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Sample records for malignant colorectal disease-a

  1. Ablative Therapies for Colorectal Polyps and Malignancy

    PubMed Central

    Hochwald, Steven N.; Nurkin, Steven

    2014-01-01

    Endoscopic techniques are gaining popularity in the management of colorectal polyps and occasionally superficial cancers. While their use is in many times palliative, they have proven to be curative in carefully selected patients with polyps or malignancies, with less morbidity than radical resection. However, one should note that data supporting local and ablative therapies for colorectal cancer is scarce and may be subject to publication bias. Therefore, for curative intent, these techniques should only be considered in highly select cases as higher rates of local recurrences have also been reported. The aim of this review is to explain the different modalities of local and ablative therapies specific to colorectal neoplasia and explain the indications and circumstances where they have been most successful. PMID:25089281

  2. 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.

  3. Evidence-based Clinical Management of Acute Malignant Colorectal Obstruction.

    PubMed

    Shimura, Takaya; Joh, Takashi

    2016-04-01

    Acute malignant colorectal obstruction (AMCO) is an emergency associated with colorectal cancer (CRC). Emergency surgery is standard therapy for AMCO, and 1-stage surgery without colostomy is preferable, but it is occasionally difficult in the emergency setting. A self-expandable metallic stent (SEMS) enables noninvasive colonic decompression and subsequent 1-stage surgery, which has been widely applied for CRC with AMCO. However, recent accumulation of high-quality evidence has highlighted some problems and the limited efficacy of SEMS for AMCO. In palliative settings, SEMS placement reduces hospital stay and short-term complication rates, whereas it increases the frequency of long-term complications, such as delayed perforation. SEMS placement does not seem compatible with recent standard chemotherapy including bevacizumab. As a bridge to surgery, while SEMS placement provides a lower clinical success rate than emergency surgery, it can facilitate primary anastomosis without stoma. However, evidence regarding long-term survival outcomes with SEMS in both palliative and bridge to surgery settings is lacking. The efficacy of transanal colorectal tube placement, another endoscopic treatment, has been reported, but its clinical evidence level is low due to the limited number of studies. This review article comprehensively summarizes the current knowledge about surgical and endoscopic management of CRC with AMCO. PMID:26796083

  4. Proactive Management for Gastric, Colorectal and Appendiceal Malignancies: Preventing Peritoneal Metastases with Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

    PubMed

    Sammartino, Paolo; Biacchi, Daniele; Cornali, Tommaso; Cardi, Maurizio; Accarpio, Fabio; Impagnatiello, Alessio; Sollazzo, Bianca Maria; Di Giorgio, Angelo

    2016-06-01

    An integrated treatment strategy using peritonectomy procedures plus hyperthermic intraperitoneal chemotherapy (HIPEC) is now a clinical standard of care in selected patients with peritoneal metastases and primary peritoneal tumors. This comprehensive approach can offer many patients, who hitherto had no hope of cure, a good quality of life and survival despite limited morbidity. The increasingly successful results and chance of interfering in the natural history of disease has prompted research to develop for some clinical conditions a therapeutic strategy designed to prevent malignant peritoneal dissemination before it becomes clinically evident and treat it microscopically (tertiary prevention). The main factor governing successful cytoreductive surgery and predicting outcome is the extent of peritoneal spread assessed with the peritoneal cancer index (PCI). In peritoneal metastases from colorectal and gastric cancer the PCI score acquires a specific role acting as the cut-off between patients who can undergo curative surgery or palliation. Long-term results show that the only group enjoying favorable results are patients with limited disease (a statistical minority). By applying to appropriately selected patients with primary malignancies a proactive management strategy including HIPEC we can treat patients with microscopic peritoneal dissemination and therefore at PCI 0. Among treated conditions pseudomyxoma peritonei enjoys the best results. But a major future advance comes from identifying among lesions at major risk of pseudomyxoma. PMID:27065712

  5. Colorectal cancer surveillance in inflammatory bowel disease: A critical analysis.

    PubMed

    Desai, Devendra; Desai, Nutan

    2014-11-16

    Colonoscopic surveillance is advocated in patients with inflammatory bowel disease (IBD) for detection of dysplasia. There are many issues regarding surveillance in IBD: the risk of colorectal cancer seems to be decreasing in the majority of recently published studies, necessitating revisions of surveillance strategy; surveillance guidelines are not based on concrete evidence; commencement and frequency of surveillance, cost-effectiveness and adherence to surveillance have been issues that are only partly answered. The traditional technique of random biopsy is neither evidence-based nor easy to practice. Therefore, highlighting abnormal areas with newer technology and biopsy from these areas are the way forward. Of the newer technology, digital mucosal enhancement, such as high-definition white light endoscopy and chromoendoscopy (with magnification) have been incorporated in guidelines. Dyeless chromoendoscopy (narrow band imaging) has not yet shown potential, whereas some forms of digital chromoendoscopy (i-Scan more than Fujinon intelligent color enhancement) have shown promise for colonoscopic surveillance in IBD. Other techniques such as autofluorescence imaging, endomicroscopy and endocytoscopy need further evidence. Surveillance with genetic markers (tissue, serum or stool) is at an early stage. This article discusses changing epidemiology of colorectal cancer development in IBD and critically evaluates issues regarding colonoscopic surveillance in IBD. PMID:25400868

  6. Venous Thromboembolism Following Colorectal Surgery for Suspected or Confirmed Malignancy

    PubMed Central

    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. PMID:22084669

  7. 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

  8. Near-Infrared Spectroscopy as a Diagnostic Tool for Distinguishing between Normal and Malignant Colorectal Tissues

    PubMed Central

    Chen, Hui; Lin, Zan; Mo, Lin; Wu, Tong; Tan, Chao

    2015-01-01

    Cancer diagnosis is one of the most important tasks of biomedical research and has become the main objective of medical investigations. The present paper proposed an analytical strategy for distinguishing between normal and malignant colorectal tissues by combining the use of near-infrared (NIR) spectroscopy with chemometrics. The successive projection algorithm-linear discriminant analysis (SPA-LDA) was used to seek a reduced subset of variables/wavenumbers and build a diagnostic model of LDA. For comparison, the partial least squares-discriminant analysis (PLS-DA) based on full-spectrum classification was also used as the reference. Principal component analysis (PCA) was used for a preliminary analysis. A total of 186 spectra from 20 patients with partial colorectal resection were collected and divided into three subsets for training, optimizing, and testing the model. The results showed that, compared to PLS-DA, SPA-LDA provided more parsimonious model using only three wavenumbers/variables (4065, 4173, and 5758 cm−1) to achieve the sensitivity of 84.6%, 92.3%, and 92.3% for the training, validation, and test sets, respectively, and the specificity of 100% for each subset. It indicated that the combination of NIR spectroscopy and SPA-LDA algorithm can serve as a potential tool for distinguishing between normal and malignant colorectal tissues. PMID:25654106

  9. Optical diagnosis of malignant colorectal polyps: is it feasible?

    PubMed Central

    van der Vlugt, Manon; van Doorn, Sascha Corrie; Wang, Junfeng; Bastiaansen, Barbara AJ; Brosens, Lowewijk AA; Fockens, Paul; Dekker, Evelien

    2016-01-01

    Background and study aims: As colorectal cancer screening programs are being implemented worldwide, an increasing number of early (T1) cancers are being diagnosed. These cancers should be recognized during colonoscopy because they require a specific therapeutic approach. Several studies have shown that Asian experts can reliably recognize T1 cancers during colonoscopy. In daily practice, however, accurate endoscopic diagnosis of T1 cancers still seems challenging. We evaluated the performance of optical diagnosis of T1 cancers by European colonoscopy experts, general gastroenterologists and gastrointestinal fellows. Patients and methods: We collected endoscopic images of 43 colonic lesions: 19 T1 cancers (excluding intramucosal carcinoma) and 24 benign polyps ranging from 7 mm to 30 mm in size. Seven colonoscopy experts, 7 general gastroenterologists, and 14 gastrointestinal fellows assessed these images. We calculated sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) and their 95 % confidence intervals for optical diagnosis of T1 cancers. Results: Overall sensitivity for correct diagnosis of T1 cancers was 60 % (95 % CI;45 – 72). Sensitivity was highest for experts (67 %: 95 %CI; 48 – 81), when compared to general gastroenterologists (53 %: 95 %CI; 37 – 69) and gastrointestinal fellows (59 %: 95 %CI;45 – 72). The overall NPV was 75 % (95 %CI;60 – 86); NPV was lowest for general gastroenterologists 72 % (95 %CI;57 – 83) vs 78 % (95 %CI;63 – 89) for experts and 75 % (95 %CI;60 – 85) for gastrointestinal fellows. Conclusions: In this image-based study, both sensitivity for the optical diagnosis of a T1 cancer and NPV for excluding a T1 cancer were insufficient. Experts performed best with a sensitivity of 67 % and a NPV of 78 %, while the performance of fellows in the last year of training was comparable to that of experts. Our study

  10. Clinical meaning of age-related expression of fecal cytokeratin 19 in colorectal malignancy

    PubMed Central

    2009-01-01

    Background Colorectal cancer (CRC) is one of the leading causes of malignant death worldwide. Because young age of onset is often considered a poor prognostic factor for CRC, it is important to identify the poor outcomes of CRC in a younger population and to consider an aggressive approach by implementing early treatment. Our aim was to specifically quantify the fecal cytokeratin 19 (CK19) transcript from CRC patients and investigate its correlation with clinical stage, tumor malignancy, and age. Methods The quantitation of fecal CK19 transcript was determined by a quantitative real-time reverse transcription polymerase chain in 129 CRC patients (45 younger than 60 years at diagnosis) and 85 healthy controls. The levels of CK19 protein were examined both in colonic cell lines and tissues. Results The analysis of 45 younger CRC patients (age ≤ 60 years) revealed that patients at the M1 stage had significantly higher expression levels of fecal CK19 mRNA when compared with healthy controls (p < 0.001) and patients at the M0 stage (p = 0.004). Additionally, the degree of consistency between the mean level of fecal CK19 mRNA and the distant metastatic rate in each age interval was up to 89% (p = 0.042). Conclusion These results indicate that high levels of fecal CK19 mRNA represent a potential marker for colorectal malignancy and for aggressive treatment of younger CRC patients. PMID:19849844

  11. Synchronous colorectal malignancy and abdominal aortic aneurysm treated with endovascular aneurysm repair followed by laparoscopic colectomy.

    PubMed

    Kawai, Kazushige; Sunami, Eiji; Tanaka, Junichiro; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Nozawa, Hiroaki; Kazama, Shinsuke; Kanazawa, Takamitsu; Hosaka, Akihiro; Ishihara, Soichiro; Yamaguchi, Hironori; Shigematsu, Kunihiro; Watanabe, Toshiaki

    2015-04-01

    Although the incidence of synchronous abdominal aortic aneurysm (AAA) and malignancies is increasing, there has been no clear consensus in the surgical treatment of such patients. The focus on surgical treatments with minimal invasiveness, such as endovascular aneurysm repair (EVAR) for AAA and laparoscopic colectomy for colorectal cancer, has increased; however, the clinical applicability of combination treatment with EVAR and laparoscopic colectomy has not been established. A 61-year-old man was diagnosed with AAA, advanced sigmoid colon cancer, and coronary artery stenosis. Because the patient also had chronic renal failure with nephrotic syndrome, among several other comorbidities, surgery was considered to be associated with high risks in this patent. Sequential treatments with percutaneous coronary intervention, EVAR, and laparoscopic colectomy were successfully performed. Staged treatment of EVAR followed by laparoscopic colectomy may be a promising strategy for high-risk patients with AAA associated with malignancy. PMID:25875539

  12. Synchronous Colorectal Malignancy and Abdominal Aortic Aneurysm Treated With Endovascular Aneurysm Repair Followed by Laparoscopic Colectomy

    PubMed Central

    Kawai, Kazushige; Sunami, Eiji; Tanaka, Junichiro; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Nozawa, Hiroaki; Kazama, Shinsuke; Kanazawa, Takamitsu; Hosaka, Akihiro; Ishihara, Soichiro; Yamaguchi, Hironori; Shigematsu, Kunihiro; Watanabe, Toshiaki

    2015-01-01

    Although the incidence of synchronous abdominal aortic aneurysm (AAA) and malignancies is increasing, there has been no clear consensus in the surgical treatment of such patients. The focus on surgical treatments with minimal invasiveness, such as endovascular aneurysm repair (EVAR) for AAA and laparoscopic colectomy for colorectal cancer, has increased; however, the clinical applicability of combination treatment with EVAR and laparoscopic colectomy has not been established. A 61-year-old man was diagnosed with AAA, advanced sigmoid colon cancer, and coronary artery stenosis. Because the patient also had chronic renal failure with nephrotic syndrome, among several other comorbidities, surgery was considered to be associated with high risks in this patent. Sequential treatments with percutaneous coronary intervention, EVAR, and laparoscopic colectomy were successfully performed. Staged treatment of EVAR followed by laparoscopic colectomy may be a promising strategy for high-risk patients with AAA associated with malignancy. PMID:25875539

  13. Colonic perforation after stent placement for malignant colorectal obstruction--causes and contributing factors.

    PubMed

    Datye, Arundhati; Hersh, Jeff

    2011-05-01

    Self-expanding metal stents (SEMS) are used to manage malignant colorectal obstruction. Colonic perforation is the most worrisome complication from colonic stenting. We reviewed causes and contributing factors of perforation with colonic stent placement in patients with malignant colorectal obstruction. Articles from both English and foreign language publications were identified from Medline. Data were collected on causes, timing, treatment and mortality related to perforation. A total of 2287 patients from 82 articles were included in this analysis, which showed an overall perforation rate of 4.9%. Perforation rates for palliation and bridge to surgery (BTS) were not significantly different (4.8% vs. 5.4%, p = 0.66); over 80% occurred within 30 days of stent placement (half during or within one day of the procedure). The mortality rate related to perforation was 0.8% per stented patient, but the mortality of patients experiencing perforation was 16.2%. There was no significant difference (p = 0.78) in the mortality rates between the palliation and the BTS group and concomitant chemotherapy, steroids, and radiotherapy are risk factors of perforation. The overall perforation related mortality is far less than that of patients undergoing emergency surgery for bowel obstruction. PMID:20929424

  14. Morphology as a risk factor for the malignant potential of T2 colorectal cancer

    PubMed Central

    Mori, Yuichi; Kudo, Shin-Ei; Endo, Shungo; Maeda, Chiyo; Mukai, Shumpei; Maeda, Yasuharu; Kataoka, Shinichi; Takeda, Kenichi; Ichimasa, Katsuro; Miyachi, Hideyuki; Sawada, Naruhiko; Hidaka, Eiji; Ishida, Fumio

    2016-01-01

    Currently, depressed type T1 colorectal cancer is often detected and its malignant potential is being revealed. However, few reports have focused on the morphology of T2 colorectal cancer types. The aim of the present retrospective study was to clarify the characteristics of colorectal T2 cancer types derived from depressed type T1 cancer. The present study included 195 patients with colorectal T2 cancer surgically resected at a referral hospital between April 2001 and April 2009. A total of 48 lesions (25%) with lymph node metastasis and 4 (2%) with distant metastasis were found. The lesions were classified by their form during endoscopy into four categories: Group A, depressed type (the periphery consists of normal mucosa); group B, laterally spreading type; group C, protruded type; group D, ulcerative type (the periphery consists of neoplastic mucosa). Tumor size, lymphatic and venous involvement, lymph node metastasis, and distant metastasis were compared between the four categories. The distribution of patients were as follows: Group A, 73 (37%), group B, 26 (13%), group C, 24 (12%) and group D, 72 (37%). The average tumor size for each category was 23, 51, 30 and 36 mm for groups A, B, C and D, respectively. The number of positive findings for lymphatic involvement, venous involvement, lymph node metastasis and distant metastasis for each category were: Group A, 50 (69%), 54 (74%), 19 (26%) and 1 (1%); group B, 14 (54%), 12 (46%), 8 (31%) and 0 (0%); group C, 14 (58%), 8 (33%), 6 (25%) and 0 (0%); group D 35 (49%), 41 (57%), 16 (22%) and 3 (4%). Group A demonstrated a significantly smaller tumor size (P<0.01), and higher rates of lymphatic and venous involvement (P=0.0333 and P=0.0019, respectively). No significant differences were observed between categories with regards to nodal and distant metastases. Of the T2 cancer types, ~40% were the depressed type. Compared with the other forms, depressed type lesions exhibited a smaller tumor size, and higher rates

  15. 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

  16. Systemic therapy of non-colorectal gastrointestinal malignancies in the elderly.

    PubMed

    Desai, Avni M; Lichtman, Stuart M

    2015-12-01

    In the coming years life expectancy is expected to increase and with this the percentage of the population above age 65 will grow. Patients above 65 make up more than two thirds of those currently diagnosed with gastrointestinal malignancies. Available evidence based medicine does not focus on the average patient, above the age 70, encountered in every day practice. Most guidelines and clinical trials are not designed to take into account the special considerations needed when treating the elderly such as functional status, comorbidities, polypharmacy, life expectancy, and social support. The majority of available data is based on retrospective reviews or subset analyses of larger studies where the elderly represent a fraction of the studied population. This review focuses on the toxicities and tolerability of current standard therapies for non-colorectal gastrointestinal malignancies, including gastroesophageal, pancreatic, bile duct and hepatocellular cancers in the elderly. With careful patient selection and geriatric assessment the elderly can safely benefit from standard therapies offered to younger patients. PMID:26779365

  17. Systemic therapy of non-colorectal gastrointestinal malignancies in the elderly

    PubMed Central

    Desai, Avni M.; Lichtman, Stuart M.

    2015-01-01

    In the coming years life expectancy is expected to increase and with this the percentage of the population above age 65 will grow. Patients above 65 make up more than two thirds of those currently diagnosed with gastrointestinal malignancies. Available evidence based medicine does not focus on the average patient, above the age 70, encountered in every day practice. Most guidelines and clinical trials are not designed to take into account the special considerations needed when treating the elderly such as functional status, comorbidities, polypharmacy, life expectancy, and social support. The majority of available data is based on retrospective reviews or subset analyses of larger studies where the elderly represent a fraction of the studied population. This review focuses on the toxicities and tolerability of current standard therapies for non-colorectal gastrointestinal malignancies, including gastroesophageal, pancreatic, bile duct and hepatocellular cancers in the elderly. With careful patient selection and geriatric assessment the elderly can safely benefit from standard therapies offered to younger patients. PMID:26779365

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

    PubMed

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

    2016-09-01

    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

  19. 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.

  20. Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis

    PubMed Central

    Zhou, Wei-Jie; Geng, Zhen H; Chi, Shan; Zhang, Wenli; Niu, Xiao-Feng; Lan, Shu-Jue; Ma, Li; Yang, Xuesong; Wang, Li-Jing; Ding, Yan-Qing; Geng, Jian-Guo

    2011-01-01

    The Slit family of guidance cues binds to Roundabout (Robo) receptors and modulates cell migration. We report here that ectopic expression of Slit2 and Robo1 or recombinant Slit2 treatment of Robo1-expressing colorectal epithelial carcinoma cells recruited an ubiquitin ligase Hakai for E-cadherin (E-cad) ubiquitination and lysosomal degradation, epithelial-mesenchymal transition (EMT), and tumor growth and liver metastasis, which were rescued by knockdown of Hakai. In contrast, knockdown of endogenous Robo1 or specific blockade of Slit2 binding to Robo1 prevented E-cad degradation and reversed EMT, resulting in diminished tumor growth and liver metastasis. Ectopic expression of Robo1 also triggered a malignant transformation in Slit2-positive human embryonic kidney 293 cells. Importantly, the expression of Slit2 and Robo1 was significantly associated with an increased metastatic risk and poorer overall survival in colorectal carcinoma patients. We conclude that engagement of Robo1 by Slit2 induces malignant transformation through Hakai-mediated E-cad ubiquitination and lysosomal degradation during colorectal epithelial cell carcinogenesis. PMID:21283129

  1. High Blood Glucose Levels Correlate with Tumor Malignancy in Colorectal Cancer Patients.

    PubMed

    Cui, Ge; Zhang, Ting; Ren, Fan; Feng, Wen-Ming; Yao, Yunliang; Cui, Jie; Zhu, Guo-Liang; Shi, Qi-Lin

    2015-01-01

    BACKGROUND Research shows that type 2 diabetes mellitus (T2DM) affects the risk and prognosis of colorectal cancer (CRC). Here, we conducted a retrospective study to investigate whether the clinicopathological features of CRC patients correlate with their blood glucose levels. MATERIAL AND METHODS We enrolled 391 CRC patients hospitalized in our center between 2008 and 2013. Data of their first fasting plasma glucose (FPG) and 2-h postprandial glucose (2hPPG) level after admission, their clinicopathological features, and survival were collected. The correlations between blood glucose level and clinicopathological features were analyzed by Pearson chi-square analysis. Patient survival was analyzed by Kaplan-Meier and Cox-regression analysis. RESULTS There were 116 out of the 391 CRC patients who had high blood glucose level (H-G group, 29.67%), among which 58 (14.83%), 18 (4.60%), and 40 (10.23%) were diabetes mellitus (DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG), respectively, while 275 (70.33%) patients had normal glucose level (N-G group). Compared with the N-G group, patients in the H-G group had larger tumor diameters and lower tumor differentiation (p<0.05). A higher ratio of patients in the H-G group also had more advanced TNM staging and more ulcerative CRC gross type (p<0.05). No significant difference was observed in patient overall survival among different glucose groups. No effect of insulin therapy on CRC development and patient survival was observed. CONCLUSIONS Blood glucose level in CRC patients correlates significantly with local tumor malignancy, but no significant effect on distant metastasis and patient overall survival was observed. PMID:26644185

  2. High Blood Glucose Levels Correlate with Tumor Malignancy in Colorectal Cancer Patients

    PubMed Central

    Cui, Ge; Zhang, Ting; Ren, Fan; Feng, Wen-Ming; Yao, Yunliang; Cui, Jie; Zhu, Guo-Liang; Shi, Qi-Lin

    2015-01-01

    Background Research shows that type 2 diabetes mellitus (T2DM) affects the risk and prognosis of colorectal cancer (CRC). Here, we conducted a retrospective study to investigate whether the clinicopathological features of CRC patients correlate with their blood glucose levels. Material/Methods We enrolled 391 CRC patients hospitalized in our center between 2008 and 2013. Data of their first fasting plasma glucose (FPG) and 2-h postprandial glucose (2hPPG) level after admission, their clinicopathological features, and survival were collected. The correlations between blood glucose level and clinicopathological features were analyzed by Pearson chi-square analysis. Patient survival was analyzed by Kaplan-Meier and Cox-regression analysis. Results There were 116 out of the 391 CRC patients who had high blood glucose level (H-G group, 29.67%), among which 58 (14.83%), 18 (4.60%), and 40 (10.23%) were diabetes mellitus (DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG), respectively, while 275 (70.33%) patients had normal glucose level (N-G group). Compared with the N-G group, patients in the H-G group had larger tumor diameters and lower tumor differentiation (p<0.05). A higher ratio of patients in the H-G group also had more advanced TNM staging and more ulcerative CRC gross type (p<0.05). No significant difference was observed in patient overall survival among different glucose groups. No effect of insulin therapy on CRC development and patient survival was observed. Conclusions Blood glucose level in CRC patients correlates significantly with local tumor malignancy, but no significant effect on distant metastasis and patient overall survival was observed. PMID:26644185

  3. Implications of current therapeutic approaches in colorectal cancer for other gastrointestinal malignancies.

    PubMed

    Lembersky, B C

    1991-02-01

    Novel immunotherapeutic strategies for combating colon cancer are also being explored in pancreatic, hepatic, and esophageal cancers. Preliminary clinical trials in patients with pancreatic cancer suggest a therapeutic role for anti-idiotypic antibodies against tumor-specific monoclonal antibodies (MoAbs)--eg, CO17-1A, BW 494/32--but not for MoAbs when used alone. Adding low doses of interferon gamma to CO17-1A enhances in vitro antibody-dependent cellular cytotoxicity against pancreatic tumor cells; CO17-1A plus a regimen of 5-FU/doxorubicin/mitomycin has resulted in beneficial therapeutic effect. Treatments with immunotoxins, radiolabeled MoAbs, and adoptive immunotherapy are still being tested preclinically. In 105 patients with unresectable hepatocellular cancer, a 7% complete and 41% partial regression rate with 131I-labeled antiferritin has been reported. In several patients, radiolabeled antiferritin caused sufficient shrinkage of lesions to permit curative resection. Pretreatment with low-dose doxorubicin may improve the efficacy of low-dose radiolabeled antiferritin antibody therapy. Chemoembolization of primary hepatocellular carcinoma, based on the concept of regional therapy for metastatic colorectal cancer, has shown considerable palliative and survival benefit in patients with unresectable disease. Although adoptive immunotherapy has been used to treat hepatocellular carcinoma, the results have been disappointing. The development of immunotherapeutic approaches to esophageal cancer is less advanced than that for other gastrointestinal malignancies. Paralleling the successful use of 5-FU/interferon alfa-2a in colon cancer are two phase II studies that have evaluated this combination in patients with locally advanced esophageal cancer. The objective response rate (27%) was encouraging. PMID:1992529

  4. 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. PMID:25745996

  5. Endoscopic palliation of colorectal benign and malignant tumors: YAG laser therapy

    NASA Astrophysics Data System (ADS)

    Norberto, Lorenzo; Ranzato, Riccardo; Marino, Saverio; Angriman, Imerio; Vella, Vincenzo; Donadi, Michele; D'Amico, D. F.

    1997-12-01

    From November 1, 1992 to January 31, 1997, we treated 189 pts: 113 males and 76 females, of mean age 67 yrs. 148 pts were affected with colo-rectal cancer and 41 pts with extensive carpet benign tumors. Tumor location was: rectum in 115 pts, recto-sigmoid joint in 31 pts, colo-rectal anastomosis in 25 pts, sigmoid colon in 15 pts, descending colon in 2 pts and cecum in 1 pt. 26 pts were treated with diathermo-therapy, 15 pts with dilatation, 12 pts with radiotherapy, 5 pts with chemotherapy, 1 pt with chemotherapy and radiotherapy. Yag-laser palliation gave good results in 90% (170 - 189) with an average survival of 24 weeks; there were complications due to the treatment in due pts (1%) without hospital mortality.

  6. Total thyroidectomy as the single surgical option for benign and malignant thyroid disease: a surgical challenge

    PubMed Central

    Tympa, Aliki; Arkadopoulos, Nikolaos; Nikolakopoulos, Fotios; Petropoulou, Thalia; Smyrniotis, Vassilios

    2013-01-01

    Introduction Total thyroidectomy has been the treatment of choice for patients with malignant thyroid disease. However, the efficacy and safety of this procedure for patients with benign disease is still a matter of debate. The aim of this study is to show that total thyroidectomy can be safely performed for both malignant and benign disease. Material and methods A retrospective study on 216 patients was conducted. Once an indication for surgery was established, our single surgical treatment was total thyroidectomy. Age, sex, nature of thyroid disease, final pathology and postoperative complications were recorded. Results For both benign and malignant disease, total thyroidectomy resulted in no permanent laryngeal nerve injury and no permanent hypoparathyroidism. Temporary laryngeal nerve palsy occurred in 0.9% and 3% of patients with benign and malignant disease respectively (p = 0.245). Six percent of patients with benign and 10.0% of patients with malignant thyroid disease suffered temporary hypoparathyroidism (p = 0.280). Immediate reoperation for postoperative hemorrhage was performed in 1.7% of patients with benign disease and in 1.0% of patients with malignancy with an uneventful outcome (p = 0.650). Conclusions When performed by surgeons experienced in endocrine surgery, total thyroidectomy may be considered as the treatment of choice for both malignant and benign thyroid disease requiring surgical treatment. Total thyroidectomy virtually eliminates the requirement of completion thyroidectomy for incidentally diagnosed thyroid carcinoma and significantly reduces the rate of reoperation for recurrent disease, as it provides an immediate and permanent cure for all benign thyroid diseases, with a low incidence of postoperative complications. PMID:23515861

  7. Outcome of stenting in biliary and pancreatic benign and malignant diseases: A comprehensive review

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Baron, Todd H; Luigiano, Carmelo

    2015-01-01

    Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review, relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases. PMID:26290631

  8. Outcome of stenting in biliary and pancreatic benign and malignant diseases: A comprehensive review.

    PubMed

    Mangiavillano, Benedetto; Pagano, Nico; Baron, Todd H; Luigiano, Carmelo

    2015-08-14

    Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review, relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases. PMID:26290631

  9. Colorectal Cancer with Residual Polyp of Origin: A Model of Malignant Transformation.

    PubMed

    Druliner, Brooke R; Rashtak, Shahrooz; Ruan, Xiaoyang; Bae, Taejeong; Vasmatzis, Nikolaos; O'Brien, Daniel; Johnson, Ruth; Felmlee-Devine, Donna; Washechek-Aletto, Jill; Basu, Nivedita; Liu, Hongfang; Smyrk, Thomas; Abyzov, Alexej; Boardman, Lisa A

    2016-08-01

    The majority of colorectal cancers (CRCs) arise from adenomatous polyps. In this study, we sought to present the underrecognized CRC with the residual polyp of origin (CRC RPO+) as an entity to be utilized as a model to study colorectal carcinogenesis. We identified all subjects with biopsy-proven CRC RPO+ that were evaluated over 10 years at Mayo Clinic, Rochester, MN, and compared their clinical and pathologic characteristics to CRC without remnant polyps (CRC RPO-). Overall survival and disease-free survival overlap with an equivalent hazard ratio between CRC RPO+ and RPO- cases when age, stage, and grade are adjusted. The somatic genomic profile obtained by whole genome sequencing and the gene expression profiles by RNA-seq for CRC RPO+ tumors were compared with that of age -and gender-matched CRC RPO- evaluated by The Cancer Genome Atlas. CRC RPO+ cases were more commonly found with lower-grade, earlier-stage disease than CRC RPO-. However, within the same disease stage and grade, their clinical course is very similar to that of CRC RPO-. The mutation frequencies of commonly mutated genes in CRC are similar between CRC RPO+ and RPO- cases. Likewise, gene expression patterns are indistinguishable between the RPO+ and RPO- cases. We have confirmed that CRC RPO+ is clinically and biologically similar to CRC RPO- and may be utilized as a model of the adenoma to carcinoma transition. PMID:27567950

  10. Small Bowel Adenocarcinoma as the Cause of Gastrointestinal Bleeding in Celiac Disease: A Rare Malignancy in a Common Disease

    PubMed Central

    Fallah, Jaleh; Afari, Maxwell Eyram; Cordova, Alfredo C.; Olszewski, Adam J.; Minami, Taro

    2015-01-01

    Introduction. Celiac disease is associated with an increased risk of small bowel malignancies, particularly lymphoma. Its association with small bowel carcinoma is less known. Case Description. We report a case of an 89-year-old woman with celiac disease who experienced recurrent episodes of gastrointestinal bleeding and was ultimately found to have adenocarcinoma of the small intestine. Discussion and Evaluation. Diagnosis of small bowel adenocarcinoma is often delayed because of the need for specialized modalities, which are often deferred in the inpatient setting. Although resection is the modality of choice for small bowel tumors, a majority is either locally advanced or metastatic at diagnosis, and even localized cancers have worse prognosis than stage-matched colorectal tumors. The role of adjuvant chemotherapy is uncertain, but it is often offered extrapolating data from other gastrointestinal cancers. Small bowel carcinomas occurring in the context of celiac disease appear to be associated with higher rates of microsatellite instability than sporadic tumors, although other specific genomic abnormalities and mechanisms of carcinogenesis in celiac disease remain unknown. Conclusion. Recurrent episodes of gastrointestinal bleeding in a patient with celiac disease should prompt an early evaluation of the small bowel to assure timely diagnosis of carcinoma at an early curable stage. PMID:26290763

  11. Fine-needle aspiration biopsy and other biopsies in suspected intraocular malignant disease: a review.

    PubMed

    Eide, Nils; Walaas, Lisa

    2009-09-01

    Ocular oncologists require a strong indication for intraocular biopsy before the procedure can be performed because it carries a risk for serious eye complications and the dissemination of malignant cells. The purpose of this review is to evaluate the extent to which this restricted practice is supported by evidence from previous reports and to outline our main indications and contraindications. The different intraocular biopsy techniques in the anterior and posterior segment are discussed with a focus on our preferred method, fine-needle aspiration biopsy (FNAB). In the literature, complications are typically under-reported, which reduces the possibilities of evaluating the risks correctly and of making fair comparisons with other biopsy methods. In FNAB, the exact placement of the needle is critical, as is an accurate assessment of the size of the lesion. Fine-needle aspiration biopsy is usually not a reliable diagnostic tool in lesions < 2 mm in thickness. It is very advantageous to have a cytopathologist present in the operating theatre or close by. This ensures adequate sampling and encourages repeated biopsy attempts if necessary. This approach reduces false negative results to < 3%. Adjunct immunocytochemistry is documented to increase specificity and is essential for diagnosis and management in about 10% of cases. In some rare pathological processes the diagnosis depends ultimately on the identification of specific cell markers. An accurate diagnosis may have a decisive influence on prognosis. The cytogenetic prognostications made possible after FNAB are reliable. Biopsy by FNA has a low complication rate. The calculated risk for retinal detachment is < 4%. Intraocular haemorrhage is frequently observed, but clears spontaneously in nearly all cases. Only a single case of epibulbar seeding of malignant cells at the scleral pars plana puncture site of transvitreal FNAB has been documented. Endophthalmitis has been reported and adequate standard preoperative

  12. Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview

    PubMed Central

    Frick, Vilma Oliveira; Rubie, Claudia; Keilholz, Ulrich; Ghadjar, Pirus

    2016-01-01

    Chemokines belong to a superfamily of small, cytokine-like proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20 (CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer (CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies. PMID:26811629

  13. Phospholipase Cδ1 induces E-cadherin expression and suppresses malignancy in colorectal cancer cells

    PubMed Central

    Satow, Reiko; Hirano, Tamaki; Batori, Ryosuke; Nakamura, Tomomi; Murayama, Yumi; Fukami, Kiyoko

    2014-01-01

    Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in CRC predict the ineffectiveness of EGF receptor-targeted therapy. Previous transcriptional microarray analysis suggests the association between phospholipase Cδ1 (PLCδ1) expression and KRAS mutation status in CRC. However, both the roles and the regulatory mechanisms of PLCδ1 in CRC are not known. Here, we found that the expression of PLCδ1, one of the most basal PLCs, is down-regulated in CRC specimens compared with normal colon epithelium by immunohistochemistry. Furthermore, we examined the roles of PLCδ1 in CRC cell lines that harbor an activating KRAS mutation. Ectopic expression of PLCδ1 in CRC cells induced the expression of E-cadherin, whereas knockdown of PLCδ1 repressed the expression of E-cadherin. Moreover, the overexpression of PLCδ1 suppressed the expression of several mesenchymal genes and reduced cell motility, invasiveness, and in vivo tumorigenicity of SW620 CRC cells. We also showed that PLCδ1 expression is repressed by the KRAS/mitogen-activated protein kinase kinase (MEK) pathway. Furthermore, PLCδ1 suppressed the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 through E-cadherin induction in CRC cells, suggesting the presence of a negative regulatory loop between KRAS/MEK/ERK signaling and PLCδ1. These data indicate that PLCδ1 has tumor-suppressive functions in CRC through E-cadherin induction and KRAS/MEK/ERK signal attenuation. PMID:25197077

  14. Claudin-3 Overexpression Increases the Malignant Potential of Colorectal Cancer Cells: Roles of ERK1/2 and PI3K-Akt as Modulators of EGFR signaling

    PubMed Central

    de Souza, Waldemir F.; Fortunato-Miranda, Natalia; Robbs, Bruno K.; de Araujo, Wallace M.; de-Freitas-Junior, Julio C.; Bastos, Lilian G.; Viola, João P. B.; Morgado-Díaz, José A.

    2013-01-01

    The altered expressions of claudin proteins have been reported during the tumorigenesis of colorectal cancer. However, the molecular mechanisms that regulate these events in this cancer type are poorly understood. Here, we report that epidermal growth factor (EGF) increases the expression of claudin-3 in human colorectal adenocarcinoma HT-29 cells. This increase was related to increased cell migration and the formation of anchorage-dependent and anchorage-independent colonies. We further showed that the ERK1/2 and PI3K-Akt pathways were involved in the regulation of these effects because specific pharmacological inhibition blocked these events. Genetic manipulation of claudin-1 and claudin-3 in HT-29 cells showed that the overexpression of claudin-1 resulted in decreased cell migration; however, migration was not altered in cells that overexpressed claudin-3. Furthermore, the overexpression of claudin-3, but not that of claudin-1, increased the tight junction-related paracellular flux of macromolecules. Additionally, an increased formation of anchorage-dependent and anchorage-independent colonies were observed in cells that overexpressed claudin-3, while no such changes were observed when claudin-1 was overexpressed. Finally, claudin-3 silencing alone despite induce increase proliferation, and the formation of anchoragedependent and -independent colonies, it was able to prevent the EGF-induced increased malignant potential. In conclusion, our results show a novel role for claudin-3 overexpression in promoting the malignant potential of colorectal cancer cells, which is potentially regulated by the EGF-activated ERK1/2 and PI3K-Akt pathways. PMID:24069372

  15. The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

    PubMed

    Renaud, Florence; Mariette, Christophe; Vincent, Audrey; Wacrenier, Agnès; Maunoury, Vincent; Leclerc, Julie; Coppin, Lucie; Crépin, Michel; Van Seuningen, Isabelle; Leteurtre, Emmanuelle; Buisine, Marie-Pierre

    2016-03-15

    The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention. PMID:26476272

  16. 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

  17. 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

  18. Long noncoding RNA SPRY4-IT1 promotes malignant development of colorectal cancer by targeting epithelial–mesenchymal transition

    PubMed Central

    Cao, Dong; Ding, Qiong; Yu, Wubin; Gao, Ming; Wang, Yilian

    2016-01-01

    The clinical significance and biological functions of long noncoding RNA SPRY4 intronic transcript 1 (SPRY4-IT1) in colorectal cancer (CRC) remain largely unclear. Herein, we are the first to report that the SPRY4-IT1 was significantly upregulated in CRC tissues, serum, and cells. Higher SPRY4-IT1 expression was markedly associated with advanced Tumor Node Metastasis (TNM) stage in a cohort of 84 CRC patients. Multivariate analyses indicated that SPRY4-IT1 expression could be useful as an independent predictor for overall survival. Further in vitro experiments revealed that knockdown of SPRY4-IT1 inhibited the proliferation, migration, and invasion of CRC cells and induced cell cycle arrestment. Moreover, we confirmed that the expression of epithelial–mesenchymal transition-related genes was modulated through alteration of SPRY4-IT1 expression. These results suggest that SPRY4-IT1, as an oncogenic regulator, may serve as a candidate prognostic marker and potential target for CRC therapies. PMID:27621655

  19. Long noncoding RNA SPRY4-IT1 promotes malignant development of colorectal cancer by targeting epithelial-mesenchymal transition.

    PubMed

    Cao, Dong; Ding, Qiong; Yu, Wubin; Gao, Ming; Wang, Yilian

    2016-01-01

    The clinical significance and biological functions of long noncoding RNA SPRY4 intronic transcript 1 (SPRY4-IT1) in colorectal cancer (CRC) remain largely unclear. Herein, we are the first to report that the SPRY4-IT1 was significantly upregulated in CRC tissues, serum, and cells. Higher SPRY4-IT1 expression was markedly associated with advanced Tumor Node Metastasis (TNM) stage in a cohort of 84 CRC patients. Multivariate analyses indicated that SPRY4-IT1 expression could be useful as an independent predictor for overall survival. Further in vitro experiments revealed that knockdown of SPRY4-IT1 inhibited the proliferation, migration, and invasion of CRC cells and induced cell cycle arrestment. Moreover, we confirmed that the expression of epithelial-mesenchymal transition-related genes was modulated through alteration of SPRY4-IT1 expression. These results suggest that SPRY4-IT1, as an oncogenic regulator, may serve as a candidate prognostic marker and potential target for CRC therapies. PMID:27621655

  20. 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.

  1. 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. PMID:19531654

  2. Colorectal cancer in adolescents.

    PubMed Central

    Shankar, A.; Renaut, A. J.; Whelan, J.; Taylor, I.

    1999-01-01

    Colorectal cancer, one of the most common malignancies among adults, is rare in adolescence. This low incidence coupled with non-specific symptoms and aggressive natural history leads to a poorer prognosis than in reported adult series. This article describes two cases of colorectal cancer in adolescents and reviews the literature regarding this rare condition. Earlier diagnosis and a greater understanding of the natural history may lead to improved treatment with concomitant improvements in survival. Images Figure 1 Figure 2 PMID:10364965

  3. PTEN Overexpression Cooperates With Lithium to Reduce the Malignancy and to Increase Cell Death by Apoptosis via PI3K/Akt Suppression in Colorectal Cancer Cells.

    PubMed

    de Araujo, Wallace Martins; Robbs, Bruno Kaufmann; Bastos, Lilian G; de Souza, Waldemir F; Vidal, Flávia C B; Viola, João P B; Morgado-Diaz, Jose A

    2016-02-01

    Lithium is a well-established non-competitive inhibitor of glycogen synthase kinase-3β (GSK-3β), a kinase that is involved in several cellular processes related to cancer progression. GSK-3β is regulated upstream by PI3K/Akt, which is negatively modulated by PTEN. The role that lithium plays in cancer is controversial because lithium can activate or inhibit survival signaling pathways depending on the cell type. In this study, we analyzed the mechanisms by which lithium can modulate events related to colorectal cancer (CRC) progression and evaluated the role that survival signaling pathways such as PI3K/Akt and PTEN play in this context. We show that the administration of lithium decreased the proliferative potential of CRC cells in a GSK-3β-independent manner but induced the accumulation of cells in G2/M phase. Furthermore, high doses of lithium increased apoptosis, which was accompanied by decreased proteins levels of Akt and PTEN. Then, cells that were induced to overexpress PTEN were treated with lithium; we observed that low doses of lithium strongly increased apoptosis. Additionally, PTEN overexpression reduced proliferation, but this effect was minor compared with that in cells treated with lithium alone. Furthermore, we demonstrated that PTEN overexpression and lithium treatment separately reduced cell migration, colony formation, and invasion, and these effects were enhanced when lithium treatment and PTEN overexpression were combined. In conclusion, our findings indicate that PTEN overexpression and lithium treatment cooperate to reduce the malignancy of CRC cells and highlight lithium and PTEN as potential candidates for studies to identify new therapeutic approaches for CRC treatment. PMID:26224641

  4. A Randomised Controlled Trial of Intravenous Zoledronic Acid in Malignant Pleural Disease: A Proof of Principle Pilot Study

    PubMed Central

    Clive, Amelia O.; Hooper, Clare E.; Edey, Anthony J.; Morley, Anna J.; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P.; Sequeiros, Iara; Lyen, Stephen M.; Milton, Tim; Kahan, Brennan C.; Maskell, Nick A.

    2015-01-01

    Introduction Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. Methods We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Results Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI −4.7 to 13.0)) or change in DCE-MRI iAUC (AMD −15.4 (95%CI −58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. Conclusions This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. Trial Registration UK Clinical

  5. Chemoprevention of colorectal cancer.

    PubMed

    Lang, Michaela; Gasche, Christoph

    2015-01-01

    Colorectal cancer has become one of the most prevalent malignant diseases for both men and women. Patients with inflammatory bowel diseases or certain inherited cancer syndromes are at high risk of developing colorectal cancer and have naturally the highest need for cancer prevention. In familial adenomatous polyposis (FAP) and Lynch syndrome, most of the underlying germline mutations can be detected by DNA sequencing, and medical counselling of affected individuals involves both surveillance tests and chemopreventive measures. However, as the mechanisms leading to colorectal cancer differ in these high-risk groups, the molecular action of chemopreventive drugs needs to be adjusted to the certain pathway of carcinogenesis. In the last decades, a number of drugs have been tested, including sulindac, aspirin, celecoxib, and mesalazine, but some of them are still controversially discussed. This review summarizes the advances and current standards of colorectal cancer prevention in patients with inflammatory bowel disease, FAP and Lynch syndrome. PMID:25531498

  6. Colorectal polyps

    MedlinePlus

    ... SJ, et al. United States Multi-Society Task Force on Colorectal Cancer. Guidelines for colonoscopy surveillance after ... consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology . 2012;143:844-857. ...

  7. 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 ...

  8. Colorectal Cancer

    MedlinePlus

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

  9. Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: A review of the literature

    PubMed Central

    Wang, Rosy; Leong, Rupert W

    2014-01-01

    To examine and evaluate recent evidence regarding the epidemiology, pathogenesis and management of colorectal cancer (CRC) development in inflammatory bowel disease (IBD)-primary sclerosing cholangitis (PSC) patients. Using the PubMed database, a literature search was conducted for relevant articles in English from the past 10 years. Relevant studies investigating PSC as a risk factor for CRC in IBD in the context of incidence and prevalence, pathogenesis, prevention and prognosis were included in this review. Recent evidence increasingly points to PSC as a significant risk factor in the development of CRC in patients with concomitant IBD. PSC may be an important risk factor for CRC in different populations worldwide. The mechanism for this increase in risk is still unclear. The efficacy of UDCA as a chemopreventive agent remains controversial. Liver transplantation does not halt the development of CRC, although there is not enough evidence to suggest that it is associated with increased incidence of CRC. While routine colonoscopic surveillance should be performed in patients with concurrent PSC and IBD, more high-level evidence is required to support the benefits of the procedure. While many new developments have taken place in the last decade, the pathogenesis and optimal management of CRC development in IBD-PSC patients remain unclear. PMID:25083052

  10. Synchronous bilateral primary breast malignant phyllodes tumor and carcinoma of the breast with Paget’s disease: a case report and review of the literature

    PubMed Central

    Zhao, Hongyuan; Cheng, Xiaoming; Sun, Suhong; Yang, Weiming; Kong, Fanli; Zeng, Feng

    2015-01-01

    Synchronous bilateral primary breast malignant phyllodes tumor or/and carcinoma of the breast with Paget’s disease is rare. In the article, we present a case of bilateral carcinoma of the breast with Paget’s disease of the right breast and malignant phyllodes tumor of the left breast. A 44-years-old Chinese woman presented with a 1 month history of the right breast nipple with eczema and fester and growing and palpable mass of left breast. Molybdenum target X-ray revealed microcalcification in the right breast, which was highly suspected of malignant tumor, and round-like mass with smooth surface and homogeneous density in the left breast. Color ultrasound showed a lobulated lump which circumferential blood flows around in the left breast, and which did not show any mass in the right breast. The patient was undertaken the bilateral modified radical mastectomy. The histological diagnosis was Paget’s disease associated with infiltrating ductal carcinoma in the right breast and malignant phyllodes tumor the left breast. The patient also received 6 cycles of the postoperative adjuvant chemotherapy by using T.T. regimen comprised docetaxel (100 mg) and pirarubicin (60 mg). PMID:26770378

  11. Primary Prevention of Colorectal Cancer

    PubMed Central

    Chan, Andrew T.; Giovannucci, Edward L.

