  10. Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

    PubMed Central

    Suri, Anil; Jagadish, Nirmala; Saini, Shikha; Gupta, Namita

    2015-01-01

    Colorectal cancer ranks third among the estimated cancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor associated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions. PMID:26691579

  11. Extracellular matrix gene expression profiling using microfluidics for colorectal carcinoma stratification

    PubMed Central

    Hayes, Christopher J.; Dowling, Catriona M.; Dwane, Susan; McCumiskey, Mary E.; Tormey, Shona M.; Anne Merrigan, B.; Coffey, John C.; Kiely, Patrick A.; Dalton, Tara M.

    2016-01-01

    In cancer, biomarkers have many potential applications including generation of a differential diagnosis, prediction of response to treatment, and monitoring disease progression. Many molecular biomarkers have been put forward for different diseases but most of them do not possess the required specificity and sensitivity. A biomarker with a high sensitivity has a low specificity and vice versa. The inaccuracy of the biomarkers currently in use has led to a compelling need to identify more accurate markers with diagnostic and prognostic significance. The aim of the present study was to use a novel, droplet-based, microfluidic platform to evaluate the prognostic value of a panel of thirty-four genes that regulate the composition of extracellular matrices in colorectal carcinoma. Our method is a novel approach as it uses using continuous-flowing Polymerase Chain Reaction for the sensitive detection and accurate quantitation of gene expression. We identified a panel of relevant extracellular matrix genes whose expression levels were measured by real-time quantitative polymerase chain reaction using Taqman® reagents in twenty-four pairs of matched colorectal cancer tumour and associated normal tissue. Differential expression patterns occurred between the normal and malignant tissue and correlated with histopathological parameters and overall surgical staging. The findings demonstrate that a droplet-based microfluidic quantitative PCR system enables biomarker classification. It was further possible to sub-classify colorectal cancer based on extracellular matrix protein expressing groups which in turn correlated with prognosis. PMID:27822332

  12. High incidence of LRAT promoter hypermethylation in colorectal cancer correlates with tumor stage

    PubMed Central

    Pincas, Hanna; Huang, Jianmin; Zachariah, Emmanuel; Zeng, Zhaoshi; Notterman, Daniel A.; Paty, Philip; Barany, Francis

    2015-01-01

    Lecithin:retinol acyltransferase (LRAT) is a major enzyme involved in vitamin A/retinol metabolism, which regulates various physiological processes like cell proliferation and differentiation. LRAT expression is reduced in numerous cancers, yet the underlying mechanisms have remained undefined. We hypothesized that methylation silencing may contribute to decreased LRAT gene expression in colorectal cancer (CRC). LRAT hypermethylation status was analyzed in five CRC cell lines, 167 colorectal tumors, and 69 adjacent normal colonic mucosae, using a quantitative bisulfite/PCR/LDR/Universal Array assay. LRAT transcription levels were determined by real-time RT-PCR in a subset of tumors and matched normal tissues and in CRC cell lines that were treated with a demethylating agent, 5-aza-2′-deoxycytidine. The incidence of LRAT hypermethylation was significantly higher in colorectal tumors than in adjacent normal mucosae (p = 0.0025). Aberrant methylation occurred in 51 % of microsatellite-stable CRCs, in 84 % of microsatellite-unstable CRCs, and in 12 out of 13 colonic polyps. The number of hypermethylated LRAT events was inversely correlated with CRC stage (p < 0.0001). Importantly, LRAT hypermethylation was associated with decreased mRNA level in CRC clinical specimens, and demethylation treatment resulted in LRAT transcriptional reactivation. Our data support the idea that LRAT promoter hypermethylation associates with LRAT gene expression in CRC. The higher frequency of LRAT hypermethylation in colonic polyps and early-stage CRCs indicates that it may occur early in malignant progression. PMID:25260806

  13. Circadian clock circuitry in colorectal cancer

    PubMed Central

    Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Papa, Gennaro; Piepoli, Ada

    2014-01-01

    Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer. PMID:24764658

  14. Circadian clock circuitry in colorectal cancer.

    PubMed

    Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Papa, Gennaro; Piepoli, Ada

    2014-04-21

    Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.

  15. Nutritional status assessment in colorectal cancer patients.

    PubMed

    Lopes, Joana Pedro; de Castro Cardoso Pereira, Paula Manuela; dos Reis Baltazar Vicente, Ana Filipa; Bernardo, Alexandra; de Mesquita, María Fernanda

    2013-01-01

    The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery procedure. The sample was divided between convention and fast-track procedures. Most of the individuals were overweight or obese but had lost weight on the past six months. Despite mild, there were signs of malnutrition in this sample with high losses of fat free mass, weight and also fat mass during the hospitalization period. These results reinforce the importance of malnutrition assessment in colorectal patients as well as consider weight loss on the past months and body composition in order to complement nutritional status evaluation.

  16. TAS-102 for Metastatic Colorectal Cancer

    Cancer.gov

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

  17. Antisense therapeutics for tumor treatment: the TGF-beta2 inhibitor AP 12009 in clinical development against malignant tumors.

    PubMed

    Schlingensiepen, K H; Fischer-Blass, B; Schmaus, S; Ludwig, S

    2008-01-01

    Overexpression of the cytokine transforming growth factor-beta 2 (TGF-beta2) is a hallmark of various malignant tumors including pancreatic carcinoma, malignant glioma, metastasizing melanoma, and metastatic colorectal carcinoma. This is due to the pivotal role of TGF-beta2 as it regulates key mechanisms of tumor development, namely immunosuppression, metastasis, angiogenesis, and proliferation. The antisense technology is an innovative technique offering a targeted approach for the treatment of different highly aggressive tumors and other diseases. Antisense oligonucleotides are being developed to inhibit the production of disease-causing proteins at the molecular level. The immunotherapeutic approach with the phosphorothioate oligodeoxynucleotide AP 12009 for the treatment of malignant tumors is based on the specific inhibition of TGF-beta2. After providing preclinical proof of concept, the safety and efficacy of AP 12009 were assessed in clinical phase I/II open-label dose-escalation studies in recurrent or refractory high-grade glioma patients. Median survival time after recurrence exceeded the current literature data for chemotherapy. Currently, phase I/II study in advanced pancreatic carcinoma, metastatic melanoma, and metastatic colorectal carcinoma and a phase IIb study in recurrent or refractory high-grade glioma are ongoing. The preclinical as well as the clinical results implicate targeted TGF-beta2 suppression as a promising therapeutic approach for malignant tumor therapy.

  18. Abdominal metastases from colorectal cancer: intraperitoneal therapy

    PubMed Central

    Guend, Hamza; Patel, Sunil

    2015-01-01

    Patients with peritoneal metastasis from colorectal cancer represent a distinct subset with regional disease rather than systemic disease. They often have poorer survival outcomes with systemic chemotherapy. Optimal cytoreductive surgery and intraperitoneal chemotherapy (IPC) offers such patients a more directed therapy with improved survival. In this review, we discuss the diagnosis, evaluation and classification, as well as rational for treatment of peritoneal carcinomatosis (PC) secondary to colorectal cancer. PMID:26697203

  19. Percutaneous ablation of colorectal lung metastases

    PubMed Central

    Solomon, Stephen B.

    2015-01-01

    Lung metastasectomy can prolong survival in patients with metastatic colorectal carcinoma. Thermal ablation offers a potential solution with similar reported survival outcomes. It has minimal effect on pulmonary function, or quality of life, can be repeated, and may be considered more acceptable to patients because of the associated shorter hospital stay and recovery. This review describes the indications, technique, reported outcomes, complications and radiologic appearances after thermal ablation of colorectal lung metastases. PMID:26697202

  20. Clinicopathologic and Molecular Features of Colorectal Adenocarcinoma with Signet-Ring Cell Component

    PubMed Central

    Gao, Jing; Li, Jian; Li, Jie; Qi, Changsong; Li, Yanyan; Li, Zhongwu; Shen, Lin

    2016-01-01

    Background We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component. Methods Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing. Results A slight male predominance was detected in these patients (59.0%). Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54) cases with KRAS mutations in 16.7% (9/54) cases and Nras mutations in 5.4%(3/54) cases. BRAF V600E mutation was detected in 3.7% (2/54) cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9%) cases were composed of ≥50% signet-ring cells; 22 (36.1%) cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences. Conclusions Colorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal

  1. Basic and clinical aspects of malignant melanoma

    SciTech Connect

    Nathanson, L. )

    1987-01-01

    This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.

  2. Development of Small Molecules Targeting the Wnt Signaling Pathway in Cancer Stem Cells for the Treatment of Colorectal Cancer.

    PubMed

    Song, Lele; Li, Yuemin; He, Baoming; Gong, Yuan

    2015-09-01

    Colorectal cancer (CRC) was ranked third in morbidity and mortality in the United States in 2013. Although substantial progress has been made in surgical techniques and postoperative chemotherapy in recent years, the prognosis for colon cancer is still not satisfactory, mainly because of cancer recurrence and metastasis. The latest studies have shown that cancer stem cells (CSCs) play important roles in cancer recurrence and metastasis. Drugs that target CSCs might therefore have great therapeutic potential in prevention of cancer recurrence and metastasis. The wingless-int (Wnt) signaling pathway in CSCs has been suggested to play crucial roles in colorectal carcinogenesis, and has become a popular target for anti-CRC therapy. Dysregulation of the Wnt signaling pathway, mostly by inactivating mutations of the adenomatous polyposis coli tumor suppressor or oncogenic mutations of β-catenin, has been implicated as a key factor in colorectal tumorigenesis. Abnormal increases of β-catenin levels represents a common pathway in Wnt signaling activation and is also observed in other human malignancies. These findings highlight the importance of developing small-molecule drugs that target the Wnt pathway. Herein we provide an overview on the current development of small molecules that target the Wnt pathway in colorectal CSCs and discuss future research directions.

  3. Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2014 for treatment of colorectal cancer.

    PubMed

    Watanabe, Toshiaki; Itabashi, Michio; Shimada, Yasuhiro; Tanaka, Shinji; Ito, Yoshinori; Ajioka, Yoichi; Hamaguchi, Tetsuya; Hyodo, Ichinosuke; Igarashi, Masahiro; Ishida, Hideyuki; Ishihara, Soichiro; Ishiguro, Megumi; Kanemitsu, Yukihide; Kokudo, Norihiro; Muro, Kei; Ochiai, Atsushi; Oguchi, Masahiko; Ohkura, Yasuo; Saito, Yutaka; Sakai, Yoshiharu; Ueno, Hideki; Yoshino, Takayuki; Boku, Narikazu; Fujimori, Takahiro; Koinuma, Nobuo; Morita, Takayuki; Nishimura, Genichi; Sakata, Yuh; Takahashi, Keiichi; Tsuruta, Osamu; Yamaguchi, Toshiharu; Yoshida, Masahiro; Yamaguchi, Naohiko; Kotake, Kenjiro; Sugihara, Kenichi

    2015-04-01

    Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.

  4. Gut microbiota imbalance and colorectal cancer

    PubMed Central

    Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde

    2016-01-01

    The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603

  5. Circulating cytokeratin-positive cells and tumor budding in colorectal cancer

    PubMed Central

    Märkl, Bruno; Wilhelms, Narjes; Anthuber, Matthias; Schenkirsch, Gerhard; Schlimok, Günter; Oruzio, Daniel

    2016-01-01

    AIM To investigate whether circulating cytokeratin-positive (CK+) cells in the mesenteric blood of resected colorectal specimens are prognostic and correlate with tumor budding. METHODS Fifty-six colorectal specimens were collected between 9/2007 and 7/2008. Blood from the mesenteric vein was drawn immediately after receiving the fresh and unfixed specimens in the pathology department. After separation of the mononuclear cells by Ficoll-Hypaque density-gradient centrifugation, cytological smears were immunocytochemically stained for CK18. Tumor budding was evaluated on slides stained for pan-cytokeratin. The identification of ≥ 30 buds/1.3 mm2 was defined as high grade budding. RESULTS CK+ cells and clusters were identified in 29 (48%) and 14 (25%) of the samples, respectively. Two cells were identified in one of three non-malignant cases. Clusters were found exclusively in malignant cases. The occurrence of CK+ cells or clusters was not associated with any of the evaluated clinicopathological factors, including surgical technique and tumor budding. Moreover, the occurrence of CK+ cells or clusters had no influence on the cancer-specific survival [75 mo (CI: 61; 88) vs 83 mo (CI: 72; 95) and 80 mo (CI: 63; 98) vs 79 mo (CI: 69; 89), respectively]. CONCLUSION CK+ cells and showed neither prognostic significance nor an association with tumor budding. It is very likely that CK18-staining is not specific enough to identify the relevant cells. PMID:28008384

  6. Clinical and morphological characteristics of colitis carcinoma and colorectal carcinoma in young people.

    PubMed

    Hultén, L; Kewenter, J; Ahrén, C; Ojerskog, B

    1979-01-01

    Two series of young patients (less than 40 years of age) with colorectal carcinoma (22 idiopathic carcinomas and 25 carcinomas complicating ulcerative proctocolitis), well matched for age and sex, were compared with regard to clinical features, tumour morphology and stage, and ultimate outcome after surgery. The cure rate in both series was low. Although a failure to diagnose colitis carcinoma accurately at an early stage might have contributed to the poor results, such a delay could hardly be responsible for the bad prognosis in patients with idiopathic carcinoma. The vast majority of the patients in both groups studied had highly malignant and/or mucoid adenocarcinoma, and surgery was palliative in about 40% of the patients in both series, owing to widespread dissemination. The general impression gained from this study of factors of histologic grade of malignancy, extent of spread, and survival rate was that colorectal carcinomas in the young, irrespective of being idiopathic or complicating ulcerative colitis, run a rapid course and have a gloomy prognosis. The outloook depends largely on the biologic characteristics of the tumours concerned. The results support previous statements that prophylactic surgery is justified in patients with long-standing ulcerative colitis with total involvement of the colon, particularly in the young. Regrettably, patients with idiopathic carcinoma will not have this chance.

  7. Diet and Colorectal Cancer Risk: Baseline Dietary Knowledge of Colorectal Patients

    ERIC Educational Resources Information Center

    Dyer, K. J.; Fearon, K. C. H.; Buckner, K.; Richardson, R. A.

    2004-01-01

    Objective: To establish the dietary knowledge, attitudes and potential barriers to change of patients attending a colorectal outpatient clinic. Design: Use of a semistructured interview to generate qualitative and quantitative data. Setting: A regional colorectal outpatient clinic within Edinburgh. Method: Patients attending clinic with colorectal…

  8. The cytologic criteria of malignancy.

    PubMed

    Fischer, Andrew H; Zhao, Chengquan; Li, Qing Kay; Gustafson, Karen S; Eltoum, Isam-Eldin; Tambouret, Rosemary; Benstein, Barbara; Savaloja, Lynnette C; Kulesza, Peter

    2010-07-01

    Cytology and cell biology are two separate fields that share a focus on cancer. Cancer is still diagnosed based on morphology, and surprisingly little is known about the molecular basis of the defining structural features. Cytology uses the smallest possible biopsy for diagnosis by reducing morphologic "criteria of malignancy" to the smallest scale. To begin to develop common ground, members of the American Society of Cytopathology Cell Biology Liaison Working Group classify some of the "criteria of malignancy" and review their relation to current cell biology concepts. The criteria of malignancy are extremely varied, apparently reflecting many different pathophysiologies in specific microenvironments. Criteria in Group 1 comprise tissue-level alterations that appear to relate to resistance to anoikis, alterations in cell adhesion molecules, and loss of apical-basal polarity. Criteria in Group 2 reflect genetic instability, including chromosomal and possibly epigenetic instability. Criteria in Groups 3 are subcellular structural changes involving cytoplasmic components, nuclear lamina, chromatin and nucleoli that cannot be accounted for by genetic instability. Some distinct criteria in Group 3 are known to be induced by cancer genes, but their precise structural basis remains obscure. The criteria of malignancy are not closely related to the histogenetic classification of cancers, and they appear to provide an alternative, biologically relevant framework for establishing common ground between cytologists and cell biologists. To understand the criteria of malignancy at a molecular level would improve diagnosis, and likely point to novel cell physiologies that are not encompassed by current cell biology concepts.

  9. The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial–mesenchymal transition

    PubMed Central

    Komiya, Y; Onodera, Y; Kuroiwa, M; Nomimura, S; Kubo, Y; Nam, J-M; Kajiwara, K; Nada, S; Oneyama, C; Sabe, H; Okada, M

    2016-01-01

    Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial–mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth. In the present study, ARHGEF5 was upregulated during tumor growth factor-β-induced EMT in human epithelial MCF10A cells, and promoted cell migration by activating the Rho-ROCK pathway. ARHGEF5 was necessary for the invasive and in vivo metastatic activity of human colorectal cancer HCT116 cells. These findings underscore the crucial role of ARHGEF5 in cell migration and invasion/metastasis. An in vivo tumorigenesis assay revealed that ARHGEF5 had the potential to promote tumor growth via the phosphatidylinositol 3-kinase (PI3K) pathway. However, ARHGEF5 was not required for tumor growth in epithelial-like human colorectal cancer HCT116 and HT29 cells, whereas the growth of mesenchymal-like SW480 and SW620 cells depended on ARHGEF5. Induction of EMT by tumor necrosis factor-α or Slug in HCT116 cells resulted in the dependence of tumor growth on ARHGEF5. In these mesenchymal-like cells, Akt was activated via ARHGEF5 and its activity was required for tumor growth. Analysis of a transcriptome data set revealed that the combination of ARHGEF5 upregulation and E-cadherin downregulation or Snail upregulation was significantly correlated with poor prognosis in patients with colorectal cancers. Taken together, our findings suggest that EMT-induced ARHGEF5 activation contributes to the progression of tumor malignancy. ARHGEF5 may serve as a potential therapeutic target in a subset of malignant tumors that have undergone EMT. PMID

  10. Role of surgical resection for non-colorectal non-neuroendocrine liver metastases

    PubMed Central

    Takemura, Nobuyuki; Saiura, Akio

    2017-01-01

    It is widely accepted that the indications for hepatectomy in colorectal cancer liver metastases and liver metastases of neuro-endocrine tumors result in relatively better prognoses, whereas, the indications and prognoses of hepatectomy for non-colorectal non-neuroendocrine liver metastases (NCNNLM) remain controversial owing to the limited number of cases and the heterogeneity of the primary diseases. There have been many publications on NCNNLM; however, its background heterogeneity makes it difficult to reach a specific conclusion. This heterogeneous disease group should be discussed in the order from its general to specific aspect. The present review paper describes the general prognosis and risk factors associated with NCNNLM while specifically focusing on the liver metastases of each primary disease. A multidisciplinary approach that takes into consideration appropriate timing for hepatectomy combined with chemotherapy may prolong survival and/or contribute to the improvement of the quality of life while giving respite from systemic chemotherapy. PMID:28261381

  11. Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer

    PubMed Central

    Bai, Shuang; Feng, Qiang; Pan, Xin-Yan; Zou, Hong; Chen, Hao-Bin; Wang, Peng; Zhou, Xin-Liang; Hong, Yan-Ling; Song, Shu-Ling; Yang, Ju-Lun

    2017-01-01

    Colorectal cancer (CRC) is the most common gastrointestinal type of cancer. The overexpression of Ras proteins, particularly p21Ras, are involved in the development of CRC. However, the subtypes of the p21Ras proteins that are overexpressed and the mutation status remain unknown restricting the development of therapeutic antibodies targeting p21Ras proteins. The present study aimed to investigate the mutation status of ras genes associated with Ras proteins that are overexpressed in CRC and explore whether or not wild-type p21Ras could be a target for CRC therapy. p21Ras expression was examined immunohistochemically in normal colorectal epithelium, benign lesions and malignant colorectal tumor tissues by monoclonal antibody (Mab) KGH-R1 which is able to react with three types of p21Ras proteins: H-p21Ras, N-p21Ras and K-p21Ras. Then, the expression levels of p21Ras subtypes were determined in CRC by a specific Mab for each p21Ras subtype. Mutation status of ras genes in p21Ras-overexpressing CRC was detected by DNA sequencing. There was rare p21Ras expression in normal colorectal epithelium but a high level of p21Ras expression in CRC, with a significant increase from normal colorectal epithelium to inflammatory polyps, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and invasive colorectal adenocarcinoma, respectively. Overexpression of K-p21Ras was found in all CRC tissues tested, overexpression of N-p21Ras was found in 85.7% of the CRC tissues, while H-p21Ras expression was not found in any CRC tissue. DNA sequencing showed that there were no K-ras mutations in 60% of the K-p21Ras-overexpressing CRC, while 40% of the CRC tissues harbored K-ras mutations. N-ras mutations were not found in any N-p21Ras-overexpressing CRC. Our findings indicate that overexpression of wild-type p21Ras may play a prominent role in the development of CRC in addition to ras mutations and could be a promising target for CRC therapy. PMID:28259994

  12. Hereditary colorectal cancer in the general population: from cancer registration to molecular diagnosis

    PubMed Central

    de Leon, M P.; Pedroni, M; Benatti, P; Percesepe, A; Di, G; Foroni, M; Rossi, G; Genuardi, M; Neri, G; Leonardi, F; Viel, A; Capozzi, E; Boiocchi, M; Roncucci, L

    1999-01-01

    BACKGROUND—Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common inherited disorders predisposing to cancer. The genes responsible for the disease have recently been cloned and characterised; their mutations induce a generalised genomic instability which is particularly evident at microsatellite loci (replication error (RER)+ phenotype).
AIMS—To investigate how to select individuals and families in the general population who should be screened for constitutional mutations predisposing to colorectal cancer.
PATIENTS/METHODS—Between 1984 and 1995, 1899 colorectal malignancies in 1831 patients were registered, and in 1721 of these (94%), family trees could be obtained. Patients and families were classified into five categories according to a more or less likely genetic basis: HNPCC; "suspected" HNPCC; juvenile cases; aspecific cancer aggregation; sporadic cases. In 18 families with HNPCC as well as in 18 with suspected HNPCC, microsatellite instability in tumour tissues and constitutional mutations of two DNA mismatch repair genes (MSH2 and MLH1) could be evaluated. RER status was studied with five markers (BAT40, D2S123, D18S57, D17S787, and BAT26) in paraffin embedded tissues. Germline mutations of MSH2 or MLH1 genes were assessed on DNA and RNA extracted from lymphomonocytic cells, using reverse transcription polymerase chain reaction, single strand conformation polymorphism analysis, and direct DNA sequencing.
RESULTS—HNPCC represented 2.6% and suspected HNPCC 4.6% of all registered colorectal neoplasms. Eleven out of 18 HNPCC families (61%) showed microsatellite instability as opposed to four (of 18) suspected HNPCC (22%; p<0.02). Three germline mutations (two in MSH2 and one in MLH1 gene) were found in three different large HNPCC families, whereas no mutations were detected in suspected HNPCC.
CONCLUSIONS—In this study of cancer genetic epidemiology, data from a tumour registry were analysed and this ultimately

  13. Laparoscopic and open resection for colorectal cancer: an evaluation of cellular immunity

    PubMed Central

    2010-01-01

    Background Colorectal cancer is one kind of frequent malignant tumors of the digestive tract which gets high morbidity and mortality allover the world. Despite the promising clinical results recently, less information is available regarding the perioperative immunological effects of laparoscopic surgery when compared with the open surgery. This study aimed to compare the cellular immune responses of patients who underwent laparoscopic(LCR) and open resections(OCR) for colorectal cancer. Methods Between Mar 2009 and Sep 2009, 35 patients with colorectal carcinoma underwent LCR by laparoscopic surgeon. These patients were compared with 33 cases underwent conventional OCR by colorectal surgeon. Clinical data about the patients were collected prospectively. Comparison of the operative details and postoperative outcomes between laparoscopic and open resection was performed. Peripheral venous blood samples from these 68 patients were taken prior to surgery as well as on postoperative days(POD) 1, 4 and 7. Cell counts of total white blood cells, neutrophils, lymphocyte subpopulations, natural killer(NK) cells as well as CRP were determined by blood counting instrument, flow cytometry and hematology analyzer. Results There was no difference in the age, gender and tumor status between the two groups. The operating time was a little longer in the laparoscopic group (P > 0.05), but the blood loss was less (P = 0.039). Patients with laparoscopic resection had earlier return of bowel function and earlier resumption of diet as well as shorter median hospital stay (P < 0.001). Compared with OCR group, cell numbers of total lymphocytes, CD4+T cells and CD8+T cells were significant more in LCR group (P < 0.05) on POD 4, while there was no difference in the CD45RO+T or NK cell numbers between the two groups. Cellular immune responds were similar between the two groups on POD1 and POD7. Conclusions Laparoscopic colorectal resection gets less surgery stress and short-term advantages

  14. CRCHD Launches National Colorectal Cancer Outreach and Screening Initiative

    Cancer.gov

    The NCI CRCHD launches National Screen to Save Colorectal Cancer Outreach and Screening Initiative which aims to increase colorectal cancer screening rates among racially and ethnically diverse and rural communities.

  15. [Colorectal cancer in twins. Report of two cases].

    PubMed

    Białek, Andrzej; Homa, Katarzyna; Marlicz, Krzysztof

    2003-01-01

    Colorectal cancer is one of the most common neoplasms that often occurs in several members of family. In this communication we present the case of synchronous colorectal cancers with similar localization and similar clinical course in monozygotic twins.

  16. Colorectal (Colon) Cancer: What Are the Risk Factors?

    MedlinePlus

    ... Cancer Home What Are the Risk Factors for Colorectal Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Your risk of getting colorectal cancer increases as you get older. More than 90% ...

  17. Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population

    PubMed Central

    Alkhayal, Khayal A.; Awadalia, Zainab H.; Vaali-Mohammed, Mansoor-Ali; Al Obeed, Omar A.; Al Wesaimer, Alanoud; Halwani, Rabih; Zubaidi, Ahmed M.

