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Sample records for malignant colorectal disease-a

  1. Hypercalcemia of Malignancy and Colorectal Cancer.

    PubMed

    Galindo, Rodolfo J; Romao, Isabela; Valsamis, Ageliki; Weinerman, Stuart; Harris, Yael Tobi

    2016-02-01

    Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control.

  2. Hypercalcemia of Malignancy and Colorectal Cancer

    PubMed Central

    Galindo, Rodolfo J.; Romao, Isabela; Valsamis, Ageliki; Weinerman, Stuart; Harris, Yael Tobi

    2016-01-01

    Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control. PMID:26998187

  3. Nonpolypoid colorectal neoplasms: gender differences in prevalence and malignant potential.

    PubMed

    Rondagh, Eveline J A; Masclee, Ad A M; van der Valk, Mirthe E; Winkens, Bjorn; de Bruïne, Adriaan P; Kaltenbach, Tonya; Soetikno, Roy M; Sanduleanu, Silvia

    2012-01-01

    Colonoscopy may fail to prevent colorectal cancer, especially in the proximal colon and in women. Nonpolypoid colorectal neoplasms may potentially explain some of these post-colonoscopy cancers. In the present study, we aimed to examine the prevalence and malignant potential of nonpolypoid colorectal neoplasms in a large population, with special attention to gender and location. We performed a cross-sectional study of all consecutive patients undergoing elective colonoscopy at a single academic medical center. The endoscopists were familiarized on the detection and treatment of nonpolypoid lesions. Advanced histology was defined by the presence of high-grade dysplasia or early cancer. We included 2310 patients (53.9% women, mean age 58.4 years) with 2143 colorectal polyps. Prevalences of colorectal neoplasms and nonpolypoid colorectal neoplasms were lower in women than in men (20.9% vs. 33.7%, p < 0.001 and 3.0% vs. 5.5%, p = 0.002). In women, nonpolypoid colorectal neoplasms were significantly more likely to contain advanced histology than polypoid ones (OR 2.89, 95% CI 1.24-6.74, p = 0.01), while this was not the case in men (OR 0.91, 95% CI 0.40-2.06, p = 0.83). Proximal neoplasms with advanced histology were more likely to be nonpolypoid than distal ones (OR 4.68, 95% CI 1.54-14.2, p = 0.006). Nonpolypoid mechanisms may play an important role in colorectal carcinogenesis, in both women and men. Although women have fewer colorectal neoplasms than men, they have nonpolypoid colorectal neoplasms, which frequently contain advanced histology.

  4. 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.

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

    PubMed

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

    1992-10-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-05-01

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

  9. Gynecological malignancy risk in colorectal cancer survivors: A population-based cohort study.

    PubMed

    Chang, Wei-Chun; Muo, Chih-Hsin; Liang, Ji-An; Sung, Fung-Chang; Kao, Chia-Hung

    2015-10-01

    This study was carried out to assess the risk of gynecological malignancy in colorectal cancer survivors using a population-based retrospective cohort study. Using the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 37,176 patients with colorectal cancer diagnosed in 1998-2009, aged 20 years and above, without other cancer history. We also randomly selected 148,700 women without any cancer in the comparison cohort, frequency matched by age and diagnosis date. Incidences and hazards of breast, cervix, endometrial and ovarian cancers were evaluated by 201l. The overall incidence of the 4 types of gynecological cancer was 39.0% higher in colorectal cancer patients than in comparisons (2.99 vs. 2.14 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.46 (95% confidence interval (CI) = 1.31-1.62). Breast cancer accounted for most subsequent cancer. The multivariable Cox method measured HR was the highest for endometrial cancer (3.40, 95% CI = 2.59-4.47) for the colorectal cohort relative to comparisons, followed by ovarian cancer and breast cancer, except cervix cancer. The risk of gynecological malignancies was apparently elevated for colorectal cancer survivors <50 years of age. Follow-up measures are suggested for women with colorectal cancer for early detection and prevention of the subsequent gynecological malignancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Significance of histologic criteria for the management of patients with malignant colorectal polyps and polypectomy.

    PubMed

    Netzer, P; Binek, J; Hammer, B; Lange, J; Schmassmann, A

    1997-09-01

    The management of invasive cancer in colorectal polyps (malignant polyps) is controversial, particularly with regard to the different sets of histologic criteria for deciding whether malignant colorectal polyps should be treated by polypectomy alone or be followed by surgical resection. We report on the outcome of patients in accordance with the histologic assessment of their malignant polyps. Malignant polyps were defined as having favourable histology (free margin, grade I or II, and no angiolymphatic invasion) or unfavorable histology (no free margin, grade III, or angiolymphatic invasion). Malignant polyps with favourable histology were treated by endoscopic polypectomy alone, whereas further therapy was recommended for malignant polyps with unfavourable histology. Residual cancer in a resection specimen and local or metastatic recurrence during the follow-up period (mean, 60 months; range, 12 - 120) were defined as adverse outcome. Thirty-seven malignant polyps were detected in 35 (0.5%) of 6605 patients. Five of these 35 patients were treated by primary bowel resection and analysed separately. In the other 30 patients the following unfavourable histologic signs were detected in 20 (62.5%) of 32 malignant polyps; no free margin in 16, grade III in 1, and angiolymphatic invasion in 3 polyps. Twelve polyps with favourable histology had no adverse outcome; in contrast, 5 of 20 polyps with unfavourable histology had an average outcome (P < 0.05). Locally excised malignant polyps without unfavourable histologic signs may not need further surgical treatment; for all other malignant polyps an ensuing bowel resection is recommended.

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2011-01-01

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

  13. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-09-01

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

  16. [Treatment of malignant colorectal obstruction by means of endoscopic insertion of self-expandable metallic stents].

    PubMed

    García-Cano, J; González Martín, J A; Redondo-Cerezo, E; Morillas Ariño, J; Pérez García, J I; Pérez Vigara, M G; Gómez Ruiz, C J; Pérez Sola, A

    2003-10-01

    Self-expandable metallic stents are being used increasingly to treat the obstruction of different segments of the digestive tract and biliary tree. We present our centre experience on the initial resolution of malignant colorectal obstruction by means of this type of stents. During a 18-month period, 13 patients patients suffering from malignant obstruction at the level of rectum, sigmoid or descending colon tried to be initially treated by means of endoscopic insertion of stents (non covered enteral Wallstents). Ten procedures were performed with both endoscopy and fluroscopy and three with only endoscopy. In 12 of the 13 patients (92,3%) the obstruction was solved by means of correct stent insertion. All the exclusively endoscopic procedures (without fluoroscopy) were successful. Six (50 %) patients with tumours at the rectosigmoid underwent later scheduled surgery. In the remaining six ones (a patient with an ovarian carcinoma and five with colonic adenocarcinoma) the stents were considered to be a palliative definitive treatment. Stent migration was observed in two of these patients and both were extracted endoscopically. Only one patient needed to have another stent inserted. A tumoural colo-vesical fistula developed in another patient in the palliative group, inside the previous inserted stent, and was treated by coaxial insertion of an esophageal Ultraflex. There were no other complications or mortality related to the endoscopic procedures. Self-expandable metallic stents might be considered, in general, as the initial treatment for the malignant obstruction at the level of rectum, sigmoid and descending colon

  17. 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

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

    PubMed Central

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

    2016-01-01

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

  19. Endoscopic and surgical treatment of malignant colorectal polyps: a population-based comparative study.

    PubMed

    Mounzer, Rawad; Das, Ananya; Yen, Roy D; Rastogi, Amit; Bansal, Ajay; Hosford, Lindsay; Wani, Sachin

    2015-03-01

    Long-term population-based data comparing endoscopic therapy (ET) and surgery for management of malignant colorectal polyps (MCPs) are limited. To compare colorectal cancer (CRC)-specific survival with ET and surgery. Population-based study. Patients with stage 0 and stage 1 MCPs were identified from the Surveillance Epidemiology and End Results (SEER) database (1998-2009). Demographic characteristics, tumor size, location, treatment modality, and survival were compared. Propensity-score matching and Cox proportional hazards regression models were used to evaluate the association between treatment and CRC-specific survival. ET and surgery. Mid-term (2.5 years) and long-term (5 years) CRC-free survival rates and independent predictors of CRC-specific mortality. Of 10,403 patients with MCPs, 2688 (26%) underwent ET and 7715 (74%) underwent surgery. Patients undergoing ET were more likely to be older white men with stage 0 disease. Surgical patients had more right-sided lesions, larger MCPs, and stage 1 disease. There was no difference in the 2.5-year and 5-year CRC-free survival rates between the 2 groups in stage 0 disease. Surgical resection led to higher 2.5-year (97.8% vs 93.2%; P < .001) and 5-year (96.6% vs 89.8%; P < .001) CRC-free survival in stage 1 disease. These results were confirmed by propensity-score matching. ET was a significant predictor for CRC-specific mortality in stage 1 disease (hazard ratio 2.40; 95% confidence interval, 1.75-3.29; P < .001). Comorbidity index not available, selection bias. ET and surgery had comparable mid- and long-term CRC-free survival rates in stage 0 disease. Surgical resection is the recommended treatment modality for MCPs with submucosal invasion. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  20. 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.

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

    PubMed

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

    2012-04-01

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

  2. Physical interaction between human ribonucleotide reductase large subunit and thioredoxin increases colorectal cancer malignancy.

    PubMed

    Lou, Meng; Liu, Qian; Ren, Guoping; Zeng, Jiling; Xiang, Xueping; Ding, Yongfeng; Lin, Qinghui; Zhong, Tingting; Liu, Xia; Zhu, Lijun; Qi, Hongyan; Shen, Jing; Li, Haoran; Shao, Jimin

    2017-04-14

    Ribonucleotide reductase (RR) is the rate-limiting enzyme in DNA synthesis by catalyzing the reduction of ribonucleotides to deoxyribonucleotides. During each enzymatic turnover, reduction of the active site disulfide in the catalytic large subunit is performed by a pair of shuttle cysteine residues in its C-terminal tail. Thioredoxin (Trx) and Glutaredoxin (Grx) are ubiquitous redox proteins, catalyzing thiol-disulfide exchange reactions. Here, immunohistochemical examination of clinical colorectal cancer (CRC) specimens revealed that human thioredoxin1 (hTrx1), but not human glutaredoxin1 (hGrx1), was upregulated along with human RR large subunit (RRM1) in cancer tissues, and the expression levels of both proteins were correlated with cancer malignancy stage. Ectopically expressed hTrx1 significantly increased RR activity, DNA synthesis, and cell proliferation and migration. Importantly, inhibition of both hTrx1 and RRM1 produced a synergistic anti-cancer effect in CRC cells and xenograft mice. Furthermore, hTrx1 rather than hGrx1 was the efficient reductase for RRM1 regeneration. We also observed a direct protein-protein interaction between RRM1 and hTrx1 in CRC cells. Interestingly, besides the known two conserved cysteines, a third one (Cys779) in the RRM1 C-terminus was essential for RRM1 regeneration and binding to hTrx1, while both Cys32 and Cys35 in hTrx1 played a counterpart role. Our findings suggest that the upregulated RRM1 and hTrx1 in CRC directly interact with each other and promote RR activity, resulting in enhanced DNA synthesis and cancer malignancy. We propose that the RRM1-hTrx1 interaction might be a novel potential therapeutic target for cancer treatment.

  3. The management of malignant polyps in colorectal cancer screening programmes: A retrospective Italian multi-centre study.

    PubMed

    Fasoli, Renato; Nienstedt, Richard; De Carli, Nicola; Monica, Fabio; Guido, Ennio; Valiante, Flavio; Armelao, Franco; de Pretis, Giovanni

    2015-08-01

    Although recognition of colorectal malignant polyps is increasing, treatment plans lack the evidence of randomised trials. To retrospectively evaluate presentation, management and outcomes of screen-detected colorectal malignant polyps, with special focus on the role of histological factors in therapeutic decision-making. We retrospectively analysed data regarding malignant polyps detected during faecal immuno-chemical test-based screening programmes in five centres in North-Eastern Italy between April 2008 and April 2013. 306 malignant polyps in 306 patients were included; 72 patients underwent surgery directly (23.6%). Of 234 patients treated endoscopically, 133 subsequently underwent radicalisation surgery (56.8%) and in 17 there was evidence of residual disease (12.8%). Involved, unsafe (<1mm) or invaluable resection margins and sessile morphology represented the most frequent determinants of subsequent surgery. The mean number of nodes harvested during radicalisation surgery was 7.1±6.4 (range 0-29). Histological diagnosis was re-evaluated according to new guidelines in 125 cases (41%); in 18 this led to modification of the risk class (14.4%). Although the rate of surgical treatment following endoscopic resection is similar to other studies, residual disease at surgery was lower than most international series. Adhering to the new histological reporting system and respecting guidelines on node harvesting may favourably influence prognosis. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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

    PubMed Central

    2013-01-01

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

  5. Outcomes of secondary self-expandable metal stents versus surgery after delayed initial palliative stent failure in malignant colorectal obstruction.

    PubMed

    Yoon, Jin Young; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2013-01-01

    When re-intervention is required due to an occluded first colorectal self-expanding metal stent for malignant colorectal obstruction, serious controversies exist regarding whether to use endoscopic re-stenting or surgery. To compare the clinical outcomes in patients who underwent stent re-insertion versus palliative surgery as a second intervention. A total of 115 patients who received either self-expandable metal stent (SEMS) insertion or palliative surgery for treatment of a second occurrence of malignant colorectal obstruction after the first SEMS placement were retrospectively studied between July 2005 and December 2009. The median overall survival (8.2 vs. 15.5 months) and progression-free survival (4.0 vs. 2.7 months) were not significantly different between the stent and surgery groups (p = 0.895 and 0.650, respectively). The median lumen patency in the stent group was 3.4 months and that in the surgery group was 7.9 months (p = 0.003). The immediate complication rate after second stent insertion was 13.9% and late complication rate was observed in 12 of 79 (15.2%) patients. There was no mortality related to the SEMS procedure. The complication and mortality rates associated with palliative surgery were 3.5% (2/57) and 12.3% (7/57), respectively. Although there is no significant difference in the overall survival between stenting and surgery, a secondary stent insertion had a lower mortality rate despite a shorter duration of temporary colorectal decompression compared to that of palliative surgery.

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

    PubMed

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

    2016-08-02

    The balance between hope-hopelessness plays an important role in the way terminally ill patients report quality of life, and personal resilience may be related to hope at the end of life. The objective of this study was to explore associations between personal resilience, hope, and other possible predictors of hope in advanced cancer patients. A cross-sectional pilot study was carried out with metastatic colorectal cancer patients in a tertiary hospital. The patients answered the Connor-Davidson Resilience Scale, Herth Hope Index, Barthel Index, an instrument addressing family and social support, visual-numeric scales for pain and suffering, a two-item screening for depression, socio-demographic and socio-economic information about the family. Forty-four patients were interviewed (mean age 56 years; range 29-86). A strong correlation was noted between resilience and hope (0.63; p < 0.05). No correlation was found between hope and independence for activities of daily living, support from family and community, and pain and suffering levels. Of the 44 patients, 20 presented with depressive symptoms. These depressive patients had lower resilience (p = 0.005) and hope (p = 0.003), and higher scores of suffering (p < 0.001). The association between resilience and hope kept stable after adjusting for age, gender, and presence of depression (p < 0.001). Given that resilience is a dynamic, changeable path that can improve hope, resilience-fostering interventions should be most valued in palliative care settings and should be commenced as soon as possible with cancer patients. Patients with advanced stages of non-malignant conditions would also probably benefit from such interventions.

  7. A large-scale measurement of dielectric properties of normal and malignant colorectal tissues obtained from cancer surgeries at Larmor frequencies.

    PubMed

    Li, Zhou; Deng, Guanhua; Li, Zhe; Xin, Sherman Xuegang; Duan, Song; Lan, Maoying; Zhang, Sa; Gao, Yixin; He, Jun; Zhang, Songtao; Tang, Hongming; Wang, Weiwei; Han, Shuai; Yang, Qing X; Zhuang, Ling; Hu, Jiani; Liu, Feng

    2016-11-01

    Knowledge of dielectric properties of malignant human tissues is necessary for the recently developed magnetic resonance (MR) technique called MR electrical property tomography. This technique may be used in early tumor detection based on the obvious differentiation of the dielectric properties between normal and malignant tissues. However, the dielectric properties of malignant human tissues in the scale of the Larmor frequencies are not completely available in the literature. In this study, the authors focused only on the dielectric properties of colorectal tumor tissue. The dielectric properties of 504 colorectal malignant samples excised from 85 patients in the scale of the Larmor frequencies were measured using the precision open-ended coaxial probe method. The obtained complex-permittivity data were fitted to the single-pole Cole-Cole model. The median permittivity and conductivity for the malignant tissue sample were 79.3 and 0.881 S/m at 128 MHz, which were 14.6% and 17.0% higher, respectively, than those of normal tissue samples. Significant differences between normal and malignant tissues were found for the dielectric properties (p < 0.05). Experimental results indicated that the dielectric properties were significantly different between normal and malignant tissues for colorectal tissue. This large-scale clinical measurement provides more subtle base data to validate the technique of MR electrical property tomography.

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

    PubMed Central

    Cheung, Dae Young; Lee, Yong Kook

    2014-01-01

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

  9. Short-term and long-term outcomes after simultaneous resection of colorectal malignancies and synchronous liver metastases.

    PubMed

    de Santibañes, Eduardo; Fernandez, Diego; Vaccaro, Carlos; Quintana, Guillermo Ojea; Bonadeo, Fernando; Pekolj, Juan; Bonofiglio, Carlos; Molmenti, Ernesto

    2010-09-01

    We evaluated the simultaneous resection of colorectal malignancies and synchronous liver metastases. Between June 1982 and June 2006, a total of 752 patients underwent resection of colorectal hepatic metastases. In all, 185 (25%) of them underwent simultaneous resection of the hepatic lesions and the corresponding primary tumors. The median hospital stay was 8 days (range 4-24 days), with a median operating time of 4 h (range 2-8 h). Altogether, 62 (33.5%) patients required intraoperative transfusion of packed red blood cells (median 2.1 IU, range 1-5 IU), and 25 (13.5%) were given frozen fresh plasma (median 2.1 IU, range 1-4 IU). The morbidity rate was 20.5%. There were two postoperative deaths (mortality rate 1.08%) within 30 days of the surgical intervention. Major hepatectomy was associated with greater morbidity (37.2% vs. 16.2%, P < 0.01) and mortality (4.7% vs. 0%, P < 0.05) rates. For the overall survivals (OS) at 3 and 5 years were 60.1% (52.3-67.85%) and 36.1% (27.4-44.8%), respectively. Disease-free survivals (DFS) at 3 and 5 years were 37.7% (30.2-45.3%) and 26.5% (18.7-34.3%), respectively. Transfusion of blood products, CEA level > or = 200 ng/dl, and N2 node status were found to be prognostic factors by univariate analysis. CEA level > or = 200 ng/dl and N2 node status achieved prognostic significance by multivariate analysis. The simultaneous resection of colorectal malignancies and synchronous liver metastases is safe, avoids an additional intervention, can be performed with low morbidity and mortality, and is associated with good oncologic outcomes. Node stage N2 and CEA level > or = 200 ng/dl should be given special consideration when selecting patients.

  10. 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.

  11. Clinical outcomes and risk factors for technical and clinical failures of self-expandable metal stent insertion for malignant colorectal obstruction.

    PubMed

    Yoon, Jin Young; Jung, Yoon Suk; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2011-10-01

    Although self-expandable metal stent (SEMS) insertion is widely used for relief of malignant colorectal obstructions, the immediate technical and clinical failure rates of SEMSs and the associated risk factors remain largely unknown. To identify rates and factors predictive of technical and clinical failure of SEMSs when their use is attempted for the decompression of malignant colorectal obstruction. Retrospective chart review. A tertiary-care academic medical center in South Korea. This study involved a total of 412 patients with malignant colorectal obstruction in whom SEMS insertion was attempted. Placement of colonic SEMSs. Technical success and immediate and long-term clinical success rates. Technical and clinical failures were found in 36 of 276 patients (13.0%) and 39 of 240 patients (16.3%) in the palliative group, respectively, and in 3 of 136 patients (2.2%) and 7 of 133 patients (5.3%) in the preoperative group, respectively. Factors associated with technical failure were extracolonic origin of tumor, the presence of carcinomatosis, and a proximal obstruction site. Factors associated with long-term clinical failure in the palliative group were combined dilation procedure, no additional chemotherapy, and extracolonic origin of the tumor. In the preoperative group, only older patients had both higher technical failure and clinical failure rates. This was a single-institution, retrospective analysis. Although colorectal SEMS placement is generally safe and effective, it is associated with clinically important technical and clinical failure rates. The identification of risk factors for the failure of colorectal SEMSs found in this study might help physicians decide between surgical decompression and endoscopic stenting in patients with malignant colorectal obstruction. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  12. Mesenchymal Stem Cells Engineered to Secrete Pigment Epithelium-Derived Factor Inhibit Tumor Metastasis and the Formation of Malignant Ascites in a Murine Colorectal Peritoneal Carcinomatosis Model.

    PubMed

    Yang, Liping; Zhang, Yuwei; Cheng, Liuliu; Yue, Dan; Ma, Jinhu; Zhao, Da; Hou, Xiaoming; Xiang, Rong; Cheng, Ping

    2016-03-01

    The therapeutic effects of conventional treatments for advanced colorectal cancer with colorectal peritoneal carcinomatosis (CRPC) and malignant ascites are not very encouraging. Vascular endothelial growth factor-A/vascular permeability factors (VEGF-A/VPF) play key roles in the formation of malignant ascites. In previous work, we demonstrated that pigment epithelium-derived factor (PEDF) antagonized VEGF-A and could repress tumor growth and suppress metastasis in several cancer types. Thus, PEDF may be a therapeutic candidate for treating malignant ascites. Mesenchymal stem cells (MSCs) are promising tools for delivering therapeutic agents in cancer treatment. In the study, MSCs derived from bone marrow were efficiently engineered to secrete human PEDF by adenoviral transduction. Then, intraperitoneal Ad-PEDF-transduced MSCs were analyzed with respect to CRPC and malignant ascites in a CT26 CRPC model. MSCs engineered to secrete PEDF through adenoviral transduction significantly inhibited tumor metastasis and malignant ascites formation in CT26 CRPC mice. Antitumor mechanisms of MSCs-PEDF (MSCs transduced with Ad-PEDF: MOI 500) were associated with inhibiting tumor angiogenesis, inducing apoptosis, and restoring the VEGF-A/sFLT-1 ratio in ascites. Moreover, MSC-mediated Ad-PEDF delivery reduced production of adenovirus-neutralizing antibodies, prolonged PEDF expression, and induced MSCs-PEDF migration toward tumor cells. As a conclusion, MSCs engineered to secrete PEDF by adenoviral transduction may be a therapeutic approach for suppressing tumor metastasis and inhibiting malignant ascites production in CRPC.

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

    PubMed Central

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

    2015-01-01

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

  14. Improving results of surgery for fecal peritonitis due to perforated colorectal disease: A single center experience.

    PubMed

    Mineccia, Michela; Zimmitti, Giuseppe; Ribero, Dario; Giraldi, Francesco; Bertolino, Franco; Brambilla, Romeo; Ferrero, Alessandro

    2016-01-01

    fecal peritonitis due to colorectal perforation is a dramatic event characterized by high mortality. Our study aims at determining how results of sigmoid resection (eventually extended to upper rectum) for colorectal perforation with fecal peritonitis changed in recent years and which factors affected eventual changes. Seventy-four patients were operated on at our institution (2005-2014) for colorectal perforation with fecal peritonitis and were divided into two numerically equal groups (operated on before (ERA1-group) and after (ERA2-group) May 2010). Mannheim Peritonitis Index (MPI) was calculated for each patient. Characteristics of two groups were compared. Predictors of postoperative outcomes were identified. Postoperative overall complications, major complications, and mortality occurred in 59%, 28%, and 18% of cases, respectively, and were less frequent in ERA2-group (51%, 16%, and 8%, respectively), compared to ERA1-group (68%, 41%, and 27%, respectively; p = .155, .02, and .032, respectively). Such results paralleled lower MPI values in ERA2-group, compared to ERA1-group (23(16-39) vs. 28(21-43), p = .006). Using receiver operating characteristic analysis, the best cut-off value for MPI for predicting postoperative complications and mortality was 28.5. MPI>28 was the only independent predictor of postoperative overall (p = .009, OR = 4.491) and major complications (p < .001, OR = 23.182) and was independently associated with a higher risk of mortality (p = .016, OR = 13.444), as well as duration of preoperative peritonitis longer than 24 h (p = .045, OR = 17.099). results of surgery for colorectal perforation with fecal peritonitis have improved over time, matching a concurrent decrease of MPI values and a better preoperative patient management. MPI value may help in selecting patients benefitting from surgical treatment. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  15. 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

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

    SciTech Connect

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

    2006-11-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. Diffuse intrapulmonary malignant mesothelioma masquerading as interstitial lung disease: a distinctive variant of mesothelioma.

    PubMed

    Larsen, Brandon T; Klein, Julianne R H; Hornychová, Helena; Nuti, Rathna; Thirumala, Seshadri; Leslie, Kevin O; Colby, Thomas V; Tazelaar, Henry D

    2013-10-01

    Malignant mesothelioma typically encases lungs as a thick rind, while relatively sparing lung parenchyma. We describe an unusual presentation of mesothelioma characterized by diffuse intrapulmonary growth, with absent or inconspicuous pleural involvement, clinically simulating interstitial lung disease (ILD). We identified 5 patients (median age 56 y, all men) with diffuse intrapulmonary malignant mesothelioma in our pathology consultation practice from 2009 to 2012. Clinical history, imaging, and pathology materials were reviewed. Symptoms included chronic dyspnea (4 cases), cough (3), and acute dyspnea with bilateral pneumothorax (1). Chest imaging showed irregular opacities (5), reticulation (4), pleural effusions (2), and subpleural nodular densities (1), without radiologic evidence of pleural disease or masses. A clinicoradiologic diagnosis of ILD was made in all cases, and wedge biopsies were performed. Histologic evaluation revealed a neoplastic proliferation of bland epithelioid or spindled cells, showing various growth patterns simulating silicotic nodules, desquamative interstitial pneumonia, organizing pneumonia, and Langerhans cell histiocytosis. Some areas mimicked adenocarcinoma, with lepidic, acinar, micropapillary, and solid patterns. Initial diagnoses by referring pathologists included reactive changes (1), hypersensitivity pneumonitis versus drug reaction (1), desquamative interstitial pneumonia versus neoplasm (1), and mesothelioma (2). Microscopic pleural involvement was identified in 4 cases. Immunohistochemistry confirmed the characteristic immunophenotype of mesothelioma in all cases. Median survival of 3 patients treated with chemotherapy was 28 months. Two patients received no therapy and survived 3 and 4 weeks, respectively. "Diffuse intrapulmonary malignant mesothelioma" is a rare variant with a distinctive presentation that clinically mimics ILD. Recognition is essential to avoid misdiagnosis.

  19. 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

  20. 5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study

    PubMed Central

    van Staa, T P; Card, T; Logan, R F; Leufkens, H G M

    2005-01-01

    Background and aims: The objective of this study was to evaluate the risk of colorectal cancer (CRC) in patients taking aminosalicylates (5-ASA) for inflammatory bowel disease (IBD). Methods: The General Practice Research Database (GPRD) which contains the primary care records of five million people in the UK was used to identify users of mesalazine, balsalazide, olsalazine, or sulfasalazine with a history of IBD. In a nested case control analysis, each incident CRC case with any use of a 5-ASA in the six months before the CRC diagnosis was matched by age, sex, and calendar time to six control patients who were also currently using a 5-ASA. Patients were then classified according to regularity of use. The analysis was controlled for body mass index, IBD duration, history of colorectal polyps, use of non-steroidal anti-inflammatory drugs, paracetamol, aspirin, immunosuppressants, oral and rectal glucocorticoids, prior gastrointestinal hospitalisation, recorded colonoscopy, and number of visits to the general practitioner for IBD symptoms in the 6–24 months before diagnosis. Results: The study population included 18 969 patients, of whom 100 had developed CRC during 5-ASA exposure. Most of these cases had a history of ulcerative colitis (76 patients). In the case control analysis, regular users, defined as having six or more 5-ASA prescriptions in the previous 12 months, were found to have a decreased risk of CRC compared with irregular users (crude odds ratio (OR) 0.7 (0.44–1.03); adjusted OR 0.60 (0.38–0.96)). Regular users of sulfasalazine with 6–12 prescriptions before had an adjusted OR of 0.95 (0.22–4.11); with 13–30 prior prescriptions this was 0.41 (0.14–1.20) and with >30 prior prescriptions this was 0.77 (0.37–1.60). For mesalazine users, these values were 1.13 (0.49–2.59), 0.30 (0.11–0.83), and 0.31 (0.11–0.84), respectively. Conclusion: These results show that regular 5-ASA use is associated with some reduction in the risk of CRC

  1. Survival of Colorectal Cancer in Patients With or Without Inflammatory Bowel Disease: A Meta-Analysis.

    PubMed

    Ou, Baochi; Zhao, Jingkun; Guan, Shaopei; Lu, Aiguo

    2016-03-01

    Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), but little is known about the influence of IBD on CRC prognosis. The aim of this study was to perform a meta-analysis to compare survival in CRC patients with IBD (IBD-CRC) and without IBD. An electronic search was conducted via PubMed, Embase, and the Cochrane Library to identify eligible trials until July 2015. We pooled the hazard ratios (HRs) and their 95% confidence intervals (CIs) to quantitatively assess the survival of CRC in patients with or without IBD. In addition, clinicopathological parameters of IBD-CRC versus non-IBD CRC were evaluated. Twelve studies containing a total of 3472 IBD-CRC patients were eligible according to our selection criteria. Our analysis indicated that CRC patients with IBD had shorter overall survival than those without IBD (HR 1.24, 95% CI 1.19-1.29). IBD-CRC showed a propensity to develop in proximal colon [odds ratio (OR) 2.52, 95% CI 1.35-4.72] and correlated with worse differentiation of tumor (OR 1.59, 95% CI 1.26-1.99) compared to non-IBD CRC. Meta-regression analysis showed that sample size (P = 0.002) could explain 99.01% inter-study heterogeneity. This meta-analysis found poorer overall survival in CRC patients with IBD than CRC patients without IBD, and further prospective research to confirm these findings is warranted.