    2010-01-01

    Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of the dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and the maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and non-steroidal anti-inflammatory drugs and post-menopausal hormones for women are associated with significant reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence. PMID:20420944

  12. [Tumor markers for colorectal cancer].

    PubMed

    Yamamoto, H; Miyake, Y; Noura, S; Ogawa, M; Yasui, M; Ikenaga, M; Sekimoto, M; Monden, M

    2001-09-01

    CEA and CA19-9 are the two most common tumor markers for colorectal cancer that are currently utilized clinically. The positive rate of CEA is 40-60% and that of CA19-9 is 30-50%. Simultaneous use of the two markers is useful in evaluating the therapeutic effect and monitoring the recurrence of advanced colorectal cancer. Surgical specimens may also provide useful information for the appropriate treatment of patients. Using surgically resected lymph nodes, we examined micrometastasis to assess the spread of the cancer cells and the malignant potential of colorectal cancer. Immunohistochemical analysis using anti-cytokeratin antibody revealed no significant impact of micrometastasis on patient prognosis, while RT-PCR assay using CEA as a genetic marker suggested a positive value in predicting a rapid recurrence. Among various molecular markers, we found that CDC25B phosphatase was a powerful prognostic factor for colorectal cancer. Diagnosis of the existence and malignant potential of cancer cells, together with serum tumor marker levels, may help to construct a more useful system for the better treatment of colorectal cancer. PMID:11579645

  13. 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

  14. 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.

  15. 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

  16. Systemic Treatment of Colorectal Cancer

    PubMed Central

    Wolpin, Brian M.; Mayer, Robert J.

    2008-01-01

    Colorectal cancer is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. Over the past 12 years, significant progress has been made in the systemic treatment of this malignant condition. Six new chemotherapeutic agents have been introduced, increasing median overall survival for patients with metastatic colorectal cancer from less than 9 months with no treatment to approximately 24 months. For patients with stage III (lymph node positive) colon cancer, an overall survival benefit for fluorouracil-based chemotherapy has been firmly established, and recent data have shown further efficacy for the inclusion of oxaliplatin in such adjuvant treatment programs. For patients with stage II colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at higher risk for disease recurrence. Ongoing randomized clinical trials are evaluating how best to combine currently available therapies, while smaller studies are evaluating new agents, with the goal of continued progress in prolonging life among patients with metastatic colorectal cancer and increasing cure rates among those with resectable disease. PMID:18471507

  17. Role of self expandable stents in management of colorectal cancers

    PubMed Central

    Cetinkaya, Erdinc; Dogrul, Ahmet Bulent; Tirnaksiz, Mehmet Bulent

    2016-01-01

    Acute malignant colorectal obstruction is a complication of colorectal cancer that can occur in 7%-29% of patients. Self-expanding metallic stent placement for malignant colorectal obstruction has gained popularity as a safe and effective procedure for relieving obstruction. This technique can be used in the palliation of malignant colorectal obstruction, as a bridge to elective surgery for resectable colorectal cancers, palliation of extracolonic malignant obstruction, and for nonmalignant etiologies such as anastomotic strictures, Crohn’s disease, radiation therapy, and diverticular diseases. Self-expanding metallic stent has its own advantages and disadvantages over the surgery in these indications. During the insertion of the self-expanding metallic stent, and in the follow-up, short term and long term morbidities should be kept in mind. The most important complications of the stents are perforation, stent obstruction, stent migration, and bleeding. Additionally, given the high risk of perforation, if a patient is treated or being considered fortreatmentwith antiangiogenic agents such as bevacizumab, it is not recommended to use self-expanding metallic stent as a palliative treatment for obstruction. Therefore, there is a need for careful clinical evaluation for each patient who is a candidate for this procedure. The purpose of this review was to evaluate self-expanding metallic stent in the management of the obstruction of the colon due to the colorectal and extracolonic obstruction. PMID:26798442

  18. 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 ...

  19. Industrial risk factors for colorectal cancer

    SciTech Connect

    Lashner, B.A.; Epstein, S.S. )

    1990-01-01

    Colorectal cancer is the second most common malignancy in the United States, and its incidence rates have sharply increased recently, especially in males. Industrial exposures, both occupational and environmental, are important colorectal cancer risk factors that are generally unrecognized by clinicians. Migration studies have documented that colorectal cancer is strongly associated with environmental risk factors. The causal role of occupational exposures is evidenced by a substantial literature associating specific work practices with increased colorectal cancer risks. Industrially related environmental exposures, including polluted drinking water and ionizing radiation, have also been associated with excess risks. Currently, there is a tendency to attribute colorectal cancer, largely or exclusively, to dietary and other lifestyle factors, thus neglecting these industrially related effects. Concerted efforts are needed to recognize the causal role of industrial risk factors and to encourage government and industry to reduce carcinogenic exposures. Furthermore, cost-effective screening programs for high-risk population groups are critically needed to further reduce deaths from colorectal cancer. 143 references.

  20. Five Myths about Colorectal Cancer

    MedlinePlus

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

  1. 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.

  2. 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. PMID:26966404

  3. 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

  4. [Clinicopathological characteristics of colorectal carcinoma in the elderly].

    PubMed

    Tao, Kaixiong; Gao, Jinbo; Wang, Guobin

    2016-05-01

    Elderly patients with colorectal cancer have different clincopathological characteristics from younger patients. Colorectal cancers tend to localize in the proximal colon, from cecum to the splenic flexure in the elderly patients. Changes in the stools, rectal bleeding or black stool, abdominal pain, fatigue, weight loss and anemia are the common symptoms. Analysis showed that age is one of independent risk factors for lower completion rates of colonoscopy. Therefore, the choice of diagnosis methods in elderly patients should be careful. Achieving a clear diagnosis and avoiding complications should be considered at the same time. Most colorectal cancers in elderly are highly and moderately differentiated adenocarcinomas and locally advanced, and have less lymphatic and blood metastasis. The proportion of poorly differentiated adenocarcinoma increases with the increase of age, which should be concerned. Multiple colorectal cancers and colorectal cancer with extra-colorectal malignancy are not rare in the elderly patients. The common extra-colorectal tumors consist of gastric cancer, lung cancer, biliary carcinoma, pancreas cancer and malignancy from blood system. Molecular events, such as mutations of KARS, BRAF, TP53 and deficiency of DNA mismatch repair, are more frequent in elderly colorectal cancer patients. Many factors have impact on treatment decision in elderly patients with colorectal cancer, including age, comorbidities, physiological functions of organs and willingness of patients and their relatives. Although surgery is still the main treatment, the proportion of radical surgery is lower and emergency surgery is higher as compared to younger patients. With the development of minimally invasive surgical techniques and advances in anesthesia and perioperative management, laparoscopic surgery has become widespread in elderly patients with colorectal cancer. In addition, more attention should be paid to adjuvant therapy. Comprehensive individualized

  5. Colorectal Cancer Prevention

    MedlinePlus

    ... Genetics of Colorectal Cancer Colorectal cancer is the second leading cause of death from cancer in the ... professional versions have detailed information written in technical language. The patient versions are written in easy-to- ...

  6. 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

    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-1a-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

  7. 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.

  8. Colorectal Subepithelial Lesions

    PubMed Central

    2015-01-01

    Most of subepithelial lesion (SEL) being identified was accidentally discovered as small bulging lesion covered with normal mucosa from endoscopic screening. The type of treatment and prognosis vary depending on the type of tumor, it would be crucial to perform an accurate differential diagnosis. Since the differentiation of SEL relied on the indirect findings observed from the mucosal surface using an endoscopy only in the past, it was able to confirm the presence of lesion only but difficult to identify complex detailed nature of the lesion. However, after the endoscopic ultrasonography (EUS) was introduced, it became possible to identify extrinsic compression, and size of intramural tumors, internal properties and contour so that it gets possible to have differential diagnosis of lesions and prediction on the lesion whether it is malignant or benign. In addition, the use of EUS-guided fine needle aspiration and EUS-guided core biopsy made it possible to make histological differential diagnosis. This study intended to investigate endoscopic and EUS findings, histological diagnosis, treatment regimen and impression of colorectal SELs. PMID:26240803

  9. 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. PMID:25379783

  10. Metabolites of tobacco smoking and colorectal cancer risk.

    PubMed

    Cross, Amanda J; Boca, Simina; Freedman, Neal D; Caporaso, Neil E; Huang, Wen-Yi; Sinha, Rashmi; Sampson, Joshua N; Moore, Steven C

    2014-07-01

    Colorectal cancer is not strictly considered a tobacco-related malignancy, but modest associations have emerged from large meta-analyses. Most studies, however, use self-reported data, which are subject to misclassification. Biomarkers of tobacco exposure may reduce misclassification and provide insight into metabolic variability that potentially influences carcinogenesis. Our aim was to identify metabolites that represent smoking habits and individual variation in tobacco metabolism, and investigate their association with colorectal cancer. In a nested case-control study of 255 colorectal cancers and 254 matched controls identified in the Prostate, Lung, Colorectal and Ovarian cancer screening trial, baseline serum was used to identify metabolites by ultra-high-performance liquid-phase chromatography and mass spectrometry, as well as gas chromatography with tandem mass spectrometry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Self-reported current smoking was associated with serum cotinine, O-cresol sulfate and hydroxycotinine. Self-reported current smoking of any tobacco (OR = 1.90, 95% CI: 1.02-3.54) and current cigarette smoking (OR = 1.51, 95% CI: 0.75-3.04) were associated with elevated colorectal cancer risks, although the latter was not statistically significant. Individuals with detectable levels of hydroxycotinine had an increased colorectal cancer risk compared with those with undetectable levels (OR = 2.68, 95% CI: 1.33-5.40). Although those with detectable levels of cotinine had a suggestive elevated risk of this malignancy (OR = 1.81, 95% CI: 0.98-3.33), those with detectable levels of O-cresol sulfate did not (OR = 1.16, 95% CI: 0.57-2.37). Biomarkers capturing smoking behavior and metabolic variation exhibit stronger associations with colorectal cancer than self-report, providing additional evidence for a role for tobacco in this malignancy. PMID:24648381

  11. 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. PMID:16475029

  12. 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

  13. 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

  14. Local inflammatory response in colorectal cancer.

    PubMed

    Łaskowski, P; Klim, B; Ostrowski, K; Szkudlarek, M; Litwiejko-Pietryńczak, E; Kitlas, K; Nienartowicz, S; Dzięcioł, J

    2016-06-01

    Type and intensity of tumor-infiltrating lymphocytes (TILs) in close proximity to the primary tumor are prognostically significant in postoperative patients. High intensity of TILs is considered to be a prognostically beneficial factor. The research included 66 postoperative colorectal cancer patients. The control group comprised 20 colon segments. Monoclonal antibodies LCA, CD3, CD4, CD5, CD8, CD20, CD23 and CD138 were used to differentiate between T and B lymphocytes. Types of cells in the infiltrate were defined. We found greater numbers of T and B lymphocytes located in close proximity to the cancerous tissue when compared to the control group. T lymphocyte intensity in the inflammatory infiltrations was directly correlated with the size of resected tumors, presence of regional lymphatic node metastases and histological grade of malignancy. Lymphocytic infiltrations of greater intensity located in close proximity to the primary tumor were found in subjects with less advanced colorectal cancer. The research presented here proves direct dependence between the immune system and colorectal cancer. The presence of lymphocytes in the inflammatory infiltrations located in close proximity to the cancerous tissue has been proved to be prognostically beneficial. The obtained results support the application of immunotherapy in colorectal cancer treatment. PMID:27543872

  15. 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.

  16. 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

  17. CCX-CKR expression in colorectal cancer and patient survival.

    PubMed

    Zhu, Yunxiang; Tang, Wentao; Liu, Yun; Wang, Guanghui; Liang, Zhonglin; Cui, Long

    2014-01-01

    Colorectal cancer is one of the most common malignant cancers, with bad prognosis when distal metastasis occurs. The current study aimed to investigate the potential value of using CCX-CKR expression for the prognosis of colorectal cancer patients. The results showed that CCX-CKR expression was a negative predictor of cancer metastasis, and that it was positively correlated to the patients’ survival rate. Finally, we found that CCX-CKR expression in vitro could modulate cellular migration and invasion abilities, potentially via the regulation of other chemotactic factors/receptors. PMID:24338720

  18. 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

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

    PubMed Central

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

    2016-01-01

    Colorectal cancer screening dates to the discovery of pre-cancerous 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. PMID:26934885

  20. 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.

  1. Primary prevention of colorectal cancer. The WHO Collaborating Centre for the Prevention of Colorectal Cancer.

    PubMed Central

    Shike, M.; Winawer, S. J.; Greenwald, P. H.; Bloch, A.; Hill, M. J.; Swaroop, S. V.

    1990-01-01

    Colorectal cancer is the third most common malignant neoplasm worldwide. Epidemiological and laboratory animal studies have established a link between various nutritional factors and the etiology of this cancer. Recent studies in genetic epidemiology and molecular biology have shown that inherited genetic factors also play an important role in colorectal carcinogenesis. Thus, genetic-nutritional interactions may form the basis for the development of this cancer. Nutritional factors that appear to promote or attenuate the carcinogenic process in the colon include fat, excess calories, fibre, calcium, selenium, and various vitamins. Strategies for primary prevention of colorectal cancer should therefore be targeted to all populations who are at risk because of dietary and hereditary predisposition. Based on current knowledge, recommended nutrition guidelines for reducing the risk of colon cancer include decreased fat consumption, adequate amounts of fruits, vegetables, and calcium, and avoidance of overweight. Research to further elucidate the role of diet in colorectal carcinogenesis should include randomized studies in humans, testing of various nutritional regimens, and the use of colonic adenomas and markers of cell proliferation and differentiation as end-points. PMID:2203551

  2. Molecular characteristics and predictors of survival in patients with malignant neuroendocrine tumors

    PubMed Central

    Arnold, Christian N.; Nagasaka, Takeshi; Goel, Ajay; Scharf, Iris; Grabowski, Patricia; Sosnowski, Andrea; Schmitt-Gräff, Annette; Boland, C. Richard; Arnold, Rudolf; Blum, Hubert E.

    2010-01-01

    To better understand the molecular pathogenesis of neuroendocrine tumors (NET), we investigated the molecular and clinical characteristics of malignant poorly differentiated colorectal NET and compared these findings with sporadic CRC and well-differentiated benign and malignant fore-/midgut NET. Tumors were analyzed and correlated for microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). NET were scored for proliferation using Ki-67. A total of 34 malignant poorly differentiated colorectal NET, 38 well-differentiated benign and malignant fore-/midgut-NET and 150 sporadic colorectal cancers (CRC) with known MSI status were investigated. Among the sporadic CRC, CIMP was significantly correlated with MSI-high (MSI-H) (p < 0.001). Of the 34 colorectal NET, 0/1 of the MSI-H, 3/5 (60%) of the MSI-L and 13/19 (68%) of the MSS tumors were CIMP+ (p = 0.17). Of the fore-/midgut-NET, none was MSI-H. 20/34 (59%) colorectal NET vs. 11/38 (29%) fore-/midgut-NET were CIMP+ (p = 0.01). The Ki-67 index was significantly higher in poorly differentiated colorectal NET compared to the less malignant fore-/midgut-NET (p < 0.0001). Besides the location in the colon, Ki-67 predicted poor outcome in NET (p < 0.0001). CIMP status did not affect survival. In NET, p16 methylation predicted a poor outcome (p = 0.0004). We conclude that molecular pathogenesis in sporadic CRC and poorly differentiated colorectal NET is different despite some similarities. Main differences between malignant well-differentiated and poorly differentiated NET are the Ki-67 proliferation rate and differential methylation in tumor-associated genes. Predictors of a poor outcome in patients with NET are poor differentiation, a high Ki-67 index and p16 methylation. PMID:18646189

  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. PMID:27341596

  4. Colorectal Cancer Coalition

    MedlinePlus

    ... Million Strong Shop Join the Movement Share Your Story Check our Calendar Colorectal Support Community Latest News Help Wanted Read Blogs Get Social Free Printable Coloring Sheets Action Alerts About Our ...

  5. What Is Colorectal Cancer?

    MedlinePlus

    ... on staging, see “ Colorectal cancer stages ” The normal colon and rectum The colon and rectum are parts ... through the anus . Types of cancer in the colon and rectum Adenocarcinomas make up more than 95% ...

  6. Epidemiology of colorectal cancer.

    PubMed

    Boyle, Peter; Leon, Maria Elena

    2002-01-01

    Colorectal cancer is a important public health problem: there are nearly one million new cases of colorectal cancer diagnosed world-wide each year and half a million deaths. Recent reports show that, in the US, it was the most frequent form of cancer among persons aged 75 years and older. Given that the majority of cancers occur in elder people and with the ageing of the population in mind, this observation gives further impetus to investigating prevention and treatment strategies among this subgroup of the population. Screening research, recommendations and implementation is an obvious priority. While there are many questions to be resolved, it is apparent that many facets of colorectal cancer are becoming increasingly understood and prospects for prevention are becoming apparent. Achieving colorectal cancer control is the immediate challenge. PMID:12421722

  7. Tests for Colorectal Cancer

    MedlinePlus

    ... to look for colorectal cancer Imaging tests use sound waves, x-rays, magnetic fields, or radioactive substances to ... has spread to the liver. Ultrasound Ultrasound uses sound waves and their echoes to create images of the ...

  8. [Colorectal foreign bodies].

    PubMed

    Thim, Troels; Laurberg, Søren

    2006-09-25

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

  9. Screening for colorectal cancer.

    PubMed

    He, Jin; Efron, Jonathan E

    2011-01-01

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

  10. Colorectal carcinoma: Pathologic aspects

    PubMed Central

    Fleming, Matthew; Ravula, Sreelakshmi; Tatishchev, Sergei F.

    2012-01-01

    Colorectal carcinoma is one of the most common cancers and one of the leading causes of cancer-related death in the United States. Pathologic examination of biopsy, polypectomy and resection specimens is crucial to appropriate patient managemnt, prognosis assessment and family counseling. Molecular testing plays an increasingly important role in the era of personalized medicine. This review article focuses on the histopathology and molecular pathology of colorectal carcinoma and its precursor lesions, with an emphasis on their clinical relevance. PMID:22943008

  11. Screening for colorectal cancer.

    PubMed Central

    Campbell, W. J.; Moorehead, R. J.

    1997-01-01

    Colorectal carcinoma represents a major cause of cancer deaths in the United Kingdom. Tumours detected at an early or even premalignant stage have a better prognosis. In this review we consider the argument for screening for colorectal carcinomas and discuss the means available and the implications of implementing screening programmes using some of these methods. A suggestion is made for the more rational use of limited resources to target those at greatest risk. PMID:9185482

  12. [Epidemiology of colorectal cancer].

    PubMed

    Bouvier, Anne-Marie; Launoy, Guy

    2015-06-01

    The incidence of colorectal cancer increased in France until the 2000s' then decreased. Time trends in incidence for this cancer varied according to its sublocation along the gut. Incidence increased for right and left colon cancers, whereas it remained stable for sigmoid cancers in males and decreased in females. Incidence decreased over time for rectal cancers. The proportion of colorectal cancer in the overall French cancer prevalence is 12%. In 2008, 121,000 patients had a colorectal cancer diagnosed in the 5 previous years. The cumulative risk of colorectal cancer increased from 3.9% for males born around 1900 to 4.9% for those born around 1930 and then slightly decreased, being 4.5% among those born around 1950. It remained at the same level for females and was 2.9% for those born around 1950. The prognosis of colorectal cancer improved over time. Net 5-year survival increased in males from 53% for cancers diagnosed between 1989 and 1991 to 58% for those diagnosed between 2001 and 2004. The highest improvement of 10 year survival rates concerned left colon and rectosigmoid junction (+19% in a decade). The progressive set up of national colorectal screening since the early 2000's and the introduction of recent immunological tests in 2015 should decrease the mortality for this cancer and, at term, should decrease its incidence too. PMID:26298897

  13. Malignant thymoma.

    PubMed

    Wang, L S; Huang, M H; Lin, T S; Huang, B S; Chien, K Y

    1992-07-15

    Sixty-one patients underwent operations for malignant thymomas between 1961 and 1989. Twenty-three patients had associated myasthenia gravis (MG), an incidence of 37.7%. Upon being admitted to the hospital, the patients' most common symptoms included chest pain, MG, cough, and dyspnea. Only 7 of 61 (11.5%) patients had no symptom. Tumor staging of 58 patients with invasive thymomas was performed according to Masaoka classification. The patients were classified as follows: Stage II disease, 5; Stage III, 41; Stage IVa, 8; and Stage IVb, 4. In addition, thymic carcinoma was present in three patients. The series had a resection rate of 55.7%. The incidence of operative complications was 16.3%. Only one patient died of myocardial infarction; the incidence of operative mortality was 1.6%. The patients with MG had a higher rate of resection (69.6%) and a higher incidence of complete thymectomy (14 of 23 patients; 60.9%). Mixed lymphoepithelial tumors and epithelial cell predominant tumors were the most frequent histologic patterns (45.9% and 34.4%, respectively). Fifty-two patients had postoperative radiation therapy, and 10 patients had chemotherapy. The overall cumulative survival rates in the series were 59% and 34% at 5 and 10 years, respectively. The results demonstrated that the factors affecting the prognosis may include resectability, postoperative irradiation or chemotherapy, MG, and tumor staging. The influence of histologic variation on survival rates could not be clearly defined in the series. Surgical resection, particularly complete thymectomy, followed by irradiation is the primary option of therapeutic management for malignant thymoma. PMID:1617594

  14. The topography of colorectal cancer varies by race/ethnicity and affects the utility of flexible sigmoidoscopy.

    PubMed

    Theuer, C P; Taylor, T H; Brewster, W R; Campbell, B S; Becerra, J C; Anton-Culver, H

    2001-12-01

    Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at "average" risk for the development of colorectal cancer either with flexible sigmoidoscopy and fecal occult blood testing (FOBT) or with colonoscopy. Patients who elect flexible sigmoidoscopy and FOBT undergo full colonoscopy only if left-sided neoplasia is detected or if the FOBT is positive. Unfortunately in blacks and whites most right-sided colorectal lesions are unaccompanied by left-sided sentinel lesions, which leads some to prefer colonoscopic screening in these patients. The topography of colorectal cancer in Asians and Latinos is unavailable. We used 1988-1995 California Cancer Registry data to determine the topography of 105,906 consecutive colorectal cancers among Asian, black, Latino, and white patients. We found that the proportion of colorectal cancer distal to the splenic flexure and therefore detectable by flexible sigmoidoscopy varied by ethnicity: Asian (71%) > Latino (63%) > white (57%) > black (55%); P < 0.001. These differences were significant after adjusting for age and sex. The risk of distal disease relative to whites was 1.61 in Asians, 1.15 in Latinos, and 0.82 in blacks (P < 0.001). Flexible sigmoidoscopy detects a higher proportion of colorectal cancers in Asians and Latinos than in whites or blacks. Further study is needed to assess whether the topography of benign colorectal neoplasia parallels that of malignant disease. Colorectal screening recommendations may need to incorporate racial and ethnic differences in colorectal neoplasia topography. PMID:11768820

  15. The TNF family member APRIL promotes colorectal tumorigenesis

    PubMed Central

    Lascano, V; Zabalegui, L F; Cameron, K; Guadagnoli, M; Jansen, M; Burggraaf, M; Versloot, M; Rodermond, H; van der Loos, C; Carvalho-Pinto, C E; Kalthoff, H; Medema, J P; Hahne, M

    2012-01-01

    The tumor necrosis factor (TNF) family member APRIL (A proliferation inducing ligand) is a disease promoter in B-cell malignancies. APRIL has also been associated with a wide range of solid malignancies, including colorectal cancer (CRC). As evidence for a supportive role of APRIL in solid tumor formation was still lacking, we studied the involvement of APRIL in CRC. We observed that ectopic APRIL expression exacerbates the number and size of adenomas in ApcMin mice and in a mouse model for colitis-associated colon carcinogenesis. Furthermore, knockdown of APRIL in primary spheroid cultures of colon cancer cells and both mouse and human CRC cell lines reduced tumor clonogenicity and in vivo outgrowth. Taken together, our data therefore indicate that both tumor-derived APRIL and APRIL produced by non-tumor cells is supportive in colorectal tumorigenesis. PMID:22705846

  16. Core value of laparoscopic colorectal surgery

    PubMed Central

    Li, Xin-Xiang; Wang, Ren-Jie

    2015-01-01

    Since laparoscopy was first used in cholecystectomy in 1987, it has developed quickly and has been used in most fields of traditional surgery. People have now accepted its advantages like small incision, quick recovery, light pain, beauty and short hospital stays. In early times, there are still controversies about the application of laparoscopy in malignant tumor treatments, especially about the problems of oncology efficacy, incision implantation and operation security. However, these concerns have been fully eliminated by evidences on the basis of evidence-basis medicine. In recent years, new minimally invasive technologies are appearing continually, but they still have challenges and may increase the difficulties of radical dissection and the risks of potential complications, so they are confined to benign or early malignant tumors. The core value of the laparoscopic technique is to ensure the high quality of tumor’s radical resection and less complications. On the basis of this, it is allowed to pursue more minimally invasive techniques. Since the development of laparoscopic colorectal surgery is rapid and unceasing, we have reasons to believe that laparoscopic surgery will become gold standard for colorectal surgery in the near future. PMID:26676111

  17. Transcatheter therapy for malignant neoplasms.

    PubMed Central

    Coldwell, D M; Mortimer, J E

    1989-01-01

    Interventional radiology has developed into a subspecialty with application in the treatment and palliation of patients with advanced malignant diseases. A directed catheter delivers high concentrations of chemotherapy directly into the tumor bed. Embolic particles may be injected to stop hemorrhage or to occlude the blood supply of a cancer, resulting in pain relief or tumor shrinkage. These techniques can be incorporated into a multidisciplinary approach to cancer. Images PMID:2686168

  18. Developments in Colorectal Cancer Screening

    MedlinePlus

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

  19. Get Tested for Colorectal Cancer

    MedlinePlus

    ... section Colorectal Cancer 4 of 6 sections Take Action! Take Action: Get Tested The best way to prevent colorectal ... I at Risk? 5 of 6 sections Take Action: Healthy Habits Quit smoking. People who smoke are ...

  20. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

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

  1. Risks of Colorectal Cancer Screening

    MedlinePlus

    ... Genetics of Colorectal Cancer Colorectal cancer is the second leading cause of death from cancer in the ... professional versions have detailed information written in technical language. The patient versions are written in easy-to- ...

  2. Endobronchial metastases of colorectal cancer.

    PubMed

    Rosado Dawid, Natalia-Zuberoa; Villegas Fernández, Francisco Ramón; Rodríguez Cruz, María Del Mar; Ramos Meca, Asunción

    2016-04-01

    Colorectal metastases affecting trachea or bronchi are highly unusual. Up to 26% of endotracheal/endobronchial metastases are due to colorectal cancer. Treatment and palliative management rely on a multidisciplinary team to improve their quality of life. PMID:26856850

  3. 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 ( ...

  4. 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

  5. [Low colorectal anastomosis by the anterior perineal approach. 29 cases].

    PubMed

    Bricot, R; Le Treut, Y P; Kadji, C A; Bardot, J; Rodde, J M

    1985-12-14

    Using the combined abdominoperineal approach to the rectum through the recto-genital space, very low colo-rectal anastomosis can be performed without damaging the anal sphincter. Twenty-nine patients were operated upon by this procedure for malignant or benign disease of the lower two-thirds of the rectum: there was 2 failure; 6 patients developed transient perineal fistula; 27 patients now have normal anal continence. This technique has been considerably facilitated, notably in males, by stapled anastomosis. PMID:2934722

  6. Public Awareness of Colorectal Cancer Screening: Knowledge, Attitudes, and Interventions for Increasing Screening Uptake

    PubMed Central

    Gimeno Garcia, Antonio Z.; Hernandez Alvarez Buylla, Noemi; Nicolas-Perez, David; Quintero, Enrique

    2014-01-01

    Colorectal cancer ranks as one of the most incidental and death malignancies worldwide. Colorectal cancer screening has proven its benefit in terms of incidence and mortality reduction in randomized controlled trials. In fact, it has been recommended by medical organizations either in average-risk or family-risk populations. Success of a screening campaign highly depends on how compliant the target population is. Several factors influence colorectal cancer screening uptake including sociodemographics, provider and healthcare system factors, and psychosocial factors. Awareness of the target population of colorectal cancer and screening is crucial in order to increase screening participation rates. Knowledge about this disease and its prevention has been used across studies as a measurement of public awareness. Some studies found a positive relationship between knowledge about colorectal cancer, risk perception, and attitudes (perceived benefits and barriers against screening) and willingness to participate in a colorectal cancer screening campaign. The mentioned factors are modifiable and therefore susceptible of intervention. In fact, interventional studies focused on average-risk population have tried to increase colorectal cancer screening uptake by improving public knowledge and modifying attitudes. In the present paper, we reviewed the factors impacting adherence to colorectal cancer screening and interventions targeting participants for increasing screening uptake. PMID:24729896

  7. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    PubMed

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-14

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  8. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    PubMed Central

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  9. 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

  10. Malignant hyperpyrexia

    PubMed Central

    Isaacs, Hyam; Barlow, M. B.

    1973-01-01

    The history, clinical presentation, and management of malignant hyperpyrexia are presented. The aetiology seems to be associated with some inherited abnormality which affects the movement and binding of calcium ions in the sarcoplasmic reticulum, sarcoplasm, and mitochondria. Whether this is a primary muscular defect or secondary to some trophic neural influence is yet to be established. The subjects carrying the abnormal trait show evidence of a myopathy which is subclinical in most instances and revealed only by estimation of serum CPK or biopsy. In some families where the myopathy is clinically obvious there may be, in addition, a variety of musculoskeletal abnormalities. A plea is made for routine monitoring of temperature during anaesthesia and for procainamide or procaine to be readily available in all operating theatres. A history of anaesthetic deaths in a family calls for special care, and, if the serum CPK is elevated, suxamethonium and halothane are to be avoided. Families with orthopaedic and muscular abnormalities are at increased risk and should have estimation of serum CPK before surgery. As a bonus of this study it is suggested that serum CPK estimations be used to screen pigs for selective breeding and so eliminate the disease, which causes soft exudative pork. Images PMID:4708457

  11. Primary hepatic malignant melanoma: a case report.

    PubMed

    Du, Fangjuan; Yang, Maowu; Fang, Jingzhong; Jing, Changchun

    2015-01-01

    Primary hepatic malignant melanoma is a very rare disease. In order to provide clues concerning diagnosis, differential diagnosis and pathogenesis of the disease, a case of a 49 year-old female patient with primary hepatic malignant melanoma is presented. B-mode ultrasound and Contrast-enhanced abdominal computerized tomography (CT) examinations revealed that nodules of varying sizes are diffusely distributed in her enlarged liver. Pathological examination revealed that tumor cells with poor differentiation were located in nests with prominent melanin deposition. Immuno-histochemical staining showed that the tumor cells were positive for HMB-45 and S-100 protein. No evidence for primary malignant melanoma of other sites had been found by comprehensive examinations. Therefore, the patient was diagnosed with primary malignant melanoma of liver. Our case showed that primary malignant melanoma of liver is of histological heterogeneity, and immunohistochemical staining may aid in differential diagnosis between it and other hepatic neoplasms. PMID:25973128

  12. Management of resectable colorectal lung metastases.

    PubMed

    Moorcraft, Sing Yu; Ladas, George; Bowcock, Anne; Chau, Ian

    2016-03-01

    Lung metastases occur in 10-20 % of patients with colorectal cancer. The biology of colorectal lung metastases is poorly understood, however lung metastases are more common in patients with rectal cancer and in patients with RAS mutations. Although the majority of patients have extrapulmonary disease, a small proportion of patients with lung metastases are suitable for lung metastasectomy and surgical resection has become a standard of care, based on data from retrospective series demonstrating a 5-year overall survival of 40-68 %. However, there remains uncertainty regarding the optimal management approach for these patients due to the lack of evidence from randomized controlled trials and current practice varies between institutions. For example, the role for neoadjuvant and adjuvant chemotherapy is not yet defined and there are no randomized trials comparing surgery with alternative treatment options such as radiofrequency ablation and stereotactic ablative radiotherapy. Further research is needed to improve the selection of patients for surgery, but favourable prognostic factors include a normal pre-operative CEA, solitary metastasis, complete resection and a long disease-free interval. There is also evidence that patients with resectable liver and lung metastases may benefit from resection of both sites of disease, and that re-resection may be of benefit in selected patients who relapse with resectable lung metastases. This article summarizes the biology of colorectal lung metastases and discusses the management of patients with lung metastases. PMID:26659389

  13. Resection of Diminutive and Small Colorectal Polyps: What Is the Optimal Technique?

    PubMed Central

    Lee, Jun

    2016-01-01

    Colorectal polyps are classified as neoplastic or non-neoplastic on the basis of malignant potential. All neoplastic polyps should be completely removed because both the incidence of colorectal cancer and the mortality of colorectal cancer patients have been found to be strongly correlated with incomplete polypectomy. The majority of colorectal polyps discovered on diagnostic colonoscopy are diminutive and small polyps; therefore, complete resection of these polyps is very important. However, there is no consensus on a method to remove diminutive and small polyps, and various techniques have been adopted based on physician preference. The aim of this article was to review the diverse techniques used to remove diminutive and small polyps and to suggest which technique will be the most effective. PMID:27450226

  14. 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

  15. Management of Colorectal Trauma

    PubMed Central

    2011-01-01

    Although the treatment strategy for colorectal trauma has advanced during the last part of the twentieth century and the result has improved, compared to other injuries, problems, such as high septic complication rates and mortality rates, still exist, so standard management for colorectal trauma is still a controversial issue. For that reason, we designed this article to address current recommendations for management of colorectal injuries based on a review of literature. According to the reviewed data, although sufficient evidence exists for primary repair being the treatment of choice in most cases of nondestructive colon injuries, many surgeons are still concerned about anastomotic leakage or failure, and prefer to perform a diverting colostomy. Recently, some reports have shown that primary repair or resection and anastomosis, is better than a diverting colostomy even in cases of destructive colon injuries, but it has not fully established as the standard treatment. The same guideline as that for colonic injury is applied in cases of intraperitoneal rectal injuries, and, diversion, primary repair, and presacral drainage are regarded as the standards for the management of extraperitoneal rectal injuries. However, some reports state that primary repair without a diverting colostomy has benefit in the treatment of extraperitoneal rectal injury, and presacral drainage is still controversial. In conclusion, ideally an individual management strategy would be developed for each patient suffering from colorectal injury. To do this, an evidence-based treatment plan should be carefully developed. PMID:21980586

  16. Role of microRNA-7 in digestive system malignancy

    PubMed Central

    Chen, Wan-Qun; Hu, Ling; Chen, Geng-Xin; Deng, Hai-Xia

    2016-01-01

    There are several malignancies of the digestive system (including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA (miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies. PMID:26798443

  17. [Nutrition and colorectal cancer].

    PubMed

    Ströhle, Alexander; Maike, Wolters; Hahn, Andreas

    2007-01-01

    Diet plays an important role in the pathogenesis of colorectal cancer. Current prospective cohort studies and metaanalysis enable a reevaluation of how food or nutrients such as fiber and fat influence cancer risk. Based on the evidence criteria of the WHO/FAD, risk reduction by a high intake of fruit is assessed as possible, while a lowered risk by a high vegetable intake is probable. Especially raw vegetables and fruits seem to exert anticancer properties. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as probable whereas the evidence of an increased risk by high consumption of refined white flour products and sweets is (still) insufficient despite some evidences. There is a probable risk reducing effect of milk and dairy products. e available data on eggs and red meat indicate a possible risk increasing influence. Stronger clues for a risk increasing effect have been shown for meat products leading to an evidence assessed as probable. Owing to varied interpretations of the data on fiber, the evidence of a risk reducing effect relating to colorectal cancer is assessed as possible or insufficient. The available data on alcohol consumption indicate a possible risk increasing effect. In contrast to former evaluations, diets rich in fat seem to increase colorectal cancer risk only indirectly as part of a hypercaloric diet by advancing the obesity risk. Thus, the evidence of obesity, especially visceral obesity, as a risk of colorectal cancer is judged as convincing today. Prospective cohort studies suggest that people who get higher than average amounts of folic acid from multivitamin supplements have lower risks of colorectal cancer. The evidence for a risk reducing effect of calcium, selenium, vitamin D and vitamin E on colorectal cancer is insufficient. As primary prevention, a diet rich in vegetables, fruits, whole grain products, and legumes added by low-fat dairy products, fish, and poultry can be recommended. In

  18. 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. PMID:27102079

  19. 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.

  20. Colorectal cancer: Metastases to a single organ

    PubMed Central

    Vatandoust, Sina; Price, Timothy J; Karapetis, Christos S

    2015-01-01

    Colorectal cancer (CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site (solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ. PMID:26557001

  1. Prognostic Value of Colorectal Cancer Biomarkers

    PubMed Central

    Bianchi, Paolo; Laghi, Luigi; Delconte, Gabriele; Malesci, Alberto

    2011-01-01

    Despite the large amount of data in cancer biology and many studies into the likely survival of colorectal cancer (CRC) patients, knowledge regarding the issue of CRC prognostic biomarkers remains poor. The Tumor-Node-Metastasis (TNM) staging system continues to be the most powerful and reliable predictor of the clinical outcome of CRC patients. The exponential increase of knowledge in the field of molecular genetics has lead to the identification of specific alterations involved in the malignant progression. Many of these genetic alterations were proposed as biomarkers which could be used in clinical practice to estimate CRC prognosis. Recently there has been an explosive increase in the number of putative biomarkers able to predict the response to specific adjuvant treatment. In this review we explore and summarize data concerning prognostic and predictive biomarkers and we attempt to shed light on recent research that could lead to the emergence of new biomarkers in CRC. PMID:24212797

  2. Potential role of probiotics on colorectal cancer prevention

    PubMed Central

    2012-01-01

    Background Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. Discussion Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention. Summary Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways. PMID:23173670

  3. Worldwide variations in colorectal cancer.

    PubMed

    Center, Melissa M; Jemal, Ahmedin; Smith, Robert A; Ward, Elizabeth

    2009-01-01

    Previous studies have documented significant international variations in colorectal cancer rates. However, these studies were limited because they were based on old data or examined only incidence or mortality data. In this article, the colorectal cancer burden and patterns worldwide are described using the most recently updated cancer incidence and mortality data available from the International Agency for Research on Cancer (IARC). The authors provide 5-year (1998-2002), age-standardized colorectal cancer incidence rates for select cancer registries in IARC's Cancer Incidence in Five Continents, and trends in age-standardized death rates by single calendar year for select countries in the World Health Organization mortality database. In addition, available information regarding worldwide colorectal cancer screening initiatives are presented. The highest colorectal cancer incidence rates in 1998-2002 were observed in registries from North America, Oceania, and Europe, including Eastern European countries. These high rates are most likely the result of increases in risk factors associated with "Westernization," such as obesity and physical inactivity. In contrast, the lowest colorectal cancer incidence rates were observed from registries in Asia, Africa, and South America. Colorectal cancer mortality rates have declined in many longstanding as well as newly economically developed countries; however, they continue to increase in some low-resource countries of South America and Eastern Europe. Various screening options for colorectal cancer are available and further international consideration of targeted screening programs and/or recommendations could help alleviate the burden of colorectal cancer worldwide. PMID:19897840

  4. Malignant teratoma (image)

    MedlinePlus

    A malignant teratoma is a type of cancer consisting of cysts that contain one or more of the three primary embryonic germ layers: ectoderm, mesoderm, and endoderm. Because malignant teratomas have usually spread by the time of diagnosis, ...

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

    PubMed

    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

  6. 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

  7. 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). PMID:26830034

  8. [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. PMID:24160954

  9. [Epigenetics and colorectal cancer].

    PubMed

    Menéndez, Pablo; Villarejo, Pedro; Padilla, David; Menéndez, José María; Rodríguez Montes, José Antonio

    2012-05-01

    The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease. PMID:22425513

  10. Techniques for colorectal anastomosis

    PubMed Central

    Ho, Yik-Hong; Ashour, Mohamed Ahmed Tawfik

    2010-01-01

    Colorectal anastomotic leak remains one of the most feared post-operative complications, particularly after anterior resection of the rectum with, the shift from abdomino-peritoneal resections to total mesorectal excision and primary anastomosis. The literature fails to demonstrate superiority of stapled over hand-sewn techniques in colorectal anastomosis, regardless of the level of anastomosis, although a high stricture rate was noted in the former technique. Thus, improvements in safety aspects of anastomosis and alternatives to hand-sewn and stapled techniques are being sought. Here, we review alternative anastomotic techniques used to fashion bowel anastomosis. Compression anastomosis using compression anastomotic clips, endoluminal compression anastomotic rings, AKA-2, biofragmental anastomotic rings, or Magnamosis all involve the concept of creating a sutureless end-to-end anastomosis by compressing two bowel ends together, leading to a simultaneous necrosis and healing process that joins the two lumens. Staple line reinforcement is a new approach that reduce the drawbacks of staplers used in colorectal practice, i.e. leakage, bleeding, misfiring, and inadequate tissue approximation. Various non-absorbable, semi or fully absorbable materials are now available. Two other techniques can provide alternative anastomotic support to the suture line: a colorectal drain and a polyester stent, which can be utilized in ultra-low rectal excision and can negate the formation of a defunctioning stoma. Doxycycline coated sutures have been used to overcome the post-operative weakness in anastomosis secondary to rapid matrix degradation mediated by matrix metalloproteinase. Another novel technique, the electric welding system, showed promising results in construction of a safe, neat, smooth sutureless bowel anastomosis. Various anastomotic techniques have been shown to be comparable to the standard techniques of suturing and stapling. However, most of these alternatives need

  11. Pediatric Salivary Gland Malignancies.

    PubMed

    Ord, Robert A; Carlson, Eric R

    2016-02-01

    Pediatric malignant salivary gland tumors are extremely rare. The percentage of malignant tumors is higher than that seen in adults, although the outcomes in terms of survival are better in pediatric patients. The mainstay of treatment is surgical excision with negative margins. This article reviews current concepts in demographics, etiology, management, and outcomes of malignant salivary tumors in children. PMID:26614703

  12. 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

  13. Relationship between duodenal bile acids and colorectal neoplasia.

    PubMed Central

    Moorehead, R J; Campbell, G R; Donaldson, J D; McKelvey, S T

    1987-01-01

    To investigate a possible relationship between bile acids and colorectal neoplasia duodenal bile acids were analysed in 50 patients with colorectal adenomas and 14 with carcinoma. Using gas liquid and high performance liquid chromatography a small, but significant increase in the proportion of chenodeoxycholic acid was found in the bile of adenoma patients compared with controls (mean % +/- SD 31.0 +/- 10.8, 26.4 +/- 8.3, p = 0.01). The difference in the proportions of chenodeoxycholic acid correlated with increasing malignant potential of the adenomas as determined by increasing size, histological type, degree of dysplasia and number present. In carcinoma patients an increase in the proportion of chenodeoxycholic acid was also observed compared with controls (mean % +/- SD, 47.2 +/- 9.6, 28.0 +/- 4.5, p less than 0.01). The proportions of other bile acids in those with adenoma or carcinoma were normal. PMID:3428671

  14. Laparoscopic Colorectal Surgery: An Update (with Special Reference to Indian Scenario).

    PubMed

    Moirangthem, G S

    2014-04-01

    Laparoscopic cholecystectomy, being already declared as gold standard technique, laparoscopic surgery has advanced far and wide, touching almost every corner of the abdomen. This advancement has gradually expanded to colorectal surgery which is done for malignant diseases as well. However, laparoscopic colorectal surgery has not been accepted as quickly as was laparoscopic cholecystectomy. This is because of its steep learning curve, concerns with oncological outcomes, lack of randomized control trials (RCTs) and initial reports on high port site recurrences which occurred after curative resections. But all these initial concerns have been overcome by doing a series of RCTs globally, in the past decade, that revealed that laparoscopic colorectal surgery for malignant disease offered short term benefits without compromising on oncological principles of radicality of resection, tumour resection margins and completeness of lymph node harvesting as compared to those of open surgery. Favourable post-operative results with respect to less blood loss, less pain, lesser surgical site infections, lesser requirement of analgesics, early return of bowel function and shorter hospital stay in patients who underwent laparoscopic colorectal resections were obtained in studies done on individual series, including those done in India and more recently, in large trials. An update on recent studies done on laparoscopic colorectal surgery by reviewing many RCTs and individual series, including our experiences, was made, to support the advantages of this procedure which were obtained when it was carried out by skilled hands. PMID:24959478

  15. Malrotation of the Intestine in Adult and Colorectal Cancer.

    PubMed

    Ray, Dipankar; Morimoto, Mitsuaki

    2015-12-01

    Malrotation of the gut is a congenital anomaly and usually presents in childhood. Rarely, it may present in adults. Patients may be asymptomatic, and malrotation is detected during investigations, operation or autopsy. It can cause longstanding abdominal symptoms like pain, dyspepsia or acute abdomen due to volvulus. In adults, malrotation is found with different gastrointestinal malignancies like gastric, hepatobiliary, pancreatic and, in particular, colorectal neoplasms. We are reporting a case of 60-year-old female presented with carcinoma caecum along with malrotation of the gut. It is the first case report from India. We also reviewed documented cases of malrotation associated with colorectal malignancies. A large number of cases have been reported in Japan as compared to rest of the world. Malrotation in adults is probably associated with gastrointestinal malignancies. Possible causes of this association can be genetic factors or gut changes like chronic inflammation. These associations need further study to consider intestinal malrotation as premalignant lesion which may be very important in follow-up of children with malrotation. PMID:26884662

  16. [Prevalence and trend of gastrointestinal malignant tumors in the elderly over 75 years old in China].