    2016-01-01

    Background Vitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. Genetic variants in the VDR gene have been associated with several cancers in different population including colorectal cancer. Objective To assess the association of VDR gene polymorphisms in relation with colorectal cancer (CRC) in a Saudi population. Methods The polymorphisms of VDR gene (BsmI, FokI, ApaI and TaqI) were analyzed by the polymerase chain reaction amplification of segments of interest followed by Sanger sequencing. One hundred diagnosed CRC patients and 100 healthy control subjects that were age and gender matched were recruited. Results We did not observe significant association of any of the four VDR polymorphisms with colorectal cancer risk in the overall analysis. Although not statistically significant, the AA genotype of BsmI conferred about two-fold protection against CRCs compared to the GG genotype. Stratification of the study subjects based on age and gender suggests statistically significant association of CRC with the ‘C’ allele of ApaI in patients >57 years of age at disease diagnosis and BsmI polymorphism in females. In addition, statistically significant differences were observed for the genotypic distributions of VDR-BsmI, ApaI and TaqI SNPs between Saudi Arabian population and several of the International HapMap project populations. Conclusion Despite the absence of correlation of the examined VDR polymorphisms with CRCs in the combined analysis, ApaI and BsmI loci are statistically significantly associated with CRC in elderly and female patients, respectively. These findings need further validation in larger cohorts prior to utilizing these SNPs as potential screening markers for colorectal cancers in Saudi population. PMID:27309378

  18. Blood transfusions and local tumor recurrence in colorectal cancer. Evidence of a noncausal relationship.

    PubMed Central

    Busch, O R; Hop, W C; Marquet, R L; Jeekel, J

    1994-01-01

    OBJECTIVE. The authors analyzed the effect of blood transfusions on the pattern of colorectal cancer recurrence. BACKGROUND. Retrospective studies suggest that blood transfusions are associated with a poor prognosis in patients who undergo operations for colorectal malignancies. In a previously published, randomized trial, it was investigated whether autologous blood transfusions could overcome this putative detrimental effect. However, this did not appear to be the case. METHODS. In the current study, the authors analyzed the patterns of recurrence in 420 patients who underwent curative operations for colorectal cancer. RESULTS. Patients who did not require transfusions (N = 143) had significantly better disease-free survival than those who did need transfusions (N = 277); percentages at 4 years were 73% and 59%, respectively (p = 0.001). No difference was found between both groups in comparing cumulative percentages of patients having metastases; percentages at 4 years were 25% in the group that did not undergo transfusion and 27% in the transfused group. The percentage of cases having local recurrence, however, was significantly increased (p = 0.0006) in the transfused group as compared with the group that did not undergo transfusion; percentages at 4 years were 20% and 3%, respectively. The groups of patients receiving only allogeneic, only autologous, or both types of transfusions all had a significantly higher incidence of local recurrence than the patients who did not receive transfusions, but no differences were found between these three groups. CONCLUSIONS. These findings suggest that the association between blood transfusions and prognosis in colorectal cancer is a result of the circumstances that necessitate transfusions, leading to the development of local recurrences, but not of distant metastases. PMID:7986147

  19. Differential expression of epidermal growth factor-related proteins in human colorectal tumors.

    PubMed Central

    Ciardiello, F; Kim, N; Saeki, T; Dono, R; Persico, M G; Plowman, G D; Garrigues, J; Radke, S; Todaro, G J; Salomon, D S

    1991-01-01

    Amphiregulin (AR) and cripto are proteins that are structurally related to epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). AR is also functionally related to this family of growth regulatory molecules and is able to bind and activate the 170-kDa EGF receptor (EGFR). Human EGFR-3 (HER3)/ERBB3 is a recently identified protein related to the EGFR that is widely expressed in breast carcinomas and is a candidate receptor for EGF-like growth factors. Differential expression of these putative ligands and receptors in transformed cells suggests that they may function in an autocrine manner to regulate tumor cell growth. Specific mRNA transcripts for TGF-alpha [4.8 kilobases (kb)], AR (1.4 kb), cripto (2.2 kb), and HER3 (6.2 kb) were expressed in a majority of human colon cancer cell lines. HER3 mRNA was detected in 55% of primary or metastatic human colorectal carcinomas but in only 22% of normal colon mucosa and 32% of normal liver samples. In contrast, cripto and AR mRNA were expressed in 60-70% of primary or metastatic human colorectal cancers but in only 2-7% of normal human colonic mucosa. Immunostaining also detected AR protein in primary and metastatic colorectal tumors but not in normal colon or uninvolved liver. These findings suggest that cripto and AR may be useful markers to discriminate between normal and malignant colonic epithelium and may provide a selective growth advantage for colorectal carcinomas. Images PMID:1715580

  20. ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma

    PubMed Central

    2009-01-01

    Background Cancer cells display widespread changes in DNA methylation that may lead to genetic instability by global hypomethylation and aberrant silencing of tumor suppressor genes by focal hypermethylation. In turn, altered DNA methylation patterns have been used to identify putative tumor suppressor genes. Methods In a methylation screening approach, we identified ECRG4 as a differentially methylated gene. We analyzed different cancer cells for ECRG4 promoter methylation by COBRA and bisulfite sequencing. Gene expression analysis was carried out by semi-quantitative RT-PCR. The ECRG4 coding region was cloned and transfected into colorectal carcinoma cells. Cell growth was assessed by MTT and BrdU assays. ECRG4 localization was analyzed by fluorescence microscopy and Western blotting after transfection of an ECRG4-eGFP fusion gene. Results We found a high frequency of ECRG4 promoter methylation in various cancer cell lines. Remarkably, aberrant methylation of ECRG4 was also found in primary human tumor tissues, including samples from colorectal carcinoma and from malignant gliomas. ECRG4 hypermethylation associated strongly with transcriptional silencing and its expression could be re-activated in vitro by demethylating treatment with 5-aza-2'-deoxycytidine. Overexpression of ECRG4 in colorectal carcinoma cells led to a significant decrease in cell growth. In transfected cells, ECRG4 protein was detectable within the Golgi secretion machinery as well as in the culture medium. Conclusions ECRG4 is silenced via promoter hypermethylation in different types of human cancer cells. Its gene product may act as inhibitor of cell proliferation in colorectal carcinoma cells and may play a role as extracellular signaling molecule. PMID:20017917

  1. Adjuvant chemotherapy with 5-fluorouracil in a patient with colorectal cancer and Familial Mediterranean Fever.

    PubMed

    Purim, Ofer; Sulkes, Aaron; Brenner, Baruch

    2007-07-01

    Colorectal cancer is a common malignancy often requiring adjuvant chemotherapy. Familial Mediterranean Fever is a chronic hereditary disease which is relatively prevalent in the Middle East and is associated with recurrent episodes of serosal, synovial or cutaneous inflammations. The aim of this paper was to describe a patient with Familial Mediterranean Fever who received fluorouracil-based adjuvant chemotherapy for colorectal cancer. A 56-year-old man with Familial Mediterranean Fever and amyloidosis was referred for evaluation and treatment following surgery for colorectal cancer. In light of his relatively young age, good general state of health and apparently well-controlled Familial Mediterranean Fever, he was treated with chemotherapy consisting of four cycles of 5-fluorouracil and leucovorin. The patient's clinical course during chemotherapy was unremarkable except for one minor attack of Familial Mediterranean Fever. The patient's follow-up was notable for periodic fluctuations in serum carcinoembryonic antigen levels, up to 4-fold of normal. The Familial Mediterranean Fever remained stable. Although our patient showed a good tolerability of treatment, the administration of chemotherapy to patients with Familial Mediterranean Fever raises several concerns. These include a potential deterioration in the Familial Mediterranean Fever status owing to chemotherapy-induced stress, the potential effect of Familial Mediterranean Fever or its treatment on the tolerability of chemotherapy and an overlapping toxicity of the drugs used to treat the two diseases. An increase in serum carcinoembryonic antigen in this setting may be related to the underlying pathophysiologic mechanism of Familial Mediterranean Fever but does not necessarily indicate disease recurrence. Clinicians should be aware of these issues considering the recent worldwide increase in colorectal cancer.

  2. Elevated Level of Serum Carcinoembryonic Antigen (CEA) and Search for a Malignancy: A Case Report

    PubMed Central

    Saif, Muhammad W

    2016-01-01

    Carcinoembryonic antigen (CEA) has been shown to be associated with tumor burden in patients with colorectal cancer. However, it is also elevated to a significant degree in a number of other malignant and non-malignant conditions. We report a case of reversible CEA elevation in a patient using lithium for bipolar disorder. A 58-year-old female with a longstanding smoking history and a past medical history of chronic obstructive pulmonary disease (COPD), bipolar illness, hypothyroidism, and obesity was found to have an elevated CEA level of 11.2 ng/ml (normal level <5 ng/ml) in the workup for postmenopausal bleeding. Her history was not positive for malignancy of colorectum, ovaries, thyroid, or breast.  She underwent a large number of imaging and endoscopic studies to evaluate for colorectal, breast, ovarian, and lung cancer; however, it did not reveal any evidence of malignancy. Upon review of her medications, she reported that she had recently started lithium for her bipolar illness. We followed up her CEA level while her dose of lithium was reduced from 450 to 300 mg per day. Her CEA level decreased from 25 mg/dl to 6.1 mg/dl and remained stable over the course of the next eight months. Our case is the first case report that identifies lithium as a potential cause of reversible CEA elevation. The underlying mechanism is yet to be elucidated, but it underscores the importance of investigating the medications as part of the workup. PMID:27446768

  3. XYY male and hematologic malignancy.

    PubMed

    Oguma, N; Shigeta, C; Kamada, N

    1996-09-01

    Two cases of XYY male with refractory anemia with excess of blasts are reported, and previous reported XYY males with hematologic malignancy are reviewed. Altogether 26 cases were collected for analysis: acute myeloid leukemia (10), acute lymphocytic leukemia (seven), acute leukemia (two), chronic myelocytic leukemia (three), myelodysplastic syndrome (three), and essential thrombocythemia (one). The age at the time of diagnosis ranged in age from 7.5 to 81 years. In three of six XYY/XY mosaicism cases, XYY clone was associated with malignancy. However, in two cases XYY clone was not involved. The evidence presented here suggests that the event of an XYY male with hematologic malignancy is incidental rather than a genetic etiology.

  4. Cyclosporin-A associated malignancy

    PubMed Central

    Durnian, Jonathan M; Stewart, Rosalind MK; Tatham, Richard; Batterbury, Mark; Kaye, Stephen B

    2007-01-01

    The use of cyclosporin is well established within the ophthalmology community, especially against sight threatening intraocular inflammation. It is well known however, that immunosuppression in general is a risk factor for the development of malignancy and numerous studies point to the risk imposed by cyclosporin. This article analyses and reviews all relevant studies with regard to the development of malignancy associated with the use of cyclosporin and extrapolates this into the ophthalmic setting. This is to enable clinicians to assess the risks in individual patients and to present a monitoring regime which can be used in patients undergoing cyclosporin treatment. The review is solely concerned with the risk of the development of malignancy following cyclosporin immunosuppression and not with any other adverse effect. PMID:19668519

  5. Eosinophilic Dermatosis of Hematologic Malignancy.

    PubMed

    Lucas-Truyols, S; Rodrigo-Nicolás, B; Lloret-Ruiz, C; Quecedo-Estébanez, E

    2017-03-22

    Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients.

  6. Mucosa-associated lymphoid tissue lymphoma with unusual 18F-FDG hypermetabolism arising at the colorectal anastomosis

    PubMed Central

    Zhang, Na-Sha; Shi, Fang; Kong, Li; Zhu, Hui

    2017-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma usually originates from the stomach and presents with low 18F-fluorodeoxyglucose (FDG) avidity with average maximum standard uptake value of 3.6. Colorectal MALT lymphoma is a rare entity that contributes to 1.6% of all MALT lymphomas and < 0.2% of large intestinal malignancies. The case reported herein firstly revealed stage IIE MALT lymphoma with unexpected higher 18F-FDG avidity of 18.9 arising at the colorectal anastomosis in a patient with a surgical history for sigmoid adenocarcinoma, which was strongly suspected as local recurrence before histopathological and immunohistochemical examinations. After accurate diagnosis, the patient received four cycles of standard R-CVP regimen (rituximab, cyclophosphamide, vincristine and prednisone), combined target therapy and chemotherapy, instead of radiotherapy recommended by National Comprehensive Cancer Network guidelines. He tolerated the treatment well and reached complete remission. PMID:28210093

  7. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  8. Second Malignant Neoplasms Following Radiotherapy

    PubMed Central

    Kumar, Sanath

    2012-01-01

    More than half of all cancer patients receive radiotherapy as a part of their treatment. With the increasing number of long-term cancer survivors, there is a growing concern about the risk of radiation induced second malignant neoplasm [SMN]. This risk appears to be highest for survivors of childhood cancers. The exact mechanism and dose-response relationship for radiation induced malignancy is not well understood, however, there have been growing efforts to develop strategies for the prevention and mitigation of radiation induced cancers. This review article focuses on the incidence, etiology, and risk factors for SMN in various organs after radiotherapy. PMID:23249860

  9. [Kinase inhibitors against hematological malignancies].

    PubMed

    Tojo, Arinobu

    2014-06-01

    Dysregulation of protein phosphorylation, especially on tyrosine residues, plays a crucial role in development and progression of hematological malignancies. Since remarkable success in imatinib therapy of CML and Ph+ALL, extensive efforts have made to explore candidate molecular targets and next breakthrough drugs. Now that next generation ABL kinase inhibitors are available for CML, the therapeutic algorithm has been revolutionized. As for AML and lymphoid malignancies, many kinase inhibitors targeting FLT3, BTK and aurora-A are on early and late clinical trials, and a number of promising drugs including ibrutinib are picked up for further evaluation.

  10. Genetics of Colorectal Cancer (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of colorectal cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for colorectal cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary colorectal cancer syndrome are also discussed.

  11. Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells

    PubMed Central

    Guy, M; Moorghen, M; Bond, J A; Collard, T J; Paraskeva, C; Williams, A C

    2001-01-01

    The aim of this study was to investigate the regulation of Rb protein expression in relation to increased differentiation and induction of apoptosis in colonic epithelial cells. In vivo, Rb protein expression was found to be down-regulated towards the top of the normal colonic crypt, coincident with the region of differentiation and apoptosis, but highly expressed in colonic carcinoma tissue. Using in vitro models to study the regulation of Rb expression in pre-malignant colonic epithelial cells, we have been able to show for the first time that Rb protein expression is transcriptionally down-regulated in differentiated pre-malignant cells (in post-confluent cultures) but not in malignant colorectal epithelial cells. Furthermore, suppression of rb protein function by the HPV-E7 viral oncoprotein increased both spontaneous and DNA damage-induced apoptosis. These results suggest that Rb is able to act as a survival factor in colonic epithelial cells by suppressing apoptosis, and that over-expression of pRb in colorectal tumour cells can cause a loss of sensitivity to apoptotic signalling, resulting in aberrant cell survival and resistance to therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11207048

  12. Enhanced immunoPET of ALCAM-positive colorectal carcinoma using site-specific ⁶⁴Cu-DOTA conjugation.

    PubMed

    Tavaré, Richard; Wu, Wei H; Zettlitz, Kirstin A; Salazar, Felix B; McCabe, Katelyn E; Marks, James D; Wu, Anna M

    2014-10-01

    Activated leukocyte cell adhesion molecule (ALCAM) is an immunoglobulin superfamily cell adhesion molecule that is aberrantly expressed in a wide variety of human tumors, including melanoma, prostate cancer, breast cancer, colorectal carcinoma, bladder cancer and pancreatic adenocarcinoma. This wide spectrum of human malignancies makes ALCAM a prospective pan-cancer immunoPET target to aid in detection and diagnosis in multiple malignancies. In this study, we assess site-specific versus non-site-specific conjugation strategies for (64)Cu-DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) immunoPET imaging of a fully human ALCAM cys-diabody (cDb) with a reduced linker length that retains its bivalent binding ability. ALCAM constructs with linker lengths of eight, five and three amino acids were produced to make true non-covalent site-specifically modified cDbs. Characterization by gel electrophoresis, size exclusion chromatography, flow cytometry and mass spectrometry of the various constructs was performed. To demonstrate the increased utility of targeting multiple malignancies expressing ALCAM, we compare the targeting of the site-specific versus non-site-specific conjugated cDbs to the human colorectal cancer xenograft LS174T. Interestingly, the conjugation strategy not only affects tumor targeting but also hepatic and renal uptake/clearance.

  13. Prognostic value of innate and adaptive immunity in colorectal cancer.

    PubMed

    Grizzi, Fabio; Bianchi, Paolo; Malesci, Alberto; Laghi, Luigi

    2013-01-14

    Colorectal cancer (CRC) remains one of the major public health problems throughout the world. Originally depicted as a multi-step dynamical disease, CRC develops slowly over several years and progresses through cytologically distinct benign and malignant states, from single crypt lesions through adenoma, to malignant carcinoma with the potential for invasion and metastasis. Moving from histological observations since a long time, it has been recognized that inflammation and immunity actively participate in the pathogenesis, surveillance and progression of CRC. The advent of immunohistochemical techniques and of animal models has improved our understanding of the immune dynamical system in CRC. It is well known that immune cells have variable behavior controlled by complex interactions in the tumor microenvironment. Advances in immunology and molecular biology have shown that CRC is immunogenic and that host immune responses influence survival. Several lines of evidence support the concept that tumor stromal cells, are not merely a scaffold, but rather they influence growth, survival, and invasiveness of cancer cells, dynamically contributing to the tumor microenvironment, together with immune cells. Different types of immune cells infiltrate CRC, comprising cells of both the innate and adaptive immune system. A relevant issue is to unravel the discrepancy between the inhibitory effects on cancer growth exerted by the local immune response and the promoting effects on cancer proliferation, invasion, and dissemination induced by some types of inflammatory cells. Here, we sought to discuss the role played by innate and adaptive immune system in the local progression and metastasis of CRC, and the prognostic information that we can currently understand and exploit.

  14. Anastomotic dehiscence (AD) in colorectal cancer surgery: mechanical anastomosis versus manual anastomosis

    PubMed Central

    Oprescu, C; Beuran, M; Nicolau, AE; Negoi, I; Venter, MD; Morteanu, S; Oprescu-Macovei, AM

    2012-01-01

    Introduction: Anastomotic dehiscence (AD) is the “Achilles heel" for resectional colorectal pathology and is the most common cause of postoperative morbidity and mortality. AD incidence is 3-8%; mortality rate due to AD two decades ago was around 60% and at present is 10% [4-6]. This paper analyzes the incidence of AD after colorectal resection performed both in emergency and elective situations, depending on the way it is done: manually or mechanically. Methods: Retrospective, single-center, observational study of patients operated in the period from 1st of January 2009 to 31th of December 2011 for malignant colorectal pathology in the Emergency Clinical Hospital of Bucharest. We evaluated the incidence of digestive fistulas according to the segment of digestive tract and time from hospital admission, to the way the anastomosis was achieved (mechanical vs. Manual), to the complexity of intervention, to the transfusion requirements pre/intra or postoperative, to the past medical history of patients (presence of colorectal inflammatory diseases: ulcerative colitis and Crohn's disease), to the average length of hospital stay and time of postoperative resumption of bowel transit. Results: We included 714 patients who had surgery between 1st of January 2009 and 31th of December 2011. 15.26% (109/714) of the cases were operated in emergency conditions. Of the 112 cases of medium and lower rectum, 76 have “benefited" from preoperative radiotherapy with a fistula rate of 22.36% (17/76). The incidence of anastomotic dehiscence in the group with preoperative radiotherapy and mechanical anastomosis was 64.7% (11/17) versus 35.3% (6/17) incidence recorded in the group with manual anastomosis. Colorectal inflammatory diseases have been found as a history of pathology in 41 patients - incidence of fistulas in this group was of 12.2% (5/41), compared to only 6.83% (46/673) incidence seen in patients without a history of such disease. For the group with bowel inflammatory

  15. Worldwide burden of colorectal cancer: a review.

    PubMed

    Favoriti, Pasqualino; Carbone, Gabriele; Greco, Marco; Pirozzi, Felice; Pirozzi, Raffaele Emmanuele Maria; Corcione, Francesco

    2016-03-01

    Colorectal cancer is a major public health problem, being the third most commonly diagnosed cancer and the fourth cause of cancer death worldwide. There is wide variation over time among the different geographic areas due to variable exposure to risk factors, introduction and uptake of screening as well as access to appropriate treatment services. Indeed, a large proportion of the disparities may be attributed to socioeconomic status. Although colorectal cancer continues to be a disease of the developed world, incidence rates have been rising in developing countries. Moreover, the global burden is expected to further increase due to the growth and aging of the population and because of the adoption of westernized behaviors and lifestyle. Colorectal cancer screening has been proven to greatly reduce mortality rates that have declined in many longstanding as well as newly economically developed countries. Statistics on colorectal cancer occurrence are essential to develop targeted strategies that could alleviate the burden of the disease. The aim of this paper is to provide a review of incidence, mortality and survival rates for colorectal cancer as well as their geographic variations and temporal trends.

  16. Cutavirus in Cutaneous Malignant Melanoma

    PubMed Central

    Fridholm, Helena; Vinner, Lasse; Kjartansdóttir, Kristín Rós; Friis-Nielsen, Jens; Asplund, Maria; Herrera, Jose A.R.; Steiniche, Torben; Mourier, Tobias; Brunak, Søren; Willerslev, Eske; Izarzugaza, Jose M.G.; Hansen, Anders J.; Nielsen, Lars P.

    2017-01-01

    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains to be investigated. PMID:28098541

  17. Malignant haemangioendothelioma involving the liver

    PubMed Central

    Pollard, Stella M.; Millward-Sadler, G. H.

    1974-01-01

    The features of four cases of malignant haemangioendothelioma involving the liver and other organs are described. Two cases were associated with a microangiopathic haemolytic anaemia. The nature of the tumours and possible pathogenesis for the anaemias are discussed. Images PMID:4832301

  18. The Origin of Malignant Malaria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasmodium falciparum is the causative agent of malignant malaria, which is among the most severe human infectious diseases. Despite its overwhelming significance to human health, the parasite’s origins remain unclear. The favored origin hypothesis holds that P. falciparum and its closest known rel...

  19. Comparative analysis of colorectal carcinoma staging using operative, histopathology and computed tomography findings

    PubMed Central

    Singla, Subhash Chander; Kaushal, Dhawal; Sagoo, Harinder Singh; Calton, Nalini

    2017-01-01

    Background: The staging of colorectal carcinoma using 3 modalities viz operative, histopathology and CT scan has been subject of interest in accurately defining the extent of disease. This retrospective as well as prospective study was carried out at CMC, Ludhiana, Punjab from November 2011 to May 2014. Aim: The objective of this study was to assess the usefulness and accuracy of CT scan findings to state the extent and spread of colorectal malignancy and to correlate these findings with histopathological diagnosis. Method: A total of 31 biopsy proven patients showing variable bowel wall thickening involving the colon /rectum on CECT (Contrast Enhanced Computed Tomography) were included in the study. The tumours were staged based on the CT scan findings and were compared with the operative and histopathological findings. Observations: Rectum was the most common site of involvement followed by the recto-sigmoid involvement. Metastasis was observed in 5 cases out of the 31 malignant cases. Five of the 7 cases were correctly staged as T1 & T2 lesions on CT having a sensitivity of 83.3%, specificity of 92%, and positive predictive value of 71.4% and a negative predictive value of 95.8% in the diagnosis of T1 and T2 lesions. 15 of the 16 cases were correctly staged as T3 lesions. CT had a sensitivity of 88.2%, specificity of 93.8%, and positive predictive value of 93.8% and a negative predictive value of 86.7% in the diagnosis of T3 lesions. All the 8 cases were correctly staged as T4 lesions. CT had a sensitivity of 100%, specificity of 100%, and positive predictive value of 100% and a negative predictive value of 100% in the diagnosis of T4 lesions. Conclusion: We conclude that CT scan is an excellent modality in diagnosing malignant lesions of the colon and rectum. PMID:28251101

  20. A Rare Presentation of Peritoneal Tuberculosis Mimicking Malignancy

    PubMed Central

    Swe, Thein; Naing, Akari Thein; Phyo, Zaw Win; Thwin, Malar

    2016-01-01

    Our search of literature revealed combined elevations of serum cancer antigen 125 levels and rheumatoid factor levels in a patient with peritoneal tuberculosis has rarely been reported. Thus, we describe the case of a 63-year-old female with large abdominal ascites and malignancy was ruled out with biopsy. High levels of serum cancer antigen and rheumatoid factor were noted. Physicians should be aware that tuberculosis infection could induce elevation of rheumatoid factor levels in the absence of rheumatologic symptoms or disease. A high index of suspicion is required because peritoneal tuberculosis is a great mimicker of other abdominal pathology, especially intraabdominal malignancies and can mislead physicians to undergo unnecessary interventions. PMID:27900335

  1. Autofluorescence spectroscopy of colorectal carcinoma: ex vivo study

    NASA Astrophysics Data System (ADS)

    Horak, Ladislav; Svec, Alexandr; Lezal, Dimitrij; Zavadil, Jiri

    2003-10-01

    Diagnosis established by means of fluorescence spectroscopy is currently used in the field of urology and bronchology. Its major advantage is that it allows the diagnosis of epithelial dysplasia or malignant proliferation even if routine diagnostic endoscopy fails to reveal any macroscopic changes. The authors present results of their observations that deal with fluorescence diagnosis of colorectal carcinoma. They examined the wet microscopic mounts of healthy colon mucosa and compared them to that prepared from colon mucosa affected by adenocarcinoma. The diagnosis of adenocarcinoma was verified by using clinical and histology means. Fluorescence spectra of tissue samples, excited by means of 488 and 514.5 nm lines of Ar ion laser and/or by He-Ne laser line 632.8 nm, have been studied. This study demonstrated differences in both the spectral shape and in the signal intensity (at unchanged spectral shape) of photoluminescence spectra emitted from tissue affected by adenocarcinoma as compared to that of healthy colon mucosa. The results encourage us to continue the study aimed at development of the diagnostic system usable in the clinical practice.

  2. Discovery and Validation of Hypermethylated Markers for Colorectal Cancer

    PubMed Central

    2016-01-01

    Colorectal carcinoma (CRC) is one of the most prevalent malignant tumors worldwide. Screening and early diagnosis are critical for the clinical management of this disease. DNA methylation changes have been regarded as promising biomarkers for CRC diagnosis. Here, we map DNA methylation profiling on CRC in six CRCs and paired normal samples using a 450 K bead array. Further analysis confirms the methylation status of candidates in two data sets from the Gene Expression Omnibus. Receiver operating characteristic (ROC) curves are calculated to determine the diagnostic performances. We identify 1549 differentially methylated regions (DMRs) showing differences in methylation between CRC and normal tissue. Two genes (ADD2 and AKR1B1), related to the DMRs, are selected for further validation. ROC curves show that the areas under the curves of ADD2 and AKR1B1 are higher than that of SEPT9, which has been clinically used as a screening biomarker of CRC. Our data suggests that aberrant DNA methylation of ADD2 and AKR1B1 could be potential screening markers of CRC. PMID:27493446

  3. American Cancer Society Colorectal Cancer Survivorship Care Guidelines

    PubMed Central

    El-Shami, Khaled; Oeffinger, Kevin C.; Erb, Nicole L.; Willis, Anne; Bretsch, Jennifer; Pratt-Chapman, Mandi L.; Cannady, Rachel; Wong, Sandra L.; Rose, Johnie; Barbour, April; Stein, Kevin; Sharpe, Katherine; Brooks, Durado D.; Cowens-Alvarado, Rebecca L.

