Chan, Andrew T.; Giovannucci, Edward L.
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
Tárraga López, Pedro J; Albero, Juan Solera; Rodríguez-Montes, José Antonio
INTRODUCTION Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. Colorectal cancer (CRC) is the third most frequent cancer in men, after lung and prostate cancer, and is the second most frequent cancer in women after breast cancer. It is also the third cause of death in men and women separately, and is the second most frequent cause of death by cancer if both genders are considered together. CRC represents approximately 10% of deaths by cancer. Modifiable risk factors of CRC include smoking, physical inactivity, being overweight and obesity, eating processed meat, and drinking alcohol excessively. CRC screening programs are possible only in economically developed countries. However, attention should be paid in the future to geographical areas with ageing populations and a western lifestyle.19,20 Sigmoidoscopy screening done with people aged 55–64 years has been demonstrated to reduce the incidence of CRC by 33% and mortality by CRC by 43%. OBJECTIVE To assess the effect on the incidence and mortality of CRC diet and lifestyle and to determine the effect of secondary prevention through early diagnosis of CRC. METHODOLOGY: A comprehensive search of Medline and Pubmed articles related to primary and secondary prevention of CRC and subsequently, a meta-analysis of the same blocks are performed. RESULTS 225 articles related to primary or secondary prevention of CRC were retrieved. Of these 145 were considered valid on meta-analysis: 12 on epidemiology, 56 on diet and lifestyle, and over 77 different screenings for early detection of CRC. Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. There is no doubt whatsoever which environmental factors, probably diet, may account for these cancer rates. Excessive alcohol consumption and cholesterol-rich diet are associated with a high risk of colon cancer. A diet poor in folic acid and vitamin B6 is also
Martínez, María Elena
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
Early detection of cancer through screening is an important step in decreasing both morbidity and mortality. Likewise, specific modifiable lifestyle behaviors are associated with reduced risk of colorectal cancer. Lifestyle practices have also been shown to maximize health after the primary treatmen...
Kuipers, Ernst J.; Grady, William M.; Lieberman, David; Seufferlein, Thomas; Sung, Joseph J.; Boelens, Petra G.; van de Velde, Cornelis J. H.; Watanabe, Toshiaki
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
Bae, Susie; Asadi, Muslim; Jones, Ian; McLaughlin, Stephen; Bui, Andrew; Steele, Malcolm; Tie, Jeanne; Gibbs, Peter
Oncology literature is increasingly recognizing prevalence of second primary cancers including several longitudinal studies showing an increased risk of colorectal cancer following a prostate cancer diagnosis. A retrospective study was conducted to examine the relationship between prior prostate cancer diagnoses and subsequent colorectal cancer diagnoses. A multi-centre prospective colorectal cancer registry was queried for patients with a prior history of prostate, breast or lung cancer. Characteristics of these patients were compared to patients with colorectal cancer and no prior cancer history. Of 4660 cases of colorectal cancer diagnosed between 1998 and 2011, 2665 (57.2%) were male, median age was 68 years. For patients with a history of prostate cancer (n = 111), breast cancer (n = 61) and lung cancer (n = 23), the great majority of subsequent colorectal cancer diagnoses occurred in the initial 2 to 4 years after the first cancer diagnosis. This was accompanied by an increased rate of asymptomatic colorectal cancer at presentation, due to both screen detected and incidental cancer diagnoses. There was no clear relationship between any prostate cancer treatment and subsequent colorectal cancer risk, location or timing. In the modern era, there is an increased rate of colorectal cancer diagnosis in years shortly following another common cancer history. This is consistently seen across different primary tumour streams including prostate, breast and lung cancers and in part contributed by screen detected and incidental colorectal cancer diagnoses. Future studies should consider this potential confounding factor when asserting an increased rate of colorectal cancer as a second primary cancer. © 2013 The Authors. ANZ Journal of Surgery © 2013 Royal Australasian College of Surgeons.
... 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 ...
Jayasekara, Harindra; Reece, Jeanette C; Buchanan, Daniel D; Rosty, Christophe; Dashti, S Ghazaleh; Ait Ouakrim, Driss; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Giles, Graham G; Ahnen, Dennis J; Lowery, Jan; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Parry, Susan; Jenkins, Mark A; Win, Aung Ko
Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour-related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997-2012, except those identified as high-risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person-years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30-5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80-6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC.