    PubMed

    Zheng, Ying; Wu, Chunxiao

    2016-05-25

    Gastrointestinal malignant tumors are the most common malignant neoplasms among the elderly people over 75 years old in China. There are 122.1 thousand new gastric cases and 78.2 thousand new colorectal cancer cases diagnosed each year in China, which accounts for 42.73% and 18.08% respectively of the cases with same age in the world. The gastric cancer accounts for 25.13% and colorectal cancer accounts for 28.86%of all the malignancies in the elderly. The gastric cancer death accounts for 36.38% and colorectal cancer death accounts for 44.68% in those people over 75 years old in China. It was estimated that the risk of developing gastrointestinal malignant tumors of these elderly people was about 5-6 times and the risk of death of gastrointestinal malignant tumors was about 7-8 times of the general population. Compared with the general population and the people of 55-74 years old, the incidence of gastric cancer in the elderly decreased more slowly and the incidence of colorectal cancer increased more quickly over the past 40 years, which brought significant double burden. The survival rate of gastrointestinal malignant tumors in these elderly was lower than that of the general population. We summarized the incidence, mortality, survival and trend of gastrointestinal malignant tumors in the Chinese elderly, in order to provide data for predicting the age distribution and disease burden in the future, to improve the awareness for cancer prevention and control among these elderly, and to call attention to epidemiology, preclinical and clinical medicine for the elderly, especially in the field of study on the influence between comorbidity and cancer treatment, with the aim of improving survival and quality of life among the elderly. PMID:27215509

  17. Segmental neurofibromatosis and malignancy.

    PubMed

    Dang, Julie D; Cohen, Philip R

    2010-01-01

    Segmental neurofibromatosis is an uncommon variant of neurofibromatosis type I characterized by neurofibromas and/or café-au-lait macules localized to one sector of the body. Although patients with neurofibromatosis type I have an associated increased risk of certain malignancies, malignancy has only occasionally been reported in patients with segmental neurofibromatosis. The published reports of patients with segmental neurofibromatosis who developed malignancy were reviewed and the characteristics of these patients and their cancers were summarized. Ten individuals (6 women and 4 men) with segmental neurofibromatosis and malignancy have been reported. The malignancies include malignant peripheral nerve sheath tumor (3), malignant melanoma (2), breast cancer (1), colon cancer (1), gastric cancer (1), lung cancer (1), and Hodgkin lymphoma (1). The most common malignancies in patients with segmental neurofibromatosis are derived from neural crest cells: malignant peripheral nerve sheath tumor and malignant melanoma. The incidence of malignancy in patients with segmental neurofibromatosis may approach that of patients with neurofibromatosis type I. PMID:21137621

  18. Recent Developments in Colorectal Imaging

    PubMed Central

    Pickhardt, Perry J.

    2014-01-01

    Purpose of review The aim of this review is to provide an update on important recent advances in radiologic colorectal imaging, with emphasis on detection, staging, and surveillance of colorectal neoplasia. Recent findings Colorectal imaging advances with magnetic resonance (MR), CT colonography (CTC), and positron emission tomography (PET) over the past year or so have been substantial. Progress in MR imaging for rectal cancer was most notable in terms of assessment of response to neoadjuvant therapy. Continued maturation and clinical validation of CTC was observed for the evaluation of advanced neoplasia, among other areas. Multimodality approaches to colorectal imaging that incorporate functional PET data have also made impressive strides forward. Summary Recent advances in cross-sectional and functional radiologic imaging of the colorectum will positively impact the clinical capabilities for noninvasive evaluation of colorectal neoplasia PMID:25394232

  19. Functional TLR5 genetic variants affect human colorectal cancer survival.

    PubMed

    Klimosch, Sascha N; Försti, Asta; Eckert, Jana; Knezevic, Jelena; Bevier, Melanie; von Schönfels, Witigo; Heits, Nils; Walter, Jessica; Hinz, Sebastian; Lascorz, Jesus; Hampe, Jochen; Hartl, Dominik; Frick, Julia-Stefanie; Hemminki, Kari; Schafmayer, Clemens; Weber, Alexander N R

    2013-12-15

    Toll-like receptors (TLR) are overexpressed on many types of cancer cells, including colorectal cancer cells, but little is known about the functional relevance of these immune regulatory molecules in malignant settings. Here, we report frequent single-nucleotide polymorphisms (SNP) in the flagellin receptor TLR5 and the TLR downstream effector molecules MyD88 and TIRAP that are associated with altered survival in a large cohort of Caucasian patients with colorectal cancer (n = 613). MYD88 rs4988453, a SNP that maps to a promoter region shared with the acetyl coenzyme-A acyl-transferase-1 (ACAA1), was associated with decreased survival of patients with colorectal cancer and altered transcriptional activity of the proximal genes. In the TLR5 gene, rs5744174/F616L was associated with increased survival, whereas rs2072493/N592S was associated with decreased survival. Both rs2072493/N592S and rs5744174/F616L modulated TLR5 signaling in response to flagellin or to different commensal and pathogenic intestinal bacteria. Notably, we observed a reduction in flagellin-induced p38 phosphorylation, CD62L shedding, and elevated expression of interleukin (IL)-6 and IL-1β mRNA in human primary immune cells from TLR5 616LL homozygote carriers, as compared with 616FF carriers. This finding suggested that the well-documented effect of cytokines like IL-6 on colorectal cancer progression might be mediated by TLR5 genotype-dependent flagellin sensing. Our results establish an important link between TLR signaling and human colorectal cancer with relevance for biomarker and therapy development. PMID:24154872

  20. A Comprehensive Study of Extramural Venous Invasion in Colorectal Cancer

    PubMed Central

    McClelland, David; Murray, Graeme I

    2015-01-01

    Colorectal cancer is a common malignancy and a leading cause of cancer related death. Cancer staging following resection is key to determining any adjuvant therapy in those patients with high risk disease. In colorectal cancer, tumour stage and lymph node stage are the main pathological factors which have been considered to influence outcome. Increasing emphasis is now being placed on other factors, especially the presence of extramural venous invasion (EMVI). It is important to understand the relationship of EMVI with other pathological factors and to confirm that in an individual centre that EMVI is being detected at an appropriate rate and is of prognostic significance. This comprehensive study assesses the reporting and prognostic significance of EMVI in a single centre, using prospectively collected data from histopathology reports of a cohort of 2405 patients who underwent surgery for colorectal cancer over a nine year period. Overall, EMVI was reported in 27.9% of colorectal cancer excision specimens. In tumours (n = 1928) that had not received neoadjuvant therapy, the presence of EMVI varied significantly depending on tumour site (χ2 = 12.03, p<0.005), tumour stage (χ2 = 268.188, p<0.001), lymph node stage (χ2 = 294.368, p<0.001) and Dukes’ stage (χ2 = 253.753, p<0.001). Multivariate analysis confirmed EMVI as a significant independent prognostic indicator (p<0.001). In conclusion, the presence of EMVI as an independent prognostic indicator is shown and is related to other pathological and prognostic factors. This study emphasises the requirement for the accurate identification of EMVI in colorectal cancer excision specimens and also understanding the relationship of EMVI with other prognostic factors. PMID:26671331

  1. Comparison of robotic and laparoscopic colorectal resections with respect to 30-day perioperative morbidity

    PubMed Central

    Feinberg, Adina E.; Elnahas, Ahmad; Bashir, Shaheena; Cleghorn, Michelle C.; Quereshy, Fayez A.

    2016-01-01

    Background Robotic surgery has emerged as a minimally invasive alternative to traditional laparoscopy. Robotic surgery addresses many of the technical and ergonomic limitations of laparoscopic surgery, but the literature regarding clinical outcomes in colorectal surgery is limited. We sought to compare robotic and laparoscopic colorectal resections with respect to 30-day perioperative outcomes. Methods The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all patients who underwent robotic or laparoscopic colorectal surgery in 2013. We performed a logistic regression analysis to compare intraoperative variables and 30-day outcomes. Results There were 8392 patients who underwent laparoscopic colorectal surgery and 472 patients who underwent robotic colorectal surgery. The robotic cohort had a lower incidence of unplanned intraoperative conversion (9.5% v. 13.7%, p = 0.008). There were no significant differences between robotic and laparoscopic surgery with respect to other intraoperative and postoperative outcomes, such as operative duration, length of stay, postoperative ileus, anastomotic leak, venous thromboembolism, wound infection, cardiac complications and pulmonary complications. On multivariable analysis, robotic surgery was protective for unplanned conversion, while male sex, malignancy, Crohn disease and diverticular disease were all associated with open conversion. Conclusion Robotic colorectal surgery has comparable 30-day perioperative morbidity to laparoscopic surgery and may decrease the rate of intraoperative conversion in select patients. PMID:27240135

  2. High Prevalence of Human Papillomavirus in Colorectal Cancer in Hispanics: A Case-Control Study

    PubMed Central

    Bernabe-Dones, Raul D.; Gonzalez-Pons, Maria; Villar-Prados, Alejandro; Lacourt-Ventura, Mercedes; Rodríguez-Arroyo, Heriberto; Fonseca-Williams, Sharon; Velazquez, Francisco E.; Diaz-Algorri, Yaritza; Lopez-Diaz, Sofia M.; Rodríguez, Nayra; Yamamura, Yasuhiro; Cruz-Correa, Marcia

    2016-01-01

    The role of Human Papillomavirus (HPV) in colorectal carcinogenesis remains elusive. Based on the high incidence of HPV-associated malignancies among Puerto Rican Hispanics, this study aimed to assess the prevalence of HPV infection and viral integration in colorectal tissues in order to evaluate its putative role in colorectal cancer (CRC). In this case-control study, the prevalence of HPV infection in CRC (cases n = 45) and normal colon mucosa from cancer-free subjects (controls n = 36) was assessed by a nested PCR strategy. HPV-16 genotyping was performed in HPV-positive tissues and the physical status of the HPV-16 genome was determined by E2 detection. HPV was detected in 19 of 45 (42.2%) CRC cases (mean age 61.1 ± 10.7 years, 24 males) and in 1 of 36 (2.8%) controls (mean age 60.9 ± 9.6 years, 24 males) with an OR = 25.58 (95% CI 3.21 to 203.49). HPV-16 was detected in 63.2% of the HPV-positive colorectal tumors; genome integration was observed in all HPV-16 positive cases. This is the first report showing the high prevalence of HPV infections in Caribbean Hispanic colorectal tumors. Despite evidence of HPV integration into the host genome, further mechanistic analysis examining HPV oncoprotein expression and the putative role of these oncoproteins in colorectal carcinogenesis is warranted. PMID:26904111

  3. 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

  4. High Prevalence of Human Papillomavirus in Colorectal Cancer in Hispanics: A Case-Control Study.

    PubMed

    Bernabe-Dones, Raul D; Gonzalez-Pons, Maria; Villar-Prados, Alejandro; Lacourt-Ventura, Mercedes; Rodríguez-Arroyo, Heriberto; Fonseca-Williams, Sharon; Velazquez, Francisco E; Diaz-Algorri, Yaritza; Lopez-Diaz, Sofia M; Rodríguez, Nayra; Yamamura, Yasuhiro; Cruz-Correa, Marcia

    2016-01-01

    The role of Human Papillomavirus (HPV) in colorectal carcinogenesis remains elusive. Based on the high incidence of HPV-associated malignancies among Puerto Rican Hispanics, this study aimed to assess the prevalence of HPV infection and viral integration in colorectal tissues in order to evaluate its putative role in colorectal cancer (CRC). In this case-control study, the prevalence of HPV infection in CRC (cases n = 45) and normal colon mucosa from cancer-free subjects (controls n = 36) was assessed by a nested PCR strategy. HPV-16 genotyping was performed in HPV-positive tissues and the physical status of the HPV-16 genome was determined by E2 detection. HPV was detected in 19 of 45 (42.2%) CRC cases (mean age 61.1 ± 10.7 years, 24 males) and in 1 of 36 (2.8%) controls (mean age 60.9 ± 9.6 years, 24 males) with an OR = 25.58 (95% CI 3.21 to 203.49). HPV-16 was detected in 63.2% of the HPV-positive colorectal tumors; genome integration was observed in all HPV-16 positive cases. This is the first report showing the high prevalence of HPV infections in Caribbean Hispanic colorectal tumors. Despite evidence of HPV integration into the host genome, further mechanistic analysis examining HPV oncoprotein expression and the putative role of these oncoproteins in colorectal carcinogenesis is warranted. PMID:26904111

  5. CD133: A cancer stem cells marker, is used in colorectal cancers

    PubMed Central

    Ren, Fei; Sheng, Wei-Qi; Du, Xiang

    2013-01-01

    Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and self-renewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD133, have been of great interest. CD133, a five-transmembrane glycoprotein, is widely used as a marker to identify and isolate colorectal cancer stem cells. This marker has been investigated to better understand the characteristics and functions of cancer stem cells. Moreover, it can also be used to predict tumor progression, patient survival, chemoradiotherapy resistance and other clinical parameters. In this review, we discuss the use of CD133 in the identification of colorectal cancer stem cell, which is currently controversial. Although the function of CD133 is as yet unclear, we have discussed several possible functions and associated mechanisms that may partially explain the role of CD133 in colorectal cancers. In addition, we focus on the prognostic value of CD133 in colorectal cancers. Finally, we predict that CD133 may be used as a possible target for colorectal cancer treatment. PMID:23674867

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

    PubMed Central

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

    2015-01-01

    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. PMID:25805923

  7. Transarterial approaches to primary and secondary hepatic malignancies.

    PubMed

    Habib, Ali; Desai, Kush; Hickey, Ryan; Thornburg, Bartley; Lewandowski, Robert; Salem, Riad

    2015-08-01

    Transarterial therapies in the setting of primary and secondary liver malignancies are becoming an essential part of the oncology landscape. Most patients with hepatic malignancies are not candidates for curative surgical intervention, thereby warranting exploration of alternative means of treatment that preserves quality of life while providing clinical benefit. Herein, the data for intra-arterial chemoinfusion, transarterial chemoembolization, drug-eluting beads, and radioembolization are discussed in the setting of malignancies within the liver; outcome data relating to survival, time-to-progression, time-to-recurrence, and adverse events are presented. Further data regarding different treatment paradigms for hepatocellular carcinoma, metastatic colorectal carcinoma, neuroendocrine tumours, and intrahepatic cholangiocarcinoma are also provided. In light of these and forthcoming data, transarterial therapies seem to offer a viable treatment pathway for select populations of patients. PMID:25985939

  8. 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

  9. Familial colorectal cancer.

    PubMed

    Lung, M S; Trainer, A H; Campbell, I; Lipton, L

    2015-05-01

    Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up. PMID:25955461

  10. Expression profile of mucin-associated sialyl-Tn antigen in Chinese patients with different colorectal lesions (adenomas, carcinomas)

    PubMed Central

    Xu, Feng; Fan, Cuizhen; Fan, Shanshan; Liu, Fuquan; Wen, Tao; An, Guangyu; Feng, Guosheng

    2015-01-01

    Background: The sialyl-Tn (sTn) antigen is a mucin-associated carbohydrate antigen expressed by numerous human carcinomas, and is also claimed to be a prognostic factor in colorectal cancer. But the associations between sTn and colorectal cancer remain elusive and controversial. Here, we investigated the expression profile of sTn antigen in a series of human colorectal tissue samples including normal colon, colorectal adenomas, and colorectal carcinomas (CRCs), with an aim to analyzing whether sTn plays a role in the progression and development of Chinese patients with CRCs. Methods: Immunohistochemical staining of sTn antigen was performed in formalin-fixed, paraffin-embedded colonic sections from 4 healthy controls, 44 patients with colorectal adenomas, and 186 patients with primary CRCs. Results: No sTn antigen was detected in normal colonic tissues. There were 41 of 44 patients with colorectal adenomas (93.2%), and 141 of 186 patients with CRCs (75.8%) found to express sTn antigen. The patterns of sTn localization were different in adenomas and carcinomas of colonic tissues. Colorectal adenomas showed predominant supranuclear distribution of sTn antigen, while carcinomas revealed apical membrane, mucin droplet and diffuse cytoplasmic localization. Notably, sTn was significantly associated with the degree of differentiation (P = 0.006) and perineural invasion (P = 0.041) of the tumors, but was independent of age, gender, tumor location, depth of penetration, status of lymph nodes, lymphovascular invasion and TNM stage. Conclusions: These results indicate that sTn may play a role in initiating colorectal carcinogenesis and promoting tumor progression. Determination of sTn expression and localization may assist in evaluating malignant status of colorectal lesions. PMID:26617889

  11. 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. PMID:25712400

  12. Academic Colorectal Surgery Job Search

    PubMed Central

    Kalady, Matthew F.

    2014-01-01

    The field of academic colorectal surgery encompasses a vast array of possibilities. Clinical care accompanied by research, teaching, innovation, and/or administration provides the foundation for what is considered an academic career. For those choosing academic colorectal surgery, the process of finding and selecting a first job can provoke much angst. This article describes some strategies to approach the academic colorectal job search and provides insight into deciding a career focus, exploring relevant positions, weighing specific factors, and negotiating your first offer. PMID:25067918

  13. Academic colorectal surgery job search.

    PubMed

    Kalady, Matthew F

    2014-06-01

    The field of academic colorectal surgery encompasses a vast array of possibilities. Clinical care accompanied by research, teaching, innovation, and/or administration provides the foundation for what is considered an academic career. For those choosing academic colorectal surgery, the process of finding and selecting a first job can provoke much angst. This article describes some strategies to approach the academic colorectal job search and provides insight into deciding a career focus, exploring relevant positions, weighing specific factors, and negotiating your first offer. PMID:25067918

  14. Role of laparoscopy in hepatobiliary malignancies.

    PubMed

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

    2016-04-01

    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 T[2] 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

  15. 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

  16. Minimal invasive treatments for liver malignancies.

    PubMed

    Orsi, Franco; Varano, Gianluca

    2015-11-01

    Minimal invasive therapies have proved useful in the management of primary and secondary hepatic malignancies. The most relevant aspects of all these therapies are their minimal toxicity profiles and highly effective tumor responses without affecting the normal hepatic parenchyma. These unique characteristics coupled with their minimally invasive nature provide an attractive therapeutic option for patients who previously may have had few alternatives. Combination of these therapies might extend indications to bring curative treatment to a wider selected population. The results of various ongoing combination trials of intraarterial therapies with targeted therapies are awaited to further improve survival in this patient group. This review focuses on the application of ablative and intra-arterial therapies in the management of hepatocellular carcinoma and hepatic colorectal metastasis. PMID:26050603

  17. 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. PMID:25665006

  18. 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 ...

  19. Malignancy after renal transplantation.

    PubMed

    Zeier, Martin; Hartschuh, Wolfgang; Wiesel, Manfred; Lehnert, Thomas; Ritz, Eberhard

    2002-01-01

    Malignancy following renal transplantation is an important medical problem during the long-term follow-up. The overall incidence of malignancy at this time is 3 to 5 times higher than in the general population. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). The type of malignancy is different in various countries and dependent on genetic and environmental factors. Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse are additional risk factors. Malignancy may even be transplanted by the graft. Previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and postmalignancy screening. Finally, every dialysis patient on the waiting list should undergo a regular screening program before and after renal transplantation to detect a potentially malignant tumor in an early stage. In addition to specific oncological treatment, managing a malignancy after renal transplantation should include modification of immunosuppression. PMID:11774131

  20. 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

  1. [Colorectal carcinoma as a cause of acute abdominal illness].

    PubMed

    Lipská, L; Visokai, V; Bergmann, P; Trubac, M; Cech, P; Strupová, L; Levý, M

    2008-01-01

    Colorectal carcinoma (KCR) is the commonest malignancy in male patients and the second commonest in female patients in the Czech Republic. During 1990-2006, 1162 patients with colorectal carcinomas were operated in the FTNsP (Faculty Thomayer Hospital) Surgical Clinic. 212 patients aged between 39 to 94 y.o.a.(the median of 70 y.o.a) were managed urgently for acute abdominal illness. In this group of urgently managed patients, the mortality rate was 17% and the morbidity rate was 38%. Future prospects of any colorectal carcinoma patient with acute abdominal illness depend on the procedure's radicality, which is limited by the overall patient's condition. The preoperative care aims to improve the patient's overall condition to such a degree, to allow for surgery fulfilling principles of oncosurgical radicality. According to this report's data, such urgent surgical procedures do not result in increased mortality or morbidity rates, compared to these in planned procedures, and show the best results in this patient group. PMID:18432070

  2. Colorectal Cancer Screening in an Equal Access Healthcare System

    PubMed Central

    DeBarros, Mia; Steele, Scott R.

    2013-01-01

    Introduction: The military health system (MHS) a unique setting to analyze implementation programs as well as outcomes for colorectal cancer (CRC). Here we look at the efficacy of different CRC screening methods, attributes and results within the MHS, and current barriers to increase compliance. Materials and Methods: A literature search was conducted utilizing PubMed and the Cochrane library. Key-word combinations included colorectal cancer screening, racial disparity, risk factors, colorectal cancer, screening modalities, and randomized control trials. Directed searches were also performed of embedded references. Results: Despite screening guidelines from several national organizations, extensive barriers to widespread screening remain, especially for minority populations. These barriers are diverse, ranging from education and access problems to personal beliefs. Screening rates in MHS have been reported to be generally higher at 71% compared to national averages of 50-65%. Conclusion: CRC screening can be highly effective at improving detection of both pre-malignant and early cancers. Improved patient education and directed efforts are needed to improve CRC screening both nationally and within the MHS. PMID:23459768

  3. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    PubMed

    Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain B; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess H; Tai, Joyce A; Tan, Joanna H; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte A E; van Dam, Rob M; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y; Hillmer, Axel M; Tan, Min-Han

    2016-06-29

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease. PMID:27358499

  4. Nrf2 as a Chemopreventive Target in Colorectal Cancer

    PubMed Central

    Saw, Constance Lay Lay; Kong, Tony Ah-Ng

    2012-01-01

    Introduction Numerous epidemiological studies have linked consumption of cruciferous vegetables to a reduced risk of colorectal cancer (CRC) in individuals. It is currently well accepted that chronic inflammation is a contributing factor in 15-20% malignancies including CRC. Many chemopreventive compounds are effective in preclinical systems and many on-going clinical trials are showing promising findings. Many of these compounds could activate the antioxidant responsive element (ARE), a critical regulatory element for phase II protective/detoxification and anti-oxidative stress enzymes mediated by nuclear factor-erythroid 2-related factor 2 (Nrf2). Recently, Nrf2 has emerged as a novel target for the prevention of CRC. Areas covered A full literature search was performed using PubMed with the key words ‘ARE, Nrf2, colon, colorectal cancer, chemoprevention, cancer prevention’, and all relevant publications are included. Expert opinion The use of Nrf2 knockout mice has provided key insights into the toxicological and chemopreventive importance of this pathway. Mounting evidence has revealed that Nrf2 is a critical regulator of inflammation as well, a major driving force for CRC progression and formation. Targeting the Nrf2/ARE pathway may present a novel therapeutic approach for the treatment of not only colorectal inflammatory diseases but the frequent subsequent development of CRC as well. PMID:21261563

  5. Primary malignant melanoma

    PubMed Central

    Mısır, A. Ferhat; Durmuşlar, Mustafa C.; Zerener, Tamer; Gün, Banu D.

    2016-01-01

    Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period. PMID:27052289

  6. The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors.

    PubMed

    Smith, Myles J; Smith, Henry G; Mahar, Alyson L; Law, Calvin; Ko, Yoo-Joung

    2016-10-15

    A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox-proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5-year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05-2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies. PMID:27299364

  7. Molecular genetics of colorectal cancer.

    PubMed

    Bogaert, Julie; Prenen, Hans

    2014-01-01

    Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer. PMID:24714764

  8. Xenovaccinotherapy for colorectal cancer.

    PubMed

    Seledtsov, Victor I; Niza, Natalya A; Felde, Mariya A; Shishkov, Alexey A; Samarin, Denis M; Seledtsova, Galina V; Seledtsov, Dmitriy V

    2007-01-01

    The objectives of this phase I-II trial were to assess the toxicity, immunological and clinical responses induced in 37 patients with stage IV colorectal cancer by the subcutaneous administration of a xenogenic polyantigenic vaccine (XPV) prepared from disrupted murine melanoma (B16) and carcinoma (LLC) cells. An inducing course of vaccinotherapy consisted of 10 immunizations (5 at weekly and 5 at fortnight intervals). Twenty-four hours later each of first 5 vaccinations the patient was subcutaneously given a low dose of the recombinant interleukin-2 (IL-2). A consolidating course of vaccinotherapy consisted of monthly vaccinations. No grade III or IV toxicities, but also laboratory and clinical signs of developing systemic autoimmune disorders were noted in any XPV-treated patient. A significant increase in cell-mediated immunoreactivity to both LLC and B16 antigens (Ags) occurred in the patients after inducing vaccinations, as determined by delayed-type hypersensitivity (DTH) skin reactions, as well as by blood lymphocyte proliferation responses. Vaccinations also led to increased cell-mediated reactivity to murine non-tumor, spleen cell (SC)-associated Ags. This reactivity, however, was not as significant as that to tumor-associated antigens (TAAs). XPV was also found to capable of generating IgG antibody-mediated responses. With immunotherapy concentrations of both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) detectably elevated in patients' sera, suggesting intensification of T helper 1-/T helper 2-mediated responses in the XPV-treated patients. The average survival of the XPV-treated patients was noticeably superior than was that of the clinically comparable control patients (17 vs 7 months). Collectively the results suggest that xenogenic TAAs are safe to use, able to induce measurable cellular and humoral immune responses, and may be clinically effective in certain colorectal cancer patients. PMID:17258887

  9. Drugs Approved for Malignant Mesothelioma

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Malignant Mesothelioma This page lists cancer ... in malignant mesothelioma that are not listed here. Drugs Approved for Malignant Mesothelioma Alimta (Pemetrexed Disodium) Pemetrexed ...

  10. Advances in endoscopic ultrasound imaging of colorectal diseases

    PubMed Central

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-01-01

    malignant subepithelial tumours. Recent reports suggest that EUS elastography enables highly accurate discrimination of colorectal adenocarcinomas from adenomas, while inflammatory bowel disease phenotypes can be distinguished based on the strain ratio calculation. Among EUS-guided therapies, the drainage of abdominal and pelvic collections has been regarded as a safe and effective procedure to be used as an alternative for the transcutaneous route, while the placing of fiducial markers under EUS guidance for targeted radiotherapy in rectal cancer or the use of contrast microbubbles as drug-delivery vehicles represent experimental therapeutic applications that could greatly impact the forthcoming management of patients with colorectal diseases, pending on further investigations. PMID:26855535

  11. Advances in endoscopic ultrasound imaging of colorectal diseases.

    PubMed

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-02-01

    malignant subepithelial tumours. Recent reports suggest that EUS elastography enables highly accurate discrimination of colorectal adenocarcinomas from adenomas, while inflammatory bowel disease phenotypes can be distinguished based on the strain ratio calculation. Among EUS-guided therapies, the drainage of abdominal and pelvic collections has been regarded as a safe and effective procedure to be used as an alternative for the transcutaneous route, while the placing of fiducial markers under EUS guidance for targeted radiotherapy in rectal cancer or the use of contrast microbubbles as drug-delivery vehicles represent experimental therapeutic applications that could greatly impact the forthcoming management of patients with colorectal diseases, pending on further investigations. PMID:26855535

  12. 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

  13. SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer.

    PubMed

    Mansour, Mohammed A; Hyodo, Toshinori; Akter, Khondker Ayesha; Kokuryo, Toshio; Uehara, Keisuke; Nagino, Masato; Senga, Takeshi

    2016-01-26

    Special AT-rich sequence-binding protein 1 and 2 (SATB1/2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB2 acts as a tumor suppressor in laryngeal squamous cell carcinoma and colon cancer, whereas SATB1 promotes the progression of numerous types of cancers. In this study, we examined the effects of SATB1 and SATB2 on the malignant characteristics of colorectal cancer cells. SATB1 and SATB2 expression were negatively correlated in colorectal cancer specimens. SATB1 expression was increased, whereas SATB2 expression was reduced, in colorectal cancer tissues compared to control tissues. Exogenous expression of SATB2 in colorectal cancer cells suppressed cell proliferation, colony formation and tumor proliferation in mice. c-Myc was reduced by SATB2 expression, and exogenous expression of c-Myc in SATB2-expressing cells restored proliferation, colony formation and in vivo tumor growth of colorectal cancer cells. We also showed that c-Myc reduction by SATB2 was mediated by the inactivation of ERK5. In contrast, SATB1 promoted c-Myc expression. The expression of SATB1 in colorectal cancer tissues was positively correlated with c-Myc expression, and SATB1 knockdown reduced c-Myc expression in colorectal cancer cells. Finally, we showed that SATB1 knockdown in colorectal cancer cells suppressed cell proliferation, colony formation and cell invasion. Our results reveal interesting features of how the structural homologs SATB1 and SATB2 exert opposing functions in colorectal tumorigenesis. PMID:26701851

  14. SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer

    PubMed Central

    Mansour, Mohammed A.; Hyodo, Toshinori; Akter, Khondker Ayesha; Kokuryo, Toshio; Uehara, Keisuke; Nagino, Masato; Senga, Takeshi

    2016-01-01

    Special AT-rich sequence-binding protein 1 and 2 (SATB1/2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB2 acts as a tumor suppressor in laryngeal squamous cell carcinoma and colon cancer, whereas SATB1 promotes the progression of numerous types of cancers. In this study, we examined the effects of SATB1 and SATB2 on the malignant characteristics of colorectal cancer cells. SATB1 and SATB2 expression were negatively correlated in colorectal cancer specimens. SATB1 expression was increased, whereas SATB2 expression was reduced, in colorectal cancer tissues compared to control tissues. Exogenous expression of SATB2 in colorectal cancer cells suppressed cell proliferation, colony formation and tumor proliferation in mice. c-Myc was reduced by SATB2 expression, and exogenous expression of c-Myc in SATB2-expressing cells restored proliferation, colony formation and in vivo tumor growth of colorectal cancer cells. We also showed that c-Myc reduction by SATB2 was mediated by the inactivation of ERK5. In contrast, SATB1 promoted c-Myc expression. The expression of SATB1 in colorectal cancer tissues was positively correlated with c-Myc expression, and SATB1 knockdown reduced c-Myc expression in colorectal cancer cells. Finally, we showed that SATB1 knockdown in colorectal cancer cells suppressed cell proliferation, colony formation and cell invasion. Our results reveal interesting features of how the structural homologs SATB1 and SATB2 exert opposing functions in colorectal tumorigenesis. PMID:26701851

  15. Malignant melanoma maxilla

    PubMed Central

    Devi, Seema; Sinha, Richi; Singh, Rakesh Kumar

    2015-01-01

    A malignant melanoma is a highly lethal melanocytic neoplasm. A neoplasm usually affects the skin. Malignant melanomas in the head and neck region are rare, accounting for less than 1% of all melanomas. Malignant melanoma of the nose and paranasal sinuses is an aggressive disease typically presenting at an advanced stage, with a 5-year survival rate ranging 20-30%. Melanomas are tumors arising from melanocytes, which are neuroectodermally derived cells located in the basal layers of the skin. This is a case report of a 35-year-old male, who presented with very aggressive disease and developed liver metastasis. PMID:26668467

  16. Procaine in Malignant Hyperpyrexia

    PubMed Central

    Moulds, R. F. W.; Denborough, M. A.

    1972-01-01

    The caffeine contracture of normal human muscle, which has been used as a model for malignant hyperpyrexia, is greatly potentiated by halothane. Prior administration of procaine markedly reduces the halothane-potentiated caffeine contracture, and procaine given at the height of the contracture induces relaxation. Lignocaine, on the other hand, produces a variable response and sometimes increases the contracture. The muscle from a patient with an inherited susceptibility to malignant hyperpyrexia contracted spontaneously with halothane alone, and this contracture was reversed by procaine. These experiments support the therapeutic use of procaine in malignant hyperpyrexia. PMID:4642792

  17. Concentrations of cadmium and selected essential elements in malignant large intestine tissue

    PubMed Central

    Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

    2015-01-01

    Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

  18. Laparoscopic Colorectal Training Gap in Colorectal and Surgical Residents

    PubMed Central

    Soliman, Mark; Williamson, Paul; Ferrara, Andrea

    2016-01-01

    Background and Objectives: Laparoscopic colorectal surgery is an established safe procedure with demonstrated benefits. Proficiency in this specialty correlates with the volume of cases. We examined training in this surgical field for both general surgery and colon and rectal surgery residents to determine whether the number of cases needed for proficiency is being realized. Methods: We examined the Accreditation Council for Graduate Medical Education (ACGME) and American Board of Colorectal Surgeons (ABCRS) operative statistics for graduating general surgery and colon and rectal surgery residents. Results: Although the number of advanced laparoscopy cases had increased for general surgery residents, there was still a significant gap in case volume between the average number of laparoscopic colorectal operations performed by graduating general surgery residents (21.6) and those performed by graduating colon and rectal surgery residents (81.9) in 2014. Conclusion: There is a gap between general surgery and colon and rectal surgery residency training for laparoscopic colorectal surgery. General surgery residents are not meeting the volume of cases necessary for proficiency in colorectal surgery. This deficit represents a structural difference in training. PMID:27493468

  19. Laparoscopic resection for colorectal diseases: short-term outcomes of a single center

    PubMed Central

    Attaallah, Wafi; Babayev, Hayyam; Yardımcı, Samet; Cingi, Asım; Uğurlu, Mustafa Ümit; Günal, Ömer

    2016-01-01

    Objective Even though, laparoscopy is not accepted as the current gold standard in colorectal surgery, it can be performed as safely as open surgery. It is also widely accepted that the technique has many advantages. In this study, we evaluated the results of 33 patients with laparoscopic colorectal resection. Material and Methods Thirty-three patients who underwent laparoscopic colon surgery between January 2013 and September 2014 in the General Surgery Clinic at Marmara University Hospital were included in the study. Patients were evaluated in terms of their demographic and tumor histopathologic characteristics, type of surgery and early postoperative complications. Results Laparoscopic colorectal resection was performed for 33 patients who had malignant or benign lesions. The median age was 60 (35–70), and 18 (55%) were male patients. The majority of the patients (90%) were diagnosed with colorectal adenocarcinoma. Half of the patients were T3 and 67% had N0 stage. The median number of retrieved lymph nodes was 17 (4–28). Negative surgical margins were obtained in all patients. The postoperative hospital stay was 5 (4–16) days. Postoperative early complications were observed in only 5 patients. The majority of complications were treated without the need for surgery. No mortality was recorded in this series of patients. Conclusion This study showed that laparoscopic colorectal surgery could be performed safely based on its low complication rate, short length of hospital stay, providing sufficient surgical resection and lymph node dissection. PMID:27528823

  20. 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. PMID:27221111

  1. Epidemiology and molecular genetics of colorectal cancer in iran: a review.

    PubMed

    Malekzadeh, Reza; Bishehsari, Faraz; Mahdavinia, Mahboobeh; Ansari, Reza

    2009-03-01

    Although the incidence of colorectal cancer in Iranian older age subjects is currently very low compared to Western population, the younger generation is experiencing an accelerated rate approaching the Western rates and the burden of disease will increase dramatically in near future. The high frequency of positive family history of colorectal cancer in Iranian patients indicates that a significant number of colorectal cancers in Iran arise in family members and relatives of colorectal cancer patients. It is clear that the familial clustering of colorectal cancer is more often seen in younger probands and cancer located in the right side of the colon. These epidemiologic findings call for a broader attempt to promote public awareness and screening strategies in those families with a member affected by colorectal cancer, especially at younger age or with proximal tumors. Based on our present understanding, the possibility of preventing or curing most colon and rectal cancers is now plausible. The molecular biology of colon cancer has been the subject of many researches and is better understood than those for any other solid cancer and have established an important example for cancer research. It is now clear that colorectal cancer develops as the result of genetic and epigenetic alterations that lead to malignant transformation of normal mucosa. In spite of these scientific progresses and the fact that screening can reduce the rate of death by detecting early cancer or premalignant polyps, the rate of screening is very low globally and negligible in Iran and many other developing countries which is due to cost, resistance by physicians, patients, and the healthcare system. In Iran screening should at least be started in family members at earlier age with colonoscopy as the preferred modality of screening method. PMID:19249887

  2. Aquaporins: Their role in gastrointestinal malignancies.

    PubMed

    Nagaraju, Ganji Purnachandra; Basha, Riyaz; Rajitha, Balney; Alese, Olatunji Boladale; Alam, Afroz; Pattnaik, Subasini; El-Rayes, Bassel

    2016-04-01

    Aquaporins (AQPs) are small (~30 kDa monomers) integral membrane water transport proteins that allow water to flow through cell membranes in reaction to osmotic gradients in cells. In mammals, the family of AQPs has thirteen (AQP0-12) unique members that mediate critical biological functions. Since AQPs can impact cell proliferation, migration and angiogenesis, their role in various human cancers is well established. Recently, AQPs have been explored as potential diagnostic and therapeutic targets in gastrointestinal (GI) cancers. GI cancers encompass multiple sites including the colon, esophagus, stomach and pancreas. Research in the last three decades has revealed biological aspects and signaling pathways critical for the development of GI cancers. Since the majority of these cancers are very aggressive and rapidly metastasizes, identifying effective targets is crucial for treatment. Preclinical studies have utilized inhibitors of specific AQPs and knock down of AQP expression using siRNA. Although several studies have explored the role of AQPs in colorectal, esophageal, gastric, hepatocellular and pancreatic cancers, there is no comprehensive review compiling the available information on GI cancers as has been published for other malignancies such as ovarian cancer. Due to the similarities and association of various sites of GI cancers, it is helpful to consider these results collectively in order to better understand the role of specific AQPs in critical GI cancers. This review summarizes the current knowledge of the role of AQPs in GI malignancies with particular focus on diagnosis and therapeutic applications. PMID:26780474

  3. How to decide on stent insertion or surgery in colorectal obstruction?

    PubMed Central

    Zahid, Assad; Young, Christopher John

    2016-01-01

    Colorectal cancer is one of the most common cancers in western society and malignant obstruction of the colon accounts for 8%-29% of all large bowel obstructions. Conventional treatment of these patients with malignant obstruction requiring urgent surgery is associated with a greater physiological insult on already nutritionally replete patients. Of late the utility of colonic stents has offered an option in the management of these patients in both the palliative and bridge to surgery setting. This has been the subject of many reviews which highlight its efficacy, particulary in reducing ostomy rates, allowing quicker return to oral diet, minimising extended post-operative recovery as well as some quality of life benefits. The uncertainity in managing patients with malignant colonic obstructions has lead to a more cautious use of stenting technology as community equipoise exists. Decision making analysis has demonstrated that surgeons’ favored the use of stents in the palliative setting preferentially when compared to the curative setting where surgery was preferred. We aim to review the literature regarding the use of stent or surgery in colorectal obstruction, and then provide a discourse with regards to the approach in synthesising the data and applying it when deciding the appropriate application of stent or surgery in colorectal obstruction. PMID:26843916

  4. How to decide on stent insertion or surgery in colorectal obstruction?

    PubMed

    Zahid, Assad; Young, Christopher John

    2016-01-27

    Colorectal cancer is one of the most common cancers in western society and malignant obstruction of the colon accounts for 8%-29% of all large bowel obstructions. Conventional treatment of these patients with malignant obstruction requiring urgent surgery is associated with a greater physiological insult on already nutritionally replete patients. Of late the utility of colonic stents has offered an option in the management of these patients in both the palliative and bridge to surgery setting. This has been the subject of many reviews which highlight its efficacy, particulary in reducing ostomy rates, allowing quicker return to oral diet, minimising extended post-operative recovery as well as some quality of life benefits. The uncertainity in managing patients with malignant colonic obstructions has lead to a more cautious use of stenting technology as community equipoise exists. Decision making analysis has demonstrated that surgeons' favored the use of stents in the palliative setting preferentially when compared to the curative setting where surgery was preferred. We aim to review the literature regarding the use of stent or surgery in colorectal obstruction, and then provide a discourse with regards to the approach in synthesising the data and applying it when deciding the appropriate application of stent or surgery in colorectal obstruction. PMID:26843916

  5. Panuveal malignant mesenchymoma.

    PubMed

    Pe'er, J; Neudorfer, M; Ron, N; Anteby, I; Lazar, M; Rosenmann, E

    1995-09-01

    Intraocular malignant mesenchymal tumors are very rare, and only a few case reports of such primary and metastatic tumors have been reported. We report a case of a malignant mesenchymoma involving the entire uveal tract. A 21-year-old woman presented with a tumor on the whole iris of the right eye, which caused intractable glaucoma. Upon enucleation of the eye, a very anaplastic tumor was found to occupy the whole uveal tract; its features were compatible with a tumor of mesenchymal origin, including rhabdomyosarcomatous and liposarcomatous characteristics. Choroidal osteoma was a coincidental finding. The histologic findings of the tumor were of two types of malignant mesenchymal tumors, and therefore the diagnosis of malignant mesenchymoma was made. This is to our knowledge the first tumor of its kind to be reported intraocularly. PMID:7668945

  6. [Rheumatoid arthritis and malignancy].