    2016-01-01

    Colorectal cancer (CRC) is the third most common malignant disease in the United States (U.S.). Almost two-thirds of CRC survivors are living 5 years following diagnosis. The prevalence of CRC survivors is likely to increase dramatically over the coming decades with further advances in early detection and treatment and the aging and growth of the U.S. population. Survivors are at risk for a CRC recurrence, a new primary CRC, other cancers, as well as both short and long-term adverse effects of the CRC and the modalities used to treat it. CRC survivors may also have psychological, reproductive, genetic, social, and employment concerns following treatment. Communication and coordination of care between the treating oncologist and the primary care clinician is critical to effectively and efficiently manage the long-term care of CRC survivors. The following guidelines are intended to assist primary care clinicians in delivering risk-based health care for CRC survivors who have completed active therapy. PMID:26348643

  4. Immunotherapy of Metastatic Colorectal Cancer: Prevailing Challenges and New Perspectives

    PubMed Central

    Zumwalt, Timothy J; Goel, Ajay

    2015-01-01

    Patients with recurring or metastatic colorectal cancer (mCRC) have strikingly low long-term survival, while conventional treatments such as chemotherapeutic intervention and radiation therapy marginally improve longevity. Although, many factors involving immunosurveillance and immunosuppression were recently validated as important for patient prognosis and care, a multitude of experimental immunotherapies designed to combat unresectable mCRC have, in few cases, successfully mobilized antitumor immune cells against malignancies, nor conclusively or consistently granted protection, complete remission, and/or stable disease from immunotherapy – of which benefit less than 10% of those receiving therapy. After decades of progress, however, new insights into the mechanisms of immunosuppression, tolerance, and mutation profiling established novel therapies that circumvent these immunological barriers. This review underlines the most exciting methods to date that manipulate immune cells to curb mCRC, including adoptive cell therapy, dendritic cell vaccines, and checkpoint inhibitor antibodies – of which hint at effective and enduring protection against disease progression and undetected micrometastases. PMID:26441489

  5. Colorectal carcinoma in a Southern Mediterranean country: The Libyan scenario

    PubMed Central

    Bodalal, Zuhir; Bendardaf, Riyad

    2014-01-01

    AIM: To study the salient features of colorectal cancer (CRC) in Libya. METHODS: Patients records were gathered at the primary oncology clinic in eastern Libya for the period of one calendar year (2012). Using this data, various parameters were analyzed and age-standardized incidence rates were determined using the direct method and the standard population. RESULTS: During 2012, 174 patients were diagnosed with CRC, 51.7% (n = 90) male and 48.3% (n = 84) females. The average age was 58.7 (± 13.4) years, with men around 57.3 (± 13) years old and women usually 60.1 (± 13.8) years of age. Libya has the highest rate of CRC in North Africa, with an incidence closer to the European figures. The age-standardized rate for CRC was 17.5 and 17.2/100000 for males and females respectively. It was the second most common cancer, forming 19% of malignancies, with fluctuation in ranking and incidence in different cities/villages. Increasingly, younger ages are being afflicted and a higher proportion of patients are among the > 40 years subset. Nearly two-thirds presented at either stage III (22.4%) or IV (38.4%). CONCLUSION: Cancer surveillance systems should be established in order to effectively monitor the situation. Likewise, screening programs are invaluable in the Libyan scenario given the predominance of sporadic cases. PMID:24734155

  6. ASSOCIATION BETWEEN HUMAN PAPILLOMAVIRUS AND COLORECTAL ADENOCARCINOMA AND ITS INFLUENCE ON TUMOR STAGING AND DEGREE OF CELL DIFFERENTIATION

    PubMed Central

    PICANÇO-JUNIOR, Olavo Magalhães; OLIVEIRA, Andre Luiz Torres; FREIRE, Lucia Thereza Mascarenhas; BRITO, Rosangela Baia; VILLA, Luisa Lina; MATOS, Délcio

    2014-01-01

    Background Colorectal cancer is one of the most common types of neoplasia among the worldwide adult population. Among neoplasms of the gastrointestinal tract, it is ranked second in relation to prevalence and mortality, but its etiology is only known in around 5% of the cases. It is believed that 15% of malignant diseases are related to viral oncogenesis. Aim To correlate the presence of HPV with the staging and degree of cell differentiation among patients with colorectal adenocarcinoma. Methods A retrospective case-control study was conducted on 144 patients divided between a test group of 79 cases of colorectal cancer and a control group to analyze 144 patients aged 25 to 85 years (mean, 57.85 years; standard deviation, 15.27 years and median, 58 years). Eighty-six patients (59.7%) were male. For both groups, tissue samples from paraffin blocks were subjected to DNA extraction followed by the polymerase chain reaction using generic and specific primers for HPV 16 and 18. Dot blot hybridization was also performed with the aim of identifying HPV DNA. Results The groups were shown to be homogenous regarding sex, age and site of HPV findings in the samples analyzed. Out of the 41 patients with HPV, 36 (45.6%) were in the cases and five (7.7%) were in the control group (p<0.001). All the HPV cases observed comprised HPV 16, and HPV 18 was not shown in any of the cases studied. There were no significant differences in comparisons of sex, age and site regarding the presence of HPV in either of the groups. It was not observe any significant difference in relation to staging or degree of cell differentiation among the patients with colorectal cancer. Conclusion Human papillomavirus type 16 is present in individuals with colorectal carcinoma. However, its presence was unrelated to staging or degree of differentiation. PMID:25184765

  7. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer.

    PubMed

    Kim-Schulze, Seunghee; Kim, Hong Sung; Wainstein, Alberto; Kim, Dae Won; Yang, Wein Cui; Moroziewicz, Dorota; Mong, Phyllus Y; Bereta, Michal; Taback, Bret; Wang, Qin; Kaufman, Howard L

    2008-12-01

    The gastrointestinal mucosa contains an intact immune system that protects the host from pathogens and communicates with the systemic immune system. Absorptive epithelial cells in the mucosa give rise to malignant tumors although the interaction between tumor cells and the mucosal immune system is not well defined. The pathophysiology of colorectal cancer has been elucidated through studies of hereditary syndromes, such as familial adenomatous polyposis, a cancer predisposition syndrome caused by germline mutations in the adenomatous polyposis coli tumor suppressor gene. Patients with FAP develop adenomas and inevitably progress to invasive carcinomas by the age of 40. To better delineate the role of mucosal immunity in colorectal cancer, we evaluated the efficacy of intrarectal recombinant vaccinia virus expressing the human carcinoembryonic Ag (CEA) in a murine FAP model in which mice are predisposed to colorectal cancer and also express human CEA in the gut. Mucosal vaccination reduced the incidence of spontaneous adenomas and completely prevented progression to invasive carcinoma. The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs. Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments. Thus, intrarectal vaccination induces mucosal and systemic antitumor immunity and prevents progression of spontaneous colorectal cancer. These results have implications for the prevention of colorectal cancer in high-risk individuals.

  8. [Current concepts in the genetics of hereditary and sporadic colorectal cancer and the role of genetics in patient management. Hereditary colorectal cancers].

    PubMed

    Lakatos, Péter László; Lakatos, László

    2006-02-26

    Colorectal cancer (CRC) is the second leading cause of mortality of malignant diseases in Hungary and according to the incidence and prevalence of CRC Hungary is second among European countries. Hence, it is of outstanding interest to know the current concepts on pathogenesis and genetical background of CRC, as well as incorporate this knowledge in the everyday practice. In the first part of the review authors address the genetic background of hereditary colorectal cancer syndromes. In fact, a positive family history may be found in 20-30% and genetically defined trait (e.g. familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers-syndrome (PJS)) is responsible for 3-5% of all colon cancers. Germline mutations of tumor suppressor gene, APC (5q21) are found in 70-90% of the cases. Until now more than 300 mutations were identified. Though a typical mutation was not found, the location of the mutation is associated to the clinical phenotype and prognosis. Of note, beside APC mutations, biallelic mutations of the MYH gene may be found in a subset of individuals with FAP. The diagnosis of HNPCC is based on family history and the presence of Amsterdam I-Il or Bethesda criteria. The genetic background and clinical phenotype of the syndrome is heterogeneous. Mutations of different mismatch repair genes (mainly hMLH1 or hMSH2) may be identified in most cases. Genetic testing is advised in first degree relatives of FAP patients, if genetic testing is not available colonoscopic surveillance should be done starting at the age of 10-12 years. Due to the high number of mutation genetic testing is difficult in HNPCC families and colonoscopic screening should be advised to affected families.

  9. First surgical tumour reduction of peritoneal surface malignancy in a rat's model.

    PubMed

    Hartmann, Jens; Kilian, Maik; Atanassov, Vladimir; Braumann, Chris; Ordemann, Juergen; Jacobi, Christoph A

    2008-01-01

    Surgical therapy of peritoneal surface malignancy from colorectal origin in combination with Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) has now become an established treatment approach in very few specialised centres. A peritonectomy procedure is possible to perform with additional HIPEC in patients. An experimental model to simulate peritonectomy procedure and HIPEC does not exist so far in rats. Nevertheless, animal models seem to be very important for evaluation of new therapeutic opportunities and toxicity of different multimodal therapies. In a first step we analysed the surgical tumour debulking of peritoneal surface malignancy in rats. A peritoneal surface malignancy from colonic origin was induced in 75 male BD IX rats. Twenty one days after induction of peritoneal surface malignancy rats were randomised and animals intend to create an operation with surgical tumour debulking. There was no tumour growth in two animals. The aim of the peritonectomy procedure was the complete tumour reduction. In this study the results of the surgical approach will be described. A complete tumour reduction (R0) was achieved in 34 animals. In 39 rats a macroscopic tumour deposit was left behind (R2). The intraoperative experimental Peritoneal Cancer Index (ePCI) was used to describe tumour weight and number of tumour inoculations. Both parameters were found to be dependent factors of complete tumour reduction. Six animals died due to therapeutical interventions. Surgical tumour debulking in rats with peritoneal surface malignancy is possible with high reliability and a low mortality rate. This animal model could be an important step for investigation of multimodal treatment options and toxicity in treatment regimens of peritoneal surface malignancy.

  10. [Antibiotic prophylaxis in colorectal surgery].

    PubMed

    Dellamonica, P; Bernard, E

    1994-01-01

    In elective colorectal surgery, the benefit of preoperative antibiotic prophylaxis is well established, with a reduction in wound infection rate to less than 10%. The antimicrobial agent used has to be active against aerobic and anaerobic pathogens such as Escheria coli and Bacteriodes fragilis. The efficacy of three schemes of administration: oral and/or parenteral prophylaxis associated with a mechanical preparation, has been demonstrated. Oral antibiotic administration is current practice in USA; the most widely used oral regimen is the combination of erythromycin and neomycin given the day before surgery. Parenteral prophylaxis with a cephalosporin active against Bacteriodes fragilis such as cefoxitin and cefotetan, is preferred in Europe. The issue of whether a systemic prophylaxis should be added to the oral regimen or not has not yet been resolved. However it seems that the association should be proposed in various situations: patients with a high risk factors score (rectal resection and operations lasting more than three hours), patients with incomplete mechanical preparation, delay of the onset of surgery after the last oral dose.

  11. Colorectal carcinoma in Hong Kong.

    PubMed

    Wong, J; Ong, G B

    1978-04-01

    The clinical and pathological features of colorectal carcinoma occurring in 470 Chinese patients in Hong Kong are reported. There was a preponderance of advanced stages of the disease in spite of the presence of a large number of well-differentiated lesions. Polyposis coli was the predisposing cause in 1% of our patients, and none of them had ulcerative colitis. The clinical features of our patients on presentation were generally similar to those exhibited by Caucasians. An abdominal mass was palpable in about half of patients with colonic lesions, and virtually all rectal cancers could be felt by rectal examination. Almost a quarter of our patients presented with complications. In 2% of our patients the initial diagnosis was acute appendictis. A high resection rate was achieved, but many radical resections turned out to be only palliative. Our operative mortality was 8.3%, although for social reasons, the "in-hospital" mortality was 19.2%. The corrected five-year survival rate was 42.7% when curative resection was attempted.

  12. Oral bisphosphonates and colorectal cancer.

    PubMed

    Vogtmann, Emily; Corley, Douglas A; Almers, Lucy M; Cardwell, Chris R; Murray, Liam J; Abnet, Christian C

    2017-03-10

    Use of oral bisphosphonates has been associated with a decreased risk of colorectal cancer (CRC), but the association may be related to residual confounding by healthy lifestyle or body mass index (BMI). Therefore, we conducted a prospective nested case-control study within the Kaiser Permanente, Northern California health system cohort. In total, 12,505 CRC cases were individually matched to 599,534 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression models with adjustment for important covariates extracted from the database. Participants who had ever used oral bisphosphonates were less likely than non-users to be diagnosed with CRC (OR 0.82; 95% CI: 0.74, 0.89). Colon and rectum site-specific associations were similar to the overall association. A stronger inverse association for ever use of bisphosphonates was observed for men (OR 0.63; 95% CI: 0.47, 0.85), however when stratified by previous lower endoscopy, the association was only observed in the participants who did not have a previous lower endoscopy (OR 0.73 (0.64, 0.83)). In conclusion, we found that oral bisphosphonate use was associated with a decreased odds of CRC, however this association may be due to residual confounding by BMI or another confounder.

  13. Genetic Architecture of Colorectal Cancer

    PubMed Central

    Peters, Ulrike; Bien, Stephanie; Zubair, Niha

    2015-01-01

    Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3–5%) of cases arises from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well-defined genes. In contrast, CRC is predominantly a late-onset “sporadic” disease, developing in individuals with no obvious hereditary syndrome. In recent years genome-wide association studies have discovered over 40 genetic regions to be associated with weak effects on sporadic CRC and it has been estimated that increasingly large genome-wide scans will identify many additional novel genetic regions. Subsequent experimental validations have identified the causally related variant(s) in a limited number of these genetic regions. Further biological insight could be obtained through ethnically diverse study populations, larger genetic sequencing studies, and development of higher-throughput functional experiments. Along with inherited variation, integration of the tumour genome may shed light on the carcinogenic processes in CRC. In addition to summarizing the genetic architecture of CRC, this review discusses genetic factors that modify environmental predictors of CRC, as well as examples of how genetic insight has improved clinical surveillance, prevention, and treatment strategies. In summary, substantial progress has been made in uncovering the genetic architecture of CRC and continued research efforts are expected to identify additional genetic risk factors that further our biological understanding of this disease. PMID:26187503

  14. Oral bisphosphonates and colorectal cancer

    PubMed Central

    Vogtmann, Emily; Corley, Douglas A.; Almers, Lucy M.; Cardwell, Chris R.; Murray, Liam J.; Abnet, Christian C.

    2017-01-01

    Use of oral bisphosphonates has been associated with a decreased risk of colorectal cancer (CRC), but the association may be related to residual confounding by healthy lifestyle or body mass index (BMI). Therefore, we conducted a prospective nested case-control study within the Kaiser Permanente, Northern California health system cohort. In total, 12,505 CRC cases were individually matched to 599,534 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression models with adjustment for important covariates extracted from the database. Participants who had ever used oral bisphosphonates were less likely than non-users to be diagnosed with CRC (OR 0.82; 95% CI: 0.74, 0.89). Colon and rectum site-specific associations were similar to the overall association. A stronger inverse association for ever use of bisphosphonates was observed for men (OR 0.63; 95% CI: 0.47, 0.85), however when stratified by previous lower endoscopy, the association was only observed in the participants who did not have a previous lower endoscopy (OR 0.73 (0.64, 0.83)). In conclusion, we found that oral bisphosphonate use was associated with a decreased odds of CRC, however this association may be due to residual confounding by BMI or another confounder. PMID:28281559

  15. Precancerous Lesions in Colorectal Cancer

    PubMed Central

    Sandouk, Fayez; Al Jerf, Feras; Al-Halabi, M. H. D. Bassel

    2013-01-01

    Colorectal cancer (CRC) is the third most common cause of cancer death in the world. The incidence rate (ASR) and age distribution of this disease differ between most of African-Middle-Eastern (AMAGE) and North America and Europe for many reasons. However, in all areas, “CRC” is considered as one of the most preventable cancers, because it might develop from variant processes like polyps and IBD in addition to the genetic pathogenesis which became very well known in this disease. We tried in this paper to review all the possible reasons of the differences in incidence and age between the west and AMAGE. Also we reviewed all the mutations that lead to the hereditary and familiar clustering of this disease with the correlations with the surrounding food and environment of different areas. Then, we focused on the precancerous pathology of this disease with special focusing on early detection depending on new endoscopy technology and most important genetic studies. We lastly reviewed the evidence of some of the surveillance and put suggestions about future surveillance programs and how important those programs are on the psychological aspect of the patients and their families. PMID:23737765

  16. Calcium remodeling in colorectal cancer.

    PubMed

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2017-01-10

    Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca(2+) stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca(2+)-release activated Ca(2+) channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca(2+) stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity.

  17. Determinants of metastatic competency in colorectal cancer.

    PubMed

    Tauriello, Daniele V F; Calon, Alexandre; Lonardo, Enza; Batlle, Eduard

    2017-01-01

    Colorectal cancer (CRC) is one of the most common cancer types and represents a major therapeutic challenge. Although initial events in colorectal carcinogenesis are relatively well characterized and treatment for early-stage disease has significantly improved over the last decades, the mechanisms underlying metastasis - the main cause of death - remain poorly understood. Correspondingly, no effective therapy is currently available for advanced or metastatic disease. There is increasing evidence that colorectal cancer is hierarchically organized and sustained by cancer stem cells, in concert with various stromal cell types. Here, we review the interplay between cancer stem cells and their microenvironment in promoting metastasis and discuss recent insights relating to both patient prognosis and novel targeted treatment strategies. A better understanding of these topics may aid the prevention or reduction of metastatic burden.

  18. Mass screening for colorectal cancer in Hungary.

    PubMed Central

    Preisich, P; Siba, S; Szakátsy, E

    1987-01-01

    Haemoccult screening for colorectal tumours was carried out in Hungary in small cities and villages around Budapest. Haemoccult slides were supplied to 17,662 individuals over 40 years of age, and 15,431 (87%) were returned. Of these, 346 (2.2%) were positive and 18 colorectal carcinomas were detected. Additionally, 24 patients with one or more polyps greater than 1 cm diameter were found. Of the screened cases of cancer 39% were in Dukes' stage A and B, a rate twice as good as when screening was not done. The cost per tumour detected amounted to about three times more than one monthly income, indicating that the costs of screening for colorectal cancer are relatively much higher in Hungary than in Western countries. All expenses were met from state funds. PMID:3625689

  19. [Argyrophilic nucleolar organizer regions (AgNORs) as malignancy biomarkers in colorectal neoplasms].

    PubMed

    Santacroce, L; Bufo, P; Gagliardi, S; Mastropasqua, M G; Losacco, T

    2001-01-01

    The high incidence of intestinal cancer has aroused strong interest in researching and trying to discover its morphologic precursors. In this contest the study of nucleolar organizing regions could be interesting as prognostic factor for bowel neoplasm and useful for differential diagnosis of intestinal diseases. The Authors report on the results of their study performed on 30 selected samples from 6 different bowel lesions.

  20. Sequential compression devices as prophylaxis for venous thromboembolism in high-risk colorectal surgery patients: reconsidering American Society of Colorectal Surgeons parameters.

    PubMed

    Ramirez, Jesus I; Vassiliu, Pantelis; Gonzalez-Ruiz, Claudia; Vukasin, Petar; Ortega, Adrian; Kaiser, Andreas M; Beart, Robert W

    2003-11-01

    The American Society of Colorectal Surgeons (ASCRS) recently endorsed low-molecular-weight heparin and low-dose heparin as primary prophylaxis for venous thromboembolism (VTE) in highest-risk patients. Our study evaluates the feasibility of sequential compression device (SCD) use for VTE prophylaxis in these patients. Computerized databases of discharge diagnoses from three hospitals were reviewed. All patients with colorectal cancer or inflammatory bowel disease during a 7-year period were identified. Those who underwent major abdominal surgery and received VTE prophylaxis exclusively with SCDs were selected for the study. Patients diagnosed with postoperative VTE were identified through review of the three databases and of patient records for 90 days after surgery. One thousand two hundred eighty-one patients classified as highest-risk under the published ASCRS parameters underwent major abdominal surgery and received SCDs perioperatively. The incidence of clinically detectable postoperative VTE was 0.78 per cent. There were trends toward lower incidence among patients with malignancy (0.53%) compared with inflammatory bowel disease (1.48%, P = 0.09), and those with abdominal compared to pelvic procedures (0.62% vs. 1.04%, P = 0.41). Prophylaxis for perioperative VTE solely with SCD is a viable option for patients classified as highest-risk under ASCRS parameters.

  1. ACR Appropriateness Criteria colorectal cancer screening.

    PubMed

    Yee, Judy; Kim, David H; Rosen, Max P; Lalani, Tasneem; Carucci, Laura R; Cash, Brooks D; Feig, Barry W; Fowler, Kathryn J; Katz, Douglas S; Smith, Martin P; Yaghmai, Vahid

    2014-06-01

    Colorectal cancer is the third leading cause of cancer deaths in the United States. Most colorectal cancers can be prevented by detecting and removing the precursor adenomatous polyp. Individual risk factors for the development of colorectal cancer will influence the particular choice of screening tool. CT colonography (CTC) is the primary imaging test for colorectal cancer screening in average-risk individuals, whereas the double-contrast barium enema (DCBE) is now considered to be a test that may be appropriate, particularly in settings where CTC is unavailable. Single-contrast barium enema has a lower performance profile and is indicated for screening only when CTC and DCBE are not available. CTC is also the preferred test for colon evaluation following an incomplete colonoscopy. Imaging tests including CTC and DCBE are not indicated for colorectal cancer screening in high-risk patients with polyposis syndromes or inflammatory bowel disease. This paper presents the updated colorectal cancer imaging test ratings and is the result of evidence-based consensus by the ACR Appropriateness Criteria Expert Panel on Gastrointestinal Imaging. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

  2. Skin: A mirror of internal malignancy

    PubMed Central

    Vora, Rita V.; Kota, RahulKrishna S.; Diwan, Nilofar G.; Jivani, Nidhi B.; Gandhi, Shailee S.

    2016-01-01

    Skin manifestations are a reflection of many of the internal diseases. Sometimes, skin disease may be the only manifestation of the internal disease. Internal malignancies may give rise to a number of cutaneous manifestations through their immunological, metabolic, and metastatic consequences. Curth proposed criteria to establish a causal relationship between a dermatosis and a malignant internal disease. Malignancy can present with a plethora of cutaneous manifestations. Here, we describe in brief about various skin manifestations of internal malignancies. PMID:28144085

  3. Perendoscopic Nd:YAG laser therapy of colorectal neoplasms

    NASA Astrophysics Data System (ADS)

    Norberto, Lorenzo; Ranzato, Riccardo; Marino, Saverio; Erroi, F.; Angriman, Imerio; Donadi, Michele; Paratore, S.; Scuderi, G.; D'Amico, D. F.

    1996-01-01

    The range of application of Nd:YAG laser is now wide and of particular interest in the treatment of neoplastic lesions of the large bowel, both benign and malignant, which, besides the debilitating of vegetative lesions, may also provide a good hemostasis of the bleeding ones. Yag laser treatment of malignancies is indicated in patients not suitable for surgery due to the extent of the disease or to the high anesthesiologic/surgical risk. The treatment of choice for benign neoplasms is represented by endoscopic polypectomy, being Yag laser therapy reserved to patients with very large polyps and with a high anesthesiologic risk. Yag laser therapy is also recommended in teleangiectasies with active or previous bleeding, since it allows the complete ablation of such lesions with subsequent outstanding hemostasis. Furthermore this treatment may be advantageously associated to other operative endoscopic procedures, such as diatermotherapy, dilatation and injection therapy. It is also to be outlined that Yag laser therapy is currently used to cure benign diseases and for the palliation of advanced cancer in inoperable patients. Our laser instrument is an Nd:Yag laser MBB Medilas 2 with maximum power of 100 watts at the tip, with 'non-contact' laser fibers. We use flexible optic fiberendoscopes of several sizes, according to the type of lesion to be treated. Moreover we have employed both Savary dilators of progressive caliber from 5 to 15 mm and Rigiflex pneumatic balloons. Adequate bowel preparation by means of isosmotic solution was achieved in patients with non stenotic neoplasm, or evacuative enemas and fluid diet in patients with bowel neoplastic stenoses. The patients were premedicated with benzodiazepines. Stenotic malignant lesions have been treated with endoscopic dilatation before laser treatment. At each session 4,000 - 8,000 joules of energy were administered; all patients received an average of 5 - 6 laser sessions. Followup laser sessions have then been

  4. Malignant melanoma of the foot and ankle.

    PubMed

    John, K J; Hayes, D W; Green, D R; Dickerson, J

    2000-04-01

    Malignant melanoma is a serious and devastating skin disease that podiatrists may be called upon to treat. It is pertinent that delays in diagnosis and treatment of malignant melanoma be avoided. Some of the topics discussed in this article are causes, clinical features, classification, and treatment of malignant melanoma, focusing on the foot and ankle.

  5. Abnormal activated partial thromboplastin time and malignancy.

    PubMed

    Delicata, M; Hambley, H

    2011-08-01

    Malignancy often results in clotting abnormalities. The aetiology of haemostasis problems in cancer is complex, and is still not completely understood. We describe a case of a patient with malignant mesothelioma, who was found to have elevated activated partial thromboplastin time, due to lupus anticoagulant. We suggest that patients with malignancy should have their coagulation checked prior to any invasive procedures.

  6. Malignant Transformation of Pulmonary Benign Metastasizing Leiomyoma

    PubMed Central

    Song, Kyung Sub; Keum, Dong Yoon; Hwang, Il Seon

    2017-01-01

    Pulmonary benign metastasizing leiomyoma (PBML) is defined as metastasis of a leiomyoma to lung tissue. It was first reported in 1937. P BML is known as a benign disease, but can undergo malignant transformation. Only 1 case of the malignant transformation of PBML to leiomyosarcoma has been reported previously. In this report, we present a case of malignant transformation of PBML. PMID:28180107

  7. Single-site Laparoscopic Colorectal Surgery Provides Similar Clinical Outcomes Compared to Standard Laparoscopic Surgery: An Analysis of 626 Patients

    PubMed Central

    Sangster, William; Messaris, Evangelos; Berg, Arthur S.; Stewart, David B.

    2015-01-01

    BACKGROUND Compared to standard laparoscopy, single-site laparoscopic colorectal surgerymay potentially offer advantages by creating fewer surgical incisions and providing a multi-functional trocar. Previous comparisons, however, have been limited by small sample sizes and selection bias. OBJECTIVE To compare 60-day outcomes between standard laparoscopic and single-site laparoscopic colorectal surgery patients undergoing elective and urgent surgeries. DESIGN This was an unselected retrospective cohort study comparing patients who underwent elective and unplanned standard laparoscopic or single-site laparoscopic colorectal resections for benign and malignant disease between 2008 and 2014. Outcomes were compared using univariate analyses. SETTING This study was conducted at a single institution. PATIENTS A total of 626 consecutive patients undergoing laparoscopic colorectal surgery were included. MAIN OUTCOME MEASURES Morbidity and mortality within 60 postoperative days. RESULTS 318 (51%) and 308 (49%) patients underwent standard laparoscopic and single-site laparoscopic procedures, respectively. No significant difference was noted in mean operative time (Standard laparoscopy 182.1 ± 81.3 vs. Single-site laparoscopy 177±86.5, p=0.30) and postoperative length of stay (Standard laparoscopy 4.8±3.4 vs. Single-site laparoscopy 5.5 ± 6.9, p=0.14). Conversions to laparotomy and 60-day readmissions were also similar for both cohorts across all procedures performed. A significant difference was identified in the number of patients who developed postoperative complications (Standard laparoscopy 19.2% vs. Single-site laparoscopy 10.7%, p=0.004), especially with respect to surgical-site infections (Standard laparoscopy 11.3% vs. Single-site laparoscopy 5.8%, p=0.02). LIMITATIONS This was a retrospective, single institution study. CONCLUSIONS Single-site laparoscopic colorectal surgery demonstrates similar results to standard laparoscopic colorectal surgery in regards to

  8. Amyopathic Dermatomyositis: A Concise Review of Clinical Manifestations and Associated Malignancies.

    PubMed

    Udkoff, Jeremy; Cohen, Philip R

    2016-10-01

    Amyopathic dermatomyositis is a rare, idiopathic, connective tissue disease that presents with dermatologic lesions of classic dermatomyositis but lacks the myopathy of this disease. Cutaneous manifestations may include Gottron's sign, heliotrope rash, and characteristic patterns of poikiloderma. There is a substantial risk for developing interstitial lung disease or malignancy in patients with amyopathic dermatomyositis. A literature review of amyopathic dermatomyositis was performed using the PubMed medical database. The key features of amyopathic dermatomyositis, including autoantibodies, clinical presentation and dermatologic manifestations, epidemiology, history, associated malignancies, management, and pathogenesis, are summarized in this review. Cancer (solid tumor) (73/79, 89 %) and hematologic malignancies (9/79, 11 %) were reported in 79 patients, with three patients having more than one malignancy. In addition, there were six patients with amyopathic dermatomyositis who had tumor of unknown primary, and eight patients with cancer-associated amyopathic dermatomyositis for whom no additional details were provided. From the group of 73 tumors for whom primary origin and sex were available, malignancy of the genitourinary organs (24/73, 33 %), aerorespiratory organs (15/73, 21 %), and breast (14/73, 19 %) were the most commonly observed solid organ tumors. Tumors of the genitourinary organs (15/48, 31 %) and breast (14/48, 29 %) were the most frequent neoplasms in women, accounting for 29 of 48 (60 %) cancers, with the most common sites being breast (14/48, 29 %), ovary (8/48, 17 %), and cervix or uterus (5/48, 10 %). In men, tumors of the aerorespiratory (9/25, 36 %) and genitourinary (9/25, 36 %) tracts were the most common neoplasms, accounting for 72 % (18/25) of cancers; the most common sites of primary malignancy were nasopharyngeal (6/25, 24 %), bladder (4/25, 16 %), and either colorectal, lung or prostate cancer (three cancers each

  9. Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the fukuoka colorectal cancer study.