  2. Pharmacologic rationale for treatments of peritoneal surface malignancy from colorectal cancer

    PubMed Central

    Sugarbaker, Paul H; Van der Speeten, Kurt; Stuart, O Anthony

    2010-01-01

    The peritoneal surfaces of the abdomen and pelvis are important sites for the dissemination of gastrointestinal and gynecologic malignancy. Transcoelomic dissemination of cancer cells gives rise to carcinomatosis, which, without special treatment, is a fatal manifestation of these diseases. To treat peritoneal carcinomatosis, cytoreductive surgery removes gross disease plus perioperative intraperitoneal and perioperative intravenous chemotherapy eradicates microscopic residual disease and chemical compatibilities. Chemotherapy agents are administered either by the intraperitoneal or intravenous route, based on their pharmacologic properties. A peritoneal-plasma barrier, which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity, results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration of the intraperitoneal chemotherapy is facilitated by moderate hyperthermia (41-42°C). Targeting of intravenous chemotherapy to the peritoneal surface is facilitated by the intraperitoneal heat. A constant dose of chemotherapy agent and volume of carrier solution, based on body surface area, allows prediction of systemic drug exposure and systemic toxicity. Timing of the hyperthermic chemotherapy as a scheduled part of the surgical procedure to uniformly expose all peritoneal surfaces is crucial to success. PMID:21160813

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

    PubMed Central

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

    2016-01-01

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

  4. Colorectal cancer in inflammatory bowel diseases: a population-based study (1976-2008).

    PubMed

    Peyrin-Biroulet, Laurent; Lepage, Côme; Jooste, Valérie; Guéant, Jean-Louis; Faivre, Jean; Bouvier, Anne-Marie

    2012-12-01

    Few data are available on the incidence, characteristics, treatment, and prognosis of inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) in population-based cohorts. Among the 19,451 new cases of CRC recorded in the Burgundy digestive cancer registry between 1976 and 2008, all cases of IBD-associated CRC were identified. Incidence rates were age-standardized according to the world standard population. Prognosis was determined using univariate and multivariate relative survival. Thirty-eight IBD-associated CRC were identified (ulcerative colitis, n = 29; Crohn's disease, n = 9). The mean age at CRC diagnosis was greater for patients without IBD than those with IBD (70.9 vs. 56.9 years, respectively; P < 0.001). Distributions of gender, stage at presentation, location, and histological type of CRC did not differ from those of sporadic cases. The overall world age-standardized incidence of IBD-associated CRC per 100,000 was 0.11 (standard deviation [SD]: 0.03) for men and 0.06 (SD: 0.02) for women. Only age was independently associated with IBD-associated CRC (odds ratio [OR]: 0.22; 95% confidence interval [CI]: 0.12-0.43; P < 0.001). Treatment modalities did not differ between IBD and non-IBD patients. Five-year relative survival was 51.9% (95% CI: 51.1-52.8%) in non-IBD patients and 41.3% (95% CI: 24.6-57.2%) in IBD patients (P = 0.201). After adjustment for age, gender, and stage at diagnosis, the excess hazard of death was 1.46 times higher in IBD than in non-IBD patients (95% CI: 0.94-2.27; P = 0.070). Apart from age, the characteristics of IBD-associated CRC were similar to those of non-IBD CRC. The prognosis of CRC may be poorer in patients with IBD than in those without IBD. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

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

    PubMed Central

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

    2017-01-01

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

  6. Prevalence and malignancy risk of focal colorectal incidental uptake detected by 18F-FDG-PET or PET/CT: a meta-analysis

    PubMed Central

    Treglia, Giorgio; Taralli, Silvia; Salsano, Marco; Muoio, Barbara; Sadeghi, Ramin; Giovanella, Luca

    2014-01-01

    Background The aim of the study was to meta-analyze published data about prevalence and malignancy risk of focal colorectal incidentalomas (FCIs) detected by Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (18F-FDG-PET or PET/CT). Methods A comprehensive computer literature search of studies published through July 31st 2012 regarding FCIs detected by 18F-FDG-PET or PET/CT was performed. Pooled prevalence of patients with FCIs and risk of malignant or premalignant FCIs after colonoscopy or histopathology verification were calculated. Furthermore, separate calculations for geographic areas were performed. Finally, average standardized uptake values (SUV) in malignant, premalignant and benign FCIs were reported. Results Thirty-two studies comprising 89,061 patients evaluated by 18F-FDG-PET or PET/CT were included. The pooled prevalence of FCIs detected by 18F-FDG-PET or PET/CT was 3.6% (95% confidence interval [95% CI]: 2.6–4.7%). Overall, 1,044 FCIs detected by 18F-FDG-PET or PET/CT underwent colonoscopy or histopathology evaluation. Pooled risk of malignant or premalignant lesions was 68% (95% CI: 60–75%). Risk of malignant and premalignant FCIs in Asia-Oceania was lower compared to that of Europe and America. A significant overlap in average SUV was found between malignant, premalignant and benign FCIs. Conclusions FCIs are observed in a not negligible number of patients who undergo 18F-FDG-PET or PET/CT studies with a high risk of malignant or premalignant lesions. SUV is not reliable as a tool to differentiate between malignant, premalignant and benign FCIs. Further investigation is warranted whenever FCIs are detected by 18F-FDG-PET or PET/CT. PMID:24991198

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

    PubMed

    Hoshiba, Takashi; Tanaka, Masaru

    2016-11-01

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

  8. Loss of fatty acid synthase suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway.

    PubMed

    Chang, Ligong; Wu, Peng; Senthilkumar, Ravichandran; Tian, Xiaoqiang; Liu, Hui; Shen, Xia; Tao, Zijian; Huang, Peilin

    2016-01-01

    Altered cellular metabolism has received increased attention as an important hallmark of cancer. Activation of FASN has been found to be involved in many human tumors. Despite extensive research in FASN function on cancer, the underlying mechanism is not entirely understood yet. Cerulenin was used to suppress the FASN expression in human colorectal cancer cell lines (HT29 and LoVo). Expression of PI3K, Akt, p-Akt, mTOR, p-mTOR, FASN, and AZGP1 was measured using western blotting and qPCR. ATP and lactic acid were assessed to investigate the activation of energy metabolism. Cell cytotoxicity assay was studied by cell counting kit-8 assay. The capacity of cell proliferation and migration was investigated by clonogenic and invasion assay. Analysis of apoptosis and the cell cycle was detected by flow cytometry. We found that the expression of FASN was down-regulated, while the expression of PI3K, p-Akt, p-mTOR, and AZGP1 was down-regulated in HT29 and LoVo cells treated with FASN inhibitor. Proliferation was reduced in FASN inhibitor-treated cells, which is consistent with an increased apoptosis rate. Furthermore, the migration of FASN inhibitor-treated cells was decreased and the content of ATP and lactic acid was also dropped. These findings suggest that inhibited FASN suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway. The results have paved the way to understand the relations of FASN, mTOR signaling pathway, and energy metabolism in colorectal cancer cells.

  9. 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

  10. Intact and cleaved forms of the urokinase receptor enhance discrimination of cancer from non-malignant conditions in patients presenting with symptoms related to colorectal cancer

    PubMed Central

    Lomholt, A F; Høyer-Hansen, G; Nielsen, H J; Christensen, I J

    2009-01-01

    Background: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality in developed countries. It is known that early detection results in improved survival, and consequently there is a need for improved diagnostic tools in CRC. The plasma level of soluble urokinase plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer. Methods: In a case–control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured in citrate plasma collected before endoscopical examination, using three different Time Resolved – Fluorescence Immuno Assays (TR-FIA's). Results: All soluble uPAR forms were found to be significantly higher in cancer patients than in patients presenting with other non-malignant findings; uPAR(I) P=0.0006, suPAR(I–III) P<0.0001 and suPAR(I–III)+(II–III) P<0.0001, whereas no significant difference was found when performing similar comparisons for patients presenting with adenomas. The odds ratio (OR) for the comparison of uPAR(I) in patients with CRC to subjects with other non-malignant findings was 3.44 (95% CI:1.86–6.37). CRC patients had a mean elevated level of 20.9% (95% CI:10.2–32.6) for suPAR(I–III) and 18.5% (95% CI:9.0–28.8) for suPAR(I–III)+(II–III) compared with subjects with non-malignant findings. Conclusions: The findings confirm reports on increased uPAR expression in cancer patients and in particular elevated levels of suPAR in blood from CRC patients and indicate that suPAR levels in blood are increasing during carcinogenesis. Although none of

  11. Comparison of through-the-scope stent insertion with standard stent insertion for the management of malignant colorectal obstruction: a prospective study.

    PubMed

    Wan, Y; Zhu, Y-Q; Chen, N-W; Wang, Z-G; Cheng, Y-S; Shi, J

    2016-10-01

    The aim of the present study was to compare the feasibility, safety and efficacy of the through-the-scope (TTS) stent technique to that of the standard metallic stent technique for the management of malignant colorectal obstruction. Fifty-two patients scheduled to receive stent insertion for the management of acute obstructive colorectal cancer were enrolled in our study and divided into a TTS stent group (n = 24) and a standard stent group (n = 28). The stent insertion procedure was performed under endoscopic and fluoroscopic guidance in all patients. The success rate, complications, fluoroscopic time, and clinical remission rate were recorded and compared. The technique success rate was 100 % (24/24) in the TTS stent group and 78.6 % (22/28) in the standard stent group (p = 0.03). In five patients in the standard stent group, the stent failed to pass through occlusive lesions because of the stiffness of the stent system. Serious bleeding occurred in one patient in the standard stent group. The fluoroscopy time in the TTS stent group was significantly reduced (12.9 ± 6.6 min) compared with that of the standard stent group (24.8 ± 9.8 min; p < 0.01). Silent perforation occurred in 17.9 % (5/28) of the cases in the standard stent group compared with none in the TTS (p = 0.03). Clinical remission was achieved in 97.1 % (23/24) and 78.6 % (22/28) of patients in the TTS and standard stent groups, respectively (p = 0.11). The TTS stent is safer and more feasible for the management of malignant colorectal obstructions than the standard stent, and the TTS technique provides a higher success rate, a similar clinical remission rate, and a markedly reduced fluoroscopic time.

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

    PubMed Central

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

    2016-01-01

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

  13. Self-expandable stent before elective surgery vs. emergency surgery for the treatment of malignant colorectal obstructions: comparison of primary anastomosis and morbidity rates.

    PubMed

    Martinez-Santos, Cristina; Lobato, Rosa F; Fradejas, José Manuel; Pinto, Isabel; Ortega-Deballón, Pablo; Moreno-Azcoita, Mariano

    2002-03-01

    At present there are not enough studies that demonstrate the usefulness of self-expandable stents in patients with left-sided malignant colon and rectal obstruction. We evaluated primary anastomosis and morbidity rates obtained with this method in comparison with the results of the emergency surgical treatment. From February 1994 to November 1999, 72 consecutive patients with left-sided malignant colorectal obstruction were enrolled. Forty-three patients were assigned to the study group (preoperative stent and elective surgical treatment or palliative stent, depending on the assessment of the stage of the tumor) and 29 to the control group (emergency surgical treatment). The resection was not indicated in 18 cases in the study group (after preoperative staging in 17 and intraoperative staging in 1) and in 3 cases in the control group. In the study group, the obstruction was relieved in 41 cases (95 percent) after the stent placement. Of 26 patients who underwent surgical treatment, a primary anastomosis was possible in 22 (84.6 vs. 41.4 percent in the control group, P = 0.0025), with lower need for a colostomy (15.4 vs. 58.6 percent in the control group). The anastomotic failure rate was similar and the reintervention rate was lower (0 vs. 17 percent, P = 0.014). The total stay (14.23 vs. 18.52 days; P = 0.047), the intensive care unit stay (0.3 vs. 2.9 days; P = 0.015), and the number of patients with severe complications (11.6 vs. 41.2 percent; P = 0.008) were significantly lower in the study group. In our patients with left-sided malignant colon and rectal obstruction, placement of a preoperative stent prevented 17 (94 percent) of 18 of unnecessary operations and a large number of colostomies after elective surgery. These results were obtained with a lower severe complication rate as well as a shorter hospital stay.

  14. Laparoscopic resection with natural orifice specimen extraction versus conventional laparoscopy for colorectal disease: a meta-analysis.

    PubMed

    Ma, Bin; Huang, Xuan-Zhang; Gao, Peng; Zhao, Jun-Hua; Song, Yong-Xi; Sun, Jing-Xu; Chen, Xiao-Wan; Wang, Zhen-Ning

    2015-11-01

    We wished to determine the effects of laparoscopic resection using natural orifice specimen extraction (NOSE) for patients with colorectal disease through a meta-analysis. A study search was undertaken in PubMed, EMBASE, and Cochrane databases for eligible studies until December 2014. Duration of hospital stay, operation time, time to first flatus, pain score, cosmetic result, postoperative complications, and disease-free survival (DFS) were the main endpoints. The results were analyzed using RevMan v5.3. Nine clinical studies involving 837 patients were included for final analyses. Laparoscopic resection with NOSE had a shorter duration of hospital stay (weighted mean difference (WMD) = -0.62 days, 95 % confidence interval (CI) [-0.95, -0.28], p < 0.01) and time to first flatus (WMD = -0.59 days, 95 % CI [-0.78, -0.41], p < 0.01), less postoperative pain (WMD = -1.43, 95 % CI [-1.95, -0.90], p < 0.01), and postoperative complications (odds ratio (OR) = 0.51, 95 % CI [0.36, 0.74], p < 0.01) with better cosmetic result (WMD = 1.37, 95 % CI [0.59, 2.14], p < 0.01). However, the operation time was significantly longer in the NOSE group (WMD = 20.97 min, 95 % CI [4.33, 37.62], p = 0.01). No significant difference was observed in DFS (hazard ratio (HR) = 0.88, 95 % CI [0.49, 1.57], p = 0.67). Our meta-analysis supported the notion that laparoscopic resection with NOSE for colorectal disease can significantly reduce the duration of hospital stay, accelerate postoperative recovery with better cosmetic results, and in particular, result in less postoperative pain and fewer complications.

  15. 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

  16. Colorectal Stents: Current Status

    PubMed Central

    Lee, Jeong-Mi

    2015-01-01

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

  17. Survival after colorectal cancer in patients with Crohn's disease: A nationwide population-based Danish follow-up study.

    PubMed

    Larsen, Mette; Mose, Hanne; Gislum, Mette; Skriver, Mette V; Jepsen, Peter; Nørgård, Bente; Sørensen, Henrik T

    2007-01-01

    Patients with Crohn's disease (CD) are at increased risk of colorectal cancer (CRC), but little is known about the impact of CD on CRC prognosis. Based on nationwide population-based registries, we compared survival among CRC patients with CD and CRC patients without CD. We used the Danish Cancer Registry and the Danish Hospital Discharge Registry to identify all patients diagnosed with CRC, with and without CD, in Denmark between 1977 and 1999. We ascertained the stage distribution at the time of CRC diagnosis and 1- and 5-yr survival both for patients with Crohn-associated CRC and patients with non-Crohn CRC. Cox regression was used to compute hazard ratios (HRs), adjusting for gender, age, calendar year, and stage. We identified 100 CRC patients with CD and 71,438 CRC patients without CD. At the time of diagnosis, patients with CD were younger, but stage distributions were similar in the two groups. The overall HR for CRC with CD compared to CRC without CD was 1.82 (95% CI 1.36-2.43) after 1 yr of follow-up, and 1.57 (95% CI 1.24-1.99) after 5 yr of follow-up. Subanalyses showed that the effect of CD on CRC survival was more pronounced in the youngest patients (0-59 yr), in men, and in patients whose tumors had regional spread. We found that CD worsens the prognosis of CRC, particularly CRC with regional spread.

  18. 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.

  19. 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.

  20. The risk of colorectal cancer in inflammatory bowel disease: a hospital-based cohort study from Korea.

    PubMed

    Lee, Ho-Su; Park, Sang Hyoung; Yang, Suk-Kyun; Ye, Byong Duk; Kim, Ji-Hun; Kim, Seon-Ok; Soh, Jae Seung; Lee, Seohyun; Bae, Jung Ho; Lee, Hyo Jeong; Yang, Dong-Hoon; Kim, Kyung-Jo; Byeon, Jeong-Sik; Myung, Seung-Jae; Yoon, Yong Sik; Yu, Chang Sik; Kim, Jin-Ho

    2015-02-01

    Limited data are available on the incidence and risk factors of colorectal cancer (CRC) in Asian patients with inflammatory bowel disease (IBD). Information on 5212 Korean patients with IBD (2414 with Crohn's disease [CD] and 2798 with ulcerative colitis [UC]) was retrieved from the IBD registry of Asan Medical Center. Data on CRC incidence for the entire Korean population were derived from the Korean Statistical Information Service. During 39,951 person-years of follow-up (17,679 for CD and 22,272 for UC), 30 patients (12 with CD and 18 with UC) developed CRC. The standardized incidence ratio (SIR) of CRC was 6.0 (95% confidence interval [CI], 3.10-10.48) for CD and 1.68 (95% CI, 1.00-2.66) for UC; it was 9.69 (95% CI, 5.01-16.93) for CD with colonic involvement and 4.31 (95% CI, 2.46-7.00) for extensive UC. The SIR was also increased in patients diagnosed with IBD at younger than 30 years old. CRC location was the low rectum in 11 of 12 CD patients (91.7%). The cumulative probability of rectal cancer was higher in CD patients with a perianal fistula than in those without a perianal fistula (p = 0.02). A high prevalence of perianal fistulas in Korean CD patients may be the cause of the predominance of low rectal cancer in this population and the higher SIR of CRC in Koreans than in Westerners. In contrast, the SIR of CRC in Korean UC patients may be similar to that in Western UC patients.

  1. Atypical placental site nodule (APSN) and association with malignant gestational trophoblastic disease; a clinicopathologic study of 21 cases.

    PubMed

    Kaur, Baljeet; Short, Dee; Fisher, Rosemary A; Savage, Philip M; Seckl, Michael J; Sebire, Neil J

    2015-03-01

    The WHO Classification of Gestational Trophoblastic Tumors classifies placental site nodule (PSN) as a benign tumor-like trophoblastic neoplasm. Cases of PSN with atypical features were described [atypical placental site nodule (APSN)] and we started registering APSN in our unit in 2005. The aim of this study is to present our initial experience with these lesions. The Trophoblastic Disease Unit database was searched to identify all patients who were either referred with, or on review were diagnosed with, APSN from September 2005 to May 2013. Case notes and the pathology findings for these patients were retrieved and reviewed. A total of 21 cases of APSN were included, 3 of which were associated with gestational trophoblastic neoplasm on follow-up or review. Malignant gestational trophoblastic disease was associated with 3/21 (14%) cases of APSN, either concurrently or developing/manifesting within 16 mo of APSN diagnosis. None of these patients had raised serum hCG levels either at presentation or follow-up. Presence of APSN should indicate a thorough clinical and radiologic investigation and follow-up if diagnosed on curettage specimens. With increased recognition of this entity and corresponding larger series with longer follow-up, more accurate patient counseling will be possible.

  2. [Obesity and colorectal cancer].

    PubMed

    Na, Soo-Young; Myung, Seung-Jae

    2012-01-01

    Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.

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

    PubMed

    Zheng, Han-Han; Jiang, Xue-Liang

    2016-04-01

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

  4. Adiponectin and colorectal cancer.

    PubMed

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

    2017-02-01

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

  5. MicroRNAs expression in normal and malignant colon tissues as biomarkers of colorectal cancer and in response to pomegranate extracts consumption: Critical issues to discern between modulatory effects and potential artefacts.

    PubMed

    Nuñez-Sánchez, María A; Dávalos, Alberto; González-Sarrías, Antonio; Casas-Agustench, Patricia; Visioli, Francesco; Monedero-Saiz, Tamara; García-Talavera, Noelia V; Gómez-Sánchez, María B; Sánchez-Álvarez, Carmen; García-Albert, Ana M; Rodríguez-Gil, Francisco J; Ruiz-Marín, Miguel; Pastor-Quirante, Francisco A; Martínez-Díaz, Francisco; Tomás-Barberán, Francisco A; García-Conesa, María Teresa; Espín, Juan Carlos

    2015-10-01

    MicroRNAs (miRs) are proposed as colorectal cancer (CRC) biomarkers. Pomegranate ellagic acid and their microbiota metabolites urolithins exert anticancer effects in preclinical CRC models, and target normal and malignant colon tissues in CRC patients. Herein, we investigated whether the intake of pomegranate extract (PE) modified miRs expression in surgical colon tissues versus biopsies from CRC patients. We conducted a randomized, double-blind, controlled trial. Thirty-five CRC patients consumed 900 mg PE daily before surgery. Control CRC patients (no PE intake, n = 10) were included. Our results revealed: (1) significant differences for specific miRs between malignant and normal tissues modifiable by the surgical protocols; (2) opposed trends between -5p and -3p isomolecules; (3) general induction of miRs attributable to the surgery; (4) moderate modulation of various miRs following the PE intake, and (5) no association between tissue urolithins and the observed miRs changes. PE consumption appears to affect specific colon tissue miRs but surgery critically alters miRs levels hindering the discrimination of significant changes caused by dietary factors and the establishment of genuine differences between malignant and normal tissues as biomarkers. The components responsible for the PE effects and the clinical relevance of these observations deserve further research. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

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

    2003-11-17

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

  7. Site-specific methylation of CpG nucleotides in the hTERT promoter region can control the expression of hTERT during malignant progression of colorectal carcinoma.

    PubMed

    Choi, Jee-Hye; Park, Soo Hyun; Park, Jina; Park, Borae G; Cha, Seong-Jae; Kong, Kwang-Hoon; Lee, Kwang-Ho; Park, Ae Ja

    2007-09-28

    Expression of hTERT has been recognized an important factor in cellular aging and immortalization. Therefore, to analyze regulatory mechanism of hTERT expression, we investigated the CpG methylation pattern of the hTERT promoter as an epigenetic mechanism and its implication in transcriptional regulation of hTERT using tissues of colorectal carcinoma. As a result, we were able to observe an increased pattern of hTERT expression according to the malignant progression of colorectal carcinoma. Additionally, we could find that hTERT expression was induced when the P1 and P2 region of hTERT were sufficiently hypermethylated and, oppositely, the G1 region of hTERT was hypomethylated. Importantly, we could find three specific CpG sites (7th CpG of P2 and 11th and 2nd-10th CpGs of P1) closely related with the increasing of hTERT expression. These findings may provide important clues to deducing the expression mechanisms of hTERT.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  10. Colorectal stenting as a bridge to surgery reduces morbidity and mortality in left-sided malignant obstruction: a predictive risk score-based comparative study.

    PubMed

    Cennamo, Vincenzo; Luigiano, Carmelo; Manes, Gianpiero; Zagari, Rocco Maurizio; Ansaloni, Luca; Fabbri, Carlo; Ceroni, Liza; Catena, Fausto; Pinna, Antonio Daniele; Fuccio, Lorenzo; Mussetto, Alessandro; Casetti, Tino; Coccolini, Federico; D'Imperio, Nicola; Bazzoli, Franco

    2012-06-01

    The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity model, and its Portsmouth and colorectal modifications are used to predict postoperative mortality and morbidity after colorectal surgery. To compare stent placement as a bridge to surgery vs. emergency surgical resection in patients with acute left-sided colorectal cancer obstruction using P-POSSUM and CR-POSSUM. From January 2008 to December 2009, the physiological and operative scores, morbidity and mortality predicted by the P-POSSUM and CR-POSSUM scores were collected in all consecutive patients with LCCO who underwent surgical resection directly (Group A) or after stent placement (Group B). Eighty-six patients were enrolled (Group A-41 and Group B-45). The observed 30-day mortality rate was 9.8% (4/41) in Group A and 2.4% (1/45) in Group B. The 30-day morbidity rate was 61% (25/41) in Group A and 29% (13/45) in Group B. The mean values of P-POSSUM morbidity (A=70.5% vs. B=34.3%; p=0.001), P-POSSUM mortality (A=13.6% vs. B=2.4%; p=0.001) and CR-POSSUM mortality (A=15.1% vs. B=4.9%; p=0.001) were significantly lower in the Group B patients than in the Group A patients. Bridge to surgery strategy reduces the surgical risks in LCCO, and P-POSSUM and CR-POSSUM scores represent a good tool for comparing the two strategies. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  11. 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 ...

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

    PubMed

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

    2017-01-01

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

  13. The long non-coding RNA SNHG3 functions as a competing endogenous RNA to promote malignant development of colorectal cancer.

    PubMed

    Huang, Weizhen; Tian, Yunming; Dong, Shaoting; Cha, Yinlian; Li, Jun; Guo, Xiaohong; Yuan, Xia

    2017-09-01

    Accumulating evidence has revealed that aberrantly expressed long non-coding transcripts are involved in the development and progression of colorectal cancer (CRC). Small nucleolar RNA host gene 3 (SNHG3) is a newly identified lncRNA, and little is known about its clinical significance and biological functions in the development of CRC. In the present study, we found that the expression of SNHG3 was significantly upregulated in CRC, and upregulation of SNHG3 predicted poor prognosis for patients with CRC as determined through analysis of the data obtained from TCGA database. Gain-of function and loss-of function assays revealed that SNHG3 markedly promoted cellular proliferation of CRC cells. Gene Set Enrichment Analysis (GSEA) suggested that high expression of SNHG3 was positively associated with c-Myc and its targets genes. Furthermore, ectopic overexpression of SNHG3 increased the expression of c-Myc and its target genes, whereas inhibition of SNHG3 had opposite effect on the expression of c-Myc and its targets. Mechanistic investigations demonstrated that SNHG3 functioned as a competing endogenous RNA (ceRNA) to 'sponge' miR-182-5p, thus leading to the release of c-Myc from miR-182-5p and modulating the expression of c-Myc. In conclusion, SNHG3 promoted CRC progression via sponging miR-182-5p and upregulating c-Myc and its target genes.

  14. 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

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

    PubMed Central

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

    2016-01-01

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

  16. 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

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

    PubMed Central

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

    2015-01-01

    Abstract The purpose of this study is to determine the features of second primary malignancies (SPMs) among patients with prior colorectal cancer (CRC) using a nationwide population-based dataset. Patients with CRC newly diagnosed between 1996 and 2011, and >1 year of follow-up were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of SPMs in patients with CRC were calculated. During the 16-year study period, 4259 SPMs developed among 98,876 CRC patients. The median duration of follow-up was 4.03 years. The SIR for all SPMs was 1.13 (95% confidence interval = 1.10–1.17). Compared with the general population, a higher incidence of thyroid, prostate, ovarian, and hematologic malignancies developed among patients with colon cancer, whereas the risk for bone and soft tissue cancers increased among patients with rectal cancer. The risk for breast, bladder, kidney, lung, and uterine cancers was significantly higher in patients with colon and rectal cancers than the general population. The risk for liver and biliary tract cancers declined in patients with rectal cancer. Based on multivariate analysis among patients with CRC, age ≥70 years, men, chronic obstructive pulmonary disease (COPD), cirrhosis, and dyslipidemia were independent predictors of an SPM. In conclusion, patients with CRC were at increased risk for a second cancer. The pattern of SPMs was distinct between patients with colon and rectal cancer. Age, men, COPD, cirrhosis, and dyslipidemia were independent risk factors for SPMs. Surveillance and education should be provided for survivors with respect to risk for SPMs. PMID:26131831

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

    PubMed

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

    2015-07-01

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

  19. 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.

  20. Age, gender, will, and use of home-visit nursing care are critical factors in home care for malignant diseases; a retrospective study involving 346 patients in Japan

    PubMed Central

    2011-01-01

    Background We aimed to clarify the factors affecting outcomes of home care for patients with malignant diseases. Methods Of 607 patients who were treated in 10 clinics specialized in home care between January and December 2007 at Chiba, Fukuoka, Iwate, Kagoshima, Tochigi and Tokyo prefectures across Japan, 346 (57%; 145 men and 201 women) had malignant diseases. We collected information on medical and social backgrounds, details of home care, and its outcomes based on their medical records. Results Median age of the patients was 77 years (range, 11-102), and 335 patients were economically self-sufficient. Their general condition was poor; advanced cancer (n = 308), performance status of 3-4 (n = 261), and dementia (n = 121). At the beginning of home care, 143 patients and 174 family members expressed their wish to die at home. All the patients received supportive treatments including fluid replacement and oxygenation. Median duration of home care was 47 days (range, 0-2,712). 224 patients died at home. For the remaining 122, home care was terminated due to complications (n = 109), change of attending physicians (n = 8), and others (n = 5). The factors which inhibited the continuity of home care were the non-use of home-visit nursing care (hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.05-3.00, p = 0.03), the fact that the patients themselves do not wish to die at home (HR = 1.83, CI: 1.09-3.07, p = 0.02), women (HR = 1.81, CI: 1.11-2.94, p = 0.02), and age (HR = 0.98, CI: 0.97-1.00, p = 0.02). Conclusions Continuation of home care is influenced by patients' age, gender, will, and use of home-visit nursing. PMID:22044683

  1. [Colorectal cancer screening].

    PubMed

    Castells, Antoni

    2015-09-01

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

  2. Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease? A double-blind, randomised, multicentre comparison. ANZ-Organon Investigators' Group.

    PubMed

    Gallus, A; Cade, J; Ockelford, P; Hepburn, S; Maas, M; Magnani, H; Bucknall, T; Stevens, J; Porteous, F

    1993-10-18

    This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. "Intent to treat" analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy ("compliant patients") were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.

  3. Biomarkers for Colorectal Cancer

    PubMed Central

    Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro; Ishigamori, Rikako

    2010-01-01

    Colorectal cancer (CRC) is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy significantly improves the detection rate of CRC, but the examination is expensive and inconvenient. Therefore, we need novel biomarkers that are non-invasive to enable us to detect CRC quite early. A number of validation studies have been conducted to evaluate genetic, epigenetic or protein markers for identification in the stool and/or serum. Currently, the fecal occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics will lead to the discovery of novel non-invasive biomarkers. PMID:20957089

  4. Second Cancers After Colorectal Cancer

    MedlinePlus

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

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

    ClinicalTrials.gov

    2017-05-02

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

  6. 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

  7. Colorectal polyps and polyposis syndromes

    PubMed Central

    Shussman, Noam; Wexner, Steven D.