    PubMed

    Kameda, Tomohiro; Dobashi, Hiroaki

    2016-06-01

    Rheumatoid arthritis (RA) is associated with excess mortality. Especially, malignancy is a major cause of mortality. According to previous reports, the overall incidence of malignancies in RA patients has been reported to be comparable or slightly higher than that in general population. The increased incidence of malignant lymphoma and lung cancer has been reported to be consistent in most studies. The use of some csDMARD was also reported as risk factors for malignancy. Recently, MTX associated lymphoproliferative disorder(MTX-LPD) is one of the important complications in RA treatment. We revealed the mean MTX dose was demonstrated to be an independent risk factor regarding MTX-LPD onset in RA patients. This data suggest that the treatment with higher MTX dose promotes LPD onset in Japanese RA patients. PMID:27311195

  7. Gynecologic malignancy in pregnancy

    PubMed Central

    Ji, Yong Il

    2013-01-01

    Gynecologic malignancy during pregnancy is a stressful problem. For the diagnosis and treatment of malignancy during pregnancy, a multidisciplinary approach is needed. Patients should be advised about the benefits and risk of treatment. When selecting a treatment for malignancy during pregnancy, the physiologic changes that occur with the pregnancy should be considered. Various diagnostic procedures that do not harm the fetus can be used. Laparoscopic surgery or laparotomy may be safely performed. The staging approach and treatment should be standard. Systemic chemotherapy during the first trimester should be delayed if possible. Radiation therapy should preferably start postpartum. Although delivery should be delayed preferably until after 35 weeks of gestation, termination of pregnancy may be considered when immediate treatment is required. Subsequent pregnancies do not increase the risk of malignancy recurrence. PMID:24328018

  8. Chemoembolization of hepatic malignancy.

    PubMed

    Gonsalves, Carin F; Brown, Daniel B

    2009-01-01

    Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization represents an essential component of interventional oncology. This article discusses patient selection, procedure technique, results, and complications associated with transarterial chemoembolization. PMID:18668189

  9. The Malignant Protein Puzzle.

    PubMed

    Walker, Lary C; Jucker, Mathias

    2016-01-01

    When most people hear the words malignant and brain, cancer immediately comes to mind. But our authors argue that proteins can be malignant too, and can spread harmfully through the brain in neurodegenerative diseases that include Alzheimer's, Parkinson's, CTE, and ALS. Studying how proteins such as PrP, amyloid beta, tau, and others aggregate and spread, and kill brain cells, represents a crucial new frontier in neuroscience. PMID:27408676

  10. Disentangling the Association between Statins, Cholesterol, and Colorectal Cancer: A Nested Case-Control Study

    PubMed Central

    Mamtani, Ronac; Lewis, James D.; Scott, Frank I.; Ahmad, Tariq; Goldberg, David S.; Datta, Jashodeep; Yang, Yu-Xiao; Boursi, Ben

    2016-01-01

    cancer was lower in statin users versus nonusers, no difference was observed among those who continued versus discontinued statin therapy, suggesting the potential for indication bias. The association between decreased serum cholesterol and colorectal cancer risk suggests a cholesterol-lowering effect of undiagnosed malignancy. Clinical judgment should be used when considering causes of cholesterol reduction in patients, including those on statin therapy. PMID:27116322

  11. Sorafenib Tosylate in Treating Patients With Malignant Mesothelioma.

    ClinicalTrials.gov

    2013-06-04

    Epithelial Mesothelioma; Recurrent Malignant Mesothelioma; Sarcomatous Mesothelioma; Stage IA Malignant Mesothelioma; Stage IB Malignant Mesothelioma; Stage II Malignant Mesothelioma; Stage III Malignant Mesothelioma; Stage IV Malignant Mesothelioma

  12. Malignant Tourette syndrome.

    PubMed

    Cheung, Min-Yuen Cynthia; Shahed, Joohi; Jankovic, Joseph

    2007-09-15

    The aim of this work was to draw attention to potentially life-threatening symptoms associated with Tourette syndrome (TS) and to explore their relationship to TS comorbidities. Medical records of all patients with TS evaluated at our Movement Disorders Clinic between July 2003 and July 2006 were reviewed. Data on patients with malignant TS, defined as >or=2 emergency room (ER) visits or >or=1 hospitalizations for TS symptoms or its associated behavioral comorbidities, were entered into a dataset and analyzed. Five illustrative cases are described. Of 333 TS patients evaluated during the 3-year period, 17 (5.1%) met the criteria for malignant TS. Hospital admission or ER visits were for tic-related injuries, self-injurious behavior (SIB), uncontrollable violence and temper, and suicidal ideation/attempts. Compared with patients with nonmalignant TS, those with malignant TS were significantly more likely to have a personal history of obsessive compulsive behavior/disorder (OCB/OCD), complex phonic tics, coprolalia, copropraxia, SIB, mood disorder, suicidal ideation, and poor response to medications. Although TS is rarely a disabling disorder, about 5% of patients referred to a specialty clinic have life-threatening symptoms. Malignant TS is associated with greater severity of motor symptoms and the presence of >or=2 behavioral comorbidities. OCD/OCB in particular may play a central role in malignant TS; obsessive compulsive qualities were associated with life-threatening tics, SIB, and suicidal ideation. Malignant TS is more refractory to medical treatment than nonmalignant TS. PMID:17566119

  13. Colorectal Cancer Screening: Tests, Strategies, and Perspectives

    PubMed Central

    Stracci, Fabrizio; Zorzi, Manuel; Grazzini, Grazia

    2014-01-01

    Screening has a central role in colorectal cancer (CRC) control. Different screening tests are effective in reducing CRC-specific mortality. Influence on cancer incidence depends on test sensitivity for pre-malignant lesions, ranging from almost no influence for guaiac-based fecal occult blood testing (gFOBT) to an estimated reduction of 66–90% for colonoscopy. Screening tests detect lesions indirectly in the stool [gFOBT, fecal immunochemical testing (FIT), and fecal DNA] or directly by colonic inspection [flexible sigmoidoscopy, colonoscopy, CT colonography (CTC), and capsule endoscopy]. CRC screening is cost-effective compared to no screening but no screening strategy is clearly better than the others. Stool tests are the most widely used in worldwide screening interventions. FIT will soon replace gFOBT. The use of colonoscopy as a screening test is increasing and this strategy has superseded all alternatives in the US and Germany. Despite its undisputed importance, CRC screening is under-used and participation rarely reaches 70% of target population. Strategies to increase participation include ensuring recommendation by physicians, introducing organized screening and developing new, more acceptable tests. Available evidence for DNA fecal testing, CTC, and capsule endoscopy is reviewed. PMID:25386553

  14. Cytokine-Induced Modulation of Colorectal Cancer.

    PubMed

    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

  15. 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

  16. Irreversible Electroporation for Colorectal Liver Metastases.

    PubMed

    Scheffer, Hester J; Melenhorst, Marleen C A M; Echenique, Ana M; Nielsen, Karin; van Tilborg, Aukje A J M; van den Bos, Willemien; Vroomen, Laurien G P H; van den Tol, Petrousjka M P; Meijerink, Martijn R

    2015-09-01

    Image-guided tumor ablation techniques have significantly broadened the treatment possibilities for primary and secondary hepatic malignancies. A new ablation technique, irreversible electroporation (IRE), was recently added to the treatment armamentarium. As opposed to thermal ablation, cell death with IRE is primarily induced using electrical energy: electrical pulses disrupt the cellular membrane integrity, resulting in cell death while sparing the extracellular matrix of sensitive structures such as the bile ducts, blood vessels, and bowel wall. The preservation of these structures makes IRE attractive for colorectal liver metastases (CRLM) that are unsuitable for resection and thermal ablation owing to their anatomical location. This review discusses different technical and practical issues of IRE for CRLM: the indications, patient preparations, procedural steps, and different "tricks of the trade" used to improve safety and efficacy of IRE. Imaging characteristics and early efficacy results are presented. Much is still unknown about the exact mechanism of cell death and about factors playing a crucial role in the extent of cell death. At this time, IRE for CRLM should only be reserved for small tumors that are truly unsuitable for resection or thermal ablation because of abutment of the portal triad or the venous pedicles. PMID:26365546

  17. New era of colorectal cancer screening

    PubMed Central

    El Zoghbi, Maysaa; Cummings, Linda C

    2016-01-01

    Colorectal cancer (CRC) is the 2nd most common cancer in women and 3rd most common cancer in men worldwide. Most CRCs develop from adenomatous polyps arising from glandular epithelium. Tumor growth is initiated by mutation of the tumor suppressor gene APC and involves other genetic mutations in a stepwise process over years. Both hereditary and environmental factors contribute to the development of CRC. Screening has been proven to reduce the incidence of CRC. Screening has also contributed to the decrease in CRC mortality in the United States. However, CRC incidence and/or mortality remain on the rise in some parts of the world (Eastern Europe, Asia, and South America), likely due to factors including westernized diet, lifestyle, and lack of healthcare infrastructure. Multiple screening options are available, ranging from direct radiologic or endoscopic visualization tests that primarily detect premalignant or malignant lesions such as flexible sigmoidoscopy, optical colonoscopy, colon capsule endoscopy, computed tomographic colonography, and double contrast barium enema - to stool based tests which primarily detect cancers, including fecal DNA, fecal immunochemical test, and fecal occult blood test. The availability of some of these tests is limited to areas with high economic resources. This article will discuss CRC epidemiology, pathogenesis, risk factors, and screening modalities with a particular focus on new technologies. PMID:26981176

  18. 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

  19. Animal Models of Colorectal Cancer

    PubMed Central

    Johnson, Robert L.; Fleet, James C.

    2012-01-01

    Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650

  20. 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

  1. Malignant Potential of Gastrointestinal Cancers Assessed by Structural Equation Modeling

    PubMed Central

    Onodera, Kei; Takahashi, Hiroaki; Okahara, Satoshi; Kodaira, Junichi; Oohashi, Hirokazu; Isshiki, Hiroyuki; Kawakami, Kentaro; Yamashita, Kentaro; Shinomura, Yasuhisa; Hosokawa, Masao

    2016-01-01

    Background Parameters reported in pathologic reviews have been failing to assess exactly the malignant potential of gastrointestinal cancers. We hypothesized that malignant potential could be defined by common latent variables (hypothesis I), but there are substantial differences in the associations between malignant potential and pathologic parameters according to the origin of gastrointestinal cancers (hypothesis II). We shed light on these issues by structural equation modeling. Materials and Methods We conducted a cross-sectional survey of 217 esophageal, 192 gastric, and 175 colorectal cancer patients who consecutively underwent curative surgery for their pathologic stage I cancers at Keiyukai Sapporo Hospital. Latent variables identified by factor analysis and seven conventional pathologic parameters were introduced in the structural equation modeling analysis. Results Because latent variables were disparate except for their number, 'three' in the examined gastrointestinal cancers, the first hypothesis was rejected. Because configural invariance across gastrointestinal cancers was not approved, the second hypothesis was verified. We could trace the three significant paths on the causal graph from latent variables to lymph node metastasis, which were mediated through depth, lymphatic invasion, and matrilysin expression in esophageal cancer, whereas only one significant path could be traced in both gastric and colorectal cancer. Two of the three latent variables were exogenous in esophageal cancer, whereas one factor was exogenous in the other gastrointestinal cancers. Cancer stemness promoted viability in esophageal cancer, but it was suppressed in others. Conclusion These results reflect the malignant potential of esophageal cancer is higher than that of the other gastrointestinal cancers. Such information might contribute to refining clinical treatments for gastrointestinal cancers. PMID:26889682

  2. 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

  3. Simulants of Malignant Melanoma

    PubMed Central

    Piérard-Franchimont, Claudine; Delvenne, Philippe

    2015-01-01

    During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN) of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential) and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential). In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM) variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas), and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present. PMID:26779311

  4. 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

  5. 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

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

    PubMed

    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

    2016-06-01

    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

  7. Histopathologic Prolife of Primary Gastrointestinal Malignancies in Uyo City (Niger-Delta Region of Nigeria)

    PubMed Central

    Abudu, Emmanuel K.; Akinbami, Oluyinka S.

    2016-01-01

    Incidence of gastrointestinal malignancy is gradually increasing. The aim of the study is to investigate age, sex and relative frequencies of various gastrointestinal malignancies diagnosed between January 2007 and December 2014 in the University of Uyo Teaching Hospital, and in a Private Specialist Laboratory, Uyo, Akwa Ibom State, Nigeria. All histological-diagnosed cases of gastrointestinal malignancies seen during the study period were recruited noting their bio-data and histopathological characteristics. A total of 67 patients aged 6-77 years (mean 58.0, SD 7.4) were enrolled; a male to female ratio of 1.3:1 was recorded. The most common age group and anatomical site affected with gastrointestinal malignancy were 61-70 years (23 cases, 34.3%) and colo-rectum cancers (36 cases, 53.7%). The small intestine and stomach were second and third leading anatomic sites involved in gastrointestinal malignancies, accounting for 13 (19.4%) and 8 (11.9%) cases respectively. Adenocarcinoma accounted for the majority of gastrointestinal malignancies (57 cases, 85.1%). Lymphoma and carcinoid tumor were also common, accounting for 3 (4.5%) cases each. Colorectal carcinoma was the most common type of gastrointestinal malignancies (53.7%) with adenocarcinoma being the predominant histological subtype of gastrointestinal malignancies. PMID:27134715

  8. 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. PMID:25267242

  9. Gut Microbiome and Colorectal Adenomas

    PubMed Central

    Dulal, Santosh; Keku, Temitope O.

    2015-01-01

    The trillions of bacteria that naturally reside in the human gut collectively constitute the complex system known the gut microbiome, a vital player for the host’s homeostasis and health. However, there is mounting evidence that dysbiosis, a state of pathological imbalance in the gut microbiome is present in many disease states. In this review, we present recent insights concerning the gut microbiome’s contribution to the development of colorectal adenomas and the subsequent progression to colorectal cancer (CRC). In the United States alone, CRC is the second leading cause of cancer deaths. As a result, there is a high interest in identifying risk factors for adenomas, which are intermediate precursors to CRC. Recent research on CRC and the microbiome suggest that modulation of the gut bacterial composition and structure may be useful in preventing adenomas and CRC. We highlight the known risk factors for colorectal adenomas and the potential mechanisms by which microbial dysbiosis may contribute to the etiology of CRC. We also underscore novel findings from recent studies on the gut microbiota and colorectal adenomas along with current knowledge gaps. Understanding the microbiome may provide promising new directions towards novel diagnostic tools, biomarkers, and therapeutic interventions for CRC. PMID:24855012

  10. Minilaparoscopic Colorectal Resections: Technical Note

    PubMed Central

    Bona, S.; Molteni, M.; Montorsi, M.

    2012-01-01

    Laparoscopic colorectal resections have been shown to provide short-term advantages in terms of postoperative pain, general morbidity, recovery, and quality of life. To date, long-term results have been proved to be comparable to open surgery irrefutably only for colon cancer. Recently, new trends keep arising in the direction of minimal invasiveness to reduce surgical trauma after colorectal surgery in order to improve morbidity and cosmetic results. The few reports available in the literature on single-port technique show promising results. Natural orifices endoscopic techniques still have very limited application. We focused our efforts in standardising a minilaparoscopic technique (using 3 to 5 mm instruments) for colorectal resections since it can provide excellent cosmetic results without changing the laparoscopic approach significantly. Thus, there is no need for a new learning curve as minilaparoscopy maintains the principle of instrument triangulation. This determines an undoubted advantage in terms of feasibility and reproducibility of the procedure without increasing operative time. Some preliminary experiences confirm that minilaparoscopic colorectal surgery provides acceptable results, comparable to those reported for laparoscopic surgery with regard to operative time, morbidity, and hospital stay. Randomized controlled studies should be conducted to confirm these early encouraging results. PMID:22548166

  11. 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.

  12. Helicobacter pylori and Gastrointestinal Malignancies.

    PubMed

    Venerito, Marino; Vasapolli, Riccardo; Rokkas, Theodoros; Malfertheiner, Peter

    2015-09-01

    Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population

  13. Percentage of Adults Who Receive Colorectal Cancer Screening as Appropriate

    MedlinePlus

    ... Appropriate Percentage of Adults Who Receive Colorectal Cancer Screening as Appropriate Colorectal cancer is the second leading ... Percentage of Adults Who Receive Recommended Colorectal Cancer Screening by Age Group 78pm-ubty Download these data » ...

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

    MedlinePlus

    ... Next Topic Additional resources for 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 ...

  15. 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.

  16. Robotic Versus Laparoscopic Colorectal Surgery

    PubMed Central

    Jackson, Nicole R.; Hauch, Adam T.; Hu, Tian; Kandil, Emad

    2014-01-01

    Background: Robotic approaches have become increasingly used for colorectal surgery. The aim of this study is to examine the safety and efficacy of robotic colorectal procedures in an adult population. Study Design: A systematic review of articles in both PubMed and Embase comparing laparoscopic and robotic colorectal procedures was performed. Clinical trials and observational studies in an adult population were included. Approaches were evaluated in terms of operative time, length of stay, estimated blood loss, number of lymph nodes harvested, and perioperative complications. Mean net differences and odds ratios were calculated to examine treatment effect of each group. Results: Two hundred eighteen articles were identified, and 17 met the inclusion criteria, representing 4,342 patients: 920 robotic and 3,422 in the laparoscopic group. Operative time for the robotic approach was 38.849 minutes longer (95% confidence interval: 17.944 to 59.755). The robotic group had lower estimated blood loss (14.17 mL; 95% confidence interval: –27.63 to –1.60), and patients were 1.78 times more likely to be converted to an open procedure (95% confidence interval: 1.24 to 2.55). There was no difference between groups with respect to number of lymph nodes harvested, length of stay, readmission rate, or perioperative complication rate. Conclusions: The robotic approach to colorectal surgery is as safe and efficacious as conventional laparoscopic surgery. However, it is associated with longer operative time and an increased rate of conversion to laparotomy. Further prospective randomized controlled trials are warranted to examine the cost-effectiveness of robotic colorectal surgery before it can be adopted as the new standard of care. PMID:25489216

  17. Malignant Catarrhal Fever

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Malignant catarrhal fever (MCF) is a frequently fatal viral disease of ruminant species, particularly cattle, bison, and deer. Clinical signs vary between species. Two major epidemiologic types of MCF exist, and are defined by the ruminant species that serve as natural reservoir hosts for infection...

  18. [Malignant peritoneal mesothelioma].

    PubMed

    Scripcariu, V; Dajbog, Elena; Lefter, L; Ferariu, D; Pricop, Adriana; Grigoraş, M; Dragomir, Cr

    2006-01-01

    Mesothelioma is a neoplasm originating from the mesothelial surface lining cells of the serous human cavities. It may involve the pleura, less frequently the peritoneum rarely, the pericardium, the tunica vaginalis testis and ovarian epithelium. Asbestos has been widely used in industry. A causal relationship between asbestos exposure and pleural, peritoneal and pericardial malign mesothelioma was suggested, the risk of cancer being correlated to cumulate exposure. Studies from National Cancer Institute, USA, show that the malignant mesothelioma is a rare and aggressive asbestos related malignancy. The symptomatology is insidious and poses difficult problems in diagnosis and treatment. This paper presents the case of a 59 year old patient with malignant peritoneal mesothelioma who worked almost 40 years as an electrician, exposed to asbestos fibers. He was hospitalized for important weight loss, abdominal pain and tiredness being diagnosed after imaging tests with a giant tumor, localized at the abdominal upper level, which seems to originate from the spleen's superior pole. During surgery we discovered a tumor with cystic parts, intense vascularized, which turn to be adherent in the upper side to the lower face of the left midriff cupola, to the spleen superior pole and 1/3 middle level of the great gastric curve. It was performed surgical ablation of the tumor, splenectomy with favorable postoperative evolution, the patient being now under chemotherapy treatment. PMID:17283842

  19. Immunotherapy for malignant glioma

    PubMed Central

    Suryadevara, Carter M.; Verla, Terence; Sanchez-Perez, Luis; Reap, Elizabeth A.; Choi, Bryan D.; Fecci, Peter E.; Sampson, John H.

    2015-01-01

    Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12–15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS)-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs) is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM. PMID:25722935

  20. Chromosome 5 allele loss in human colorectal carcinomas.

    PubMed

    Solomon, E; Voss, R; Hall, V; Bodmer, W F; Jass, J R; Jeffreys, A J; Lucibello, F C; Patel, I; Rider, S H

    That the sporadic and inherited forms of a particular cancer could both result from mutations in the same gene was first proposed by Knudson. He further proposed that these mutations act recessively at the cellular level, and that both copies of the gene must be lost for the cancer to develop. In sporadic cases both events occur somatically whereas in dominant familial cases susceptibility is inherited through a germline mutation and the cancer develops after a somatic change in the homologous allele. This model has since been substantiated in the case of retinoblastoma, Wilms tumour, acoustic neuroma and several other tumours, in which loss of heterozygosity was shown in tumour material compared to normal tissue from the same patient. The dominantly inherited disorder, familial adenomatous polyposis (FAP, also called familial polyposis coli), which gives rise to multiple adenomatous polyps in the colon that have a relatively high probability of progressing to a malignant adenocarcinoma, provides a basis for studying recessive genes in the far more common colorectal carcinomas using this approach. Following a clue as to the location of the FAP gene given by a case report of an individual with an interstitial deletion of chromosome 5q, who had FAP and multiple developmental abnormalities, we have examined sporadic colorectal adenocarcinomas for loss of alleles on chromosome 5. Using a highly polymorphic 'minisatellite' probe which maps to chromosome 5q we have shown that at least 20% of this highly heterogeneous set of tumours lose one of the alleles present in matched normal tissue. This parallels the assignment of the FAP gene to chromosome 5 (see accompanying paper) and suggests that becoming recessive for this gene may be a critical step in the progression of a relatively high proportion of colorectal cancers. PMID:2886919

  1. Predicting postoperative mortality in patients undergoing colorectal surgery.

    PubMed

    Slim, Karem; Panis, Yves; Alves, Arnaud; Kwiatkowski, Fabrice; Mathieu, Pierre; Mantion, Georges

    2006-01-01

    Well-known and suitable instruments for surgical audit are the POSSUM and P-POSSUM scoring systems. But these scores have not been well validated across the countries. The objective of the present study was to assess the predictive value of scores for colorectal surgery in France. Patients operated on for colorectal malignant or diverticular diseases, whether electively or on emergency basis, within a 4-month period were included in a prospective multicenter study conducted by the French Association for Surgery (Association Française de Chirurgie, AFC). The main outcome measure was postoperative in-hospital mortality. Independent factors leading to death were assessed by multivariate logistic regression analysis (AFC-index). The ratio of expected versus observed deaths was calculated, and the predictive value of the POSSUM and P-POSSUM scores were analyzed by the receiver operating characteristic (ROC) curve. A total of 1426 patients were included. The in-hospital death rate was 3.4%. Four independent preoperative factors (AFC-index) have been found: emergency surgery, loss of more than 10% of weight, neurological disease history, and age > 70 years. POSSUM had a poor predictive value; it overestimated postoperative death in all cases. P-POSSUM had a good predictive value, except for elective surgery, where it overestimated postoperative death twofold. The predictive value of the AFC-index was also good. It had the same sensitivity and specificity as the P-POSSUM. POSSUM has not been validated in France in the field of colorectal surgery. P-POSSUM was as predictive as the AFC-index which is a simpler instrument based on four clinical parameters (without any mathematical formulas). PMID:16369701

  2. Malignant Melanoma of the Foot

    MedlinePlus

    ... Javascript in your browser. Malignant Melanoma of the Foot What is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  3. 1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms.

    PubMed Central

    Kane, K F; Langman, M J; Williams, G R

    1995-01-01

    Epidemiological studies suggest that 1,25-dihydroxyvitamin D3 (D3) protects against colorectal carcinogenesis. Animal and in vitro studies show an antiproliferative effect of D3 in a variety of tumours including those of large bowel origin. D3 actions are mediated by D3 receptors (VDR) alone or by VDR in conjunction with retinoid X receptors (RXRs) in all D3 responsive tissues. The expression of mRNAs encoding VDR and RXRs in normal and malignant human colorectum was determined. Full length VDR (4.6 kB), RXR alpha (5.5 kB), and RXR gamma (3.5 and 7 kB) mRNAs were expressed in all tissues, but RXR beta mRNA was not expressed in any. VDR expression was reduced in 12 carcinomas relative to paired normal mucosa, and RXR alpha expression was reduced in nine. There was no correlation between VDR or RXR alpha expression and the site, grade of differentiation, or Dukes's staging of the tumour. The finding of persistent VDR and RXR coexpression in all colorectal tumours provides a rational basis for exploring a role for D3 in the treatment of colorectal malignancy. Images Figure 1 Figure 2 PMID:7883226

  4. Colorectal cancer mimics: a review of the usual suspects with pathology correlation.

    PubMed

    Ganguly, Akash; Meredith, Sara; Probert, Cairine; Kraecevic, Jasna; Anosike, Chinedum

    2016-09-01

    Colorectal cancer is the third most commonly diagnosed cancer in men and second most commonly diagnosed cancer in women worldwide. Initial diagnosis of colorectal malignancy is generally made on colonoscopy, sigmoidoscopy or digital rectal examination; however, with increased use of CT as primary investigation in patients with lower gastrointestinal symptoms, the diagnosis of colon cancer is often first apparent to a radiologist prior to more invasive tests. CT can demonstrate a discrete soft-tissue mass that narrows the colonic lumen or focal nodular wall thickening/stricture and a variety of pericolonic changes. Pattern of wall thickening has been described as an aid to differential diagnosis; however, significant overlap remains between primary colonic tumor and non-colonic tumors or benign conditions. Imaging is non-specific, and appropriate clinical history, direct inspection, histological analysis, and sometimes discussion at MDT are essential for accurate diagnosis and treatment planning. In this article, we will review the imaging features of some of these benign and malignant mimics of colorectal cancer, with accompanying histology slides where appropriate. PMID:27178338

  5. Plasminogen activators in experimental colorectal neoplasia: a role in the adenoma-carcinoma sequence?

    PubMed Central

    Gelister, J S; Lewin, M R; Driver, H E; Savage, F; Mahmoud, M; Gaffney, P J; Boulos, P B

    1987-01-01

    An important step in the transition from adenomatous polyp to invasive carcinoma is the degradation of the epithelial basement membrane. By the generation of plasmin, plasminogen activators may play an important role in regulating the extracellular protease activity required for this event to occur. The production of biofunctional urokinase and of tissue plasminogen activator was therefore investigated in the dimethylhydrazine induced rat model of colorectal neoplasia. Both adenomatous polyps (p values less than 0.001) and colorectal carcinomas (p values less than 0.001) were demonstrated to produce a significant excess of both urokinase and tissue plasminogen activator when compared with macroscopically normal colon. There was, however, no increased production of either enzyme by macroscopically normal preneoplastic colon when compared with control colon. This enhanced capacity of colorectal tumours to produce plasminogen activators and generate plasmin is thus a feature of both the premalignant as well as the malignant phenotype. These enzymes may contribute to the malignant potential of adenomatous polyps and to the invasive capacity of established carcinomas. PMID:3115868

  6. Immunohistochemical Expression of Dual-Specificity Protein Phosphatase 4 in Patients with Colorectal Adenocarcinoma

    PubMed Central

    Sim, Jongmin; Yi, Kijong; Kim, Hyunsung; Ahn, Hyein; Chung, Yumin; Rehman, Abdul; Jang, Se Min; Lee, Kang Hong; Jang, Kiseok; Paik, Seung Sam

    2015-01-01

    The role of dual-specificity protein phosphatase 4 (DUSP4) appears to vary with the type of malignant tumors and is still controversial. The purpose of our study was to clarify the exact role of DUSP4 expression in colorectal adenocarcinoma. We constructed tissue microarrays and investigated DUSP4 expression by immunohistochemistry. DUSP4 was more frequently expressed in adenocarcinomas and lymph node/distant metastases compared to that in normal colorectal tissues and tubular adenomas (P < 0.001). Mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (P < 0.001). DUSP4 expression was significantly correlated with older age (P = 0.017), male gender (P = 0.036), larger tumor size (P = 0.014), nonmucinous tumor type (P = 0.023), and higher T stage (P = 0.040). Kaplan-Meier survival curves revealed a significant effect of DUSP4 expression on both overall survival and disease-free survival in AJCC stage I (P = 0.008 and P = 0.003, resp., log-rank test) and male gender (P = 0.017 and P = 0.049, resp., log-rank test). DUSP4 protein is frequently upregulated in colorectal adenocarcinoma and may play an important role in carcinogenesis and cancer progression and may be a marker of adverse prognosis. PMID:25688264

  7. Mass Spectrometry-Based N-Glycomics of Colorectal Cancer

    PubMed Central

    Sethi, Manveen K.; Fanayan, Susan

    2015-01-01

    Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. An increased molecular understanding of the CRC pathology is warranted to gain insights into the underlying molecular and cellular mechanisms of the disease. Altered protein glycosylation patterns are associated with most diseases including malignant transformation. Recent advances in mass spectrometry and bioinformatics have accelerated glycomics research and present a new paradigm for cancer biomarker discovery. Mass spectrometry (MS)-based glycoproteomics and glycomics, therefore, hold considerable promise to improve the discovery of novel biomarkers with utility in disease diagnosis and therapy. This review focuses on the emerging field of glycomics to present a comprehensive review of advances in technologies and their application in studies aimed at discovering novel glycan-based biomarkers. We will also discuss some of the challenges associated with using glycans as biomarkers. PMID:26690136

  8. Metastatic Colorectal Cancer Resembling Severe Preeclampsia in Pregnancy

    PubMed Central

    Khangura, Raminder Kaur; Khangura, Charanpreet Kaur; Desai, Anagha; Goyert, Gregory; Sangha, Roopina

    2015-01-01

    Although colorectal cancer (CRC) is the third most common cancer in women, it is a rare malignancy in pregnancy. Symptoms of CRC such as fatigue, malaise, nausea, vomiting, rectal bleeding, anemia, altered bowel habits, and abdominal mass are often considered typical symptoms of pregnancy. Many cases of CRC are diagnosed in advanced stages due to missed warning signs of CRC, which may be misinterpreted as normal symptoms related to pregnancy. This report reviews 2 cases of CRC diagnosed within a 4-month interval at our institution. Both cases were initially thought to be atypical presentations of preeclampsia. Prenatal history, hospital course, and postpartum course were reviewed for both patients. CRC is often diagnosed at advanced stages in pregnancy. Common physiological symptoms of pregnancy should be scrutinized carefully and worked up appropriately, especially if symptoms remain persistent or increase in intensity or severity. PMID:26770850

  9. 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

  10. Mass Spectrometry-Based N-Glycomics of Colorectal Cancer.

    PubMed

    Sethi, Manveen K; Fanayan, Susan

    2015-01-01

    Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. An increased molecular understanding of the CRC pathology is warranted to gain insights into the underlying molecular and cellular mechanisms of the disease. Altered protein glycosylation patterns are associated with most diseases including malignant transformation. Recent advances in mass spectrometry and bioinformatics have accelerated glycomics research and present a new paradigm for cancer biomarker discovery. Mass spectrometry (MS)-based glycoproteomics and glycomics, therefore, hold considerable promise to improve the discovery of novel biomarkers with utility in disease diagnosis and therapy. This review focuses on the emerging field of glycomics to present a comprehensive review of advances in technologies and their application in studies aimed at discovering novel glycan-based biomarkers. We will also discuss some of the challenges associated with using glycans as biomarkers. PMID:26690136

  11. Methylator phenotype in colorectal cancer: A prognostic factor or not?

    PubMed

    Gallois, C; Laurent-Puig, P; Taieb, J

    2016-03-01

    Colorectal cancer (CRC) is due to different types of genetic alterations that are translated into different phenotypes. Among them, CpG island methylator phenotype (CIMP+) is the most recently involved in carcinogenesis of some CRC. The malignant transformation in this case is mainly due to the transcriptional inactivation of tumor suppressor genes. CIMP+ are reported to be more frequently found in the elderly and in women. The tumors are more frequently located in the proximal part of the colon, BRAF mutated and are associated with microsatellite instability (MSI) phenotype. All sporadic MSI CRC belong to the methylator phenotype, however some non MSI CRC may also harbor a methylator phenotype. The prognostic value of CIMP is not well known. Most studies show a worse prognosis in CIMP+ CRC, and adjuvant treatments seem to be more efficient. We review here the current knowledge on prognostic and predictive values in CIMP+ CRC. PMID:26702883

  12. Immunotherapy in human colorectal cancer: Challenges and prospective.

    PubMed

    Sun, Xuan; Suo, Jian; Yan, Jun

    2016-07-28

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

  13. Review on the immunotherapy strategies against metastatic colorectal carcinoma.

    PubMed

    Signorini, Lucia; Delbue, Serena; Ferrante, Pasquale; Bregni, Marco

    2016-10-01

    Colorectal cancer (CRC) is one of the most common malignancies throughout the world and the leading cause of cancer-related mortality in Western countries. Recent progress in CRC treatment options, such as surgery, chemotherapy, radiotherapy and target therapy, has improved the prognosis, but advanced disease with recurrence or distant metastasis is usually incurable and has an unfavorable prognosis. The introduction of immunotherapy-associated strategies, both active and passive, to the treatment of CRC aims to overcome the limits of classical treatments. We review the state of the art for CRC with respect to different immunotherapeutic approaches, such as the use of cancer vaccines and/or adoptive cellular therapy, their most current advances and limitations and perspectives for further improvements. PMID:27605072

  14. Radiofrequency Ablation of Liver Metastases from Colorectal Cancer: A Literature Review

    PubMed Central

    Kudo, Masatoshi

    2013-01-01

    Liver metastases occur in up to 60% of patients with colorectal cancer, and the control of liver metastases is considered to be of primary importance because it is a critical factor in determining prognosis. Radiofrequency ablation (RFA) therapy is one of the least invasive techniques for unresectable hepatic malignancies and can be performed safely using percutaneous, laparoscopic, or open surgical techniques. The local tumor progression rates after RFA for colorectal liver metastases range from 8.8% to 40.0%, and 5-year survival rates range from 20.0% to 48.5%. No prospective, randomized trials comparing the efficacy of RFA with that of surgical resection for colorectal liver metastases are currently available. However, some retrospective studies have reported that patients who received RFA had a survival rate similar to that observed in surgically treated groups, while other studies have reported better survival among patients who underwent surgical resection. The use of a laparoscopic or open surgical approach allows the repeated placement of RFA electrodes at multiple sites to ablate larger tumors. An accurate evaluation of treatment response is very important for the success of RFA therapy because a sufficient safety margin (at least 0.5 cm) can prevent local tumor progression. This review critically summarizes the current status of RFA for liver metastases from colorectal cancer. PMID:23422905

  15. Isolation of genes involved in colorectal metastasis by differential display of mRNA species

    SciTech Connect

    Gustafson, C.; Chenevix-Trench, G.; Antalis, T.

    1994-09-01

    The genetic events that give rise to malignant colorectal tumors have been determined in some detail. Much less is known about the genes involved in metastasis of these neoplasms. A useful resource to study this process is the pair of cell lines, SW480 and SW620, which are derived from the primary and metastatic components, respectively, of the same colorectal tumor. We are using the method of differential display of mRNA species to isolate genes that are differentially expressed in these two cell lines. Differential display is carried out in triplicate, using three different RNA extractions from each cell line. Only fragments that are consistently up- or down-regulated in one cell line compared to another are examined further. Less than 1% of fragments are differentially expressed. These are cloned, sequenced, and used for Northern blot and reverse transcriptase-PCR in order to examine their differential expression further. The RNA sources for this expression analysis are (i) SW480 and SW620 cells, (ii) other pairs of primary and metastatic colorectal cell lines, (iii) primary and metastatic tissue from patients with colorectal cancer.

  16. Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma

    PubMed Central

    Giannakis, Marios; Mu, Xinmeng Jasmine; Shukla, Sachet A.; Qian, Zhi Rong; Cohen, Ofir; Nishihara, Reiko; Bahl, Samira; Cao, Yin; Amin-Mansour, Ali; Yamauchi, Mai; Sukawa, Yasutaka; Stewart, Chip; Rosenberg, Mara; Mima, Kosuke; Inamura, Kentaro; Nosho, Katsuhiko; Nowak, Jonathan A.; Lawrence, Michael S.; Giovannucci, Edward L.; Chan, Andrew T.; Ng, Kimmie; Meyerhardt, Jeffrey A.; Van Allen, Eliezer M.; Getz, Gad; Gabriel, Stacey B.; Lander, Eric S.; Wu, Catherine J.; Fuchs, Charles S.; Ogino, Shuji; Garraway, Levi A.

    2016-01-01

    Summary Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs), memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies. PMID:27149842

  17. Lectin reactivities as intermediate biomarkers in premalignant colorectal epithelium.

    PubMed

    Boland, C R; Martin, M A; Goldstein, I J

    1992-01-01

    Normal colonic epithelial cells undergo maturation as they traverse the crypt to the lumenal surface. The binding of lectins to goblet cell mucins and other glycoconjugates changes as the cells migrate and differentiate. Additional stepwise modifications in glycoconjugate expression occur in premalignant and malignant neoplasms that may be detected by lectin binding studies. The lectins Dolichos biflorus agglutinin (DBA) and soybean agglutinin (SBA) have been developed as markers of differentiation in normal-appearing colonic epithelium. Using a quantitative biometric system to score tissues, reduced levels of lectin binding have been found in rectal tissue from patients with familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer. The lectin Amaranthus caudatus agglutinin (ACA) binds to a cytoplasmic glycoconjugate expressed at the base of the colonic crypt and serves as a possible proliferation marker in the distal, but not proximal, colon. ACA binding increases in tandem with increased levels of proliferation (using BrdU incorporation) in neoplastic tissues. Binding by the peanut lectin (PNA) occurs late in the adenoma-to-carcinoma sequence--in larger adenomas and in cancers--and serves as a marker of advancing neoplasia. Lectins identify the stepwise changes that occur during normal differentiation, proliferation and in advancing neoplasia. By selecting the appropriate probe, biomarkers may be developed for early, intermediate, and late events in colorectal cancer. PMID:1469891

  18. 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

  19. 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

  20. Colorectal Cancer Screening, Version 1.2015.

    PubMed

    Provenzale, Dawn; Jasperson, Kory; Ahnen, Dennis J; Aslanian, Harry; Bray, Travis; Cannon, Jamie A; David, Donald S; Early, Dayna S; Erwin, Deborah; Ford, James M; Giardiello, Francis M; Gupta, Samir; Halverson, Amy L; Hamilton, Stanley R; Hampel, Heather; Ismail, Mohammad K; Klapman, Jason B; Larson, David W; Lazenby, Audrey J; Lynch, Patrick M; Mayer, Robert J; Ness, Reid M; Rao, M Sambasiva; Regenbogen, Scott E; Shike, Moshe; Steinbach, Gideon; Weinberg, David; Dwyer, Mary A; Freedman-Cass, Deborah A; Darlow, Susan

    2015-08-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening provide recommendations for selecting individuals for colorectal cancer screening, and for evaluation and follow-up of colon polyps. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Colorectal Cancer Screening panel meeting. Major discussion topics this year were the state of evidence for CT colonography and stool DNA testing, bowel preparation procedures for colonoscopy, and guidelines for patients with a positive family history of colorectal cancer. PMID:26285241

  1. Transarterial Therapy for Colorectal Liver Metastases.

    PubMed

    Bhutiani, Neal; Martin, Robert C G

    2016-04-01

    Until recently, hepatic arterial therapies (HAT) had been used for colorectal liver metastases after failure of first-, second-, and third-line chemotherapies. HAT has gained greater acceptance in patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The current data demonstrate that HAT is a safe and effective option for preoperative downsizing, optimizing the time to surgery, limiting non-tumor-bearing liver toxicity, and improving overall survival after surgery in patients with colorectal liver-only metastases. The aim of this review is to present the current data for HAT in liver-only and liver-dominant colorectal liver metastases. PMID:27017870

  2. Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.

    PubMed

    Lin, Jieru E; Colon-Gonzalez, Francheska; Blomain, Erik; Kim, Gilbert W; Aing, Amanda; Stoecker, Brian; Rock, Justin; Snook, Adam E; Zhan, Tingting; Hyslop, Terry M; Tomczak, Michal; Blumberg, Richard S; Waldman, Scott A

    2016-01-15

    Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations revealed that obesity reversibly silenced guanylin expression through calorie-dependent induction of endoplasmic reticulum stress and the unfolded protein response in intestinal epithelial cells. In transgenic mice, enforcing specific expression of guanylin in intestinal epithelial cells restored GUCY2C signaling, eliminating intestinal tumors associated with a high calorie diet. Our findings show how caloric suppression of the guanylin-GUCY2C signaling axis links obesity to negation of a universal tumor suppressor pathway in colorectal cancer, suggesting an opportunity to prevent colorectal cancer in obese patients through hormone replacement with the FDA-approved oral GUCY2C ligand linaclotide. PMID:26773096

  3. Endoscopic submucosal dissection vs laparoscopic colorectal resection for early colorectal epithelial neoplasia

    PubMed Central

    Hon, Sophie SF; Ng, Simon SM; Wong, Tiffany CL; Chiu, Philip WY; Mak, Tony WC; Leung, WW; Lee, Janet FY

    2015-01-01

    AIM: To compare the short term outcome of endoscopic submucosal dissection (ESD) with that of laparoscopic colorectal resection (LC) for the treatment of early colorectal epithelial neoplasms that are not amenable to conventional endoscopic removal. METHODS: This was a retrospective cohort study. The clinical data of all consecutive patients who underwent ESD for endoscopically assessed benign lesions that were larger than 2 cm in diameter from 2009 to 2013 were collected. These patients were compared with a cohort of controls who underwent LC from 2005 to 2013. Lesions that were proven to be malignant by initial endoscopic biopsies were excluded. Mid and lower rectal lesions were not included because total mesorectal excision, which bears a more complicated postoperative course, is not indicated for lesions without histological proof of malignancy. Both ESD and LC were performed by the same surgical unit with a standardized technique. The patients were managed according to a standard protocol, and they were closely monitored for complications after the procedures. All hospital records were reviewed, and the following data were compared between the ESD and LC groups: patient demographics, size and location of the lesions, procedure time, short-term clinical outcomes and pathology results. RESULTS: From 2005 to 2013, 65 patients who underwent ESD and 55 patients who underwent LC were included in this study. The two groups were similar in terms of sex (P = 0.41) and American Society of Anesthesiologist class (P = 0.58), although patients in the ESD group were slightly older (68.6 ± 9.4 vs 64.6 ± 9.9, P = 0.03). ESD could be accomplished with a shorter procedure time (113 ± 66 min vs 153 ± 43 min, P < 0.01) for lesions of comparable size (3.0 ± 1.2 cm vs 3.4 ± 1.4 cm, P = 0.22) and location (colon/rectum: 59/6 vs colon/rectum: 52/3, P = 0.43). ESD appeared to be associated with a lower short-term complication rate, but the difference did not reach statistical

  4. 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

  5. Microbiome and Malignancy

    PubMed Central

    Plottel, Claudia S.; Blaser, Martin J.

    2011-01-01

    Current knowledge is insufficient to explain why only a proportion of individuals exposed to environmental carcinogens or carrying a genetic predisposition to cancer develop disease. Clearly, other factors must be important and one such element that has recently received attention is the human microbiome, the residential microbes including Bacteria, Archaea, Eukaryotes, and viruses that colonize humans. Here, we review principles and paradigms of microbiome-related malignancy, as illustrated by three specific microbial-host interactions. We review the effects of the microbiota on local and adjacent-neoplasia, present the estrobolome model of distant effects, and discuss the complex interactions with a latent virus leading to malignancy. These are separate facets of a complex biology interfacing all the microbial species we harbor from birth onward toward early reproductive success and eventual senescence. PMID:22018233

  6. 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.

  7. 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.

  8. Ovarian metastasis from colorectal cancer.

    PubMed

    Birnkrant, A; Sampson, J; Sugarbaker, P H

    1986-11-01

    Controversies exist regarding the surgical treatment of the ovaries in women with primary colorectal cancer. A review of the authors' experience and the surgical literature reveals an incidence of ovarian metastases from colorectal cancer of approximately 6 percent. This problem may occur somewhat more frequently in premenopausal women. Resection of the ovaries at the time of colectomy is unlikely to affect survival. Removal of the ovaries at the time of bowel resection will prevent repeat laparotomy to resect an ovarian mass in approximately 2 percent of women with large bowel cancer. Oophorectomy should be performed in all postmenopausal females at the time of primary resection. Oophorectomy should be performed in premenopausal women if any gross abnormality of the ovary is detected or if peritoneal implants are seen at the time of primary resection. PMID:3533472

  9. Telomere function in colorectal cancer.

    PubMed

    Frías, Cristina; Morán, Alberto; de Juan, Carmen; Ortega, Paloma; Fernández-Marcelo, Tamara; Sánchez-Pernaute, Andrés; Torres, Antonio José; Díaz-Rubio, Eduardo; Benito, Manuel; Iniesta, Pilar

    2009-10-15

    Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world. Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length. It is achieved mainly, by telomerase activation. Thus, the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized. Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours. Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis. Taking into account all the results achieved by different groups, quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma. PMID:21160767

  10. Pembrolizumab in Treating Patients With Malignant Mesothelioma

    ClinicalTrials.gov

    2016-05-10

    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

  11. Treatment of Malignant Pheochromocytoma

    PubMed Central

    Ajallé, R.; Plouin, P. F.; Pacak, K.; Lehnert, H.

    2013-01-01

    Pheochromocytoma (PCC) is a rare disease, mainly sporadic, but also associated with some familial disorders, with a malignancy frequency of approximately 10%. Only the presence of distant metastases, derived from large pleomorphic chromaffin cells, is widely accepted as a criterion of malignancy. Variable symptoms may be caused by production and release of catecholamines. Since there is no curative treatment for malignant PCC and due to its unfavorable prognosis, assuring quality of life is one of the main therapeutic objectives. Besides a long-term medical treatment of symptoms using selective α-1 blockers and nonselective, noncompetitive α- and / or β-blockers, debulking surgery is the first treatment step. In case of a sufficient uptake of 123I-MIBG treatment with targeted radiation therapy, use of 131I-MIBG is an option as an adjuvant therapy, following debulking surgery. Chemotherapy should be applied to patients without positive MIBG-scan, with no response to 131I-MIBG or progression after radionuclide treatment, and especially in cases with high proliferation index. The most effective chemotherapy regimen appears to be the CVD-scheme, including cyclophosphamide, vincristine, and dacarbazine. The so-called targeted molecular therapies with treatment combinations of temozolomide and thalidomide, or sunitinib monotherapy, and novel therapeutic somatostatin analogues have shown promising results and should thus encourage clinical trials to improve the prognosis of metastatic PCC. Within this review the current treatment modalities and novel molecular strategies in the management of this disease are discussed and a treatment algorithm is suggested. PMID:19672813

  12. 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

  13. [Malignant biliary obstruction].

    PubMed

    Hucl, Tomáš

    2016-01-01

    Pancreatic cancer and cholangiocarcinoma are the most common causes of malignant biliary obstruction. They are diseases of increasing incidence and unfavorable prognosis. Only patients with localized disease indicated for surgery have a chance of long-term survival. These patients represent less than 20 % of all patients, despite the progress in our diagnostic abilities.Locally advanced and metastatic tumors are treated with palliative chemotherapy or chemoradiotherapy; the results of such treatments are unsatisfactory. The average survival of patients with unresectable disease is 6 months and only 5-10 % of patients survive 5 years.Biliary drainage is an integral part of palliative treatment. Endoscopically or percutaneosly placed stents improve quality of life, decrease cholestasis and pruritus, but do not significantly improve survival. Biliary stents get occluded over time, possibly resulting in acute cholangitis and require repeated replacement.Photodynamic therapy and radiofrequency ablation, locally active endoscopic methods, have been increasingly used in recent years in palliative treatment of patients with malignant biliary obstruction. In photodynamic therapy, photosensitizer accumulates in tumor tissue and is activated 48 hours later by light of a specific wave length. Application of low voltage high frequency current during radiofrequency ablation results in tissue destruction by heat. Local ablation techniques can have a significant impact in a large group of patients with malignant biliary obstruction, leading to improved prognosis, quality of life and stent patency. PMID:26898789

  14. Endometriosis-associated Malignancy

    PubMed Central

    Krawczyk, N.; Banys-Paluchowski, M.; Schmidt, D.; Ulrich, U.; Fehm, T.

    2016-01-01

    Endometriosis is a common condition in women of reproductive age. According to several epidemiological studies endometriosis may be associated with increased risk of various malignancies. However, endometriosis-associated malignancy (EAM) is defined by certain histological criteria. About 80 % of EAM have been found in the ovary, whereas 20 % are localized in extragonadal sites like intestine, rectovaginal septum, abdominal wall, pleura and others. Some authors suggest that EAM arise from atypical endometriosis as an intermediate lesion between endometriosis and cancer. Moreover, a number of genetic alterations, like loss of heterozygosity (LOH), PTEN, ARID1 A and p53 mutations have been found in both endometriosis and EAM. Endometriosis-associated ovarian cancer (EAOC) is mostly a well or intermediately differentiated tumor of endometrioid or clear cell histological sub-type. Women affected by EAOC are on average five to ten years younger than non-EAOC patients; in most of the cases EAOC is a low stage disease with favorable clinical outcome. Since EAM is a rare condition systematic data on EAM are still missing. A systematic retrospective study on endometriosis-associated malignancies (EAM study) is currently being conducted by the Endometriosis Research Foundation together with the study groups on ovarian and uterine tumors of the working group for gynecological oncology (AGO) (gyn@mlk-berlin.de). PMID:26941451

  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. 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

  17. Subnuclear Proteomics in Colorectal Cancer

    PubMed Central

    Albrethsen, Jakob; Knol, Jaco C.; Piersma, Sander R.; Pham, Thang V.; de Wit, Meike; Mongera, Sandra; Carvalho, Beatriz; Verheul, Henk M. W.; Fijneman, Remond J. A.; Meijer, Gerrit A.; Jimenez, Connie R.