    PubMed

    Morita, Makiko; Yin, Guang; Yoshimitsu, Shin-ichiro; Ohnaka, Keizo; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2013-01-01

    One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.

  10. Malignant change in dermatitis artefacta.

    PubMed Central

    Alcolado, J. C.; Ray, K.; Baxter, M.; Edwards, C. W.; Dodson, P. M.

    1993-01-01

    Dermatitis artefacta is a chronic skin lesion produced by self-trauma. Avoidance of further trauma, topical steroids and psychological therapy all play a part in the treatment of such lesions. Unresolved lesions may become large and disfiguring and subject to infection. We report a case of one such lesion in an elderly woman who persistently excoriated a cholecystectomy scar over 40 years. Malignant transformation occurred in a manner analogous to the neoplastic change observed in other types of chronic ulcer (Marjolin's ulcer). The squamous cell carcinoma presented with widespread metastases from which the patient eventually died. Recent literature concerning Marjolin's ulcers is reviewed and it is noted that this is the first reported case of death caused by malignant change in dermatitis artefacta. Images Figure 1 PMID:8234114

  11. Gastrointestinal Malignancy and the Microbiome

    PubMed Central

    Abreu, Maria T.; Peek, Richard M.

    2014-01-01

    Microbial species participate in the genesis of a substantial number of malignancies—in conservative estimates, at least 15% of all cancer cases are attributable to infectious agents. Little is known about the contribution of the gastrointestinal (GI) microbiome to the development of malignancies. Resident microbes can promote carcinogenesis by inducing inflammation, increasing cell proliferation, altering stem cell dynamics, and producing metabolites such as butyrate, which affect DNA integrity and immune regulation. Studies in humans and rodent models of cancer have identified effector species and relationships among members of the microbial community in the stomach and colon that increase the risk for malignancy. Strategies to manipulate the microbiome, or the immune response to such bacteria, could be developed to prevent or treat certain GI cancers. PMID:24406471

  12. Report From the Jerusalem Workshop on Lynch Syndrome-Hereditary Nonpolyposis Colorectal Cancer

    PubMed Central

    Boland, C. Richard; Shike, Moshe

    2011-01-01

    A Workshop was held in Jerusalem, Israel, on October 26 and 27, 2009 to discuss the management of Lynch syndrome-hereditary nonpolyposis colorectal cancer (CRC), with the primary goal to develop consensus for the optimal management of this disease. A second goal was to identify areas of research with the potential to advance the clinical management of Lynch syndrome. The perspectives and recommendations from the workshop are meant to be a platform for discussion and deliberation. The Workshop was organized by Moshe Shike (Memorial Sloan Kettering Cancer Center, New York) and sponsored by The Colon Cancer Foundation. More details of each presentation are available in an on-line supplement. PMID:20416305

  13. Estrogen receptor alpha polymorphisms and the risk of malignancies.

    PubMed

    Anghel, Andrei; Narita, Diana; Seclaman, Edward; Popovici, Emilian; Anghel, Mariana; Tamas, Liviu

    2010-12-01

    Estrogens represent risk factors for endocrine-related cancers and play also an important role in the development and progression of other malignancies. In order to analyze the associations between estrogen receptor gene alpha polymorphisms and cancers susceptibility, we genotyped six single nucleotide polymorphisms (SNPs) in 163 Caucasian cancer patients--103 breast cancers and 60 other malignancies (colorectal, bladder, hepatocellular carcinoma and acute myeloid leukemia)--and 114 healthy controls using hybridization probes. We performed Armitage`s association trend-test to evaluate the risk. Linkage disequilibrium (LD) was assessed for each pair of markers. The genotypes CC and CT of rs3798577 were significantly associated with the cancers risk (p-trend breast = 4 × 10(-5); p-trend cancers = 1 × 10(-5)); in discrepancy with breast cancer where the C-allele represented the risk allele, for bladder, hepatocellular carcinomas and leukemia, the T allele seems to confer susceptibility. The minor G allele of rs1801132 was protective in our cases (p = 1 × 10(-4)); for rs2228480, the heterozygous frequency was higher for cancer groups (p = 0.03); the SNP pairs rs2228480&rs3798577 and rs2234693&rs9340799 were in low LD; the haplotypes T-A of rs2234693&rs9340799 and G-C of rs2228480&rs3798577 showed a trend to be higher represented in breast cancers; T allele of rs2234693 was higher expressed in breast, colon cancers and leukemia; rs2077647 was associated with colon (p = 0.008, C-risk allele) and bladder (p = 0.01, T-risk allele) cancers. We concluded that ESR1 polymorphisms may have distinct impact in carcinogenesis and further genotyping will establish whether these findings remain significant in larger cohorts.

  14. [Malignant fibrous histiocytoma. Case report].

    PubMed

    Morlino, A; Rossi, M T; Fabrizio, T; Scutari, F

    2010-03-01

    Malignant fibroous histiocytoma (MFH) is an aggressive soft tissue sarcoma, that most frequently occurs in the muscles of the extremities and in abdominal or in retroperitoneal space of young adults. It is seldom confined to the skin and subcutaneous tissue. It is rarely diagnosed before excision and pathological exam, and has an unfavorable prognostic in some cases. This work reports the case of a 94 years old patient with originally cutaneous MFH stressing the importance of the early diagnosis.

  15. Clinical, pathologic, and molecular features of early-onset colorectal carcinoma.

    PubMed

    Yantiss, Rhonda K; Goodarzi, Mahmoud; Zhou, Xi K; Rennert, Hanna; Pirog, Edyta C; Banner, Barbara F; Chen, Yao-Tseng

    2009-04-01

    The incidence of colorectal carcinoma has increased among patients <40 years of age for unclear reasons. In this study, we describe the clinical, pathologic, and molecular features of colorectal carcinomas that developed in young patients. We compiled a study group of 24 patients <40 years of age with colorectal carcinoma, and 45 patients > or =40 years of age served as controls. Cases were evaluated for clinical risk factors of malignancy and pathologic features predictive of outcome. The tumors were immunohistochemically stained for O6-methylguanine methyltransferase, MLH-1, MSH-2, MSH-6, beta-catenin, chemokine (C-X-C motif) receptor 4, epidermal growth factor receptor, TP53, p16, survivin, and alpha-methylacyl-CoA racemase; assessed for microsatellite instability and mutations in beta-catenin, APC, EGFR, PIK3CA, KRAS, and BRAF; evaluated for micro-RNA expression (miR-21, miR-20a, miR-183, miR-192, miR-145, miR-106a, miR-181b, and miR-203); and examined for evidence of human papillomavirus infection. One study patient each had ulcerative colitis and hereditary nonpolyposis colorectal cancer. Ninety-two percent of tumors from young patients occurred in the distal colon (P=0.006), particularly the rectum (58%, P=0.02), and 75% were stage III or IV. Tumors from young patients showed more frequent lymphovascular (81%, P=0.03) and/or venous (48%, P=0.003) invasion, an infiltrative growth pattern (81%, P=0.03), and alpha-methylacyl-CoA racemase expression (83%, P=0.02) compared with controls. Carcinomas in this group showed significantly increased expression of miR-21, miR-20a, miR-145, miR-181b, and miR-203 (P< or =0.005 for all comparisons with controls). These results indicate that early-onset carcinomas commonly show pathologic features associated with aggressive behavior. Posttranslational regulation of mRNA and subsequent protein expression may be particularly important to the development of colorectal carcinomas in young patients.

  16. Malignant cancer and invasive placentation

    PubMed Central

    D'Souza, Alaric W.; Wagner, Günter P.

    2014-01-01

    Cancer metastasis is an invasive process that involves the transplantation of cells into new environments. Since human placentation is also invasive, hypotheses about a relationship between invasive placentation in eutherian mammals and metastasis have been proposed. The relationship between metastatic cancer and invasive placentation is usually presented in terms of antagonistic pleiotropy. According to this hypothesis, evolution of invasive placentation also established the mechanisms for cancer metastasis. Here, in contrast, we argue that the secondary evolution of less invasive placentation in some mammalian lineages may have resulted in positive pleiotropic effects on cancer survival by lowering malignancy rates. These positive pleiotropic effects would manifest themselves as resistance to cancer cell invasion. To provide a preliminary test of this proposal, we re-analyze data from Priester and Mantel (Occurrence of tumors in domestic animals. Data from 12 United States and Canadian colleges of veterinary medicine. J Natl Cancer Inst 1971;47:1333-44) about malignancy rates in cows, horses, cats and dogs. From our analysis we found that equines and bovines, animals with less invasive placentation, have lower rates of metastatic cancer than felines and canines in skin and glandular epithelial cancers as well as connective tissue sarcomas. We conclude that a link between type of placentation and species-specific malignancy rates is more likely related to derived mechanisms that suppress invasion rather than different degrees of fetal placental aggressiveness. PMID:25324490

  17. Targeting hedgehog in hematologic malignancy.

    PubMed

    Irvine, David A; Copland, Mhairi

    2012-03-08

    The Hedgehog pathway is a critical mediator of embryonic patterning and organ development, including hematopoiesis. It influences stem cell fate, differentiation, proliferation, and apoptosis in responsive tissues. In adult organisms, hedgehog pathway activity is required for aspects of tissue maintenance and regeneration; however, there is increasing awareness that abnormal hedgehog signaling is associated with malignancy. Hedgehog signaling is critical for early hematopoietic development, but there is controversy over its role in normal hematopoiesis in adult organisms where it may be dispensable. Conversely, hedgehog signaling appears to be an important survival and proliferation signal for a spectrum of hematologic malignancies. Furthermore, hedgehog signaling may be critical for the maintenance and expansion of leukemic stem cells and therefore provides a possible mechanism to selectively target these primitive cell subpopulations, which are resistant to conventional chemotherapy. Indeed, phase 1 clinical trials of hedgehog pathway inhibitors are currently underway to test this hypothesis in myeloid leukemias. This review covers: (1) the hedgehog pathway and its role in normal and malignant hematopoiesis, (2) the recent development of clinical grade small molecule inhibitors of the pathway, and (3) the potential utility of hedgehog pathway inhibition as a therapeutic strategy in hemato-oncology.

  18. Giant Malignant Pheochromocytoma with Palpable Rib Metastases

    PubMed Central

    Gokce, Gokhan; Kilicli, Fatih; Elagoz, Sahande; Ayan, Semih; Gultekin, Emin Yener

    2014-01-01

    Pheochromocytoma is a rare and usually benign neuroendocrine neoplasm. Only 10% of all these tumors are malignant and there are no definitive histological or cytological criteria of malignancy. Single malignancy criteria are the presence of advanced locoregional disease or metastases. We report a case, with a giant retroperitoneal tumor having multiple metastases including palpable rib metastases, who was diagnosed as a malignant pheochromocytoma. The patient was treated with surgery. The literature was reviewed to evaluate tumor features and current diagnostic and therapeutic approaches for patients with metastatic or potentially malignant pheochromocytoma. PMID:25152826

  19. Naked megakaryocyte nuclei: a clue to malignancy.

    PubMed

    Lefkowitz, M; Lefkowitz, E

    1977-10-01

    Bone marrow smears from 63 patients with various malignancies and a series of 51 controls were examined for the presence and percentage of naked megakaryocyte nuclei (NMN). Patients with malignancy had more than 15% NMN, which, when compared with the incidence in controls, was statistically significant. The etiology of this artifact is unknown. It is a clue to the presence of malignancy, and might be useful in following treated cases of malignancy for evidence of relapse. NMN should not be confused with metastatic malignant cells.

  20. Immunotherapy and immunoescape in colorectal cancer

    PubMed Central

    Mazzolini, Guillermo; Murillo, Oihana; Atorrasagasti, Catalina; Dubrot, Juan; Tirapu, Iñigo; Rizzo, Miguel; Arina, Ainhoa; Alfaro, Carlos; Azpilicueta, Arantza; Berasain, Carmen; Perez-Gracia, José L; Gonzalez, Alvaro; Melero, Ignacio

    2007-01-01

    Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma. PMID:17990348

  1. URINARY MUTAGENICITY AND COLORECTAL ADENOMA RISK

    EPA Science Inventory

    Abstract

    We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenici...

  2. BK polyomavirus association with colorectal cancer development.

    PubMed

    Khabaz, M N; Nedjadi, T; Gari, M A; Al-Maghrabi, J A; Atta, H M; Basuni, A A; Elderwi, D A

    2016-05-06

    The development of human neoplasms can be provoked by exposure to one of several viruses. Burkitt lymphoma, cervical carcinoma, and hepatocellular carcinoma are associated with Epstein-Barr, human papilloma, and hepatitis B virus infections, respectively. Over the past three decades, many studies have attempted to establish an association between colorectal cancer and viruses, with debatable results. The aim of the present research was to assess the presence of BK polyomavirus (BKV) DNA and protein in colorectal cancer samples from patients in the Western Province of Saudi Arabia. DNA extracted from archival samples of colorectal cancer tissues was analyzed for BKV sequences using polymerase chain reaction (PCR)-based techniques. In addition, expression of a BKV protein was assessed using immunohistochemical staining. None of the tumor and control samples examined tested positive for BKV DNA in PCR assays. Furthermore, immunohistochemical staining failed to detect viral proteins in both cancer and control specimens. These results may indicate that BKV is not associated with the development of colorectal adenocarcinoma in patients in the Western Province of Saudi Arabia.

  3. Diet and supplements and their impact on colorectal cancer

    PubMed Central

    Pericleous, Marinos; Mandair, Dalvinder

    2013-01-01

    Background Colorectal cancer is the third commonest cancer and the third leading cause of cancer death among men and women. It has been proposed that dietary factors are responsible for 70-90% of colorectal cancer and diet optimization may prevent most cases. Aim To evaluate the role of dietary components and supplements in colorectal cancer. Methods Bibliographical searches were performed in Pubmed for the terms “diet and colorectal cancer”, “diet and colon cancer”, “diet and rectal cancer”, “nutrition and colorectal cancer”, “probiotics and colorectal cancer”, “prebiotics and colorectal cancer”, “alcohol and cancer” and “colorectal cancer epidemiology”. Results Consumption of processed or red meat, especially when cooked at high temperatures may be associated with increased risk of colorectal cancer. The evidence for dietary fibre is unclear but foods that contain high amounts of fibre are usually rich in polyphenols which have been shown to alter molecular processes that can encourage colorectal carcinogenesis. Meta-analyses provide evidence on the benefits of circulating, diet-derived and supplemented, vitamin D and Calcium. We also found that diets rich in Folate may prevent colorectal carcinoma. The evidence on dietary micronutrients such as Zinc and Selenium in association with colorectal cancer is not conclusive. It has been suggested that there may be a direct association between alcohol intake and colorectal cancer. In vitro and in vivo studies have highlighted a possible protective role of prebiotics and probiotics. Conclusions The lack of randomized trials and the presence of confounding factors including smoking, physical activity, obesity and diabetes may often yield inconclusive results. Carefully designed randomized trials are recommended. PMID:24294513

  4. Dietary patterns and colorectal cancer risk in a Korean population

    PubMed Central

    Park, Yoon; Lee, Jeonghee; Oh, Jae Hwan; Shin, Aesun; Kim, Jeongseon

    2016-01-01

    Abstract Colorectal cancer (CRC) has been recognized as one of the major malignancies in Korea. Analyses of dietary patterns can provide insight into the complex interactions of foods, nutrients, and biologically active components within a diet, which vary among populations. We aimed to investigate the associations between dietary patterns and colorectal cancer risk in Koreans. In a study of 923 cases and 1846 controls, principal component analysis was used to identify dietary patterns based on 33 predefined food groups using a 106-item semiquantitative food frequency questionnaire (SQFFQ). The associations between dietary patterns and CRC risk were assessed using binary and polytomous logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Three dietary patterns (traditional, Westernized, and prudent) were derived. The proportion of total variation explained by 3 patterns was 24.2% for men and 25.3% for women. The traditional and prudent patterns were inversely associated with CRC risk [OR and 95% CI for the highest intake tertile of pattern score vs. the lowest = 0.35 (0.27–0.46) and 0.37 (0.28–0.48), respectively], whereas the Westernized pattern showed a positive association, especially among women [OR = 2.13 (1.35–3.34) for the highest tertile vs. the lowest]. A decrease in CRC risk among those with the highest intake of the prudent pattern was observed in all anatomical subsites in both men [OR = 0.36 (0.19–0.68) for proximal colon; 0.21 (0.12–0.36) for distal colon; 0.28 (0.18–0.44) for rectum] and women [OR = 0.28 (0.11–0.71); 0.27 (0.13–0.54); 0.45 (0.25–0.83)]. Our results indicate that individuals who prefer the Westernized dietary pattern should be made aware of their increased CRC risk. The traditional dietary pattern and the prudent pattern, which are rich in fruits and dairy products, are recommended for the Korean population to prevent CRC. PMID:27336862

  5. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible

    PubMed Central

    Majumdar, Sumit; Kotina, Sreekanth; Uppala, Divya; Kumar, Singam Praveen

    2016-01-01

    Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive tumor that is usually found in the extremities, trunk and infrequently found in the head and neck area particularly in the jaws, arising from the cells allied with nerve sheath. Mandibular MPNST may either arise from a preexisting neurofibroma or develop de novo. Because of the greater variability from case to case in overall appearance both clinically and histologically, a case of MPNST of the mandible in a 25-year-old female patient is reported. The lesion was excised and immunohistological studies (S-100 & Neuron specific enolase) were conducted to confirm the neural origin. PMID:27504425

  6. Validating Billing/Encounter Codes as Indicators of Lung, Colorectal, Breast, and Prostate Cancer Recurrence using Two Large Contemporary Cohorts

    PubMed Central

    Hassett, Michael J.; Ritzwoller, Debra P.; Taback, Nathan; Carroll, Nikki; Cronin, Angel M.; Ting, Gladys V.; Schrag, Deb; Warren, Joan L.; Hornbrook, Mark C.; Weeks, Jane C.

    2012-01-01

    Background A substantial proportion of cancer-related mortality is attributable to recurrent, not de novo metastatic disease, yet we know relatively little about these patients. To fill this gap, investigators often use administrative codes for secondary malignant neoplasm or chemotherapy to identify recurrent cases in population-based datasets. However, these algorithms have not been validated in large, contemporary, routine care cohorts. Objective To evaluate the validity of secondary malignant neoplasm and chemotherapy codes as indicators of recurrence after definitive local therapy for stage I-III lung, colorectal, breast, and prostate cancer. Research Design, Subjects & Measures We assessed the sensitivity, specificity, and positive predictive value (PPV) of these codes 14- and 60-months after diagnosis using two administrative datasets linked with gold-standard recurrence status information: CanCORS/Medicare (diagnoses 2003-2005) and HMO/Cancer Research Network (diagnoses 2000-2005). Results We identified 929 CanCORS/Medicare patients and 5298 HMO/CRN patients. Sensitivity, specificity, and PPV ranged widely depending on which codes were included and the type of cancer. For patients with lung, colorectal, and breast cancer, the combination of secondary malignant neoplasm and chemotherapy codes was the most sensitive (75%-85%); no code-set was highly sensitive and highly specific. For prostate cancer, no code-set offered even moderate sensitivity (≤19%). Conclusions Secondary malignant neoplasm and chemotherapy codes could not identify recurrent cancer without some risk of misclassification. Findings based on existing algorithms should be interpreted with caution. More work is needed to develop a valid algorithm that can be used to characterize outcomes and define patient cohorts for comparative effectiveness research studies. PMID:23222531

  7. The Expression and Significance of Feces Cyclooxygensae-2 mRNA in Colorectal Cancer and Colorectal Adenomas

    PubMed Central

    Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

    2017-01-01

    Background/Aim: This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. Materials and Methods: The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. Results: The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842, P = 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525, P = 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. Conclusions: High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer. PMID:28139497

  8. Correlations Between Cutaneous Malignant Melanoma and Other Cancers: An Ecological Study in Forty European Countries

    PubMed Central

    Serrano, Pablo Fernandez-Crehuet; Serrano, Jose Luis Fernandez-Crehuet; Allam, Mohamed Farouk; Navajas, Rafael Fernandez-Crehuet

    2016-01-01

    Background: The presence of noncutaneous neoplasms does not seem to increase the risk of cutaneous malignant melanoma; however, it seems to be associated with the development of other hematological, brain, breast, uterine, and prostatic neoplasms. An ecological transversal study was conducted to study the geographic association between cutaneous malignant melanoma and 24 localizations of cancer in forty European countries. Methods: Cancer incidence rates were extracted from GLOBOCAN database of the International Agency for Research on Cancer. We analyzed the age-adjusted and gender-stratified incidence rates for different localizations of cancer in forty European countries and calculated their correlation using Pearson's correlation test. Results: In males, significant correlations were found between cutaneous malignant melanoma with testicular cancer (r = 0.83 [95% confidence interval (CI): 0.68–0.89]), myeloma (r = 0.68 [95% CI: 0.46–0.81]), prostatic carcinoma (r = 0.66 [95% CI: 0.43–0.80]), and non-Hodgkin lymphoma (NHL) (r = 0.63 [95% CI: 0.39–0.78]). In females, significant correlations were found between cutaneous malignant melanoma with breast cancer (r = 0.80 [95% CI: 0.64–0.88]), colorectal cancer (r = 0.72 [95% CI: 0.52–0.83]), and NHL (r = 0.71 [95% CI: 0.50–0.83]). Conclusions: These correlations call to conduct new studies about the epidemiology of cancer in general and cutaneous malignant melanoma risk factors in particular. PMID:27217938

  9. Implementation Intentions and Colorectal Screening

    PubMed Central

    Greiner, K. Allen; Daley, Christine M.; Epp, Aaron; James, Aimee; Yeh, Hung-Wen; Geana, Mugur; Born, Wendi; Engelman, Kimberly K.; Shellhorn, Jeremy; Hester, Christina M.; LeMaster, Joseph; Buckles, Daniel; Ellerbeck, Edward F.

    2015-01-01

    Background Low-income and racial/ethnic minority populations experience disproportionate colorectal cancer (CRC) burden and poorer survival. Novel behavioral strategies are needed to improve screening rates in these groups. Purpose To test a theoretically based “implementation intentions” intervention for improving CRC screening among unscreened adults in urban safety-net clinics. Design Randomized controlled trial. Setting/participants Adults (N=470) aged ≥50 years, due for CRC screening, from urban safety-net clinics were recruited. Intervention The intervention (conducted in 2009–2011) was delivered via touchscreen computers that tailored informational messages to decisional stage and screening barriers. The computer then randomized participants to generic health information on diet and exercise (Comparison group) or “implementation intentions” questions and planning (Experimental group) specific to the CRC screening test chosen (fecal immunochemical test or colonoscopy). Main outcome measures The primary study outcome was completion of CRC screening at 26 weeks based on test reports (analysis conducted in 2012–2013). Results The study population had a mean age of 57 years, and was 42% non-Hispanic African American, 28% non-Hispanic white, and 27% Hispanic. Those receiving the implementation intentions–based intervention had higher odds (AOR=1.83, 95% CI=1.23, 2.73) of completing CRC screening than the Comparison group. Those with higher self-efficacy for screening (AOR=1.57, 95% CI=1.03, 2.39), history of asthma (AOR=2.20, 95% CI=1.26, 3.84), no history of diabetes (AOR=1.86, 95% CI=1.21, 2.86), and reporting they had never heard that “cutting on cancer” makes it spread (AOR=1.78, 95% CI=1.16, 2.72) were more likely to complete CRC screening. Conclusions The results of this study suggest that programs incorporating an implementation intentions approach can contribute to successful completion of CRC screening even among very low-income and

  10. Glasgow Prognostic Score (GPS) can be a useful indicator to determine prognosis of patients with colorectal carcinoma.

    PubMed

    Nozoe, Tadahiro; Matono, Rumi; Ijichi, Hideki; Ohga, Takefumi; Ezaki, Takahiro

    2014-01-01

    The Glasgow Prognostic Score (GPS), an inflammation-based score, has been used to predict the biologic behavior of malignant tumors. The aim of the current study was to elucidate a further significance of GPS in colorectal carcinoma. Correlation of GPS and modified GPS (mGPS), which are composed of combined score provided for serum elevation of C-reactive protein and hypoalbuminemia examined before surgical treatment, with clinicopathologic features was investigated in 272 patients with colorectal carcinoma. Survival of GPS 1 patients was significantly worse than that of GPS 0 patients (P= 0.009), and survival of GPS 2 patients was significantly worse than that of GPS 1 patients (P < 0.0001). Similarly, survival of mGPS 1 patients was significantly worse than that of mGPS 0 patients (P = 0.009), and survival of mGPS 2 patients was significantly worse than that of mGPS 1 patients (P = 0.0006). Multivariate analysis demonstrated that GPS (P < 0.0001) as well as tumor stage (P= 0.004) and venous invasion (P = 0.011) were factors independently associated with worse prognosis. Both GPS and mGPS could classify outcome of patients with a clear stratification, and could be applied as prognostic indicators in colorectal carcinoma.

  11. Expression of apical junction complex proteins in colorectal mucosa of miniature dachshunds with inflammatory colorectal polyps

    PubMed Central

    YOKOYAMA, Nozomu; OHTA, Hiroshi; KAGAWA, Yumiko; LEELA-ARPORN, Rommaneeya; DERMLIM, Angkhana; NISA, Khoirun; MORITA, Tomoya; OSUGA, Tatsuyuki; SASAKI, Noboru; MORISHITA, Keitaro; NAKAMURA, Kensuke; TAKIGUCHI, Mitsuyoshi

    2017-01-01

    We examine the expression of tight junction and adherence junction proteins in the colorectal mucosa of miniature dachshunds (MDs) with inflammatory colorectal polyps (ICRPs). Colorectal mucosa samples were endoscopically obtained from 8 MDs with ICRPs and 8 control dogs for immunoblotting. Paraffin-embedded tissues of surgically resected inflamed lesions from another 5 MDs with ICRPs and full-thickness colorectal specimens from 5 healthy beagles were obtained for immunohistochemistry. The expression patterns of claudin-1, -2, -3, -4, -5, -7 and -8, E-cadherin and β-catenin were analyzed in the non-inflamed mucosa and inflamed mucosa of ICRPs and colorectal mucosa of control dogs by immunoblotting. The localization of these proteins in the inflamed lesions was analyzed by immunohistochemistry. The expressions of each of claudin, E-cadherin and β-catenin were not significantly different between control dogs and non-inflamed colonic mucosa from MDs with ICRPs. In contrast, only E-cadherin and β-catenin were detected in the inflamed lesions of MDs with ICRPs. By immunohistochemistry, claudin-2, -3, -4, -5 and -7, E-cadherin and β-catenin were expressed in the colorectal epithelium within the inflamed mucosa, but not in granulation tissue. Distributions of claudin-2, -3, -4, -5, and -7, E-cadherin and β-catenin in the colonic epithelium were not different between MDs with ICRPs and control dogs. These results indicated that no significant alteration was detected in several tight junction or adherence junction proteins expression in the colorectal epithelium of ICRPs. PMID:28090006

  12. Meningioma after radiotherapy for malignancy.

    PubMed

    Morgenstern, Peter F; Shah, Kalee; Dunkel, Ira J; Reiner, Anne S; Khakoo, Yasmin; Rosenblum, Marc K; Gutin, Philip

    2016-08-01

    Complications of radiation exposure have gained importance with increasing cancer survivorship. Secondary malignancies have been associated with cranial radiation exposure. We present our experience with intracranial radiation-induced meningioma (RIM) and discuss the implications of its presentation and natural history for patient management. Patients diagnosed with meningioma who had received radiation therapy between 1960 and 2014 were identified. Records were retrospectively reviewed for details of radiation exposure, previous malignancies, meningioma subtypes, multiplicity and pathologic descriptions, treatment and follow-up. Thirty patients were diagnosed with RIM. Initial malignancies included acute lymphocytic leukemia (33.3%), medulloblastoma (26.7%) and glioma (16.7%) at a mean age of 8.1years (range 0.04-33years). The mean radiation dose was 34Gy (range 16-60Gy) and latency time to meningioma was 26years (range 8-51years). Twenty-one patients (70%) underwent surgery. Of these, 57.1% of tumors were World Health Organization (WHO) grade I while 42.9% were WHO II (atypical). The mean MIB-1 labeling index for patients with WHO I tumors was 5.44%, with 33.3% exhibiting at least 5% staining. Mean follow-up after meningioma diagnosis was 5.8years. Mortality was zero during the follow-up period. Meningioma is an important long-term complication of therapeutic radiation. While more aggressive pathology occurs more frequently in RIM than in sporadic meningioma, it remains unclear whether this translates into an effect on survival. Further study should be aimed at delineating the risks and benefits of routine surveillance for the development of secondary neoplasms after radiation therapy.