    2014-01-01

    A polyp is defined as any mass protruding into the lumen of a hollow viscus. Colorectal polyps may be classified by their macroscopic appearance as sessile (flat, arising directly from the mucosal layer) or pedunculated (extending from the mucosa through a fibrovascular stalk). Colorectal polyps may also be histologically classified as neoplastic or as non-neoplastic (hyperplastic, hamartomatous, or inflammatory). The neoplastic polyps are of primary importance because they harbor a malignant potential, which represents a stage in the development of colorectal cancer. For this reason, it is essential to identify these polyps at a sufficiently early stage, when a simple outpatient procedure to remove them can interrupt the development of colorectal cancer and prevent disease and death. When invasive carcinoma arises in a polyp, careful consideration must be given to ensuring the adequacy of treatment. Although most neoplastic polyps do not evolve into cancer, it is well accepted that the majority of colorectal carcinomas evolve from adenomatous polyps; the sequence of events leading to this transformation is referred to as the adenoma-to-carcinoma sequence. The presence of a systemic process that promotes the development of multiple gastro-intestinal polyps is termed ‘polyposis’. Hereditary gastro-intestinal polyposis syndromes account for approximately 1% of all cases of colorectal cancer and are associated with a broad spectrum of extra-colonic tumors. Early detection and accurate classification of these syndromes are essential, in order to initiate a surveillance program for the early detection of cancer. Several polyposis syndromes have been described, each having its own genetic basis and characteristic polyp distribution, clinical presentation, and malignancy risk. Diagnostic modalities and treatment options for neoplastic polyps—as well as the most prevalent polyposis syndromes—are reviewed below. PMID:24760231

  8. COLORECTAL CANCER

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  10. Genetic factors and colorectal cancer in Ashkenazi Jews.

    PubMed

    Locker, Gershon Y; Lynch, Henry T

    2004-01-01

    The observed increased incidence of colorectal cancer in Ashkenazi Jews compared to other populations is unexplained but likely has a genetic component. The I1307K APC polymorphism/mutation is carried by 6-8% of Ashkenazim and increases the risk of colorectal cancer 1.5-2 fold. There are few differences between the phenotype of colorectal cancer in I1307K carriers and sporadic cases. It is estimated that the mutation accounts for 6% of cases of colorectal cancer in Jews of Eastern European heritage. It should not be the subject of mass screening in Ashkenazi Jews, although it may be important in cases of familial colorectal cancer. Even rarer is the 1906G-->C MSH2 mutation carried by less than 1% of Ashkenazim, but as with other HNPCC mutations likely associated with a high risk of malignancy. Mutations at 15q13-14 are associated with the colorectal adenoma and carcinoma syndrome (CRAC) described in Ashkenazi families. The prevalence of the mutation is not known, nor its significance as a cause of colorectal cancer. Despite the paucity of genetic explanations for the high risk of colorectal cancer in Ashkenazim, that risk warrants aggressive colorectal cancer screening and particular attention to family history of malignancy in all Jews of Ashkenazi descent.

  11. KISS1 expression in colorectal cancer.

    PubMed

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

    2013-10-01

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

  12. Canine olfactory detection of malignant melanoma

    PubMed Central

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

    2013-01-01

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

  13. [The colorectal carcinoma risk factors].

    PubMed

    Sobczak, Andrzej; Wawrzyn-Sobczak, Katarzyna; Sobaniec-Lotowska, Maria

    2005-12-01

    Colorectal carcinoma constitutes the second, as for the rate, death cause due to a malignant disease both in the western countries and in Poland. Despite deep knowledge concerning morphogenesis and spread of colorectal carcinoma as well as vast achievements in surgery, chemo- and radiotherapy, the percentage of 5-year-survivals still reaches 40%. According to most authors there are 4 risk factor categories: epidemiological, intestinal, dietetic, and mixed. It is well-known that colorectal carcinoma, like neoplasms localized in other organs and systems, is a disease, in which genetic mutations of somatic cells are the molecular base/source of the disease. The inner innervation of the colon seems to play an important role in carcinoma pathogenesis and spread. At present, 80% of colorectal carcinomas are diagnosed in the advanced stage, with infiltration exceeding the intestinal wall or spreading to neighboring organs, which gives full clinical symptoms. The prognosis as to survival and disease progression is usually poor. Therefore, the ways of early diagnosis, monitoring, and the knowledge of etiological factors are so important in medical practice.

  14. Mesothelioma - malignant

    MedlinePlus

    ... Names Mesothelioma - malignant; Malignant pleura mesothelioma (MPM) Images Respiratory system References Broaddus VC, Robinson BWS. Pleural tumors. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

  15. Pleural malignancies.

    PubMed

    Friedberg, Joseph S; Cengel, Keith A

    2010-07-01

    Pleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent. Copyright 2010 Elsevier Inc. All rights reserved.

  16. 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 ...

  17. Safety and efficacy of palliative systemic chemotherapy combined with colorectal self-expandable metallic stents in advanced colorectal cancer: A multicenter study.

    PubMed

    Cézé, Nicolas; Charachon, Antoine; Locher, Christophe; Aparicio, Thomas; Mitry, Emmanuel; Barbieux, Jean-Pierre; Landi, Bruno; Dorval, Etienne; Moussata, Driffa; Lecomte, Thierry

    2016-04-01

    Self-expandable metallic stent (SEMS) placement is an accepted palliative therapy for management of acute malignant bowel obstruction in advanced colorectal cancer. Nevertheless, data are lacking on the effects of systemic chemotherapy combined with colorectal SEMS. The aim of this study was to investigate the safety and efficacy of palliative chemotherapy for advanced colorectal cancer combined with colorectal SEMS placement. This multicentre retrospective study included all consecutive advanced colorectal cancer patients who received first-line palliative chemotherapy combined with endoscopic stenting for colorectal cancer with obstruction. We analyzed the number of cycles and the type of combination used. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, response rate, grade 3-4 toxicity and the outcomes of SEMS for malignant colorectal obstruction. A total of 38 patients were included. Among them, 25 patients received oxaliplatin and 5-fluorouracil combination chemotherapy. Objective response and stabilization occurred in 38 and 24% of patients, respectively. The median overall survival and progression-free survival from the start of chemotherapy were 18 and 5months, respectively. The objective response rate and overall disease control rate were 38 and 62%, respectively. Toxicity was generally acceptable. Major complications related to stenting included perforation (8%), stent migration (5%), and reobstruction secondary to tumor ingrowths (13%). Chemotherapy combined with colonic stenting as a first-line treatment seems to be a valid option in advanced colorectal cancer patients with malignant colorectal obstruction. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Blood-based Biomarkers at Large Bowel Endoscopy and Prediction of Future Malignancies

    PubMed Central

    Kring, Thomas S.; Piper, Thomas B.; Jørgensen, Lars N.; Olsen, Jesper; Rahr, Hans B.; Nielsen, Knud T.; Laurberg, Søren; Davis, Gerard; Dowell, Barry; Johansen, Julia S.; Christensen, Ib J.; Brünner, Nils; Nielsen, Hans J.

    2015-01-01

    Soluble cancer-related protein biomarker levels may be increased in subjects without findings at large bowel endoscopy performed due to symptoms associated with colorectal cancer. The present study focused on a possible association between increased biomarker levels in such subjects and subsequent development of malignant diseases. In a major study of 4,990 subjects undergoing large bowel endoscopy, 691 were without pathology and comorbidity. Plasma levels of TIMP-1, CEA, CA19-9, and YKL-40 were determined in samples collected just before endoscopy and compared with subsequent development of a malignant disease within a period of 7–8 years. The upper 90% limits of the reference levels of every single protein were used to differentiate between normal and increased levels. The levels were separated into three groups: 0, none of the biomarkers increased; 1, one biomarker increased; 2, two or more biomarkers increased. A total of 43 subjects developed a primary malignant disease in the observation period. Univariatly, increase of all four biomarkers was significantly associated with subsequent development of a malignant disease. A multivariate analysis showed that increased biomarker levels were associated with subsequent development of a malignant disease (P = 0.002). The cumulative risk of developing malignant disease within the first 5 years after endoscopy was group 0, 3.3%; group 1, 5.8%; group 2, 7.8%. It is concluded that increased levels of plasma TIMP-1, CEA, CA19-9, and serum YKL-40 at large bowel endoscopy without findings may be associated with an increased risk of developing a subsequent malignant disease. PMID:26526637

  19. [New advances in hereditary colorectal cancer].

    PubMed

    Moreira, Leticia

    2015-09-01

    Colorectal cancer is the most frequent malignancy in both sexes in Spain. Between 20% and 25% of affected individuals have a family history of the disease, and 5% to 6% have a germ mutation, i.e. the disease develops in the context of a hereditary syndrome. The importance of identifying patients with hereditary syndromes predisposing them to colorectal cancer lies in the possibility of applying preventive measures, screening, and more appropriate management of both patients and their families. The present article outlines the most important studies presented at the congress of the American Gastroenterological Association. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. Malignant hyperthermia

    MedlinePlus

    ... counseling is recommended for anyone with a family history of myopathy, muscular dystrophy, or malignant ... et al, eds. Harrison's Principles of Internal Medicine . 17th ed. [online version]. New York, NY: McGraw ...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2017-01-01

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

  4. MicroRNAs: Clinical Relevance in Colorectal Cancer.

    PubMed

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

    2015-11-25

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

  5. 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

    2012-07-26

    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.

  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 Central

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

    2012-01-01

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

  7. 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

  8. Serrated pathway in colorectal carcinogenesis

    PubMed Central

    Yamane, Letícia; Scapulatempo-Neto, Cristovam; Reis, Rui Manuel; Guimarães, Denise Peixoto

    2014-01-01

    Serrated adenocarcinoma is a recently described subset of colorectal cancer (CRC), which account for about 10% of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC. Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps (HPs), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and mixed polyps. HPs are the most common serrated polyp followed by SSA and TSA. This distinct histogenesis is believed to have a major influence in prevention strategies, patient prognosis and therapeutic impact. Genetically, serrated polyps exhibited also a distinct pattern, with KRAS and BRAF having an important contribution to its development. Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype. In the present review we will address the current knowledge of serrated polyps, clinical pathological features and will update the most recent findings of its molecular pathways. The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development. PMID:24627599

  9. Early diagnosis for colorectal cancer in China

    PubMed Central

    Zhang, Ya-Li; Zhang, Zhen-Su; Wu, Ba-Ping; Zhou, Dian-Yuan

    2002-01-01

    AIM: To review the present studies on early diagnosis of colorectal cancer. METHODS: The detective rate for early cancer is 1.7%-26.1% based on various statistical data, with much higher detective rate in endoscopy. Since early cancer means invasion involved in the mucosa or submucosa, the diagnosis can only be made when the invasive depth is identified. Pathological tissue materials from both surgical operation or endoscopic resection are suitable for early cancer evaluation. RESULTS: Incidence of polyp malignancy is 1.4%-20.4%. The various constitutive proportion of polyps may explain the different rates. Malignant incidence is higher in adenomatous polyps, that for villous polyps can reach 21.3%-58.3%. Type II early stage of colorectal carcinoma is rarely reported in China. It is shownd that majority of them were not malignant, most of type IIa being adenoma or hyperplasia, and IIb being inflammatory and IIc might be the isolated ulcers. The occurrence of malignancy of type II is far lower than that of polypoid lesion. In China, the qualitative diagnosis and classification of neoplasm generally adopted the WHO standard, including surgical excision or biopsies. There is impersonal evaluation between colorectal pre-malignancy and cancer. The former emphasizes the dysplasia of nuclei and gland, while the latter is marked with cancer invasion. Diagnosis of early stage colorectal cancer in endoscopy is made with too much caution which made the detective rate much lower. Mass screening for asymptomatic subjects and follow-up for high risk population are mainly used to find the early stage colorectal cancer in China. Fecal occult blood test is also widely made as primary screening test, galactose oxygenase test of rectal mucus (T antigen), fecal occult albumin test are also used. The detective rate of colorectal cancer is 24-36.5 per 105 mass population. CONCLUSION: Although carcinoma associated antigen in blood or stool, microsatellite DNA instability for high risk

  10. 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.

  11. 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.

  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. Epigenetics in diagnosis of colorectal cancer.

    PubMed

    Sameer, Aga Syed; Nissar, Saniya

    2016-03-01

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

  14. 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.

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

    PubMed

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

    2015-08-01

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

  16. Robotics in colorectal surgery.

    PubMed

    Kariv, Y; Delaney, C P

    2005-10-01

    A minimally invasive approach has not yet become the gold standard in colorectal procedures, despite its proven advantages in postoperative recovery. This is in part the result of the technical limitations in today's standard laparoscopy, and the advanced surgical skills that are required. Robotic technology overcomes some of these limitations by successfully providing intuitive motion and enhanced precision and accuracy, in an environment that is much more ergonomic. While currently performed in only few designated centers, this technology has already been applied in almost every major procedure performed to treat both benign and malignant conditions of the large bowel. The feasibility of performing these procedures using robotic systems has been reported in several series. Conversion and complication rates are low, and short term results are comparable to conventional laparoscopy. However, no clear advantages to patients have been demonstrated yet. Furthermore, robotic technology is associated with a significant increase in time consumed during surgery and cost of care. Nevertheless, a great potential for patients benefit in the future may exist with this technology. Increasing clinical experience with these systems, further technological developments, and continuous research are required before robotic technology can be routinely incorporated into surgical procedures on the colon and rectum.

  17. 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.

  18. Malignant hyperthermia.

    PubMed

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

    1986-10-01

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

  19. [How I treat colorectal cancer. I. Prevention and adjuvant treatment].

    PubMed

    Bours, V; Jerusalem, G; Fillet, G

    1998-04-01

    Colorectal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Belgium and in other western countries. Prevention implies a modification of alimentation and maybe a chronic uptake of acetylsalicylic acid. Treatment of colorectal cancers is based on surgery and the prognosis is determined by the locoregional or metastatic tumor spread. Complete resection of any Astler Coller stage C colorectal malignant tumor has to be followed by a 5-fluorouracil-based adjuvant chemotherapy. In these protocols, 5-fluorouracil is administered together with folinic acid or levamisole. The administration of an adjuvant chemotherapy could also be considered for stage BII diseases. As rectal cancers are characterized by high local relapse rates, their treatment should associate radiotherapy, given either post-surgery or preferentially pre-surgery, with resection and chemotherapy. Appropriate treatment of colorectal cancers thus requires a concerted multidisciplinary approach.

  20. Malignant hyperthermia

    PubMed Central

    2012-01-01

    Malignant hyperthermia (MH) is an uncommon, life-threatening pharmacogenetic disorder of the skeletal muscle. It presents as a hypermetabolic response in susceptible individuals to potent volatile anesthetics with/without depolarizing muscle relaxants; in rare cases, to stress from exertion or heat stress. Susceptibility to malignant hyperthermia (MHS) is inherited as an autosomally dominant trait with variable expression and incomplete penetrance. It is known that the pathophysiology of MH is related to an uncontrolled rise of myoplasmic calcium, which activates biochemical processes resulting in hypermetabolism of the skeletal muscle. In most cases, defects in the ryanodine receptor are responsible for the functional changes of calcium regulation in MH, and more than 300 mutations have been identified in the RYR1 gene, located on chromosome 19q13.1. The classic signs of MH include increase of end-tidal carbon dioxide, tachycardia, skeletal muscle rigidity, tachycardia, hyperthermia and acidosis. Up to now, muscle contracture test is regarded as the gold standard for the diagnosis of MHS though molecular genetic test is used, on a limited basis so far to diagnose MHS. The mortality of MH is dramatically decreased from 70-80% to less than 5%, due to an introduction of dantrolene sodium for treatment of MH, early detection of MH episode using capnography, and the introduction of diagnostic testing for MHS. This review summarizes the clinically essential and important knowledge of MH, and presents new developments in the field. PMID:23198031

  1. Malignant hyperthermia.

    PubMed

    Bandschapp, Oliver; Girard, Thierry

    2012-07-31

    Malignant hyperthermia (MH) is a subclinical myopathy, usually triggered by volatile anaesthetics and depolarising muscle relaxants. Clinical symptoms are variable, and the condition is sometimes difficult to identify. Nevertheless, rapid recognition and specific as well as symptomatic treatment are crucial to avoid a lethal outcome. Molecular genetic investigations have confirmed the skeletal muscle type ryanodine receptor to be the major MH locus with more than 70% of MH families carrying a mutation in this gene. There is no screening method to test for MH, as current tests are invasive (open muscle biopsy) or restricted to MH families with known MH-associated mutations (molecular genetic testing). The prevalence of the MH trait is unknown, because the clinical penetrance after contact with triggering agents is very variable. More recently, MH mutations have been associated with rhabdomyolysis following statin therapy or with non-pharmacological triggering, such as exertional heat stroke.

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

    PubMed

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

    2015-03-21

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

  3. Gastrins, iron and colorectal cancer.

    PubMed

    Baldwin, Graham S

    2009-09-01

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

  4. Colorectal Cancer Presenting with Constipation During Pregnancy

    PubMed Central

    Povlow, Michael R

    2017-01-01

    Colorectal cancer is a rare occurrence during pregnancy and can present with symptoms that are common during pregnancy such as constipation.This can make the diagnosis of colorectal cancer during pregnancy difficult. Management of colorectal cancer during pregnancy is similar to the treatment of non-pregnant patients, but with fetal safety in mind. This case report describes a 33-year-old female gravida two para one (G2P1) at 29 weeks gestation who presented with a complete bowel obstruction. Colonoscopy, magnetic resonance imaging (MRI) and later resection showed an obstructing malignancy which was then resected through an exploratory laparotomy with left hemicolectomy. Postoperatively, there was a concern for sepsis, so labor was induced and the baby was delivered vaginally. The patient then continued with chemotherapy with hematology-oncology. High clinical suspicion is needed to diagnose colorectal cancer during pregnancy. Once diagnosed, surgery can be considered if resectable, taking into account gestational age. Fetal safety is a major consideration during treatment. PMID:28553568

  5. Synchronous trifocal colorectal cancer

    PubMed Central

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

    2016-01-01

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

  6. Epigenetics and Colorectal Cancer

    PubMed Central

    Lao, Victoria Valinluck; Grady, William M.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

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

    PubMed

    Martínez, María Elena

    2005-01-01

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

  8. Venous thromboembolic disease in colorectal patients.

    PubMed

    McNally, Michael P; Burns, Christopher J

    2009-02-01

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

  9. [Malignant hyperthermia].

    PubMed

    Metterlein, T; Schuster, F; Graf, B M; Anetseder, M

    2014-12-01

    Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle relaxant succinylcholine can induce a potentially fatal metabolic increase in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca) concentration. Mutations in the dihydropyridine ryanodine receptor complex in combination with the trigger substances are responsible for an uncontrolled release of Ca from the sarcoplasmic reticulum. This leads to activation of the contractile apparatus and a massive increase in cellular energy production. Exhaustion of the cellular energy reserves ultimately results in local muscle cell destruction and subsequent cardiovascular failure. The clinical picture of MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac arrhythmia whereas the body temperature rise, after which MH is named, often occurs later. Decisive for the course of MH episodes is a timely targeted therapy. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced to well under 10 %. An MH predisposition can be detected using the invasive in vitro contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures are in the developmental stage.

  10. 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

  11. Malignant abdominal rocks: where do they come from?

    PubMed Central

    Cheng, Joan M.; Kim, Kyung Won; Saboo, Sachin S.; Baez, Juan C.; Shinagare, Atul B.

    2013-01-01

    Abstract For the radiologist, calcifications in an abdominal malignancy raise questions of both diagnostic and prognostic significance. Although certain cancers are well known to calcify, such as colorectal and ovarian, malignant abdominal calcifications actually arise from a wide variety of epithelial, mesenchymal, lymphoid, or germ cell neoplasms. The pathophysiology of calcification in abdominal malignancies is heterogeneous and incompletely understood. Calcifications may present primarily, in untreated tumors, or develop during treatment; the latter can occur in variable clinical settings. A basic understanding of the varied pathogenic etiology can assist the radiologist in assessing disease status. By presenting an assortment of calcified abdominal malignancies on computed tomography in varied clinical settings, we aim not only to inform the differential diagnosis, but also to clarify the prognosis of calcifications in abdominal malignancies. PMID:24334568

  12. Aetiology of colorectal cancer and relevance of monogenic inheritance

    PubMed Central

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

    2004-01-01

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

  13. 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

  14. 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

  15. Obesity and Colorectal Cancer.

    PubMed

    Jochem, Carmen; Leitzmann, Michael

    There is strong evidence that modifiable lifestyle factors such as obesity play a key role in colorectal carcinogenesis. Epidemiologic data have consistently reported a positive association between obesity and colorectal cancer. The relative risk associated with general obesity (as assessed by BMI) is higher in men than in women and for cancer of the colon than for cancer of the rectum. Abdominal obesity (as assessed by waist circumference (WC) or waist-to-hip ratio) is associated with an increased risk of colorectal cancer in both sexes, with stronger associations for cancer of the colon than for cancer of the rectum. Plausible biological mechanisms include insulin resistance, hyperinsulinemia, chronic inflammation, altered levels of growth factors, adipocytokines and steroid hormones. In addition to its effect on colorectal cancer incidence, obesity may play a role in colorectal cancer recurrence, treatment outcomes and survival. Understanding the effects of childhood and adolescent obesity and weight change over the life course in relation to future risk of colorectal cancer is incomplete but essential for targeted preventive recommendations. This chapter summarizes the current evidence on the relationship between obesity and colorectal cancer and colorectal adenoma, a common precursor lesion.

  16. Statin-induced muscle toxicity and susceptibility to malignant hyperthermia and other muscle diseases: a population-based case-control study including 1st and 2nd degree relatives.

    PubMed

    Hedenmalm, Karin; Granberg, Arzu Gunes; Dahl, Marja-Liisa

    2015-01-01

    Case reports have suggested an association between susceptibility to malignant hyperthermia (MH) and other muscle diseases in subjects with statin-induced muscle toxicity. The aim of the study was to further scrutinize this association in a population-based case-control study including 1st and 2nd degree relatives. Spontaneously reported cases with muscle disorders associated with statin therapy until September 2006 were identified in the Swedish Adverse Drug Reaction Registry at the Medical Products Agency. For each case, ten population-based controls, matched on year of birth and gender, were randomly selected from the National Registry of Swedish Citizens. First and 2nd degree relatives to cases and controls were identified in the Swedish Multi-Generation Registry. ICD codes that could be associated with susceptibility to MH or other muscle diseases were chosen, and subjects were followed until December 2007 with regard to occurrence of selected ICD codes in the Swedish Registries for Cause of Death and Hospital Discharge Diagnoses, respectively. The chosen ICD codes were significantly overrepresented in case families compared with control families (RR 1.56; 95 % CI 1.15-2.10). The strongest associations were identified for a diagnosis of drug-induced or specified or unspecified myopathy (RR 52; 95 % CI 22-123) or a diagnosis of unspecified hyperthermia in combination with drug-induced or specified or unspecified myopathy (RR 30; 95 % CI 6-148). In contrast, a diagnosis of unspecified hyperthermia in the absence of drug-induced or specified or unspecified myopathy was significantly underrepresented among case families (RR 0.42; 95 % CI 0.23-0.76). In a case-control study including 1st and 2nd degree relatives, statin-induced muscle toxicity was significantly associated with a diagnosis of drug-induced or specified or unspecified myopathy and with a diagnosis of unspecified hyperthermia in combination with a diagnosis of drug-induced or specified or unspecified

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

    PubMed

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

    2016-03-01

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

  18. Detection of colorectal cancer using time-resolved autofluorescence spectrometer

    NASA Astrophysics Data System (ADS)

    Fu, Sheng; Kwek, Leong-Chuan; Chia, Teck-Chee; Lim, Chu-Sing; Tang, Choong-Leong; Ang, Wuan-Suan; Zhou, Miao-Chang; Loke, Po-Ling

    2006-04-01

    As we know Quantum mechanics is a mathematical theory that can describe the behavior of objects that are at microscopic level. Time-resolved autofluorescence spectrometer monitors events that occur during the lifetime of the excited state. This time ranges from a few picoseconds to hundreds of nanoseconds. That is an extremely important advance as it allows environmental parameters to be monitored in a spatially defined manner in the specimen under study. This technique is based on the application of Quantum Mechanics. This principle is applied in our project as we are trying to use different fluorescence spectra to detect biological molecules commonly found in cancerous colorectal tissue and thereby differentiate the cancerous and non-cancerous colorectal polyps more accurately and specifically. In this paper, we use Fluorescence Lifetime Spectrometer (Edinburgh Instruments FL920) to measure decay time of autofluorescence of colorectal cancerous and normal tissue sample. All specimens are from Department of Colorectal Surgery, Singapore General Hospital. The tissues are placed in the time-resolved autofluorescence instrument, which records and calculates the decay time of the autofluorescence in the tissue sample at the excitation and emission wavelengths pre-determined from a conventional spectrometer. By studying the decay time,τ, etc. for cancerous and normal tissue, we aim to present time-resolved autofluorescence as a feasible technique for earlier detection of malignant colorectal tissues. By using this concept, we try to contribute an algorithm even an application tool for real time early diagnosis of colorectal cancer for clinical services.

  19. Epigenetics in diagnosis of colorectal cancer

    PubMed Central

    Sameer, Aga Syed; Nissar, Saniya

    2016-01-01

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

  20. The Heterocellular Emergence of Colorectal Cancer.

    PubMed

    Tape, Christopher J

    2017-02-01

    Tissues contain multiple different cell types and can be considered to be heterocellular systems. Signaling between different cells allows tissues to achieve phenotypes that no cell type can achieve in isolation. Such emergent tissue-level phenotypes can be said to 'supervene upon' heterocellular signaling. It is proposed here that cancer is also an emergent phenotype that supervenes upon heterocellular signaling. Using colorectal cancer (CRC) as an example, I review how heterotypic cells differentially communicate to support emergent malignancy. Studying tumors as integrated heterocellular systems - rather than as solitary expansions of mutated cells - may reveal novel ways to treat cancer.

  1. 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.

  2. Malignant hyperthermia

    PubMed Central

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

    2007-01-01

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

  3. Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

    DTIC Science & Technology

    2013-09-01

    the focus area is “inflammatory response in the development of colorectal cancer”. Inflammatory bowel disease ( IBD ) is associated with the development...of colorectal cancer; however, little is known about the mechanisms responsible for the progression of IBD to malignancy. The purpose of the work...the growth and survival of human colon cancer cells growing in vitro and as tumor xenografts in nude mice and to develop a MUC1+/ IL -10-/- model of

  4. [Chemoprevention of colorectal cancer].

    PubMed

    Herszényi, László; Juhász, Márk; Prónai, László; Tulassay, Zsolt

    2004-03-21

    Although colorectal cancer is one of the most preventable forms of cancer, it remains the second leading cause of cancer death worldwide. Primary prevention involves the identification and elimination of factors, which cause or promote colorectal cancer. The goal of screening is to prevent colorectal cancer mortality through the detection and treatment of premalignant adenomas and curable-stage cancer. Most colorectal cancers are believed to arise from adenomatous polyps. Early identification and removal of adenomas can prevent the development of colorectal cancer. Chemoprevention is the use of specific chemical compounds to prevent, inhibit, or reverse carcinogenesis. Several chemoprevention options have been investigated and confirmed as effective. Aspirin and other nonsteroidal anti-inflammatory drugs are the most widely studied agents, their use has been consistently associated with reduction in the risk of mortality and the incidence of colorectal adenomas and cancers. The selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) have been demonstrated to decrease the number and the size of polyps in patients with familial adenomatous polyposis syndrome. Because the gastrointestinal toxicity of coxibs is lower, it might be safer than aspirin or other non-selective nonsteroidal anti-inflammatory drugs for long-term use. This review aims to summarize the recent theoretical and practical advances in the chemoprevention of colorectal cancer.

  5. Robotic colorectal surgery.

    PubMed

    Baik, Seung Hyuk

    2008-12-31

    Robotic colorectal surgery has gradually been performed more with the help of the technological advantages of the da Vinci system. Advanced technological advantages of the da Vinci system compared with standard laparoscopic colorectal surgery have been reported. These are a stable camera platform, three-dimensional imaging, excellent ergonomics, tremor elimination, ambidextrous capability, motion scaling, and instruments with multiple degrees of freedom. However, despite these technological advantages, most studies did not report the clinical advantages of robotic colorectal surgery compared to standard laparoscopic colorectal surgery. Only one study recently implies the real benefits of robotic rectal cancer surgery. The purpose of this review article is to outline the early concerns of robotic colorectal surgery using the da Vinci system, to present early clinical outcomes from the most current series, and to discuss not only the safety and the feasibility but also the real benefits of robotic colorectal surgery. Moreover, this article will comment on the possible future clinical advantages and limitations of the da Vinci system in robotic colorectal surgery.

  6. Colorectal cancer screening.

    PubMed

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

    2017-01-01

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

  7. Colorectal cancer screening

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Curing patients with liver metastases from colorectal cancer.

    PubMed

    2011-04-01

    Colorectal cancer is the third commonest malignancy worldwide and the second commonest cause of cancer-related deaths.1,2 Around 15-25% of patients with colorectal cancer have metastases at presentation, and a further 20-25% develop them subsequently.3 Management for metastatic disease is mainly palliative and traditionally 5-year survival has been rare.3-5 In colorectal cancer, metastases mostly occur in the liver and in 30-50% of patients with liver involvement, this is the only site of spread. For those with liver-only metastases, resection of these lesions provides a chance of longer-term survival or even cure (e.g. 5-year survival 25-71%).4,6-13 Here we focus on recent advances in chemotherapy for patients with initially unresectable liver metastases, aimed at rendering such lesions operable, with potential improvements in survival.4,13,14.

  11. 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.

  12. Pro-inflammatory prostaglandins and progression of colorectal cancer

    PubMed Central

    Wang, Dingzhi; DuBois, Raymond N.

    2008-01-01

    Chronic inflammation is a risk factor for several gastrointestinal malignancies, including esophageal, gastric, hepatic, pancreatic and colorectal cancer. It has long been known that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the relative risk of developing colorectal cancer. NSAIDs exert their anti-inflammatory and anti-tumor effects primarily by inhibiting activity of cyclooxygenase (COX) enzymes. Cyclooxygenase enzymes catalyze the conversion of arachidonic acid into prostanoids, including prostaglandins (PGs) and thromboxanes (TXs). Emerging evidence demonstrates that prostaglandins play an important role in inflammation and cancer. In this review, we highlight recent breakthroughs in our understanding of the roles of the different prostaglandins in colorectal cancer (CRC) and inflammatory bowel disease (IBD). These findings may provide a rationale for the development of new anti-inflammatory therapeutic approaches to cancer prevention and/or treatment. PMID:18406516

  13. Colorectal cancer statistics, 2017.

    PubMed

    Siegel, Rebecca L; Miller, Kimberly D; Fedewa, Stacey A; Ahnen, Dennis J; Meester, Reinier G S; Barzi, Afsaneh; Jemal, Ahmedin

    2017-05-06

    Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged ≥50 years declined by 32%, with the drop largest for distal tumors in people aged ≥65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48-0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85-0.96; female IRR, 1.00; 95% CI, 0.93-1.08). Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged <50 years, CRC incidence rates increased by 22% from 2000 to 2013, driven solely by tumors in the distal colon (IRR, 1.24; 95% CI, 1.13-1.35) and rectum (IRR, 1.22; 95% CI, 1.13-1.31). Similar to incidence patterns, CRC death rates decreased by 34% among individuals aged ≥50 years during 2000 through 2014, but increased by 13% in those aged <50 years. Progress against CRC can be accelerated by increasing initiation of screening at age 50 years (average risk) or earlier (eg, family history of CRC/advanced adenomas) and eliminating disparities in high-quality treatment. In addition, research is needed to elucidate causes

  14. Colorectal Cancer Prevention

    MedlinePlus

    ... linked to a decreased risk of colorectal cancer. Aspirin Studies have shown that taking aspirin lowers the ... cancer: Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin It is not known if the use of ...