    2010-01-01

    Abnormalities in nuclear phenotype and chromosome structure are key features of cancer cells. Investigation of the protein determinants of nuclear subfractions in cancer may yield molecular insights into aberrant chromosome function and chromatin organization and in addition may yield biomarkers for early cancer detection. Here we evaluate a proteomics work flow for profiling protein constituents in subnuclear domains in colorectal cancer tissues and apply this work flow to a comparative analysis of the nuclear matrix fraction in colorectal adenoma and carcinoma tissue samples. First, we established the reproducibility of the entire work flow. In a reproducibility analysis of three nuclear matrix fractions independently isolated from the same colon tumor homogenate, 889 of 1,047 proteins (85%) were reproducibly identified at high confidence (minimally two peptides per protein at 99% confidence interval at the protein level) with an average coefficient of variance for the number of normalized spectral counts per protein of 30%. This indicates a good reproducibility of the entire work flow from biochemical isolation to nano-LC-MS/MS analysis. Second, using spectral counting combined with statistics, we identified proteins that are significantly enriched in the nuclear matrix fraction relative to two earlier fractions (the chromatin-binding and intermediate filament fractions) isolated from six colorectal tissue samples. The total data set contained 2,059 non-redundant proteins. Gene ontology mining and protein network analysis of nuclear matrix-enriched proteins revealed enrichment for proteins implicated in “RNA processing” and “mRNA metabolic process.” Finally, an explorative comparison of the nuclear matrix proteome in colorectal adenoma and carcinoma tissues revealed many proteins previously implicated in oncogenesis as well as new candidates. A subset of these differentially expressed proteins also exhibited a corresponding change at the mRNA level

  18. 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

  19. Liver Metastases in Colorectal Cancer.

    PubMed

    Folprecht, Gunnar

    2016-01-01

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

  20. ADAMTS Expression in Colorectal Cancer

    PubMed Central

    Filou, Serafula; Korpetinou, Aggeliki; Kyriakopoulou, Dora; Bounias, Dimitrios; Stavropoulos, Michael; Ravazoula, Panagiota; Papachristou, Dionysios J.; Theocharis, Achilleas D.; Vynios, Demitrios H.

    2015-01-01

    ADAMTSs are a family of secreted proteinases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). By acting on a large panel of extracellular substrates, they control several cell functions such as fusion, adhesion, proliferation and migration. Through their thrombospondin motifs they also possess anti-angiogenic properties. We investigated whether ADAMTSs participate in colorectal cancer progression and invasion. Their expression was investigated at both mRNA and protein levels. Using RT-PCR, the expression of ADAMTS-1, -4, -5 and ADAMTS-20 was estimated in colorectal tumors of different cancer stage and anatomic site and 3 cell lines of different aggressiveness. An overexpression of ADAMTS-4 and -5 was observed, especially in tissue samples, whereas ADAMTS-1 and -20 were found to be down-regulated. Western blot analysis further supported the RT-PCR findings, revealing in addition the degradation of ADAMTS-1 and -20 in cancer. In situ expression and localization of ADAMTS-1, -4, -5 and -20 was also investigated by immunohistochemical analysis. Our data suggest a positive correlation between ADAMTS-4 and -5 expression and cancer progression, in contrast with the anti-angiogenic members of the family, ADAMTS-1 and -20, which were found to be down-regulated. Our findings support the notion that overexpression of ADAMTS-4 and ADAMTS-5 in colorectal cancer might be a possible invasive mechanism of cancer cells in order to degrade proteoglycans of ECM. PMID:25786261

  1. [Maintenance therapy for colorectal cancer].

    PubMed

    Yamaguchi, Shigeo; Kato, Shunsuke

    2014-08-01

    Some trials have demonstrated the benefits of maintenance chemotherapy for advanced colorectal cancer. In chemotherapeutic strategies for advanced colorectal cancer, chemotherapy-related toxicity prevention and quality of life(QOL)maintenance are more important than the introduction of a strong regimen, especially when additional surgery is not possible. In Japan, the combination of a folinic acid/5-fluorouracil/oxaliplatin(FOLFOX)regimen and bevacizumab is a popular first-line chemotherapy regimen. However, despite its effectiveness, neuropathy or hand-foot syndrome after 5 or 6 cycles tends to lead to chemotherapy withdrawal. CAIRO3 trial reported the effectiveness of capecitabine and bevacizumab as a maintenance chemotherapy regimen. Additionally, the ML18147 trial demonstrated that bevacizumab beyond progression(BBP)prolonged overall survival(OS)and progression free survival(PFS)in patients with advanced colorectal cancer. Although those trials demonstrated the effectiveness of continuous or maintenance bevacizumab administration, no trials have compared the effectiveness of cytotoxic drugs with bevacizumab as maintenance therapies. Moreover, controversy exists regarding the selection of drugs as a maintenance therapy and the identification of patients who would benefit from maintenance therapy. PMID:25132024

  2. 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. PMID:25408419

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

    PubMed Central

    LUNEVICIUS, RAIMUNDAS; POSKUS, TOMAS; SAMALAVICIUS, NARIMANTAS E.

    2015-01-01

    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. PMID:26171046

  4. CG100649, a novel COX-2 inhibitor, inhibits colorectal adenoma and carcinoma growth in mouse models.

    PubMed

    Kim, Sun-Hee; Margalit, Ofer; Katoh, Hiroshi; Wang, Dingzhi; Wu, Hong; Xia, Dianren; Holla, Vijaykumar R; Yang, Peiying; DuBois, Raymond N

    2014-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) can reduce the risk of developing colorectal cancer (CRC) and are being considered for use as adjuvant therapy for treatment of CRC patients. However, long-term use of most NSAIDs, except aspirin, increases cardiovascular risk, hampering use of these drugs in CRC prevention and possibly for treatment. CG100649 is a new member of the COXIB family, which is proposed to inhibit both COX-2 and carbonic anhydrase-I/-II (CA-I/-II) activity. Using mouse models, we show here that CG100649 inhibits premalignant and malignant colorectal lesions in mouse models, partly through inhibiting tumor cell proliferation. These pre-clinical findings suggest a need for further exploration of CG100649 for CRC prevention and treatment. The long-term safety profile of CG100649, particularly regarding its effect on cardiovascular risk, is yet to be determined. PMID:25085205

  5. 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…

  6. Economic Burden of Colorectal Cancer in Korea

    PubMed Central

    Byun, Ju-Young; Oh, In-Hwan; Kim, Young Ae; Seo, Hye-Young; Lee, Yo-Han

    2014-01-01

    Objectives The incidence and survival rate of colorectal cancer in Korea are increasing because of improved screening, treatment technologies, and lifestyle changes. In this aging population, increases in economic cost result. This study was conducted to estimate the economic burden of colorectal cancer utilizing claims data from the Health Insurance Review and Assessment Service. Methods Economic burdens of colorectal cancer were estimated using prevalence data and patients were defined as those who received ambulatory treatment from medical institutions or who had been hospitalized due to colorectal cancer under the International Classification of Disease 10th revision codes from C18-C21. The economic burdens of colorectal cancer were calculated as direct costs and indirect costs. Results The prevalence rate (per 100 000 people) of those who were treated for colorectal cancer during 2010 was 165.48. The economic burdens of colorectal cancer in 2010 were 3 trillion and 100 billion Korean won (KRW), respectively. Direct costs included 1 trillion and 960 billion KRW (62.85%), respectively and indirect costs were 1 trillion and 160 billion (37.15%), respectively. Conclusions Colorectal cancer has a large economic burden. Efforts should be made to reduce the economic burden of the disease through primary and secondary prevention. PMID:24744825

  7. ACR Appropriateness Criteria Radiologic Management of Hepatic Malignancy.

    PubMed

    Kouri, Brian E; Abrams, Ross A; Al-Refaie, Waddah B; Azad, Nilofer; Farrell, James; Gaba, Ron C; Gervais, Debra A; Gipson, Matthew G; Kolbeck, Kenneth J; Marshalleck, Francis E; Pinchot, Jason W; Small, William; Ray, Charles E; Hohenwalter, Eric J

    2016-03-01

    Management of primary and secondary hepatic malignancy is a complex problem. Achieving optimal care for this challenging population often requires the involvement of multiple medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and loco-regional therapies, such as thermal ablation and transarterial embolization techniques. This article provides a review of treatment strategies for the three most common subtypes of hepatic malignancy treated with loco-regional therapies: hepatocellular carcinoma, neuroendocrine metastases, and colorectal metastases. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three 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. PMID:26944037

  8. Molecular Diagnostic Applications in Colorectal Cancer

    PubMed Central

    Huth, Laura; Jäkel, Jörg; Dahl, Edgar

    2014-01-01

    Colorectal cancer, a clinically diverse disease, is a leading cause of cancer-related death worldwide. Application of novel molecular diagnostic tests, which are summarized in this article, may lead to an improved survival of colorectal cancer patients. Distinction of these applications is based on the different molecular principles found in colorectal cancer (CRC). Strategies for molecular analysis of single genes (as KRAS or TP53) as well as microarray based techniques are discussed. Moreover, in addition to the fecal occult blood testing (FOBT) and colonoscopy some novel assays offer approaches for early detection of colorectal cancer like the multitarget stool DNA test or the blood-based Septin 9 DNA methylation test. Liquid biopsy analysis may also exhibit great diagnostic potential in CRC for monitoring developing resistance to treatment. These new diagnostic tools and the definition of molecular biomarkers in CRC will improve early detection and targeted therapy of colorectal cancer.

  9. Intraoral malignant melanoma

    PubMed Central

    Babburi, Suresh; Subramanyam, R. V.; Aparna, V.; Sowjanya, P.

    2013-01-01

    Primary oral mucosal melanoma is a rare aggressive neoplasm and accounts for only 0.2-8% of all reported melanomas. It is a malignant neoplasm of melanocytes that may arise from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is considered to be the most deadly and biologically unpredictable of all human neoplasms, having the worst prognosis. In this article, we report a case of oral melanoma in a 52-year-old female patient with a chief complaint of black discolouration of the maxillary gingiva and palate. PMID:24249959

  10. Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer

    PubMed Central

    de Boer, Esther; van der Vegt, Bert; van der Sluis, Tineke; Kooijman, Paulien; Low, Philip S.; van der Zee, Ate G. J.; Arts, Henriette J. G.; van Dam, Gooitzen M.; Bart, Joost

    2015-01-01

    Aims Tumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-α) has already been identified as a suitable target for cancer therapy and imaging. FR-α is present on ~40% of human cancers. FR-β is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-β expression in solid tumors. Additional or simultaneous expression of FR-β could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-β is evaluated in ovarian, breast and colorectal cancer. Methods FR-β expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) of 339 ovarian cancer patients, 418 breast cancer patients, on 20 slides of colorectal cancer samples and on 25 samples of diverticulitis. Results FR-β expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples. Expression was weak or moderate. Of the diverticulitis samples, 80% were positive for FR-β expression in macrophages. FR-β status neither correlated to known disease-related variables, nor showed association with overall survival and progression free survival in ovarian and breast cancer. In breast cancer, negative axillary status was significantly correlated to FR-β expression (p=0.022). Conclusions FR-β expression was low or absent in the majority of ovarian, breast and colorectal tumor samples. From the present study we conclude that the low FR-β expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes. Due to weak expression, FR-β is not regarded as a suitable target in colorectal cancer. PMID:26248049

  11. Relationship Between Chronic Inflammation and the Stage and Histopathological Size of Colorectal Carcinoma

    PubMed Central

    Rasic, Ismar; Radovic, Svjetlana; Aksamija, Goran

    2016-01-01

    Objectives: The association of inflammatory reactions with almost all types of cancer supports the concept that inflammation is a critical component of tumor progression. The present study aimed to evaluate the relationship of serum markers of chronic inflammation with the stage of and histopathological size of colorectal carcinoma (CRC). Methods: This cross-sectional study included 90 patients of both sexes, mean age 66.2 (range 47-78) years, with clinically and histologically confirmed CRC, who were admitted to the Clinic for abdominal surgery UCCS for surgical treatment of CRC. The patients according to the stage of disease were divided into three groups (stage II–IV). The control group consisted of 30 subjects with no signs of malignancy and acute inflammatory diseases. Staging of CRC was done according to the TNM classification. In each patient, the preoperative blood samples were taken for determination of the parameters of inflammation: the erythrocyte sedimentation rate, white blood cells, C-reactive protein (CRP), fibrinogen and alpha 2 globulins. Results: It was confirmed that increasing markers of inflammation followed increasing stages of colorectal cancer, depth of tumor invasion and the occurrence of metastatic disease. CRP is a biomarker that consistently and significantly increases from the second to the fourth stage of colorectal cancer (7.2 (2.3-14.6) mg/L vs. 21.85 (12.3-41) mg/L vs. 38.6 (21.5-79) mg/L; p<0.01) and significantly correlates positively with the stage of CRC (r= 0.783, p<0.001), and the tumor size (r=0.249, p<0.05). Conclusion: The study results point to an increase in the degree of chronic inflammation throughout the progression of colorectal cancer. The most consistent marker of chronic inflammation that accompanies the progression of colorectal carcinoma is CRP. PMID:27147782

  12. A Big Bang model of human colorectal tumor growth

    PubMed Central

    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

    2015-01-01

    What happens in the early, still undetectable human malignancy 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 sub-clones 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 revealed the absence of selective sweeps, uniformly high intra-tumor heterogeneity (ITH), and sub-clone 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 sub-clone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH with significant clinical implications. PMID:25665006

  13. Radioimmunotherapy of malignancies

    SciTech Connect

    Reilly, R.M. )

    1991-05-01

    The critical issues in radioimmunotherapy are highlighted, and novel ways of improving the therapeutic indexes of radioimmunotherapeutic agents are outlined. The use of radioactively labeled monoclonal antibodies to treat malignant tumors has been investigated in animals and humans. Radionuclides suitable for labeling antibodies for such use include iodine 125, iodine 131, yttrium 90, rhenium 188, and copper 67. Radiobiological factors to be considered in radioimmunotherapy include the size and density of the tumor and the ability of a radiolabeled antibody to penetrate the tumor nodule. The dose of radiation required to destroy a tumor varies; however, the whole-body dose must not exceed 200 rads to avoid irreversible toxicity to the bone marrow. Despite the theoretical inadequacy of radiation doses to tumors indicated by conventional dosimetry, responses have been observed in animals and humans. More reliable and accurate dosimetric methods are under development. The induction of human antimouse antibodies can alter the pharmacokinetics of radiolabeled antibodies. Improving the therapeutic index of radioimmunotherapeutic agents may be achieved through regional therapy, administering a secondary antibody to improve clearance, combining radioimmunotherapy with external-beam irradiation, using an avidin-biotin conjugate system to deliver the radiolabeled antibodies, and addressing the problem of tumor antigen heterogeneity. Researchers are working to reduce or eliminate the clinical problems associated with radioimmunotherapy. Hematologic malignancies, such as lymphomas, are more likely than solid tumors to respond satisfactorily. 110 refs.

  14. Pleural malignancies including mesothelioma.

    PubMed

    Hillerdal, G

    1995-07-01

    Malignant mesothelioma is caused almost exclusively by occupational exposure to asbestos. During the past few years, however, increasing evidence has mounted that background exposure to asbestos could be sufficient to cause mesothelioma. Treatment of malignant mesothelioma remains a big problem. Some new approaches are on their way, and the most exciting ones are local immunotherapy in very early cases. Some success has been reported with local interferon treatment. As for treatment of metastatic pleural disease, the main purpose is symptomatic relief of dyspnea caused by fluid accumulation. The best way to achieve a lasting palliation is pleurodesis, and the most common way to do this, is by chemical means. The drug of choice in the United States has for many years been tetracycline, but since injectable tetracycline is no longer available, some substitute must be found. The substance that will "win" is not yet clear, but the two leading contestants are talc and doxycycline. Bleomycin also has its supporters, and a dark horse is quinacrine, which although not easily available in the United States, has been used in many European centers for decades. PMID:9363074

  15. Radiotherapy of malignant melanoma

    SciTech Connect

    Cooper, J.S.

    1985-04-01

    The role of radiotherapy in the treatment of malignant melanoma is limited, and surgery generally forms the mainstay of medical practice. However, there are some circumstances in which radiotherapy should be considered the treatment of choice. Symptomatic metastatic lesions in bone or brain can effectively be palliated in a substantial proportion of instances. At the current stage of our knowledge, conventionally fractionated treatment of such lesions forms the standard against which other treatments should be measured. In contrast, metastatic lesions to skin or lymph nodes that do not overlie critical normal structures probably are better treated by high-dose-per-fraction techniques. Radiotherapy may play a definitive role in the treatment of lentigo maligna. The precise optimal energy of the beam to be used remains to be defined. Slightly more penetrating radiation appears to be required for lentigo maligna melanomas. Here, too, the optimal energy remains to be defined. The treatment of nonlentigenous melanomas primarily by radiotherapy is unproved in my opinion. Certainly, the data from the Princess Margaret Hospital is exciting, but I believe it must be corroborated by a well-designed trial before it can be accepted without question. Future directions in treatment of malignant melanoma are likely to include further trials of unconventional fractionation and the use of radiosensitizing agents in conjunction with radiotherapy. The time for dermatologists and radiation therapists to cooperate in such studies is at hand.

  16. A Case of von Hippel–Lindau Disease with Colorectal Adenocarcinoma, Renal Cell Carcinoma and Hemangioblastomas

    PubMed Central

    Heo, Su Jin; Lee, Choong-kun; Hahn, Kyu Yeon; Kim, Gyuri; Hur, Hyuk; Choi, Sung Hoon; Han, Kyung Seok; Cho, Arthur; Jung, Minkyu

    2016-01-01

    von Hippel–Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome associated with mutations of the VHL tumor suppressor gene located on chromosome 3p25. The loss of functional VHL protein contributes to tumorigenesis. This condition is characterized by development of benign and malignant tumors in the central nervous system (CNS) and the internal organs, including kidney, adrenal gland, and pancreas. We herein describe the case of a 74-year-old man carrying the VHL gene mutation who was affected by simultaneous colorectal adenocarcinoma, renal clear cell carcinoma, and hemangioblastomas of CNS. PMID:25715769

  17. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma

    PubMed Central

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  18. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma.

    PubMed

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  19. 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

  20. 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

  1. 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. PMID:26779313

  2. Smoking and risk of colorectal cancer.

    PubMed Central

    Knekt, P.; Hakama, M.; Järvinen, R.; Pukkala, E.; Heliövaara, M.

    1998-01-01

    Tobacco smoking was studied in relation to colorectal cancer in 56 973 Finnish men and women initially free from cancer. Smoking status was determined by a health questionnaire. During a follow-up period of 28 years, from the baseline in 1966-72 to the end of 1994, 457 cases of colorectal cancer occurred. There was no significant association between baseline smoking status and colorectal cancer risk over the total follow-up period. The sex- and age-adjusted relative risk of colorectal cancer between smokers and non-smokers was 1.06 (95% confidence interval 0.84-1.33). For follow-up periods of 11-20 years, however, the relative risk was 1.57 (95% confidence interval 1.09-2.24). In a subgroup in which smoking habits were assessed twice, the relative risk of colorectal cancer among persistent smokers was 1.71 (95% confidence interval 1.09-2.68) compared with others. The results of the present prospective study are consistent with the possibility that smoking increases the risk of colorectal cancer after a relatively long induction period. To clarify the role of smoking in colorectal cancer development, further cohort studies are needed with long follow-up periods and allowing for control of dietary and other potential confounding factors. PMID:9662264

  3. Examining the Association Between Cigarette Smoking and Colorectal Cancer Using Historical Case-Control Data

    PubMed Central

    Peppone, Luke J.; Hyland, Andrew; Moysich, Kirsten B.; Reid, Mary E.; Piazza, Kenneth M.; Purnell, Jason Q.; Mustian, Karen M.; Morrow, Gary R.

    2010-01-01

    BACKGROUND The majority of recent, well-designed studies have shown that long-term cigarette smoking increases colorectal cancer risk, but older studies with shorter durations of exposure often found no association. This study aimed to examine colorectal cancer risk by smoking exposure using data collected in the late 1950s and early 1960s. METHODS This case-control study examined colorectal cancer risk by lifetime smoking history. There were 1,365 patients who visited Roswell Park Cancer Institute (RPCI) between 1957 and 1965 diagnosed with primary, incident colorectal cancers that were matched to 4,096 malignancy-free controls on gender and age. Odds ratios were calculated using separate logistic regression models for each smoking exposure, while controlling for other tobacco use, county of residence, race, age, gender, and body mass index (BMI). RESULTS The adjusted OR for individuals who reported their greatest level of smoking to be more than 1 pack/day was 0.87 (95% CI=0.67–1.15). Among those who smoked 42 or more years, the adjusted OR was 0.89 (95% CI=0.68–1.15) compared to those who never smoked. For individuals who smoked more than 45 pack-years, the OR was 0.92 (95% CI=0.72–1.19). The results did not differ significantly by gender, although men had considerably greater exposure compared to women. Results also did not differ by colorectal sub-site. CONCLUSION No association was found between long-term cigarette smoking and colorectal cancer risk. These results are in accord with studies that followed cohorts throughout the 1950s and 1960s. Methodological limitations, such as missing data on covariates and the higher incidence of smoking-related illness in a hospital setting, may have contributed to the null results found in this study. Prolonged population exposure to cigarettes and perhaps a changing product may explain why more recent studies have reported a positive association between smoking and colorectal cancer. PMID:19683487

  4. Chemokine CXCL14 is associated with prognosis in patients with colorectal carcinoma after curative resection

    PubMed Central

    2013-01-01

    Background The chemokine CXCL14 has been reported to play an important role in the progression of many malignancies such as breast cancer and papillary thyroid carcinoma, but the role of CXCL14 in colorectal carcinoma (CRC) remains to be established. The purpose of this study was to investigate the expression pattern and significance of CXCL14 in CRC progression. Method 265 colorectal carcinoma specimens and 129 matched adjacent normal colorectal mucosa specimens were collected. Expression of CXCL14 in clinical samples was examined by immunostaining. The effect of CXCL14 on colorectal carcinoma cell proliferation was measured by MTT assay, BrdU incorporation assay and colony formation assay. The impact of CXCL14 on migration and invasion of colorectal carcinoma cells was determined by transwell assay and Matrigel invasion assay, respectively. Results CXCL14 expression was significantly up-regulated in tumor tissues compared with adjacent nontumorous mucosa tissues (P < 0.001). Tumoral CXCL14 expression levels were significantly correlated with TNM (Tumor-node-metastasis) stage, histodifferentiation, and tumor size. In multivariate Cox regression analysis, high CXCL14 expression in tumor specimens (n = 91) from stage I/II patients was associated with increased risk for disease recurrence (risk ratio, 2.92; 95% CI, 1.15-7.40; P = 0.024). Elevated CXCL14 expression in tumor specimens (n = 135) from stage III/IV patients correlated with worse overall survival (risk ratio, 3.087; 95% CI, 1.866-5.107; P < 0.001). Functional studies demonstrated that enforced expression of CXCL14 in SW620 colorectal carcinoma cells resulted in more aggressive phenotypes. In contrast, knockdown of CXCL14 expression could mitigate the proliferative, migratory and invasive potential of HCT116 colorectal carcinoma cells. Conclusion Taken together, CXCL14 might be a potential novel prognostic factor to predict the disease recurrence and overall survival and could be a

  5. Adrenalectomy for solitary adrenal metastasis from colorectal cancer: A case report

    PubMed Central

    Kosmidis, Christopher; Efthimiadis, Christopher; Anthimidis, George; Levva, Sofia; Ioannidou, Georgia; Zaramboukas, Thomas; Emmanouilides, Christos; Baka, Sofia; Kosmidou, Maria; Basdanis, Georgios; Fachantidis, Epaminondas

    2008-01-01

    Background Patients with adrenal metastasis from various primary tumours are regarded as cases of diffuse systemic spread and considered unsuitable for surgical resection. We herein report an operable case of heterochronic adrenal metastasis from colorectal carcinoma in a 63-year-old woman. Case presentation Sixteen months after low anterior resection for the primary tumour, left lower pneumonectomy was performed for a solitary lung metastasis. Four months later a right adrenal metastasis was detected by magnetic resonance imaging (MRI), as sole evidence of metastatic disease. A right adrenalectomy was performed. The histopathological examination revealed adenocarcinoma compatible with the colorectal carcinoma resected 19 months earlier. The patient received adjuvant chemotherapy after each operation and is alive and free of disease 21 months after the adrenalectomy. Conclusion The possibility of adrenal metastasis should be considered in the follow-up of patients after primary surgery for colorectal cancer, even though other sites are the main metastatic sites. Although the prognosis of adrenal metastasis from colorectal cancer is poor, we suggest that patients with solitary adrenal metastasis may benefit from complete removal of it. PMID:18638404

  6. [Malignant tumors of the colon and rectum].

    PubMed

    Komljenović, Zoran; Prodanović, Lazar; Lukić, Vladan; Randelović, Tomo; Drljević, Milorad; Rakić, Mile

    2003-01-01

    The authors present their five year long experience in surgical treatment of colorectal cancer at Zvornik Health Center. 77 patients diagnosed with colorectal cancer underwent surgery during the five year period (1998-2002). This number represented about 2% of the total number of surgeries performed during the same time period. 80% of surgical interventions were elective, (82 patients), and 20% urgent (35 patients). Standard surgical procedures were applied in determining of the anatomical location of the pathological substrate. Aggravating factors in successful application of surgical intervention in treatment of colorectal cancer are: late diagnosis of colorectal cancer, low level of health education of the population, inadequate training of the physicians in primary health care, nonexistent national program for early detection of noninfectious diseases. In cases where colorectal cancer was diagnosed in an advanced stage, two-stage treatment and multi modal approach in combination with chemotherapy were treatments of choice. Incidence of colorectal cancer is still on the rise. PMID:14569684

  7. Association of a genetic variant in microRNA-146a with risk of colorectal cancer: a population-based case-control study.

    PubMed

    Mao, Yingying; Li, Yingjun; Jing, Fangyuan; Cai, Shaofang; Zhang, Zhenyu; Li, Qilong; Ma, Xinyuan; Wang, Jianbing; Jin, Mingjuan; Chen, Kun

    2014-07-01

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate target gene expression at the posttranscriptional level. Although recent studies have indicated that miR-146a is involved in the tumorigenesis of various types of malignancies, few studies have investigated its role in colorectal cancer. In the current study, we examined the expression of miR-146a in colorectal cancer tissue and adjacent normal controls using publicly available expression profiling data. We then conducted a population-based case-control study which included 554 colorectal cancer cases and 566 matched healthy controls to assess the association of a genetic variant (rs2910164) in miR-146a with colorectal cancer susceptibility. We observed decreased expression of miR-146a in rectal cancer tissue compared with adjacent normal controls (P < 0.001). Association between miR-146a rs2910164 polymorphism and risk of colorectal cancer was detected with effect modification by alcohol drinking status (P for interaction = 0.010). Among non-alcohol drinkers, individuals with CC/CG genotype had an increased risk of developing colorectal cancer compared with those carrying GG genotype (odds ratio (OR) = 1.63, 95 % confidence interval (CI): 1.07 ∼ 2.47). Our findings indicate an association between miR-146a dysregulation and colorectal cancer, and suggest that miR-146a may play a role in colorectal carcinogenesis. Further large population-based prospective studies as well as mechanistic investigations are warranted to validate our findings. PMID:24740563

  8. Bcl-B Expression in Human Epithelial and Nonepithelial Malignancies

    PubMed Central

    Krajewska, Maryla; Kitada, Shinichi; Winter, Jane N.; Variakojis, Daina; Lichtenstein, Alan; Zhai, Dayong; Cuddy, Michael; Huang, Xianshu; Luciano, Frederic; Baker, Cheryl H.; Kim, Hoguen; Shin, Eunah; Kennedy, Susan; Olson, Allen H.; Badzio, Andrzej; Jassem, Jacek; Meinhold-Heerlein, Ivo; Duffy, Michael J.; Schimmer, Aaron D.; Tsao, Ming; Brown, Ewan; Sawyers, Anne; Andreeff, Michael; Mercola, Dan; Krajewski, Stan; Reed, John C.

    2014-01-01

    Purpose Apoptosis plays an important role in neoplastic processes. Bcl-B is an antiapoptotic Bcl-2 family member, which is known to change its phenotype upon binding to Nur77/TR3. The expression pattern of this protein in human malignancies has not been reported. Experimental Design We investigated Bcl-B expression in normal human tissues and several types of human epithelial and nonepithelial malignancy by immunohistochemistry, correlating results with tumor stage, histologic grade, and patient survival. Results Bcl-B protein was strongly expressed in all normal plasma cells but found in only18%of multiple myelomas (n = 133). Bcl-B immunostaining was also present in normal germinal center centroblasts and centrocytes and in approximately half of diffuse large B-cell lymphoma (n =48) specimens, whereas follicular lymphomas (n = 57) did not contain Bcl-B. In breast (n = 119), prostate (n = 66), gastric (n = 180), and colorectal (n = 106) adenocarcinomas, as well as in non – small cell lung cancers (n = 82), tumor-specific overexpression of Bcl-B was observed. Bcl-B expression was associated with variables of poor prognosis, such as high tumor grade in breast cancer (P = 0.009), microsatellite stability (P = 0.0002), and left-sided anatomic location (P = 0.02) of colorectal cancers, as well as with greater incidence of death from prostate cancer (P = 0.005) and shorter survival of patients with small cell lung cancer (P = 0.009). Conversely, although overexpressed in many gastric cancers, Bcl-B tended to correlate with better outcome (P = 0.01) and more differentiated tumor histology (P < 0.0001). Conclusions Tumor-specific alterations in Bcl-B expressionmay define subsets of nonepithelial and epithelial neoplasms with distinct clinical behaviors. PMID:18483366

  9. Colorectal Cancer Screening in Vietnamese Americans

    PubMed Central

    Nguyen, Bang H.

    2008-01-01

    Background Rates of colorectal cancer screening in Vietnamese Americans are lower than those in non-Hispanic whites. This paper describes rates of colorectal screening, identifies determinants, and recommends educational strategies to improve screening. Methods A cross-sectional sample of 867 Vietnamese aged 50 to 74 drawn from a sampling frame of individuals in the Alameda and Santa Clara Counties, California and Harris County, Texas area telephone directories with Vietnamese surnames were interviewed in 2004. Results Colorectal screening recognition, receipt, currency, and intention rates were low. Conclusions: While the screening rates are low, Vietnamese are receptive to screening if providers recommend it. PMID:18444045

  10. Sunburn and malignant melanoma.

    PubMed Central

    Green, A.; Siskind, V.; Bain, C.; Alexander, J.

    1985-01-01

    We investigated the relationship between cutaneous malignant melanoma and multiple sunburns in the Queensland population. Interview data were gathered from 236 case-control pairs concerning their lifetime experience of severe sunburns, their occupational and recreational sun exposure, and their skin type. Excluding the lentigo maligna melanoma subtype, an association between multiple sunburns and melanoma was evident. After controlling for other major risk factors there was a significant dose-response relationship (P less than 0.05): the estimated relative risk associated with 2-5 sunburns in life was 1.5, and with 6 or more was 2.4. This observation extends the hitherto circumstantial evidence of a causal relationship between exposure to solar ultraviolet radiation and melanoma, and suggests that precautionary measures could prevent the development of this disease in a proportion of cases in fair-skinned populations. PMID:3970815

  11. 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

  12. Atypical neuroleptic malignant syndrome.

    PubMed

    Collins, Ann; Davies, Drew; Menon, Sharmila

    2016-01-01

    A 57-year-old man was admitted to a psychiatric ward in a confused state. He had a 30-year history of lately stable schizophrenia and antipsychotic medication had recently been reduced. The clinical picture was characterised by confusion, agitation, autonomic instability, muscle rigidity and elevated creatine kinase. Despite no other identifiable cause, physicians were reluctant to accept a diagnosis of neuroleptic malignant syndrome (NMS) due to the absence of fever. Despite acute renal failure, the patient was repeatedly transferred between medical and psychiatric wards; diagnosis and management were delayed, with potentially catastrophic consequences. NMS is a rare, life-threatening neurological disorder that can present atypically and requires emergency medical rather than psychiatric care. Clinicians must proactively distinguish between medical emergencies (including acute confusional states/delirium) and mental illness. Prompt, accurate diagnosis, management on the appropriate ward and effective teamwork between specialties are essential to improve patient outcomes in this potentially fatal condition. PMID:27298291

  13. Evaluation of Screening Strategies for Pre-malignant Lesions using a Biomathematical Approach

    PubMed Central

    Jeon, Jihyoun; Meza, Rafael; Moolgavkar, Suresh H.; Georg Luebeck, E.

    2008-01-01

    We derive mathematical expressions for the size distribution of screen-detectable pre-malignant lesions, both conditional and unconditional on no prior detection of cancer in the tissue of interest, based on a general multistage clonal expansion model of carcinogenesis. We apply these expressions to simulate the natural history of colorectal cancer and to evaluate the effect of a screen for adenomatous polyps and concomitant intervention on cancer risk. Our approach allows the efficient simulation of multiple screens and interventions and determination of the optimal timing of the screens. We further demonstrate the utility of our approach by computing the benefits of up to two colonoscopies on the lifetime risk of colorectal cancer. PMID:18374369

  14. Primary intrahepatic malignant epithelioid mesothelioma

    PubMed Central

    Perysinakis, Iraklis; Nixon, Alexander M.; Spyridakis, Ioannis; Kakiopoulos, George; Zorzos, Charalampos; Margaris, Ilias

    2014-01-01

    INTRODUCTION Primary malignant hepatic mesotheliomas are extremely rare. We report the case of a patient with primary intrahepatic malignant mesothelioma who was treated in our department. PRESENTATION OF CASE A 66-year old male patient was admitted to our department for the evaluation of anemia. An abdominal computed tomography scan revealed a large space occupying lesion in the right liver lobe. DISCUSSION The tumor was subsequently resected and a diagnosis of primary intrahepatic malignant mesothelioma was made after pathologic examination. The patient did not receive adjuvant therapy and is currently alive and free of disease, 36 months after the resection. CONCLUSION To our knowledge this is the eighth adult case of primary intrahepatic malignant mesothelioma reported in the literature. These tumors are rarely diagnosed preoperatively. Absence of previous asbestos exposure does not exclude malignant mesothelioma from the differential diagnosis. Proper surgical treatment may offer prolonged survival to the patient, without adjuvant therapy. PMID:25460485

  15. 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

  16. Clinicopathological Characteristics of Laterally Spreading Colorectal Tumor

    PubMed Central

    Xiang, Li; Wang, Yadong; Wang, Xianfei; Li, Aimin; Liu, Side

    2014-01-01

    Background and Aims Laterally spreading tumor (LST) is a colorectal pre-cancerous lesion. Previous studies have demonstrated distinct LST clinicopathological characteristics in different populations. This study evaluated clinicopathological characteristics of LST in a Chinese population. Methods A total of 259 Chinese LST patients with 289 lesions were recruited for endoscopic and clinicopathological analyses. Results Among these 289 lesions, 185 were granular type (LST-G), whereas 104 were non-granular type (LST-NG). LST-G lesions were further classified into homogeneous G-type and nodular mixed G-type, while LST-NG lesions were further classified into flat elevated NG-type and pseudo-depressed NG-type. Clinically, these four LST subtypes showed distinct clinicopathological characteristics, e.g., lesion size, location, or histopathological features (high-grade intraepithelial neoplasia and submucosal carcinoma). The nodular mixed G-type showed larger tumor size and higher incidence of high-grade intraepithelial neoplasia compared to the other three subtypes, while pseudo-depressed NG-type lesions showed the highest incidence of submucosal carcinoma. Noticeably, no diffidence was detected between the lesions of homogeneous G-type and flat elevated NG-type with regard to the histopathological features. Histology of the malignancy potential was associated with nodular mixed G-type [OR = 2.41, 95% CI (1.09–5.29); P = 0.029], flat elevated NG-type [OR = 3.49, 95% CI (1.41–8.22); P = 0.007], Diameter ≥30 mm [OR = 2.56, 95% CI (1.20–5.20); P = 0.009], Villous adenoma [OR = 2.76, 95% CI (1.01–7.58); P = 0.048] and serrated adenoma [OR = 6.99, 95% CI (1.81–26.98); P = 0.005]. Conclusion Chinese LSTs can be divided into four different subtypes, which show distinct clinicopathological characteristics. Morphology, size and pathological characteristics are all independent predictors of advanced histology. PMID:24751926

  17. 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

  18. Micronucleus analysis in patients with colorectal adenocarcinoma and colorectal polyps

    PubMed Central

    Karaman, Ali; Binici, Doğan Nasır; Kabalar, Mehmet Eşref; Çalıkuşu, Züleyha

    2008-01-01

    AIM: To determine, by counting micronucleus (MN) frequencies, whether chromosomal or DNA damage have an effect on the pathogenesis of early colorectal adenocarcinoma (CRC). METHODS: We analyzed MN frequencies in 21 patients with CRC, 24 patients with colon polyps [10 neoplastic polyps (NP) and 14 non-neoplastic polyps (NNP)] and 20 normal controls. RESULTS: MN frequency was significantly increased in CRC patients and in NP patients compared with controls (3.72 ± 1.34, 3.58 ± 1.21 vs 1.97 ± 0.81, P < 0.001). However, there was no difference in the MN frequency between CRC patients and NP patients (P > 0.05). Similarly, there was no difference in the MN frequency between NNP patients (2.06 ± 0.85) and controls (P > 0.05). CONCLUSION: Our results suggest increased chromosome/DNA instabilities may be associated with the pathogenesis of early CRC. PMID:19058310

  19. The Tumor Microenvironment in Colorectal Carcinogenesis

    PubMed Central

    Peddareddigari, Vijay G.; Wang, Dingzhi

    2010-01-01

    Colorectal cancer is the second leading cause of cancer-related mortality in the United States. Therapeutic developments in the past decade have extended life expectancy in patients with metastatic disease. However, metastatic colorectal cancers remain incurable. Numerous agents that were demonstrated to have significant antitumor activity in experimental models translated into disappointing results in extending patient survival. This has resulted in more attention being focused on the contribution of tumor microenvironment to the progression of a number of solid tumors including colorectal cancer. A more complete understanding of interactions between tumor epithelial cells and their stromal elements will enhance therapeutic options and improve clinical outcome. Here we will review the role of various stromal components in colorectal carcinogenesis and discuss the potential of targeting these components for the development of future therapeutic agents. PMID:21209781

  20. 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

  1. Tests to Detect Colorectal Cancer and Polyps

    MedlinePlus

    ... be acceptable screening tests for colorectal cancer: High-sensitivity fecal occult blood tests (FOBT). Both polyps and ... higher than that of gFOBT or FIT. Test sensitivity for adenomas is low. False-positive test results ...

  2. 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.

  3. Non-coding RNAs Functioning in Colorectal Cancer Stem Cells.

    PubMed

    Fanale, Daniele; Barraco, Nadia; Listì, Angela; Bazan, Viviana; Russo, Antonio

    2016-01-01

    In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main signaling pathways involved in the homeostasis of colorectal (CRC) stem cells are the Wnt, Notch, Sonic Hedgehog, and Bone Morfogenic Protein (BMP) pathways, which are mostly responsible for all the features that have been widely referred to stem cells. The same pathways have been identified in colorectal cancer stem cells (CRCSCs), conferring a more aggressive phenotype compared to non-stem CRC cells. Recently, several evidences suggested that non-coding RNAs (ncRNAs) may play a crucial role in the regulation of different biological mechanisms in CRC, by modulating the expression of critical stem cell transcription factors that have been found active in CSCs. In this chapter, we will discuss the involvement of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in stemness acquisition and maintenance by CRCSCs, through the regulation of pathways modulating the CSC phenotype and growth, carcinogenesis, differentiation, and epithelial to mesenchymal transition (EMT). PMID:27573896

  4. Human Blood Autoantibodies in the Detection of Colorectal Cancer.

    PubMed

    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

  5. 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

  6. 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

  7. 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

  8. Unique complications of robotic colorectal surgery.

    PubMed

    Ramamoorthy, Sonia; Obias, Vincent

    2013-02-01

    Robotic approaches in all surgical realms have seen tremendous growth over the previous few years. Taking advantage of 3-dimensional visualization, improved articulation, and the opportunity for an enhanced ability to suture/operate in the deep pelvis all provide theoretical and real advantages in colorectal surgery. This article reviews the potential advantages and disadvantages, current indications, future directions, and lessons learned for robotic approaches in colorectal surgery. PMID:23177076

  9. 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

  10. Clinicopathological significance of vascular endothelial growth factor, thymidine phosphorylase and microvessel density in colorectal cancer.

    PubMed

    Kimura, Yutaka; Morohashi, Satoko; Yoshizawa, Tadashi; Suzuki, Takahiro; Morohashi, Hajime; Sakamoto, Yoshiyuki; Koyama, Motoi; Murata, Akihiko; Kijima, Hiroshi; Hakamada, Kenichi

    2016-02-01

    Colorectal cancer is a common malignant disease, the incidence of which is increasing worldwide, therefore, identifying novel prognostic factors to improve adjuvant therapeutic strategies or postoperative monitoring is required. Angiogenesis, which is assessed by microvessel density (MVD), is significant in tumor growth and metastasis. However, the association between angiogenesis and clinical outcome remains controversial. In the present study, 84 surgically resected cases of colorectal cancer were examined to clarify the clinicopathological significance of vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cluster of differentiation (CD)34 expression levels. VEGF expression was identified to be significantly correlated with TP expression (r=0.45; P<0.0001) and MVD in the high VEGF expression group was observed to be significantly greater than that in the low VEGF expression group (P=0.0194). In the Dukes' stage D group, the MVD in the high TP expression group was significantly greater than that in the low TP expression group (P=0.0149). High VEGF expression was subsequently correlated with a short overall survival rate for patients exhibiting lymph node metastasis (P=0.0128); however, there was no significant difference in overall survival rate regarding the expression levels of TP and CD34. The results of the present study indicate that VEGF expression may serve as a prognostic factor for colorectal cancer patients exhibiting lymph node metastasis. Furthermore, angiogenesis, as assessed by MVD, is an important prognostic factor for tumor growth at the primary site. PMID:26676225

  11. 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

    2016-03-11

    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. PMID:25849747

  12. Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis.

    PubMed

    Lin, Jiumao; Wei, Lihui; Shen, Aling; Cai, Qiaoyan; Xu, Wei; Li, Huang; Zhan, Youzhi; Hong, Zhenfeng; Peng, Jun

    2013-02-01

    Sonic hedgehog (SHH) signaling pathway promotes the process of angiogenesis, contributing to the growth and progression of many human malignancies including colorectal cancer (CRC), which therefore has become a promising target for cancer chemotherapy. Hedyotis diffusa Willd (HDW), as a well-known traditional Chinese herbal medicine, has long been used in China for the clinic treatment of various cancers. Recently, we reported that HDW can inhibit colorectal cancer growth in vivo and in vitro via suppression of the STAT3 pathway. In addition, we demonstrated the anti-angiogenic activity of HDW in vitro. To further elucidate the mechanism of the tumoricidal activity of HDW, by using a CRC mouse xenograft model we evaluated the in vivo effect of the ethanol extract of HDW (EEHDW) on tumor angiogenesis, and investigated the underlying molecular mechanisms. We found that EEHDW could significantly reduce intratumoral microvessel density (MVD), indicating its activity of antitumor angiogenesis in vivo. EEHDW suppressed the activation of SHH signaling in CRC xenograft tumors since it significantly decreased the expression of key mediators of SHH pathway. EEHDW treatment inhibited the expression of the critical SHH signaling target gene VEGF-A as well as its specific receptor VEGFR2. Taken together, we propose for the first time that Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of SHH-mediated tumor angiogenesis. PMID:23291612

  13. 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. PMID:23259783

  14. 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

  15. 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

  16. Meta-analysis of diffusion-weighted magnetic resonance imaging in identification of colorectal cancer

    PubMed Central

    Jia, Hongyuan; Ma, Xuelei; Zhao, Yang; Zhao, Jingyi; Liu, Rongjun; Chen, Zihang; Chen, Jinna; Huang, Jingwen; Li, Yanyan; Zhang, Jing; Wang, Feng

    2015-01-01

    Purpose: This meta-analysis aimed to evaluate the performance of diffusion-weighted magnetic resonance imaging (DWI) in identification of colorectal cancer. Methods: A systematic literature search was performed for studies that evaluated the diagnostic accuracy of DWI in identification of colorectal cancer. Methodological quality was assessed by Quality Assessment for Studies of Diagnostic Accuracy 2 (QUADAS 2) tool. After extracting data, we estimated the pooled sensitivity, specificity, likelihood ratios, and constructed summary receiver operating characteristics (SROC) curve. Results: Ten studies involving 367 malignant lesions and 178 benign lesions were considered eligible after full-text review. The pooled sensitivity and specificity were 0.95 (95% CI: 0.90-0.97) and 0.93 (95% CI: 0.85-0.97), respectively. Positive likelihood ratio and negative likelihood ratio were 12.8 (95% CI: 5.99-27.4) and 0.06 (95% CI: 0.03-0.11), respectively. The area under SROC curve was 0.98. Conclusions: Our meta-analysis indicates that DWI is a highly accurate diagnostic method in identification of colorectal cancer. PMID:26770325

  17. 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. PMID:15075784

  18. Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma.