  13. Genetic alterations and oxidative metabolism in sporadic colorectal tumors from a Spanish community.

    PubMed

    Oliva, M R; Ripoll, F; Muñiz, P; Iradi, A; Trullenque, R; Valls, V; Drehmer, E; Sáez, G T

    1997-04-01

    Deletions of loci on chromosomes 5q, 17p, 18q, and 22q, together with the incidence of p53 mutations and amplification of the double minute-2 gene were investigated in the sporadic colorectal tumors of 44 patients from a Spanish community. Chromosome deletions were analyzed by means of loss of heterozygosity analysis using a restriction fragment length polymorphism assay. Allelic losses were also detected by polymerase chain reaction (PCR)-single-stranded conformation polymorphism (SSCP) analysis of a polymorphic site in intron 2 of the p53 gene. The percentages of genetic deletions on the screened chromosomes were 39.3% (5q), 58.3% (17p), 40.9% (18q), and 40% (22q). Mutations in p53 exons 2-9 were examined by PCR-SSCP analysis and direct sequencing of the mutated region. Twenty of 44 tumor samples (45.45%) showed mutations at various exons except for exons 2, 3, and 9, the most frequent changes being G-->T transversion and C-->T transition. Because oxygen-free radicals play a role in the carcinogenesis process, we evaluated the oxidative status of the colorectal tumors. Antioxidant activities, lipid peroxidation, and DNA-damaged product concentrations in colon tumors and normal mucosa were compared. In tumor tissues, superoxide dismutase and catalase decreased fourfold and twofold, respectively, whereas glutathione peroxidase and reduced glutathione increased threefold. Malondialdehyde and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were twofold higher in colorectal tumors than in normal mucosa. Seven of 10 DNA tumor samples (70%) showing higher values of 8-OHdG also had genetic alterations at different chromosomal loci. In these samples, the p53 gene was deleted or mutated in 71.4% of cases. We concluded that the observed changes in the oxidative metabolism of the tumor cells and the consecutive increase in DNA damage may potentiate the genomic instability of different chromosomal regions, leading to further cell malignancy and tumor expansion.

  14. The clinical analysis of acute pancreatitis in colorectal cancer patients undergoing chemotherapy after operation

    PubMed Central

    Ji, Yanlei; Han, Zhen; Shao, Limei; Li, Yunling; Zhao, Long; Zhao, Yuehuan

    2015-01-01

    Acute pancreatitis is a rare complication in postoperative colorectal cancer patients after FOLFOX6 (oxaliplatin + calcium folinate +5-FU [5-fluorouracil]) chemotherapy. In this paper, a total of 62 patients with gastrointestinal cancer were observed after the burst of acute pancreatitis. Surgery of the 62 cases of colorectal cancer patients was completed successfully. But when they underwent FOLFOX6 chemotherapy, five patients got acute pancreatitis (8.06%), four (6.45%) had mild acute pancreatitis, and one (1.61%) had severe acute pancreatitis, of which two were males (3.23%) and three females (4.84%). No patients (0.00%) had acute pancreatitis on the 1st day after chemotherapy; one patient (1.61%) got it in the first 2 and 3 days after chemotherapy; and three others (4.83%) got it in the first 4 days after chemotherapy. In the 62 patients with malignant tumors, the body mass index (BMI) was less than 18 (underweight) in six of them, with two cases of acute pancreatitis (33.33%); the BMI was 18–25 (normal weight) in 34 cases, with one case (2.94%) of acute pancreatitis; the BMI was 25–30 (overweight) in 13 cases, with 0 cases (0.00%) of acute pancreatitis; and the BMI was ≥30 (obese) in nine patients, with two cases of acute pancreatitis (22.22%). After symptomatic treatment, four patients were cured and one died; the mortality rate was 1.61%. Most of them appeared in the first 4 days after chemotherapy; the probability of this complication is significantly higher in slim and obese patients than in normal weight patients. Postoperative colorectal cancer patients after FOLFOX6 chemotherapy have a sudden onset of acute pancreatitis occult, especially in patients with severe acute pancreatitis; the symptoms are difficult to control, there is high mortality and it is worthy of clinician’s attention. PMID:26392780

  15. Adherence to colonoscopy recommendations for first-degree relatives of young patients diagnosed with colorectal cancer

    PubMed Central

    Garcia, Guilherme H; Riechelmann, Rachel P; Hoff, Paulo M

    2015-01-01

    OBJECTIVES: Colorectal cancer is the third leading cause of cancer death in the United States. The American College of Gastroenterology recommends screening for first-degree relatives of patients diagnosed with colorectal cancer before the age of 50. A colonoscopy is one of the most commonly recommended exams due to its specificity and the possibility to resect pre-malignant lesions. Nevertheless, the rate of physician adherence to this recommendation is unknown. METHODS: This transversal study was performed at a major cancer center in Brazil with 62 patients, aged 18 to 50, who completed a questionnaire on information received from their physicians regarding screening their first-degree relatives. We used the answers from patients who provided explicit consent. RESULTS: Two hundred and three patients were eligible to participate and 93 (45.8%) agreed to complete the questionnaire. Twenty-three questionnaires (24.73%) were returned and 39 were completed by telephone. Of the patients who answered the questionnaire, 39 (62.9%) had received a colonoscopy recommendation for their first-degree relatives and 23 (37.1%) were not informed of the recommendation. Among the patients who received the recommendations, 20.51% affirmed that all relatives completed the exam and 51.28% stated that no relatives completed the exam. DISCUSSION: The adherence rate of our physicians to the ACG guideline recommendations was 62.9%. Considering that our study was performed at a leading center for cancer treatment in Latin America, we had expected better adherence. The results show that adherence to the colorectal cancer screening recommendations for high-risk patients must be improved. PMID:26598083

  16. Inhibition of TMEM16A Expression Suppresses Growth and Invasion in Human Colorectal Cancer Cells

    PubMed Central

    Sui, Yujie; Sun, Meiyan; Wu, Fei; Yang, Longfei; Di, Weihua; Zhang, Guizhen; Zhong, Lili; Ma, Zhiming; Zheng, Jinhao; Fang, Xuedong; Ma, Tonghui

    2014-01-01

    Metastasis leads to poor prognosis in colorectal cancer patients, and there is a growing need for new therapeutic targets. TMEM16A (ANO1, DOG1 or TAOS2) has recently been identified as a calcium-activated chloride channel (CaCC) and is reported to be overexpressed in several malignancies; however, its expression and function in colorectal cancer (CRC) remains unclear. In this study, we found expression of TMEM16A mRNA and protein in high-metastatic-potential SW620, HCT116 and LS174T cells, but not in primary HCT8 and SW480 cells, using RT-PCR, western blotting and immunofluorescence labeling. Patch-clamp recordings detected CaCC currents regulated by intracellular Ca2+ and voltage in SW620 cells. Knockdown of TMEM16A by short hairpin RNAs (shRNA) resulted in the suppression of growth, migration and invasion of SW620 cells as detected by MTT, wound-healing and transwell assays. Mechanistically, TMEM16A depletion was accompanied by the dysregulation of phospho-MEK, phospho-ERK1/2 and cyclin D1 expression. Flow cytometry analysis showed that SW620 cells were inhibited from the G1 to S phase of the cell cycle in the TMEM16A shRNA group compared with the control group. In conclusion, our results indicate that TMEM16A CaCC is involved in growth, migration and invasion of metastatic CRC cells and provide evidence for TMEM16A as a potential drug target for treating metastatic colorectal carcinoma. PMID:25541940

  17. Ultrastructural organization of thrombocytes in normal monkeys (Macaca arctoides) and in those with experimental viral malignant lymphoma.

    PubMed

    Chuvirov, G N; Fomenko, V N

    1978-01-01

    Data on platelet ultrastructure of 6 M. arctoides monkeys investigated before and during experimental viral malignant lymphoma are presented. It has been established that the inner structure of thrombocytes in healthy monkeys was almost similar to that of man. In experimental malignant lymphoma, irrespective of the clinical period of the disease, a decrease of alpha-, beta- and sigma-granules, a decrease of the functional activity of thrombocytes and an increase of delta-granules and glycogen granulation content were observed. The above mentioned disturbances can be a result of changes of megakaryocytes in malignant lymphoma. No viral particles in thrombocytes of neither healthy nor sick monkeys have been revealed.

  18. Emerging role of vitamin D in colorectal cancer.

    PubMed

    Kang, Wonmo; Lee, Sujin; Jeon, Eunyi; Yun, Ye-Rang; Kim, Kook-Hyun; Jang, Jun-Hyeog

    2011-08-15

    Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D(3) reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer.

  19. Colorectal Carcinogenesis, Radiation Quality, and the Ubiquitin-Proteasome Pathway

    PubMed Central

    Datta, Kamal; Suman, Shubhankar; Kumar, Santosh; Fornace, Albert J

    2016-01-01

    Adult colorectal epithelium undergoes continuous renewal and maintains homeostatic balance through regulated cellular proliferation, differentiation, and migration. The canonical Wnt signaling pathway involving the transcriptional co-activator β-catenin is important for colorectal development and normal epithelial maintenance, and deregulated Wnt/β-catenin signaling has been implicated in colorectal carcinogenesis. Colorectal carcinogenesis has been linked to radiation exposure, and radiation has been demonstrated to alter Wnt/β-catenin signaling, as well as the proteasomal pathway involved in the degradation of the signaling components and thus regulation of β-catenin. The current review discusses recent progresses in our understanding of colorectal carcinogenesis in relation to different types of radiation and roles that radiation quality plays in deregulating β-catenin and ubiquitin-proteasome pathway (UPP) for colorectal cancer initiation and progression. PMID:26819641

  20. [Lymphadenopathy: demarcation to malignant lymphomas].

    PubMed

    Feller, A C

    2013-05-01

    Recognition of the differential diagnosis between lymphadenitis and malignant lymphoma requires good knowledge of the basic forms of the disease as well in depth knowledge of the structure of the individual compartments. There are defined forms of lymphadenitis where the differential diagnosis to certain lymphoma entities is known. Other reactive structural alterations show indistinct limits so that a decision is only possible after using additional techniques, such as immunohistochemistry and molecular analyses. Finally, there are marginal areas which can only be clarified by including clinical data.

  1. miR-429 mediates tumor growth and metastasis in colorectal cancer

    PubMed Central

    Han, Yantao; Zhao, Qian; Zhou, Jie; Shi, Rui

    2017-01-01

    Colorectal cancer (CRC), presenting the third most common malignancy worldwide. In recent years, the aberrantly upregulation or downregulation of miRNAs in CRC have been evidenced in a number of studies. In this study, our results showed that the expression of miR-429 was significantly higher in CRC tissue compared with adjacent non-tumor tissue. In addition, our findings showed that miR-429 level was significantly associated with clinicoplathological features and prognosis of patients with CRC. Moreover, our findings showed that miR-429 exerted oncogenic effect by directly targeting HOXA5, a transcription factor of HOX families that is involved in the development and progression of CRC. PMID:28337372

  2. Dietary non-nutritive factors in targeting of regulatory molecules in colorectal cancer: an update.

    PubMed

    Pandurangan, Ashok Kumar; Esa, Norhaizan Mohd

    2013-01-01

    Colorectal cancer (CRC), a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation, and programmed cell death, is the third most common malignant neoplasm worldwide. A number of promising targets such as inducible nitric acid (iNOS), cyclooxygenase (COX)-2, NF-E2-related factor 2 (Nrf2), Wnt/β-catenin, Notch and apoptotic signaling have been identified by researchers as useful targets to prevent or therapeutically inhibit colon cancer development. In this review article, we aimed to explore the current targets available to eliminate colon cancer with an update of dietary and non-nutritional compounds that could be of potential use for interaction with regulatory molecules to prevent CRC.

  3. Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor

    SciTech Connect

    Fan Junkai; Xiao Tian; Gu Jinfa; Wei Na; He Lingfeng; Ding Miao; Liu Xinyuan

    2008-09-19

    Angiogenesis plays a key role in the development of a wide variety of malignant tumors. The approach of targeting antiangiogenesis has become an important field of cancer gene therapy. In this study, the antiangiogenesis protein K5 (the kringle 5 of human plasminogen) has been mutated by changing leucine71 to arginine to form mK5. Then the ZD55-mK5, which is an oncolytic adenovirus expressing mK5, was constructed. It showed stronger inhibition on proliferation of human umbilical vein endothelial cell. Moreover, in tube formation and embryonic chorioallantoic membrane assay, ZD55-mK5 exhibited more effective antiangiogenesis than ZD55-K5. In addition, ZD55-mK5 generated obvious suppression on the growth of colorectal tumor xenografts and prolonged the life span of nude mice. These results indicate that ZD55-mK5 is a potent agent for inhibiting the tumor angiogenesis and tumor growth.

  4. The Structure and Clinical Roles of MicroRNA in Colorectal Cancer

    PubMed Central

    2016-01-01

    Colorectal cancer (CRC) is one of the most prevalent types of malignancies, particularly among individuals aged between 50 and 75. The global incidence of CRC has been steadily on the rise due in no small part to an aging population and a shift in lifestyle as well as eating habits. MicroRNAs are a group of small, noncoding, and endogenous RNA molecules that have recently emerged as key players in a broad range of pathological pathways. Moreover, dysregulation of microRNAs has been implicated in cancer development and metastasis. This review is intended to provide a brief overview of the structure, functions, and clinical roles of microRNAs. In particular, the review will focus on the discovery, the underlying mechanistic roles, and the diagnostic as well as therapeutic potentials of CRC-specific miRNAs. PMID:28115926

  5. Recent insights into nanotechnology development for detection and treatment of colorectal cancer

    PubMed Central

    Viswanath, Buddolla; Kim, Sanghyo; Lee, Kiyoung

    2016-01-01

    The global incidence of colorectal cancer (CRC) is 1.3 million cases. It is the third most frequent cancer in males and females. Most CRCs are adenocarcinomas and often begin as a polyp on the inner wall of the rectum or colon. Some of these polyps become malignant, eventually. Detecting and removing these polyps in time can prevent CRC. Therefore, early diagnosis of CRC is advantageous for preventive and instant action interventions to decrease the mortality rates. Nanotechnology has been enhancing different methods for the detection and treatment of CRCs, and the research has provided hope within the scientific community for the development of new therapeutic strategies. This review presents the recent development of nanotechnology for the detection and treatment of CRC. PMID:27330292

  6. Nicotinamide N-methyltransferase enhances the capacity of tumorigenesis associated with the promotion of cell cycle progression in human colorectal cancer cells.

    PubMed

    Xie, Xinyou; Yu, Haitao; Wang, Yanzhong; Zhou, Yanwen; Li, Guiling; Ruan, Zhi; Li, Fengying; Wang, Xiuhong; Liu, Huixing; Zhang, Jun

    2014-12-15

    Nicotinamide N-methyltransferase (NNMT), an enzyme involved in the biotransformation and detoxification of many drugs and xenobiotic compounds, has been found to be overexpressed in several malignancies, including colorectal cancer. However, the biological function of NNMT and the related mechanisms in colorectal cancer have not been elucidated. In the present study, we investigated the effects of NNMT on tumorigenesis by overexpressing NNMT in the human colorectal cancer cells line SW480 which lacks constitutive NNMT expression, and downregulating NNMT expression in HT-29 cells, which exhibit high endogenous expression of NNMT. We found that NNMT significantly accelerates cell proliferation, enhances colony formation in vitro and tumorigenicity in mice; it also inhibits apoptosis, promotes cell cycle progression, increases ATP and 1-methylnicotinamide level and decreases ROS level. We also showed that 1-methylnicotinamide accelerates cell growth, inhibits apoptosis, promotes cell cycle progression, attenuates ROS production and increases ATP level. Our results indicate that NNMT enhances the capacity of tumorigenesis associated with the inhibition of cell apoptosis and the promotion of cell cycle progression in human colorectal cancer cells and the 1-methylnicotinamide increased by NNMT mediates the cellular effects of NNMT in cells. NNMT may play a vital role in energy balance and ROS induction.

  7. Clinicopathological and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) overexpression in colorectal cancer: a meta-analysis

    PubMed Central

    Zhao, Yang; Dai, Cong; Wang, Meng; Kang, Huafeng; Lin, Shuai; Yang, Pengtao; Liu, Xinghan; Liu, Kang; Xu, Peng; Zheng, Yi; Li, Shanli; Dai, Zhijun

    2016-01-01

    Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and the increasing amount of evidences suggest that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in colorectal cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of MACC1 overexpression on clinicopathological features and survival outcomes in colorectal cancer. PubMed, CNKI, and Wanfang databases were searched for relevant articles published update to December 2015. Correlation of MACC1 expression level with overall survival (OS), disease-free survival (DFS), and clinicopathological features were analyzed. In this meta-analysis, fifteen studies with a total of 2,161 colorectal cancer patients were included. Our results showed that MACC1 overexpression was significantly associated with poorer OS and DFS. Moreover, MACC1 overexpression was significantly associated with gender, localization, TNM stage, T stage, and N stage. Together, our meta-analysis showed that MACC1 overexpression was significantly associated with poor survival rates, regional invasion and lymph-node metastasis. MACC1 expression level can serve as a novel prognostic factor in colorectal cancer patients. PMID:27542234

  8. Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer

    PubMed Central

    Raman, Maya; Ambalam, Padma; Kondepudi, Kanthi Kiran; Pithva, Sheetal; Kothari, Charmy; Patel, Arti T.; Purama, Ravi Kiran; Dave, J.M.; Vyas, B.R.M.

    2013-01-01

    Colorectal Cancer (CRC) is the second leading cause of cancer-related mortality and is the fourth most common malignant neoplasm in USA. Escaping apoptosis and cell mutation are the prime hallmarks of cancer. It is apparent that balancing the network between DNA damage and DNA repair is critical in preventing carcinogenesis. One-third of cancers might be prevented by nutritious healthy diet, maintaining healthy weight and physical activity. In this review, an attempt is made to abridge the role of carcinogen in colorectal cancer establishment and prognosis, where special attention has been paid to food-borne mutagens and functional role of beneficial human gut microbiome in evading cancer. Further the significance of tailor-made prebiotics, probiotics and synbiotics in cancer management by bio-antimutagenic and desmutagenic activity has been elaborated. Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host. Prebiotics are a selectively fermentable non-digestible oligosaccharide or ingredient that brings specific changes, both in the composition and/or activity of the gastrointestinal microflora, conferring health benefits. Synbiotics are a combination of probiotic bacteria and the growth promoting prebiotic ingredients that purport “synergism.” PMID:23511582

  9. Interleukin-6 promotes tumor progression in colitis-associated colorectal cancer through HIF-1α regulation

    PubMed Central

    Han, Jun; Xi, Qiulei; Meng, Qingyang; Liu, Jingzheng; Zhang, Yongxian; Han, Yusong; Zhuang, Qiulin; Jiang, Yi; Ding, Qiurong; Wu, Guohao

    2016-01-01

    Interleukin-6 (IL-6) is a well-known etiological factor of colitis-associated colorectal cancer (CAC) and has a significant role in CAC progression. In addition, hypoxia-inducible factor 1α (HIF-1α) serves a primary role in the progression of CAC. However, the association between IL-6 and HIF-1α during the progression of CAC remains unclear. To investigate this association, the present study induced CAC in a mouse model using azoxymethane and dextran sulfate sodium. In addition, an anti-IL-6 receptor antibody was used to inhibit IL-6. In this model, anti-IL-6 receptor antibody treatment significantly inhibited the development of CAC and the expression of HIF-1α, in colorectal adenomas and adenocarcinomas. In patients with CAC, the HIF-1α gene was demonstrated to be overexpressed in tumor tissue compared with adjacent non-malignant tissue. Furthermore, HIF-1α mRNA expression was positively correlated with serum IL-6 concentration. The results of the present study suggest that IL-6 promotes CAC progression, in the early stage of the disease, through HIF-1α regulation. PMID:28105173

  10. [The Alliance for the Prevention of Colorectal Cancer in Spain. A civil commitment to society].

    PubMed

    Morillas, Juan Diego; Castells, Antoni; Oriol, Isabel; Pastor, Ana; Pérez-Segura, Pedro; Echevarría, José Manuel; Caballero, Begoña; González-Navarro, Andrés; Bandrés, Fernando; Brullet, Enric; Iniesta, Antonio; Carballo, Fernando; Bouzas, Rosa; Ariza, Aurelio; Ibisate, Alfredo; García-Alfonso, Pilar; Escudero, Beatriz; Camacho, Silvia; Fernández-Marcos, Ana; González, Teresa; Quintero, Enrique; Lanas, Angel; Marzo, Mercè; Mascort, Juanjo; Andréu, Monserrat; Cerezo, Laura; Vázquez-Sequeiros, Enrique; Borrás, Josep María; Salas, Dolores; Ascunce, Nieves; Portillo, Isabel; Herráiz, Mayte; Valle, María Luisa; Sotoca, Amalia; Nieto, Santiago; Hué, Carlos; Paz-Ares, Luis

    2012-03-01

    Colorectal cancer (CRC) is the most common malignant tumor in Spain, when men and women are considered together, and the second leading cause of cancer death. Every week in Spain over 500 cases of CRC are diagnosed, and nearly 260 people die from the disease. Epidemiologic estimations for the coming years show a significant increase in the number of annual cases. CRC is a perfectly preventable tumor and can be cured in 90% of cases if detected in the early stages. Population-based screening programs have been shown to reduce the incidence of CRC and mortality from the disease. Unless early detection programs are established in Spain, it is estimated that in the coming years, 1 out of 20 men and 1 out of 30 women will develop CRC before the age of 75. The Alliance for the Prevention of Colorectal Cancer in Spain is an independent and non-profit organization created in 2008 that integrates patients' associations, altruistic non-governmental organizations and scientific societies. Its main objective is to raise awareness and disseminate information on the social and healthcare importance of CRC in Spain and to promote screening measures, early detection and prevention programs. Health professionals, scientific societies, healthcare institutions and civil society should be sensitized to this highly important health problem that requires the participation of all sectors of society. The early detection of CRC is an issue that affects the whole of society and therefore it is imperative for all sectors to work together.

  11. Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer.

    PubMed

    Raman, Maya; Ambalam, Padma; Kondepudi, Kanthi Kiran; Pithva, Sheetal; Kothari, Charmy; Patel, Arti T; Purama, Ravi Kiran; Dave, J M; Vyas, B R M

    2013-01-01

    Colorectal Cancer (CRC) is the second leading cause of cancer-related mortality and is the fourth most common malignant neoplasm in USA. Escaping apoptosis and cell mutation are the prime hallmarks of cancer. It is apparent that balancing the network between DNA damage and DNA repair is critical in preventing carcinogenesis. One-third of cancers might be prevented by nutritious healthy diet, maintaining healthy weight and physical activity. In this review, an attempt is made to abridge the role of carcinogen in colorectal cancer establishment and prognosis, where special attention has been paid to food-borne mutagens and functional role of beneficial human gut microbiome in evading cancer. Further the significance of tailor-made prebiotics, probiotics and synbiotics in cancer management by bio-antimutagenic and desmutagenic activity has been elaborated. Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host. Prebiotics are a selectively fermentable non-digestible oligosaccharide or ingredient that brings specific changes, both in the composition and/or activity of the gastrointestinal microflora, conferring health benefits. Synbiotics are a combination of probiotic bacteria and the growth promoting prebiotic ingredients that purport "synergism."

  12. Applications of monoclonal antibodies and recombinant cytokines for the treatment of human colorectal and other carcinomas

    SciTech Connect

    Greiner, J.W.; Smalley, R.V.; Borden, E.C.; Martin, E.W.; Guadagni, F.; Roselli, M.; Schlom, J. )

    1991-01-01

    Monoclonal antibodies (MAbs) which recognize a human tumor antigen, termed tumor-associated glycoprotein-72 (TAG-72), have successfully been used to localize primary as well as metastatic colorectal tumor lesions in patients. The localization of the anti-TAG-72 MAbs has also been exploited intraoperatively using a hand-held gamma probe. That procedure, termed radioimmunoguided surgery (RIGS), has identified occult tumors which were not detected using standard external imaging techniques. In another clinical trial, interferon-gamma (IFN-gamma) was administered intraperitoneally to patients diagnosed with either gastrointestinal or ovarian carcinoma with secondary ascites. Analysis of the tumor cells isolated from the malignant ascites revealed a substantial increase in TAG-72 expression on the surface of tumor cells isolated from seven of eight patients. The results provide evidence that the combination of an anti-carcinoma MAb with the administration of a cytokine, such as IFN-gamma, may be an effective approach for the detection and subsequent treatment, of colorectal carcinoma. 15 references.

  13. Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer.

    PubMed Central

    Baró, L.; Hermoso, J. C.; Núñez, M. C.; Jiménez-Rios, J. A.; Gil, A.

    1998-01-01

    We evaluated total plasma fatty acid concentrations and percentages, and the fatty acid profiles for the different plasma lipid fractions and red blood cell lipids, in 17 patients with untreated colorectal cancer and 12 age-matched controls with no malignant diseases, from the same geographical area. Cancer patients had significantly lower total plasma concentrations of saturated, monounsaturated and essential fatty acids and their polyunsaturated derivatives than healthy controls; when the values were expressed as relative percentages, cancer patients had significantly higher proportions of oleic acid and lower levels of linoleic acid than controls. With regard to lipid fractions, cancer patients had higher proportions of oleic acid in plasma phospholipids, triglycerides and cholesterol esters, and lower percentages of linoleic acid and its derivatives. On the other hand, alpha-linolenic acid was significantly lower in triglycerides from cancer patients and tended to be lower in phospholipids. Its derivatives also tended to be lower in phospholipids and triglycerides from cancer patients. Our findings suggest that colorectal cancer patients present abnormalities in plasma and red blood cell fatty acid profiles characterized by lower amounts of most saturated, monounsaturated and essential fatty acids and their polyunsaturated derivatives, especially members of the n-6 series, than their healthy age-matched counterparts. These changes are probably due to metabolic changes caused by the illness per se but not to malnutrition. PMID:9667678

  14. Current companion diagnostics in advanced colorectal cancer; getting a bigger and better piece of the pie

    PubMed Central

    Loree, Jonathan M.; Raghav, Kanwal P. S.