Crosara Teixeira, Marcela; Braghiroli, Maria Ignez; Sabbaga, Jorge; Hoff, Paulo M
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
Takorov, Ivelin; Lukanova, Tsonka; Atanasov, Boiko; Dzharov, Georgi; Djurkov, Ventzeslav; Odisseeva, Evelina; Vladov, Nikola
Backgrounds/Aims Synchronous liver metastases (SLMs) are found in 15-25% of patients at the time of diagnosis with colorectal cancer, which is limited to the liver in 30% of patients. Surgical resection is the most effective and potentially curative therapy for metastatic colorectal carcinoma (CRC) of the liver. The comparison of simultaneous resection of primary CRC and synchronous liver metastases with staged resections is the subject of debate with respect to morbidity. Laparoscopic surgery improves postoperative recovery, diminishes postoperative pain, reduces wound infections, shortens hospitalization, and yields superior cosmetic results, without compromising the oncological outcome. The aim of this study is therefore to evaluate our initial experience with simultaneous laparoscopic resection of primary CRC and SLM. Methods Currently, laparoscopic resection of primary CRC is performed in more than 53% of all patients in our surgical department. Twenty-six patients with primary CRC and a clinical diagnosis of SLM underwent combined laparoscopic colorectal and liver surgery. Six of them underwent laparoscopic colorectal resection combined with major laparoscopic liver resection. Results The surgical approaches were total laparoscopic (25 patients) or hybrid technique (1 patients). The incision created for the extraction of the specimen varied between 5 and 8cm. The median operation time was 223 minutes (100 to 415 min.) with a total blood loss of 180 ml (100-300 ml). Postoperative hospital stay was 6.8 days (6-14 days). Postoperative complications were observed in 6 patients (22.2%). Conclusions Simultaneous laparoscopic colorectal and liver resection appears to be safe, feasible, and with satisfying short-term results in selected patients with CRC and SLM. PMID:28261695
... 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 ...
Yano, Elizabeth M; Soban, Lynn M; Parkerton, Patricia H; Etzioni, David A
To identify primary care practice characteristics associated with colorectal cancer (CRC) screening performance, controlling for patient-level factors. Primary care director survey (1999-2000) of 155 VA primary care clinics linked with 38,818 eligible patients' sociodemographics, utilization, and CRC screening experience using centralized administrative and chart-review data (2001). Practices were characterized by degrees of centralization (e.g., authority over operations, staffing, outside-practice influence); resources (e.g., sufficiency of nonphysician staffing, space, clinical support arrangements); and complexity (e.g., facility size, academic status, managed care penetration), adjusting for patient-level covariates and contextual factors. Chart-based evidence of CRC screening through direct colonoscopy, sigmoidoscopy, or consecutive fecal occult blood tests, eliminating cases with documented histories of CRC, polyps, or inflammatory bowel disease. After adjusting for sociodemographic characteristics and health care utilization, patients were significantly more likely to be screened for CRC if their primary care practices had greater autonomy over the internal structure of care delivery (p<.04), more clinical support arrangements (p<.03), and smaller size (p<.001). Deficits in primary care clinical support arrangements and local autonomy over operational management and referral procedures are associated with significantly lower CRC screening performance. Competition with hospital resource demands may impinge on the degree of internal organization of their affiliated primary care practices.
Norwati, Daud; Harmy, Mohamed Yusoff; Norhayati, Mohd Noor; Amry, Abdul Rahim
The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics.
Lao, Victoria Valinluck; Welcsh, Piri; Luo, Yanxin; Carter, Kelly T; Dzieciatkowski, Slavomir; Dintzis, Suzanne; Meza, Jane; Sarvetnick, Nora E; Monnat, Raymond J; Loeb, Lawrence A; Grady, William M
Deregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Altered expression levels of these enzymes in colorectal cancer (CRC) may influence the response of the cancers to irinotecan. Thus, we assessed RECQ helicase (WRN, BLM, RECQL, RECQL4, and RECQL5) expression in primary CRCs, matched normal colon, and CRC cell lines. We found that BLM and RECQL4 mRNA levels are significantly increased in CRC (P = .0011 and P < .0001, respectively), whereas RECQL and RECQL5 are significantly decreased (P = .0103 and P = .0029, respectively). RECQ helicase expression patterns varied between specific molecular subtypes of CRCs. The mRNA and protein expression of the majority of the RECQ helicases was closely correlated, suggesting that altered mRNA expression is the predominant mechanism for deregulated RECQ helicase expression. Immunohistochemistry localized the RECQ helicases to the nucleus. RECQ helicase expression is altered in CRC, suggesting that RECQ helicase expression has potential to identify CRCs that are susceptible to specific chemotherapeutic agents.