    PubMed

    Starzynska, T; Marsh, P J; Schofield, P F; Roberts, S A; Myers, K A; Stern, P L

    1994-05-01

    The 5T4 oncofetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumour cells and metastatic spread. The 5T4 antigen phenotype of 72 colorectal cancers has been compared with the clinical outcome of the patients in order to assess its relationship with prognosis. Forty per cent of tumours were 5T4 positive; the remainder were either unlabelled or exhibited stroma-associated labelling only. There was a significant correlation between 5T4 expression in the malignant cells and unfavourable course of disease (P < 0.001). The 5 year survival with 5T4-positive tumours was 22% compared with 75% for patients with 5T4-negative tumours; median survival was 24 versus > 90 months respectively. Stratified analysis showed that 5T4 antigen tumour positivity was acting independently of each of stage, site of tumour, age or sex. There were significant differences in survival for patients with Dukes' B and C stage carcinomas (P = 0.001 and P = 0.034). The results suggest that in colorectal cancer immunohistochemical assessment of 5T4 expression may be useful in identifying patients at high risk for tumour recurrence and for whom additional treatment strategies might be most appropriate. PMID:8180020

  19. Increase in apoptosis by combination of metformin with silibinin in human colorectal cancer cells

    PubMed Central

    Tsai, Cheng-Chia; Chuang, Tang-Wei; Chen, Li-Jen; Niu, Ho-Shan; Chung, Kun-Ming; Cheng, Juei-Tang; Lin, Kao-Chang

    2015-01-01

    AIM: To investigate the effect of metformin on silibinin-induced apoptosis in human colorectal cancer (COLO 205) cells. METHODS: MTT assays were performed to quantify cell viability. Western blot assays were applied to identify the expression of signaling proteins. RESULTS: The combined treatment of COLO 205 cells with metformin and silibinin decreased cell survival at a dose insufficient to influence the non-malignant cells [Human colonic epithelial cells (HCoEpiC)]. Silibinin and metformin increased phosphatase and tensin homolog and 5’-adenosine monophosphate-activated protein kinase expression in COLO 205 cells and inhibited the phosphorylation of mammol/Lalian target of rapamycin. This combined treatment resulted in an increase in the expression of activated caspase 3 and apoptosis inducing factor, indicating apoptosis. CONCLUSION: The combined treatment of human colorectal cancer cells with silibinin and metformin may induce apoptosis at a dose that does not affect HCoEpiC. This finding reveals a potential therapeutic strategy for the treatment of colorectal cancer. PMID:25892866

  20. Laparoscopic Colorectal Resection in Octogenarian Patients

    PubMed Central

    Xie, Minghao; Qin, Huabo; Luo, Qianxin; He, Xiaosheng; Lan, Ping; Lian, Lei

    2015-01-01

    Abstract The population older than 80 years has been increasing. A significant proportion of colorectal diseases that require colorectal resection occur in very elderly patients. However, the benefits of laparoscopy remain controversial in octogenarians. A systematic review and meta-analysis of observational study was performed to compare clinical outcomes between laparoscopic versus open colorectal resection in octogenarians. The PubMed, EMBASE, Ovid, Web of Science, and Cochrane databases from the years 1990 to 2015 were searched for studies that compare surgical outcomes between laparoscopic and open colorectal resection in octogenarians (≥80 years old). Seven eligible studies including 528 laparoscopic and 484 open colorectal resections were identified. Laparoscopic approach was associated with lower rate of mortality (odds ratio [OR] 0.48, P = 0.03), overall complications (OR 0.54, P < 0.001), and prolonged ileus (OR 0.56, P = 0.009), quicker bowel function return (standardized mean difference [SMD] −0.50, P < 0.001), and shorter length of hospital stay (SMD −0.47, P = 0.007). No differences were found in anastomotic leak (OR 1.16, P = 0.72), respiratory complication (OR 0.60, P = 0.07), and reoperation (OR 0.85, P = 0.69). Laparoscopic colorectal resection is as safe as open approach, and the short-term outcomes appear to be more favorable in octogenarians. PMID:26496302

  1. 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

  2. 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

  3. Variation in the Association Between Colorectal Cancer Susceptibility Loci and Colorectal Polyps by Polyp Type

    PubMed Central

    Burnett-Hartman, Andrea N.; Newcomb, Polly A.; Hutter, Carolyn M.; Peters, Ulrike; Passarelli, Michael N.; Schwartz, Malaika R.; Upton, Melissa P.; Zhu, Lee-Ching; Potter, John D.; Makar, Karen W.

    2014-01-01

    We conducted a case-control study of the association between subsets of colorectal polyps, including adenomas and serrated polyps, and single-nucleotide polymorphisms (SNPs) related to colorectal cancer through prior genome-wide association studies (GWAS). Participants were enrollees in the Group Health Cooperative (Seattle, Washington) aged 24–79 years who received a colonoscopy from 1998 to 2007, donated a buccal or blood sample, and completed a structured questionnaire. We performed genotyping of 13 colorectal cancer susceptibility SNPs. Polytomous logistic regression models were used to estimate odds ratios and 95% confidence intervals for associations between polyps and the colorectal cancer risk allele for each SNP under a log-additive model. Analyses included 781 controls, 489 cases with adenoma, 401 cases with serrated polyps, and 188 cases with both polyp types. The following SNPs were associated with advanced adenomas: rs10936599, rs10795668, rs16892766, and rs9929218 (P < 0.05). For nonadvanced adenomas and for serrated polyps overall, only rs961253 was statistically significant (P < 0.05). These associations were in the same directions as those in prior colorectal cancer GWAS. No SNP was significantly associated with hyperplastic polyps, and only rs6983267 was significantly associated with sessile serrated polyps, but this association was opposite of that found in colorectal cancer GWAS. Our results suggest that the association between colorectal cancer susceptibility SNPs and colorectal polyps varies by polyp type. PMID:24875374

  4. 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…

  5. Childhood ovarian malignancy.

    PubMed

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-04-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4 and karyopherin-2 (KPNA2) have been helpful in differentiating ovarian yolk sac tumor from dysgerminoma, teratomas, and other pictures of hepatoid, endometrioid, clear cell carcinomatous, and adenocarcinomatous tissues with varied malignant potential. Before platinum therapy, these tumors were almost fatal in children. Fertility-conserving surgery with bleomycin, etoposide, and cisplatin has dramatically changed the survival rates in these patients. This modality gives cancer cure with healthy offspring to female patients with childhood ovarian tumor. Evidence also supports this protocol resulting in successful pregnancy rates and safety of cytotoxic drugs in children born to these patients. PMID:24757335

  6. [Malignant Pleural Mesotheliomas].

    PubMed

    Biancosino, C; Redwan, B; Krüger, M; Eberlein, M; Bölükbas, S

    2016-09-01

    Malignant pleural mesotheliomas (MPM) are very aggressive tumors, which originate from the mesothelial cells of the pleural surface. The main risk factor associated with MPM is exposure to asbestos. The latency period between asbestos exposure and MPM can be 30-60 years. Clinical symptoms and signs are often nonspecifc. The diagnosis of MPM requires an adequate tissue specimen for pathological examination, and video assisted thoracoscopic surgey (VATS) is associated with the highest diagnostic yield. MPM are histologically classified into epitheloid, sacromatoid and biphasic (mixed) sub-types. Accurate staging with invasive tests, if needed, is an important step before an interdisciplinary team can decide on an optimal (multi-modal) treatment approach. A multi-modal treatment approach (surgery, radiation oncology and chemotherapy) is superior to all approaches relying only on a single modality, if the patient qualifies for it from an oncological and functional standpoint. The goal of the surgical therapy is to achieve macroscopic complete resection. There are two competing surgical approaches and philosophies: extrapleural pneumonectomy (EPP) and radical pleurectomy (RP). Over the last years a paradigm shift from EPP to RP occurred and RP is now often the preferred surgical option. PMID:27612329

  7. Combined inhibition of MEK and Aurora A kinase in KRAS/PIK3CA double-mutant colorectal cancer models.

    PubMed

    Davis, S Lindsey; Robertson, Kelli M; Pitts, Todd M; Tentler, John J; Bradshaw-Pierce, Erica L; Klauck, Peter J; Bagby, Stacey M; Hyatt, Stephanie L; Selby, Heather M; Spreafico, Anna; Ecsedy, Jeffrey A; Arcaroli, John J; Messersmith, Wells A; Tan, Aik Choon; Eckhardt, S Gail

    2015-01-01

    Aurora A kinase and MEK inhibitors induce different, and potentially complementary, effects on the cell cycle of malignant cells, suggesting a rational basis for utilizing these agents in combination. In this work, the combination of an Aurora A kinase and MEK inhibitor was evaluated in pre-clinical colorectal cancer models, with a focus on identifying a subpopulation in which it might be most effective. Increased synergistic activity of the drug combination was identified in colorectal cancer cell lines with concomitant KRAS and PIK3CA mutations. Anti-proliferative effects were observed upon treatment of these double-mutant cell lines with the drug combination, and tumor growth inhibition was observed in double-mutant human tumor xenografts, though effects were variable within this subset. Additional evaluation suggests that degree of G2/M delay and p53 mutation status affect apoptotic activity induced by combination therapy with an Aurora A kinase and MEK inhibitor in KRAS and PIK3CA mutant colorectal cancer. Overall, in vitro and in vivo testing was unable to identify a subset of colorectal cancer that was consistently responsive to the combination of a MEK and Aurora A kinase inhibitor. PMID:26136684

  8. Differences in T-cell immunity toward tumor-associated antigens in colorectal cancer and breast cancer patients.

    PubMed

    Nagorsen, Dirk; Scheibenbogen, Carmen; Schaller, Gerhard; Leigh, Binta; Schmittel, Alexander; Letsch, Anne; Thiel, Eckhard; Keilholz, Ulrich

    2003-06-10

    There is increasing evidence that tumors elicit specific T-cell responses in a substantial proportion of patients. Recently, we have shown that in patients with colorectal cancer specific T cells against the tumor-associated antigens (TAA) Ep-CAM, her-2/neu or CEA can be detected in peripheral blood using IFNgamma-ELISPOT assay. In our study, we have analyzed T-cell responses against HLA-A*0201-restricted epitopes of these TAA in peripheral blood of patients with breast cancer and colorectal cancer. Surprisingly, a complete absence of ex vivo T-cell responses against these TAA was found in 20 patients with breast cancer. In contrast, specific T cells were detectable in 12 of 49 patients with colorectal cancer against at least 1 of these TAA, confirming our previous results. T-cell responses against influenza-derived peptides were similar in both malignancies. The results of our study indicate a difference either of tumor immunogenicity or of the migratory pattern of tumor-specific T cells between breast cancer and colorectal cancer patients. The findings reported here have implications for the development of antigen-specific T-cell therapies. PMID:12673683

  9. High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell

    PubMed Central

    Shin, Young-Joo; Kim, Mi-Sook; Kim, Moon-Sun; Lee, Joonseok; Kang, Miae; Jeong, Jae-Hoon

    2013-01-01

    Overexpression of high-mobility group box 2 (HMGB2) is recently reported in several malignant cancers and was correlated with poor response to preoperative chemoradiotherapy of colorectal cancer patients. To enhance the chemoradiotherapy efficacy, the biological function of HMGB2 was investigated with respect to radiation response. HMGB2 gene knockdown cells were constructed by infecting shRNA expressing lentivirus and clonogenic assay was performed to count the radiosensitivity. HMGB2 knockdown sensitized HCT-116 and HT-29 colorectal cancer cells to ionizing radiation. This could be due to an increased DNA damage and an inefficient DNA damage repair in HMGB2 knockdown cells. In addition, an exposure to radiation downregulated HMGB2 expression in colorectal cancer cells with an intact TP53 gene. HMGB2 gene expression of TP53-mutant cell was not affected by irradiation. p53-mediated downregulation of HMGB2 was confirmed by direct activation of p53 using Nutlin-3 or by inducing p53 expression using Tet-On system. Luciferase reporter assay showed that HMGB2 promoter activity was inversely correlated with the amount p53 cotransfected. Our study revealed that HMGB2 is necessary to protect colorectal cancer cells from DNA damage and efficient DNA repair and p53-mediated downregulation is a critical mechanism of modulating HMGB2 expression. PMID:23255232

  10. Combined inhibition of MEK and Aurora A kinase in KRAS/PIK3CA double-mutant colorectal cancer models

    PubMed Central

    Davis, S. Lindsey; Robertson, Kelli M.; Pitts, Todd M.; Tentler, John J.; Bradshaw-Pierce, Erica L.; Klauck, Peter J.; Bagby, Stacey M.; Hyatt, Stephanie L.; Selby, Heather M.; Spreafico, Anna; Ecsedy, Jeffrey A.; Arcaroli, John J.; Messersmith, Wells A.; Tan, Aik Choon; Eckhardt, S. Gail

    2015-01-01

    Aurora A kinase and MEK inhibitors induce different, and potentially complementary, effects on the cell cycle of malignant cells, suggesting a rational basis for utilizing these agents in combination. In this work, the combination of an Aurora A kinase and MEK inhibitor was evaluated in pre-clinical colorectal cancer models, with a focus on identifying a subpopulation in which it might be most effective. Increased synergistic activity of the drug combination was identified in colorectal cancer cell lines with concomitant KRAS and PIK3CA mutations. Anti-proliferative effects were observed upon treatment of these double-mutant cell lines with the drug combination, and tumor growth inhibition was observed in double-mutant human tumor xenografts, though effects were variable within this subset. Additional evaluation suggests that degree of G2/M delay and p53 mutation status affect apoptotic activity induced by combination therapy with an Aurora A kinase and MEK inhibitor in KRAS and PIK3CA mutant colorectal cancer. Overall, in vitro and in vivo testing was unable to identify a subset of colorectal cancer that was consistently responsive to the combination of a MEK and Aurora A kinase inhibitor. PMID:26136684

  11. 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. PMID:25782566

  12. Increased expression of multidrug resistance related proteins Pgp, MRP1, and LRP/MVP occurs early in colorectal carcinogenesis.

    PubMed Central

    Meijer, G A; Schroeijers, A B; Flens, M J; Meuwissen, S G; van der Valk, P; Baak, J P; Scheper, R J

    1999-01-01

    AIM: To analyse the expression of multidrug resistance (MDR) related proteins at different steps in colorectal carcinogenesis. METHODS: The presence of three MDR related proteins (Pgp, MRP1, and LRP/MVP) was studied by means of immunohistochemistry in normal, adenomatous, and malignant colorectal epithelium. Formaldehyde fixed, paraffin embedded tissue sections of 17 samples of colorectal tissue were used (normal mucosa, n = 4; adjacent mucosa, n = 5; adenoma, n = 5; carcinoma, n = 3). RESULTS: For all three proteins, expression was found in the surface epithelium and the upper parts of the crypts in normal colon. In the adenomas, staining was seen along the complete length of the crypts. In the carcinomas analysed, all epithelium showed positive staining. Mucosa adjacent to either carcinoma or adenoma showed staining patterns mostly resembling those of normal mucosa, but sometimes some extension of staining was seen along the crypt. CONCLUSIONS: These proteins already show increased expression in the adenoma stage. In the absence of adequate mucin production in adenomas, MDR related proteins could be an important factor in protecting the epithelium against further environmentally induced genetic damage. This could be one of the reasons why only about 5% of colorectal adenomas will actually progress to carcinomas. Images PMID:10562814

  13. DNA Methylation and Colorectal Cancer

    PubMed Central

    Ashktorab, Hassan; Brim, Hassan

    2014-01-01

    Colorectal cancer (CRC) is one of the major cancers in the world and second death-causing cancer in the US. CRC development involves genetic and epigenetic alterations. Changes in DNA methylation status are believed to be involved at different stages of CRC. Promoter silencing via DNA methylation and hypomethylation of oncogenes alter genes’ expression, and can be used as a tool for the early detection of colonic lesions. DNA methylation use as diagnostic and prognostic marker has been described for many cancers including CRC. CpG Islands Methylator Phenotype (CIMP) is one of the underlying CRC mechanisms. This review aims to define methylation signatures in CRC. The analysis of DNA methylation profile in combination with the pathological diagnosis would be useful in predicting CRC tumors’ evolution and their prognostic behavior. PMID:25580099

  14. Targeted nanoparticles for colorectal cancer.

    PubMed

    Cisterna, Bruno A; Kamaly, Nazila; Choi, Won Il; Tavakkoli, Ali; Farokhzad, Omid C; Vilos, Cristian

    2016-09-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could take advantage of differentially expressed molecules on the surface of tumor cells, providing effective release of cytotoxic drugs. Several efforts have recently reported the use of diverse molecules as ligands on the surface of nanoparticles to interact with the tumor cells, enabling the effective delivery of antitumor agents. Here, we present recent advances in targeted nanoparticles against CRC and discuss the promising use of ligands and cellular targets in potential strategies for the treatment of CRCs. PMID:27529192

  15. Translation initiation in colorectal cancer.

    PubMed

    Parsyan, Armen; Hernández, Greco; Meterissian, Sarkis

    2012-06-01

    Colorectal cancers (CRC) are one of the most common causes of morbidity and mortality in high-income countries. Targeted screening programs have resulted in early treatment and a substantial decrease in mortality. However, treatment strategies for CRC still require improvement. Understanding the etiology and pathogenesis of CRC would provide tools for improving treatment of patients with this disease. It is only recently that deregulation of the protein synthesis apparatus has begun to gain attention as a major player in cancer development and progression. Among the numerous steps of protein synthesis, deregulation of the process of translation initiation appears to play a key role in cancer growth and proliferation. This manuscript discusses a fascinating and rapidly growing field exploring translation initiation as a fundamental component in CRC development and progression and summarizing CRC treatment perspectives based on agents targeting translation initiation. PMID:22418835

  16. Biomarkers in Colorectal Cancer Screening.

    PubMed

    Nguyen, Minhhuyen T; Weinberg, David S

    2016-08-01

    Colorectal cancer (CRC) is the third most common cause of cancer death in men and women in the United States. The main goals of screening are to prevent carcinogenesis (via adenoma detection and removal) and detect cancer at an early, curable stage. CRC mortality is steadily dropping in the United States, partly because of greater screening utilization. However, nearly 1 in 3 average-risk people are not up to date with standard CRC screening recommendations. This review surveys a wide range of CRC biomarkers in various stages of development, which may offer attractive risk stratification tools; a few have reached the commercial stage. If widely accepted, these tools may contribute to shift CRC screening practices away from 1-step colonoscopy to a 2-step risk stratification process of predictive biomarker measurements followed by colonoscopy for lower-risk patients with a positive result. Such strategies could potentially increase the rate of CRC screening. PMID:27496118

  17. Autophagy in colorectal cancer: An important switch from physiology to pathology

    PubMed Central

    Burada, Florin; Nicoli, Elena Raluca; Ciurea, Marius Eugen; Uscatu, Daniel Constantin; Ioana, Mihai; Gheonea, Dan Ionut

    2015-01-01

    Colorectal cancer (CRC) remains a leading cause of cancer death in both men and women worldwide. Among the factors and mechanisms that are involved in the multifactorial etiology of CRC, autophagy is an important transformational switch that occurs when a cell shifts from normal to malignant. In recent years, multiple hypotheses have been considered regarding the autophagy mechanisms that are involved in cancer. The currently accepted hypothesis is that autophagy has dual and contradictory roles in carcinogenesis, but the precise mechanisms leading to autophagy in cancer are not yet fully defined and seem to be context dependent. Autophagy is a surveillance mechanism used by normal cells that protects them from the transformation to malignancy by removing damaged organelles and aggregated proteins and by reducing reactive oxygen species, mitochondrial abnormalities and DNA damage. However, autophagy also supports tumor formation by promoting access to nutrients that are critical to the metabolism and growth of tumor cells and by inhibiting cellular death and increasing drug resistance. Autophagy studies in CRC have focused on several molecules, mainly microtubule-associated protein 1 light chain 3, beclin 1, and autophagy related 5, with conflicting results. Beneficial effects were observed for some agents that modulate autophagy in CRC either alone or, more often, in combination with other agents. More extensive studies are needed in the future to clarify the roles of autophagy-related genes and modulators in colorectal carcinogenesis, and to develop potential beneficial agents for the prognosis and treatment of CRC. PMID:26600927

  18. Colorectal (Colon) Cancer: Questions to Ask Your Doctor

    MedlinePlus

    ... Stay Informed Cancer Home Questions to Ask Your Doctor About Colorectal Cancer Language: English Español (Spanish) Recommend ... helps pay for colorectal cancer screening. Ask Your Doctor Do I need to get a screening test ...

  19. What Should You Ask Your Doctor about Colorectal Cancer?

    MedlinePlus

    ... colorectal cancer survivor What should you ask your doctor about colorectal cancer? It’s important to have frank, ... treatment? Do I need to see any other doctors or health professionals? If I’m concerned about ...

  20. Korean Guidelines for Colorectal Cancer Screening and Polyp Detection

    PubMed Central

    Lee, Bo-In; Hong, Sung Pil; Kim, Seong-Eun; Kim, Se Hyung; Hong, Sung Noh; Yang, Dong-Hoon; Shin, Sung Jae; Lee, Suck-Ho; Park, Dong Il; Kim, Young-Ho; Kim, Hyun Jung; Yang, Suk-Kyun; Kim, Hyo Jong; Jeon, Hae Jeong

    2012-01-01

    Now colorectal cancer is the second most common cancer in males and the fourth most common cancer in females in Korea. Since most of colorectal cancers occur after the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are one of the most effective methods to prevent colorectal cancer. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish Korean guideline for colorectal cancer screening and polyp detection. The guideline was developed by the Korean Multi-Society Take Force and we tried to establish the guideline by evidence-based methods. Parts of the statements were draw by systematic reviews and meta-analyses. Herein we discussed epidemiology of colorectal cancers and adenomas in Korea and optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations. PMID:22741131

  1. Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance.

    PubMed Central

    Tollenaar, R. A.; van Krieken, J. H.; van Slooten, H. J.; Bruinvels, D. J.; Nelemans, K. M.; van den Broek, L. J.; Hermans, J.; van Dierendonck, J. H.

    1998-01-01

    To evaluate the prognostic significance of immunohistochemically detected p53 and Bcl-2 proteins in colorectal cancer, tissue sections from 238 paraffin-embedded colorectal carcinomas were immunostained for p53 (MAb DO-7 and CM-1 antiserum) and Bcl-2 (MAb Bcl-2:124). Staining patterns were assessed semiquantitatively and correlated with each other and with sex, age, tumour site, Dukes' classification, tumour differentiation, mucinous characteristics, lymphocyte and eosinophilic granulocyte infiltration, and patient survival. In our series, 35% of carcinomas showed no nuclear staining and 34% (DO-7) to 40% (CM-1) showed staining in over 30% of tumour cell nuclei. A majority of carcinomas that had been immunostained with CM-1 showed cytoplasmic staining, but this was not observed with DO-7. With respect to Bcl-2, 51% of tumours were completely negative, 32% displayed weak and 15% moderate staining; only 3% showed strong positive staining. No evidence was found for reciprocity between Bcl-2 expression and nuclear p53 accumulation. From 13 cases containing tumour-associated adenoma, four were Bcl-2 negative in premalignant and malignant cells, in another four cases these cells showed similar staining intensities and in the remaining cases only the malignant colorectal cells were Bcl-2 negative. Therefore, our data indicate that Bcl-2 is dispensable in the progression towards carcinoma. Except for an association between nuclear p53 accumulation and mucinous tumours (P = 0.01), no significant correlation was found between the clinicopathological parameters mentioned above and immunostaining pattern of (nuclear or cytoplasmic) p53 or Bcl-2. PMID:9667656

  2. Bile duct malignancies.

    PubMed

    Tucek, S; Tomasek, J; Halámkova, J; Kiss, I; Andrasina, T; Hemmelová, B; Adámková-Krákorová, D; Vyzula, R

    2010-01-01

    Bile duct malignancies include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gall bladder carcinoma (GC) and carcinoma of Vater's ampulla (ampulloma). Bile duct neoplasms are rare tumours with overall poor prognosis. The overall incidence affects up to 12.5 per 100,000 persons in the Czech Republic. The mortality rate has risen recently to 9.5 per 100,000 persons. The incidence and mortality have been remarkably stable over the past 3 decades. The survival rate of patients with these tumours is poor, usually not exceeding 12 months. The diagnostic process is complex, uneasy and usually late. Most cases are diagnosed when unresectable, and palliative treatment is the main approach of medical care for these tumours. The treatment remains very challenging. New approaches have not brought much improvement in this field. Standards of palliative care are lacking and quality of life assessments are surprisingly not common. From the scarce data it seems, however, that multimodal individually tailored treatment can prolong patients'survival and improve the health-related quality of life. The care in specialized centres offers methods of surgery, interventional radiology, clinical oncology and high quality supportive care. These methods are discussed in the article in greater detail. Improvements in this field can be sought in new diagnostic methods and new procedures in surgery and interventional radiology. Understanding the tumour biology on the molecular level could shift the strategy to a more successful one, resulting in more cured patients. Further improvements in palliative care can be sought by defining new targets and new drug development. The lack of patients with bile duct neoplasms has been the limiting factor for any improvements. A new design of larger randomized international multicentric clinical trials with prompt data sharing could help to overcome this major problem. Defining standards of palliative care is a necessity

  3. Malignant hyperthermia: a review.

    PubMed

    Rosenberg, Henry; Pollock, Neil; Schiemann, Anja; Bulger, Terasa; Stowell, Kathryn

    2015-01-01

    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, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1 % of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the

  4. KLF4 Expression Correlates with the Degree of Differentiation in Colorectal Cancer

    PubMed Central

    Hu, Ruolei; Zuo, Yan; Zuo, Li; Liu, Chao; Zhang, Sumei; Wu, Qiang; Zhou, Qing; Gui, Shuyu; Wei, Wei

    2011-01-01

    Background/Aims Krüppel-like factor 4 (KLF4) is an epithelial-specific transcription factor primarily expressed in the gastrointestinal tract that mediates growth arrest in the colonic epithelium. We tried to find whether KLF4 expression is associated with the progression and differentiation of colorectal cancer. Methods We detected KLF4 expression in 109 colorectal specimens (40 normal appearing mucosa, 7 adenomas, and 62 carcinomas) by immunohistochemistry using a tissue microarray. Western blot and RT-PCR analyses were also performed. Results The upregulation of KLF4 expression in carcinoma tissue was statistically significant (p<0.05) when compared to normal appearing mucosa. The negative and weak positive staining rates in normal appearing mucosa, adenoma, and carcinoma were 42.5%, 71.4%, and 82.3%, respectively, indicating a decreased degree of KLF4 expression over the course of progressive transformation of normal cells into malignant derivatives. KLF4 protein levels showed no correlation with sex, age, or metastatic state (p>0.05), while KLF4 protein expression correlated with the diagnostic stage (p<0.05). Furthermore, strong KLF4 staining was detected in 22.9% (11/48) and 0% (0/14) of well/moderately and poorly differentiated colorectal cancers, respectively. Our results clearly indicate that KLF4 protein expression significantly correlates with the degree of differentiation in colorectal cancers (p<0.05). KLF4 expression in RKO cells is also upregulated by butyrate, an inducer of differentiation. Conclusions Downregulation of KLF4 expression may lead to more poorly differentiated tumors. PMID:21814594

  5. 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

  6. Quantitative analysis of colorectal mucosal lesions by autofluorescence endoscopy: discrimination of carcinomas from other lesions.

    PubMed

    Arita, Keiko; Mitsuyama, Keiichi; Kawano, Hiroshi; Hasegawa, Shin; Maeyama, Yasuhiko; Masuda, Junya; Akagi, Yoshito; Watanabe, Yasutomo; Okabe, Yoshinobu; Tsuruta, Osamu; Sata, Michio

    2011-07-01

    A newly developed autofluorescence (AF) imaging technique was applied during colonoscopy in a clinical setting. This pilot study was conducted to evaluate the clinical feasibility of applying AF endoscopy for distinguishing colorectal lesions. A total of 54 colorectal mucosal lesions obtained from 43 patients who underwent both white-light and AF endoscopy and were treated by endoscopy or surgery were assessed. Of the lesions, 11 were hyperplastic polyps, 30 were adenomas and 13 were carcinomas. To quantify the AF intensity, a color-contrast index (CCI) was determined and evaluated in relation to the histology, size and shape of each lesion. CCI was significantly associated with the histology and size of the lesions, but not their shape. CCI increased as the malignant potential increased (in the order of hyperplastic polyps→adenomas→carcinomas), irrespective of the lesion size (r=0.797, p<0.0001 for size>8 mm; r=0.622, p=0.0045 for size>8 mm but >15 mm; r=0.644, p=0.0071 for size>15 mm). In each size group, CCI tended to be higher for carcinomas than for adenomas, and also higher for adenomas than for hyperplastic polyps. CCI allowed discrimination of adenomas/carcinomas from hyperplastic polyps with 95.3% sensitivity and 63.6% specificity (cut-off value, 14.5), and of colorectal carcinomas from adenomas with 84.6% sensitivity and 80.0% specificity (cut-off value, 28.0). These results suggest that the quantitative analysis of AF intensity using CCI is helpful to discriminate among different types of colorectal mucosal lesions, including carcinomas. PMID:21573495

  7. Staging of colorectal cancer using contrast-enhanced multidetector computed tomographic colonography

    PubMed Central

    Narayanan, Srikala; Kalra, Naveen; Bhatia, Anmol; Wig, Jaidev; Rana, Surinder; Bhasin, Deepak; Vaiphei, Kim; Khandelwal, Niranjan

    2014-01-01

    INTRODUCTION Preoperative staging is essential for the optimal treatment and surgical planning of colorectal cancers. This study was aimed to evaluate the accuracy of colorectal cancer staging done using contrast-enhanced multidetector computed tomographic colonography (CEMDCTC). METHODS We recruited 25 patients with 28 proven colorectal cancers. A 16-slice multidetector computed tomography scanner was used to generate two-dimensional multiplanar reformatted sagittal, coronal and oblique coronal images, and three-dimensional virtual colonography (endoluminal) images. Axial and reformatted views were analysed, and TNM staging was done. Patients underwent surgery and conventional colonoscopy, and surgical histopathological correlation was obtained. RESULTS The diagnostic accuracies for TNM colorectal cancer staging were 92.3% for T staging, 42.3% for N staging and 96.1% for M staging using CEMDCTC. There was excellent positive correlation for T staging between CEMDCTC and both surgery (κ-value = 0.686) and histopathology (κ-value = 0.838) (p < 0.0001), and moderate positive correlation for N staging between CEMDCTC and surgery (κ-value = 0.424; p < 0.0001). The correlation between CEMDCTC and histopathology for N staging was poor (κ-value = 0.186; p < 0.05); the negative predictive value was 100% for lymph node detection. Moderate positive correlation was seen for M staging between CEMDCTC and both surgery (κ-value = 0.462) and histopathology (κ-value = 0.649). No false negatives were identified in any of the M0 cases. CONCLUSION CEMDCTC correlated well with pathologic T and M stages, but poorly with pathologic N stage. It is an extremely accurate tool for T staging, but cannot reliably distinguish between malignant lymph nodes and enlarged reactive lymph nodes. PMID:25630322

  8. 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.

  9. AMG 319 Lymphoid Malignancy FIH

    ClinicalTrials.gov

    2016-01-20

    Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Oncology; Oncology Patients; T Cell Lymphoma; Tumors

  10. 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.

  11. Ibrutinib for B cell malignancies

    PubMed Central

    2014-01-01

    Research over the role of Bruton’s agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223. This review discussed in details the role of BTK in B-cell signaling, molecular interactions between B cell lymphoma/leukemia cells and their microenvironment. Clinical trials of the novel BTK inhibitor, ibrutinib (PCI-32765), in B cell malignancies were summarized. PMID:24472371

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

    PubMed Central

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

    2010-01-01

    Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma. The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm. Immunohistochemical stains that may be useful in the differential diagnosis of metastatic colorectal tumors to the ovary and primary ovarian tumors are detailed. PMID:21160859

  13. Telomerase Activation in Hematological Malignancies.

    PubMed

    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. Microwave Ablation of Hepatic Malignancy

    PubMed Central

    Lubner, Meghan G.; Brace, Christopher L.; Ziemlewicz, Tim J.; Hinshaw, J. Louis; Lee, Fred T.

    2013-01-01

    Microwave ablation is an extremely promising heat-based thermal ablation modality that has particular applicability in treating hepatic malignancies. Microwaves can generate very high temperatures in very short time periods, potentially leading to improved treatment efficiency and larger ablation zones. As the available technology continues to improve, microwave ablation is emerging as a valuable alternative to radiofrequency ablation in the treatment of hepatic malignancies. This article reviews the current state of microwave ablation including technical and clinical considerations. PMID:24436518

  15. Expression of the Microtubule-Associated Protein MAP9/ASAP and Its Partners AURKA and PLK1 in Colorectal and Breast Cancers

    PubMed Central

    Pillaire, Marie-Jeanne; Cazaux, Christophe

    2014-01-01

    Background. Colorectal and breast cancers are among the most common cancers worldwide. They result from a conjugated deficiency of gene maintenance and cell cycle control. Objective. We investigate the expression of the microtubule-associated protein MAP9/ASAP and its two partners AURKA and PLK1 in colorectal tumors as well as in ductal breast cancers. Materials and Methods. 26 colorectal cancer samples and adjacent normal tissues and 77 ductal breast cancer samples from grade I to grade III were collected. Real-time quantitative PCR was used to analyse the expression of MAP9, AURKA, and PLK1. Results. Expression of MAP9 is downregulated in colorectal cancer compared to normal tissues (P > 10−3), whereas those of AURKA and PLK1 are upregulated (P > 10−4). In ductal breast cancer, we found a grade-dependent increase of AURKA expression (P > 10−3), while the variations of expression of MAP9 and PLK1 are not significant (P > 0.2). Conclusions. MAP9 downregulation is associated with colorectal malignancy and could be used as a disease marker and a new drug target, while AURKA and PLK1 are upregulated. In ductal breast cancer, AURKA overexpression is strongly associated with the tumor grade and is therefore of prognostic value for the progression of the disease. PMID:24876664

  16. Cryptococcus neoformans infection in malignancy.

    PubMed

    Schmalzle, Sarah A; Buchwald, Ulrike K; Gilliam, Bruce L; Riedel, David J

    2016-09-01

    Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection. PMID:26932366

  17. 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.

  18. Genetic Variants Associated with Colorectal Adenoma Susceptibility

    PubMed Central

    Abulí, Anna; Castells, Antoni; Bujanda, Luis; Lozano, Juan José; Bessa, Xavier; Hernández, Cristina; Álvarez-Urturi, Cristina; Pellisé, Maria; Esteban-Jurado, Clara; Hijona, Elizabeth; Burón, Andrea; Macià, Francesc; Grau, Jaume; Guayta, Rafael

    2016-01-01

    Background Common low-penetrance genetic variants have been consistently associated with colorectal cancer risk. Aim To determine if these genetic variants are associated also with adenoma susceptibility and may improve selection of patients with increased risk for advanced adenomas and/or multiplicity (≥ 3 adenomas). Methods We selected 1,326 patients with increased risk for advanced adenomas and/or multiplicity and 1,252 controls with normal colonoscopy from population-based colorectal cancer screening programs. We conducted a case-control association study analyzing 30 colorectal cancer susceptibility variants in order to investigate the contribution of these variants to the development of subsequent advanced neoplasia and/or multiplicity. Results We found that 14 of the analyzed genetic variants showed a statistically significant association with advanced adenomas and/or multiplicity: the probability of developing these lesions increased with the number of risk alleles reaching a 2.3-fold risk increment in individuals with ≥ 17 risk alleles. Conclusions Nearly half of the genetic variants associated with colorectal cancer risk are also related to advanced adenoma and/or multiplicity predisposition. Assessing the number of risk alleles in individuals within colorectal cancer screening programs may help to identify better a subgroup with increased risk for advanced neoplasia and/or multiplicity in the general population. PMID:27078840

  19. 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.

  20. The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial-mesenchymal transition.

    PubMed

    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

  1. Clinicopathologic Features of Colorectal Carcinoma in HIV-Positive Patients

    PubMed Central

    Sigel, Carlie; Cavalcanti, Marcela S.; Daniel, Tanisha; Vakiani, Efsevia; Shia, Jinru; Sigel, Keith

    2016-01-01

    Background Emerging evidence suggests differences in colo-rectal cancer in HIV-infected patients (HIV+) compared with HIV− patients. Microsatellite instability (MSI), occurring in a subset of colorectal cancer, is present at a higher rate in certain cancers in HIV+ patients. Colorectal cancer with MSI share some characteristics with those reported for HIV+ colorectal cancer. On this premise, we studied clinical and pathologic features of HIV+ colorectal cancer and evaluated for MSI using matched HIV− colorectal cancer controls. Methods Two nested, matched cohorts were identified from a hospital-based cohort of colorectal cancer patients. HIV+ colo-rectal cancers were identified and random control patients were matched for selected characteristics. Mismatch repair protein (MMR) IHC was performed as the detection method for MSI. Variables were compared between cases and controls using fixed-effects logit modeling to account for matching. Results We included 184 colorectal cancer samples (38 HIV+, 146 HIV− control). Median patient age at colorectal cancer onset was 55. When compared with HIV− colorectal cancer, HIV+patients were more likely to have smoked (P = 0.001), have right-sided colorectal cancer (37% vs. 14%; P = 0.003), and tumor-infiltrating lymphocytes (TIL) above 50/10 high-power fields (21% vs. 7%). There was no difference in MMR protein expression (P = 0.6). HIV+ colorectal cancer patients had reduced overall survival (P = 0.02) but no difference in progression-free survival. Conclusions HIV+ patients developed colorectal cancer at a lower median age than population estimates, had a higher frequency of right-sided disease, and increased TILs, suggesting potential biologic differences compared with uninfected patients. Impact Clinicopathologic differences in colorectal cancer of HIV+ persons may have implications for tumor pathogenesis. PMID:27197294

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

    PubMed

    Asad-Ur-Rahman, Fnu; 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

  4. 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.

  5. Discovery and Validation of Hypermethylated Markers for Colorectal Cancer.

    PubMed

    Wei, Jiufeng; Li, Guodong; Dang, Shuwei; Zhou, Yuhui; Zeng, Kai; Liu, Ming

    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

  6. 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

  7. 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

  8. Reversibility of Aberrant Global DNA and Estrogen Receptor-α Gene Methylation Distinguishes Colorectal Precancer from Cancer

    PubMed Central

    Shen, Rulong; Tao, Lianhui; Xu, Yiqing; Chang, Shi; Van Brocklyn, James; Gao, Jian-Xin

    2009-01-01

    Alterations in the global methylation of DNA and in specific regulatory genes are two epigenetic alterations found in cancer. However, the significance of epigenetic changes for diagnosis and/or prognosis of colorectal cancer have not been established, although it has been extensively investigated. Recently we have identified a new type of cancer cell called precancerous stem cells (pCSCs) and proposed that cancer may arise from a lengthy development process of tumor initiating cells (TICs) → pCSCs → cancer stem cells (CSCs) → cancer, which is in parallel to histological changes of hyperplasia (TICs) → precancer (pCSCs) → carcinoma (CSCs/cancer cells), accompanied by clonal evolutionary epigenetic and genetic alterations. In this study, we investigated whether aberrant DNA methylation can be used as a biomarker for the differentiation between premalignant and malignant lesions in the colorectum. The profile of global DNA and estrogen receptor (ER)-α gene methylation during cancer development was determined by analysis of 5-methylcytosine (5-MeC) using immunohistochemical (IHC) staining, dot blot analysis or a quantitative gene methylation assay (QGMA). Herein we show that global DNA hypomethylation and ER-α gene hypermethylation are progressively enhanced from hyperplastic polyps (HPs) → adenomatous polyps (APs) → adenomatous carcinoma (AdCa). The aberrant methylation can be completely reversed in APs, but not in AdCa by a nonsteroidal anti-inflammatory drug (NSAID) celecoxib, which is a selective inhibitor of cyclooxygenase-2 (Cox-2), suggesting that the epigenetic alterations between colorectal precancer (AP) and cancer (AdCa) are fundamentally different in response to anti-cancer therapy. In normal colorectal mucosa, while global DNA methylation was not affected by aging, ER-α gene methylation was significantly increased with aging. However, this increase did not reach the level observed in colorectal APs. Taken together, reversibility of

  9. Detection of colonic cells in peripheral blood of colorectal cancer patients by means of reverse transcriptase and polymerase chain reaction.

    PubMed Central

    Castells, A.; Boix, L.; Bessa, X.; Gargallo, L.; Piqué, J. M.

    1998-01-01

    Circulating tumour cells play a central role in the metastatic process, but little is known about the relationship between this cellular subpopulation and the development of secondary disease. This study was aimed at assessing the presence of colonic cells in peripheral blood of patients with colorectal cancer in different evolutionary stages, by means of reverse transcriptase polymerase chain reaction (RT-PCR) targeted to carcinoembryonic antigen (CEA) mRNA. In vitro sensitivity was established in a recovery experiment by preparing serial colorectal cancer cell dilutions. Thereafter, 95 colorectal cancer patients and a control group including healthy subjects (n=11), patients with other gastrointestinal neoplasms (n=11) or inflammatory bowel disease (n=9) were analysed. Specific cDNA primers for CEA transcripts were used to apply RT-PCR to peripheral blood samples. Tumour cells were detected down to five cells per 10 ml blood, thus indicating a sensitivity limit of approximately one tumour cell per 10(7) white blood cells. CEA mRNA expression was detected in 39 out of 95 colorectal cancer patients (41.1%), there being a significant correlation with the presence of distant metastases at inclusion. None of the healthy volunteers and only 1 of 11 patients (9.1%) with other gastrointestinal neoplasms had detectable CEA mRNA in peripheral blood. By contrast, CEA mRNA was detected in five of the nine patients (55.6%) with inflammatory bowel disease. These results confirm that it is feasible to amplify CEA mRNA in the peripheral blood, its presence being almost certainly derived from circulating malignant cells in colorectal cancer patients. However, CEA mRNA detectable in blood of patients with inflammatory bowel disease suggests the presence of circulating non-neoplastic colonic epithelial cells. Images Figure 2 Figure 3 PMID:9823981

  10. 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

  11. Epigenetics and Colorectal Cancer Pathogenesis

    PubMed Central

    Bardhan, Kankana; Liu, Kebin

    2013-01-01

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy. PMID:24216997

  12. Relationship between intestinal microbiota and colorectal cancer

    PubMed Central

    Cipe, Gokhan; Idiz, Ufuk Oguz; Firat, Deniz; Bektasoglu, Huseyin

    2015-01-01

    The human gastrointestinal tract hosts a complex and vast microbial community with up to 1011-1012 microorganisms colonizing the colon. The gut microbiota has a serious effect on homeostasis and pathogenesis through a number of mechanisms. In recent years, the relationship between the intestinal microbiota and sporadic colorectal cancer has attracted much scientific interest. Mechanisms underlying colonic carcinogenesis include the conversion of procarcinogenic diet-related factors to carcinogens and the stimulation of procarcinogenic signaling pathways in luminal epithelial cells. Understanding each of these mechanisms will facilitate future studies, leading to the development of novel strategies for the diagnosis, treatment, and prevention of colorectal cancer. In this review, we discuss the relationship between colorectal cancer and the intestinal microbiota. PMID:26483877

  13. Treatment of peritoneal metastases from colorectal cancer

    PubMed Central

    März, Loreen; Piso, Pompiliu

    2015-01-01

    Peritoneal seedings of a colorectal tumor represent the second most frequent site of metastasis (after the liver). In the era of 5-fluorouracil (5-FU)-only chemotherapy, the prognosis was poor for colorectal cancer with peritoneal metastases. Within the last few years, new chemotherapeutic and targeted agents have improved the prognosis; however, the response to these treatments seems to be lower than that for liver metastases. The combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have further improved both disease-free survival and overall survival. Keeping this in mind, every patient presenting with peritoneal metastases from colorectal cancer should be evaluated and receive adequate treatment, if possible in the above-mentioned combination. This paper reviews recent advancements in the therapy of peritoneal carcinomatosis. PMID:26424828

  14. The stability of colorectal cancer mathematical models

    NASA Astrophysics Data System (ADS)

    Khairudin, Nur Izzati; Abdullah, Farah Aini

    2013-04-01

    Colorectal cancer is one of the most common types of cancer. To better understand about the kinetics of cancer growth, mathematical models are used to provide insight into the progression of this natural process which enables physicians and oncologists to determine optimal radiation and chemotherapy schedules and develop a prognosis, both of which are indispensable for treating cancer. This thesis investigates the stability of colorectal cancer mathematical models. We found that continuous saturating feedback is the best available model of colorectal cancer growth. We also performed stability analysis. The result shows that cancer progress in sequence of genetic mutations or epigenetic which lead to a very large number of cells population until become unbounded. The cell population growth initiate and its saturating feedback is overcome when mutation changes causing the net per-capita growth rate of stem or transit cells exceed critical threshold.

  15. Tissue Specific Promoters in Colorectal Cancer

    PubMed Central

    Rama, A. R.; Aguilera, A.; Melguizo, C.; Caba, O.; Prados, J.

    2015-01-01

    Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment. PMID:26648599

  16. Mini-invasive surgery for colorectal cancer

    PubMed Central

    Zeng, Wei-Gen; Zhou, Zhi-Xiang

    2014-01-01

    Laparoscopic techniques have been extensively used for the surgical management of colorectal cancer during the last two decades. Accumulating data have demonstrated that laparoscopic colectomy is associated with better short-term outcomes and equivalent oncologic outcomes when compared with open surgery. However, some controversies regarding the oncologic quality of mini-invasive surgery for rectal cancer exist. Meanwhile, some progresses in colorectal surgery, such as robotic technology, single-incision laparoscopic surgery, natural orifice specimen extraction, and natural orifice transluminal endoscopic surgery, have been made in recent years. In this article, we review the published data and mainly focus on the current status and latest advances of mini-invasive surgery for colorectal cancer. PMID:24589210

  17. [Colorectal carcinoma in Cronkhite-Canada syndrome].

    PubMed

    Zügel, N P; Hehl, J A; Jechart, G; Tannapfel, A; Wienbeck, M; Witte, J

    2001-05-01

    We report a 63-year-old lady with Cronkhite-Canada syndrome, who developed colorectal cancer. A hemicolectomy was performed, and the tumor specimen was prepared for DNA-analysis and immunohistochemical screening. We found a mutation of p53 gene without APC- and ras-gene alteration and expression of erbB2-protooncogen. The polyps in non-hereditary Cronkhite-Canada-syndrom are neither adenomatous nor hyperplastic, but patients often develop colorectal cancers. The steps of mutation do not follow the adenoma-carcinoma sequence, first described by Vogelstein 1988. This and previous observations suggest that carcinogenesis in Cronkhite-Canada syndrome follows another independent sequence. PMID:11413916

  18. Cytology of canine malignant histiocytosis.

    PubMed

    Brown, Diane E.; Thrall, Mary Anna; Getzy, David M.; Weiser, M. Glade; Ogilvie, Gregory K.