  15. Epidemiology of colorectal cancer

    PubMed Central

    Marley, Andrew R; Nan, Hongmei

    2016-01-01

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

  16. Colorectal Cancer Coalition

    MedlinePlus

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

  17. 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

  18. Core value of laparoscopic colorectal surgery.

    PubMed

    Li, Xin-Xiang; Wang, Ren-Jie

    2015-12-10

    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.

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

    PubMed

    Schattner, Ami

    2017-03-08

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

  20. 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

  1. Stenting for malignant colonic obstruction: a comparison of efficacy and complications in colonic versus extracolonic malignancy.

    PubMed

    Keswani, Rajesh N; Azar, Riad R; Edmundowicz, Steven A; Zhang, Qin; Ammar, Tarek; Banerjee, Bhaskar; Early, Dayna S; Jonnalagadda, Sreenivasa S

    2009-03-01

    Self-expandable metal stent placement for palliation of malignant colonic obstruction for colorectal cancer (CRC) is safe and efficacious. In contrast, outcomes of stent placement for extracolonic malignancy (ECM) are unclear. To compare the success and complication rates of colorectal stenting in patients with CRC versus those with ECM. Retrospective chart review. Tertiary-care academic medical center. Between September 2000 and December 2007, all patients with malignant colon obstruction in whom endoscopy was performed with the intention of placing a colonic metal stent. Technical and clinical success rates, surgical interventions, and procedure-related complications. Colonic stenting was performed for CRC in 34 patients and for ECM in 15 patients. Patients with CRC were more likely to have clinical success after all endoscopic therapy (94.1%) than those with ECM (20.0%) (P < .0001). Surgical diversion to relieve persistent obstructive symptoms was required in significantly more patients with ECM. Five patients with ECM (33.3%) had at least one complication, including 2 deaths, compared with 3 patients with CRC (8.8%) (P = .046). Only underlying ECM was predictive of failed colon stent placement by multivariate analysis (hazard ratio 21.0, P = .0013). A history of radiation therapy was the sole predictor of complications (hazard ratio 7.8, P = .048). Single institution, retrospective analysis, relatively small sample size. Colon stenting for large-bowel obstruction from ECM is infrequently successful and is associated with a significantly higher risk of complications in comparison with patients with CRC.

  2. [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.

  3. Colorectal endometriosis and fertility.

    PubMed

    Daraï, Emile; Cohen, Jonathan; Ballester, Marcos

    2017-02-01

    The goal of this review was to assess the impact of colorectal endometriosis on spontaneous fertility and the potential benefit of Medically Assisted Reproduction (MAR) (in vitro fertilization and intrauterine insemination) and surgery on fertility outcomes. MEDLINE search for articles on fertility in women with DIE published between 1990 and December 2015 using the following terms: "deep endometriosis", "deep infiltrating endometriosis", "bowel endometriosis", "colorectal endometriosis", "fertility", "infertility", "IVF-ICSI", "Assisted Reproductive Techniques (ART)", and "MAR". Spontaneous pregnancy rate (PR) in patients undergoing resection of DIE but leaving in situ colorectal endometriosis was 26.5% (95% CI=14-39). PR after MAR was 27.4% (95% CI=19-35) and the overall PR was 37.9% (95% CI=29-37). After colorectal surgery, among the 855 patients with and without proved infertility, the spontaneous PR was 31.4% (95% CI=28-34) without difference between the groups. PR after MAR was 19.8% (95% CI=17-22). PR after MAR in patients with and without proved infertility was 21.4% (95% CI=18-25) and 15.5% (95% CI=11-20), respectively. The overall PR after colorectal surgery was 51.1% (95% CI=48-54). Our review supports a potential benefit of surgery on fertility outcomes for women with colorectal endometriosis. Further studies are required to determine whether surgical management should be first-intention or restricted to failure of MAR. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Role of microRNA-7 in digestive system malignancy.

    PubMed

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

    2016-01-15

    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.

  5. Maspin, a Marker of Serrated Colorectal Polyps.

    PubMed

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

    2015-07-01

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

  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. Colorectal Cancer Risk Assessment Tool

    MedlinePlus

    ... Colorectal Cancer Risk Factors Download SAS and Gauss Code Page Options Print Page Quick Links Colon and Rectal Cancer Home Page Colon and Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps ...

  8. 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 ( ...

  9. Colorectal Cancer: Symptoms, Diagnosis, Treatment

    MedlinePlus

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

  10. 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

  11. [Malignant soft tissue tumors].

    PubMed

    Schauer, A; Altmannsberger, M

    1984-01-01

    This article is a survey of actual aspects. With regard to frequency, the malignant fibrous histocytoma comes first, followed by lipo- and fibrosarcoma, synovial sarcoma, malignant schwannoma, malignant tumours proceeding from arteries and veins and the unstriated musculature. Staging and grading of these tumours are difficult. Until now their overall TNM-classification was not possible due to insufficient hard criteria.

  12. Developments in Colorectal Cancer Screening

    MedlinePlus

    ... tested at age 45. Read More "Colorectal Cancer" Articles Colorectal Cancer: A Personal Journey / The Importance of Early Detection / Developments in Colorectal Cancer Screening Summer 2016 Issue: Volume 11 Number 2 Page ... Us | Viewers & Players Friends of the National Library of Medicine (FNLM)

  13. Colorectal Cancer: A Personal Journey

    MedlinePlus

    ... detection is early cure!” Read More "Colorectal Cancer" Articles Colorectal Cancer: A Personal Journey / The Importance of Early Detection / Developments in Colorectal Cancer Screening Summer 2016 Issue: Volume 11 Number 2 Page ... Us | Viewers & Players Friends of the National Library of Medicine (FNLM)

  14. Precursors to Lymphoproliferative Malignancies

    PubMed Central

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

    2013-01-01

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

  15. Obesity and colorectal cancer.

    PubMed

    Aleksandrova, Krasimira; Nimptsch, Katharina; Pischon, Tobias

    2013-01-01

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

  16. Colorectal cancer surveillance in Hodgkin lymphoma survivors at increased risk of therapy-related colorectal cancer: study design.

    PubMed

    Rigter, Lisanne S; Spaander, Manon C W; Moons, Leon M; Bisseling, Tanya M; Aleman, Berthe M P; de Boer, Jan Paul; Lugtenburg, Pieternella J; Janus, Cecile P M; Petersen, Eefke J; Roesink, Judith M; Raemaekers, John M M; van der Maazen, Richard W M; Cats, Annemieke; Bleiker, Eveline M A; Snaebjornsson, Petur; Carvalho, Beatriz; Lansdorp-Vogelaar, Iris; Jóźwiak, Katarzyna; Te Riele, Hein; Meijer, Gerrit A; van Leeuwen, Flora E; van Leerdam, Monique E

    2017-02-07

    Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach. We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires. This prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived ≥8 years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6-8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. Vasculitis associated with malignancy.

    PubMed

    Mertz, L E; Conn, D L

    1992-02-01

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

  2. 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

  3. The significance of measuring monocyte tissue factor activity in patients with breast and colorectal cancer

    PubMed Central

    Lwaleed, B A; Chisholm, M; Francis, J L

    1999-01-01

    Monocytes express tissue factor (mTF) in several conditions including cancer where levels may be valuable in assessing tumour presence and progression. Using a two-stage kinetic chromogenic assay (KCA), mTF levels were measured in controls [normal subjects (n = 60) and patients undergoing hernia repair or cholecystectomy (n = 60)], in patients with benign and malignant disease of the breast (n = 83) and of the large bowel (n = 62). This was performed under fresh (resting) conditions and after incubation for 6 h without (unstimulated) and with (stimulated) Escherichia coli endotoxin. The malignant groups showed higher mTF levels than each of the three controls for resting (P < 0.05 breast, P < 0.05 colorectal) unstimulated (P < 0.05 breast, P < 0.05 colorectal) and stimulated cells (P < 0.001 breast, P < 0.01 colorectal). Similarly, the benign inflammatory groups had higher mTF levels than controls for resting (P < 0.05 colorectal), unstimulated (P < 0.05 colorectal) and stimulated cells (P < 0.01 breast, P < 0.01 colorectal). There was no significant difference between malignant and benign inflammatory groups in each organ. mTF levels showed an increase corresponding to that of histological tumour progression and were higher in non-surviving patients. In conclusion, mTF levels are raised in malignant and inflammatory disease compared to controls and patients with non-inflammatory conditions. Stimulated cells give better discrimination between the groups and may be of value in identifying high risk individuals. mTF levels showed an association with tumour grade or stage and the patients' survival time. © 1999 Cancer Research Campaign PMID:10390009

  4. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2001-01-01

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

  6. Rheumatic Diseases and Malignancies

    PubMed Central

    BOJINCA, Violeta; JANTA, Iustina

    2012-01-01

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

  7. 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.

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

    PubMed

    Zheng, Ying; Wu, Chunxiao

    2016-05-01

    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.

  9. Perioperative Systemic Therapy and Surgery Versus Surgery Alone for Resectable Colorectal Peritoneal Metastases.

    ClinicalTrials.gov

    2017-05-05

    Colorectal Cancer; Colorectal Neoplasms; Colorectal Carcinoma; Colorectal Adenocarcinoma; Colorectal Cancer Metastatic; Peritoneal Carcinoma; Peritoneal Neoplasms; Peritoneal Cavity Cancer; Peritoneal Carcinomatosis; Peritoneal Metastases

  10. Equipment-based image-enhanced endoscopy for differentiating colorectal polyps.

    PubMed

    Koo, Ja Seol

    2014-07-01

    The use of colonoscopy for the screening and surveillance of colorectal cancer has increased. However, the miss rate of advanced colorectal neoplasm is known to be 2% to 6%, which could be affected by the image intensity of colorectal lesions. Image-enhanced endoscopy (IEE) is capable of highlighting lesions, which can improve the colorectal adenoma detection rate and diagnostic accuracy. Equipment-based IEE methods, such as narrow band imaging (NBI), Fujinon intelligent color enhancement (FICE), and i-Scan, are used to observe the mucosal epithelium of the microstructure and capillaries of the lesion, and are helpful in the detection and differential diagnosis of colorectal tumors. Although NBI is similar to chromoendoscopy in terms of adenoma detection rates, NBI can be used to differentiate colorectal polyps and to predict the submucosal invasion of malignant tumors. It is also known that FICE and i-Scan are similar to NBI in their detection rates of colorectal lesions. Through more effective and advanced endoscopic equipment, diagnostic accuracy could be improved and new treatment paradigms developed.

  11. 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.

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

    PubMed

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

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

  13. Risk and protective factors for development of colorectal polyps and cancer (Bulgarian experience).

    PubMed

    Kotzev, I; Mirchev, M; Manevska, B; Ivanova, I; Kaneva, M

    2008-01-01

    Colorectal cancer takes third place among all malignancies in the Varna region. The present study aims to determine the typical and distinguishing risk and protective factors for colorectal polyps and cancer formation. 166 patients with large bowel polyps and 107 patients with colorectal cancer were questioned, examined endoscopically and histologically. Logistic regression analysis was used to find a possible correlation between alimentary habits, way of life, and risk for colorectal polyps and cancer formation. The latter have been used to define a strategy for their prevention. Our results showed that fried, preserved, and grilled meat, consumption of animal fats, sugar, and being overweight are positively associated with colorectal polyps. In contrast, consumption of fruit, vegetables, rye- and brown bread, green tea, vegetable food, yoghourt, vegetarian food, fish, lamb, hare, garlic, boiled food, and mineral water, have strong protective effect against large bowel polyps. We have confirmed the role of the well-known risk factors for colorectal cancer, and discovered an association between H. pylori infection, age, villous component in the adenomatous polyps, and family history for any neoplasia and large bowel carcinoma. We suggest the following protective factors for CRC: vegetarian food, plant oil, rural life, aspirin intake, legumes, fish, fruit and vegetable consumption. We observe a similarity between the risk factors for colorectal polyps and cancer formation. They act simultaneously and depend on genetic predisposition. A combination of endoscopic treatment and correction of the alimentary factors could be used as a means of cancer prevention.

  14. Correlation between the expression of methionine adenosyltransferase and the stages of human colorectal carcinoma.

    PubMed

    Ito, K; Ikeda, S; Kojima, N; Miura, M; Shimizu-Saito, K; Yamaguchi, I; Katsuyama, I; Sanada, K; Iwai, T; Senoo, H; Horikawa, S

    2000-01-01

    Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (AdoMet) from ATP and L-methionine. AdoMet is the major methyl donor in most transmethylation reactions in vivo, and it is also the propylamino donor in the biosynthesis of polyamines. In the present study, we assessed MAT activity in human colons with colorectal carcinoma and the values were compared with those of morphologically normal adjacent mucosa. Higher levels of MAT activity were observed in the colorectal carcinoma than in the normal colon. The ratio of MAT activity in tumor tissue versus normal tissue seemed to be correlated well will the stage of the colorectal tumor. Furthermore, immunoblot analysis showed that the high levels of MAT activity observed in colorectal carcinoma were due to the increased amounts of MAT protein. Immunohistochemical analysis revealed that MAT was most abundant in goblet cells, particularly in granules in the supranuclear area of these cells. In the colorectal carcinoma tissues, MAT was strongly stained in the cancerous cells and localized in granules in the supranuclear region. The results of this preliminary study suggest that determination of the relative ratio of MAT activity in both normal and tumor regions in human colorectal carcinoma could be a clinically useful tool for determining the stage of malignancy of colorectal carcinomas.

  15. [SURGICAL TREATMENT OF THE LIVER METASTASES FROM COLORECTAL CANCER

    PubMed

    Ruiz, Eloy; Celis, Juan; Berrospi, Francisco; Payet, Eduardo

    2000-01-01

    OBJECTIVE: In the absence of extra hepatic disease, the hepatic resection is the treatment of choice for liver metastases from colorectal carcinoma, but a no treatment attitude or the use of chemotherapy still persists in some health centers. This study was done to evaluate the peri operative morbi-mortality and survival after resection of hepatic metastases from colorectal cancer in our institution.METHODS: Clinical, pathologic and outcome data of patients undergoing liver resection for metastatic colorectal cancer at the Instituto de Enfermedades Neoplasicas de Lima Peru between January 1986 and July 2000 was examined.RESULTS: Of 300 liver resections, 24 were performed in patients with liver metastases of colorectal cancer; 17 patients were men and 7 women, who ranged in age from 21 to 79 years ( a mean of 52.66 years), the site of primary disease was the rectum in 7 and colon in 17, 20 patients were Dukes C and 4 Dukes B.Synchronous secondary disease were found in 9 patients and metachronous lesions were found in 15 patients Forty nine metastases were resected (Mean size 4.5 cm, range 1.5 cm 24 cm)Seven patients underwent right hepatectomy, one right hepatectomy plus non anatomic wedge resection, two right trisegmentectomy, 4 left lobectomy and ten a non anatomical resection.The overall post operative morbidity was 8% and the 30 day post operative mortality rate was 0% Estimated three and five year survival rates using Kaplan-Meier method was 50 % and 20% respectively.CONCLUSION: Hepatic resection for a secondary malignant liver growth from colorectal cancer is relatively safe with low morbidity and mortality rates, an remains the only potentially curative treatment. We continue to recommend an aggressive surgical approach to hepatic metastases of colorectal origin in the abscense of extra hepatic disease.

  16. [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

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

    PubMed

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

    2015-09-01

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

  18. 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.

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

    ClinicalTrials.gov

    2017-07-11

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

  20. Pinworm infection masquerading as colorectal liver metastasis

    PubMed Central

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

    2012-01-01

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

  1. Bronchial malignant melanoma.

    PubMed

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

    1980-01-01

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

  2. Malignant tumors —

    Cancer.gov

    Main criteria for malignancy include size over 5 mm in diameter, invasion of airways, blood or lymphatic vessels, regional and distant metastasis, and ability to grow upon transplantation. Nuclear and cellular atypia, and loss of architecture should be considered as ancillary criteria for defining malignancy.

  3. Gastrins, iron homeostasis and colorectal cancer.

    PubMed

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

    2011-05-01

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

  4. Morphologic reappraisal of serrated colorectal polyps.

    PubMed

    Torlakovic, Emina; Skovlund, Eva; Snover, Dale C; Torlakovic, Goran; Nesland, Jahn M

    2003-01-01

    The "hyperplastic polyp" is considered a benign lesion with no malignant potential, whereas "serrated adenoma" is a precursor of adenocarcinoma. The morphologic complexity of the serrated adenoma varies from being clearly adenomatous to being difficult to distinguish from hyperplastic polyp, which creates a need for more detailed morphologic analysis of all serrated polyps. We evaluated 24 morphologic variables in 289 serrated polyps from the colon and rectum. Cluster analysis and discriminant analysis were performed. A subset of polyps was immunostained for hMLH1 and hMSH2. Major differences were found between right-sided and left-sided polyps. A distinct group of serrated polyps with abnormal proliferation was identified throughout the colon and rectum. These polyps demonstrated decreased expression of hMHL1 and hMSH2 compared with polyps with normal proliferation. Left-sided serrated polyps with normal proliferation further clustered into three groups: vesicular cell-type, goblet cell-type, and mucin-poor-type. We recommend evaluation of the localization, size, and morphologic features when serrated polyps are included in colorectal carcinogenesis research. Polyps with abnormal proliferation are similar to the polyps in "hyperplastic polyposis" and, because of their decreased expression of hMLH1 and hMSH2, may be the subset of polyps associated with the development of colorectal carcinoma via the microsatellite instability pathway.

  5. Urinary tissue factor activity in colorectal disease.

    PubMed

    Carty, N; Taylor, I; Roath, O S; el-Baruni, K; Francis, J L

    1990-10-01

    Procoagulant activity (PCA) in normal urine has been recognized for over 50 years. Although tissue factor (TF) is produced by certain tumours, and is increased in both tumour-associated macrophages and blood monocytes, the possibility that it might also be increased in urine has not been studied in patients with cancer. We have measured urinary PCA in hospital controls without inflammatory or neoplastic disease (n = 79), in patients with rheumatoid arthritis (n = 8), inflammatory bowel disease (n = 19), colorectal cancer (n = 70) and in patients undergoing colonoscopy (n = 50). Urinary PCA was higher (P less than 0.001) in patients with colorectal cancer and inflammatory bowel disease than controls or patients with rheumatoid arthritis. Fourteen (88 per cent) out of 16 colonoscopy patients subsequently found to have carcinoma or inflammatory bowel disease had levels above the control upper quartile, compared with 8 (24 per cent) out of 34 with normal colonoscopy (P less than 0.001). TF inhibitors confirmed the nature of the PCA and Western blotting studies indicated a urinary TF molecular weight of approximately 38,000. These studies provide further evidence of abnormal haemostasis in malignancy and suggest that determination of urinary TF may provide a useful screening test in patients undergoing colonoscopy.

  6. Gastrins, Iron Homeostasis and Colorectal Cancer

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2008-01-01

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

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

    PubMed

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

    2009-06-01

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

  9. Colorectal tumors: the histology report.

    PubMed

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

    2011-03-01

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

  10. 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

  11. 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).

  12. Colorectal cancer screening in Asia.

    PubMed

    Ng, Siew C; Wong, Sunny H

    2013-01-01

    The incidence and mortality of colorectal cancer are rapidly rising in several countries in Asia. However, screening guidelines are lacking. Review of literature and local data published in peer review journals. The incidence, anatomical distribution and mortality of colorectal cancer among Asian populations are comparable to those in Western countries. Flat and depressed colonic lesions are not uncommon. Male gender, smoking, obesity, metabolic syndrome and family history are risk factors for colorectal cancer. Certain ethnic groups in Asia have increased susceptibility to colorectal cancer. Faecal occult blood test, flexible sigmoidoscopy and colonoscopy are recommended options for colorectal cancer screening in Asia. Regular screening should start at the age of 50 years. The optimal screening method in Asia remains unclear. Faecal immunochemical test has been suggested as the first choice of screening test in countries with limited resources. The role of nurse endoscopists in performing endoscopic procedures for colorectal cancer screening in Asia has not been defined. There is low public awareness and little support by health authorities for screening and prevention of this emerging disease. Screening for colorectal cancer should be a national health priority in most Asian countries. Studies on barriers to screening, education of the public and engagement of family physicians are important strategies in promoting colorectal cancer screening. With more health-care support, increased public acceptance and better access to the general population, colorectal cancer screening in Asia can be rewarding.

  13. General Information about Malignant Mesothelioma

    MedlinePlus

    ... form in the lining of the chest or abdomen. Malignant mesothelioma is a disease in which malignant ( ... that examine the inside of the chest and abdomen are used to detect (find) and diagnose malignant ...

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

    PubMed

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

    1980-07-08

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

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

    PubMed

    Clark, Christopher R; Starr, Timothy K

    2016-01-14

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

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

    PubMed Central

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

    2015-01-01

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

  17. 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

  18. Clinical features of Bacteroides bacteremia and their association with colorectal carcinoma.

    PubMed

    Yoshino, Y; Kitazawa, T; Ikeda, M; Tatsuno, K; Yanagimoto, S; Okugawa, S; Ota, Y; Yotsuyanagi, H

    2012-02-01

    We investigated the clinical features of Bacteroides bacteremia for 5 years to determine the risk factors for mortality and to ascertain whether bacteremia due to Bacteroides spp. is associated with colorectal carcinoma. This study comprised a review of all patients with Bacteroides bacteremia at a teaching hospital in Tokyo from April 2003 to March 2008. We also conducted a case-control study between Bacteroides bacteremia and bacteremia due to other pathogens. During the study period, 25 cases of bacteremia were due to Bacteroides spp. Bacteroides bacteremia was associated with a high mortality rate (24%). Malignancy (76%) was the major comorbidity, followed by a history of surgery (40%). Colorectal carcinoma was the most frequent (n = 8, 32%) of the comorbid malignancies and was recognized as the primary infection site in six cases. Prevalence of colorectal carcinoma as comorbidity was significantly higher in Bacteroides bacteremia than in other bacteremia. In the Bacteroides bacteremia cases of this study, colorectal carcinoma was the major comorbidity and primary infection site. Colorectal carcinoma screening in Bacteroides bacteremia patients is potentially an important diagnostic marker for the early detection of this infection in the future.

  19. [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.

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

    PubMed

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

    2003-08-21

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

  1. 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

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

    PubMed Central

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

    2016-01-01

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

  3. Colorectal cancer screening.

    PubMed

    Bessa Caserras, Xavier

    2016-09-01

    In the latest meeting of the American Gastroenterological Association, several clinical studies were presented that aimed to evaluate the various colorectal cancer screening strategies, although most assessed the various aspects of faecal immunochemical testing (FIT) and colonoscopy. Data were presented from consecutive FIT-based screening rounds, confirming the importance of adherence to consecutive screening rounds, achieving a similar or superior diagnostic yield to endoscopic studies. There was confirmation of the importance of not delaying endoscopic study after a positive result. Participants with a negative FIT (score of 0) had a low risk for colorectal cancer. Several studies seemed to confirm the importance of high-quality colonoscopy in colorectal cancer screening programmes. The implementation of high-quality colonoscopies has reduced mortality from proximal lesions and reduced interval cancers in various studies. Finally, participants with a normal colonoscopy result or with a small adenoma are at low risk for developing advanced neoplasms during follow-up. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  4. Differential distributions of CSE1L/CAS and E-cadherin in the polarized and non-polarized epithelial glands of neoplastic colorectal epithelium.

    PubMed

    Uen, Wu-Ching; Tai, Cheng-Jeng; Shen, Shing-Chuan; Lee, Woan-Ruoh; Tsao, Tang-Yi; Deng, Win-Ping; Chiou, Hung-Yi; Hsu, Chung-Huei; Hsieh, Cheng-I; Liao, Ching-Fong; Jiang, Ming-Chung

    2010-10-01

    Colorectal glands are important functional organs in colorectal tissue and are also the origin of colorectal carcinomas. Epithelial cell polarization of colorectal glands is related to structural integrity and physiological functions of colorectal glands as well as colorectal carcinoma formation. The cellular apoptosis susceptibility (CSE1L/CAS) protein has been shown to induce polarity formation of human colorectal cells in cell culture. E-cadherin expression in epithelial cells is crucial for the establishment and maintenance of epithelial cell polarity. In this study we examined the distributions of CSE1L and E-cadherin in the epithelial glands of normal and neoplastic colorectal epithelium and correlated these to polarity formation in the colorectal glands. Our results showed that CSE1L was differentially stained in the epithelial glands of neoplastic colorectal epithelium, and the staining was related to gland epithelial cell polarization and E-cadherin distribution. CSE1L was associated E-cadherin in GST pull-down experiments and immunoprecipitation assays. Basolateral staining of CSE1L and E-cadherin were seen in the polarized glands of normal and neoplastic colorectal epithelium. Absence of basolateral CSE1L staining in neoplastic epithelium glands was associated with loss of gland epithelial cell polarity, and this was parallel with E-cadherin staining. The non-polarized areas in epithelium glands showed a patchy staining for CSE1L and E-cadherin. These results indicate that examination of CSE1L and E-cadherin distribution in colorectal epithelium glands may be valuable for evaluating the malignance of colorectal disease.

  5. Asbestos-related malignancy

    SciTech Connect

    Antmann, K.; Aisner, J.

    1986-01-01

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

  6. 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

  7. What Is Malignant Mesothelioma?

    MedlinePlus

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

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

    PubMed Central

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

    2016-01-01

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

  9. [Colorectal cancer screening with colonoscopy].

    PubMed

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

    2013-01-01

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

  10. Minimally Invasive Surgery for the Treatment of Colorectal Cancer

    PubMed Central

    Karcz, W. Konrad; von Braun, William

    2016-01-01

    Background Reduction in operative trauma along with an improvement in endoscopic access has undoubtedly occupied surgical minds for at least the past 3 decades. It is not at all surprising that minimally invasive colon surgery has come a long way since the first laparoscopic appendectomy by Semm in 1981. It is common knowledge that the recent developments in video and robotic technologies have significantly furthered advancements in laparoscopic and minimally invasive surgery. This has led to the overall acceptance of the treatment of benign colorectal pathology via the endoscopic route. Malignant disease, however, is still primarily treated by conventional approaches. Methods and Results This review article is based on a literature search pertaining to advances in minimally invasive colorectal surgery for the treatment of malignant pathology, as well as on personal experience in the field over the same period of time. Our search was limited to level I and II clinical papers only, according to the evidence-based medicine guidelines. We attempted to present our unbiased view on the subject relying only on the evidence available. Conclusion Focusing on advances in colorectal minimally invasive surgery, it has to be stated that there are still a number of unanswered questions regarding the surgical management of malignant diseases with this approach. These questions do not only relate to the area of boundaries set for the use of minimally invasive techniques in this field but also to the exact modality best suited to the treatment of every particular case whilst maintaining state-of-the-art oncological principles. PMID:27493947

  11. Differential Measurements of Oxidatively Modified Proteins in Colorectal Adenopolyps

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. CDKL1 promotes tumor proliferation and invasion in colorectal cancer

    PubMed Central

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

    2017-01-01

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

  14. Microsatellite Instability in Colorectal Cancer

    PubMed Central

    Boland, C. Richard; Goel, Ajay

    2011-01-01

    Microsatellite instability (MSI) is a hypermutable phenotype caused by the loss of DNA mismatch repair activity. MSI is detected in about 15% of all colorectal cancers; 3% are of these are associated with Lynch syndrome and the other 12% are caused by sporadic, acquired hypermethylation of the promoter of the MLH1 gene, which occurs in tumors with the CpG island methylator phenotype. Colorectal tumors with MSI have distinctive features, including a tendency to arise in the proximal colon, lymphocytic infiltrate, and a poorly differentiated, mucinous or signet ring appearance. They have a slightly better prognosis than colorectal tumors without MSI and do not have the same response to chemotherapeutics. Discovery of MSI in colorectal tumors has increased awareness of the diversity of colorectal cancers and implications for specialized management of patients. PMID:20420947

  15. Immunohistochemical and mutational analysis of apoptosis-inducing factor (AIF) in colorectal carcinomas.

    PubMed

    Jeong, Eun Goo; Lee, Jong Woo; Soung, Young Hwa; Nam, Suk Woo; Kim, Sang Ho; Lee, Jung Young; Yoo, Nam Jin; Lee, Sug Hyung

    2006-12-01

    Apoptosis-inducing factor (AIF) has a principal role in caspase-independent apoptosis. In addition, AIF has a vital oxidoreductase activity that is required for cell survival. It may be important to identify the alterations of the AIF gene and AIF protein expression to see the function of AIF in human cancers. In this study we analyzed the expression of AIF protein in 103 colorectal carcinomas by immunohistochemistry. We also analyzed the mutation in exons 10-15 of AIF encoding the region that possesses the cell death function of AIF by single-strand conformation polymorphism (SSCP) in 48 colorectal, 48 gastric, 48 breast and 48 hepatocellular carcinomas, and 48 leukemias. By immunohistochemistry, AIF protein expression was detected in both cancer cells and normal mucosal epithelial cells in all of the 103 colorectal carcinoma tissues. However, the cancer cells showed higher intensities of AIF immunostaining than the normal cells in 83 cases (80.5%). AIF immunoreactivities were observed in the cancers irrespective of their location or the depth of invasion. Mutational analysis detected one AIF mutation in the colorectal carcinomas, but none in the other cancers. The AIF mutation detected was a two-base deletion mutation in intron 15. The increased expression of AIF in the malignant colorectal epithelial cells compared to the normal mucosal epithelial cells suggests that AIF expression may play a role in colorectal tumorigenesis. The data also suggest that somatic mutation of AIF is a rare event in common human cancers.

  16. 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

  17. TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis.

    PubMed

    Li, Changfeng; Gao, Yongjian; Li, Yongchao; Ding, Dayong

    2017-09-16

    Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. Methotrexate (MTX) is one of the earliest cytotoxic drugs and serves as an anti-metabolite and anti-folate chemotherapy for various types of cancer. However, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the efficacy of MTX therapies in clinics. Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years. More and more evidences have shown that lncRNAs play regulatory roles in various biological activities and disease progression including drug resistance in cancer cells. Here, we observed lncRNA TUG1 was associated to the MTX resistant in colorectal cancer cells. Firstly, quantitative analysis indicated that TUG1 was significantly increased in tumors which were resistant to MTX treatment. TUG1 knockdown re-sensitized the MTX resistance in colorectal cancer cells, which were MTX-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis. Copyright © 2017. Published by Elsevier Inc.