    2017-01-01

    While the treatment of colorectal cancer continues to rely heavily on conventional cytotoxic therapy, an increasing number of targeted agents are under development. Many of these treatments require companion diagnostic tests in order to define an appropriate population that will derive benefit. In addition, a growing number of biomarkers provide prognostic information about a patient’s malignancy. As we learn more about these biomarkers and their assays, selecting the appropriate companion diagnostic becomes increasingly important. In the case of many biomarkers, there are numerous assays which could provide the same information to a treating physician, however each assay has strengths and weaknesses. Institutions must balance cost, assay sensitivity, turn-around time, and labor resources when selecting which assay to offer. In this review we will discuss the current state of companion diagnostics available in metastatic colorectal cancer and explore emerging biomarkers and their assays. We will focus on KRAS, BRAF, HER2, and PIK3CA testing, as well as microsatellite stability assessment and multigene panels. PMID:28280626

  15. Cell-free nucleic acids as noninvasive biomarkers for colorectal cancer detection

    PubMed Central

    Mansour, Hicham

    2014-01-01

    Cell-free nucleic acids (CFNA) have been reported by several authors in blood, stool, and urine of patients with colorectal cancer (CRC). These genetic biomarkers can be an indication of neoplastic colorectal epithelial cells, and can thus potentially be used as noninvasive tests for the detection of the disease in CRC patients and monitor their staging, without the need to use heavier and invasive tools. In a number of test-trials, these genetic tests have shown the advantage of non-invasiveness, making them well accepted by most of the patients, without major side effects. They have also shown a promising sensitivity and specificity in the detection of malignant and premalignant neoplasms. Moreover, costs for performing such tests are very low. Several studies reported and confirmed the proof of the principle for these genetic tests for screening, diagnosis, and prognosis; the main challenge of translating this approach from research to clinical laboratory is the validation from large and long-term randomized trials to prove sustainable high sensitivity and specificity. In this paper, we present a review on the noninvasive genetics biomarkers for CRC detection described in the literature and the challenges that can be encountered for validation processes. PMID:25221563

  16. Aurora kinase B/C inhibition impairs malignant glioma growth in vivo.

    PubMed

    Diaz, Roberto Jose; Golbourn, Brian; Shekarforoush, Maryam; Smith, Christian A; Rutka, James T

    2012-07-01

    Inhibition of Aurora kinase B has been evaluated as a therapy to block solid tumor growth in breast cancer, hepatocellular carcinoma, lung adenocarcinoma, and colorectal cancer models. Aurora kinase inhibitors are in early clinical trials for the treatment of leukemia. We hypothesized that Aurora B inhibition would reduce malignant glioma cell viability and result in impaired tumor growth in vivo. Aurora B expression is greater in cultured malignant glioma U251 cells compared to proliferating normal human astrocytes, and expression is maintained in U251 flank xenografts. Aurora B inhibition with AZD1152-HQPA blocked cell division in four different p53-mutant glioma cell lines (U251, T98G, U373, and U118). AZD1152-HQPA also inhibited Aurora C activation loop threonine autophosphorylation at the effective antiproliferative concentrations in vitro. Reduction in cell viability of U251 (p53(R273H)) cells was secondary to cytokinesis blockade and apoptosis induction following endoreplication. AZD1152-HQPA inhibited the growth of U251 tumor xenografts and resulted in an increase in tumor cell apoptosis both in vitro and in vivo. Subcutaneous administration of AZD1152-HQPA (25 mg/kg/day × 4 days; 2 cycles spaced 7 days apart) resulted in a prolongation in median survival after intracranial inoculation of U251 cells in mice (P = 0.025). This is the first demonstration that an Aurora kinase inhibitor can inhibit malignant glioma growth in vivo at drug doses that are clinically relevant.

  17. Simplified and optimized multispectral imaging for 5-ALA-based fluorescence diagnosis of malignant lesions

    PubMed Central

    Minamikawa, Takeo; Matsuo, Hisataka; Kato, Yoshiyuki; Harada, Yoshinori; Otsuji, Eigo; Yanagisawa, Akio; Tanaka, Hideo; Takamatsu, Tetsuro

    2016-01-01

    5-aminolevulinic acid (5-ALA)-based fluorescence diagnosis is now clinically applied for accurate and ultrarapid diagnosis of malignant lesions such as lymph node metastasis during surgery. 5-ALA-based diagnosis evaluates fluorescence intensity of a fluorescent metabolite of 5-ALA, protoporphyrin IX (PPIX); however, the fluorescence of PPIX is often affected by autofluorescence of tissue chromophores, such as collagen and flavins. In this study, we demonstrated PPIX fluorescence estimation with autofluorescence elimination for 5-ALA-based fluorescence diagnosis of malignant lesions by simplified and optimized multispectral imaging. We computationally optimized observation wavelength regions for the estimation of PPIX fluorescence in terms of minimizing prediction error of PPIX fluorescence intensity in the presence of typical chromophores, collagen and flavins. By using the fluorescence intensities of the optimized wavelength regions, we verified quantitative detection of PPIX fluorescence by using chemical mixtures of PPIX, flavins, and collagen. Furthermore, we demonstrated detection capability by using metastatic and non-metastatic lymph nodes of colorectal cancer patients. These results suggest the potential and usefulness of the background-free estimation method of PPIX fluorescence for 5-ALA-based fluorescence diagnosis of malignant lesions, and we expect this method to be beneficial for intraoperative and rapid cancer diagnosis. PMID:27149301

  18. Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy—current perspectives

    PubMed Central

    Spiliotis, J.; Halkia, E.; de Bree, E.

    2016-01-01

    Peritoneal carcinomatosis (ptc) represents advanced malignant disease and has generally been associated with a grim prognosis. Peritoneal surface malignancy is often the major source of morbidity and mortality; it is of major concern in cancer management. Although ptc is categorized as metastatic disease, it represents a special disease pattern considered to be a locoregional disease limited to the abdominal cavity. The combination of cytoreductive surgery (crs) and intraoperative hyperthermic intraperitoneal chemotherapy (hipec) has successfully been used as locoregional treatment for selected patients with ptc from gastric, colorectal, and ovarian cancer; with mesothelioma; and with pseudomyxoma peritonei. In the prophylactic setting, hipec can also be used to prevent ptc in high-risk patients, and the first results of the “second-look” approach are promising. Patient selection—in which the risks of perioperative morbidity and mortality, which are analogous to those for any other major gastrointestinal surgery, are assessed—is of utmost importance. Those risks have to be weighed against the anticipated survival benefit, which depends mainly on tumour biology, extent of disease, and probability of achieving complete crs. The present review discusses the principles of crs and hipec, the most significant recent clinical data, and current perspectives concerning the application of this treatment modality in various malignancies. Ongoing trials and future directions are noted. It appears that the combination of crs and hipec is an indispensable tool in the oncologist’s armamentarium. PMID:27330364

  19. DREMECELS: A Curated Database for Base Excision and Mismatch Repair Mechanisms Associated Human Malignancies

    PubMed Central

    Shukla, Ankita; Singh, Tiratha Raj

    2016-01-01

    DNA repair mechanisms act as a warrior combating various damaging processes that ensue critical malignancies. DREMECELS was designed considering the malignancies with frequent alterations in DNA repair pathways, that is, colorectal and endometrial cancers, associated with Lynch syndrome (also known as HNPCC). Since lynch syndrome carries high risk (~40–60%) for both cancers, therefore we decided to cover all three diseases in this portal. Although a large population is presently affected by these malignancies, many resources are available for various cancer types but no database archives information on the genes specifically for only these cancers and disorders. The database contains 156 genes and two repair mechanisms, base excision repair (BER) and mismatch repair (MMR). Other parameters include some of the regulatory processes that have roles in these disease progressions due to incompetent repair mechanisms, specifically BER and MMR. However, our unique database mainly provides qualitative and quantitative information on these cancer types along with methylation, drug sensitivity, miRNAs, copy number variation (CNV) and somatic mutations data. This database would serve the scientific community by providing integrated information on these disease types, thus sustaining diagnostic and therapeutic processes. This repository would serve as an excellent accompaniment for researchers and biomedical professionals and facilitate in understanding such critical diseases. DREMECELS is publicly available at http://www.bioinfoindia.org/dremecels. PMID:27276067

  20. Nurses' attitudes towards the sexuality of colorectal patients.

    PubMed

    Beck, M; Justham, D

    This article reviews the literature on nurses' attitudes towards sexuality and highlights a range of studies carried out on functional outcomes following colorectal surgery. The article provides nurses with an insight into colorectal cancer, the prevalence of sexual dysfunction in men and women following colorectal surgery and the importance of addressing the various aspects of sexuality in a sensitive manner to provide patients with holistic care.

  1. Natural history of colorectal cancer in hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II).

    PubMed

    Lynch, H T; Watson, P; Lanspa, S J; Marcus, J; Smyrk, T; Fitzgibbons, R J; Kriegler, M; Lynch, J F

    1988-06-01

    Approximately 5 to 6 percent of the total colorectal cancer burden is accounted for by hereditary nonpolyposis colorectal cancer (HNPCC). Because clinical premonitory signs such as those seen in familial polyposis coli (FPC) are lacking, the clinician must recognize clinical findings and family history typical of HNPCC. The authors have described colorectal cancer expression from a survey of ten HNPCC kindreds. Kindred members with colorectal cancer differed significantly (P less than .05) from patients with sporadic colorectal cancer: 1) mean age of initial colon cancer diagnosis was 44.6 years; 2) 72.3 percent of first colon cancers were located in the right colon, and only 25 percent were in the sigmoid colon and rectum; 3) 18.1 percent had synchronous colon cancers; and 4) 24.2 percent developed metachronous colon cancer, with a risk for metachronous lesions in ten years of 40 percent. Affecteds and their first-degree relatives should undergo early intensive education and surveillance. In families with an early age of onset, colonoscopy should begin at age 25, and biannually thereafter, with fecal occult blood testing of the stool semiannually. Third-party carriers must become more responsive to the costly surveillance measures required for these otherwise healthy patients.

  2. [Diabetes in patients with malignant tumors].

    PubMed

    Lengyel, Zoltán; Boér, Katalin; Halászlaki, Csaba; Németh, Zsuzsanna

    2013-09-01

    Disturbances of the carbohydrate metabolism are fairly common is patients with malignancy. On the other hand, diabetes appears to have an effect on the development and progression of various tumors. Malignant diseases and the therapies used in their treatment often have an impact on carbohydrate metabolism, while diabetes may hinder specific oncotherapy or influence oncological therapeutic decisions. Several complications of malignant diseases and some of the medications used in their treatment, such as steroids or parenteral nutrition, may raise blood glucose levels. The various obstacles of oral nutrition frequently seen in patients with malignancy can lead to hypoglycaemia in patients with diabetes. Our article endeavours to review the pathophysiological and clinical connection between diabetes and malignant diseases and the use of insulin, oral antidiabetic drugs and diet in patients with malignant disease.

  3. Prediagnostic Plasma Adiponectin and Survival among Patients with Colorectal Cancer.

    PubMed

    Chong, Dawn Q; Mehta, Raaj S; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A; Ng, Kimmie; Wu, Kana; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Chan, Andrew T

    2015-12-01

    Circulating adiponectin is inversely related to the risk of colorectal cancer. However, its influence on colorectal cancer survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with colorectal cancer. We identified 621 incident colorectal cancer cases who provided blood specimens prior to diagnosis within the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to colorectal cancer. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21-2.97; P(trend) = 0.01) for colorectal cancer-specific mortality and 1.66 (95% CI, 1.15-2.39; P(trend) = 0.009) for overall mortality. The apparent increased risk in colorectal cancer-specific mortality was more pronounced in patients with metastatic disease (HR, 3.02: 95% CI, 1.50-6.08). Among patients with colorectal cancer, prediagnostic plasma adiponectin is associated with an increased risk of colorectal cancer-specific and overall mortality and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings.

  4. Matrix metalloproteinase-13 refines pathological staging of precancerous colorectal lesions

    PubMed Central

    Wernicke, Anna-Katharina; Churin, Yuri; Sheridan, Diana; Windhorst, Anita; Tschuschner, Annette; Gattenlöhner, Stefan; Roderfeld, Martin; Roeb, Elke

    2016-01-01

    An exact classification of precancerous stages of colorectal polyps might improve therapy and patients' outcome. Here we investigate the association between grade of dysplasia and Matrix metalloproteinase-13 (MMP-13) expression in 137 biopsies from patients with cancerous and non-cancerous colorectal adenomas. A reproducible staining procedure for histologic MMP-13 analysis in routinely fixed colorectal biopsy specimens has been established. A newly adopted immunoreactive scoring system for MMP-13 was demonstrated as reliable readout. The strength of the association between pathologic stage and immunoreactive MMP-13 scoring emphasizes its eligibility for diagnosis in precancerous colorectal lesions. PMID:27716617

  5. Imaging probe for tumor malignancy

    NASA Astrophysics Data System (ADS)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro

    2009-02-01

    Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

  6. Malignant melanoma of the skin

    PubMed Central

    Armstrong, B. K.; Holman, C. D. J.

    1987-01-01

    Ultra-violet radiation (UVR) in sunlight is thought to be the main cause of malignant melanoma in lightly-pigmented populations. Individuals with fair skin, fair hair, blue eyes and/or a tendency to burn rather than tan when exposed to the sun are at particularly high risk of melanoma and should be given special attention in primary prevention programmes. Intermittent exposure to the sun, as in recreational exposure, may be a more potent cause of melanoma than more continuous exposure. Primary prevention offers the best prospects for a substantial reduction in mortality from malignant melanoma. However, there is little evidence available to judge the effectiveness of primary prevention of melanoma through reduction of exposure to the sun. Education for reducing exposure to the sun is common in high-risk populations but has never been evaluated adequately. Mortality from melanoma could also possibly be reduced by earlier diagnosis through education or screening of high-risk groups. Regular screening of patients with the familial dysplastic naevus syndrome should reduce their mortality from melanoma. PMID:3301043

  7. Oncolytic Virotherapy for Hematological Malignancies

    PubMed Central

    Bais, Swarna; Bartee, Eric; Rahman, Masmudur M.; McFadden, Grant; Cogle, Christopher R.

    2012-01-01

    Hematological malignancies such as leukemias, lymphomas, multiple myeloma (MM), and the myelodysplastic syndromes (MDSs) primarily affect adults and are difficult to treat. For high-risk disease, hematopoietic stem cell transplant (HCT) can be used. However, in the setting of autologous HCT, relapse due to contamination of the autograft with cancer cells remains a major challenge. Ex vivo manipulations of the autograft to purge cancer cells using chemotherapies and toxins have been attempted. Because these past strategies lack specificity for malignant cells and often impair the normal hematopoietic stem and progenitor cells, prior efforts to ex vivo purge autografts have resulted in prolonged cytopenias and graft failure. The ideal ex vivo purging agent would selectively target the contaminating cancer cells while spare normal stem and progenitor cells and would be applied quickly without toxicities to the recipient. One agent which meets these criteria is oncolytic viruses. This paper details experimental progress with reovirus, myxoma virus, measles virus, vesicular stomatitis virus, coxsackievirus, and vaccinia virus as well as requirements for translation of these results to the clinic. PMID:22312362

  8. Primary retroperitoneal malignant melanoma: A case report

    PubMed Central

    LIU, GUO-BING; WU, GUANG-YAO; GHIMIRE, PRASANNA; ZHANG, ZAI-PENG

    2011-01-01

    Primary malignant melanoma occurring at an extra cutaneous site is rare. A case of primary malignant melanoma located in the retroperitoneum of an 18-year-old female is presented in this study. Histopathological examination of the tissue biopsies at laparotomy with immunohistochemical stains confirmed a diagnosis of malignant melanoma. Further extensive clinical and radiological investigations proved the retroperitoneum to be the primary site. PMID:22848275

  9. B-Cell Hematologic Malignancy Vaccination Registry

    ClinicalTrials.gov

    2016-12-28

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  10. Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy.

    PubMed

    Sun, Natalie Z; Brezinski, Elizabeth A; Berliner, Jacqueline; Haemel, Anna; Connolly, M Kari; Gensler, Lianne; McCalmont, Timothy H; Shinkai, Kanade

    2015-08-01

    Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.

  11. T-oligo as an anticancer agent in colorectal cancer

    SciTech Connect

    Wojdyla, Luke; Stone, Amanda L.; Sethakorn, Nan; Uppada, Srijayaprakash B.; Devito, Joseph T.; Bissonnette, Marc; Puri, Neelu

    2014-04-04

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC.

  12. Chemotherapy and plasma adipokines level in patients with colorectal cancer.

    PubMed

    Słomian, Grzegorz; Świętochowska, Elżbieta; Nowak, Grzegorz; Pawlas, Krystyna; Żelazko, Aleksandra; Nowak, Przemysław

    2017-04-12

    Adipokines are molecules produced and secreted by adipose tissue and are linked to multiple malignancies. Adipokines can suppress or promote particular cell behaviors in different types of cancer. The aim of this study was to investigate the impact of chemotherapy on select adipokines in patients with colorectal cancer (CRC). Blood samples were collected from 42 patients with pathologically documented advanced CRC, who required palliative chemotherapy. Leptin, adiponectin, resistin and visfatin levels were measured by ELISA before and 3 months after the administration of chemotherapy. Among the 42 patients evaluated, 18 achieved a partial response (PR), 16 achieved stable disease (SD) and 8 patients experienced disease progression (PD). We found that 5-fluorouracil-based chemotherapy regimens significantly increased plasma levels of leptin and adiponectin and decreased plasma levels of resistin and visfatin in PR and SD patients, whereas the plasma levels of these molecules were not affected in PD patients. Furthermore, the mean plasma levels of leptin were significantly lower, and the mean plasma levels of resistin and visfatin were significantly greater in patients with PD compared with PR and SD both before and after chemotherapy treatment. We conclude that palliative chemotherapy in CRC patients, in addition to providing clinical benefits, positively affects cytokine production and secretion in PR and SD patients. Specifically, we found that palliative chemotherapy increased plasma levels of the anti-inflammatory adipokine adiponectin and decreased the plasma levels of visfatin and resistin, molecules known to promote angiogenesis and cancer cell proliferation in PR and SD patients. Moreover, the baseline values of leptin, visfatin and resistin might serve as prognostic indicators of a poor response to chemotherapy.

  13. CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance

    PubMed Central

    Kim, Kyung-Ju; Kwon, Hee Jung; Kim, Min Chong; Bae, Young Kyung

    2016-01-01

    Background CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression. Methods The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression. Results High T-CD9 (T-CD9 [+]) expression was detected in 175 samples (57.6%) and high I-CD9 (I-CD9 [+]) expression was detected in 265 samples (86.9%). Using Kaplan-Meier survival analysis, the T-CD9 (+) group showed a tendency for better disease-free survival (DFS) (p = .057). In left-sided tumors, DFS was significantly longer in the T-CD9 (+) group (p = .021) but no statistical significance was observed with right-sided tumors (p = .453). I-CD9 (+) CRCs significantly correlated with well/moderately differentiation (p = .014). In Kaplan-Meier analysis, the I-CD9 (+) group had a tendency towards worse DFS compared to the I-CD9 (–) group (p = .156). In combined survival analysis of T-CD9 and I-CD9, we found that the longest DFS was among patients in the T-CD9 (+)/I-CD9 (–) group, whereas the T-CD9 (–)/I-CD9 (+) group showed the shortest DFS (p = .054). Conclusions High expression of T-CD9 was associated with a favorable DFS, especially in left-sided CRCs. Combined evaluation of T-CD9 and I-CD9 is required to determine the comprehensive prognostic effect of CD9 in CRCs. PMID:27780340

  14. Expressions and Clinical Significances of Angiopoietin-1, Angiopoietin-2, and Tie-2 Receptor in Patients With Colorectal Cancer

    PubMed Central

    Hong, Sunghoon; Jung, Hae Il; Ahn, Tae Sung; Kim, Han-Jo; Lee, Kyu-Taek; Baek, Moo-Jun

    2017-01-01

    Purpose Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. Methods We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. Results IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). Conclusion A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer. PMID:28289658

  15. Pattern of cell kinetics in colorectal mucosa of patients with different types of adenomatous polyps of the large bowel

    SciTech Connect

    Roncucci, L.; Scalmati, A.; Ponz de Leon, M. )

    1991-08-15

    It is generally accepted that adenomatous polyps represent the natural precursor of many colorectal malignancies. The sequence, however, which leads from a normally appearing mucosa to cancer is complex and involves many steps, including a hyperproliferative mucosa with an upward expansion of the replicative compartment. The current study evaluates cell replication in normal colorectal mucosa of patients with adenomatous polyps of various types and relates the observed findings to the main clinical and morphologic features of adenomas. Forty-four patients with polyps and 27 controls entered the study. Samples of colorectal mucosa were taken at endoscopy and cell replication was evaluated with a standard autoradiographic procedure. Cell replication was expressed as labeling index (LI), in the whole crypt and in each of the five longitudinal compartments in which the crypts were divided. Total LI and LI per crypt compartment were significantly higher (P less than 0.02 and P less than 0.01, respectively) than in controls. There was no appreciable difference of LI values between patients with single or multiple, tubular or tubulovillous, small or large adenomas, but in all of these subgroups LI was significantly higher than in controls. In conclusion, in normally appearing colorectal mucosa of patients with adenomatous polyps there was a significant increase of cell replication and a marked upward expansion of the proliferative zone; these changes were more evident in the left colon and in the rectum. Finally, cell replication did not seem to be related to the number of polyps, to the most common histotypes, or to the pattern of recurrence.

  16. p53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells.

    PubMed

    Kim, Nam Hee; Cha, Yong Hoon; Kang, Shi Eun; Lee, Yoonmi; Lee, Inhan; Cha, So Young; Ryu, Joo Kyung; Na, Jung Min; Park, Changbum; Yoon, Ho-Geun; Park, Gyeong-Ju; Yook, Jong In; Kim, Hyun Sil

    2013-05-15

    p53 is a bona fide tumor suppressor gene whose loss of function marks the most common genetic alteration in human malignancy. Although the causal link between loss of p53 function and tumorigenesis has been clearly demonstrated, the mechanistic links by which loss of p53 potentiates oncogenic signaling are not fully understood. Recent evidence indicates that the microRNA-34 (miR-34) family, a transcriptional target of the p53, directly suppresses a set of canonical Wnt genes and Snail, resulting in p53-mediated suppression of Wnt signaling and the EMT process. In this study, we report that p53 regulates GSK-3β nuclear localization via miR-34-mediated suppression of Axin2 in colorectal cancer. Exogenous miR-34a decreases Axin2 UTR-reporter activity through multiple binding sites within the 5' and 3' UTR of Axin2. Suppression of Axin2 by p53 or miR-34 increases nuclear GSK-3β abundance and leads to decreased Snail expression in colorectal cancer cells. Conversely, expression of the non-coding UTR of Axin2 causes depletion of endogenous miR-34 via the miR-sponge effect together with increased Axin2 function, supporting that the RNA-RNA interactions with Axin2 transcripts act as an endogenous decoy for miR-34. Further, RNA transcripts of miR-34 target were correlated with Axin2 in clinical data set of colorectal cancer patients. Although the biological relevance of nuclear GSK-3 level has not been fully studied, our results demonstrate that the tumor suppressor p53/miR-34 axis plays a role in regulating nuclear GSK-3 levels and Wnt signaling through the non-coding UTR of Axin2 in colorectal cancer.

  17. Mesenchymal stromal cells (MSCs) and colorectal cancer: a troublesome twosome for the anti-tumour immune response?

    PubMed Central

    O'Malley, Grace; Heijltjes, Madelon; Houston, Aileen M.; Rani, Sweta; Ritter, Thomas; Egan, Laurence J.; Ryan, Aideen E.

    2016-01-01

    The tumour microenvironment (TME) is an important factor in determining the growth and metastasis of colorectal cancer, and can aid tumours by both establishing an immunosuppressive milieu, allowing the tumour avoid immune clearance, and by hampering the efficacy of various therapeutic regimens. The tumour microenvironment is composed of many cell types including tumour, stromal, endothelial and immune cell populations. It is widely accepted that cells present in the TME acquire distinct functional phenotypes that promote tumorigenesis. One such cell type is the mesenchymal stromal cell (MSC). Evidence suggests that MSCs exert effects in the colorectal tumour microenvironment including the promotion of angiogenesis, invasion and metastasis. MSCs immunomodulatory capacity may represent another largely unexplored central feature of MSCs tumour promoting capacity. There is considerable evidence to suggest that MSCs and their secreted factors can influence the innate and adaptive immune responses. MSC-immune cell interactions can skew the proliferation and functional activity of T-cells, dendritic cells, natural killer cells and macrophages, which could favour tumour growth and enable tumours to evade immune cell clearance. A better understanding of the interactions between the malignant cancer cell and stromal components of the TME is key to the development of more specific and efficacious therapies for colorectal cancer. Here, we review and explore MSC- mediated mechanisms of suppressing anti-tumour immune responses in the colon tumour microenvironment. Elucidation of the precise mechanism of immunomodulation exerted by tumour-educated MSCs is critical to inhibiting immunosuppression and immune evasion established by the TME, thus providing an opportunity for targeted and efficacious immunotherapy for colorectal cancer growth and metastasis. PMID:27542276

  18. Mesenchymal stromal cells (MSCs) and colorectal cancer: a troublesome twosome for the anti-tumour immune response?

    PubMed

    O'Malley, Grace; Heijltjes, Madelon; Houston, Aileen M; Rani, Sweta; Ritter, Thomas; Egan, Laurence J; Ryan, Aideen E

    2016-09-13

    The tumour microenvironment (TME) is an important factor in determining the growth and metastasis of colorectal cancer, and can aid tumours by both establishing an immunosuppressive milieu, allowing the tumour avoid immune clearance, and by hampering the efficacy of various therapeutic regimens. The tumour microenvironment is composed of many cell types including tumour, stromal, endothelial and immune cell populations. It is widely accepted that cells present in the TME acquire distinct functional phenotypes that promote tumorigenesis. One such cell type is the mesenchymal stromal cell (MSC). Evidence suggests that MSCs exert effects in the colorectal tumour microenvironment including the promotion of angiogenesis, invasion and metastasis. MSCs immunomodulatory capacity may represent another largely unexplored central feature of MSCs tumour promoting capacity. There is considerable evidence to suggest that MSCs and their secreted factors can influence the innate and adaptive immune responses. MSC-immune cell interactions can skew the proliferation and functional activity of T-cells, dendritic cells, natural killer cells and macrophages, which could favour tumour growth and enable tumours to evade immune cell clearance. A better understanding of the interactions between the malignant cancer cell and stromal components of the TME is key to the development of more specific and efficacious therapies for colorectal cancer. Here, we review and explore MSC- mediated mechanisms of suppressing anti-tumour immune responses in the colon tumour microenvironment. Elucidation of the precise mechanism of immunomodulation exerted by tumour-educated MSCs is critical to inhibiting immunosuppression and immune evasion established by the TME, thus providing an opportunity for targeted and efficacious immunotherapy for colorectal cancer growth and metastasis.

  19. [Esophageal, gastric and colorectal tumors].