Background Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers. Methods We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The Kaplan–Meier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar period–specific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population. Results Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97). Conclusion Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers
Pajares, José A; Perea, José
Colorectal carcinoma (CRC) is one of the most frequent cancers. Along the surface of the large bowel, several foci of CRC may appear simultaneously or over the time. The development of at least two different tumours has been defined as multiple primary CRC (MPCRC): When more than one tumour is diagnosed at the same time, it is known as synchronous CRC (SCRC), while when a second neoplasm is diagnosed some time after the resection and/or diagnosis of the first lesion, it is called metachronous CRC (MCRC). Multiple issues can promote the development of MPCRC, ranging from different personal factors, such as environmental exposure, to familial predisposition due to hereditary factors. However, most studies do not distinguish this dichotomy. High- and low-pentrance genetic variants are involved in MPCRC. An increased risk for MPCRC has been described in Lynch syndrome, familial adenomatous polyposis, and serrated polyposis. Non-syndromic familial CRCs should also be considered as risk factors for MPCRC. Environmental factors can promote damage to colon mucosae that enable the concurrence of MPCRC. Epigenetics are thought to play a major role in the carcinogenesis of sporadic MPCRC. The methylation state of the DNA depends on multiple environmental factors (e.g., smoking and eating foods cooked at high temperatures), and this can contribute to increasing the MPCRC rate. Certain clinical features may also suggest individual predisposition for MPCRC. Different etiopathogenic factors are suspected to be involved in SCRC and MCRC, and different familial vs individual factors may be implicated. MCRC seems to follow a familial pattern, whereas individual factors are more important in SCRC. Further studies must be carried out to know the molecular basis of risks for MPCRC in order to modify, if necessary, its clinical management, especially from a preventive point of view. PMID:26688706
Muliira, Joshua Kanaabi; D'Souza, Melba Sheila
Colorectal cancer is the fourth most common type of cancer in the world and every year it is responsible for 610,000 deaths worldwide. The aim of this review was to examine the effectiveness of patient navigator interventions towards enhancing uptake of colorectal cancer screening in primary care settings. Electronic databases such as PubMed, CINHAL, Google Scholar and SCOPUS were searched to retrieve articles reporting on primary studies applying any patient navigator intervention to promote uptake of colorectal cancer screening in eligible patients. The search yielded 292 articles and 15 met the inclusion criteria. All 15 studies were conducted in urban settings located in the USA. The findings of the review show that patient navigator interventions can increase colorectal cancer screening rates in diverse primary care settings. Patient navigator interventions were most effective in patients who belong to minority groups and enhanced uptake of colorectal cancer screening with rates ranging 11-91%. There is a need for further studies to examine the effectiveness of patient navigator interventions in rural populations and other countries. Such studies will help us to clearly characterize the effectiveness of patient navigator interventions. © 2015 Japan Academy of Nursing Science.
Silberhumer, Gerd R; Paty, Philip B; Denton, Brian; Guillem, Jose; Gonen, Mithat; Araujo, Raphael L C; Nash, Garret M; Temple, Larissa K; Allen, Peter J; DeMatteo, Ronald P; Weiser, Martin R; Wong, W Douglas; Jarnagin, William R; D'Angelica, Michael I; Fong, Yuman
Twenty-five percent of patients with colorectal cancer present with simultaneous liver metastasis. Complete resection is the only potential curative treatment. Due to improvements in operative and perioperative management, simultaneous liver and colon resections are an accepted procedure at specialized centers for selected patients. Nevertheless, little is known about the long-term, oncologic results of simultaneous operative procedures compared with those of staged operations. Patients with colorectal cancer and simultaneous liver metastases presenting for complete resection at a tertiary cancer center were identified. Patients who received the primary colon resection at an outside institution were excluded from analysis. Between 1984 and 2008, 429 patients underwent operative treatment for colorectal cancer with simultaneous liver metastasis. Of these, 320 (75%) had simultaneous resection and 109 had staged resection. There was no difference in the distribution of primary tumor locations between the 2 groups. Mean size of the hepatic metastases was significantly greater in the staged group (median 4 cm vs 2.5 cm; P < .01). Neither disease-free nor overall survival differed significantly between the 2 treatment strategies. The extent of the liver procedure (more than 3 segments) was identified as a risk factor for decreased disease-free and overall survival (both P < .01). Simultaneous liver and colorectal resections for metastatic colorectal cancer are associated with similar long-term cancer outcome compared with staged procedures. Copyright © 2016 Elsevier Inc. All rights reserved.