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

    PubMed

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

    2016-04-01

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

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

    PubMed

    Oddone, Enrico; Modonesi, Carlo; Gatta, Gemma

    2014-09-21

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

  20. The implications of an incidental chronic lymphocytic leukaemia in a resection specimen for colorectal adenocarcinoma.

    PubMed

    Dennis, Robert J; Alberts, Justin C

    2007-10-30

    Colorectal cancer and B cell chronic lymphocytic leukaemia (CLL) have a significant incidence, which are increasing with the aging population. Evidence has been presented in the literature to suggest that the synchronous presentation of colorectal cancer and B cell CLL may be more than simply coincidental for these two common malignancies. We report an unusual case of a presumed B cell CLL diagnosed on the basis of histological analysis of lymph nodes recovered from a resection specimen for rectal adenocarcinoma. We considered aetiological factors which may have linked the synchronous diagnosis of the two malignancies and the potential implications for the natural history of the two malignancies on one another. A 70-year-old male underwent low anterior resection with total mesorectal excision for a rectal adenocarcinoma. His co-morbid conditions were chronic obstructive airways disease and ischaemic heart disease. General examination revealed no lymphadenopathy. Full blood count, urea and electrolytes and liver function tests were all within normal limits. As well as confirming a pT3 N1 adenocarcinoma, histological analysis showed lymph nodes with an infiltrate of small lymphoid cells. Immunohistochemical studies showed these cells to be in keeping with B cell CLL. Whilst unable to identify any common aetiological factors in the two malignancies in our patient, immunosuppression and genetic abnormalities have been identified as possible bases for an observed epidemiological association between colorectal cancer and haematological malignancies. Examples such as our case of synchronous diagnosis of two malignancies in a patient are likely to increase with the aging population. The potential affects of one malignancy on the natural history of the other warrants further study. In our case, we considered that slow progression of the B cell CLL may increase the risk of recurrent rectal adenocarcinoma.

  1. Practical genetics of colorectal cancer.

    PubMed

    Lynch, Henry T; Shaw, Trudy G

    2013-06-01

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

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

    PubMed Central

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

    2011-01-01

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

  3. Early-onset colorectal cancer: a sporadic or inherited disease?

    PubMed

    Stigliano, Vittoria; Sanchez-Mete, Lupe; Martayan, Aline; Anti, Marcello

    2014-09-21

    Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a "sporadic" subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.

  4. The IASLC/ITMIG thymic malignancies staging project: development of a stage classification for thymic malignancies.

    PubMed

    Detterbeck, Frank C; Asamura, Hisao; Crowley, John; Falkson, Conrad; Giaccone, Giuseppe; Giroux, Dori; Huang, James; Kim, Jhingook; Kondo, Kazuya; Lucchi, Marco; Marino, Mirella; Marom, Edith M; Nicholson, Andrew; Okumura, Meinoshin; Ruffini, Enrico; van Schil, Paul; Stratton, Kelly

    2013-12-01

    The lack of an official-stage classification system for thymic malignancies is an issue that hampers progress in this rare disease. A collaborative effort by the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group is underway to develop proposals for such a system. A database of more than 10,000 cases worldwide has been assembled to provide a solid basis for analysis. This report outlines the structure of the effort and the process that has been designed.

  5. Evidence-Based Recommendations on Colorectal Stenting: A Report from the Stent Study Group of the Korean Society of Gastrointestinal Endoscopy

    PubMed Central

    Lee, Kwang Jae; Kim, Sang Woo; Kim, Tae Il; Lee, Jong-Hoon; Lee, Bo-In; Keum, Bora; Cheung, Dae Young

    2013-01-01

    Recently, placement of self-expandable metallic stents has been used for the treatment of colorectal obstruction. As domestic awareness of colorectal cancer has increased, the number of colorectal stenting procedures performed has also increased. We aimed to provide evidence-based recommendations for colorectal stenting to aid gastroenterologists in making informed decisions regarding the management of patients who present with colorectal obstruction. The working group consisted of eight gastroenterologists who actively practice and conduct research in the field of colorectal stenting and are the members of the Stent Study Group of the Korean Society of Gastrointestinal Endoscopy. A literature search was conducted using the PubMed, Embase, KoreaMed, and the Cochrane Library databases to identify relevant articles published between January 2001 and June 2012. Based on the modified Delphi process, 10 recommendation statements regarding indications, usefulness, methodology and complications of colorectal stenting, and alternative treatments for malignant colorectal obstruction were determined. The contents will be widely distributed, and periodically revised to reflect the latest knowledge. These evidence-based recommendations for colorectal stenting will provide gastroenterologists and patients with appropriate and balanced information, and will improve the quality of care. PMID:23964332

  6. 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

  7. [Genetics of colorectal cancer].

    PubMed

    Balaguer, Francesc

    2013-10-01

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

  8. Complications in colorectal surgery.

    PubMed

    Frischer, Jason S; Rymeski, Beth

    2016-12-01

    Colorectal pediatric surgery is a diverse field that encompasses many different procedures. The pullthrough for Hirschsprung disease, the posterior sagittal anorectoplasty for anorectal malformations including complex cloaca reconstructions and the ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis present some of the most technically challenging procedures pediatric surgeons undertake. Many children prevail successfully following these surgical interventions, however, a small number of patients suffer from complications following these procedures. Anticipated postoperative problems are discussed along with medical and surgical strategies for managing these complications. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Screening for colorectal cancer.

    PubMed

    Mandel, Jack S

    2008-03-01

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

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

    PubMed

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

    2014-04-14

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

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

    MedlinePlus

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

  12. 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.

  13. Malignant peritoneal mesothelioma

    PubMed Central

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

    2009-01-01

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

  14. Hemostasis and malignancy.

    PubMed

    Francis, J L; Biggerstaff, J; Amirkhosravi, A

    1998-01-01

    There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

  15. Malignant Vestibular Schwannoma

    PubMed Central

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

    1994-01-01

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

  16. Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2017-09-28

    Recurrent Colorectal Carcinoma; Solid Neoplasm; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  17. [Hereditary and familial colorectal cancer].

    PubMed

    Balaguer, Francesc

    2014-09-01

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

  18. [Multidisciplinary therapy of colorectal cancer].

    PubMed

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

    2001-03-18

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

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

    PubMed

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

    2016-09-01

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

  20. Giant malignant insulinoma

    PubMed Central

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

    2015-01-01

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

  1. Envy and malignant envy.

    PubMed

    Shengold, L

    1994-10-01

    Envy begins early in psychic development and is initially characterized by destructive primal hatred. With maturation, envy becomes modified in intensity. Its primal murderous quality is attenuated, and, as object relationships develop, it becomes partly transformed into jealousy. Malignant envy is a retention of, or regression to, the original primal murderous affective mix. Clinically, one sees in malignant envy the phenomenon of the subject feeling with delusional intensity that what the envied one has is not only urgently wanted but has been stolen from the self--an intensity that is reacted to defensively by projection and delusion formation. This operates as a formidable resistance in analytic work.

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

    NASA Astrophysics Data System (ADS)

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

    2006-09-01

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

  3. New methods for the staging of colorectal cancer using noninvasive techniques.

    PubMed

    Blend, M J; Abdel-Nabi, H

    1996-01-01

    Noninvasive differentiation of benign from malignant disease has emerged as an important diagnostic challenge in this age of health-care cost containment. Most physicians today acknowledge that early and accurate detection of cancer is the key to successful treatment. Antibodies have been developed and used to detect and treat tumors. In the next few years, several radiolabeled antibodies will likely receive FDA approval for imaging colorectal, lung, and prostate carcinomas, thus expanding and improving the physician's ability to detect and follow cancer in patients. There is ample evidence in the literature that suggests that imaging with labeled antibodies is clinically useful for detecting colorectal cancer in patients with suspected recurrence, in patients with presumed isolated resectable liver metastasis, and in those at high risk of the development of recurrence. This paper reviews these studies, and also discusses some data obtained from positron emission tomography (PET) imaging in colorectal patients.

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

    PubMed

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

    2000-06-01

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

  5. 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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    2017-02-20

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

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

    PubMed

    Arber, Nadir

    2008-08-01

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

  9. 15-Hydroxyprostaglandin Dehydrogenase Is Down-regulated in Colorectal Cancer*

    PubMed Central

    Backlund, Michael G.; Mann, Jason R.; Holla, Vijaykumar R.; Buchanan, F. Gregory; Tai, Hsin-Hsiung; Musiek, Erik S.; Milne, Ginger L.; Katkuri, Sharada; DuBois, Raymond N.

    2007-01-01

    Prostaglandin E2 (PGE2) can stimulate tumor progression by modulating several proneoplastic pathways, including proliferation, angiogenesis, cell migration, invasion, and apoptosis. Although steady-state tissue levels of PGE2 stem from relative rates of biosynthesis and breakdown, most reports examining PGE2 have focused solely on the cyclooxygenase-dependent formation of this bioactive lipid. Enzymatic degradation of PGE2 involves the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). The present study examined a range of normal tissues in the human and mouse and found high levels of 15-PGDH in the large intestine. By contrast, the expression of 15-PGDH is decreased in several colorectal carcinoma cell lines and in other human malignancies such as breast and lung carcinomas. Consistent with these findings, we observe diminished 15-Pgdh expression in ApcMin+/− mouse adenomas. Enzymatic activity of 15-PGDH correlates with expression levels and the genetic disruption of 15-Pgdh completely blocks production of the urinary PGE2 metabolite. Finally, 15-PGDH expression and activity are significantly down-regulated in human colorectal carcinomas relative to matched normal tissue. In summary, these results suggest a novel tumor suppressive role for 15-PGDH due to loss of expression during colorectal tumor progression. PMID:15542609

  10. 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 ...

  11. [Surgery in complicated colorectal cancer].

    PubMed

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

    2006-07-01

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

  12. Lysyl oxidase in colorectal cancer.

    PubMed

    Cox, Thomas R; Erler, Janine T

    2013-11-15

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

  13. Early malignant syphilis*

    PubMed Central

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

    2016-01-01

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

  14. Malignant tumors of childhood

    SciTech Connect

    Brooks, B.J.

    1986-01-01

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

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

    ClinicalTrials.gov

    2017-02-13

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

  16. Diabetes Mellitus and Colorectal Neoplasia

    PubMed Central

    Acevedo, Alejandro; Diaz, Yaritza; Perez, Cynthia M.; Garau, Maria; Baron, John

    2012-01-01

    Background Many studies have provided evidence for an association between obesity, physical inactivity, and western diet as risk factors for colorectal cancer (CRC). Few studies directly address the association between type 2 Diabetes Mellitus (DM) and the risk of colorectal lesions at specific anatomic locations. Methods 2,663 subjects with a previous history of adenoma(s) and removal of all current adenomas at study entry were followed for a mean time of three years across three different chemoprevention clinical trials. The primary endpoint was colorectal adenoma recurrence and number of lesions during the treatment phase; the secondary endpoints were presence of advanced colorectal neoplasia (CRN) and location of CRN. Using log linear regression, the effect of DM status on the relative risk (RR) of CRN recurrence, advanced CRN, and location of CRN was assessed. Results DM status was not significantly associated with incidence of colorectal adenomas, incidence of advanced colorectal lesions, or left-sided colorectal neoplastic lesions. Subjects with DM had a marginally increased risk of right-sided (p= 0.06) colorectal adenomas and a significant increased risk of multiple right-sided adenomas (p=0.03) in the unadjusted model; this association was not significant after adjusting for age and other potential confounders (RR=1.22, 95% CI: 0.85–1.76). Conclusion We did not observe a statistically significant increased risk in CRN recurrence for overall neoplasia, advanced neoplasia or location of neoplasia in individuals with DM compared to non-DM individuals. However, given the patterns observed in this investigation, future studies with longer follow-up time and longer DM exposure, incorporating objective measurements of type 2 DM might help elucidate the risk of CRN among individuals with DM. PMID:23560242

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    1991-01-01

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

  19. Robotics in Colorectal Surgery

    PubMed Central

    Weaver, Allison; Steele, Scott

    2016-01-01

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

  20. 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. © 2015 Royal Australasian College of Physicians.

  1. Lipidome in colorectal cancer

    PubMed Central

    Zhu, Bo; Li, Yongsheng

    2016-01-01

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

  2. Epigenetics of colorectal cancer.

    PubMed

    Goel, Ajay; Boland, C Richard

    2012-12-01

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

  3. Robotics in Colorectal Surgery.

    PubMed

    Weaver, Allison; Steele, Scott

    2016-01-01

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

  4. Treatment Options for Malignant Mesothelioma

    MedlinePlus

    ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver ... thin layer of tissue that covers the lung, chest wall, abdomen, heart, or testicles. Being exposed to asbestos ...

  5. Treatment Option Overview (Malignant Mesothelioma)

    MedlinePlus

    ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver ... thin layer of tissue that covers the lung, chest wall, abdomen, heart, or testicles. Being exposed to asbestos ...

  6. Obesity and colorectal cancer.

    PubMed

    Bardou, Marc; Barkun, Alan N; Martel, Myriam

    2013-06-01

    Excess body weight, as defined by the body mass index (BMI), has been associated with several diseases and includes subjects who are overweight (BMI ≥ 25-29.9 kg/m(2)) or obese (BMI ≥ 30 kg/m(2)). Overweight and obesity constitute the fifth leading risk for overall mortality, accounting for at least 2.8 million adult deaths each year. In addition around 11% of colorectal cancer (CRC) cases have been attributed to overweight and obesity in Europe. Epidemiological data suggest that obesity is associated with a 30-70% increased risk of colon cancer in men, whereas the association is less consistent in women. Similar trends exist for colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m(2) increase in BMI confers additional risk (HR 1.03). Obesity might be associated with worse cancer outcomes, such as recurrence of the primary cancer or mortality. Several factors, including reduced sensitivity to antiangiogenic-therapeutic regimens, might explain these differences. Except for wound infection, obesity has no significant impact on surgical procedures. The underlying mechanisms linking obesity to CRC are still a matter of debate, but metabolic syndrome, insulin resistance and modifications in levels of adipocytokines seem to be of great importance. Other biological factors such as the gut microbiota or bile acids are emerging. Many questions still remain unanswered: should preventive strategies specifically target obese patients? Is the risk of cancer great enough to propose prophylactic bariatric surgery in certain patients with obesity?

  7. 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

  8. 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

  9. Advances in endoscopic ultrasound imaging of colorectal diseases.

    PubMed

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

    2016-02-07

    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.

  10. Malignant otitis externa.

    PubMed

    Karaman, Emin; Yilmaz, Mehmet; Ibrahimov, Metin; Haciyev, Yusuf; Enver, Ozgün

    2012-11-01

    Malignant external otitis is a severe infection of the external auditory canal and skull base, which most often affects elderly patients with diabetes mellitus. This disease is still a serious disease associated with cranial nerve complications and high morbidity-mortality rate. Malignant otitis externa requires urgent diagnosis and treatment. The most effective treatment is to control the diabetes and to fight infection with the proper antibiotic and debridement necrotic tissue; sometimes, aggressive surgical management is done. We present our 5-year institutional experience in the management of this disease. The aim of this study was to present our experience with the management of malignant otitis externa. All patients' records with malignant otitis externa during the last 5 years (2007-2012) were retrieved and reviewed. Diabetes mellitus profile, erythrocyte sedimentation rate, ear swab for culture and sensitivity, computed tomography, and scintigraphy using technetium 99 and gallium 67 were investigated for all patients. During the last 5 years (2007-2012), 10 patients with the diagnosis of malignant otitis externa were admitted to our clinic for investigation and treatment. There were 7 men and 3 women, all between 64 and 83 years of age, with severe persistent otalgia, purulent otorrhea, granulation tissue in the external auditory canal, and diffuse external otitis, and there were 4 patients with facial nerve palsy. Nine patients were confirmed to have a diabetes, and 4 of these 9 cases just had chronic renal failure and underwent dialysis; the remainder 1 case had no diabetes mellitus, but with chronic renal failure on dialysis. Ear swabs for culture and sensitivity usually revealed Pseudomonas aeruginosa. Local debridement and local and systemic antibiotic treatment were sufficient to control the disease. Facial nerve decompression was done in facial paralysis. Hyperbaric oxygen therapy was performed in facial nervy palsy cases. Malignant otitis externa is

  11. 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.

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

    PubMed Central

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

    2013-01-01

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

  13. p53 polymorphism and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population.

    PubMed

    Jones, J Shawn; Chi, Xuedong; Gu, Xiangjun; Lynch, Patrick M; Amos, Christopher I; Frazier, Marsha L

    2004-09-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome of familial malignancies. Colorectal and endometrial cancers are most frequently observed. The syndrome results mainly from germ-line mutations in DNA mismatch repair genes. A common G-to-C polymorphism at codon 72 in the p53 gene has been associated with increased risk for lung, nasopharyngeal, oral, prostate, and breast cancers and may be a marker for genetic susceptibility to colorectal cancer. We studied the influence of this p53 polymorphism on HNPCC age of onset. We determined the p53 genotype of 92 Caucasian mismatch repair mutation carriers, of which, 47 had colorectal cancer. The subjects were genotyped by single-strand conformational polymorphism analysis. We tested the association between age of onset and the p53 genotypes by comparing Kaplan-Meier survival curves, evaluating the homogeneity of the curves using the log-rank test and Wilcoxon's test, and estimating the association using the Cox proportional hazards regression model to adjust for potential demographic confounding factors. The HNPCC patients who were heterozygous developed their colorectal cancer 13 years earlier than HNPCC patients who were homozygous for the wild-type allele. Combining knowledge of an individual's p53 genotype with information on other genetic and environmental risk factors may improve risk estimates and help to identify individuals who are genetically susceptible to developing HNPCC at an earlier age.

  14. Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration.

    PubMed

    Katagiri, Munetoshi; Karasawa, Hideaki; Takagi, Kiyoshi; Nakayama, Shun; Yabuuchi, Shinichi; Fujishima, Fumiyoshi; Naitoh, Takeshi; Watanabe, Mika; Suzuki, Takashi; Unno, Michiaki; Sasano, Hironobu

    2017-04-01

    It is well known that proliferating carcinoma cells preferentially use aerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) plays a pivotal role in the glycolytic pathway. Previous studies have demonstrated that HK2 activity is markedly increased in various malignant neoplasms, but the clinical and biological significance of HK2 remain largely unclear in the colorectal carcinoma. We performed immunohistochemistry for HK2 in 195 colorectal carcinoma tissues. We also used HCT8 and HT29 colon carcinoma cells in in vitro studies. HK2 immunoreactivity was detected in 100 out of 195 (51%) colorectal carcinoma tissues, and the immunohistochemical HK2 status was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage in these cases. Moreover, the HK2 status was significantly associated with increased incidence of recurrence and overall mortality of the patients, and multivariate analyses demonstrated that HK2 status was an independent prognostic factor for both disease-free and overall survival. Subsequent in vitro experiments revealed that both HCT8 and HT29 colon carcinoma cells transfected with specific siRNA for HK2 significantly decreased the lactate production, proliferation activity and migration property. These results suggest that HK2 plays important roles in the glycolytic, proliferation and migration properties of colorectal carcinoma and, therefore, HK2 status is a potent worse prognostic factor in colorectal cancer patients.

  15. Cost-effectiveness of computerized tomographic colonography versus colonoscopy for colorectal cancer screening

    PubMed Central

    Heitman, Steven J.; Manns, Braden J.; Hilsden, Robert J.; Fong, Andrew; Dean, Stafford; Romagnuolo, Joseph

    2005-01-01

    Background Computerized tomographic (CT) colonography is a potential alternative to colonoscopy for colorectal cancer screening. Its main advantage, a better safety profile, may be offset by its limitations: lower sensitivity, need for colonoscopy in cases where results are positive, and expense. Methods We performed an economic evaluation, using decision analysis, to compare CT colonography with colonoscopy for colorectal cancer screening in patients over 50 years of age. Three-year outcomes included number of colonoscopies, perforations and adenomas removed; deaths from perforation and from colorectal cancer from missed adenomas; and direct health care costs. The expected prevalence of adenomas, test performance characteristics of CT colonography and colonoscopy, and probability of colonoscopy complications and cancer from missed adenomas were derived from the literature. Costs were determined in detail locally. Results Using the base-case assumptions, a strategy of CT colonography for colorectal cancer screening would cost $2.27 million extra per 100 000 patients screened; 3.78 perforation-related deaths would be avoided, but 4.11 extra deaths would occur from missed adenomas. Because screening with CT colonography would cost more and result in more deaths overall compared with colonoscopy, the latter remained the dominant strategy. Our results were sensitive to CT colonography's test performance characteristics, the malignant risk of missed adenomas, the risk of perforation and related death, the procedural costs and differences in screening adherence. Interpretation At present, CT colonography cannot be recommended as a primary means of population-based colorectal cancer screening in Canada. PMID:16217110

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

    PubMed

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

    2017-03-08

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

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

    PubMed

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

    2013-11-01

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

  19. Pronounced chromosomal instability and multiple gene amplifications characterize ulcerative colitis-associated colorectal carcinomas.

    PubMed

    Habermann, Jens K; Upender, Madhvi B; Roblick, Uwe J; Krüger, Stefan; Freitag, Sandra; Blegen, Harald; Bruch, Hans Peter; Schimmelpenning, Hendrik; Auer, Gert; Ried, Thomas

    2003-11-01

    Patients with ulcerative colitis have a significantly increased lifetime risk for the development of colorectal carcinomas. While genetic and genomic changes during carcinogenesis have been thoroughly studied in sporadic colorectal cancers, less is known about ulcerative colitis-associated colorectal carcinomas. The aim of this study was to extend the identification of specific genomic imbalances to ulcerative colitis-associated colorectal carcinomas and to establish a comprehensive map of DNA gains and losses by investigating 23 tumor specimens from 23 patients. The molecular cytogenetic characterization was performed using comparative genomic hybridization; immunohistochemistry was used to measure proliferative activity and laminin-5 expression as a marker for invasiveness. The results indicate that these tumors are invariably aneuploid, with a high proliferative activity and increased invasive potential. The average number of copy alterations correlates with increased cyclin A levels (P=0.044), which is an independent predictor of risk of carcinoma development in ulcerative colitis. Despite severe genetic instability, the general pattern of specific chromosomal aberrations that defines sporadic colorectal carcinomas is maintained in ulcerative colitis-associated malignancies. High-level copy number increases (amplifications) are dispersed throughout the genome. Strikingly, these amplifications are much more frequent than in sporadic carcinomas and map to chromosomal regions that have not been described before.

  20. MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression

    SciTech Connect

    Zhong, Xiaohua; Xiao, Yipin; Chen, Chao Wei, Xiuwen; Hu, Chen; Ling, Xukun; Liu, Xinbin

    2015-10-16

    Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR-203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment. - Highlights: • CPEB4 is aberrantly expressed in human colorectal cancers. • Knockdown of CPEB4 inhibited colorectal cancer cell proliferation and enhanced apoptosis. • CPEB4 is a direct target of miR-203 and inversely correlates with miR-203 expression. • miR-203 inhibited cell growth and enhanced cell apoptosis in CPEB4 dependent manner. • miR-203 is an upstream regulator of the CPEB4-induced apoptosis pathway.

  1. 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.

  2. Malignancy from Radium

    PubMed Central

    Loutit, J. F.

    1970-01-01

    Human experience of the toxicity of radium acts as a guide for the setting of occupationally permissible levels for radioactive nucleides, especially bone-seekers. Reviewing the published statements and photomicrographs in early reports especially those of Martland (1931) one can make a case that malignancy was induced in bone-marrow (leukaemia, malignant myelosclerosis) as well as in bone (osteosarcoma) by radium, especially with large doses. Three case reports of radium intoxication in Britons are noted as compatible with this suggestion, after revised interpretation in two of them. ImagesFigs. 9-10Fig. 4Fig. 5Figs. 11-12Figs. 6-7Fig. 8Figs. 13-14 PMID:5271269

  3. 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.

  4. Managing Malignant Cerebral Infarction

    PubMed Central

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

    2011-01-01

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

  5. Managing malignant pericardial effusion.

    PubMed Central

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

    1989-01-01

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

  6. Palliation of malignant ascites.

    PubMed

    Rosenberg, Stefanie M

    2006-03-01

    The management of recurrent, symptomatic malignant ascites can be problematic for physicians and patients. The most common, low-risk method is large-volume paracentesis. Patient disease progression often leads to rapid reaccumulation of ascites, which requires frequent return visits to the hospital for symptom management. Other techniques have been developed to achieve palliation of symptoms, including tunneled external drainage catheters, peritoneal ports, and peritoneovenous

  7. Lymphoscintigraphy in gynecologic malignancies

    SciTech Connect

    Bloomer, W.D.

    1983-01-01

    Lymphoscintigraphy is an easily performed noninvasive procedure that offers the potential to detect small numbers of ascitic tumor cells and early diaphragmatic tumor involvement. Moreover, it can be used to delineate and define abnormalities in lymph nodes that are not routinely visualized by bipedal contrast lymphangiography, ultrasound or computed tomography. Lymphoscintigraphy is recommended as an important investigative and adjunctive procedure in diagnosing gynecologic malignancies; there does not appear to be sufficient sensitivity and specificity to justify its routine clinical use.

  8. 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

  9. 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

  10. Treatment of malignant pheochromocytoma.

    PubMed

    Adjallé, R; Plouin, P F; Pacak, K; Lehnert, H

    2009-09-01

    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 alpha-1 blockers and nonselective, noncompetitive alpha- and/or beta-blockers, debulking surgery is the first treatment step. In case of a sufficient uptake of (123)I-MIBG treatment with targeted radiation therapy, use of (131)I-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 (131)I-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.

  11. 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.

  12. [Expression of HSP70 and P53 in malignant tumor tissues and its relationship to heat syndrome of TCM].

    PubMed

    Wang, Hong-qi; Zhang, Zheng; Zhao, Yan-ping; Li, Jianguo; Chen, Kai

    2004-10-01

    To investigate the expression of HSP70 and P53 in malignant tumor tissues of patients with TCM Heat-Syndrome (HS) or with non-Heat-Syndrome (NHS). S-P immunohistochemical method was used to detect the gene expression, and ELISA and RT-PCR were adopted to determine the content of HSP70 and P53 mRNA expression in different malignant tumor tissues. (1) Positive ratio of HSP70 and P53 in the colorectal cancer of HS was significantly higher than that in colorectal cancer of NHS respectively, and the total positive ratio of the two genes in all tumors of HS was higher than those of NHS (P<0.05); (2) HSP70 expression content in colorectal, nasopharyngeal and lung cancers of HS was higher than in those of NHS respectively, and the total HSP70 expression content in tumors of HS was higher than in those of NHS (P<0.01); (3) HSP70 mRNA expression content in colorectal and lung cancers of HS was higher than in those of NHS respectively, and the total HSP70 mRNA expression content in tumors of HS was higher than in those of NHS (P<0.01). HSP70 and P53 positive ratio and HSP70 expression content in patients of malignant tumor with HS was higher than in those with NHS.

  13. Colorectal Cancer: The Importance of Early Detection

    MedlinePlus

    ... Alliance : www.ccalliance.org Read More "Colorectal Cancer" Articles Colorectal Cancer: A Personal Journey / The Importance of Early Detection / Developments in Colorectal Cancer Screening Summer 2016 Issue: Volume 11 Number 2 Page ... Us | Viewers & Players Friends of the National Library of Medicine (FNLM)

  14. Pembrolizumab in Treating Patients With Malignant Mesothelioma

    ClinicalTrials.gov

    2016-11-14

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

  15. Resistin: insulin resistance to malignancy.

    PubMed

    Codoñer-Franch, Pilar; Alonso-Iglesias, Eulalia

    2015-01-01

    Adipose tissue is recognized as an endocrine organ that secretes bioactive substances known as adipokines. Excess adipose tissue and adipose tissue dysfunction lead to dysregulated adipokine production that can contribute to the development of obesity-related co-morbidities. Among the various adipokines, resistin, which was initially considered as a determinant of the emergence of insulin resistance in obesity, has appeared as an important link between obesity and inflammatory processes. Several experimental and clinical studies have suggested an association between increased resistin levels and severe conditions associated with obesity such as cardiovascular disease and malignancies. In this review, we present the growing body of evidence that human resistin is an inflammatory biomarker and potential mediator of obesity-associated diseases. A common pathway seems to involve the combined alteration of immune and inflammatory processes that favor metabolic disturbances, atherosclerosis and carcinogenesis. The mode of action and the signaling pathways utilized by resistin in its interactions with target cells could involve oxidative and nitrosative stress. Therefore, resistin could function as a key molecule in the complications of obesity development and could potentially be used as a diagnostic and prognostic marker. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. 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

  17. Designing a robotic colorectal program.

    PubMed

    Ragupathi, Madhu; Haas, Eric M

    2011-03-01

    Designing a successful robotic colorectal program requires consideration and implementation of several important concepts with continued perseverance through many obstacles that may arise. The ideal strategy is to establish a core group of committed individuals, define the goals and vision of the program, enlist corporate partners, and gain financial support with a sound business, educational, and research plan. Factors such as cost, limited availability, and demanding training are often hindrances to the implementation of a new robotic colorectal program while scheduling conflicts and inadequate resources may present obstacles to developing a colorectal program in institutions with existing robotic surgical programs. In developing a business plan one should consider the potential for increased patient referrals and the benefits of reduced hospital stay, decreased infection and complication rates, and quicker recovery compared with open surgical procedures. The optimal robotics surgical staff will include those most eager to be trained, as they are highly motivated and have the greatest enthusiasm to succeed. The early foundation of accomplishment will be vital to the long-term success of the program. In addition to building the ideal surgical team, patient selection is one of the most crucial considerations in developing a successful robotics program. Initiating a positive impression for robotic-assisted laparoscopic colorectal procedures will be an important precursor to continued success. Likewise, maintaining a regular schedule of procedures may advance the team's competencies and deter complacency. Proper planning, deliberate implementation, and sustained perseverance are key to the successful initiation of a robotic colorectal program.

  18. Crohn's disease and colorectal cancer.

    PubMed Central

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

    1994-01-01

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

  19. 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

  20. [Spectrum and case fatality of inpatients with malignant tumors from 1995 to 2014 in Shenzhen city].