    PubMed

    Stolte, M

    2001-01-01

    The new WHO-classification of the tumours of the digestive System replaces the "blue books", and are now dealt with completely in a single book. In addition to the histological features of the lesions, the new classification also contains information on epidemiology, aetiology, endoscopy, genetic susceptibility, molecular genetics, prognosis and predictive factors. The erstwhile mostly black-and-white histological photographs have at last again been replaced by numerous colour photographs and supplemented by endoscopic and macroscopic pictures. The changes to the individual tumour classifications are only few. The former classification of the malignant lymphomas of the gastrointestinal tract has now been replaced by the classification of these lesions that has long been in use. New additions are the gastrointestinal tract has long been in use. New additions are the gastrointestinal stroma tumours (GIST) and the gastrointestinal autonomic nerve tumour (GANT). To the epithelial tumours of the oesophagus have now been added the basaloid squamous cell tumours of the vermiform appendix and the colorectum have now been added the serrated adenoma and the small-cell carcinoma. The following new chapter have been included: adenocarcinoma of the oesophagogastric junction, secondary carcinomas of the stomach, secondary tumours of the small bowel and colon, the Peutz-Jeghers syndrome, juvenile polyposis, familial adenomatosis coli, and HNPCC. For the first time the intra-epithelial neoplasias in chronic inflammatory bowel disease have been differentiated, i.e. adenomas distinguished from the dysplasias, while the latter term has now been replaced by the term "intra-epithelial neoplasias". In comparison with the former "blue books", the new WHO-classification, prepared by presentatives of numerous disciplines--for the first time including clinicians--has taken on the character of a text book.

  20. COGENT (COlorectal cancer GENeTics) revisited

    PubMed Central

    Houlston, Richard S.

    2012-01-01

    Many colorectal cancers (CRCs) develop in genetically susceptible individuals most of whom are not carriers of germ line mismatch repair or APC gene mutations and much of the heritable risk of CRC appears to be attributable to the co-inheritance of multiple low-risk variants. The accumulated experience to date in identifying this class of susceptibility allele has highlighted the need to conduct statistically and methodologically rigorous studies and the need for the multi-centre collaboration. This has been the motivation for establishing the COGENT (COlorectal cancer GENeTics) consortium which now includes over 20 research groups in Europe, Australia, the Americas, China and Japan actively working on CRC genetics. Here, we review the rationale for identifying low-penetrance variants for CRC and the current and future challenges for COGENT. PMID:22294761

  1. BRAF Mutation in Colorectal Cancer: An Update

    PubMed Central

    Barras, David

    2015-01-01

    Colorectal cancer (CRC) is still one of the deadliest cancer-related diseases. About 10% of CRC patients are characterized by a mutation in the B-Raf proto-oncogene serine/threonine kinase (BRAF) gene resulting in a valine-to-glutamate change at the residue 600 (V600E). This mutation is also present in more than 60% of melanoma patients. BRAF inhibitors were developed and found to improve patient survival; however, most patients at the end of the track ultimately develop resistance to these inhibitors. Melanoma patients benefit from the combination of BRAF inhibitors with mitogen/extracellular signal-regulated kinase (MEK) inhibitors, among others. Unfortunately, colorectal patients do not respond much efficiently, which suggests different resistance mechanisms between the two cancer types. This review aims at shedding light on recent discoveries that improve our understanding of the BRAF mutation biology in CRC. PMID:26396549

  2. In Vivo Biomarkers for Targeting Colorectal Neoplasms

    PubMed Central

    Hsiung, Pei-Lin; Wang, Thomas

    2011-01-01

    Summary Colorectal carcinoma continues to be a leading cause of cancer morbidity and mortality despite widespread adoption of screening methods. Targeted detection and therapy using recent advances in our knowledge of in vivo cancer biomarkers promise to significantly improve methods for early detection, risk stratification, and therapeutic intervention. The behavior of molecular targets in transformed tissues is being comprehensively assessed using new techniques of gene expression profiling and high throughput analyses. The identification of promising targets is stimulating the development of novel molecular probes, including significant progress in the field of activatable and peptide probes. These probes are being evaluated in small animal models of colorectal neoplasia and recently in the clinic. Furthermore, innovations in optical imaging instrumentation are resulting in the scaling down of size for endoscope compatibility. Advances in target identification, probe development, and novel instruments are progressing rapidly, and the integration of these technologies has a promising future in molecular medicine. PMID:19126961

  3. Designing effective vaccines for colorectal cancer.

    PubMed

    Patel, Sandip P; Osada, Takuya; Lyerly, H Kim; Morse, Michael A

    2014-01-01

    Achieving long-term control of colorectal cancers with therapeutic vaccines that generate potent anti-tumor T cell and antibody responses has been a goal for more than two decades. To date, clinical trials of these vaccines have demonstrated induction of immune responses, but clinical benefit has been limited. Improved vector delivery systems with enhanced immunostimulatory properties, decreased immunogenicity against vector and improved antigen presentation are some of the key features of modern tumor vaccines. Furthermore, an improved understanding of the various immunosuppressive factors in the tumor microenvironment and regional lymph nodes, coupled with a burgeoning ability to impair inhibitory immune synapses, highlights a growing opportunity to induce beneficial antigen-specific responses against tumor. The combination of improved antigenic delivery systems, coupled with therapeutic immune activation, represents state-of-the-art colorectal vaccine design concepts with the goal of augmenting immune responses against tumor and improving clinical outcomes.

  4. Genetics, Cytogenetics, and Epigenetics of Colorectal Cancer

    PubMed Central

    Migliore, Lucia; Migheli, Francesca; Spisni, Roberto; Coppedè, Fabio

    2011-01-01

    Most of the colorectal cancer (CRC) cases are sporadic, only 25% of the patients have a family history of the disease, and major genes causing syndromes predisposing to CRC only account for 5-6% of the total cases. The following subtypes can be recognized: MIN (microsatellite instability), CIN (chromosomal instability), and CIMP (CpG island methylator phenotype). CIN occurs in 80–85% of CRC. Chromosomal instability proceeds through two major mechanisms, missegregation that results in aneuploidy through the gain or loss of whole chromosomes, and unbalanced structural rearrangements that lead to the loss and/or gain of chromosomal regions. The loss of heterozygosity that occur in the first phases of the CRC cancerogenesis (in particular for the genes on 18q) as well as the alteration of methylation pattern of multiple key genes can drive the development of colorectal cancer by facilitating the acquisition of multiple tumor-associated mutations and the instability phenotype. PMID:21490705

  5. Current treatment for colorectal liver metastases

    PubMed Central

    Misiakos, Evangelos P; Karidis, Nikolaos P; Kouraklis, Gregory

    2011-01-01

    Surgical resection offers the best opportunity for survival in patients with colorectal cancer metastatic to the liver, with five-year survival rates up to 58% in selected cases. However, only a minority are resectable at the time of diagnosis. Continuous research in this field aims at increasing the percentage of patients eligible for resection, refining the indications and contraindications for surgery, and improving overall survival. The use of surgical innovations, such as staged resection, portal vein embolization, and repeat resection has allowed higher resection rates in patients with bilobar disease. The use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Ablative techniques have gained wide acceptance as an adjunct to surgical resection and in the management of patients who are not surgical candidates. Current management of colorectal liver metastases requires a multidisciplinary approach, which should be individualized in each case. PMID:22039320

  6. Choroidal and skin metastases from colorectal cancer

    PubMed Central

    Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu

    2016-01-01

    Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m2, twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer. PMID:27920486

  7. Incidence of colorectal neoplasms among male pilots

    PubMed Central

    Moshkowitz, Menachem; Toledano, Ohad; Galazan, Lior; Hallak, Aharon; Arber, Nadir; Santo, Erwin

    2014-01-01

    AIM: To assess the prevalence of colorectal neoplasms (adenomas, advanced adenomas and colorectal cancers) among Israeli military and commercial airline pilots. METHODS: Initial screening colonoscopy was performed on average-risk (no symptoms and no family history) airline pilots at the Integrated Cancer Prevention Center (ICPC) in the Tel-Aviv Medical Center. Visualized polyps were excised and sent for pathological examination. Advanced adenoma was defined as a lesion >10 mm in diameter, with high-grade dysplasia or villous histology. The results were compared with those of an age- and gender-matched random sample of healthy adults undergoing routine screening at the ICPC. RESULTS: There were 270 pilots (mean age 55.2 ± 7.4 years) and 1150 controls (mean age 55.7 ± 7.8 years). The prevalence of colorectal neoplasms was 15.9% among the pilots and 20.6% among the controls (P = 0.097, χ2 test). There were significantly more hyperplastic polyps among pilots (15.5% vs 9.4%, P = 0.004) and a trend towards fewer adenomas (14.8% vs 20.3% P = 0.06). The prevalence of advanced lesions among pilots and control groups was 5.9% and 4.7%, respectively (P = 0.49), and the prevalence of cancer was 0.7% and 0.69%, respectively (P = 0.93). CONCLUSION: There tends to be a lower colorectal adenoma, advanced adenoma and cancer prevalence but a higher hyperplastic polyp prevalence among pilots than the general population. PMID:25083084

  8. Wilson's disease: a diagnostic dilemma.

    PubMed Central

    Nazer, H; Larcher, V F; Ede, R J; Mowat, A P; Williams, R

    1983-01-01

    A 13 year old boy presented with headache, sore throat, myalgia, and fever and subsequently developed haemolytic anaemia and acute liver failure. Wilson's disease, a rare cause of acute liver failure, was diagnosed at necropsy. In such cases Wilson's disease must be diagnosed at an early stage for treatment to be effective. The most reliable indications are increased urinary and hepatic copper concentrations. PMID:6409288

  9. [Molecular genetics of colorectal cancer and carcinogenesis].

    PubMed

    Panduro Cerda, A; Lima González, G; Villalobos, J J

    1993-01-01

    Genetic and environmental aspects play an important role in the development of colorectal cancer. However, the common molecular alteration in both hereditary and sporadic colon cancer is localized in the APC gene. the APC gene maps in the long arm of chromosome 5 and was discovered in patients with familial adenomatous polyposis (FAP). The search for the APC gene led to the identification of restriction fragment length polymorphisms (RFLPs) in FAP patients. Using these RFLPs in relatives of FAP patients it is possible to make the presymptomatic and prenatal diagnosis. The FAP syndrome is an interesting model of carcinogenesis in vivo. Thus the different stages involved in the FAP syndrome which include hyperproliferative epithelium, adenoma, adenocarcinoma and metastases, have allowed the analysis of molecular alterations in oncogenes and tumor suppressor genes. The APC gene alteration if not inherited, occurs as the earliest molecular alteration in the development of colorectal cancer whereas structural alterations of the genes myc, ras, p53, MCC and DCC are considered to be late events. All these investigations have lead to 1) a better understanding of the ethiology of cancer and 2) early diagnosis of colorectal cancer in both the hereditary and sporadic forms of the disease.

  10. Colorectal cancer screening with virtual colonoscopy

    NASA Astrophysics Data System (ADS)

    Ge, Yaorong; Vining, David J.; Ahn, David K.; Stelts, David R.

    1999-05-01

    Early detection and removal of colorectal polyps have been proven to reduce mortality from colorectal carcinoma (CRC), the second leading cause of cancer deaths in the United States. Unfortunately, traditional techniques for CRC examination (i.e., barium enema, sigmoidoscopy, and colonoscopy) are unsuitable for mass screening because of either low accuracy or poor public acceptance, costs, and risks. Virtual colonoscopy (VC) is a minimally invasive alternative that is based on tomographic scanning of the colon. After a patient's bowel is optimally cleansed and distended with gas, a fast tomographic scan, typically helical computed tomography (CT), of the abdomen is performed during a single breath-hold acquisition. Two-dimensional (2D) slices and three-dimensional (3D) rendered views of the colon lumen generated from the tomographic data are then examined for colorectal polyps. Recent clinical studies conducted at several institutions including ours have shown great potential for this technology to be an effective CRC screening tool. In this paper, we describe new methods to improve bowel preparation, colon lumen visualization, colon segmentation, and polyp detection. Our initial results show that VC with the new bowel preparation and imaging protocol is capable of achieving accuracy comparable to conventional colonoscopy and our new algorithms for image analysis contribute to increased accuracy and efficiency in VC examinations.

  11. Colorectal carcinoma that afflicted King Jehoram.

    PubMed

    Liubov Louba, Ben-Noun

    2004-12-01

    This research uses the tools of modern medical science to examine the ancient descriptions of the symptoms suffered by King Jehoram who was affected by some disease. The Biblical texts were examined, and passages relating to the disease that afflicted King Jehoram, who ruled in Jerusalem 843-851 B.C., were closely studied. We have not included any commentaries, but referred only to the words of the Bible exactly as written. The Passages ''...the Lord smote him in his bowels with an incurable disease in the process of time, after the end of two years, his bowels fell out by reason of his sickness: so he died of sore diseases'' indicate that the King suffered from some kind of disease which affected his bowels. Among the various diseases which may be associated with prolapse of the bowel, colorectal carcinoma is the most acceptable. It seems that the colorectal carcinoma was poorly differentiated, invaded perirectal adipose tissue, blood vessels, and/or lymphatic vessels, and/or perineural areas, was lymph node positive and reached the 4th stage with the spread of metastases to the distal organs. Viewed by a modern physician, the story of King Jehoram unfolds as possibly the earliest description of a patient afflicted by colorectal carcinoma.

  12. Polymorphisms within inflammatory genes and colorectal cancer

    PubMed Central

    Landi, Stefano; Gemignani, Federica; Bottari, Fabio; Gioia-Patricola, Lydie; Guino, Elisabet; Cambray, María; Biondo, Sebastiano; Capella, Gabriel; Boldrini, Laura; Canzian, Federico; Moreno, Victor

    2006-01-01

    Background Chronic inflammation is a risk factor for colorectal cancer and polymorphisms in the inflammatory genes could modulate the levels of inflammation. We have investigated ten single nucleotide polymorphisms (SNPs) in the following inflammation-related genes: TLR4 (Asp299Gly), CD14 (-260 T>C), MCP1 (-2518 A>G), IL12A (+7506 A>T, +8707 A>G, +9177 T>A, +9508 G>A), NOS2A (+524T>C), TNF (-857C>T), and PTGS1 (V444I) in 377 colorectal (CRC) cancer cases and 326 controls from Barcelona (Spain). Results There was no statistically significant association between the SNPs investigated and colorectal cancer risk. Conclusion The lack of association may show that the inflammatory genes selected for this study are not involved in the carcinogenic process of colorectum. Alternatively, the negative results may derive from no particular biological effect of the analysed polymorphisms in relation to CRC. Otherwise, the eventual biological effect is so little to go undetected, unless analysing a much larger sample size. PMID:17062130

  13. Novel findings in colorectal polyp surveillance.

    PubMed

    Carballal, Sabela

    2016-09-01

    Colorectal adenomas and serrated polyps are the best characterised premalignant lesions involved in the development of colorectal cancer (CRC). Therefore, the identification and removal of these lesions, as well as post-polypectomy surveillance of affected patients, are key goals in the field of CRC prevention. Current post-polypectomy surveillance strategies differ among the various scientific societies and have several limitations that hamper their application in clinical practice. First, current surveillance intervals are based only on polyp characteristics, excluding other potential clinical conditions, such as diabetes or metabolic syndrome. Second, serrated polyps and adenomas are considered separately, but there is no recommendation in cases of the simultaneous occurrence of both types of lesion. Third, the incorporation of endoscopic technologies implies an increase in polyp detection, whose clinical impact is controversial and directly affects the number of scheduled colonoscopies with an indication of surveillance. Some of the studies presented at the AGA (American Gastroenterological Association) meeting aimed to provide new evidence on the follow-up of colorectal polyps, with a view to optimising the applicability and suitability of current surveillance strategies.

  14. Body image concerns after colorectal cancer surgery.

    PubMed

    Taylor, Claire

    Body image is understood to be a person's perception of his or her own physical appearance although, as this article highlights, it embraces a greater range of bodily attributes than is often appreciated. It can be significantly affected by a diagnosis of colorectal cancer and subsequent treatment, which may modify the way the body looks, feels and functions. One of the major aesthetic and functional consequences of colorectal cancer surgery is the possibility of stoma formation, which is of particular concern to many. However, the range of other bodily effects following surgery should not be overlooked, not least because of they may result in distress. While concerns about changes in body image generally decrease over time, people recovering from cancer treatment often feel their relationship with their body has been permanently altered. Specialist support is often required when adjusting to any changes in bodily appearance and function. Care outcomes can be improved by having a sound understanding of the body image concerns likely to arise following treatment, as well as the skills to identify and support patients at risk of altered body image. This article provides guidance to nurses caring for individuals who may be experiencing distress over how their body is now perceived by themselves and others following colorectal cancer surgery.

  15. Treatment of colorectal cancer in the elderly

    PubMed Central

    Millan, Monica; Merino, Sandra; Caro, Aleidis; Feliu, Francesc; Escuder, Jordi; Francesch, Tani

    2015-01-01

    Colorectal cancer has a high incidence, and approximately 60% of colorectal cancer patients are older than 70, with this incidence likely increasing in the near future. Elderly patients (> 70-75 years of age) are a very heterogeneous group, ranging from the very fit to the very frail. Traditionally, these patients have often been under-treated and recruited less frequently to clinical trials than younger patients, and thus are under-represented in publications about cancer treatment. Recent studies suggest that fit elderly patients can be treated in the same way as their younger counterparts, but the treatment of frail patients with comorbidities is still a matter of controversy. Many factors should be taken into account, including fitness for treatment, the wishes of the patient and family, and quality of life. This review will focus on the existing evidence for surgical, oncologic, and palliative treatment in patients over 70 years old with colorectal cancer. Careful patient assessment is necessary in order to individualize treatment approach, and this should rely on a multidisciplinary process. More well-designed controlled trials are needed in this patient population. PMID:26483875

  16. Colorectal cancer risk in hamartomatous polyposis syndromes

    PubMed Central

    Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real

    2015-01-01

    Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as “hamartomatous polyposis syndromes”, “Peutz-Jeghers syndrome”, “juvenile polyposis syndrome”, “juvenile polyp”, and “PTEN hamartoma tumour syndrome” (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented. PMID:25848489

  17. Malignant Mesothelioma: Development to Therapy

    PubMed Central

    Thompson, Joyce; Westbom, Catherine; Shukla, Arti

    2013-01-01

    Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium caused by asbestos. Asbestos use has been reduced but not completely stopped. In addition, natural or man-made disasters will continue to dislodge asbestos from old buildings into the atmosphere and as long as respirable asbestos is available, MM will continue to be a threat. Due to the long latency period of MM development, it would still take decades to eradicate this disease if asbestos was completely removed from our lives today. Therefore, there is a need for researchers and clinicians to work together to understand this deadly disease and find a solution for early diagnosis and treatment. This article focuses on developmental mechanisms as well as current therapies available for MM. PMID:23959774

  18. Isolated urachal malakoplakia mimicking malignancy

    PubMed Central

    Pakalapati, Saisriharsha; Parachuri, Sanjay; Kakarla, Venkateshwara Rao; Byrappa, Mahesh Babu

    2017-01-01

    Malakoplakia is an unusual inflammatory disease with uncertain pathogenesis affecting any organ in the body, but predominantly genitourinary tract, with specific predilection to the bladder. We report a rare case of isolated malakoplakia of the urachus in a 29-year-old male patient who presented with lower urinary tract symptoms without any hematuria. Investigations revealed sterile pyuria with no bacterial growth in urine. Radiological investigations revealed a mass in the urachal region. The patient underwent cystoscopy with biopsy followed by pelvic lymph node dissection and partial cystectomy with excision of the urachal mass. Histopathological examination of the mass revealed malakoplakia. Postoperative course was uneventful. To the best of our knowledge, this is the first ever case report of isolated urachal malakoplakia without any concomitant malignancy or bladder involvement reported in our country and one of the very few reported worldwide. PMID:28216941

  19. Secondary malignancies following cancer chemotherapy.

    PubMed

    Boffetta, P; Kaldor, J M

    1994-01-01

    Many agents used in cancer chemotherapy are known carcinogens. However, few secondary malignancies have been definitely linked to chemotherapy, since studies on this problem are complicated by methodological problems. A causal relationship has been established between alkylating agents and leukaemia and between cyclophosphamide and bladder cancer. The risk of leukaemia peaks at 5-10 years after beginning of chemotherapy and declines steadily after its end. The interaction between chemotherapy and radiotherapy has not been fully clarified, nor has the leukaemogenic potency of individual drugs, although combinations without nitrogen mustard seem to entail a lower risk. Other tumours reported at increased incidence, in particular among Hodgkin's disease patients, for whom a carcinogenic effect of chemotherapy seems plausible, are non-Hodgkin's lymphoma and lung cancer. Other secondary solid tumors have also been reported, but for none of them an independent effect of chemotherapy has been demonstrated.

  20. Diffuse Malignant Mesothelioma: A Review

    PubMed Central

    Rom, William N.; Lockey, James E.

    1982-01-01

    Diffuse malignant mesothelioma is a signal tumor of asbestos exposure. Mesothelioma incidence has been steadily rising during the past two decades, reflecting the increases in asbestos use during and following World War II. The onset of the disease follows exposure by 25 to 40 years. The dose-response relationship appears to be much lower than that for asbestosis or lung cancer—it is not known whether current levels of exposure will entail a risk for disease 30 years hence. There is no synergistic or additive interaction with smoking for this tumor. Current knowledge indicates that pleural plaques, per se, do not increase the risk for this tumor beyond that of the previous asbestos exposure alone. Durable fibers with high aspect ratios, especially amphiboles, are associated with experimental tumor induction. Treatment modalities including surgical procedures and chemotherapy with doxorubicin and 5-azacytidine offer prospects for palliation. ImagesFigure 1.Figure 2. PMID:6761970

  1. Clinical Management of Malignant Glaucoma

    PubMed Central

    Foreman-Larkin, Julie; Netland, Peter A.; Salim, Sarwat

    2015-01-01

    Malignant glaucoma remains one of the most challenging complications of ocular surgery. Although it has been reported to occur spontaneously or after any ophthalmic procedure, it is most commonly encountered after glaucoma surgery in eyes with prior chronic angle closure. The clinical diagnosis is made in the setting of a patent peripheral iridotomy and axial flattening of the anterior chamber. Intraocular pressure is usually elevated, but it may be normal in some cases. Although the exact etiology of this condition is not fully understood, several mechanisms have been proposed and it is thought to result from posterior misdirection of aqueous humor into or behind the vitreous. This review discusses pathophysiology, differential diagnosis, imaging modalities, and current treatment strategies for this rare form of secondary glaucoma. PMID:26819754

  2. Multiple malignancies in a female patient with common variable immunodeficiency syndrome

    PubMed Central

    Todorovic, Milena; Balint, Bela; Andjelic, Bosko; Mihaljevic, Biljana

    2014-01-01

    We herein present the case of a 55-year-old woman with a previous history of malignancies – uterine adenocarcinoma, basal cell carcinoma (which occurred twice consecutively), recurrent respiratory infections due to common variable immunodeficiency (CVID), and systemic granulomatous disease diagnosed at a later age. The patient suffered from diffuse large B cell lymphoma (DLBCL), which was successfully treated with R-CHOP chemotherapy, and continued with immunoglobulin supplementation. The patient was free of lymphoma and infectious complications for over 20 months despite her persistent immunodeficiency, but eventually developed colorectal adenocarcinoma. To the best of our knowledge, this is the first reported case of CVID associated with multiple solid tumours and DLBCL. PMID:25631905

  3. The identification and differentiation of secondary colorectal cancer in human liver tissue using X-ray fluorescence, coherent scatter spectroscopy, and multivariate analysis.

    PubMed

    Darvish-Molla, Sahar; Al-Ebraheem, Alia; Farquharson, Michael J

    2014-01-01

    Secondary colorectal liver cancer is the most widespread malignancy in patients with colorectal cancer. The aim of this study is to identify and differentiate between normal liver tissue and malignant secondary colorectal liver cancer tissue using X-ray scattering and X-ray fluorescence spectroscopy to investigate the best combination of data that can be used to enable classification of these two tissue types. X-ray fluorescence (XRF) and coherent scatter data were collected for 24 normal and 24 tumor matched pair tissue samples. The levels of 12 elements (P, S, K, Ca, Cr, Fe, Cu, Zn, As, Se, Br, and Rb) were measured in all samples. When comparisons were made between normal and tumor tissues, statistically significant differences were determined for K (p = 0.046), Ca (p = 0.040), Cr (p = 0.011), Fe, Cu, Zn, Br, and Rb (p < 0.01). However, for P, S, As, and Se, no statistically significant differences were found (p > 0.05). For the coherent scatter spectra collected, three peaks due to adipose, fibrous content, and water content of tissue were observed. The amplitude, full width half-maximum, and area under both fibrous content and water content peaks were found to be significantly higher in secondary colorectal liver tumors compared with surrounding normal liver tissue (p < 0.05). However, no significant differences were found for the adipose peak parameters (p > 0.05). Soft independent modeling of class analogy was performed using the XRF, coherent scatter, and elemental ratio data separately, and the accuracy of the classification of 20 unknown samples was found to be 50, 30, and 80%, respectively. Further analysis has shown that using a combination of the XRF and coherent scatter data in a single combined model gave improved normal and tumor liver tissue classification, with an accuracy that was found to be 85%.

  4. Meta-analysis of organ-specific differences in the structure of the immune infiltrate in major malignancies

    PubMed Central

    Stoll, Gautier; Bindea, Gabriela; Mlecnik, Bernhard; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido

    2015-01-01

    Anticancer immunosurveillance is one of the major endogenous breaks of tumor progression. Here, we analyzed gene expression pattern indicative of the presence of distinct leukocyte subtypes within four cancer types (breast cancer, colorectal carcinoma, melanoma, and non-small cell lung cancer) and 20 different microarray datasets corresponding to a total of 3471 patients. Multiple metagenes reflecting the presence of such immune cell subtypes were highly reproducible across distinct cohorts. Nonetheless, there were sizable differences in the correlation patterns among such immune-relevant metagenes across distinct malignancies. The reproducibility of the correlations among immune-relevant metagenes was highest in breast cancer (followed by colorectal cancer, non-small cell lung cancer and melanoma), reflecting the fact that mammary carcinoma has an intrinsically better prognosis than the three other malignancies. Among breast cancer patients, we found that the expression of a lysosomal enzyme-related metagene centered around ASAH1 (which codes for N-acylsphingosine amidohydrolase-1, also called acid ceramidase) exhibited a higher correlation with multiple immune-relevant metagenes in patients that responded to neoadjuvant chemotherapy than in non-responders. Altogether, this meta-analysis revealed novel organ-specific features of the immune infiltrate in distinct cancer types, as well as a strategy for defining new prognostic biomarkers. PMID:26059437

  5. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines

    PubMed Central

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70–90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2–3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of

  6. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    PubMed

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast

  7. Improving colorectal cancer screening: fact and fantasy

    NASA Astrophysics Data System (ADS)

    Van Dam, Jacques

    2008-02-01

    Premalignant diseases of the gastrointestinal tract, such as Barrett's esophagus, long-standing ulcerative colitis, and adenomatous polyps, have a significantly increased risk for development of adenocarcinoma, most often through an intermediate stage of dysplasia. Adenocarcinoma of the colon is the second most common cancer in the United States. Because patients with colorectal cancer often present with advanced disease, the outcomes are associated with significant morbidity and mortality. Effective methods of early detection are essential. As non-polypoid dysplasia is not visible using conventional endoscopy, surveillance of patients with Barrett's esophagus and ulcerative colitis is performed via a system in which multiple random biopsies are obtained at prescribed intervals. Sampling error and missed diagnoses occur frequently and render current screening methods inadequate. Also, the examination of a tissue biopsy is time consuming and costly, and significant intra- and inter-observer variation may occur. The newer methods discussed herein demonstrate the potential to solve these problems by early detection of disease with high sensitivity and specificity. Conventional endoscopy is based on the observation of white light reflected off the tissue surface. Subtle changes in color and shadow reveal structural changes. New developments in optical imaging go beyond white light, exploiting other properties of light. Several promising methods will be discussed at this meeting and shall be briefly discussed below. However, few such imaging modalities have arrived at our clinical practice. Some much more practical methods to improve colorectal cancer screening are currently being evaluated for their clinical impact. These methods seek to overcome limitations other than those of detecting dysplasia not visible under white light endoscopy. The current standard practice of colorectal cancer screening utilizes colonoscopy, an uncomfortable, sometimes difficult medical

  8. Rare Malignant Tumors of the Breast

    PubMed Central

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed. PMID:26664775

  9. Rare Malignant Tumors of the Breast.

    PubMed

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed.