Zygoń, Justyna; Szajewski, Mariusz; Kruszewski, Wiesław Janusz; Rzepko, Robert
Angiogenesis in the primary tumor is known to be necessary for tumor progression in adenocarcinomas of the colon. However, whether angiogenesis in the primary tumors of patients with colorectal cancer affects their prognosis has yet to be fully elucidated. The aim of the present study was to assess the association between selected pathoclinical parameters and overall survival of resectable colorectal cancer patients with the expression of angiogenesis-promoting factors, including vascular endothelial growth factor (VEGF) and Fms-like tyrosine kinase receptor (Flt-1), and microvessel density (MVD) in the primary tumor. VEGF and Flt-1 expression were assessed, as well as MVD (with anti-CD34) by immunohistochemistry in 139 archived primary colorectal cancer tissue samples. These results were compared with the overall survival of the patients and potential prognostic pathoclinical parameters. A higher MVD in the tumors expressing Flt-1 (P=0.04) was identified. However, there was no correlation between the pathoclinical parameters of colon cancer and Flt-1 expression, VEGF expression, or MVD in the tumor. Furthermore, the intensity of VEGF expression, Flt-1 expression and tumor MVD did not correlate with the overall survival of the patients. Therefore, although increased expression of VEGF and Flt-1 was correlated with an increased expression of MVD in the primary tumors of resectable colorectal cancer patients, these factors were not correlated with prognostic pathoclinical factors and overall survival. PMID:28357103
Chan, Pak Wo Webber; Ngu, Jing Hieng; Poh, Zhongxian; Soetikno, Roy
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.
Chan, Pak Wo Webber; Ngu, Jing Hieng; Poh, Zhongxian; Soetikno, Roy
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
Herszényi, László; Juhász, Márk; Prónai, László; Tulassay, Zsolt
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.
Benito-Aracil, Llúcia; Binefa-Rodriguez, Gemma; Milà-Diaz, Núria; Lluch-Canut, M Teresa; Puig-Llobet, Montse; Garcia-Martinez, Montse
To evaluate the impact of an intervention in primary care professionals on their current knowledge about colorectal cancer screening, subsequent surveillance recommendations and referral strategies. Cluster randomized controlled trial. Primary Care Centers in L'Hospitalet de Llobregat (Barcelona). Primary Care Professionals (doctors and nurses). Training session in six of the 12 centers (randomly selected) about the colorrectal cancer screening program, and three emails with key messages. Professionals and centers characteristics and two contextual variables; involvement of professionals in the screening program; information about colorectal cancer knowledge, risk factors, screening procedures, surveillance recommendations and referral strategies. The total score mean on the first questionnaire was 8.07 (1.38) and the second 8.31 (1.39). No statistically significant differences between the intervention and control groups were found, however, in 9 out of 11 questions the percentage of correct responses was increased in the intervention group, mostly related to the surveillance after the diagnostic examination. The intervention improves the percentage of correct answers, especially in those in which worst score obtained in the first questionnaire. This study shows that professionals are familiar with colorectal cancer screening, but there's a need to maintain frequent communication in order to keep up to date the information related to the colorectal cancer screening. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.
Ramos, Maria; Taltavull, Maria; Piñeiro, Pilar; Nieto, Raquel; Llagostera, Maria
To describe the cultural, social and gender features that determine attitudes to colorectal cancer screening in a target group of patients aged 50 to 69 years old in the primary health care setting. We performed a qualitative ethnographic study from a gender perspective. Participants consisted of men and women aged 50 to 69 years old in the Balearic Islands and Barcelona. Group discussion and a field diary were used. The key element was diagnosis at an early stage. Until recently, cancer was considered an incurable disease but is currently perceived as a serious health problem that can be cured if diagnosed promptly. The participants requested more information on cancer and felt they were at risk, mainly because of their age. Men tended to pay attention to symptoms while women tended to ignore them. Attitudes to colorectal cancer screening were generally positive, even to colonoscopy. Some barriers to screening were identified in women, such as a fear of having cancer. The opportunity for early diagnosis is the key element in promoting participation in a colorectal cancer screening program. Perceptions-and hence willingness to participate in screening-differ between men and women. Factors to be taken into account in the design of population-based colorectal cancer programs are health concerns in men and fear of a cancer diagnosis in women. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.
Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan
Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual
Yazici, Pinar; Onder, Akin; Benlice, Cigdem; Yigitbas, Hakan; Kahramangil, Bora; Tasci, Yunus; Aksoy, Erol; Aucejo, Federico; Quintini, Cristiano; Miller, Charles; Berber, Eren
Background The aim of this study is to compare the perioperative and oncologic outcomes of open and laparoscopic approaches for concomitant resection of synchronous colorectal cancer and liver metastases. Methods Between 2006 and 2015, all patients undergoing combined resection of primary colorectal cancer and liver metastases were included in the study (n=43). Laparoscopic and open groups were compared regarding clinical, perioperative and oncologic outcomes. Results There were 29 patients in the open group and 14 patients in the laparoscopic group. The groups were similar regarding demographics, comorbidities, histopathological characteristics of the primary tumor and liver metastases. Postoperative complication rate (44.8% vs. 7.1%, P=0.016) was higher, and hospital stay (10 vs. 6.4 days, P=0.001) longer in the open compared to the laparoscopic group. Overall survival (OS) was comparable between the groups (P=0.10); whereas, disease-free survival (DFS) was longer in laparoscopic group (P=0.02). Conclusions According to the results, in patients, whose primary colorectal cancer and metastatic liver disease was amenable to a minimally invasive resection, a concomitant laparoscopic approach resulted in less morbidity without compromising oncologic outcomes. This suggests that a laparoscopic approach may be considered in appropriate patients by surgeons with experience in both advanced laparoscopic liver and colorectal techniques. PMID:28861371
Choi, Dong-Sic; Choi, Do-Young; Hong, Bok Sil; Jang, Su Chul; Kim, Dae-Kyum; Lee, Jaewook; Kim, Yoon-Keun; Kim, Kwang Pyo; Gho, Yong Song
Cancer cells actively release extracellular vesicles (EVs), including exosomes and microvesicles, into surrounding tissues. These EVs play pleiotropic roles in cancer progression and metastasis, including invasion, angiogenesis, and immune modulation. However, the proteomic differences between primary and metastatic cancer cell-derived EVs remain unclear. Here, we conducted comparative proteomic analysis between EVs derived from human primary colorectal cancer cells (SW480) and their metastatic derivatives (SW620). Using label-free quantitation, we identified 803 and 787 proteins in SW480 EVs and SW620 EVs, respectively. Based on comparison between the estimated abundance of EV proteins, we identified 368 SW480 EV-enriched and 359 SW620 EV-enriched proteins. SW480 EV-enriched proteins played a role in cell adhesion, but SW620 EV-enriched proteins were associated with cancer progression and functioned as diagnostic indicators of metastatic cancer; they were overexpressed in metastatic colorectal cancer and played roles in multidrug resistance. As the first proteomic analysis comparing primary and metastatic cancer-derived EVs, this study increases our understanding of the pathological function of EVs in the metastatic process and provides useful biomarkers for cancer metastasis.
Redmond, Jennifer; Vanderpool, Robin; McClung, Rebecca
Background: Patients are more likely to be screened for colorectal cancer if it is recommended by a health care provider. Therefore, it is imperative that providers have access to the latest screening guidelines. Purpose: This practice-based project sought to identify Kentucky primary care providers' preferred sources and methods of receiving…
Redmond, Jennifer; Vanderpool, Robin; McClung, Rebecca
Background: Patients are more likely to be screened for colorectal cancer if it is recommended by a health care provider. Therefore, it is imperative that providers have access to the latest screening guidelines. Purpose: This practice-based project sought to identify Kentucky primary care providers' preferred sources and methods of receiving…
... 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 ( ...