    PubMed

    Wang, X B; Hong, L C; Wei, Y Z; Fu, X; Bao, X Q; Zhang, J; Hu, G; Wu, S H; Cheng, J Q

    2017-06-10

    Objective: To analyze the epidemiological features, spectrum and case fatality of malignant tumor patients in Shenzhen city, to provide evidence for the development of prevention and treatment strategies on malignant tumor in Shenzhen. Methods: All the hospitalized malignant tumor patients including deaths, were monitored from 1995 to 2014 in Shenzhen, and data was analyzed by SPSS 20.0 software. Results: There were 160 988 inpatients of malignant tumors between 1995 and 2014 in Shenzhen. The top three hospitalized tumors were lung (13.64%), liver (11.13%) and breast (7.86%) cancers. Numbers of the malignant tumor inpatients had been rapidly increasing during the past 20 years, 12.3 times in 2014 higher than in 1995. The total number of deaths due to malignant tumors was 19 460. Deaths of the top three malignant tumors were lung (24.40%), liver (19.84%) and colorectal (8.63%) cancers and the number of deaths was increasing, 12.5 times higher in 2014 than in 1995. The overall case fatality rate was 12.09%. The annual percent change (APC) of malignant tumors case fatality rate was 9.7%(95%CI: 2.0%-18.0%), during 1995-2003, with an increasing trend (t=2.72, P<0.05). The APC of case fatality rate during 2003-2014 was -3.4%(95%CI: -7.6%-1.1%), but the decreasing trend (t=-1.63, P>0.05) was not statistically significant. The top three major malignant tumors related to case fatality rate were lung cancer (21.62%), liver cancer (21.39%), and esophageal cancer (16.50%). The case fatality rates of leukemia and liver cancer had decreased during the past 20 years. The case fatality rates of cancers in lung, esophagus, stomach, breast, colorectal and nasopharyngeal, had all increased. The number of male patients was significantly exceeding the females (χ(2)=41.691, P<0.01), with sex ratio as 1.65∶1. From age 35 and on, the number of deaths due to malignant tumors increased significantly, with the peak after 60 years of age. Conclusions: The number of malignant tumor

  1. p62/sequestosome 1 in human colorectal carcinoma as a potent prognostic predictor associated with cell proliferation.

    PubMed

    Nakayama, Shun; Karasawa, Hideaki; Suzuki, Takashi; Yabuuchi, Shinichi; Takagi, Kiyoshi; Aizawa, Takashi; Onodera, Yoshiaki; Nakamura, Yasuhiro; Watanabe, Mika; Fujishima, Fumiyoshi; Yoshida, Hiroshi; Morikawa, Takanori; Sase, Tomohiko; Naitoh, Takeshi; Unno, Michiaki; Sasano, Hironobu

    2017-06-01

    p62/sequestosome 1 (p62) is a multi-domain protein that functions as a receptor for ubiquitinated targets in the selective autophagy and serves as a scaffold in various signaling cascades. p62 have been reported to be up-regulated in several human malignancies, but the biological roles and significance of p62 are still poorly understood in colorectal carcinoma. We immunohistochemically evaluated p62 in 118 colorectal adenocarcinoma and 28 colorectal adenoma cases. We used four colon carcinoma cells (HCT8, HT29, COLO320, and SW480) in the in vitro studies. p62 immunoreactivity was detected in 11% of colorectal adenoma cases and 31% of adenocarcinoma cases, while it was negligible in the normal epithelium. The immunohistochemical p62 status was significantly associated with synchronous liver metastasis, and it turned out to be an independent adverse prognostic factor in colorectal cancer patients. Following in vitro studies revealed that HCT8 and HT29 cells transfected with p62-specific siRNA showed significantly decreased cell proliferation activity, whereas COLO320 and SW480 cells transfected with p62 expression plasmid showed significantly increased cell proliferation activity. The p62-mediated cell proliferation was not associated with the autophagy activity. These findings suggest that p62 promotes the cell proliferation mainly as a scaffold protein, and that the p62 status is a potent prognostic factor in colorectal carcinoma patients. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. HER2 as an Emerging Oncotarget for Colorectal Cancer Treatment After Failure of Anti-Epidermal Growth Factor Receptor Therapy.

    PubMed

    Takegawa, Naoki; Yonesaka, Kimio

    2017-03-09

    Amplification of the HER2 gene is an indicator of poor prognosis for several kinds of malignancies such as breast and gastric cancer, and anti-HER2 targeting therapies provide clinical benefits in these patients. In 2011, HER2 was identified as a resistance molecule for de novo and secondary anti-epidermal growth factor receptor (EGFR) antibody therapy. HER2 activation provides a bypass signaling pathway after anti-EGFR antibody treatment of colorectal cancer. Cell line-based screening revealed that HER2 genomic amplification induces resistance to the anti-EGFR antibody cetuximab in colorectal cancer. Recently, HER2 itself has been recognized as a target for oncotherapy in colorectal cancer. The first part of this review provides an update on the present state of knowledge about the role of HER2 in colorectal cancer, including its prognostic relevance and role in resistance to anti-EGFR antibody treatment. In the second part of the review, we discuss the results of preclinical and clinical studies that examined the potential utility of anti-HER2 targeted therapy in colorectal cancer. Although it acts as a barrier for other molecular targeting agents such as cetuximab, HER2 itself is a promising target for oncotherapy. Current research indicates that anti-HER2 drugs will be developed further and introduced into clinical practice for the treatment of patients with HER2-positive colorectal cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Hereditary forms of colorectal cancer.

    PubMed

    Castells, Antoni

    2016-09-01

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

  4. 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

  5. [Hyperthermia of malignant tumors].

    PubMed

    Terashima, Hiromi

    2004-04-01

    The results of hyperthermia in the malignant tumors were reviewed. It is well known that hyperthermia enhances the effects of radiotherapy and chemotherapy for cancer patients. The clinical study on hyperthermia has been performed in the world since 1975. Several randomized clinical study revealed the benefits of hyperthermia in the head and neck cancers, recurrent breast cancers, and uterine cervical cancers. However, there are many difficulties to perform the hyperthermia in Japan because of lack of man-power and financial aid. Further clinical trials were recommended to obtain the evidences of hyperthermia.

  6. Disseminated Blastomycosis Mimicking Malignancy.

    PubMed

    Hsu, Jennifer L; Tjarks, B Joel; Berg, Aaron; Oliver, Tony

    2017-04-01

    Blastomycosis is an endemic fungal infection commonly found within the Mississippi and Ohio River basins and Great Lakes region. While patients typically present with acute pneumonia, Blastomyces dermatitidis has the potential to spread hematogenously, resulting in disseminated infection of multiple organs. In this report, we describe a 57-year-old male with disseminated blastomycosis acquired in South Dakota. The diagnostic evaluation was confounded by concern for malignancy given the involvement of multiple locations, including brain, lungs, adrenal glands, and testes. Despite aggressive therapy with amphotericin B, the patient succumbed to this infection. Copyright© South Dakota State Medical Association.

  7. Fifth-year surveillance computed tomography scanning after potentially curative resections for colorectal cancer.

    PubMed

    Walter, Catherine J; Al-Allak, Asmaa; Borley, Neil; Goodman, Anthony; Wheeler, James M D

    2013-02-01

    Optimal follow-up after colorectal resection for adenocarcinoma is yet to be determined. The aim of this study was to examine the role of a fifth-year surveillance Computed Tomography (CT) scan in detecting recurrence in our population. A retrospective analysis of all patients who had undergone potentially curative resections of colorectal adenocarcinomas between 2003 and 2004 was performed using electronic and casenote records. Data analysis was performed using Microsoft Office Excel 2007 and GnuPSPP statistical software. Two hundred and seven patients (111 male and 96 female) with a median age of 74 years (IQR 66-80) undergoing colorectal resections were studied. One hundred and twenty-one patients (58%) were alive and disease free at 5 years of whom 81 (67%) had received a fifth-year surveillance CT scan. Fifth-year scanning did not demonstrate any new colorectal metastases. However 6 (7%) scans revealed new, undiagnosed, non-colorectal malignancies. Thirty-four patients developed metastatic disease. All metastasis were diagnosed by 3½ years of follow-up. Eleven of these 34 cases presented after their second-year surveillance CT scan. Those patients with asymptomatic metastasis at the time of their discovery demonstrated improved likelihood of five year survival. This study showed no role for a fifth-year surveillance CT scan in the detection of resectable metastases, however there was a 7% pick up rate for detecting new malignancies. CT scanning beyond 2 years was needed to identify about one-third of the recurrences reported in this study. Copyright © 2012 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  9. Nutrients, foods, and colorectal cancer prevention.

    PubMed

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

    2015-05-01

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

  10. 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

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

    PubMed Central

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

    2016-01-01

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

  12. Laparoscopic Colectomy in the Management of Large, Sessile, Transformed Colorectal Polyps

    PubMed Central

    Nassiopoulos, Konstantinos; Menenakos, Evangelos; Chanson, Cristian; Zografos, George; Petropoulos, Panajotis

    2005-01-01

    Background: Colonic polyps are usually removed endoscopically. Surgical intervention is reserved for large, inaccessible colorectal polyps that have underdone malignant transformation. Laparoscopic management of colonic polyps has gained a well-defined role. Methods: Since 1993, 650 laparoscopic colectomies have been performed in our department. Twenty-eight patients with large, sessile, polyps that have undergone malignant transformation underwent elective laparoscopic colectomy. Operative procedures included 14 sigmoidectomies, 10 low anterior recto-sigmoid resections, 3 right colectomies, and 1 left colectomy. Central ligation of vessels and lymph node dissection were preformed in all patients. Results: The main outcome measures include conversion rate (11%), morbidity (11%), and mortality (3.5%). The mean return of bowel function was 3.1 days, liquid intake 1.4 days, solid food intake 2.5 days, and mean hospital stay 8 days. The mean specimen length was 23 cm, and the mean number of retrieved lymph nodes was 15. Malignancy according to Dukes classification was in situ, n=4; A, n=15; B, n=4; C, n=4; and D, n=1. During follow-up, 2 patients developed liver metastases. Conclusion: Laparoscopic colectomy is a technically feasible and effective method for treating large colorectal polyps that have undergone malignant transformation. PMID:15791972

  13. Selective Internal Radiation Therapy (SIRT) for liver metastases secondary to colorectal adenocarcinoma.

    PubMed

    Welsh, James S; Kennedy, Andrew S; Thomadsen, Bruce

    2006-01-01

    Selective internal radiation therapy (SIRT) is a relatively new commercially available microbrachytherapy technique for treatment of malignant hepatic lesions using (90)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. A modest number of clinical trials, preclinical animal studies, and dosimetric studies have been reported. Here we review several of the more important 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. 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.

  14. The value of single-incision laparoscopic surgery for colorectal cancer: a systematic literature review.

    PubMed

    Ma, Cong-Chao; Li, Ping; Wang, Liu-Hua; Xia, Zhao-Yun; Wu, Sheng-Wen; Wang, Shao-Jun; Lu, Chun-Ming

    2015-01-01

    Recently, single-incision laparoscopic colectomy (SILC) for colorectal malignancy is rapidly becoming the central issue for explorers of minimally invasive surgery worldwide. The aim of this systematic review was to establish the safety and efficacy of SILC for colorectal malignancy when implemented by experienced surgeons. PubMed, WHO international trial register and Embase were searched for publications concerning SILC and MLC from 2000 to 2013, with the last search on September 10, 2013. Only pure single-incision laparoscopic colonic surgery for malignant disease was included. Primary outcomes were the early postoperative complication profiles of SILC. Secondary outcomes were duration of operation time, blood loss, lymph node yields, conversion rate, distal margin of the resected tumor, and duration of hospital stay. Eight studies involving 547 patients met the inclusion criteria. Compared with multiport laparoscopic colectomy (MLC), SILC has less postoperative complication and bleeding. The conversion, the median lymph node retrieval, proximal margin of the resected tumor and distal margin of the resected tumor for malignant disease achieved with SILC was acceptable. There was no significant reduction in length of hospital stay with SILC. SILC is a technically reliable and realistic approach with short-term results similar to those obtained with the MLC procedure.

  15. Colorectal cancers and chlorinated water.

    PubMed

    El-Tawil, Ahmed Mahmoud

    2016-04-15

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

  16. 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

  17. Iron, microbiota and colorectal cancer.

    PubMed

    Ng, Oliver

    2016-10-01

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

  18. [New drugs for colorectal cancer].

    PubMed

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

    2004-09-01

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

  19. SECONDARY GASTROINTESTINAL MALIGNANCIES IN CHILDHOOD CANCER SURVIVORS: A COHORT STUDY

    PubMed Central

    Henderson, Tara O.; Oeffinger, Kevin C.; Whitton, John; Leisenring, Wendy; Neglia, Joseph; Meadows, Anna; Crotty, Catherine; Rubin, David T.; Diller, Lisa; Inskip, Peter; Smith, Susan A.; Stovall, Marilyn; Constine, Louis S.; Hammond, Sue; Armstrong, Greg T.; Robison, Leslie L.; Nathan, Paul C.

    2012-01-01

    Background Childhood cancer survivors develop gastrointestinal malignancies more frequently and at a younger age than the general population, but risk factors for their development have not been well characterized. Objective To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMN) in childhood cancer survivors. Design Retrospective cohort study. Setting The Childhood Cancer Survivor Study, a multi-center study of childhood cancer survivors diagnosed between 1970 and 1986. Patients 14,358 survivors of a malignancy diagnosed at < 21 years who had survived for 5 or more years from initial diagnosis. Measurements Standardized incidence ratios (SIR) for gastrointestinal SMN were calculated using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. Results At median follow-up of 22.8 years (range: 5.5-30.2), 45 gastrointestinal malignancies were identified. Gastrointestinal SMN risk was 4.6-fold higher in childhood cancer survivors than the general population (95% confidence interval [CI]: 3.5-6.1). Colorectal cancer SIR was 4.2 (95% CI: 2.8-6.3). The highest gastrointestinal SMN risk was associated with abdominal radiation (SIR=11.2, 95% CI: 7.6-16.4). However, survivors not exposed to radiation had a significantly increased risk (SIR=2.4, 95% CI-1.4-3.9). In addition to abdominal radiation, high dose procarbazine (RR=3.2, 95% CI 1.1-9.4) and platinum drugs (RR 7.6, 95% CI: 2.3-25.5) independently increased the gastrointestinal SMN risk. Limitations This cohort has not yet attained an age at which gastrointestinal malignancy risk is greatest. Conclusions Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMN. These findings suggest that surveillance of at-risk childhood cancer survivors should commence at a younger age than recommended for the general

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

    PubMed

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

    2014-01-01

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

  1. Immune Escape Mechanisms in Colorectal Cancer Pathogenesis and Liver Metastasis

    PubMed Central

    Remo, Andrea; Febbraro, Antonio; Sabatino, Lina; Manfrin, Erminia; Ceccarelli, Michele; Colantuoni, Vittorio

    2014-01-01

    Over the past decade, growing evidence indicates that the tumor microenvironment (TME) contributes with genomic/epigenomic aberrations of malignant cells to enhance cancer cells survival, invasion, and dissemination. Many factors, produced or de novo synthesized by immune, stromal, or malignant cells, acting in a paracrine and autocrine fashion, remodel TME and the adaptive immune response culminating in metastasis. Taking into account the recent accomplishments in the field of immune oncology and using metastatic colorectal cancer (mCRC) as a model, we propose that the evasion of the immune surveillance and metastatic spread can be achieved through a number of mechanisms that include (a) intrinsic plasticity and adaptability of immune and malignant cells to paracrine and autocrine stimuli or genotoxic stresses; (b) alteration of positional schemes of myeloid-lineage cells, produced by factors controlling the balance between tumour-suppressing and tumour-promoting activities; (c) acquisition by cancer cells of aberrant immune-phenotypic traits (NT5E/CD73, CD68, and CD163) that enhance the interactions among TME components through the production of immune-suppressive mediators. These properties may represent the driving force of metastatic progression and thus clinically exploitable for cancer prevention and therapy. In this review we summarize results and suggest new hypotheses that favour the growing impact of tumor-infiltrating immune cells on tumour progression, metastasis, and therapy resistance. PMID:24741617

  2. 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.

  3. Prevention of malignant melanoma

    PubMed Central

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

    2008-01-01

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

  4. Fiber and colorectal diseases: Separating fact from fiction

    PubMed Central

    Tan, Kok-Yang; Seow-Choen, Francis

    2007-01-01

    Whilst fruits and vegetables are an essential part of our dietary intake, the role of fiber in the prevention of colorectal diseases remains controversial. The main feature of a high-fiber diet is its poor digestibility. Soluble fiber like pectins, guar and ispaghula produce viscous solutions in the gastrointestinal tract delaying small bowel absorption and transit. Insoluble fiber, on the other hand, pass largely unaltered through the gut. The more fiber is ingested, the more stools will have to be passed. Fermentation in the intestines results in build up of large amounts of gases in the colon. This article reviews the physiology of ingestion of fiber and defecation. It also looks into the impact of dietary fiber on various colorectal diseases. A strong case cannot be made for a protective effect of dietary fiber against colorectal polyp or cancer. Neither has fiber been found to be useful in chronic constipation and irritable bowel syndrome. It is also not useful in the treatment of perianal conditions. The fiber deficit - diverticulosis theory should also be challenged. The authors urge clinicians to keep an open mind about fiber. One must be aware of the truths and myths about fiber before recommending it. PMID:17696243

  5. Colorectal cancer screening.

    PubMed

    Bretthauer, M

    2011-08-01

    Colorectal cancer (CRC) is the third most common cause of cancer death worldwide and a major health problem. In this review, the different approaches for CRC screening will be outlined with emphasis on evidence-based medicine. Evidence from randomized trials on the effectiveness of CRC screening is summarized. Several screening tools for CRC are available. They can be categorized according to their mode of action: early detection tools such as the faecal occult blood test (FOBT) and cancer prevention tools such as flexible sigmoidoscopy and colonoscopy. Meta-analyses of randomized trials show that FOBT screening reduces CRC mortality by 16% (risk ratio 0.84; 95% confidence interval (CI) 0.78-0.9) compared with 30% (risk ratio 0.7; 95% CI 0.6-0.81) for flexible sigmoidoscopy screening. FOBT screening is cheap and noninvasive, but results in large numbers of false-positive tests and needs to be repeated frequently. Flexible sigmoidoscopy is more invasive, but is effective for once-only screening. Although colonoscopy screening is used in some countries, no randomized trials have been conducted to estimate its benefit, and therefore, it should not be recommended at the present time. Faecal occult blood test and flexible sigmoidoscopy are the two CRC screening tools that can be recommended as they have been proven to reduce CRC mortality. Colonoscopy has the potential to be superior to FOBT and flexible sigmoidoscopy, but needs to be evaluated in randomized trials before any recommendation can be provided. © 2011 The Association for the Publication of the Journal of Internal Medicine.

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

    PubMed

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

    2017-02-14

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

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

    PubMed Central

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

    2017-01-01

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

  8. Absolute neutrophil values in malignant patients on cytotoxic chemotherapy.

    PubMed

    Madu, A J; Ibegbulam, O G; Ocheni, S; Madu, K A; Aguwa, E N

    2011-01-01

    A total of eighty patients with various malignancies seen between September 2008 and April 2009 at the University of Nigeria Teaching Hospital (UNTH) Ituku Ozalla, Enugu, Nigeria, had their absolute neutrophil counts, done at Days 0 and 12 of the first cycle of their various chemotherapeutic regimens. They were adult patients who had been diagnosed of various malignancies, consisting of Breast cancer 36 (45%), Non-Hodgkin's lymphoma 8 (10%), Hodgkin's lymphoma 13 (16.25%), Colorectal carcinoma 6 (7.5%), Multiple myeloma 7 (8.75%), Cervical carcinoma 1 (1.25%) and other malignancies 9 (11.25%), Manual counting of absolute neutrophil count was done using Turks solution and improved Neubauer counting chamber and Galen 2000 Olympus microscope. The socio demographic data of the patients were assessed from a questionnaire. There were 27 males (33.75%) and 53 females (66.25%). Their ages ranged from 18 - 80 years with a median of 45 years. The mean absolute neutrophil count of the respondents pre-and post chemotherapy was 3.7 +/- 2.1 x 10(9)/L and 2.5 +/- 1.6 x 10(9)/L respectively. There were significant differences in both the absolute neutrophil count (p=0.00) compared to the pre-chemotherapy values. Chemotherapeutic combinations containing cyclophosphamide and Adriamycin were observed to cause significant reduction in absolute neutrophil.

  9. Translational advances in pleural malignancies.

    PubMed

    Stathopoulos, Georgios T

    2011-01-01

    Pleural malignancies, including primary malignant pleural mesothelioma and secondary pleural metastasis of various tumours resulting in malignant pleural effusion, are frequent and lethal diseases that deserve devoted translational research efforts for improvements to be introduced to the clinic. This paper highlights select clinical advances that have been accomplished recently and that are based on preclinical research on pleural malignancies. Examples are the establishment of folate antimetabolites in mesothelioma treatment, the use of PET in mesothelioma management and the discovery of mesothelin as a marker of mesothelioma. In addition to established translational advances, this text focuses on recent research findings that are anticipated to impact clinical pleural oncology in the near future. Such progress has been substantial, including the development of a genetic mouse model of mesothelioma and of transplantable models of pleural malignancies in immunocompetent hosts, the deployment of stereological and imaging methods for integral assessment of pleural tumour burden, as well as the discovery of the therapeutic potential of aminobiphosphonates, histone deacetylase inhibitors and ribonucleases against malignant pleural disease. Finally, key obstacles to overcome towards a more rapid advancement of translational research in pleural malignancies are outlined. These include the dissection of cell-autonomous and paracrine pathways of pleural tumour progression, the study of mesothelioma and malignant pleural effusion separately from other tumours at both the clinical and preclinical levels, and the expansion of tissue banks and consortia of clinical research of pleural malignancies. © 2010 The Author. Respirology © 2010 Asian Pacific Society of Respirology.

  10. [Intraoperative staging of colorectal tumors].

    PubMed

    Abdurakhmonov, Iu B; Mel'nikov, O R; Egorenkov, V V; Moiseenko, V M

    2007-01-01

    The effectiveness of intraoperative staging of tumor by sentinel node staining with lymphotropic dyes was evaluated in 60 patients with colorectal tumors (colon carcinoma -39, rectal cancer- 21). High sensitivity (84.6% and 87.5%, respectively) and specificity (100% and 100%, respectively) for regional lymph node assessment were identified for both colonic and rectal cancer.

  11. Five Myths about Colorectal Cancer

    MedlinePlus

    ... and processed meat you eat. If you drink alcohol, limit the amount to 1 drink per day for women, 2 per day for men. Don’t use tobacco in any form. Myth: African Americans are not at risk for colorectal cancer. Truth: African-American men and women are diagnosed ...

  12. 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.

  13. [Systemic therapy for colorectal cancer].

    PubMed

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

    2005-06-01

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

  14. Malignant lymphoma of bone.

    PubMed

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

    2002-02-01

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

  15. 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. Use of a nitinol stent to palliate a colorectal neoplastic obstruction in a dog

    PubMed Central

    Culp, William T. N.; MacPhail, Catriona M.; Perry, James A.; Jensen, Tracey D.

    2015-01-01

    Case Description A 12-year-old castrated male Labrador Retriever was evaluated for clinical signs associated with colorectal obstruction. Clinical Findings The dog had a 2-week history of tenesmus and hematochezia. On rectal examination, an annular colorectal mass was palpable extending orad into the pelvic canal. The original diagnosis of the colorectal mass was a mucosal adenoma. The dog was maintained on a low-residue diet and fecal softeners for a period of 13 months after initial diagnosis. At that time, medical management was no longer effective. Treatment and Outcome Placement of a colonic stent was chosen to palliate the clinical signs associated with colorectal obstruction. By use of fluoroscopic and colonoscopic guidance, a nitinol stent was placed intraluminally to open the obstructed region. Placement of the stent resulted in improvement of clinical signs, although tenesmus and obstipation occurred periodically after stent placement. At 212 days after stent placement, the patient had extensive improvement in clinical signs with minimal complications; however, clinical signs became severe at 238 days after stent placement, and the dog was euthanized. Histologic evaluation of the rectal tumor from samples obtained during necropsy revealed that the tumor had undergone malignant transformation to a carcinoma in situ. Clinical Relevance A stent was successfully placed in the colon and rectum to relieve obstruction associated with a tumor originally diagnosed as a benign neoplasm. Placement of colorectal stents may be an option for the palliation of colorectal obstruction secondary to neoplastic disease; however, clinical signs may persist, and continuation of medical management may be necessary. PMID:21756178

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    van der Waal, Isaäc

    2014-01-01

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

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

    MedlinePlus

    ... Colorectal Cancer” Infographic Screening for Colorectal Cancer: Optimizing Quality (CME) Partners Related Links Glossary Stay Informed Cancer Home What Are the Risk Factors for Colorectal Cancer? Language: English Español (Spanish) Recommend ...

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

    PubMed

    Bernal, Giuliano

    2012-07-19

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

  1. Primary pineal malignant melanoma

    PubMed Central

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

    2011-01-01

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

  2. 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

  3. The malignant primate?

    PubMed

    de Grouchy, J

    1991-01-01

    Speciation and carcinogenesis result from genomic instability at the gametic or at the somatic levels. After an infinity of trials they occur, by chromosome rearrangements, in single individuals or in single cells and evolve by similar chromosomal or clonal evolutions. Loss of heterozygosity for the first event is essential in both processes: in evolution, a chromosomal rearrangement, a pericentric inversion or a Robertsonian fusion, must become homozygous to ensure a reproductive barrier for a new species; Knudson's two-event sequence is a similar situation in cancer. Position effect is equally important: we have shown overexpression of the SOD1 gene in the orangutan phylum probably by an intrachromosomal rearrangement; the t(9;22) in CML acts by typical position effect. Parental imprinting underlies the evolution of genome function and the unset of certain cancers. Evolution and malignancy are interweaved by viruses and oncogenes since the dawn of life. Cancer uses its intelligence to expand and to destroy the other tissues, using subtle metabolic pathways and a variety of tricks to metastasize other cells. It always wins but saws the branch on which it sits. Mankind also grows exponentially, killing thousands of other species, poisoning the oceans and soft waters, polluting the atmosphere, all for his egoistic needs. Man also travels and metastasizes other Earths. He modifies his genome or that of other species, and develops new technologies for his reproduction. He can destroy the planet in an eyeblink. To be or not to be the malignant primate, that will be the dilemma for the 21st Century.

  4. The sentinel lymph node (SLN) significance in colorectal cancer: methods and results. General report.

    PubMed

    Sfeclan, Maria Cristina; Vîlcea, Ionică Daniel; Barišić, Goran; Mogoantă, Stelian ŞtefăniŢă; Moraru, Emil; Ciorbagiu, Mihai Călin; Vasile, Ion; Vere, Cristin Constantin; Vîlcea, Alina Maria; Mirea, Cecil Sorin

    2015-01-01

    Colorectal cancer appears to be one of the most important malignancies in the world, with a survival rate depending on the TNM stage. The presence of lymph nodes metastasis indicates the necessity of adjuvant chemotherapy but exact classification of the N stage requires at least 12 lymph nodes to be pathologically examined. The sentinel lymph node (SLN) is considered to be the closest lymph node to the tumor, bearing the highest risk of malignant cells colonization. The main advantage of the sentinel lymph node mapping in colorectal cancer is identification and separate pathological examination of the nodes carrying the highest risk of metastasis. There are still open questions regarding the best method for sentinel lymph node mapping (in vivo or ex vivo), the factors influencing it, which substance is better for identification and which are the best histological methods and markers to be used. Numerous studies have discussed the quality and applicability of the method, but the importance of the SLN in colorectal carcinoma remains an open issue.