  10. Malignant gonadal tumour formation in intersexual states

    PubMed Central

    Pigott, H. W. S.

    1975-01-01

    Two cases of malignant tumour are reported in phenotypically male hermaphrodites. The importance of establishing the presence of persistent Müllerian duct structures in pseudo-hermaphrodites is discussed in relation to prophylactic castration in anticipation of malignant change. ImagesFig. 1Fig. 2 PMID:1197157

  11. [Malignant fibrous histiocytoma of the eyelid].

    PubMed

    Rossi, P; Ducasse, A; Pluot, M; Brugniart, C; Gotzamanis, A; Jouhaud, F

    2002-12-01

    Fibrous histiocytomas, mostly benign, have often been reported in the orbit, but only four lesions have been described on the eyelids, with only one malignant. The authors present a case of malignant fibrous histiocytoma of the eyelid in a 76-year-old woman with a difficult histological diagnosis. Characteristics of this pathology are explained from data in the literature.

  12. Malignant ameloblastoma: classification, diagnostic, and therapeutic challenges.

    PubMed

    Verneuil, Andrew; Sapp, Philip; Huang, Catherine; Abemayor, Elliot

    2002-01-01

    Ameloblastoma is a benign odontogenic neoplasm of the mandible and maxilla that rarely exhibits malignant behavior. We report the case of an aggressive malignant ameloblastoma of the mandible that presented with an unusual multiphasic, histologic pattern. Initial fine needle aspiration and radiographic findings showed features consistent with a benign, fibro-osseous lesion. However, aggressive growth and the association of enlarged submandibular lymph nodes suggested a more malignant potential. Treatment consisted of an angle-to-angle composite mandibular resection, right modified neck dissection, left functional supraomohyoid neck dissection, and anterior chin skin resection with iliac crest osteocutaneous free flap reconstruction. Microscopic evaluation showed primarily malignant ameloblastoma without cellular atypia and extensive fields of fibro-osseous tissue with smaller fields of clear cell odontogenic tumor. This multiphasic, histologic arrangement may explain the perplexing preoperative microscopic diagnosis, suggesting a benign fibro-osseous lesion. Of the lymph nodes analyzed, one from the right submandibular triangle exhibited metastatic, benign-appearing ameloblastoma without fibro-osseous or clear cell features. The absence of cellular features of malignancy in the tumor mass and lymph node metastasis suggest that the lesion should be classified as malignant ameloblastoma rather than ameloblastic carcinoma or odontogenic carcinoma. A malignant ameloblastoma with all 3 of the aforementioned microscopic features has not been previously reported. We review the classification of epithelial odontogenic malignancies. Lesions showing multiphasic patterns can create diagnostic dilemmas and may require extensive surgical sampling and/or removal to establish an accurate diagnosis.

  13. Primary Ovarian Malignant PEComa: A Case Report.

    PubMed

    Westaby, Joseph D; Magdy, Nesreen; Fisher, Cyril; El-Bahrawy, Mona

    2016-09-28

    Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm characterized by expression of both melanocytic and smooth muscle markers. PEComas are rarely encountered in the female genital tract. We here report a case of malignant primary PEComa of the ovary, and discuss the differential diagnosis. This represents the first case of primary typical malignant PEComa of the ovary.

  14. [Malignant schwannoma metastasizing to the heart].

    PubMed

    Menezes Júnior, A da S; Greco, O T; Fiorini, M; Pavarino, P; Corbucci, H; Caixeta, A M

    1992-01-01

    We introduce the case of a 34-year-old male with a malignant metastasizing tumor in the heart associated with skin manifestations. The patient was submitted to heart surgery to resect the tumor. The correct diagnosis was done by pathological findings and immunohistochemical methods and showed, malignant schwannoma.

  15. Colorectal cancer and consumption of beef and fat.

    PubMed Central

    Enstrom, J. E.

    1975-01-01

    Secular, socioeconomic and urban-rural gradients and geographical differences in beef and fat consumption within the United States of America are compared with corresponding data on colorectal cancer incidence and mortality rates. These results, together with the results of most previous epidemiological studies, appear to contradict the hypothesis that beef and fat consumption are involved in the aetiology of colorectal cancer. PMID:1212410

  16. High FOXRED1 expression predicted good prognosis of colorectal cancer

    PubMed Central

    Fei, Weiqiang; Liu, Shuiping; Hu, Xiaotong

    2016-01-01

    The human FAD-dependent oxidoreductase domain containing 1 (FOXRED1) protein is reported as an assembly factor which promotes the correct assembly and stability of mitochondrial Complex I (CI). Alterations of mitochondrial CI might cause tumorigenesis and metastasis, but it’s molecular mechanisms remain unclear. In this study, we selected 145 cases of colorectal cancer for immunohistochemistry to explore the role of FOXRED1 played in the tumor progression of colorectal cancer. The relationship between FOXRED1 expression and clinicopathological features of colorectal cancers was evaluated. FOXRED1 mainly localized in the cytoplasm in the colorectal cancer tissues, and had significant association with histopathological grading, depth of invasion, lymph node metastasis, distant metastasis and TNM stage (P<0.05 for each). However, age, gender and tumor location was not found to be associated with FOXRED1 expression. Colorectal cancer patients with higher expression of FOXRED1 had the higher 3 year survival rate (P=0.003). Moreover, FOXRED1 had potentiality to be an independent prognostic factor for survival in colorectal cancer (P=0.04). Low FOXRED1 expression correlated with poor prognosis of colorectal cancer and targeting this molecular will be a potential treatment strategy for colorectal cancer. PMID:27904784

  17. From dinosaurs to DNA: a history of colorectal cancer.

    PubMed

    Mulcahy, Hugh E; Hyland, John; O'Donoghue, Diarmuid P

    2003-05-01

    The roots of colorectal cancer date back to antiquity. In this short history of colorectal cancer we trace its clinical and research origins from ancient times through the dark ages, middle ages, to the scientific and medical advances of the seventeenth to twentieth centuries and into the twenty-first century.

  18. NIH study finds sigmoidoscopy reduces colorectal cancer rates

    Cancer.gov

    Study finds that flexible sigmoidoscopy is effective in reducing the rates of new cases and deaths due to colorectal cancer. Researchers found that overall colorectal cancer mortality was reduced by 26 percent and incidence was reduced by 21 percent as a

  19. Endoscopic management of acute colorectal anastomotic complications with temporary stent.

    PubMed

    Abbas, Maher A

    2009-01-01

    Acute postoperative anastomotic complications following colorectal resection include leak and obstruction. Often an operation is necessary to treat these complications. The role of endoluminal procedures to treat these complications has been limited. This article illustrates that such an approach is technically feasible and can be used to treat some colorectal anastomotic complications.

  20. Autocrine growth factors and solid tumor malignancy.

    PubMed Central

    Walsh, J. H.; Karnes, W. E.; Cuttitta, F.; Walker, A.

    1991-01-01

    The ability of malignant cells to escape the constraint that normally regulate cell growth and differentiation has been a primary focus of attention for investigators of cancer cell biology. An outcome of this attention has been the discovery that the protein products of oncogenes play a role in the activation of growth signal pathways. A second outcome, possibly related to abnormal oncogene expression, has been the discovery that malignant cells frequently show an ability to regulate their own growth by the release of autocrine growth modulatory substances. Most important, the growth of certain malignant cell types has been shown to depend on autocrine growth circuits. A malignant tumor whose continued growth depends on the release of an autocrine growth factor may be vulnerable to treatment with specific receptor antagonists or immunoneutralizing antibodies designed to break the autocrine circuit. Information is rapidly emerging concerning autocrine growth factors in selected human solid tissue malignancy. Images PMID:1926844

  1. Expression of Cellular Oncogenes in Human Malignancies

    NASA Astrophysics Data System (ADS)

    Slamon, Dennis J.; Dekernion, Jean B.; Verma, Inder M.; Cline, Martin J.

    1984-04-01

    Cellular oncogenes have been implicated in the induction of malignant transformation in some model systems in vitro and may be related to malignancies in vivo in some vertebrate species. This article describes a study of the expression of 15 cellular oncogenes in fresh human tumors from 54 patients, representing 20 different tumor types. More than one cellular oncogene was transcriptionally active in all of the tumors examined. In 14 patients it was possible to study normal and malignant tissue from the same organ. In many of these patients, the transcriptional activity of certain oncogenes was greater in the malignant than the normal tissue. The cellular fes (feline sarcoma) oncogene, not previously known to be transcribed in mammalian tissue, was found to be active in lung and hematopoietic malignancies.

  2. Malignant solitary fibrous tumor in retroperitoneum

    PubMed Central

    Zhou, Yihong; Chu, Xi; Yi, Ye; Tong, Liang; Dai, Yingbo

    2017-01-01

    Abstract Rationale: Solitary fibrous tumor (SFT) is a rare mesenchymal tumor occurs in various sites. Malignant SFT in retroperitoneum is extremely rare. Patient concerns: We report a case of malignant retroperitoneal SFT in a 59-year-old man presented with right flank pain for 1 month. Diagnoses, interventions and outcomes: A laparotomy and resection of the tumor were performed, the histopathologic and immunohistochemical findings were consistent with malignant retroperitoneal SFT. No adjuvant treatment was performed, and the patient had no signs of recurrence or metastasis at the 12 months follow-up. Lessons: Complete surgical excision is the basic treatment principle for malignant retroperitoneal SFT. The histologic features and the Ki-67 label index are helpful for the diagnosis of malignant SFT. PMID:28296778

  3. Emerging Role and Targeting of Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) in Human Malignancies

    PubMed Central

    Johnson, Benny; Mahadevan, Daruka

    2015-01-01

    Background: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a member of the CEA family of cell adhesion proteins that belong to the immunoglobulin superfamily. CEACAM6 is normally expressed on the surface of myeloid (CD66c) and epithelial surfaces. Stiochiomertic expression of members of the CEA family (CEACAM1, 5, 6, 7) on epithelia maintains normal tissue architecture through homo-and hetero-philic interactions. Dysregulated over-expression of CEACAM6 is oncogenic, is associated with anoikis resistance and an invasive phenotype mediated by excessive TGFβ, AKT, FAK and SRC signaling in human malignancies. Methods: Extensive literature review through PubMed was conducted to identify relevant preclinical and clinical research publications regarding CEACAM6 over the last decade and was summarized in this manuscript. Results: CEACAM5 and 6 are over-expressed in nearly 70% of epithelial malignancies including colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDA), hepatobiliary, gastric, breast, non-small cell lung and head/neck cancers. Importantly, CEACAM6 is a poor prognostic marker in CRC, while its expression correlates with tumor stage, metastasis and post-operative survival in PDA. CEACAM6 appears to be an immune checkpoint suppressor in hematologic malignancies including acute lymphoblastic leukemia and multiple myeloma. Several therapeutic monoclonal antibodies or antibody fragments targeting CEACAM6 have been designed and developed as a targeted therapy for human malignancies. A Llama antibody targeting CEACAM6 is being evaluated in early phase clinical trials. Conclusion: This review focuses on the role of CEACAM6 in the pathogenesis and signaling of the malignant phenotype in solid and hematologic malignancies and highlights its potential as a therapeutic target for anti-cancer therapy. PMID:27595061

  4. Biliary metastasis in colorectal cancer confers a poor prognosis: case study of 5 consecutive patients

    PubMed Central

    Koh, Frederick Hong-Xiang; Shi, Wang

    2017-01-01

    The biliary duct is an extremely rare site for colon cancer metastasis. It often leads to a diagnostic dilemma, since primary cholangiocarcinoma (potentially treatable with surgery) has a similar presentation. This paper highlights our experience with 5 consecutive patients who had colon malignancy with biliary metastasis, and prognosis of their disease. Five patients, with a history of primary colon cancer since 2010, were identified to have biliary metastasis. Of these, 4 (80.0%) patients were male. The median time to diagnosis of biliary metastasis from diagnosis of colon cancer was 59.2 months (0-70.1 months), and all exhibited symptoms of biliary obstruction or its associated complications. Evaluation of the tumour samples revealed all specimens to be negative for CK7 but positive for CK20, suggestive of a colorectal primary. The median survival of the 5 patients was 23.5 months (1.8-44.5 months) from the diagnosis of biliary metastasis. However, none of their death was related to the direct complication of biliary obstruction. Biliary metastasis is a rare entity for metastatic colon malignancy. Diagnosis may be difficult radiologically, and immunohistochemical staining may help in identification. The overall survival for these patients is dismal. PMID:28317047

  5. SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer

    PubMed Central

    Sun, Hui-Min; Mi, Yu-Shuai; Yu, Fu-Dong; Han, Yang; Liu, Xi-Sheng; Lu, Su; Zhang, Yu; Zhao, Sen-Lin; Ye, Ling; Liu, Ting-Ting; Yang, Dao-Hua; Sun, Xiao-Feng; Qin, Xue-Bin; Zhou, Zong-Guang; Tang, Hua-Mei; Peng, Zhi-Hai

    2016-01-01

    Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC. PMID:27648355

  6. Role of cancer stem cells in age-related rise in colorectal cancer

    PubMed Central

    Nangia-Makker, Pratima; Yu, Yingjie; Majumdar, Adhip PN

    2015-01-01

    Colorectal cancer (CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging. However, many probable reasons for this increase have been suggested; among others they include altered carcinogen metabolism and the cumulative effects of long-term exposure to cancer-causing agents. Herein, we propose a role for self-renewing, cancer stem cells (CSCs) in regulating these cellular events. In this editorial, we have briefly described the recent work on the evolution of CSCs in gastro-intestinal track especially in the colon, and how they are involved in the age-related rise in CRC. Focus of this editorial is to provide a description of (1) CSC; (2) epigenetic and genetic mechanisms giving rise to CSCs; (3) markers of CSC; (4) characteristics; and (5) age-related increase in CSC in the colonic crypt. PMID:26600965

  7. Changes in cellular mechanical properties during onset or progression of colorectal cancer

    PubMed Central

    Ciasca, Gabriele; Papi, Massimiliano; Minelli, Eleonora; Palmieri, Valentina; De Spirito, Marco

    2016-01-01

    Colorectal cancer (CRC) development represents a multistep process starting with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations confer a selective growth advantage to colonic epithelial cells that form first dysplastic crypts, and then malignant tumours and metastases. All these steps are accompanied by deep mechanical changes at the cellular and the tissue level. A growing consensus is emerging that such modifications are not merely a by-product of the malignant progression, but they could play a relevant role in the cancer onset and accelerate its progression. In this review, we focus on recent studies investigating the role of the biomechanical signals in the initiation and the development of CRC. We show that mechanical cues might contribute to early phases of the tumour initiation by controlling the Wnt pathway, one of most important regulators of cell proliferation in various systems. We highlight how physical stimuli may be involved in the differentiation of non-invasive cells into metastatic variants and how metastatic cells modify their mechanical properties, both stiffness and adhesion, to survive the mechanical stress associated with intravasation, circulation and extravasation. A deep comprehension of these mechanical modifications may help scientist to define novel molecular targets for the cure of CRC. PMID:27621568

  8. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention

    PubMed Central

    Piazza, Gary A.

    2015-01-01

    Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

  9. Overexpression of Rad51 Predicts Poor Prognosis in Colorectal Cancer: Our Experience with 54 Patients

    PubMed Central

    Xu, Feng; Liao, Dian-ying; Xie, Li; Wang, Jin; Luo, Feng

    2017-01-01

    Background Aberrant Rad51 expression is implicated in the progression of human malignancies. However, the role of Rad51 in colorectal cancer (CRC) remains undefined. This study aimed to establish a relationship between Rad51 and clinicopathologic features of CRC. Methods We retrospectively examined the paraffin-embedded tissue samples obtained from 54 patients with CRC who had received surgical therapies at our institution during 2006–2008. Rad51 expression in adenocarcinoma, paracancerous tissue, and normal colonic tissue was determined by immunohistochemistry. The correlation between Rad51 immunoreactivity and clinicopathologic features of these patients was evaluated. Results Rad51 immunoreactivity was detected in 67% of adenocarcinoma, 48% of paracancerous tissue, and 27% of normal colonic mucosa. Rad51 expression in adenocarcinoma was significantly higher than normal colonic tissue (p < 0.05). Rad51 was also overexpressed in poorly differentiated tumors and tumor samples from patients with lymph node metastasis (p < 0.05). Patients with Rad51 overexpression had a 69% two-year survival, 49% three-year survival, and 16% five-year survival, considerably worse than patients with negative Rad51 expression (p < 0.05). Conclusion Our data suggest that Rad51 overexpression is correlated with malignant phenotypes of CRC and may predict poor prognosis for these patients. PMID:28099437

  10. Familial colorectal adenocarcinoma and hereditary nonpolyposis colorectal cancer: a nationwide epidemiological study from Sweden

    PubMed Central

    Hemminki, K; Li, X

    2001-01-01

    Although estimates are available of the proportion of hereditary nonpolyposis colorectal cancer (HNPCC) among all colorectal cancer (CRC), its proportion among familial CRC is unclear. We estimated these proportions epidemiologically from the nationwide Swedish Family-Cancer Database on 9.6 million individuals. Colorectal adenocarcinomas were retrieved from the Cancer Registry covering years 1958–1996. Standardized incidence ratios (SIRs) were calculated for offspring (aged less than 62 years) when their parent had colorectal adenocarcinoma. In 9.82% of all families, an offspring and a parent were affected, giving a population attributable proportion of 4.91% and a familial SIR of 2.00. When offspring and parents shared the anatomic site, the SIR was 2.32 for proximal and 2.00 for distal CRC. When offspring were diagnosed before age 40 years and parents before age 50 years, the SIR was 25.72 for familial proximal CRC. In older age groups familial risks did not differ between proximal and distal CRC. Familial risks were increased also for endometrial, small intestinal and gastric cancers, manifestations in HNPCC. Depending on which assumptions were made, HNPCC was calculated to account for 20 to 50% of familial CRC, corresponding to 1 or 2.5% of all CRC among 0–61-year-old individuals. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11286479

  11. CT-guided percutaneous microwave ablation of pulmonary malignant tumors

    PubMed Central

    Ko, Wei-Chun; Lee, Yee-Fan; Chen, Yi-Chang; Chien, Ning; Huang, Yu-Sen; Tseng, Yao-Hui; Lee, Jang-Ming; Hsu, Hsao-Hsun; Chen, Jin-Shing

    2016-01-01

    Background Microwave ablation (MWA) of lung tumors is a new approach for local tumor control. The purpose of this retrospective study was to evaluate the preliminary results of safety and efficacy of MWA with a dynamic frequency range (902–928 MHz) and power (10–32 W) for local tumor control of thoracic malignancies. Methods From December 1, 2013 to February 1, 2016, there were total 32 lung tumors among 15 patients (7 men, 8 women, age range 43–82 years, mean 57.8±11.1 years of age) receiving MWA of thoracic neoplasms, including lung adenocarcinoma (n=5), metastatic colorectal cancer (n=7), invasive thymoma (n=1), metastatic uterine leiomyosarcoma (n=1), and metastatic ampullary carcinoma (n=1). Mean tumor size was 13.5 mm (range, 3.0–32.0 mm). The mean sequential ablation during each MWA was 2.3±1.1 times (range, 1–5 times). The outcomes of ablation were evaluated by follow-up computed tomography (CT) scans and the complications were assessed by medical records and CT scan after ablation. Results The mean follow-up interval of each tumor was 446.8 days (range, 196–902 days). Local tumor recurrence was found in 5 of the 32 tumors resulting in a local control rate 84.4%. No MWA-related mortality was noted. After MWA, the incidence of pneumothorax was 37.5% (12/32). Only one patient with pneumothorax required air evacuation. Third-degree skin burn adjacent to the entry site occurred in one patient and required debridement and closure with flap. Conclusions After appropriate patient selection, MWA with a dynamic frequency range (902–928 MHz) and power (10–32 W) is an effective and safe procedure for local tumor control of recurrent and metastatic lung tumors. PMID:28066666

  12. Laparoscopic combined colorectal and liver resections for primary colorectal cancer with synchronous liver metastases

    PubMed Central

    Takorov, Ivelin; Lukanova, Tsonka; Atanasov, Boiko; Dzharov, Georgi; Djurkov, Ventzeslav; Odisseeva, Evelina; Vladov, Nikola

    2016-01-01

    Backgrounds/Aims Synchronous liver metastases (SLMs) are found in 15-25% of patients at the time of diagnosis with colorectal cancer, which is limited to the liver in 30% of patients. Surgical resection is the most effective and potentially curative therapy for metastatic colorectal carcinoma (CRC) of the liver. The comparison of simultaneous resection of primary CRC and synchronous liver metastases with staged resections is the subject of debate with respect to morbidity. Laparoscopic surgery improves postoperative recovery, diminishes postoperative pain, reduces wound infections, shortens hospitalization, and yields superior cosmetic results, without compromising the oncological outcome. The aim of this study is therefore to evaluate our initial experience with simultaneous laparoscopic resection of primary CRC and SLM. Methods Currently, laparoscopic resection of primary CRC is performed in more than 53% of all patients in our surgical department. Twenty-six patients with primary CRC and a clinical diagnosis of SLM underwent combined laparoscopic colorectal and liver surgery. Six of them underwent laparoscopic colorectal resection combined with major laparoscopic liver resection. Results The surgical approaches were total laparoscopic (25 patients) or hybrid technique (1 patients). The incision created for the extraction of the specimen varied between 5 and 8cm. The median operation time was 223 minutes (100 to 415 min.) with a total blood loss of 180 ml (100-300 ml). Postoperative hospital stay was 6.8 days (6-14 days). Postoperative complications were observed in 6 patients (22.2%). Conclusions Simultaneous laparoscopic colorectal and liver resection appears to be safe, feasible, and with satisfying short-term results in selected patients with CRC and SLM. PMID:28261695

  13. Single-Incision Laparoscopic Liver Resection for Colorectal Metastasis through Stoma Site at Time of Reversal of Diversion Ileostomy: A Case Report

    PubMed Central

    Røsok, Bård I.; Edwin, Bjørn

    2011-01-01

    Minimally invasive surgical techniques for liver tumors are gaining increased acceptance as an alternative to traditional resections by laparotomy. In this article we describe a laparoscopic liver resection of a metastatic lesion in a patient primarily operated for colorectal cancer. The resection was conducted as a single port procedure through the stoma aperture at time of reversal of the diversion ileostomy. Sigle incision liver resections may be less traumatic than conventional laparoscopy and could be applied in selected patients with both benign and malignant liver tumors. PMID:22091359

  14. Single-Incision Laparoscopic Liver Resection for Colorectal Metastasis through Stoma Site at Time of Reversal of Diversion Ileostomy: A Case Report.

    PubMed

    Røsok, Bård I; Edwin, Bjørn

    2011-01-01

    Minimally invasive surgical techniques for liver tumors are gaining increased acceptance as an alternative to traditional resections by laparotomy. In this article we describe a laparoscopic liver resection of a metastatic lesion in a patient primarily operated for colorectal cancer. The resection was conducted as a single port procedure through the stoma aperture at time of reversal of the diversion ileostomy. Sigle incision liver resections may be less traumatic than conventional laparoscopy and could be applied in selected patients with both benign and malignant liver tumors.

  15. Improved radioimmunotherapy of hematologic malignancies

    SciTech Connect

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  16. Malignant mesothelioma in Hong Kong.

    PubMed

    Chang, Kwok C; Leung, Chi C; Tam, Cheuk M; Yu, Wai C; Hui, David S; Lam, Wah K

    2006-01-01

    Malignant mesothelioma (mesothelioma) is rare. We conducted the first systematic study of the epidemiology of mesothelioma in Hong Kong from 1988 to May 2002 by reviewing medical records. Mesothelioma patients were identified from the database of 12 out of 20 hospitals that would have admitted mesothelioma patients territory-wide. These 12 hospitals served 73% of the total hospital bed-years of the 20 hospitals. We identified 67 mesothelioma patients. The estimated annual incidence was one per million, which was similar to the background incidence of one to two per million among Caucasians. Occupational history was available in 43 subjects. Three quarters of mesothelioma patients with available occupational history had occupational asbestos exposure. Restricting analysis to 48 patients with accessible medical records and using 67 occupational asbestosis patients for comparison, the epidemiology of mesothelioma in Hong Kong shares similarities with the literature: mean age of 63 years upon diagnosis, mean latency of 46 years, median survival of 9.5 months, male predominance, selective presentation among women, high prevalence among workers in ships and dockyards, predominantly epithelioid type, lower prevalence of asbestos bodies, and negative association with pleural plaques. Asbestos consumption in Hong Kong rose in the 1970s and peaked in early 1980s and late 1990s. Hong Kong may encounter an epidemic of mesothelioma in the 2010s if effective occupational asbestos control measures are not in place.

  17. Novel immunotherapies in lymphoid malignancies

    PubMed Central

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J.; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted ‘breakthrough’ designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE®) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  18. PSYCHOLOGICAL ASPECTS OF HAEMATOLOGICAL MALIGNANCIES

    PubMed Central

    Kulhara, P.; Verma, S.C.; Bambery, P.; Nehra, R.

    1990-01-01

    SUMMMARY Sixty nine patients with various types of haematological malignancies were studied. Chronic myeloid leukaemia (n =32) was the commonest diagnosis. The patients were assessed on Hamilton Rating Scale for Depression, PGI-N2 Health Questionnaire and Presumptive Stressful Life Events Scale and those who had scores above the cut off points for Hamilton Rating Scale and/or PGI-N2 Health Questionnaire were assessed on Present State Examination. The patients were followed up at 3 and 6 months interval. At 3 months 51 patients were re-assessed whilst at 6 months only 26 could be re-evaluated. There were no significant changes in scores of Hamilton Rating scale and PGI-N2 Health Questionnaire at intake and subsequent follow-up assessments. No significant correlations between stressful life experience and severity of illness emerged. Twenty nine patients were interviewed on Present State Examination and of these 20 had diagnosable depressive neuroses- From consultation liaison psychiatric point of view, provision of psychiatric help to these patients is discussed. PMID:21927472

  19. Esophageal malignancy: A growing concern

    PubMed Central

    Chai, Jianyuan; Jamal, M Mazen

    2012-01-01

    Esophageal cancer is mainly found in Asia and east Africa and is one of the deadliest cancers in the world. However, it has not garnered much attention in the Western world due to its low incidence rate. An increasing amount of data indicate that esophageal cancer, particularly esophageal adenocarcinoma, has been rising by 6-fold annually and is now becoming the fastest growing cancer in the United States. This rise has been associated with the increase of the obese population, as abdominal fat puts extra pressure on the stomach and causes gastroesophageal reflux disease (GERD). Long standing GERD can induce esophagitis and metaplasia and, ultimately, leads to adenocarcinoma. Acid suppression has been the main strategy to treat GERD; however, it has not been proven to control esophageal malignancy effectively. In fact, its side effects have triggered multiple warnings from regulatory agencies. The high mortality and fast growth of esophageal cancer demand more vigorous efforts to look into its deeper mechanisms and come up with better therapeutic options. PMID:23236223

  20. Novel immunotherapies for hematological malignancies

    PubMed Central

    Nelson, Michelle H.; Paulos, Chrystal M.

    2014-01-01

    Summary The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise the state of the art in immunotherapy with a focus on strategies that exploit the patient’s immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematological malignancies, including (i) conventional monoclonal therapies like rituximab, (ii) engineered monoclonal antibodies called bispecific T cell engagers (BiTEs), (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4 and IDO), and (iv) adoptive cell transfer (ACT) therapy with T cells engineered to express chimeric antigen receptors (CARs) or T-cell receptors (TCRs). We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. PMID:25510273