    1994-01-01

    Cytologic features of bone marrow, tissue, and abdominal fluid in seven cases of malignant histiocytosis in dogs are described, and histopathology, hematology, and serum biochemistry of the cases are reviewed. Diagnosis of malignant histiocytosis was confirmed by tissue morphology and immunohistochemistry; neoplastic cells in all cases had positive immunoreactivity to lysozyme. This stain can be used to definitively establish the diagnosis of malignant histiocytosis on cytology specimens as well as tissue sections. Cytologic findings included numerous pleomorphic, large, discrete mononuclear cells with abundant, lightly basophilic, vacuolated, granular cytoplasm. Nuclei were round to oval to reniform with marked anisocytosis and anisokaryosis; nucleoli were prominent. Mitotic figures, often bizarre, were occasionally seen. Multinucleated giant cells and phagocytosis of erythrocytes and leukocytes were prominent features in cytologic preparations in four cases. Four dogs were anemic, five dogs were thrombocytopenic, and three dogs were hypercalcemic. Breeds affected included Doberman Pinscher (1), Golden Retriever (2), Flat Coated Retriever (3), and mixed-breed dog (1). PMID:12666013

  19. Gastrointestinal malignancy and the microbiome.

    PubMed

    Abreu, Maria T; Peek, Richard M

    2014-05-01

    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 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 human beings 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 gastrointestinal cancers. PMID:24406471

  20. [Genodermatoses with malignant skin tumors].

    PubMed

    Hübinger, L; Frank, J

    2014-06-01

    Cutaneous malignancies can manifest as isolated and sporadic tumors as well as multiple and disseminated tumors. In the latter case they often point to a genetic disease, which either can be restricted to the skin exclusively or also involve extracutaneous organs in the context of a hereditary tumor syndrome. Such hereditary tumor syndromes are clinically and genetically very heterogeneous. Therefore, the prevailing specific skin tumors play an important diagnostic role in the case of complex symptom constellations. Elucidation of the genetic basis of rare monogenetically inherited disorders and syndromes can contribute to a better understanding of the pathogenesis of frequently occurring cutaneous malignancies because the mutated genes often encode proteins, which have a key position in metabolic signaling pathways that are of high significance for the development of targeted therapies. Here we provide an overview of genodermatoses, which are associated with basal cell carcinomas, sebaceous carcinomas, keratoacanthomas, squamous cell carcinomas and malignant melanomas. PMID:24898507

  1. Quantum dot-based multiplexed imaging in malignant ascites: a new model for malignant ascites classification

    PubMed Central

    Zeng, Wei-Juan; Peng, Chun-Wei; Yuan, Jing-Ping; Cui, Ran; Li, Yan

    2015-01-01

    Purpose The aims of this study are to establish a new method for simultaneously detecting the interactions between cancer cells and immunocytes in malignant ascites (MA) and to propose a new model for MA classification. Methods A quantum dot (QD)-based multiplexed imaging technique was developed for simultaneous in situ imaging of cancer cells, lymphocytes, and macrophages. This method was first validated in gastric cancer tissues, and then was applied to MA samples from 20 patients with peritoneal carcinomatosis from gastrointestinal and gynecological origins. The staining features of MA and the interactions between cancer cells and immunocytes in the ascites were further analyzed and correlated with clinical features. Results The QD-based multiplexed imaging technique was able to simultaneously show gastric cancer cells, infiltrating macrophages, and lymphocytes in tumor tissue, and the technique revealed the distinctive features of the cancer tumor microenvironment. When this multiplexed imaging protocol was applied to MA cytology, different features of the interactions and quantitative relations between cancer cells and immunocytes were observed. On the basis of these features, MA could be classified into immunocyte-dominant type, immunocyte-reactive type, cancer cell-dominant type, and cell deletion type; the four categories were statistically different in terms of the ratio of cancer cells to immunocytes (P<0.001). Moreover, in the MA, the ratio of cancer cells to immunocytes was higher for patients with gynecological and gastric cancers than for those with colorectal cancer. Conclusion The newly developed QD-based multiplexed imaging technique was able to better reveal the interactions between cancer cells and immunocytes. This advancement allows for better MA classification and, thereby, allows for treatment decisions to be more individualized. PMID:25784803

  2. [Palliative surgery for malignant bowel obstruction in patients with advanced and recurrent gastroenterological cancer].

    PubMed

    Kitani, Kotaro; Yukawa, Masao; Fujiwara, Yoshinori; Tsujie, Masanori; Hara, Joji; Ikeda, Mitsunori; Sato, Katsuaki; Isono, Sayuri; Kawai, Kenji; Miura, Ken; Watatani, Masahiro; Inoue, Masatoshi

    2013-11-01

    We report the outcomes of palliative surgery for the treatment of malignant bowel obstruction in patients with advanced gastroenterological cancer. We studied 20 patients who had undergone palliative surgery over 3 years. We analyzed the clinical findings, surgical procedure, postoperative clinical course, and prognosis. The origin of the patients was colorectal cancer( 9 cases), gastric cancer( 4 cases), uterine cancer( 3 cases), pancreatic cancer( 2 cases), bladder( 1 case), and anal cancer (1 case). Small bowel obstruction was noted in 8 cases and colorectal obstruction was noted in 14 cases. Colostomy was performed in 13 cases, resection and reconstruction were performed in 6 cases, and bypass was performed in 4 cases. Ninety percent of the patients were able to eat solid food following the surgery, but 20% of the patients were forced to have bowel obstruction. The median survival time after palliative surgery was 3 (range, 0-15) months, and 6 patients (30%) died within 2 months. We concluded that palliative surgery for the treatment of malignant bowel obstruction could improve the patients' quality of life. The decision for performing palliative surgery should be made while considering the patient's prognosis, wishes, and potential for symptom improvement. PMID:24393893

  3. The multidrug resistance 1 (MDR1) gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study

    PubMed Central

    Andersen, Vibeke; Agerstjerne, Lene; Jensen, Dorte; Østergaard, Mette; Sæbø, Mona; Hamfjord, Julian; Kure, Elin; Vogel, Ulla

    2009-01-01

    Background Smoking, dietary factors, and alcohol consumption are known life style factors contributing to gastrointestinal carcinogenesis. Genetic variations in carcinogen handling may affect cancer risk. The multidrug resistance 1(MDR1/ABCB1) gene encodes the transport protein P-glycoprotein (a phase III xenobiotic transporter). P-glycoprotein is present in the intestinal mucosal lining and restricts absorption of certain carcinogens, among these polycyclic aromatic hydrocarbons. Moreover, P-glycoprotein transports various endogenous substrates such as cytokines and chemokines involved in inflammation, and may thereby affect the risk of malignity. Hence, genetic variations that modify the function of P-glycoprotein may be associated with the risk of colorectal cancer (CRC). We have previously found an association between the MDR1 intron 3 G-rs3789243-A polymorphism and the risk of CRC in a Danish study population. The aim of this study was to investigate if this MDR1 polymorphism was associated with risk of colorectal adenoma (CA) and CRC in the Norwegian population. Methods Using a case-control design, the association between the MDR1 intron 3 G-rs3789243-A polymorphism and the risk of colorectal carcinomas and adenomas in the Norwegian population was assessed in 167 carcinomas, 990 adenomas, and 400 controls. Genotypes were determined by allelic discrimination. Odds ratio (OR) and 95 confidence interval (95% CI) were estimated by binary logistic regression. Results No association was found between the MDR1 polymorphism (G-rs3789243-A) and colorectal adenomas or cancer. Carriers of the variant allele of MDR1 intron 3 had odds ratios (95% CI) of 0.97 (0.72–1.29) for developing adenomas, and 0.70 (0.41–1.21) for colorectal cancer, respectively, compared to homozygous wild type carriers. Conclusion The MDR1 intron 3 (G-rs3789243-A) polymorphism was not associated with a risk of colorectal adenomas or carcinomas in the present Norwegian study group. Thus, this

  4. Campomelic dysplasia and malignant hyperthermia

    PubMed Central

    Barros, Andreia; Teixeira, Filomena; Camacho, Maria Carmo; Alves, Cristina

    2011-01-01

    Campomelic dysplasia (CD) is a rare clinical entity, usually fatal in the first year of life. It is characterised by bowing and angulations of long bones, along with other congenital anomalies. The occurrence of malignant hyperthermia is rare, but it has been associated with skeletal dysplasias. The authors present the case of a boy, born at 40 weeks of gestational age, with multiple congenital anomalies and subsequently diagnosed with CD, who died at 16 months of age as a consequence of malignant hyperthermia. PMID:22691592

  5. Dyskeratosis congenita with malignant transformation

    PubMed Central

    Ray, Jay Gopal; Swain, Niharika; Ghosh, Ranjan; Richa; Pattanayak (Mohanty), Sweta

    2011-01-01

    Dyskeratosis congenita (DC) is a rare genodermatosis characterised by a classic triad of dystrophic nails, reticular skin pigmentation and mucous membrane leukoplakic patches, which have a high rate of malignant transformation. The case report presented here deals with a sporadic case of DC without similar clinical presentation in the first-degree and second-degree relatives. Of note in this case, there was rapid malignant transformation in the non-homogeneous nodulo-speckled leukoplakic patch on the dorsum of the tongue. PMID:22715219

  6. Stenting in Malignant Biliary Obstruction.

    PubMed

    Almadi, Majid A; Barkun, Jeffrey S; Barkun, Alan N

    2015-10-01

    Decompression of the biliary system in patients with malignant biliary obstruction has been widely accepted and implemented as part of the care. Despite a wealth of literature, there remains a significant amount of uncertainty as to which approach would be most appropriate in different clinical settings. This review covers stenting of the biliary system in cases of resectable or palliative malignant biliary obstruction, potential candidates for biliary drainage, technical aspects of the procedure, as well as management of biliary stent dysfunction. Furthermore, periprocedural considerations including proper mapping of the location of obstruction and the use of antibiotics are addressed. PMID:26431598

  7. Perendoscopic Nd:YAG laser therapy of colorectal neoplasms

    NASA Astrophysics Data System (ADS)

    Norberto, Lorenzo; Ranzato, R.; Marino, S.; Erroi, F.; Angriman, I.; Donadi, M.; 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

  8. 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

  9. [Intracytoplasmic lumina of benign and malignant breast diseases--a light and electron microscopic study].

    PubMed

    Gu, C M

    1990-07-01

    Intracytoplasmic lumina (ICLs) of 70 cases with breast carcinoma and 29 cases with benign breast diseases were observed by light and electron microscopy. ICLs were morphologically divided into two types. Type A was characterized by the presence of secretory materials stained with eosin in the lumen and Type B by the cytoplasmic vacuoles under light microscope. Electron microscopic observation on Type A ICLs showed numerous filiform microvilli projecting towards the lumen and various amounts of secretory materials in the lumen. Type B of ICLs only had scanty and short microvilli and rarely secretory materials in the lumen. The results indicated that: 1. The frequency of ICLs in breast cancer was significantly higher than that in benign breast disease (P less than 0.01). 2. The frequency of ICLs in breast cancer showed strong negative correlation with its histological grades but not with its histological types. 3. ICLs had similar frequency under both light and electron microscopes. As a relatively specific structure in breast carcinoma cells, ICLs may be helpful in the diagnosis of breast carcinoma and establishment of the breast origin for metastatic carcinoma. PMID:2176965

  10. Promoting Colorectal Cancer Screening Discussion

    PubMed Central

    Christy, Shannon M.; Perkins, Susan M.; Tong, Yan; Krier, Connie; Champion, Victoria L.; Skinner, Celette Sugg; Springston, Jeffrey K.; Imperiale, Thomas F.; Rawl, Susan M.

    2013-01-01

    Background Provider recommendation is a predictor of colorectal cancer (CRC) screening. Purpose To compare the effects of two clinic-based interventions on patient–provider discussions about CRC screening. Design Two-group RCT with data collected at baseline and 1 week post-intervention. Participants/setting African-American patients that were non-adherent to CRC screening recommendations (n=693) with a primary care visit between 2008 and 2010 in one of 11 urban primary care clinics. Intervention Participants received either a computer-delivered tailored CRC screening intervention or a nontailored informational brochure about CRC screening immediately prior to their primary care visit. Main outcome measures Between-group differences in odds of having had a CRC screening discussion about a colon test, with and without adjusting for demographic, clinic, health literacy, health belief, and social support variables, were examined as predictors of a CRC screening discussion using logistic regression. Intervention effects on CRC screening test order by PCPs were examined using logistic regression. Analyses were conducted in 2011 and 2012. Results Compared to the brochure group, a greater proportions of those in the computer-delivered tailored intervention group reported having had a discussion with their provider about CRC screening (63% vs 48%, OR=1.81, p<0.001). Predictors of a discussion about CRC screening included computer group participation, younger age, reason for visit, being unmarried, colonoscopy self-efficacy, and family member/friend recommendation (all p-values <0.05). Conclusions The computer-delivered tailored intervention was more effective than a nontailored brochure at stimulating patient–provider discussions about CRC screening. Those who received the computer-delivered intervention also were more likely to have a CRC screening test (fecal occult blood test or colonoscopy) ordered by their PCP. Trial registration This study is registered at www

  11. Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

    PubMed Central

    Burt, R. W.; Bishop, D. T.; Lynch, H. T.; Rozen, P.; Winawer, S. J.

    1990-01-01

    Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on

  12. 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

  13. Malignant transformation of uterine leiomyoma

    PubMed Central

    Al Ansari, Afaf A.; Al Hail, Fatima A.; Abboud, Emad

    2012-01-01

    A rare case of malignant transformation of uterine leiomyoma is reported. A 54 year old lady, nulliparous and 2 years postmenopausal presented to gynecology clinic with a pelvi – abdominal mass and ultrasound scan suggestive of multiple uterine fibroid. Total abdominal hysterectomy performed. Histopathology report showed leiomyosarcomative changes from benign leiomyoma within the huge mass. PMID:25003044

  14. 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...

  15. Metastatic Colorectal Cancer: Lessons Learned, Future Possibilities.

    PubMed

    Venook, Alan P

    2016-05-01

    Survival of patients with metastatic colorectal cancer has dramatically improved over the past 20 years, primarily because physicians have become adept at using the many regimens approved for this patient population. Future advances may come from understanding molecular subtypes, finding and treating new actionable mutations, and harnessing the immune system. PMID:27226509

  16. Advanced endoscopic technologies for colorectal cancer screening

    PubMed Central

    Obstein, Keith L; Valdastri, Pietro

    2013-01-01

    Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation. PMID:23382621

  17. 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...

  18. Colorectal Cancer Rates by Race and Ethnicity

    MedlinePlus

    ... getting colorectal cancer, followed by white, Hispanic, Asian/Pacific Islander (A/PI), and American Indian/Alaska Native ( ... white, Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander women. Sources: CDC’s National Program of Cancer ...

  19. 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

    2016-01-01

    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. PMID:27173319

  20. Computed tomography evaluation of colorectal carcinoma.

    PubMed

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

    1996-04-01

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

  1. Nutrients Impact the Pathogenesis and Development of Colorectal Cancer

    PubMed Central

    Du, Wan; Fang, Jing-Yuan

    2016-01-01

    Background Colorectal cancer is a commonly diagnosed cancer and the cause of many cancer deaths worldwide. Nutrients might be crucial in the pathogenesis and development of colorectal cancer. Although a number of studies have demonstrated the potential effects of nutrients, many challenges still remain Summary A tremendous amount of research has emerged concerning the roles of nutrients in colorectal cancer during the past decades. Here, we review the latest research progress on nutrients, including vitamins, folic acid, calcium, selenium and dietary fiber, involved in colorectal cancer prevention Key Message Nutrients are commonly consumed in foods or dietary supplements. It is clear that nutrients could play an important role and influence colorectal cancer outcomes. The relationship between nutrients and colorectal risk is complex. Vitamins, folic acid, calcium, selenium and dietary fiber have been proposed as potential agents to prevent colorectal cancer. However, some studies found that these nutrients did not reduce the incidence of colorectal cancer Practical Implications The supplementary dose of nutrients, the length of time required to observe the effects and confounding factors during the study might influence the role of nutrients in the prevention of colorectal cancer. Therefore, more evidence from ongoing clinical trials with different population groups and longer follow-up periods is critical to determine the relationship between nutrients and colorectal cancer. PMID:27403415

  2. Association between Gastroenterological Malignancy and Diabetes Mellitus and Anti-Diabetic Therapy: A Nationwide, Population-Based Cohort Study

    PubMed Central

    Lin, Chien-Ming; Huang, Hui-Ling; Chu, Fang-Ying; Fan, Hueng-Chuen; Chen, Hung-An; Chu, Der-Ming; Wu, Li-Wei; Wang, Chung-Ching; Chen, Wei-Liang

    2015-01-01

    Background The relationship between diabetes mellitus (DM) and cancer incidence has been evaluated in limited kinds of cancer. The effect of anti-diabetic therapy (ADT) on carcinogenesis among diabetic patients is also unclear. Materials and Methods Using population-based representative insurance claims data in Taiwan, 36,270 DM patients and 145,080 comparison subjects without DM were identified from claims from 2005 to 2010. The association between the top ten leading causes of cancer-related death in Taiwan and DM was evaluated. Whether ADT altered the risk of developing cancer was also investigated. Results Incidence of cancer at any site was significantly higher in patients with DM than in those without (p<0.001). The risk of carcinogenesis imparted by DM was greatest in gastroenterological malignancies (liver, pancreas, and colorectal cancer) as well as lung, breast and oral cancer (p<0.001). Among the oral types of ADT, metformin decreased the risk of lung and liver cancer, but had less effect on reducing the risk of colorectal cancer. α-glucosidase inhibitor decreased the risk of developing liver, colorectal, and breast cancer. Apart from intermediate-acting insulin, rapid-acting, long-acting, and combination insulin treatment significantly reduced the overall cancer risk among all DM patients. In subgroup analysis, long-acting insulin treatment significantly decreased the risk of lung, liver, and colorectal cancer. Conclusion Our results supported the notion that pre-existing DM increases the incidence of gastroenterological cancer. ADT, especially metformin, α-glucosidase inhibitor, and long-acting insulin treatment, may protect patients with DM against these malignancies. It is crucial that oncologists should closely collaborate with endocrinologists to provide an optimal cancer-specific therapy and diabetic treatment to patients simultaneously with cancer and DM. PMID:25978841

  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. All Trans-Retinoic Acid Mediates MED28/HMG Box-Containing Protein 1 (HBP1)/β-Catenin Signaling in Human Colorectal Cancer Cells.

    PubMed

    Lee, Ming-Fen; Hsieh, Nien-Tsu; Huang, Chun-Yin; Li, Chun-I

    2016-08-01

    Vitamin A is required for normal body function, including vision, epithelial integrity, growth, and differentiation. All trans-retinoic acid (ATRA), a family member of vitamin A, has been explored in treating acute promyelocytic leukemia and other types of cancer. Dysregulated Wnt/β-catenin signaling and disrupted cadherin-catenin complex often contribute to colorectal malignancy. MED28, a mammalian Mediator subunit, is found highly expressed in breast and colorectal cancers. Our laboratory has also reported that MED28 regulates cell growth, migration, and invasion in human breast cancer cells. In the current study we investigated the effect of ATRA on MED28 and Wnt/β-catenin signaling in colorectal cancer. HCT116, HT29, SW480, and SW620, four human colorectal cancer cell lines representing different stages of carcinogenesis and harboring critical genetic changes, were employed. Our data indicated that regardless of genetic variations among these cells, suppression of MED28 reduced the expression of cyclin D1, c-Myc, and nuclear β-catenin, but increased the expression of E-cadherin and HMG box-containing protein 1 (HBP1) where HBP1 has been described as a negative regulator of the Wnt/β-catenin signaling. The reporter activity of an HBP1 promoter increased upon MED28 knockdown, but decreased upon MED28 overexpression. ATRA reduced the expression of MED28 and mimicked the effect of MED28 suppression in down-regulating Wnt/β-catenin signaling. Taken together, ATRA can reverse the suppressive effect of MED28 on HBP1 and E-cadherin and inactivate the Wnt/β-catenin pathway in colorectal cancer, suggesting a protective effect of ATRA against colorectal cancer. J. Cell. Physiol. 231: 1796-1803, 2016. © 2015 Wiley Periodicals, Inc. PMID:26660958

  6. Do We Know What Causes Malignant Mesothelioma?

    MedlinePlus

    ... Next Topic Can malignant mesothelioma be prevented? Do we know what causes malignant mesothelioma? Researchers have found ... genes – the instructions for how our cells function. We usually look like our parents because they are ...

  7. Surgical quality in colorectal cancer

    PubMed Central

    Plummer, Joseph M.; Williams, Nadia; Leake, Pierre-Anthony; Ferron-Boothe, Doreen; Meeks-Aitken, Nicola; Mitchell, Derek I.; McFarlane, Michael E.; East, Jeffery

    2015-01-01

    Objective To determine the quality of surgical management offered to patients with colorectal cancer (CRC) as measured by adequacy of nodal resections and compare variations across the major hospitals in Jamaica. Method Data was obtained from the CRC Registry of patients diagnosed and treated surgically for CRC during the 3-year period commencing January 1, 2011. Variables analyzed included tumor site, stage and number of lymph nodes resected across hospitals. Results During the period under review 60% (349) of 586 patients had resections and formed the basis of this study. Of these 49% were treated at the UHWI, 27% from the KPH and STH, 15% from CRH and MRH and 8% from a private laboratory (DPS). Patient distribution was similar at UHWI compared to the others with mean age (61 vs 62) and with slightly more women having surgery (53% Vs 54%) (UHWI vs Others). For tumor grade, margin status, lymphovascular and depth of invasion (majority T3) there was no difference between UHWI and the other sites, although a smaller percentage of tumors treated at UHWI had Crohn's like reaction (p = 0.01). There was a larger proportion of sigmoid cancer at UHWI while the reverse trend was seen in cancers of the rectum (p = 0.027). The tumors treated at UHWI have a larger median number of regional nodes when compared to the other facilities (14 vs 10; p < 0.001) and also more likely to have positive nodes, as were women and younger patients. Comparison across facilities revealed that the proportion of tumors classed as well differentiated, circumferential margin involvement, and having lymphovascular invasion were higher for specimens processed at the private facility (p = 0.021, 0.035, 0.01 respectively). Histopathology reports of tumors treated at UHWI and DPS had median 14 and 18 nodes respectively while at NPH laboratory and CRH they were 9 and 10 respectively (p < 0.001), whilst those of the ascending, descending, sigmoid colon and rectum had median 15, 11, 13, 11

  8. 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

  9. Malignant phylloides tumor in pregnancy.

    PubMed

    Blaker, Kristen M; Sahoo, Sunati; Schweichler, Maria R; Chagpar, Anees B

    2010-03-01

    Malignant phylloides tumors are exceedingly rare with few cases being reported in pregnancy. We describe the first case ever reported of a malignant phylloides tumor presenting in the first trimester of pregnancy and provide insight into the complexities of management as well as a review of the known literature. An extensive PubMed literature search for "cystosarcoma," "phylloides," and "pregnancy" was performed. References of each citation were reviewed. Only six previous cases of phylloides tumor in pregnancy were found, none of which were in the first trimester. Medical records of a patient presenting to our institution at 9 weeks gestation with a malignant phylloides tumor were reviewed. We further provide a review of the current literature of the management of phylloides tumor in pregnancy. A 27-year-old white G2P0SA1 woman with no family history of breast cancer presented with a right breast mass at her first prenatal examination at 9 weeks of pregnancy. Ultrasound confirmed a solid mass measuring 24 mm. Core needle biopsy demonstrated a malignant phylloides tumor. She previously had a fibroadenoma removed from the same breast 7 years previously. The current tumor was excised to clear margins. Histopathological examination revealed a 4-cm fibroepithelial tumor with marked stromal cellularity and a high mitotic count (five to seven mitoses/high-power field), confirming the diagnosis of malignant phylloides tumor. The patient continued her pregnancy without complications. Six other cases of phylloides tumor presenting in pregnancy have been reported in the literature, one of which had bilateral disease. Of these, the average patient age was 32 years (range, 28 to 35 years). The majority of these patients presented in their third trimester (mean, 29 weeks; range, 20 to 36 weeks) and often had large tumors (mean, 15 cm; range, 5 to 21 cm). Four of the seven tumors (57%) required a mastectomy. Previous cases have shown phylloides tumors to present in the third

  10. New registry: National Cancer Patient Registry--Colorectal Cancer.

    PubMed

    Wendy, L; Radzi, M

    2008-09-01

    Colorectal cancer is emerging as one of the commonest cancers in Malaysia. Data on colorectal cancer from the National Cancer Registry is very limited. Comprehensive information on all aspects of colorectal cancer, including demographic details, pathology and treatment outcome are needed as the management of colorectal cancer has evolved rapidly over the years involving several disciplines including gastroenterology, surgery, radiology, pathology and oncology. This registry will be an important source of information that can help the development of guidelines to improve colorectal cancer care relevant to this country. The database will initially recruit all colorectal cancer cases from eight hospitals. The data will be stored on a customized web-based case report form. The database has begun collecting data from 1 October 2007 and will report on its first year findings at the end of 2008. PMID:19230248

  11. 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. PMID:22007275

  12. Emerging role of vitamin D in colorectal cancer

    PubMed Central

    Kang, Wonmo; Lee, Sujin; Jeon, Eunyi; Yun, Ye-Rang; Kim, Kook-Hyun; Jang, Jun-Hyeog

    2011-01-01

    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)D3 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. PMID:22007275

  13. 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

  14. SNAI2 modulates colorectal cancer 5-fluorouracil sensitivity through miR145 repression.

    PubMed

    Findlay, Victoria J; Wang, Cindy; Nogueira, Lourdes M; Hurst, Katie; Quirk, Daniel; Ethier, Stephen P; Staveley O'Carroll, Kevin F; Watson, Dennis K; Camp, E Ramsay

    2014-11-01

    Epithelial-to-mesenchymal transition (EMT) has been associated with poor treatment outcomes in various malignancies and is inversely associated with miRNA145 expression. Therefore, we hypothesized that SNAI2 (Slug) may mediate 5-fluorouracil (5FU) chemotherapy resistance through inhibition of miR145 in colorectal cancer and thus represents a novel therapeutic target to enhance current colorectal cancer treatment strategies. Compared with parental DLD1 colon cancer cells, 5FU-resistant (5FUr) DLD1 cells demonstrated features of EMT, including >2-fold enhanced invasion (P < 0.001) and migration, suppressed E-cadherin expression, and 2-fold increased SNAI2 expression. DLD1 and HCT116 cells with stable expression of SNAI2 (DLD1/SNAI2; HCT116/SNAI2) also demonstrated EMT features such as the decreased E-cadherin as well as significantly decreased miR145 expression, as compared with control empty vector cells. On the basis of an miR145 luciferase promoter assay, we demonstrated that SNAI2 repressed activity of the miR145 promoter in the DLD1 and HCT116 cells. In addition, the ectopic expressing SNAI2 cell lines demonstrated decreased 5FU sensitivity, and, conversely, miR145 replacement significantly enhanced 5FU sensitivity. In the parental SW620 colon cancer cell line with high SNAI2 and low miR145 levels, inhibition of SNAI2 directly with short hairpin sequence for SNAI2 and miR145 replacement therapy both decreased vimentin expression and increased in vitro 5FU sensitivity. In pretreatment rectal cancer patient biopsy samples, low miR145 expression levels correlated with poor response to neoadjuvant 5FU-based chemoradiation. These results suggested that the SNAI2:miR145 pathway may represent a novel clinical therapeutic target in colorectal cancer and may serve as a response predictor to chemoradiation therapy. PMID:25249558

  15. 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

  16. The clinical analysis of acute pancreatitis in colorectal cancer patients undergoing chemotherapy after operation.

    PubMed

    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

  17. Circulating Non-coding RNA as Biomarkers in Colorectal Cancer.

    PubMed

    Ferracin, Manuela; Lupini, Laura; Mangolini, Alessandra; Negrini, Massimo

    2016-01-01

    Recent studies suggested that colorectal cancer influences the types and quantity of nucleic acids - especially microRNAs - detected in the bloodstream. Concentration of circulating (cell-free) microRNAs, and possibly of other non-coding RNAs, could therefore serve as valuable colorectal cancer biomarker and could deliver insight into the disease process. This chapter addresses the recent discoveries on circulating microRNA and long non-coding RNA as diagnostic or prognostic biomarkers in colorectal cancer. PMID:27573900

  18. Colorectal cancer prognosis: is it all mutation, mutation, mutation?

    PubMed Central

    Hassan, A B; Paraskeva, C

    2005-01-01

    For the 500 000 new cases of colorectal cancer in the world each year, identification of patients with a worse prognosis and those who are more likely to respond to treatment is a challenge. There is an increasing body of evidence correlating genetic mutations with outcome in tumours derived from human colorectal cancer cohorts. K-ras, but not p53 or APC, mutations appear to be associated with poorer overall survival in colorectal cancer patients. PMID:16099785

  19. [Histological spectrum of malignant melanoma].

    PubMed

    Brenn, T

    2015-02-01

    The diagnosis of melanocytic tumors is one of the most problematic areas in dermatology and diagnostic pathology. Melanoma is a malignant melanocytic tumor and the risk for metastasis and associated mortality is mainly dependent on tumor thickness and depth of invasion. Early recognition and correct diagnosis is therefore important for successful and effective treatment. The correct diagnosis of melanoma is, however, challenging due to the wide morphological spectrum. Historically, the disease was subdivided into superficial spreading, nodular, lentigo maligna and acral lentiginous melanoma but many more subtypes have subsequently been added. Some of these melanoma variants also show differences relating to the genetic background, clinical presentation, prognosis and treatment and may be associated with a specific differential diagnosis. In this article four of these melanoma variants, desmoplastic melanoma, nevoid melanoma, malignant blue nevus and pigment synthesizing melanoma will be discussed in more detail. PMID:25589353

  20. 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

  1. 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

  2. Tumor Metabolism of Malignant Gliomas

    PubMed Central

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang

    2013-01-01

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation. PMID:24217114

  3. Immunological Aspects of Malignant Gliomas.

    PubMed

    Cohen-Inbar, Or; Zaaroor, Menashe

    2016-07-01

    Glioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor immune response and the micro-invasive nature of the glioma malignant cells have been explained by a multitude of immune-suppressive mechanisms, proven in different models. These immune-resistant capabilities of the tumor result in a complex interplay this tumor shares with the immune system. We present a short review on the immunology of GBM, discussing the different unique pathological and molecular features of GBM, current treatment modalities, the principles of cancer immunotherapy and the link between GBM and melanoma. Current knowledge on immunological features of GBM, as well as immunotherapy past and current clinical trials, is discussed in an attempt to broadly present the complex and formidable challenges posed by GBM. PMID:27324313

  4. IRF4: Immunity. Malignancy! Therapy?

    PubMed Central

    Shaffer, Arthur L.; Tolga Emre, N. C.; Romesser, Paul B.; Staudt, Louis M.

    2009-01-01

    IRF4, a member of the IRF family of transcription factors, is expressed in cells of the immune system where it transduces signals from various receptors to activate or repress gene expression. IRF4 expression is a key regulator of several steps in lymphoid, myeloid and dendritic cell differentiation, including the differentiation of mature B cells into antibody-secreting plasma cells. IRF4 expression is also associated with many lymphoid malignancies, with recent evidence pointing to an essential role in multiple myeloma, a malignancy of plasma cells. Interference with IRF4 expression is lethal to multiple myeloma cells, irrespective of their genetic etiology, making IRF4 an “Achilles’ heel” that may be exploited therapeutically. PMID:19383829

  5. 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.

  6. Recent insights into nanotechnology development for detection and treatment of colorectal cancer.

    PubMed

    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

  7. 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

  8. Colorectal cancer risk factors among the population of South-East Siberia: a case-control study.

    PubMed

    Zhivotovskiy, Alexey S; Kutikhin, Anton G; Azanov, Artur Z; Yuzhalin, Arseniy E; Magarill, Yuri A; Brusina, Elena B

    2012-01-01

    Colorectal cancer remains one of the most widespread malignancies in the world. However, there is a lack of comprehensive studies considering colorectal cancer risk factors among Russian populations, particularly in Siberia. The aim of this investigation was to determine the impact of various lifestyle, dietary, family, and socioeconomical factors on colorectal cancer risk in South-East Siberia. We recruited 185 Russian colorectal cancer cases and 210 gender-, age-, and ethnicity-matched asymptomatic controls with no history of any malignant tumor, using a specially designed questionnaire to obtain relevant information. After the statistical analysis, we defined several significant factors affecting colorectal cancer risk. Among these were smoking (OR=2.13, 95%CI=1.4- 3.24, P=0.0004), being overweight (BMI between 25-30, OR=2.45, 95%CI=1.49-4.03, P=0.0004), alcohol drinking (OR=8.73, 95%CI=5.49-13.87, P<0.0001), beer drinking (OR=9.24, 95%CI=5.14-16.61, P<0.0001), consumption of hard liquor (OR=9.37, 95%CI=5.92-14.82, P<0.0001), excessive red meat consumption (P<0.0001), excessive intake of red meat products (P<0.0001), excessive intake of dairy products (P<0.0001), excessive sour cream and cheese consumption (P<0.0001 and 0.0002, respectively), spicy food consumption (OR=2.87, 95%CI=1.9-4.33, P<0.0001), family history of gastrointestinal malignant tumors (OR=3.99, 95%CI=2.09-7.59, P<0.0001), and income exceeding twice the subsistence minimum (OR=5.34, 95%CI=3.35-8.53, P<0.0001). Certain factors, such as high concentration of salt in the food and precancerous colonic lesions, demonstrated borderline significance (OR=3.45, 95%CI=1.68-7.1, P=0.0008, and OR=5.25, 95%CI=1.94-14.22, P=0.001, respectively). Some factors were established as protective, like consumption of rye bread and both rye and wheat bread (OR=0.32, 95%CI=0.21-0.5, P<0,0001, and OR=0.07, 95%CI=0.02-0.21, P<0.0001, respectively), and also low concentration of salt in the food, although this was of

  9. Lack of BRAFV600E mutation in stage I and II of colorectal cancer

    PubMed Central

    Molaei, Mahsa; Kishani Farahani, Roya; Maftouh, Mina; Taleghani, Mohammad Yaghoob; Vahdatinia, Mahsa; Khatami, Fatemeh; Nazemalhosseini- Mojarad, Ehsan; Asadzadeh Aghdae, Hamid; Aboutorabi, Akram; Zali, Mohammad Reza

    2016-01-01

    Aim: We aimed to explore the frequency of BRAFV600E mutation in Iranian patients with colorectal cancer (CRC) as well as its association with clinic pathological characteristic of patients. Background: CRC is the third leading cause of cancer related death. There is a growing body of data showing the association of BRAFV600E mutation with malignant transformation and clinical outcome of different tumors, including CRC. These findings suggest that BRAFV600E mutation can be used as diagnostic and/or prognostic biomarker for management of cancer patients. Patients and methods: A total of 85 patients with sporadic tumor were recruited. BRAFV600E mutation was investigated using sequencing of extracted DNAs from formalin-fixed paraffin-embedded (FFPE) tumor tissues. Electropherograms were analyzed using Laser-gene 6 software. Results: More than 95% of patients were in stage I and II and none of them were in stage IV. Patients were mostly below 55 years old and tumors were dominantly located in the distal colon. Of note, no BRAFV600E mutations were detected in our population. Conclusion: Our results showed no V600E mutation in the BRAF gene in stage I and II of CRC patients. Further studies in multi-center settings are warranted to examine the prognostic and/or predictive value of this marker in different stages of colorectal cancer patients. PMID:27099668

  10. Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells.

    PubMed

    de Lacerda, Tonielli Cristina Sousa; Costa-Silva, Bruno; Giudice, Fernanda Salgueiredo; Dias, Marcos Vinicios Salles; de Oliveira, Gabriela Pintar; Teixeira, Bianca Luise; Dos Santos, Tiago Goss; Martins, Vilma Regina

    2016-06-01

    Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies. The generation of conventional treatments has improved, but approximately 50 % of patients with CRC who undergo potentially curative surgery ultimately relapse and die, usually as a consequence of metastatic disease. Our previous findings showed that engagement of the cellular prion protein (PrP(C)) to its ligand HSP70/90 heat shock organizing protein (HOP) induces proliferation of glioblastomas. In addition, PrP(C) has been described as an important modulator of colorectal tumor growth. Here, we investigated the biological relevance of the PrP(C)-HOP interaction in CRC cells. We demonstrate that HOP induced the migration and invasion of CRC cell lines in a PrP(C)-dependent manner and that phosphorylation of the ERK1/2 pathway is a downstream mediator of these effects. Additionally, we show that a HOP peptide with the ability to bind PrP(C) and abolish the PrP(C)-HOP interaction inhibited the migration and invasion of CRC cells. Together, these data indicate that the disruption of the PrP(C)-HOP complex could be a potential therapeutic target for modulating the migratory and invasive cellular properties that lead to metastatic CRC. PMID:27112151

  11. Alternatively spliced variants of the cell adhesion molecule CD44 and tumour progression in colorectal cancer.

    PubMed Central

    Gotley, D. C.; Fawcett, J.; Walsh, M. D.; Reeder, J. A.; Simmons, D. L.; Antalis, T. M.

    1996-01-01

    Increased expression of alternatively spliced variants of the CD44 family of cell adhesion molecules has been associated with tumour metastasis. In the present study, expression of alternatively spliced variants of CD44 and their cellular distribution have been investigated in human colonic tumours and in the corresponding normal mucosa, in addition to benign adenomatous polyps. The expression of CD44 alternatively spliced variants has been correlated with tumour progression according to Dukes' histological stage. CD44 variant expression was determined by immunohistochemisty using monoclonal antibodies directed against specific CD44 variant domains together with RT-PCR analysis of CD44 variant mRNA expression in the same tissue specimens. We demonstrate that as well as being expressed in colonic tumour cells, the full range of CD44 variants, CD44v2-v10, are widely expressed in normal colonic crypt epithelium, predominantly in the crypt base. CD44v6, the epitope which is most commonly associated with tumour progression and metastasis, was not only expressed by many benign colonic tumours, but was expressed as frequently in normal basal crypt epithelium as in malignant colonic tumour cells, and surprisingly, was even absent from some metastatic colorectal tumours. Expression of none of the CD44 variant epitopes was found to be positively correlated with tumour progression or with colorectal tumour metastasis to the liver, results which are inconsistent with a role for CD44 variants as indicators of colonic cancer progression. Images Figure 2 Figure 3 Figure 5 Figure 6 PMID:8695347

  12. Is the routine microscopic examination of proximal and distal resection margins in colorectal cancer surgery justified?

    PubMed

    Morlote, Diana M; Alexis, John B

    2016-08-01

    Microscopic examination of the proximal and distal resection margins is part of the routine pathologic evaluation of colorectal surgical specimens removed for adenocarcinoma. Anastomotic donuts are frequently received and microscopically examined. We examined 594 specimens received over a period of 10 years and found only 3 cases of definitive direct involvement of a longitudinal margin by carcinoma. All 3 cases also showed tumor at the margin grossly. One case of margin involvement by adenocarcinoma was found in which the tumor was grossly 1.7 cm away; however, this finding was likely a tumor deposit, as the patient had diffuse metastatic disease. All 242 anastomotic donuts examined were free of carcinoma. Our study suggests that the proximal and distal margins of colorectal cancer specimens need not be examined microscopically in order to accurately assess margin status in cases where the tumor is at least 2 cm away from the margin of resection. Also, in cases in which anastomotic donuts are included with the case, these should be considered the true margins of resection and may be microscopically examined in place of the bowel specimen margins when margin examination is needed. Anastomotic donuts need not be examined if the tumor is more than 2 cm away from the margin. An exception to this rule would be cases of rectal adenocarcinoma where neoadjuvant therapy is given prior to surgery. In these cases, mucosal evidence of malignancy may be absent and microscopic examination of the margins is the only way to assure complete excision. PMID:27402222

  13. 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.

  14. HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers

    PubMed Central

    Gemoll, Timo; Roblick, Uwe J.; Szymczak, Silke; Braunschweig, Till; Becker, Susanne; Igl, Bernd-Wolfgang; Bruch, Hans-Peter; Ziegler, Andreas; Hellman, Ulf; Difilippantonio, Michael J.; Ried, Thomas; Jörnvall, Hans; Auer, Gert

    2016-01-01

    DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n = 19), diploid (n = 31), and aneuploid (n = 47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers. PMID:21290163

  15. 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

  16. [Device for intraarterial access for locoregional chemotherapy in hepatic metastasis from colorectal neoplasms (technical note)].

    PubMed

    Piccinini, E E; Ugolini, G; Rosati, G; Conti, A

    1994-01-01

    Metastasis are the most common malignant lesions of the liver. Liver is the most common site of visceral metastasis from colo-rectal carcinoma. Only in few patients are the lesions surgically resectable for cure and standard intravenous chemotherapy produces a low response rate. An intrahepatic arterial device for regional chemotherapy is an effective and safe alternative for unresectable liver metastasis from colorectal carcinoma, with a significant improvement on response rates compared with conventional i.v. chemotherapy; a longer survival is also reported in patients receiving intrahepatic therapy, even if the difference is not statistically significant. The catheter is inserted through the gastro-duodenal artery and the reservoir is placed in a subcutaneous pocket on the anterior thoracic wall. The Authors discuss indications, implantation technique and complications. Intra-arterial chemotherapy is administered in ambulatorial regimen and scintigraphic scanning and/or epatic ultrasonography are performed every three months to evaluate response rate. Median survival is variable from 12 to 17 months in the different series with response rates (disappeared metastases or tumor-mass reduction over 50%) of 48%-62%. The increased tumor responses reported together with a lower systemic toxicity (compared with systemic therapy) suggest that intra-arterial chemotherapy is a reliable and well tolerated treatment. PMID:7887590

  17. Colorectal cancer screening in African Americans: practice patterns in the United States. Are we doing enough?

    PubMed Central

    Waghray, Abhijeet; Jain, Alok; Waghray, Nisheet

    2016-01-01

    Background: Colorectal cancer (CRC) is a common form of malignancy and a leading cause of death in the United States. Screening decreases CRC incidence and mortality. African Americans are at an increased risk of developing CRC, and recommendations are to initiate screening at the age of 45. This study aims to assess the rate of screening for colorectal cancer in African Americans between the ages of 45–49. Methods: African Americans between the ages of 45–49 were identified in the Explorys national database. Patients who completed a colonoscopy, sigmoidoscopy or fecal occult blood test were identified and stratified by sex and insurance status. A P value < 0.05 was considered significant. Results: A total of 181 200 African Americans were identified as eligible for screening. Only 31 480 patients (17.4%) received at least one screening procedure for CRC. The majority of patients (66.7%) were screened via colonoscopy. African American females were more likely to complete a screening test (17.8% vs 16.7%; P < 0.01). The majority of patients (66.0%) who completed a screening test had private insurance. Conclusion: Race, gender and barriers to medical care contribute to disparities in CRC screening rates. Among African Americans, CRC screening remains suboptimal. Tailored public health initiatives, medical record alerts and improved communication between providers and patients are fundamental to addressing issues that impact poor adherence to CRC screening in African Americans. PMID:27071411

  18. 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." PMID:23511582

  19. RNA interference against TRIM29 inhibits migration and invasion of colorectal cancer cells.

    PubMed

    Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling; Cao, Hua; Zhang, Jun; Liu, Jie; Sheng, Huiming

    2016-09-01

    Colorectal cancer (CRC) is one of the most common malignancies worldwide. Tripartite motif-containing 29 (TRIM29) is a member of TRIM proteins family, which plays diverse physiological and pathological roles in humans. Recent studies found that TRIM29 expressed highly in CRC and promoted cell growth in vitro. However, its function in the metastasis of CRC has not been studied. In the present study, we confirmed the previous report that TRIM29 was upregulated in CRC tissues and high levels of TRIM29 expression were associated with poor overall survival of patients. Moreover, TRIM29 knockdown significantly reduced cancer cell proliferation via notably inducing cell cycle arrest and cell apoptosis. Silencing of TRIM29 significantly inhibited the migration and invasion ability of CRC cells. The protein levels of apoptosis‑, migration‑ and invasion‑related proteins were also changed after TRIM29 knockdown. Furthermore, phosphorylation levels of JAK2 and STAT3 were clearly reduced in TRIM29 knockdown cells, indicating a possible mechanism underlying its effects on colorectal carcinogenesis. Collectively, TRIM29 may exert oncogenic effects in CRC cells via regulating JAK2/STAT3 signaling. PMID:27430345

  20. Microsatellite Instability Status of Interval Colorectal Cancers in a Korean Population

    PubMed Central

    Lee, Kil Woo; Park, Soo-Kyung; Yang, Hyo-Joon; Jung, Yoon Suk; Choi, Kyu Yong; Kim, Kyung Eun; Jung, Kyung Uk; Kim, Hyung Ook; Kim, Hungdai; Chun, Ho-Kyung; Park, Dong Il

    2016-01-01

    Background/Aims A subset of patients may develop colorectal cancer after a colonoscopy that is negative for malignancy. These missed or de novo lesions are referred to as interval cancers. The aim of this study was to determine whether interval colon cancers are more likely to result from the loss of function of mismatch repair genes than sporadic cancers and to demonstrate microsatellite instability (MSI). Methods Interval cancer was defined as a cancer that was diagnosed within 5 years of a negative colonoscopy. Among the patients who underwent an operation for colorectal cancer from January 2013 to December 2014, archived cancer specimens were evaluated for MSI by sequencing microsatellite loci. Results Of the 286 colon cancers diagnosed during the study period, 25 (8.7%) represented interval cancer. MSI was found in eight of the 25 patients (32%) that presented interval cancers compared with 22 of the 261 patients (8.4%) that presented sporadic cancers (p=0.002). In the multivariable logistic regression model, MSI was associated with interval cancer (OR, 3.91; 95% confidence interval, 1.38 to 11.05). Conclusions Interval cancers were approximately four times more likely to show high MSI than sporadic cancers. Our findings indicate that certain interval cancers may occur because of distinct biological features. PMID:27114419

  1. [Malignant wounds in palliative care].