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

    PubMed Central

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

    2015-01-01

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

  6. The Association Between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer Risk

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-15-1-0273 TITLE: The Association between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer...ADDRESS. 1. REPORT DATE August 2016 2. REPORT TYPE Annual 3. DATES COVERED 1 Aug 2015 - 31 July 2016 4. TITLE AND SUBTITLE The Association Between...molecular markers associated with an increased risk of colorectal cancer in patients with sessile serrated colorectal polyps (SSPs). The project’s

  7. Primary malignant melanoma of prostate.

    PubMed

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

    2010-05-01

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

  8. 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

  9. Combined Endoscopic Laparoscopic Surgery Procedures for Colorectal Surgery.

    PubMed

    Placek, Sarah B; Nelson, Jeffrey

    2017-04-01

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

  10. Obesity and colorectal liver metastases: Mechanisms and management.

    PubMed

    Pathak, Samir; Pandanaboyana, Sanjay; Daniels, Ian; Smart, Neil; Prasad, K R

    2016-09-01

    Colorectal cancer (CRC) is the third commonest malignancy after lung and breast cancer. The most common cause of mortality from CRC is from distant metastases. Obesity is a known risk factor for primary CRC development. However, its role in metastatic disease progression is not fully understood. The article aims to provide an overview of the role of obesity in colorectal liver metastases (CRLM). Furthermore, possible strategies to minimise this effect are discussed. An electronic search of MedLine, EMBASE, CINAHL and google scholar was performed. Relevant articles were included in the article. Obesity causes localised inflammation within the liver microenvironment which may predispose to metastases development. Furthermore, obesity causes systemic inflammation leading to release of protumourigenic growth factors. Several studies demonstrated the effects of lifestyle modification, medications, bariatric surgery and omega-3 fatty acids on steatosis within the context of liver surgery. It is currently unclear whether obesity directly leads to metastatic disease via chronic systemic inflammation or whether obesity induced steatosis provides a fertile microenvironment for metastases deposition. With a global increase in obesity useful strategies to minimise the effects of obesity on the liver include life-style modification, pre-operative dietary regimes and omega-3 fatty acids intake. Pre-operative optimisation of the patient is a key concept. Further randomised control trials are needed to guide management strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. 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

  12. 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

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

    PubMed

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

    2015-07-28

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

  14. Tumor budding in colorectal cancer--ready for diagnostic practice?

    PubMed

    Koelzer, Viktor H; Zlobec, Inti; Lugli, Alessandro

    2016-01-01

    Tumor budding is an important additional prognostic factor for patients with colorectal cancer (CRC). Defined as the presence of single tumor cells or small clusters of up to 5 cells in the tumor stroma, tumor budding has been likened to an epithelial-mesenchymal transition. Based on well-designed retrospective studies, tumor budding is linked to adverse outcome of CRC patients in 3 clinical scenarios: (1) in malignant polyps, detection of tumor buds is a risk factor for lymph node metastasis indicating the need for colorectal surgery; (2) tumor budding in stage II CRC is a highly adverse prognostic indicator and may aid patient selection for adjuvant therapy; (3) in the preoperative setting, presence of tumor budding in biopsy material may help to identify high-risk rectal cancer patients for neoadjuvant therapy. However, lack of consensus guidelines for standardized assessment still limits reporting in daily diagnostic practice. This article provides a practical and comprehensive overview on tumor budding aimed at the practicing pathologist. First, we review the prognostic value of tumor budding for the management of colon and rectal cancer patients. Second, we outline a practical, evidence-based proposal for the assessment of tumor budding in the daily sign-out. Last, we summarize the current knowledge of the molecular characteristics of high-grade budding tumors in the context of personalized treatment approaches and biomarker discovery. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Colorectal cancer screening: 20 years of development and recent progress

    PubMed Central

    Zavoral, Miroslav; Suchanek, Stepan; Majek, Ondrej; Fric, Premysl; Minarikova, Petra; Minarik, Marek; Seifert, Bohumil; Dusek, Ladislav

    2014-01-01

    Colorectal cancer (CRC) is the second most common cancer in Europe and its incidence is steadily increasing. This trend could be reversed through timely secondary prevention (screening). In the last twenty years, CRC screening programs across Europe have experienced considerable improvements (fecal occult blood testing; transition from opportunistic to population based program settings). The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates. Each year, approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy. Twenty years ago, the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000. Originally, this program was based on the guaiac fecal occult blood test (FOBT) offered by general practitioners, followed by colonoscopy in cases of FOBT positivity. The program has continuously evolved, namely with the implementation of immunochemical FOBTs and screening colonoscopy, as well as the involvement of gynecologists. Since the establishment of the Czech CRC Screening Registry in 2006, 2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program. The overall program expanded to cover 25.0% of the target population by 2011. However, stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation, which is currently being prepared. PMID:24744575

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

    PubMed

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

    2005-01-01

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

  17. Primary prevention of colorectal cancer: Myth or reality?

    PubMed Central

    Crosara Teixeira, Marcela; Braghiroli, Maria Ignez; Sabbaga, Jorge; Hoff, Paulo M

    2014-01-01

    Colorectal cancer incidence has been rising strongly in parallel with economic development. In the past few decades, much has been learned about the lifestyle, dietary and medication risk factors for this malignancy. With respect to lifestyle, compelling evidence indicates that prevention of weight gain and maintenance of a reasonable level of physical activity can positively influence in lowering the risk. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. Though quite often recommended, the role for many supplements, including omega-3, vitamin D, folate, and vitamin B6, remains unsettled. Only calcium and vitamin D supplementation appear to add a modest benefit, particularly in those with a low daily intake. With regard to chemoprevention, medications such as aspirin and nonsteroidal anti-inflammatory drugs, and postmenopausal hormonal replacement for women might be associated with substantial reductions in colorectal cancer risk, though their utility is affected by their side effect profile. However, the role of agents such as statins, bisphosphonates and antioxidants have yet to be determined. Ultimately, primary prevention strategies focusing on modifying environmental, lifestyle risk factors, and chemopreventive drugs are options that have already been tested, and may impact on colon cancer incidence. PMID:25386054

  18. The Generation and Validation of a 20-Genes Model Influencing the Prognosis of Colorectal Cancer.

    PubMed

    Xie, Xiao-Jun; Liu, Ping; Cai, Chu-Dong; Zhuang, Ying-Ru; Zhang, Li; Zhuang, Hai-Wen

    2017-11-01

    Colorectal cancer is a common malignant tumor with high incidence affecting the digestive system. This study aimed to identify the key genes relating to prognosis of colorectal cancer and to construct a prognostic model for its risk evaluation. Gene expression profiling of colorectal cancer patients, GSE17537, was downloaded from Gene Expression Omnibus database (GEO). A total of 55 samples from patients ranging from stages 1 to 4 were available. Differentially expressed genes were screened, with which single factor survival analysis was performed to identify the response genes. Interacting network and KEGG enrichment analysis of responsive genes were performed to identify key genes. In return, Fisher enrichment analysis, literature mining, and Kaplan-Meier analysis were used to verify the effectiveness of the prognostic model. The 20-gene model generated in this study posed significant influences on the prognoses (P = 9.691065e-09). Significance was verified via independent dataset GSE38832 (P = 9.86581e-07) and GSE17536 (P = 2.741e-08). The verified effective 20-gene model could be utilized to predict prognosis of patients with colorectal cancer and would contribute to post-operational treatment and follow-up strategies. J. Cell. Biochem. 118: 3675-3685, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. 3-D visualization and quantitation of microvessels in transparent human colorectal carcinoma [corrected].

    PubMed

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

    2013-01-01

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

  20. Progress and Opportunities in Molecular Pathological Epidemiology of Colorectal Premalignant Lesions

    PubMed Central

    Lochhead, Paul; Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles S.; Wu, Kana; Nishihara, Reiko; O’Brien, Michael; Ogino, Shuji

    2014-01-01

    Molecular pathological epidemiology (MPE) is integrative molecular and population health science to address molecular pathogenesis and heterogeneity of disease processes. MPE of colon and rectal premalignant lesions (including hyperplastic polyps, tubular adenomas, tubulovillous adenomas, villous adenomas, traditional serrated adenomas, sessile serrated adenomas / sessile serrated polyps, and hamartomatous polyps) can provide unique opportunities to examine the influence of diet, lifestyle and environmental exposures on specific pathways of carcinogenesis. Colorectal neoplasia can provide a practical model where both malignant epithelial tumor (carcinoma), and its precursor, are subjected to molecular pathology analyses. KRAS, BRAF, and PIK3CA oncogene mutations, microsatellite instability, CpG island methylator phenotype, and LINE-1 methylation are commonly-examined tumor biomarkers. Future opportunities include comprehensive interrogation of genomics, epigenomics and pan-omics, as well as in vivo pathology analyses of tissue microenvironment, molecular networks and interactome by endomicroscopy. Considering the colorectal continuum hypothesis and emerging roles of gut microbiota and host immunity in tumorigenesis, detailed tumor location is important information. There are unique strengths and caveats, especially with regard to case ascertainment by colonoscopy. MPE of colorectal premalignant lesions can identify etiologic exposures associated with neoplastic initiation and progression, help us better understand colorectal carcinogenesis, and facilitate personalized prevention, screening, and therapy. PMID:24935274

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

    PubMed

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

    2014-01-28

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

  2. In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components.

    PubMed

    Woischke, Christine; Schaaf, Christian W; Yang, Hui-Min; Vieth, Michael; Veits, Lothar; Geddert, Helene; Märkl, Bruno; Stömmer, Peter; Schaeffer, David F; Frölich, Matthias; Blum, Helmut; Vosberg, Sebastian; Greif, Philipp A; Jung, Andreas; Kirchner, Thomas; Horst, David

    2017-01-01

    Neuroendocrine carcinomas (NECs) of the colorectum are rare but highly aggressive neoplasms. These tumors show some shared genetic alterations with colorectal adenocarcinomas, and most of them have adjacent glandular adenoma or adenocarcinoma components. However, genetic data on colorectal NECs still are sparse and insufficient for definite conclusions regarding their molecular origin. Based on morphological characterization, panel and whole-exome sequencing, we here present results from an in-depth analysis of a collection of 15 colorectal NECs with glandular components, 10 of which by definition were mixed adenoneuroendocrine carcinomas (MANECs). Among shared genetic alterations of both tumor components, we most frequently found TP53, KRAS and APC mutations that also had highest allele frequencies. Mutations exclusive to glandular or neuroendocrine components outnumbered shared mutations but occurred at lower allele frequencies. Our findings not only provide additional evidence for a common clonal origin of colorectal NECs and adjacent glandular tumor components, but strongly suggest their development through the classical adenoma-carcinoma sequence. Moreover, our data imply early separation of glandular and neuroendocrine components during malignant transformation with subsequent independent mutational evolution.

  3. ADNP Is a Therapeutically Inducible Repressor of WNT Signaling in Colorectal Cancer.

    PubMed

    Blaj, Cristina; Bringmann, Agnes; Schmidt, Eva Marina; Urbischek, Manuela; Lamprecht, Sebastian; Fröhlich, Thomas; Arnold, Georg J; Krebs, Stefan; Blum, Helmut; Hermeking, Heiko; Jung, Andreas; Kirchner, Thomas; Horst, David

    2017-06-01

    Purpose: Constitutively active WNT signaling is a hallmark of colorectal cancers and a driver of malignant tumor progression. Therapeutic targeting of WNT signaling is difficult due to high pathway complexity and its role in tissue homeostasis. Here, we identify the transcription factor ADNP as a pharmacologically inducible repressor of WNT signaling in colon cancer.Experimental Design: We used transcriptomic, proteomic, and in situ analyses to identify ADNP expression in colorectal cancer and cell biology approaches to determine its function. We induced ADNP expression in colon cancer xenografts by low-dose ketamine in vivo Clinical associations were determined in a cohort of 221 human colorectal cancer cases.Results: ADNP was overexpressed in colon cancer cells with high WNT activity, where it acted as a WNT repressor. Silencing ADNP expression increased migration, invasion, and proliferation of colon cancer cells and accelerated tumor growth in xenografts in vivo Treatment with subnarcotic doses of ketamine induced ADNP expression, significantly inhibited tumor growth, and prolonged survival of tumor-bearing animals. In human patients with colon cancer, high ADNP expression was linked to good prognosis.Conclusions: Our findings indicate that ADNP is a tumor suppressor and promising prognostic marker, and that ketamine treatment with ADNP induction is a potential therapeutic approach that may add benefit to current treatment protocols for patients with colorectal cancer. Clin Cancer Res; 23(11); 2769-80. ©2016 AACR. ©2016 American Association for Cancer Research.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2007-11-01

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

  8. 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. ©2016 American Association for Cancer Research.

  9. Colorectal cancer stem cells.

    PubMed

    Salama, Paul; Platell, Cameron

    2009-10-01

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

  10. Oral potentially malignant disorders: is malignant transformation predictable and preventable?

    PubMed

    van der Waal, Isaäc

    2014-07-01

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

  11. 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.

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

    PubMed

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

    2017-03-20

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

  13. 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

  14. Alcohol intake, smoking, and colorectal adenoma.

    PubMed

    Park, Yeong Mi; Cho, Chang Ho; Kim, Sung Hi; Lee, Jung Eun

    2014-06-01

    Colorectal cancer is the third most common cancer in Korea. Because colorectal adenoma is a precursor lesion of colorectal cancer, primary prevention of colorectal adenomas may be important for reducing morbidity and mortality from the disease. The aim of this study is to examine the association of alcohol consumption and cigarette smoking in relation with colorectal adenoma in a cross-sectional study of Korean adults. A total of 366 participants who underwent colonoscopy were included (113 cases and 255 controls) in this study. Information on alcohol intake and cigarette smoking was collected from structured questionnaires. The odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using the multivariate logistic regression models. Alcohol intake was associated with a higher prevalence of colorectal adenoma in men; compared to non-drinkers, ORs (95% CIs) were 11.49 (2.55-51.89) for 10-20 g/day of alcohol intake and 14.15 (3.31-60.59) for â 20 g/day of alcohol intake (P for trend = 0.003). There was a weaker association of alcohol intake for women than men; however, there was a suggestive increase in the prevalence of colorectal cancer in women. Cigarette smoking was not associated with colorectal adenoma, but we cannot rule out the possibility that this was due to low statistical power. Our study provides evidence to suggest that alcohol intake may contribute to colorectal adenoma in the Korean population. Our study results demonstrate that a larger epidemiologic study is needed.

  15. [Signet ring cell colorectal carcinom - case report].

    PubMed

    Matkovčík, Z; Hlad, J

    2015-08-01

    Signet ring cell colorectal carcinoma is a rare aggressive tumor. The incidence of this desease is very low in young patients and accounts up to 1% of all surgical patients with colorectal cancer. The infrequency of the disease among young patients makes the diagnosis more difficult and the prognosis less favourable. Biopsy results are crucial for verification of signet ring cell carcinoma. Treatment is similar as in other types of colorectal cancer. We report a case of signet ring cell colon cancer in a 22 years old female patient.The aim of this paper is to point out this rare case of infrequent colorectal cancer in a young female patient.

  16. Radiotherapy for a repeatedly recurrent ameloblastoma with malignant transformation.

    PubMed

    Huang, Chun-Ming; Chen, Jin-Yi; Chen, Chung-Ho; Huang, Chih-Jen

    2014-01-01

    The role of radiation therapy (RT) for ameloblastoma remains controversial and undetermined due to the rarity of the disease. A case of repeatedly recurrent ameloblastoma with malignant transformation is presented. The clinical course and managements are described. The 63-year-old man had a recurrent ameloblastoma in the left mandible. Five years after the first surgical resection, he underwent 8 more rounds of surgical excision of the recurrent tumors. The malignant transformation occurred and the unresectable tumor invaded the masticator space, parapharyngeal space, and skull base. He received 3-dimensional conformal RT, at the dose of 66 Gray (Gy) in 33 fractions. The ulcerative exophytic mass had regressed gradually. After follow-up of 28 months, the tumor was well controlled. RT seems to be a feasible treatment option for recurrent ameloblastoma with malignant transformation. Copyright © 2013 Wiley Periodicals, Inc.

  17. Primary cerebral malignant melanoma

    PubMed Central

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

    2017-01-01

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

  18. Galectins in hematological malignancies.

    PubMed

    Giordano, Mirta; Croci, Diego O; Rabinovich, Gabriel A

    2013-07-01

    Galectins are a family of lectin molecules that have emerged as key players in inflammation and tumor progresssion by displaying intracellular and extracellular activities. This review describes the recent advances on the role of galectins in hematological neoplasms. Galectin-1 and galectin-3 are the best studied galectins in oncohematology. Increased expression of galectin-1 has been associated with tumor progression in Hodgkin's lymphoma and chronic lymphocytic leukemia, whereas galectin-3 plays a supporting role in chronic myelogenous leukemia and multiple myeloma. Functional studies have assigned a key role for galectin-1 as a negative regulator of T-cell immunity in Hodgkin's lymphoma and cutaneous T-cell lymphoma. Of therapeutic interest is the development of agents with the capacity to interfere with galectin functions. Current knowledge indicates a key role for galectins in hematological neoplasms by favoring the growth and survival of tumor cells and facilitating tumor immune escape. Intervention using specific galectin inhibitors is emerging as an attractive therapeutic option to alter the course of these malignancies.

  19. Malignancy and chronic renal failure.

    PubMed

    Peces, Ramon

    2003-01-01

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

  20. Stromal cell derived factor-1 and CXCR4 expression in colorectal cancer promote liver metastasis.

    PubMed

    Amara, Sameh; Chaar, Ines; Khiari, Meriem; Ounissi, Donia; Weslati, Marwa; Boughriba, Rahma; Hmida, Abdelmajid B; Bouraoui, Saadia

    2015-01-01

    Recent studies suggest that SDF-1 and CXCR4 are expressed in certain cancer cells, and malignant cells use this chemokine/receptor system to promote tumor progression and metastasis. However, the pathophysiological significance of their expression in colorectal cancer (CRC) tissue has not been fully elucidated. The purpose of this study was to assess SDF-1/CXCR4 expression and to explore its contribution to colorectal cancer. We examined SDF-1 and CXCR4 mRNA expression in 124 primary colorectal tumour and 35 liver metastases tissues and matched adjacent noncancerous tissues by reverse transcriptase PCR (RT-PCR). Furthermore, their expression was analyzed by immunohistochemistry. The relationship between SDF-1/CXCR4 expression and clinicopathological features were analyzed by appropriate statistics. X2 test and Kaplan-Meier analysis were used to investigate the correlation between the ligand-receptor expression and prognosis of colorectal cancer patients. The relative mRNA expression of SDF-1 and CXCR4 was significantly elevated in colorectal cancer tissues as compared with adjacent noncancerous tissues (P < 0.001). The high expression of proteins expression in colorectal cancer tissues was significantly correlated with tumor grade (P = 0.0001), clinical stage (P < 0.05), and lymphatic invasion (P < 0.05). Furthermore, patients with CXCR4 nuclear-type expression showed more frequent lymph node metastasis (p = 0.021), advanced clinical stage (p = 0.001) and lymphatic invasion (p = 0.03) than those with cytoplasm staining-type. Kaplan-Meier survival analysis revealed that high expression of the couple SDF-1/CXCR4 correlated with poor prognosis of colorectal cancer patients (P < 0.001). SDF-1 and CXCR4 may play an important role in the progression of colorectal cancer. The present data suggest that there is a significant association between SDF-1/CXCR4 to enhance the liver metastases causing poor prognosis. Those proteins may potentially be used as an independent

  1. Serum ghrelin is associated with risk of colorectal adenocarcinomas in the ATBC study.

    PubMed

    Murphy, Gwen; Cross, Amanda J; Dawsey, Sanford M; Stanczyk, Frank Z; Kamangar, Farin; Weinstein, Stephanie J; Taylor, Philip R; Männistö, Satu; Albanes, Demetrius; Abnet, Christian C; Freedman, Neal D

    2017-08-16

    Colorectal cancers are the third most common cancers in women and men in the USA. While dietary and lifestyle factors such as Western diet, physical inactivity and obesity have been linked to an increased risk of this malignancy, the mechanisms for these associations are unclear. GI hormones, including ghrelin, are involved in energy balance by mediating appetite and metabolism; however, the association between ghrelin and colorectal cancer has not been studied. We conducted a case-control study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish smokers (aged 50-69 years) to examine serum ghrelin concentration and colorectal cancer risk. Data from 284 colon and 239 rectal cancers and 523 controls (matched on age, date of blood draw and serum availability) were analysed. ORs and 95% CIs were calculated using multivariable (conditional) logistic regression. Overall, low-serum ghrelin was significantly associated with increased risk of colorectal cancer (Q1 vs Q4: OR:1.57, 95% CI 1.05 to 2.34). For individuals developing tumours within 10 years of blood draw, those in the lowest quartile of serum ghrelin concentrations were statistically significantly more likely to develop colorectal cancers than those with higher serum ghrelin concentrations (OR: 10.86, 95% CI 5.01 to 23.55). However, for individuals with tumours developing more than 20 years after blood draw, low-serum ghrelin concentrations were associated with a decreased risk of colorectal cancer relative to those with the highest serum ghrelin concentrations (OR: 0.26, 95% CI 0.11 to 0.64). Low-serum ghrelin was associated with an increased colorectal cancer risk within 10 years of blood draw with a decreased risk for developing colorectal cancer more than 20 years after blood draw. These results suggest that ghrelin concentrations may vary across the carcinogenic process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the

  2. Colorectal cancer: a study of risk factors in a tertiary care hospital of north bengal.

    PubMed

    Bhattacharya, Sumanta; Bhattacharya, Saikat; Basu, Rivu; Bera, Pranati; Halder, Aniket

    2014-11-01

    , obesity were significant risk factors in our study. Other risk factors were though not significant, but much more common in colorectal cancer patients compared to non-malignant population.

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

    PubMed

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

    2016-11-15

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

  4. Improved perioperative and short-term outcomes of robotic versus conventional laparoscopic colorectal operations.

    PubMed

    Casillas, Mark A; Leichtle, Stefan W; Wahl, Wendy L; Lampman, Richard M; Welch, Kathleen B; Wellock, Trisha; Madden, Erin B; Cleary, Robert K

    2014-07-01

    Robotic assistance may offer unique advantages over conventional laparoscopy in colorectal operations. This prospective observational study compared operative measures and postoperative outcomes between laparoscopic and robotic abdominal and pelvic resections for benign and malignant disease. From 2005 through 2012, 200 (58%) laparoscopic and 144 (42%) robotic operations were performed by a single surgeon. After adjustment for differences in demographics and disease processes using propensity score matching, all laparoscopic operations had a significantly shorter operative time (P < .01), laparoscopic left colectomies had a longer length of hospital stay (2009 and 2010: 6.5 vs 3.6 days, P = .01); and laparoscopic right colectomies had a higher risk for overall complications (P = .03) and postoperative ileus (P = .04). There were no significant differences in the outcomes of pelvic operations (P = .15). Compared with conventional laparoscopy, some types of robotic-assisted colorectal operations may offer advantages regarding postoperative length of stay and perioperative complications. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. HER-2 inhibition in gastric and colorectal cancers: tangible achievements, novel acquisitions and future perspectives

    PubMed Central

    Rihawi, Karim; Avallone, Antonio; Silvestris, Nicola; Fornaro, Lorenzo; Vasile, Enrico; Antonuzzo, Lorenzo; Leone, Francesco; Rosati, Gerardo; Giuliani, Francesco; Bordonaro, Roberto; Scartozzi, Mario; Maglio, Giovanna De; Negri, Francesca V.; Fasola, Gianpiero; Aprile, Giuseppe

    2016-01-01

    HER-2 (ErbB-2, c-erbB2 or Her2/neu), a member of the HER-family, is directly involved in the pathogenesis and progression of several human cancers; as such, it is also often considered as a poor prognostic factor. Following the revolutionary impact of anti-HER-2 therapy in breast cancer patients, the role of HER-2 and its blockade has also been extensively evaluated in other tumor types, including gastric and colorectal adenocarcinoma. The aims of this review are to recall the important results achieved with the use of HER-2 inhibitors in both gastric and colorectal cancer, and to discuss on the updates available on the role of HER-2 as prognostic and predictive factor in these malignancies. PMID:27542243

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-03-26

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

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

    ClinicalTrials.gov

    2017-05-01

    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

  9. General Aspects of Colorectal Cancer

    PubMed Central

    Centelles, Josep J.

    2012-01-01

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

  10. Stem cells and colorectal carcinogenesis

    PubMed Central

    Stoian, M; Stoica, V; Radulian, G

    2016-01-01

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

  11. General aspects of colorectal cancer.

    PubMed

    Centelles, Josep J

    2012-01-01

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

  12. Telomere function in colorectal cancer

    PubMed Central

    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

    2009-01-01

    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

  13. 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.

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

    PubMed

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

    2015-07-01

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

  15. Malignant renal tumors in children

    PubMed Central

    Sanchez, Thomas Ray; Wootton-Gorges, Sandra

    2015-01-01

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

  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. Danish Colorectal Cancer Group Database.

    PubMed

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

    2016-01-01

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

  18. Surgery for colorectal liver metastases

    PubMed Central

    Primrose, J N

    2010-01-01

    In this review the surgery of colorectal liver metastases is discussed. It has long been known that liver surgery can cure metastatic colorectal cancer although in only a small proportion of the population with the disease. However with better understanding of the natural history of the condition and advances in technique more patients can have safe, potentially curative surgery. The multidiscipline management of patients with effective chemotherapy has led to more patients benefiting from surgery after reducing the size of the metastases and allowing operation on patients who were previously inoperable. Chemotherapy also improves at least the medium-term outcome in those who are operable at the outset. Minimally invasive techniques have been developed so that major hepatectomy may be accomplished in up to half of such cases with a very short hospital stay and limited interference with quality of life. Lastly, using portal vein embolisation to cause hypertrophy of the future liver remnant and on occasions combining it with staged liver resection allows potentially curative surgery on patients who previously could not have survived resection. These developments have led to more patients being cured of advanced colorectal cancer. PMID:20424612

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  1. Colorectal cancer in young adults in a tertiary care hospital in Chhattisgarh, Raipur.

    PubMed

    Sudarshan, V; Hussain, N; Gahine, R; Mourya, J

    2013-01-01

    Carcinoma of the colon and rectum is a relatively uncommon malignancy in India when compared with the western world. Colorectal cancer is generally a disease affecting individuals 50 years of age and older and is much less common in persons under 40 years of age. It is also a very uncommon pediatric malignancy. To study the age, gender, site of primary tumor, histopathological type, and pathologic stage of colorectal cancer cases with specific reference to young adults. Tertiary care hospital, Retrospective study. We conducted a retrospective study of all colorectal carcinomas (CRC) which were diagnosed during the past 8 years i.e., from January 2003 to December 2010. Patients were divided in to two groups - 40 years and younger, and older than 40 years. The records were analyzed in detail for age, gender, site of primary tumor, histopathological type, and pathologic stage. The results of the two groups were compared and also with information from other centers. Nil. Two hundred and thirty three patients were diagnosed to have CRC. Patients diagnosed below 40 years of age comprised 39.05% and those under age 20 comprised 4. 29%. Among those under 40 years of age, majority were males (63.73%), most occurred in the rectum (84.61%). Most of them were poorly differentiated mucin-secreting adenocarcinomas (80.21%) and presented at advanced pathologic T stage (71.42%). This was similar to those reported in other literatures. However, the incidence of colorectal cancer in patients younger than 40 years is much more in our study when compared with reports from other places. CRC in our institution is more often seen in younger individuals than what is reported in population-based cancer registries from other parts of the country. The reasons for this are not clear. Therefore, further studies are required to address the role of diet and personal habits with CRC in this region. Also, a high index of suspicion among young adults is necessary.

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

    SciTech Connect

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

    2008-09-15

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

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

    PubMed Central

    2014-01-01

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

  4. The new nitinol conformable self-expandable metal stents for malignant colonic obstruction: a pilot experience as bridge to surgery treatment.

    PubMed

    Di Mitri, Roberto; Mocciaro, Filippo

    2014-01-01

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

  5. 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

  6. Malignant hyperthermia: a review.

    PubMed

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

    2015-08-04

    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

  7. Management of sessile malignant polyps: is colonoscopic polypectomy enough?

    PubMed

    Wu, Xian-rui; Liang, Jennifer; Church, James M

    2015-10-01

    The role of endoscopy in the management of malignant-pedunculated polyps has been well studied, but endoscopic management of malignant sessile polyps has not. Sometimes patients with malignant sessile polyps have comorbidities that make surgery exceptionally risky, and endoscopy beckons as a definitive management option. The aim of this study is to evaluate the potential role of endoscopy in the management of malignant sessile polyps. Patients undergoing colonoscopic polypectomy for malignant sessile polyps by a single endoscopist from 1997 to 2010 were evaluated. Demographic data, clinicopathological variables as well as long-term outcomes were recorded. Sixteen patients had malignant sessile polyps. Six (37.5 %) were male and 10 (62.5 %) were female. Mean age at diagnosis was 72.9 ± 12.2 years. Six polyps were proximal to the splenic flexure (37.5 %) and 10 (62.5 %) were distal. The mean size of the polyps was 30.5 ± 15.9 mm. All polyps were removed endoscopically but 7 patients (43.8 %) had formal colectomy following colonoscopic resection. There were no demographic differences between patients with and without surgery. Piecemeal polypectomy was necessary in 8 patients, 4 from the surgery group, and 4 from the endoscopy group. More patients in the surgery group had poorly differentiated cancers (4/6 vs. 0/6) and incomplete margins (5/6 vs. 1/6) and more patients in the endoscopically treated group had serious comorbidity (5/9 vs. 3/7). There was no procedure-related morbidity or mortality. After a mean follow-up of 48.4 ± 27.2 months, one patient from the polypectomy group patient had a local recurrence and a liver metastasis, after originally declining surgery. In the surgery group, one patient had lung metastasis. The two patients who recurred with distant metastasis died. Endoscopic management of sessile colorectal polyps appears to be feasible and safe in patients with well/moderately differentiated cancer and negative margins. Larger studies are needed

  8. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

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

  9. Genetics Home Reference: malignant hyperthermia

    MedlinePlus

    ... Genetic and Rare Diseases Information Center (2 links) King Denborough syndrome Malignant hyperthermia Educational Resources (5 links) ... Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of ...

  10. Orbital exenteration in periorbital malignancies.

    PubMed

    Roche, Phoebe; Timon, Conrad

    2012-08-01

    Orbital exenteration is a disfiguring procedure most commonly performed for locally advanced or recurrent periorbital malignancies. We performed a retrospective review of 22 patients who underwent orbital exenteration for advanced periorbital malignancy at our institution, by the senior author over a seventeen-year period. Specifically, we have reviewed the tumour histology along with stage at presentation, patient age, history of previous surgical intervention and surgical outcomes. The review highlighted two main groups who required orbital exenteration - patients with recurrent or locally advanced periorbital skin cancers, and patients with malignancy of the sinus. We discuss the presentation and management of the two pathological processes and highlight the importance of aggressive early management of periorbital malignancy with a view to prevention of exenteration and improving survival. Copyright © 2011 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  11. 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.

  12. E2F transcription factors and digestive system malignancies: how much do we know?

    PubMed

    Xanthoulis, Athanasios; Tiniakos, Dina G

    2013-06-07

    E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumor-promoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.

  13. 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

  14. [Current concepts in malignant glaucoma].

    PubMed

    Călugăru, M; Marin, C

    1990-01-01

    The paper reports on the main pathogenic types of anatomical blocking of the aqueous humor circulation in malignant glaucoma: pupillary, secondary iridolenticular, ciliovitreolenticular, iridociliovitreous blocks and in suprachoroidal effusion. The paper also presents some of the entities correlated with malignant glaucoma: glaucoma with blocked angle following the administration of miotics, traumatisms, the operations of scleral obstruction for retina detachment, panretinal photocoagulation and thrombosis of the retina central vein.

  15. Malignant tumours after renal transplantation.

    PubMed

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

    1996-10-01

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

  16. Molecular Diagnosis for Breast Malignancy

    DTIC Science & Technology

    1997-07-01

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

  17. Telomerase Activation in Hematological Malignancies

    PubMed Central

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

    2016-01-01

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

  18. Primary malignant melanoma of prostate

    PubMed Central

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

    2010-01-01

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

  19. Economic burden of colorectal cancer in Korea.

    PubMed

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

    2014-03-01

    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. 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. 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. Colorectal cancer has a large economic burden. Efforts should be made to reduce the economic burden of the disease through primary and secondary prevention.

  20. 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…

  1. Best practice in colorectal cancer care.

    PubMed

    Taylor, Claire

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

  2. Colorectal cancer in Jordan: prevention and care.

    PubMed

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

    2015-12-01

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

  3. 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…

  4. Immune Modulation in Hematologic Malignancies

    PubMed Central

    Dhodapkar, Madhav V.; Dhodapkar, Kavita M.

    2015-01-01

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

  5. γ-Catenin acts as a tumor suppressor through context-dependent mechanisms in colorectal cancer.

    PubMed

    Nagel, Jutta Maria; Lahm, Harald; Ofner, Andrea; Göke, Burkhard; Kolligs, Frank Thomas

    2017-07-06

    γ-Catenin is a protein closely related to β-catenin. While the overexpression of β-catenin has been linked with impaired prognosis and survival in various malignancies, both oncogenic and tumor suppressor functions have been described for γ-catenin. Thus, its role in cancer remains controversial. In this study, we examined the impact of γ-catenin expression on the malignant potential of colorectal cancer cells. γ-Catenin was knocked down by short interfering RNA in the γ-catenin-proficient DLD-1 cell line and stably overexpressed in the γ-catenin-deficient cell line RKO. The effects of these molecular manipulations on the malignant potential of the cell lines were tested in vitro and in vivo in a xenograft tumor model. γ-Catenin contributed to Wnt signaling independent of the cellular context. Unlike its sister molecule β-catenin, γ-catenin inhibited cellular invasion and anoikis in cells endogenously expressing γ-catenin. In line with this tumor suppressor function, its de novo expression in RKO cells inhibited proliferation via cell cycle arrest. In a xenograft tumor model, overexpression of γ-catenin starkly reduced tumor growth in vivo. This is the first report demonstrating a tumor-suppressive effect of γ-catenin in colorectal cancer both in vitro and in vivo. Detailed in vitro analysis revealed that effects of γ-catenin differ in γ-catenin proficient and deficient cells, indicating that its function in colorectal cancer is dependent on the cellular context. This finding adds to our understanding of γ-catenin and may have implications for future studies of catenin/Wnt targeted cancer therapies.