    PubMed

    Fromantin, Isabelle; Rollot, Florence; Nicodeme, Marguerite; Kriegel, Iréne

    2015-01-01

    In the alsence of effective cancer treatment, malignant wounds evolve. The decisions taken by the multi-disciplinary team with regard to their care vary depending on whether the patient is in the initial, advanced or terminal phase of palliative care. Modern dressings can be used to control bleeding, odours and drainage. The aim is to control the symptoms and improve the quality of life, until its end. PMID:26027186

  2. An analysis of malignant tumour incidence in the male population of Poland in the period 2006–2010

    PubMed Central

    Gałęziowska, Edyta

    2016-01-01

    In the period 2006–2010, the National Cancer Registry indicated a gradual increase in the incidence of malignant tumours among men, from 64,092 thousand in 2006 to 70,024 thousand in 2010. In the reference period, the number of deaths due to malignant tumours among men oscillated around 52 thousand. The aim of this study was to analyse the incidence of malignant tumours in the male population of Poland in the period 2006–2010. The study material comprised data obtained from the National Cancer Registry and from the Central Statistical Office, available on the websites of these institutions. The malignant-tumour incidence rate among the male population in 2006–2010 showed a slow but steady growth, while the death rate dropped slightly at the end of 2010. The hypothesis that the cancer-incidence risk grows with age has been proven, and a substantial increase in this risk is observed from the fourth decade of life. The most common malignant tumours in Poland in the analysed period included lung cancer, followed by prostate cancer and colorectal cancer. Future prophylactic and educational programmes should be addressed to men prior to reaching the age of increased cancer risk. PMID:26843846

  3. The role of virtual colonoscopy in colorectal screening.

    PubMed

    Patel, Jay D; Chang, Kevin J

    2016-01-01

    Colorectal cancer is the second leading cause of cancer-related deaths in the United States. The earlier colorectal cancer is detected, the better chance a person has of surviving 5 years after being diagnosed, emphasizing the need for effective and regular colorectal screening. Computed tomographic colonography has repeatedly demonstrated sensitivities equivalent to the current gold standard, optical colonoscopy, in the detection of clinically relevant polyps. It is an accurate, safe, affordable, available, reproducible, quick, and cost-effective option for colorectal screening and should be considered for mass screening. PMID:26298421

  4. Colonoscopy as a screening test for colorectal cancer.

    PubMed

    Schapira, M; Adler, M

    2005-01-01

    Colonoscopy is the current gold standard for the diagnosis and treatment of colorectal neoplasms. Several gastroenterological and/or endoscopical societies recommend screening by colonoscopy in high risk patients for colorectal cancer whilst for average risk patients colonoscopy remains a valid option. In some countries screening colonoscopy is now covered by medical insurance. It is also the final common pathway of all colorectal cancer screening methods. This paper addresses the advantages and also limitations of colonoscopy as the first procedure for colorectal screening and emphasizes the importance of organized training and continuous assessment of competence of gastroenterologists and the necessity to have quality control audits of the endoscopy units. PMID:16013645

  5. Protective effect of dietary fibers against colorectal carcinoma.

    PubMed

    Mia, M Abdur Razzaque; Siddiqui, M Nazrul Islam; Rukunuzzaman, M; Rahman, M Matiur; Deb, Kalpana

    2002-01-01

    Dietary fibers are remnant of plant cells resistant to hydrolysis by human alimentary tract enzymes. These are cellulose, hemicellulose, lignin, pectins and gums. Intake of dietary fibers or foods rich in dietary fibers decreases the incidence of colorectal carcinoma. Reduced risk of colorectal carcinoma is reported when populations with diet high in red meat and total fats switched to a diet high in total fibers and certain whole grain, goods. Fibre intake is also inversely related to mortality from colorectal carcinoma. Beneficial influence of most vegetables and fruits against colorectal carcinoma is confirmed and this is due to their fibre contents. PMID:12148400

  6. Molecular biology of malignant gliomas.

    PubMed

    Belda-Iniesta, Cristóbal; de Castro Carpeño, Javier; Casado Sáenz, Enrique; Cejas Guerrero, Paloma; Perona, Rosario; González Barón, Manuel

    2006-09-01

    Gliomas are the most common primary brain tumours. In keeping with the degree of aggressiveness, gliomas are divided into four grades, with different biological behaviour. Furthermore, as different gliomas share a predominant histological appearance, the final classification includes both, histological features and degree of malignancy. For example, gliomas of astrocytic origin (astrocytomas) are classified into pilocytic astrocytoma (grade I), astrocytoma (grade II), anaplastic astrocytoma (grade III) and glioblastoma multiforme (GMB) (grade IV). Tumors derived from oligodendrocytes include grade II (oliogodendrogliomas) and grade III neoplasms (oligoastrocytoma). Each subtype has a specific prognosis that dictates the clinical management. In this regard, a patient diagnosed with an oligodendroglioma totally removed has 10-15 years of potential survival. On the opposite site, patients carrying a glioblastoma multiforme usually die within the first year after the diagnosis is made. Therefore, different approaches are needed in each case. Obviously, prognosis and biological behaviour of malignant gliomas are closely related and supported by the different molecular background that possesses each type of glioma. Furthermore, the ability that allows several low-grade gliomas to progress into more aggressive tumors has allowed cancer researchers to elucidate several pathways implicated in molecular biology of these devastating tumors. In this review, we describe classical pathways involved in human malignant gliomas with special focus with recent advances, such as glioma stem-like cells and expression patterns from microarray studies. PMID:17005465

  7. Management of Inoperable Malignant Neoplasms.

    PubMed

    Kiess, Ana P; Quon, Harry

    2016-01-01

    For patients with inoperable salivary gland malignancy, radiation therapy has significant limitations but has been the mainstay of treatment. With standard photon radiation (X-rays), the 10-year loco-regional control (LRC) and overall survival rates are only ∼25%. Neutron radiation has potential biological advantages over photon radiation because it causes increased DNA damage, and studies of patients with inoperable salivary gland malignancy have shown improved 6-year LRC and overall survival of ∼60%. However, neutron radiation may also increase the risk of late toxicities, especially central nervous system toxicities after treatment of tumors involving the base of the skull. Proton radiation has potential physical advantages due to minimal exit dose through normal tissues, and a recent study has demonstrated 90% 5-year LRC after combined proton/photon radiation for adenoid cystic carcinoma involving the base of the skull. Stereotactic radiosurgery has also been used in combination with neutrons or standard photons as a technique to boost the skull base. The use of concurrent chemotherapy as a radiosensitizer has been considered based on extrapolation of data on squamous cell carcinomas, but further data are needed on inoperable salivary gland malignancies. Newer targeted therapies are also under investigation, and clinical trial enrollment is encouraged. PMID:27093559

  8. Comparative effectiveness in hepatic malignancies.

    PubMed

    Page, Andrew J; Cosgrove, David; Pawlik, Timothy M

    2015-01-01

    The benefits of applying comparative effectiveness research (CER) strategies to the management of cancer are important. As the incidence of cancer increases both in the United States and worldwide, accurate analysis of which tests and treatments should be applied in which situations is critical, both in terms of measurable and meaningful clinical outcomes and health care costs. In the last 20 years alone, multiple controversies have arisen in the diagnosis and treatment of primary and metastatic tumors of the liver, making the management of liver malignancies a prime example of CER. Contributing factors to the development of these controversies include improvements in molecular characterization of these diseases and technological advances in surgery and radiology. The relative speed of these advances has outpaced data from clinical trials, in turn making robust data to inform clinical practice lacking. Indeed, many of the current treatment recommendations for the management of liver malignancies are based primarily on retrospective data. We herein review select CER issues concerning select decision-making topics in the management of liver malignancies. PMID:25677025

  9. 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

  10. Survival of patients with hereditary colorectal cancer: comparison of HNPCC and colorectal cancer in FAP patients with sporadic colorectal cancer.

    PubMed

    Bertario, L; Russo, A; Sala, P; Eboli, M; Radice, P; Presciuttini, S; Andreola, S; Rodriguez-Bigas, M A; Pizzetti, P; Spinelli, P

    1999-01-18

    Conflicting data exist on the prognosis of hereditary colorectal cancer. HNPCC patients, in particular, are often reported to have a better survival. We examined 2,340 colorectal-cancer patients treated in our Institution: 144 HNPCC patients (Amsterdam Criteria), 161 FAP patients and 2,035 patients with sporadic cancer. Data on hereditary-cancer patients treated between 1980 and 1995 was collected in a registry. The 2,035 sporadic colorectal-cancer patients (controls) included all new cases treated in the Department of Gastrointestinal-Tract Surgery during the same period. Observed survival was estimated using the Kaplan-Meier method. Cumulative survival probability was estimated at 5 years within each group and stratified by various clinical and pathological variables. The age distribution at diagnosis of sporadic patients was significantly higher than that of FAP and HNPCC patients (median 60 years vs. 43 and 49 years; p < 0.0001). In the HNPCC group, 40% had a right cancer location, vs. 14% in the FAP group and 13% in the sporadic-cancer group. In the sporadic group, 51% were early-stage cancers (Dukes A or B) vs. 48.4% and 52.1% in the FAP and HNPCC groups respectively. In the HNPCC, FAP and sporadic-cancer groups, the 5-year cumulative survival rate was 56.9%, 54.4% and 50.6% respectively. Survival analysis by the Cox proportional-hazards method revealed no substantial survival advantage for HNPCC and FAP patients compared with the sporadic group, after adjustment for age, gender, stage and tumor location. The hazard ratio for HNPCC was 1.01 (95% CI 0.72-1.39) and 1.27 (95% CI 0.95-1.7) for FAP patients compared with the sporadic-colorectal-cancer group. PMID:9935197

  11. A case of syphilitic anal condylomata lata mimicking malignancy

    PubMed Central

    Tayal, Sarup; Shaban, Fadlo; Dasgupta, Kaushik; Tabaqchali, Mohamed A.

    2015-01-01

    Introduction Condylata lata in secondary syphilis is well known presentation and needs to be considered in differential diagnosis of perianal lesions. In England between 2013 and 2014 the overall incidence of infectious syphilis increased by 33% and is mainly seen in men who have sex with men. Presentation of case We report the management of a 49-years-old Caucasian homosexual man with perianal lesions that were suspicious of malignancy. After biopsies, colonoscopy, staging with computed tomography, magnetic resonance imaging and syphilis serology anal cancer was excluded and a diagnosis of syphilis was confirmed. He was referred to the sexual health clinic for the appropriate investigations and treatment. Discussion This case highlights the consideration of treatable infectious syphilis pathology. The main differential diagnosis of perianal growths to consider is condylomata acuminata (warts caused by human papillomavirus), anal cancer, syphilis, chancroid, haemorrhoids, tuberculosis and lymphogranuloma venereum. To differentiate a biopsy is needed for histopathological examination. A dense plasma cell infiltrate and numerous spirochetes visualised by immunostaining confirms condylomata lata. Conclusion In UK, it is important for colorectal surgeons to be aware of syphilitic condylomata lata and consider this when dealing with perianal lesions. It is advisable to refer patients suspected of or diagnosed with syphilis to sexual health clinics to help improve outcome. In sexual health clinics additional investigations and treatment are available in addition to partner notification and follow-up can be offered. PMID:26555060

  12. Greatwall promotes cell transformation by hyperactivating AKT in human malignancies

    PubMed Central

    Vera, Jorge; Lartigue, Lydia; Vigneron, Suzanne; Gadea, Gilles; Gire, Veronique; Del Rio, Maguy; Soubeyran, Isabelle; Chibon, Frederic; Lorca, Thierry; Castro, Anna

    2015-01-01

    The PP2A phosphatase is often inactivated in cancer and is considered as a tumour suppressor. A new pathway controlling PP2A activity in mitosis has been recently described. This pathway includes the Greatwall (GWL) kinase and its substrates endosulfines. At mitotic entry, GWL is activated and phosphorylates endosulfines that then bind and inhibit PP2A. We analysed whether GWL overexpression could participate in cancer development. We show that GWL overexpression promotes cell transformation and increases invasive capacities of cells through hyperphosphorylation of the oncogenic kinase AKT. Interestingly, AKT hyperphosphorylation induced by GWL is independent of endosulfines. Rather, GWL induces GSK3 kinase dephosphorylation in its inhibitory sites and subsequent SCF-dependent degradation of the PHLPP phosphatase responsible for AKT dephosphorylation. In line with its oncogenic activity, we find that GWL is often overexpressed in human colorectal tumoral tissues. Thus, GWL is a human oncoprotein that promotes the hyperactivation of AKT via the degradation of its phosphatase, PHLPP, in human malignancies. DOI: http://dx.doi.org/10.7554/eLife.10115.001 PMID:26613407

  13. Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer

    PubMed Central

    Tsuno, Nelson H.; Otani, Kensuke; Kawai, Kazushige; Nishikawa, Takeshi; Shuno, Yasutaka; Sasaki, Kazuhito; Hongo, Kumiko; Kaneko, Manabu; Sunami, Eiji; Takahashi, Koki; Nagawa, Hirokazu; Kitayama, Joji

    2012-01-01

    Adiponectin is a hormone secreted by adipose tissue and has a variety of functions including the inhibition of tumor growth. The expression and function of the two major adiponectin receptors, AdipoR1 and AdipoR2, in malignant tissue have not been well characterized. In the present study, we evaluated the mRNA levels of AdipoR1 and AdipoR2 expression in 48 surgically resected colorectal cancer specimens, as well as normal colonic mucosa, by quantitative RT-PCR. The values obtained were standardized by β-actin mRNA, and the correlation between their relative expression levels and the clinicopathological characteristics of the patients was examined. The relative expression levels of AdipoR1 and AdipoR2 were significantly reduced in cancer tissue compared with normal tissue (AdipoR1: 0.97±0.39 vs. 1.37±0.41, P<0.0001; AdipoR2: 0.92±0.31 vs. 1.60±0.46, P<0.0001). AdipoR1 and AdipoR2 levels were further reduced in tumors with nodal metastases and the difference was statistically significant in the case of AdipoR2 (0.79±0.27 vs. 1.02±0.30, P=0.012). The results of this study demonstrated that the expression levels of adiponectin receptors are reduced in cancer specimens compared to normal tissue, indicating a downregulation in the course of the development and progression of colorectal cancer. Since adiponectin is abundantly present in the whole body and has inhibitory effects on cancer cells, this downregulation of the receptors may be an escape mechanism of malignant cells from the suppressive effects of adiponectin. PMID:22740988

  14. 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

  15. Potential Targets for Colorectal Cancer Prevention

    PubMed Central

    Temraz, Sally; Mukherji, Deborah; Shamseddine, Ali

    2013-01-01

    The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research. PMID:23975167

  16. Plasminogen activators in human colorectal neoplasia.

    PubMed Central

    Gelister, J S; Mahmoud, M; Lewin, M R; Gaffney, P J; Boulos, P B

    1986-01-01

    A crucial step in the transition from adenomatous polyp to invasive colorectal cancer is the degradation of the epithelial basement membrane. Plasminogen activators may play a part in regulating the extracellular protease environment necessary for this to occur. Both functional and antigenic activity of the two principal activators of plasminogen, tissue plasminogen activator and urokinase, were measured in 30 colorectal cancers, matched samples of mucosa, and eight adenomatous polyps. Both polyps (p less than 0.01) and carcinomas (p less than 0.001) had raised urokinase activities compared with normal mucosa, the activity being highest in the carcinomas. Activity of tissue plasminogen activator, however, was diminished in both polyps (p less than 0.01) and carcinomas (p less than 0.001) compared with normal mucosa, the values being lowest in carcinomas. Plasmin generation by urokinase--in contrast with tissue plasminogen activator--is fibrin independent and thus less subject to physiological control. Images p730-a PMID:3094628

  17. Ziv-aflibercept in metastatic colorectal cancer

    PubMed Central

    Patel, Anuj; Sun, Weijing

    2014-01-01

    The combination of cytotoxic chemotherapy and antiangiogenic agents has become a conventional treatment option for patients with metastatic colorectal cancer. Ziv-aflibercept is a fusion protein which acts as a decoy receptor for vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PlGF); it was approved in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing fluoropyrimidine-based regimen. Herein we review the role of tumor angiogenesis as the rationale for antiangiogenic therapy, the clinical data associated with ziv-aflibercept, and its current role as a treatment option compared to other antiangiogenic agents, such as bevacizumab and regorafenib. PMID:24368879

  18. Gut Microbiota, Inflammation, and Colorectal Cancer.

    PubMed

    Brennan, Caitlin A; Garrett, Wendy S

    2016-09-01

    Colorectal cancer is the second-leading cause of cancer-related deaths in the United States and fourth-leading cause of cancer-related deaths worldwide. While cancer is largely considered to be a disease of genetic and environmental factors, increasing evidence has demonstrated a role for the microbiota (the microorganisms associated with the human body) in shaping inflammatory environments and promoting tumor growth and spread. Herein, we discuss both human data from meta'omics analyses and data from mechanistic studies in cell culture and animal models that support specific bacterial agents as potentiators of tumorigenesis-including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli. Further, we consider how microbes can be used in diagnosing colorectal cancer and manipulating the tumor environment to encourage better patient outcomes in response to immunotherapy treatments. PMID:27607555

  19. 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

  20. Endoscopic submucosal dissection for colorectal neoplasms

    PubMed Central

    Takamaru, Hiroyuki; Mori, Genki; Yamada, Masayoshi; Kinjo, Yuzuru; So, Eriko; Abe, Seiichiro; Otake, Yosuke; Nakajima, Takeshi; Matsuda, Takahisa; Saito, Yutaka

    2014-01-01

    Endoscopic submucosal dissection (ESD) is an established therapeutic technique for the treatment of gastrointestinal neoplasms. Because it is typically completed as en bloc resection, this technique provides a complete specimen for precise pathological evaluation. On the other hand, ESD is not as widely applied in treating colorectal neoplasms as with gastric cancers, due to its technical difficulty, longer procedure time, and increased risk of perforation. However, some devices that facilitate ESD and improve the safety of the procedure have been recently reported, and the use of the technique has gradually spread worldwide. Endoscopists who begin to perform ESD need to recognize the indications of ESD, the technical issue involved in this procedure, and its associated complications. This review outlines the methods and certain types of devices used for colorectal ESD. PMID:25333002

  1. Expression profile of polyunsaturated fatty acids in colorectal cancer

    PubMed Central

    Yang, Kai; Li, Hong; Dong, Jin; Dong, Yan; Wang, Chang-Zheng

    2015-01-01

    AIM: To investigate the relationship between the metabolism of polyunsaturated fatty acids (PUFAs) and tumor-associated factors for predicting the outcome of colorectal carcinoma (CRC) in Chinese patients. METHODS: Fresh-frozen malignant and normal tissues from 82 Chinese patients with CRC were analyzed for PUFA composition using gas-liquid chromatography. The levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), prostaglandin E2 and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunosorbent assay, and the levels of VEGF, p53 and Ki-67 were measured by immunohistochemistry. RESULTS: In malignant tissue, compared with normal tissue, the levels of total ω-6 PUFAs (24.64% ± 3.41% vs 26.77% ± 3.37%, P = 0.00) and linoleic acid (LA) (15.46% ± 3.51% vs 18.30% ± 2.83%, P < 0.01) were lower, whereas the levels of total ω-3 PUFAs (1.58% ± 0.74% vs 1.35% ± 0.60%, P < 0.01) and dihomo-gamma-linolenic acid (DGLA) (1.32% ± 0.69% vs 0.85% ± 0.29%, P < 0.01) were significantly higher. The ratios of arachidonic acid (AA)/LA (0.53 ± 0.22 vs 0.42 ± 0.19, P < 0.01) and AA/total ω-6 PUFAs (0.31 ± 0.09 vs 0.27 ± 0.10, P < 0.01) were also significantly higher in malignant tissue. The levels of PDGF (353.10 ± 148.85 pg/mL vs 286.09 ± 104.91 pg/mL, P < 0.01), COX-2 (125.21 ± 70.29 ng/mL vs 67.06 ± 42.22 ng/mL, P < 0.01) and VEGF (357.11 ± 128.76 pg/mL vs 211.38 ± 99.47 pg/mL, P < 0.01) were also higher in malignant tissue compared to normal tissue. COX-2 was inversely correlated with LA (R = -0.3244, P < 0.05) and positively correlated with AA/total ω-6 PUFAs (R = 0.3083, P < 0.05) and AA/LA (R = 0.3001, P < 0.05). The tissue level of LA was highest in poorly differentiated tumors (19.9% ± 6.3%, P < 0.05), while the ratio of AA/ω-3 PUFAs was lowest in these tumors (10.8 ± 2.6, P < 0.05). In VEGF-positive tumors, the level of LA was higher (16.2% ± 3.7% vs 13.9% ± 2.7%, P < 0.01), while the AA/ω-3PUFA, AA/ω-6

  2. Colorectal Stenting: An Effective Therapy for Preoperative and Palliative Treatment

    SciTech Connect

    Jost, Rahel S. Jost, Res; Schoch, Erich; Brunner, Brigit; Decurtins, Marco; Zollikofer, Christoph L.

    2007-06-15

    Purpose. To demonstrate the effectiveness of preoperative and palliative colorectal stent placement in acute colonic obstruction. Methods. Sixty-seven consecutive patients (mean age 67.3 years, range 25-93 years) with clinical and radiological signs of colonic obstruction were treated: 45 (67%) preoperatively and 22 (33%) with a palliative intent. In 59 patients (88%) the obstruction was malignant, while in 8 (12%) it was benign. A total of 73 enteric Wallstents were implanted under combined fluoroscopic/endoscopic guidance. Results. Forty-five patients were treated preoperatively with a technical success rate of 84%, a clinical success rate of 83%, and a complication rate of 16%. Of the 38 patients who were successfully stented preoperatively, 36 (95%) underwent surgery 2-22 days (mean 7.2 days) after stent insertion. The improved general condition and adequate bowel cleansing allowed single-stage tumor resection and primary end-to-end anastomosis without complications in 31 cases (86% of all operations), while only 5 patients had colostomies. Stent placement was used as the final palliative treatment in 22 patients. The technical success rate was 95%, the clinical success rate 72%, and the complication rate relatively high at 67%, caused by reocclusion in most cases. After noninvasive secondary interventions (e.g., tube placement, second stenting, balloon dilatation) the secondary patency of stents was 71% and mean reported survival time after stent insertion was 92 days (range 10-285 days). Conclusion. Preoperative stent placement in acute colonic obstruction is minimally invasive and allows an elective one-stage surgery in most cases. Stent placement also proved a valuable alternative to avoid colostomy in palliation.

  3. 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.

  4. T-oligo as an anticancer agent in colorectal cancer

    PubMed Central

    Stone, Amanda L.; Sethakorn, Nan; Uppada, Srijayaprakash B.; Devito, Joseph T.; Bissonnette, Marc

    2016-01-01

    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. PMID:24632202

  5. Increased Expression of PHGDH and Prognostic Significance in Colorectal Cancer.

    PubMed

    Jia, Xiao-Qin; Zhang, Shu; Zhu, Hui-Jun; Wang, Wei; Zhu, Jin-Hong; Wang, Xu-Dong; Qiang, Jian-Feng

    2016-06-01

    Phosphoglycerate dehydrogenase (PHGDH) plays an essential role in cancer-specific metabolic reprogramming. It has been reported as a putative metabolic oncogene in several types of human malignant tumors, such as breast cancer and melanoma. To date, PHGDH expression in colorectal cancer (CRC) as well as its association with clinicopathological characteristics and prognostic implication remain undetermined. In this study, we determined the PHGDH protein expression using tissue microarray immunohistochemistry (TMA-IHC) on 193 pairs of formalin-fixed, paraffin-embedded specimens of CRC and adjacent tissues, 25 chronic colitis, 41 low-, and 19 high-grade intraepithelial neoplasia specimens, and we also determined PHGDH mRNA level using quantitative reverse transcription PCR (qRT-PCR) on additional 23 pairs of fresh CRC tissues and adjacent tissues. We found that both PHGDH mRNA and protein was highly expressed in tumor tissues in comparison with matched adjacent non-tumor tissues, and high PHGDH protein expression was correlated with advanced TNM stage (P = .038) and larger tumor (P = .001). Multivariate Cox regression analysis showed that PHGDH protein expression (HR = 2.285, 95% CI = 1.18 to 4.41, P = .014), tumor differentiation (HR = .307, 95% CI = .154 to 0.609, P = .001), and TNM stage (HR = 1.791, 95% CI = 1.125 to 2.85, P = .014) were independent prognostic factors in CRC. Kaplan-Meier survival curves and log rank test showed that high PHGDH protein expression contributed to poor outcome in CRC patients (P < .001). In conclusion, these results suggest that assessment of PHGDH expression could be useful in identifying a high-risk subgroup of CRC. PMID:27267836

  6. [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. PMID:11894400

  7. 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

  8. 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

  9. N-glycosylation of Colorectal Cancer Tissues

    PubMed Central

    Balog, Crina I. A.; Stavenhagen, Kathrin; Fung, Wesley L. J.; Koeleman, Carolien A.; McDonnell, Liam A.; Verhoeven, Aswin; Mesker, Wilma E.; Tollenaar, Rob A. E. M.; Deelder, André M.; Wuhrer, Manfred

    2012-01-01

    Colorectal cancer is the third most common cancer worldwide with an annual incidence of ∼1 million cases and an annual mortality rate of ∼655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers. PMID:22573871

  10. Spatial Analysis of Colorectal Cancer in Iran.

    PubMed

    Pakzad, Reza; Moudi, Asieh; Pournamdar, Zahra; Pakzad, Iraj; Mohammadian-Hashejani, Abdollah; Momenimovahed, Zohre; Salehiniya, Hamid; Towhidi, Farhad; Makhsosi, Behnam Reza

    2016-01-01

    Colorectal cancer is one of the most common cancers. Due to demographic changes, it is predicted that the incidence of this cancer will increase. Variations of its incidence rate among geographical areas are due to various contributing factors. Since there have been a lack of studies on this topic in our country, the present assessment of spatial patterns of colorectal cancer incidence in Iran was performed. In this ecological study, the new cases of colon cancer were extracted from Cancer Registry Center report of the Health Deputy of Iran in 2009. The reported incidences of the disease were standardized on the basis of the World Health Organization population and the direct method. Then the data were inserted into the GIS software, and finally, using the analysis of hot spots (Getis-Ord Gi) high-risk areas were drawn. Provinces that are higher or lower than the national average (1.9 SD) were considered hot spots or cold spots, significant at the level of 0.05. A total of 6,210 cases of colorectal cancer were registered in Iran in 2009, of which 3,727 were in men and 2,783 in women (age-standardized rates of 11.3 and 10.9 per 100,000 population, respectively). The results showed that in central and northern Iran including Isfahan, Qom, Tehran, Qazvin and Mazandaran significant hot spots in men were present (p <0.05). In women also we have high incidence in northern and central states: Mazandaran province (p<0.01) and the province of Tehran (p<0.05) had higher incidences than the national average and were apparent as significant hot spots. Analysis of the spatial distribution of colorectal cancer showed significant differences between different areas pointing to the necessity for further epidemiological studies into the etiology and early detection. PMID:27165208

  11. Colorectal Cancer with Uncommon Metastatic Spread

    PubMed Central

    Dellavedova, Luca; Calcagno, Anna; Roncoroni, Lucia; Maffioli, Lorenzo Stefano

    2015-01-01

    The prevalence of bone metastases from colorectal cancer (CRC) is quite low and the presence of isolated osseous metastases at the time of diagnosis or the onset of bone metastases without other organ involvement during follow-up is even lower. Here, we present an interesting case of diffuse skeletal metastases from CRC in which both the atypical presentation of the metastatic spread and the presence of infective comorbidities created some troubles in getting the final diagnosis. PMID:26420997

  12. [Current strategy in colorectal cancer screening].

    PubMed

    Lefter, L P; Dajbog, Elena; Scripcariu, V; Dragomir, Cr

    2005-01-01

    Screening programs should begin by classifying the individual patient's level of risk based on personal, family, and medical history, which will determine the appropriate approach for each subject. The individual's risk status determines when screening should be initiated and what tests and frequency are appropriate. To achieve these aims, care systems should establish standards and operating procedures. This review focuses on colorectal cancer screening methodology highlighting the latest available strategies. PMID:16610172

  13. Future of Minimally Invasive Colorectal Surgery.

    PubMed

    Whealon, Matthew; Vinci, Alessio; Pigazzi, Alessio

    2016-09-01

    Minimally invasive surgery is slowly taking over as the preferred operative approach for colorectal diseases. However, many of the procedures remain technically difficult. This article will give an overview of the state of minimally invasive surgery and the many advances that have been made over the last two decades. Specifically, we discuss the introduction of the robotic platform and some of its benefits and limitations. We also describe some newer techniques related to robotics. PMID:27582647

  14. PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes.

    PubMed

    Rosenbaum, Matthew W; Bledsoe, Jacob R; Morales-Oyarvide, Vicente; Huynh, Tiffany G; Mino-Kenudson, Mari

    2016-09-01

    Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key suppressors of the cytotoxic immune response. PD-L1 expression on tumor cells may be induced by the immune microenvironment, resulting in immune escape (adaptive immune resistance), and an adverse prognosis in many malignancies. In colorectal carcinoma the response to PD-1/PD-L1 inhibition is correlated with microsatellite instability. However, little is known about the clinicopathologic, molecular, and prognostic characteristics of colorectal carcinoma with PD-L1 expression. We performed immunohistochemistry for PD-L1 on 181 cases of colorectal carcinoma with known microsatellite instability and mutational status, and correlated PD-L1 expression with clinicopathologic features including tumor-infiltrating lymphocyte burden/immunophenotype, tumor mutational profile, and disease-specific survival. PD-L1 was expressed in tumors from 16 patients (9%) who were more often older (P=0.006) and female (P=0.035), with tumors exhibiting a larger size (P=0.013), but lower stage (P<0.001). PD-L1 expression was associated with increased CD8 and TBET-positive tumor-infiltrating lymphocytes, medullary phenotype, poor differentiation, microsatellite instability, BRAF mutation (P<0.001 for each), and a lower frequency of KRAS mutation (P=0.012). On multivariate analysis, PD-L1 expression was associated with medullary morphology and frequent CD8-positive tumor-infiltrating lymphocytes, suggesting adaptive immune resistance. PD-L1 positivity was not predictive of survival in the entire cohort, but it was associated with a lower disease-specific survival within the microsatellite-instability high cohort. PD-L1 expression in colorectal carcinoma is associated with clinicopathologic and molecular features of the serrated pathway of colorectal carcinogenesis, and is associated with a worse outcome within microsatellite-unstable tumors. These findings support the role of PD-L1 expression in providing normally immunogenic

  15. 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

  16. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible.

    PubMed

    Majumdar, Sumit; Kotina, Sreekanth; Mahesh, Nirujogi; Uppala, Divya; Kumar, Singam Praveen

    2016-06-01

    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

  17. No association between mitochondrial DNA copy number and colorectal adenomas.

    PubMed

    Thyagarajan, Bharat; Guan, Weihua; Fedirko, Veronika; Barcelo, Helene; Tu, Huakang; Gross, Myron; Goodman, Michael; Bostick, Roberd M

    2016-08-01

    Despite previously reported associations between peripheral blood mtDNA copy number and colorectal cancer, it remains unclear whether altered mtDNA copy number in peripheral blood is a risk factor for colorectal cancer or a biomarker for undiagnosed colorectal cancer. Though colorectal adenomas are well-recognized precursor lesions to colorectal cancer, no study has evaluated an association between mtDNA copy number and colorectal adenoma risk. Hence, we investigated an association between peripheral blood mtDNA copy number and incident, sporadic colorectal adenoma in 412 colorectal adenoma cases and 526 cancer-free controls pooled from three colonoscopy-based case-control studies that used identical methods for case ascertainment, risk factor determination, and biospecimen collection. We also evaluated associations between relative mtDNA copy number and markers of oxidative stress, including circulating F2 -isoprostanes, carotenoids, and fluorescent oxidation products. We measured mtDNA copy number using a quantitative real time polymerase chain reaction (PCR). We used unconditional logistic regression to analyze the association between mtDNA copy number and colorectal adenoma risk after multivariable adjustment. We found no association between logarithmically transformed relative mtDNA copy number, analyzed as a continuous variable, and colorectal adenoma risk (odds ratio = 1.02, 95%CI: 0.82-1.27; P = 0.86). There were no statistically significant associations between relative mtDNA copy number and other markers of oxidative stress. Our findings, taken together with those from previous studies, suggest that relative mtDNA copy number in peripheral blood may more likely be a marker of early colorectal cancer than of risk for the disease or of in vivo oxidative stress. © 2015 Wiley Periodicals, Inc. PMID:26258394

  18. 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

  19. TNIK inhibition abrogates colorectal cancer stemness

    PubMed Central

    Masuda, Mari; Uno, Yuko; Ohbayashi, Naomi; Ohata, Hirokazu; Mimata, Ayako; Kukimoto-Niino, Mutsuko; Moriyama, Hideki; Kashimoto, Shigeki; Inoue, Tomoko; Goto, Naoko; Okamoto, Koji; Shirouzu, Mikako; Sawa, Masaaki; Yamada, Tesshi

    2016-01-01

    Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik−/−/Apcmin/+ mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB-0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. PMID:27562646

  20. microRNAs and Colorectal Cancer.

    PubMed

    Ress, Anna Lena; Perakis, Samantha; Pichler, Martin

    2015-01-01

    Colorectal cancer (CRC) is one of the most common types of human cancer with high cancer-related morbidity and mortality rates. The development and clinical validation of novel therapeutic avenues have improved the clinical outcome, but metastatic CRC still remains an incurable disease in most cases. The interest in discovering novel pathophysiological drivers in CRC is intensively ongoing and the search for novel biomarkers for early diagnosis, for patient's stratification for prognostic purposes or for predicting treatment response are warranted. microRNAs are small RNA molecules that regulate the expression of larger messenger RNA species by different mechanisms with the final consequence to provide a fine tuning tool for global gene expression patterns. First discovered in worms, around 15 years ago it became clear that microRNAs are also existing in humans and that they are widely involved in human carcinogenesis. Within the last years, tremendous progress in the understanding of microRNAs and their role in CRC carcinogenesis has been developed. In this book chapter, several examples of previously identified microRNAs and how they influence colorectal carcinogenesis will be discussed. The information starting at the underlying molecular mechanisms towards clinical applications will be depicted and an overview what great potential these small molecules might carry in future colorectal cancer medicine, will be discussed. PMID:26658998

  1. Implications of preoperative hypoalbuminemia in colorectal surgery.

    PubMed

    Truong, Adam; Hanna, Mark H; Moghadamyeghaneh, Zhobin; Stamos, Michael J

    2016-05-27

    Serum albumin has traditionally been used as a quantitative measure of a patient's nutritional status because of its availability and low cost. While malnutrition has a clear definition within both the American and European Societies for Parenteral and Enteral Nutrition clinical guidelines, individual surgeons often determine nutritional status anecdotally. Preoperative albumin level has been shown to be the best predictor of mortality after colorectal cancer surgery. Specifically in colorectal surgical patients, hypoalbuminemia significantly increases the length of hospital stay, rates of surgical site infections, enterocutaneous fistula risk, and deep vein thrombosis formation. The delay of surgical procedures to allow for preoperative correction of albumin levels in hypoalbuminemic patients has been shown to improve the morbidity and mortality in patients with severe nutritional risk. The importance of preoperative albumin levels and the patient's chronic inflammatory state on the postoperative morbidity and mortality has led to the development of a variety of surgical scoring systems to predict outcomes efficiently. This review attempts to provide a systematic overview of albumin and its role and implications in colorectal surgery. PMID:27231513

  2. TNIK inhibition abrogates colorectal cancer stemness.

    PubMed

    Masuda, Mari; Uno, Yuko; Ohbayashi, Naomi; Ohata, Hirokazu; Mimata, Ayako; Kukimoto-Niino, Mutsuko; Moriyama, Hideki; Kashimoto, Shigeki; Inoue, Tomoko; Goto, Naoko; Okamoto, Koji; Shirouzu, Mikako; Sawa, Masaaki; Yamada, Tesshi

    2016-01-01

    Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik(-/-)/Apc(min/+) mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB-0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apc(min/+) mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. PMID:27562646

  3. MTDH genetic variants in colorectal cancer patients

    PubMed Central

    Gnosa, Sebastian; Ticha, Ivana; Haapaniemi, Staffan; Sun, Xiao-Feng

    2016-01-01

    The colorectal carcinogenesis is a complex process encompassing genetic alterations. The oncoprotein AEG-1, encoded by the MTDH gene, was shown previously to be involved in colorectal cancer (CRC). The aim of this study was to determine the frequency and the spectrum of MTDH variants in tumor tissue, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. The corresponding normal colorectal tissue was analyzed in the carriers of exonic variant to confirm germline or somatic origin. We detected 42 intronic variants, where 25 were novel. Furthermore, we found 8 exonic variants of which four, one missense (c.977C > G-germline) and three frameshift mutations (c.533delA-somatic, c.1340dupA-unknown origin, c.1731delA-unknown origin), were novel. In silico prediction analyses suggested four deleterious variants (c.232G > T, c.533delA, c.1340dupA, and c.1731delA). There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. We described several novel exonic and intronic variants of the MTDH gene. The detection of likely pathogenic truncating mutations and alterations in functional protein domains indicate their clinical significance, although none of the variants had prognostic potential. PMID:26983693

  4. Therapeutic strategy in unresectable metastatic colorectal cancer

    PubMed Central

    Tournigand, Christophe; André, Thierry; de Gramont, Aimery

    2012-01-01

    While surgery is the cornerstone treatment for early-stage colorectal cancer, chemotherapy is the first treatment option for metastatic disease when tumor lesions are frequently not fully resectable at presentation. Mortality from colon cancer has decreased over the past 30 years, but there is still a huge heterogeneity in survival rates that can be mainly explained by patient and tumor characteristics, host response factors, and treatment modalities. The management of unresectable metastatic colorectal cancer is a global treatment strategy, which applies several lines of therapy, salvage surgery, maintenance, and treatment-free intervals. The individualization of cancer treatment is based on the evaluation of prognostic factors for survival (serum lactate dehydrogenase level, performance status), and predictive factors for treatment efficacy [Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status]. The available treatment modalities for metastatic colorectal cancer are chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), anti-angiogenic agents (e.g. bevacizumab), and anti-epidermal growth factor agents (cetuximab, panitumumab). The increasing number of active compounds dictates the strategy of trials evaluating these treatments either in combination or sequentially. Alternative outcomes that can be measured earlier than overall survival are needed to shorten the duration and reduce the size and cost of clinical trials. PMID:22423266

  5. 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

  6. Implications of preoperative hypoalbuminemia in colorectal surgery

    PubMed Central

    Truong, Adam; Hanna, Mark H; Moghadamyeghaneh, Zhobin; Stamos, Michael J

    2016-01-01

    Serum albumin has traditionally been used as a quantitative measure of a patient’s nutritional status because of its availability and low cost. While malnutrition has a clear definition within both the American and European Societies for Parenteral and Enteral Nutrition clinical guidelines, individual surgeons often determine nutritional status anecdotally. Preoperative albumin level has been shown to be the best predictor of mortality after colorectal cancer surgery. Specifically in colorectal surgical patients, hypoalbuminemia significantly increases the length of hospital stay, rates of surgical site infections, enterocutaneous fistula risk, and deep vein thrombosis formation. The delay of surgical procedures to allow for preoperative correction of albumin levels in hypoalbuminemic patients has been shown to improve the morbidity and mortality in patients with severe nutritional risk. The importance of preoperative albumin levels and the patient’s chronic inflammatory state on the postoperative morbidity and mortality has led to the development of a variety of surgical scoring systems to predict outcomes efficiently. This review attempts to provide a systematic overview of albumin and its role and implications in colorectal surgery. PMID:27231513

  7. Multiple Primary Malignancies in Patients With Hepatocellular Carcinoma

    PubMed Central

    Xu, Wei; Liao, Wenjun; Ge, Penglei; Ren, Jinjun; Xu, Haifeng; Yang, Huayu; Sang, Xinting; Lu, Xin; Mao, Yilei

    2016-01-01

    Abstract Multiple primary malignancies (MPMs) are defined as 2 or more malignancies without subordinate relationship detected in different organs of an individual patient. Reports addressing MPM patients with hepatocellular carcinoma (HCC) are rare. We perform a 26-year follow-up study to investigate characteristics and prognosis of MPM patients associated with HCC due to the scarcity of relative researches. We retrospectively analyzed records of 40 patients who were diagnosed with MPM including HCC at the Departments of Surgery at Peking Union Medical College Hospital during 1989 to 2010. Their clinical characteristics and postoperative survival were compared with those of 448 patients who had HCC only during the study period. Among the 40 MPM patients, 11 were diagnosed synchronously and 29 metachronously. The most common extra-hepatic malignancies were lung cancer (15%), colorectal (12.5%), and thyroid carcinoma (12.5%). MPM patients had a negative hepatitis B virus infection rate (P = 0.013) and lower median alfa-fetoprotein (AFP) level (P = 0.001). Post-operative 1-, 3-, and 5-year overall survival (OS) rates for MPM patients were 82.5%, 64.5%, and 38.6% respectively, and showed no significant difference with those of HCC-only patients (84.7%, 54.2%, and 38.3% P = 0.726). During follow-up, 24 MPM patients died, including 17 (70.8%) who died of HCC-related causes. In univariate analysis, synchronous diagnosis, higher gamma glutamyltransferase (GGT) and/or AFP levels, tumor >5 cm and vascular invasion were significantly associated with shorter OS, but only tumor size was an independent OS factor in Cox modeling analysis. HCC should be considered as a potential second primary for all cancer survivors. Most MPM patients died of HCC-related causes and showed no significant difference in OS compared with HCC-only patients. Tumor size of HCC, rather than MPMs itself, was the only independent OS predictor for the MPM patients. PMID:27124050

  8. Primary colorectal lymphoma comprising both components of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma combined with cytomegalovirus colitis.

    PubMed

    Katsumata, Ryo; Matsumoto, Hiroshi; Motoyasu, Osawa; Murao, Takahisa; Ishii, Manabu; Fujita, Minoru; Tokunaga, Hirotoshi; Akiyama, Takashi; Wada, Hideho; Sugihara, Takashi; Shiotani, Akiko; Haruma, Ken

    2016-04-01

    A 16-year-old girl presented to our hospital with diarrhea and abdominal pain. The macroscopic findings of colonoscopy revealed multiple submucosal tumors and multiple ulcers, which were localized in the sigmoid colon, and diffuse granular mucosa which extended to the total colon. The pathological diagnosis was malignant lymphoma comprising both components of diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma, because the large lymphoma cells were CD20+, CD10-, and CD5-. Furthermore, immunohistochemical analysis of colorectal biopsy samples from multiple ulcers revealed cytomegalovirus (CMV)-positive cells. The patient was diagnosed with primary colorectal lymphoma comprising both components of DLBCL and MALT lymphoma combined with CMV colitis. She received anti-viral medication and chemotherapy. PMID:27015999

  9. Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population

    PubMed Central

    Kabzinski, J.; Mucha, B.; Cuchra, M.; Markiewicz, L.; Przybylowska, K.; Dziki, A.; Dziki, L.; Majsterek, I.

    2016-01-01

    DNA oxidative lesions are widely considered as a potential risk factor for colorectal cancer development. The aim of this work was to determine the role of the efficiency of base excision repair, both in lymphocytes and in epithelial tissue, in patients with CRC and healthy subjects. SNPs were identified within genes responsible for steps following glycosylase action in BER, and patients and healthy subjects were genotyped. A radioisotopic BER assay was used for assessing repair efficiency and TaqMan for genotyping. Decreased BER activity was observed in lymphocyte extract from CRC patients and in cancer tissue extract, compared to healthy subjects. In addition, polymorphisms of EXO1, LIG3, and PolB may modulate the risk of colorectal cancer by decreasing (PolB) or increasing (LIG3 and EXO1) the chance of malignant transformation. PMID:26649135

  10. Management of skin rash during egfr-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations

    PubMed Central

    Melosky, B.; Burkes, R.; Rayson, D.; Alcindor, T.; Shear, N.; Lacouture, M.

    2009-01-01

    The epidermal growth factor receptor (egfr) is often overexpressed or dysregulated in a variety of solid tumours, including gastrointestinal (gi) malignancies. Agents targeting the egfr-mediated signalling pathway are increasingly part of the therapeutic armamentarium for the treatment of advanced lung, head-and-neck, and colorectal carcinoma. The egfr inhibitors (egfris) approved in Canada include the tyrosine kinase inhibitors erlotinib and gefitinib (in selected cases), and the monoclonal antibodies (mAbs) panitumumab and cetuximab. Although egfris have been proven effective in the treatment of a variety of malignancies, the entire class of agents is associated with a high prevalence of dermatologic side effects, most commonly skin rash. This reversible condition requires intervention in approximately one third of patients. A proactive, multidisciplinary approach to management can help to improve skin rash and optimize clinical outcomes by preventing egfri dose reduction or discontinuation. In addition, effective management and patient education may help to alleviate the significant social and emotional anxiety related to this manageable side effect, thus resulting in improved quality of life. The present article focuses on egfr-targeted mAbs for the treatment of gi malignancy, addressing the pathophysiology, clinical presentation, and incidence of skin rash caused by this class of agents. Recommendations aimed at establishing a framework for consistent, proactive management of skin rash in the Canadian setting are presented. PMID:19229368

  11. Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy-current perspectives.

    PubMed

    Spiliotis, J; Halkia, E; de Bree, E

    2016-06-01

    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

  12. Simplified and optimized multispectral imaging for 5-ALA-based fluorescence diagnosis of malignant lesions.

    PubMed

    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

  13. 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

  14. 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

  15. 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

  16. 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. PMID:27068012

  17. 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

  18. Liver resection for colorectal cancer metastases

    PubMed Central

    Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

    2013-01-01

    Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung

  19. 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

  20. 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