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

    PubMed Central

    Rogers, Jane E

    2017-01-01

    Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies, including colorectal cancer (CRC), making EGFR an attractive treatment option. Panitumumab and cetuximab, monoclonal antibodies (mAbs) directed at EGFR, are both currently utilized in the management of metastatic CRC (mCRC). Through the development of these agents in mCRC, key issues surrounding each mAbs use have been revealed. These key issues include negative patient outcome avoidance when determining use, the economic burden with high-cost medication, predictive biomarkers, tumor location, patient geographic location, patient quality of life, and the prevention of debilitating adverse effects. CRC remains a common malignancy, with many of these patients expected to receive targeted therapy, including EGFR mAb therapy. Oncologists must recognize these EGFR mAb factors in order to improve outcomes. This review aims to provide a chronological timeline on the development of panitumumab, clinical pearls, and guidance on the current use of panitumumab in mCRC. PMID:28435294

  7. 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

  8. The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study.

    PubMed

    Wang, Peng; Liang, Jianwei; Wang, Zheng; Hou, Huirong; Shi, Lei; Zhou, Zhixiang

    2017-05-01

    This retrospective cohort study aimed to discuss the prognostic value of p53 positive in colorectal cancer. A total of 124 consecutive patients diagnosed with colorectal cancer were evaluated at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 1 January 2009 to 31 December 2010. The expression of p53 in colorectal cancer was examined by immunohistochemistry. Based on the expression levels of p53, the 124 patients were divided into a p53 positive group and a p53 negative group. In this study, 72 patients were in the p53 positive group and 52 in the p53 negative group. The two groups were well balanced in gender, age, body mass index, American Society of Anesthesiologists scores, and number of lymph nodes harvested. p53 positive was associated with carcinoembryonic antigen ≥5 ng/mL ( p = 0.036), gross type ( p = 0.037), degree of tumor differentiation ( p = 0.026), pathological tumor stage ( p = 0.019), pathological node stage ( p = 0.004), pathological tumor-node-metastasis stage ( p = 0.017), nerve invasion ( p = 0.008), and vessel invasion ( p = 0.018). Tumor site, tumor size, and pathological pattern were not significantly different between these two groups. Disease-free survival and overall survival in the p53 positive group were significantly shorter than the p53 negative group ( p = 0.021 and 0.025, respectively). Colorectal cancer patients with p53 positive tended to be related to a higher degree of malignancy, advanced tumor-node-metastasis stage, and shorter disease-free survival and overall survival. p53 positive was independently an unfavorable prognostic marker for colorectal cancer patients.

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

    PubMed

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

    2008-06-15

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

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

    PubMed Central

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

    2014-01-01

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

  11. Alcohol drinking and colorectal cancer in Japanese: a pooled analysis of results from five cohort studies.

    PubMed

    Mizoue, Tetsuya; Inoue, Manami; Wakai, Kenji; Nagata, Chisato; Shimazu, Taichi; Tsuji, Ichiro; Otani, Tetsuya; Tanaka, Keitaro; Matsuo, Keitaro; Tamakoshi, Akiko; Sasazuki, Shizuka; Tsugane, Shoichiro

    2008-06-15

    Colorectal cancer is an alcohol-related malignancy; however, the association appears to be stronger among Asian populations with a relatively high prevalence of the slow-metabolizing aldehyde dehydrogenase variant. To examine the association between alcohol consumption and colorectal cancer in Japanese, the authors analyzed original data from five cohort studies that measured alcohol intake using validated questionnaires at baseline. Hazard ratios were calculated in the individual studies, with adjustment for a common set of variables, and then combined using a random-effects model. During 2,231,010 person-years of follow-up (ranging variously from 1988 to 2004), 2,802 colorectal cancer cases were identified. In men, multivariate-adjusted pooled hazard ratios for alcohol intakes of 23-45.9 g/day, 46-68.9 g/day, 69-91.9 g/day, and > or =92 g/day, compared with nondrinking, were 1.42 (95% confidence interval (CI): 1.21, 1.66), 1.95 (95% CI: 1.53, 2.49), 2.15 (95% CI: 1.74, 2.64), and 2.96 (95% CI: 2.27, 3.86), respectively (p for trend < 0.001). The association was evident for both the colon and the rectum. A significant positive association was also observed in women. One fourth of colorectal cancer cases in men were attributable to an alcohol intake of > or =23 g/day. An alcohol-colorectal cancer association seems to be more apparent in Japanese than in Western populations. Whether this difference can be ascribed to genetic or environmental factors needs to be clarified.

  12. Evaluation of serum cathepsin B and D in relation to clinicopathological staging of colorectal cancer

    PubMed Central

    Skrzydlewska, Elzbieta; Sulkowska, Mariola; Wincewicz, Andrzej; Koda, Mariusz; Sulkowski, Stanislaw

    2005-01-01

    AIM: Proteolytic degradation of the extracellular matrix facilitates cancer invasion and promotes metastasis. The study aims at evaluation of preoperative and postoperative serum cathepsins B and D levels in correlation with selected anatomoclinical features of colorectal cancer. METHODS: Blood samples were collected from 63 colorectal cancer patients before curative operation of the tumor 10 d later. Blood that was obtained from 20 healthy volunteers, served as a control. The activity of cathepsin B was measured with Bz-DL-arginine-pNA as a substrate at pH 6.0, while cathepsin D activity was determined with urea-denatured hemoglobin (pH 4.0). RESULTS: The preoperative and postoperative activities of cathepsin B were significantly (P < 0.00001) lower in serum of colorectal cancer patients than in control group. However, postoperative values of this protease were significantly increased in comparison with preoperative ones (P = 0.031). Activity of cathepsin D appeared to be significantly higher in colorectal cancer sera (P < 0.00001) compared with controls. No statistically significant differences between preoperative and postoperative activity of cathepsin D were noted (P = 0.09). We revealed a strong linkage of cathepsins’ levels with lymph node status and pT stage of colorectal cancer. CONCLUSION: Blood serum activities of cathepsin B and D depend on the time of sampling, tumor size and lymph node involvement. Significantly, increased activity of cathepsin D could indicate a malignant condition of the large intestine. In our work, the serum postoperative decrease of cathepsin B activity appears as an obvious concomitant of local lymph node metastasis-the well-known clinicopathological feature of poor prognosis. PMID:16015694

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

    PubMed Central

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

    1996-01-01

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

  14. Hepatic malignancies: improved treatment with intraarterial Y-90

    SciTech Connect

    Herba, M.J.; Illescas, F.F.; Thirlwell, M.P.; Boos, G.J.; Rosenthall, L.; Atri, M.; Bret, P.M.

    1988-11-01

    An improved treatment method for hepatic malignancies with yttrium-90 incorporated into the matrix of glass microspheres was evaluated prospectively. Fifteen patients with 12 metastatic colorectal cancers, one carcinoid, one islet cell tumor, and one hepatoma were treated with three dose levels: 5000 cGy (5000 rad), ten patients; 7500 cGy (7,500 rad), three patients; and 10,000 cGy (10,000 rad), two patients. Mean follow-up was 7 months (range, 2-12 months). Stable disease in the liver was seen in ten patients, four of whom had concurrent progression of extrahepatic disease, which resulted in two deaths. Two additional deaths were not directly related to the malignant process. Progression of liver disease was found in five patients, with three deaths occurring at 7-8 months. No procedural, hematologic, or pulmonary complications occurred. Late gastroduodenal ulceration occurred at 6-8 weeks in three patients who had histories of chronic alcohol abuse. This method of therapy seems to be feasible and efficient. Caution is necessary with high doses or with patients with a history of or predisposition to gastroduodenal ulcers.

  15. 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

  16. De novo malignancies after liver transplantation: a major cause of late death.

    PubMed

    Fung, J J; Jain, A; Kwak, E J; Kusne, S; Dvorchik, I; Eghtesad, B

    2001-11-01

    1. Recurrent and de novo malignancies are the second leading causes of late death in liver transplant recipients, following age-related cardiovascular complications. 2. The increased incidence of de novo malignancies in liver transplant recipients compared with the general population reflects their demographic makeup, known preexistent risk factors for cancer, greater rate of chronic viral infection, and actions of exogenous immunosuppression. 3. The greatest incidence of de novo malignancies is seen in cancers associated with chronic viral infections, such as Epstein-Barr virus-associated posttransplant lymphoproliferative disease, and skin cancers, including squamous cell carcinoma and Kaposi's sarcoma. 4. Although a greater incidence of such malignancies as oropharyngeal malignancy and colorectal cancer was noted, there did not appear to be an increased risk for liver transplant recipients matched for age, sex, and length of follow-up using modified life-table technique and Surveillance Epidemiology End Result data with a similar at-risk group. However, they may present with more advanced stages of disease. 5. An increased incidence of de novo cancers in chronically immunocompromised liver transplant recipients demands careful long-term screening protocols to help facilitate diagnosis at an earlier stage of disease.

  17. 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.

  18. 5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

    ClinicalTrials.gov

    2017-09-28

    Colorectal Adenocarcinoma; RAS Wild Type; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  19. The influence of obesity and body mass index on the outcome of laparoscopic colorectal surgery: a systematic literature review.

    PubMed

    Hotouras, A; Ribas, Y; Zakeri, S A; Nunes, Q M; Murphy, J; Bhan, C; Wexner, S D

    2016-10-01

    The relationship between obesity, body mass index (BMI) and laparoscopic colorectal resection is unclear. Our object was to assess systematically the available evidence to establish the influence of obesity and BMI on the outcome of laparoscopic colorectal resection. A search of PubMed/Medline databases was performed in May 2015 to identify all studies investigating the impact of BMI and obesity on elective laparoscopic colorectal resection performed for benign or malignant bowel disease. Clinical end-points examined included operation time, conversion rate to open surgery, postoperative complications including anastomotic leakage, length of hospital stay, readmission rate, reoperation rate and mortality. For patients who underwent an operation for cancer, the harvested number of lymph nodes and long-term oncological data were also examined. Forty-five studies were analysed, the majority of which were level IV with only four level III (Oxford Centre for Evidence-based Medicine 2011) case-controlled studies. Thirty comparative studies containing 23 649 patients including 17 895 non-obese and 5754 obese showed no significant differences between the two groups with respect to intra-operative blood loss, overall postoperative morbidity, anastomotic leakage, reoperation rate, mortality and the number of retrieved lymph nodes in patients operated on for malignancy. Most studies, including 15 non-comparative studies, reported a longer operation time in patients who underwent a laparoscopic procedure with the BMI being an independent predictor in multivariate analyses for the operation time. Laparoscopic colorectal resection is safe and technically and oncologically feasible in obese patients. These results, however, may vary outside of high volume centres of expertise. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  20. Long-term Outcomes Following Microwave Ablation for Liver Malignancies

    PubMed Central

    Leung, U.; Kuk, D.; D’Angelica, M. I.; Kingham, T. P.; Allen, P. J.; DeMatteo, R. P.; Jarnagin, W. R.; Fong, Y.

    2015-01-01

    Background Microwave ablation has emerged as a promising treatment modality for liver malignancies, but there are scant long-term follow-up data. This study evaluates long-term outcomes with a comparison of 915MHz and 2.4GHz ablation systems. Method A retrospective review of patients with malignant liver tumors undergoing operative microwave ablation with or without liver resection between 2008 and 2013 was performed. Regional or systemic (neo)adjuvant therapy was given selectively. Local recurrence was analyzed using competing risk methods with clustering and overall survival was analyzed using Kaplan-Meier curves. Results One-hundred-and-seventy-six patients with 416 tumors were analyzed. Colorectal metastases (CRLM) comprised 81.0% of tumors, hepatocellular carcinoma 8.4%, primary biliary cancer 1.7%, and non-colorectal metastases 8.9%. Median follow-up was 20.5 months. Local recurrence occurred in 33 tumors (7.9%) in 31 patients (17.6%). Recurrence rates increased with tumor size, at 1%, 9%, and 33% for tumors <1cm, 1-3cm,and >3cm respectively. On univariable analysis, local recurrence was higher with larger tumors (hazard ratio 2.05 per cm, p<0.001), perivascular (HR 3.71, p=0.001) or subcapsular position (HR 2.71, p=0.008), the 2.4GHz ablation system (HR 3.79, p=0.001), and biliary or non-CRLM histology (HR 2.47, p=0.036). On multivariable analysis, tumor size (p < 0.001) and perivascular position (p=0.045) remained significant independent predictors. Regional chemotherapy was associated with decreased local recurrence (HR 0.49, p=0.049). Overall survival at 4 years was 58% for CRLM and 79% for other pathology (p=0.36). Conclusion Microwave ablation of liver malignancies, either combined or not combined with liver resection, and selective regional and systemic therapy resulted in good long-term survival. Local recurrence rates were low with tumors less than 3cm in diameter, and those remote from vessels. PMID:25296639

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

    PubMed

    Dindar, Gokhan; Ustundag, Yucel; Karakan, Tarkan

    2014-07-21

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

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

    PubMed Central

    Dindar, Gokhan; Ustundag, Yucel; Karakan, Tarkan

    2014-01-01

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

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

    PubMed

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

    2014-10-01

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

  4. Estrogen and colorectal cancer incidence and mortality.

    PubMed

    Lavasani, Sayeh; Chlebowski, Rowan T; Prentice, Ross L; Kato, Ikuko; Wactawski-Wende, Jean; Johnson, Karen C; Young, Alicia; Rodabough, Rebecca; Hubbell, F Allan; Mahinbakht, Ali; Simon, Michael S

    2015-09-15

    The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer. In contrast, no difference in the incidence of colorectal cancer was seen in the Women's Health Initiative (WHI) randomized, placebo-controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow-up of 13.2 years. This study extends these findings by providing detailed analyses of the effects of estrogen alone on the histology, grade, and stage of colorectal cancer, relevant subgroups, and deaths from and after colorectal cancer. The WHI study was a randomized, double-blind, placebo-controlled trial involving 10,739 postmenopausal women with prior hysterectomy. Participants were assigned to conjugated equine estrogen at 0.625 mg/d (n = 5279) or a matching placebo (n = 5409). Rates of colorectal cancer diagnoses and deaths from and after colorectal cancer were assessed throughout the study. Colorectal cancer rates in the estrogen-alone and placebo groups were comparable: 0.14% and 0.12% per year, respectively (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.83-1.58; P = .43). Bowel screening examinations were comparable between the 2 groups throughout the study. The grade, stage, and location of colorectal cancer did not differ between the randomization groups. There were more colorectal cancer deaths in the estrogen-alone group (34 [0.05%] vs 24 [0.03%]; HR, 1.46, 95% CI, 0.86-2.46; P = .16), but the difference was not statistically significant. The colorectal cancer incidence was higher for participants with a history of colon polyp removal in the estrogen-alone group (0.23% vs 0.02%; HR, 13.47; nominal 95% CI, 1.76-103.0; P < .001). The use of estrogen alone in postmenopausal women with prior hysterectomy does not influence the incidence of colorectal cancer or deaths from or after colorectal cancer. A possibly higher risk of colorectal cancer in women with

  5. The Dutch surgical colorectal audit.

    PubMed

    Van Leersum, N J; Snijders, H S; Henneman, D; Kolfschoten, N E; Gooiker, G A; ten Berge, M G; Eddes, E H; Wouters, M W J M; Tollenaar, R A E M; Bemelman, W A; van Dam, R M; Elferink, M A; Karsten, Th M; van Krieken, J H J M; Lemmens, V E P P; Rutten, H J T; Manusama, E R; van de Velde, C J H; Meijerink, W J H J; Wiggers, Th; van der Harst, E; Dekker, J W T; Boerma, D

    2013-10-01

    In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated by the Dutch Institute for Clinical Auditing (DICA). This article illustrates key elements of the DSCA and results of three years of auditing. Key elements include: a leading role of the professional association with integration of the audit in the national quality assurance policy; web-based registration by medical specialists; weekly updated online feedback to participants; annual external data verification with other data sources; improvement projects. In two years, all Dutch hospitals participated in the audit. Case-ascertainment was 92% in 2010 and 95% in 2011. External data verification by comparison with the Netherlands Cancer Registry (NCR) showed high concordance of data items. Within three years, guideline compliance for diagnostics, preoperative multidisciplinary meetings and standardised reporting increased; complication-, re-intervention and postoperative mortality rates decreased significantly. The success of the DSCA is the result of effective surgical collaboration. The leading role of the ASN in conducting the audit resulted in full participation of all colorectal surgeons in the Netherlands. By integrating the audit into the ASNs' quality assurance policy, it could be used to set national quality standards. Future challenges include reduction of administrative burden; expansion to a multidisciplinary registration; and addition of financial information and patient reported outcomes to the audit data. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Survival rates and predictors of survival among colorectal cancer patients in a Malaysian tertiary hospital.

    PubMed

    Magaji, Bello Arkilla; Moy, Foong Ming; Roslani, April Camilla; Law, Chee Wei

    2017-05-18

    Colorectal cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death globally. It is the second most common cancer among both males and females in Malaysia. The economic burden of colorectal cancer is likely to increase over time owing to its current trend and aging population. Cancer survival analysis is an essential indicator for early detection and improvement in cancer treatment. However, there was a scarcity of studies concerning survival of colorectal cancer patients as well as its predictors. Therefore, we aimed to determine the 1-, 3- and 5-year survival rates, compare survival rates among ethnic groups and determine the predictors of survival among colorectal cancer patients. This was an ambidirectional cohort study conducted at the University Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia. All Malaysian citizens or permanent residents with histologically confirmed diagnosis of colorectal cancer seen at UMMC from 1 January 2001 to 31 December 2010 were included in the study. Demographic and clinical characteristics were extracted from the medical records. Patients were followed-up until death or censored at the end of the study (31st December 2010). Censored patients' vital status (whether alive or dead) were cross checked with the National Registration Department. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Log-rank test was used to compare the survival rates, while Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival. Among 1212 patients, the median survival for colorectal, colon and rectal cancers were 42.0, 42.0 and 41.0 months respectively; while the 1-, 3-, and 5-year relative survival rates ranged from 73.8 to 76.0%, 52.1 to 53.7% and 40.4 to 45.4% respectively. The Chinese patients had the lowest 5-year survival compared to Malay and Indian patients. Based on the 814

  7. Danish Colorectal Cancer Group Database

    PubMed Central

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

    2016-01-01

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

  8. 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.

  9. 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

  10. [Laparoscopic colectomy for colorectal carcinoma].

    PubMed

    Konishi, F; Kojima, M; Hoshino, T; Kanzaki, M

    2000-08-01

    Laparoscopic-assisted colectomy is considered to be a less invasive technique, and patients experience less pain and more rapid postoperative recovery. This operation has been indicated for large sessile adenomas or for early invasive carcinomas in Japan. The indications for this procedure in more advanced colorectal carcinomas is controversial. However, based on our experience with 130 cases, laparoscopic-assisted colectomy can be as curative as open colectomy provided that the patients are properly selected. In this review, the technical difficulties of this procedure are also discussed.

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

    PubMed

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

    2008-01-01

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

  12. The cytologic criteria of malignancy.

    PubMed

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

    2010-07-01

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

  13. Epidemiologic overview of malignant lymphoma.

    PubMed

    Huh, Jooryung

    2012-06-01

    Malignant lymphoma encompasses a wide variety of distinct disease entities. It is generally more common in developed countries and less common in developing countries. The East Asia region has one of the lowest incidence rates of malignant lymphoma. The incidence of malignant lymphoma around the world has been increasing at a rate of 3-4% over the last 4 decades, while some stabilization has been observed in developed countries in recent years. The reasons behind this lymphoma epidemic are poorly understood, although improving diagnostic accuracy, the recent AIDS epidemic, an aging world population and the increasing adoption of cancer-causing behaviors are suggested as contributing factors. Etiologies of malignant lymphoma include infectious agents, immunodeficiency, autoimmune disease, exposure to certain organic chemicals, and pharmaceuticals. The distribution of many subtypes exhibit marked geographic variations. Compared to the West, T/natural killer (NK) cell lymphomas (T/NK-cell lymphoma) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are relatively more common, whereas other B-cell lymphomas, particularly follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, are less common in Asia. Some subtypes of T/NK-cell lymphomas defined by Epstein-Barr virus association are predominantly Asian diseases, if not exclusively so. Both ethnic and environmental factors play roles in such diversity. In this review, we discuss the geographic distribution and etiology of malignant lymphoma, as well as the trend.

  14. Immunohistochemical Expression of PCNA and CD34 in Colorectal Adenomas and Carcinomas Using Specified Automated Cellular Image Analysis System: A Clinicopathologic Study

    PubMed Central

    Qasim, Ban J.; Ali, Hussam H.; Hussein, Alaa G.

    2012-01-01

    Background/Aim: To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters. Materials and Methods: The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 ΅m thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer). Results: PCNA expression was significantly increased in a sequence of normal mucosa–adenoma–carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma. Conclusion: PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic

  15. Familial aggregation of colorectal cancer in Egypt.

    PubMed

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

    1998-09-11

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

  16. Knowledge of colorectal cancer among older persons.

    PubMed

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

    1992-10-01

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

  17. Tailored telephone counseling increases colorectal cancer screening

    PubMed Central

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

    2015-01-01

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

  18. Colorectal smartphone apps: opportunities and risks.

    PubMed

    O'Neill, S; Brady, R R W

    2012-09-01

    The increased utilization of smartphones within the clinical environment together with connected applications (apps) provides opportunity for doctors, including coloproctologists, to integrate such technology into clinical practice. However, the reliability of unregulated medical apps has recently been called into question. Here, we review contemporary medical apps specifically themed towards colorectal diseases and assess levels of medical professional involvement in their design and content. The most popular smartphone app stores (iPhone, Android, Blackberry, Nokia, Windows and Samsung) were searched for colorectal disease themed apps, using the disease terms colorectal cancer, Crohn's disease, ulcerative colitis, diverticulitis, haemorrhoids, anal fissure, bowel incontinence and irritable bowel syndrome. A total of 68 individual colorectal themed apps were identified, amongst which there were five duplicates. Only 29% of colorectal apps had had customer satisfaction ratings and 32% had named medical professional involvement in their development or content. The benefits of apps are offset by lack of colorectal specification. There is little medical professional involvement in their design. Increased regulation is required to improve accountability of app content. © 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

  19. Primary colorectal adenocarcinoma metastatic to the breast: case report and review of nineteen cases.

    PubMed

    Shackelford, Rodney E; Allam-Nandyala, Pushpa; Bui, Marilyn M; Kiluk, John V; Esposito, Nicole Nicosia

    2011-01-01

    Metastases to the breast from extramammary primaries are uncommon and account for 0.5-6% of all breast malignancies (Georgiannos et al., 2001, and Vizcaíno et al., 2001). Malignant melanoma, lymphoma, and lung and gastric carcinomas are the most frequently encountered nonmammary metastases to the breast in adults (Georgiannos et al., 2001, and Chaignaud et al., 1994). Primary colorectal adenocarcinoma (CRC) metastatic to the breast is extremely rare, with the medical literature having only 19 recorded cases. Typically CRC metastatic to the breast is indicative of widely disseminated disease and a poor prognosis. Here we present a case of poorly differentiated colon cancer metastatic to the breast and review the current literature on this rare event.

  20. Cyclosporin-A associated malignancy

    PubMed Central

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

    2007-01-01

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

  1. XYY male and hematologic malignancy.

    PubMed

    Oguma, N; Shigeta, C; Kamada, N

    1996-09-01

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

  2. Eosinophilic Dermatosis of Hematologic Malignancy.

    PubMed

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

    Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    PubMed Central

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

    2010-01-01

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

  4. Colorectal Cancer: Genetics is Changing Everything.

    PubMed

    Obuch, Joshua C; Ahnen, Dennis J

    2016-09-01

    Cancer is fundamentally a genetic disease caused by mutational or epigenetic alterations in DNA. There has been a remarkable expansion of the molecular understanding of colonic carcinogenesis in the last 30 years and that understanding is changing many aspects of colorectal cancer care. It is becoming increasingly clear that there are genetic subsets of colorectal cancer that have different risk factors, prognosis, and response to treatment. This article provides a general update on colorectal cancer and highlights the ways that genetics is changing clinical care. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Management of colorectal cancer and diabetes

    PubMed Central

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

    2014-01-01

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

  6. Potential study perspectives on mechanisms and correlations between adiposity and malignancy.

    PubMed

    Lu, Kun; Song, Xiao-Lian; Han, Shi-Long; Wang, Chang-Hui; Zhong, Ni; Qi, Li-Feng

    2014-01-01

    Adiposity is a well-recognized risk factor of type 2 diabetes and cardiovascular disease, and recently there is increasing evidence that excess body weight is an avoidable cause of cancer, including gastrointestinal, endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal malignancies. The mechanisms whereby adiposity is associated with tumor development remains not well understood. There are some most studied hypothesized mechanisms such as, high levels of insulin and free levels of insulin-like growth factors, sex hormones, adipocytokines, and inflammatory cytokines, adiposity-induced hypoxia, and so on. The potential mechanisms and conclusions in adiposity associated with increased risk for developing malignancy, and the underlying cellular and molecular mechanisms will be studied very well in the near future.

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

    PubMed Central

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

    2016-01-01

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

  8. A hierarchical classifier based on human blood plasma fluorescence for non-invasive colorectal cancer screening.

    PubMed

    Soares, Felipe; Becker, Karin; Anzanello, Michel J

    2017-09-19

    Colorectal cancer (CRC) a leading cause of death by cancer, and screening programs for its early identification are at the heart of the increasing survival rates. To motivate population participation, non-invasive, accurate, scalable and cost-effective diagnosis methods are required. Blood fluorescence spectroscopy provides rich information that can be used for cancer identification. The main challenges in analyzing blood fluorescence data for CRC classification are related to its high dimensionality and inherent variability, especially when analyzing a small number of samples. In this paper, we present a hierarchical classification method based on plasma fluorescence to identify not only CRC, but also adenomas and other non-malignant colorectal findings that may require further medical investigation. A feature selection algorithm is proposed to deal with the high dimensionality and select discriminant fluorescence wavelengths. These are used to train a binary support vector machine (SVM) in the first level to identify the CRC samples. The remaining samples are then presented to a one-class SVM trained on healthy subjects to detect deviant samples, and thus non-malignant findings. This hierarchical design, together with the one class-SVM, aims to reduce the effects of small samples and high variability. Using a dataset analyzed in previous studies comprised of 12,341 wavelengths, we achieved much superior results. Sensitivity and specificity are 0.87 and 0.95 for CRC detection, and 0.60 and 0.79 for non-malignant findings, respectively. Compared to related work, the proposed method presented a better accuracy, required fewer features, and provides a unified approach that expands CRC detection to non-malignant findings. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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.

  10. Second Malignant Neoplasms Following Radiotherapy

    PubMed Central

    Kumar, Sanath

    2012-01-01

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

  11. [Kinase inhibitors against hematological malignancies].

    PubMed

    Tojo, Arinobu

    2014-06-01

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

  12. The colorectal microRNAome

    PubMed Central

    Cummins, Jordan M.; He, Yiping; Leary, Rebecca J.; Pagliarini, Ray; Diaz, Luis A.; Sjoblom, Tobias; Barad, Omer; Bentwich, Zvi; Szafranska, Anna E.; Labourier, Emmanuel; Raymond, Christopher K.; Roberts, Brian S.; Juhl, Hartmut; Kinzler, Kenneth W.; Vogelstein, Bert; Velculescu, Victor E.

    2006-01-01

    MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. These studies suggest that the human genome contains many more miRNAs than currently identified and provide an approach for the large-scale experimental cloning of novel human miRNAs in human tissues. PMID:16505370

  13. [Colonoscopies for colorectal cancer screening].

    PubMed

    Bessa Caserras, Xavier

    2014-09-01

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

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

    PubMed

    Jedrychowski, Wieslaw; Maugeri, Umberto

    2009-01-01

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

  15. EZH2 expression is a prognostic biomarker in patients with colorectal cancer treated with anti-EGFR therapeutics.

    PubMed

    Yamamoto, Itaru; Nosho, Katsuhiko; Kanno, Shinichi; Igarashi, Hisayoshi; Kurihara, Hiroyoshi; Ishigami, Keisuke; Ishiguro, Kazuya; Mitsuhashi, Kei; Maruyama, Reo; Koide, Hideyuki; Okuda, Hiroyuki; Hasegawa, Tadashi; Sukawa, Yasutaka; Okita, Kenji; Takemasa, Ichiro; Yamamoto, Hiroyuki; Shinomura, Yasuhisa; Nakase, Hiroshi

    2017-03-14

    The polycomb group protein enhancer of zeste homolog 2 (EZH2) is a methyltransferase that suppresses microRNA-31 (miR-31) in various human malignancies including colorectal cancer. We recently suggested that miR-31 regulates the signaling pathway downstream of epidermal growth factor receptor (EGFR) in colorectal cancer. Therefore, we conducted this study for assessing the relationship between EZH2 expression and clinical outcomes in patients with colorectal cancer treated with anti-EGFR therapeutics. We immunohistochemically evaluated EZH2 expression and assessed miR-31 and gene mutations [KRAS (codon 61/146), NRAS (codon 12/13/61), and BRAF (codon 600)] in 109 patients with colorectal cancer harboring KRAS (codon 12/13) wild-type. We also evaluated the progression-free survival (PFS) and overall survival (OS). In the result, low EZH2 expression was significantly associated with shorter PFS (log-rank test: P = 0.023) and OS (P = 0.036) in patients with colorectal cancer. In the low-miR-31-expression group and the KRAS (codon 61/146), NRAS, and BRAF wild-type groups, a significantly shorter PFS (P = 0.022, P = 0.039, P = 0.021, and P = 0.036, respectively) was observed in the EZH2 low-expression groups than in the high-expression groups. In the multivariate analysis, low EZH2 expression was associated with a shorter PFS (P = 0.046), independent of the mutational status and miR-31. In conclusion, EZH2 expression was associated with survival in patients with colorectal cancer who were treated with anti-EGFR therapeutics. Moreover, low EZH2 expression was independently associated with shorter PFS in patients with cancer, suggesting that EZH2 expression is a useful additional prognostic biomarker for anti-EGFR therapy.

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

    PubMed

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

    2015-02-15

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

  17. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

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

  18. 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 n