Hillyer, Grace Clarke; Jensen, Christopher D; Zhao, Wei K; Neugut, Alfred I; Lebwohl, Benjamin; Tiro, Jasmin A; Kushi, Lawrence H; Corley, Douglas A
For some patients, positive cancer screening test results can be a stressful experience that can affect future screening compliance and increase the use of health care services unrelated to medically indicated follow-up. Among 483,216 individuals aged 50 to 75 years who completed a fecal immunochemical test to screen for colorectal cancer at a large integrated health care setting between 2007 and 2011, the authors evaluated whether a positive test was associated with a net change in outpatient primary care visit use within the year after screening. Multivariable regression models were used to evaluate the relationship between test result group and net changes in primary care visits after fecal immunochemical testing. In the year after the fecal immunochemical test, use increased by 0.60 clinic visits for patients with true-positive results. The absolute change in visits was largest (3.00) among individuals with positive test results who were diagnosed with colorectal cancer, but significant small increases also were found for patients treated with polypectomy and who had no neoplasia (0.36) and those with a normal examination and no polypectomy performed (0.17). Groups of patients who demonstrated an increase in net visit use compared with the true-negative group included patients with true-positive results (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.54-1.66), and positive groups with a colorectal cancer diagnosis (OR, 7.19; 95% CI, 6.12-8.44), polypectomy/no neoplasia (OR, 1.37; 95% CI, 1.27-1.48), and normal examination/no polypectomy (OR, 1.24; 95% CI, 1.18-1.30). Given the large size of outreach programs, these small changes can cumulatively generate thousands of excess visits and have a substantial impact on total health care use. Therefore, these changes should be included in colorectal cancer screening cost models and their causes investigated further. Cancer 2017;123:3744-3753. © 2017 American Cancer Society. © 2017 American Cancer Society.
Yarom, Nirit; Marginean, Celia; Moyana, Terence; Gorn-Hondermann, Ivan; Birnboim, H Chaim; Marginean, Horia; Auer, Rebecca C; Vickers, Michael; Asmis, Timothy R; Maroun, Jean; Jonker, Derek
Previous studies indicate that drugs targeting the Epidermal Growth Factor Receptor (EGFR) signaling pathways can induce objective responses, prolong time to progression and improve survival of patients with metastatic colorectal cancer (mCRC). EGFR expression in the primary tumour may not predict response to these agents and data is conflicting regarding the correlation of EGFR expression in the primary tumour with the metastatic site. In other tumour sites, the presence of EGFR mutations was associated with efficacy in a subset of patients. The goal of this study is to correlate tumour EGFR expression between primary and liver metastatic sites, and to assess the mutational status in the EGFR kinase domain. This is a single center retrospective study of patients who underwent surgical resection of CRC, for whom paired paraffin-embedded tissue blocks of primary tumours and resected liver metastases were available. EGFR immunostaining and mutation analyses were preformed. Fifty six paired colorectal primaries and metastases were available for analysis. EGFR was detectable in 96.6% of the primary samples and in 89.7% of the metastatic samples. Perfect concordance in the intensity score between the primary and the metastases was found in 46.5% of the cases. While individual pairs were poorly concordant for intensity, the proportion of primaries with intense staining was similar to the proportion with intense staining in the metastatic samples. Overall survival did not correlate with either EGFR expression in the primary tumour, or with EGFR expression in the metastasis. There were 2 cases with mutations in the EGFR kinase domain. Both mutations were found in exon21 C>T. In this analysis, EGFR expression in the primary tumor site was not predictive of its level in the metastasis. EGFR expression levels in the primaries and in the metastases do not appear to be useful prognostic markers.
Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.
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.
Borowski, D W; Cawkwell, S; Zaidi, S M A; Toward, M; Maguire, N; Gill, T S
The reasons for pre-hospital delay of the diagnosis of cancer are multifactorial, but include a physician-related component. Urgent cancer pathways and direct-to-test approaches have been implemented, but the emergency presentation of colorectal cancer (CRC) remains little changed over recent years. We examined the variability between primary care providers in referral patterns and its effect on outcome. A retrospective analysis was performed of a prospectively maintained database for 2009-2014 in a UK district hospital providing bowel cancer screening and tertiary rectal cancer services. Of 1145 CRC patients, 937 (81.8%) were diagnosed with a symptomatic cancer; 229/937 (24.4%) initially presented as an emergency. Between 44 primary care providers, emergency presentation varied between 8.3% and 57.1%. Patients of providers with high levels of emergency presentations (HV) had more advanced cancers than those of providers with medium (MV) or low levels (LV) [103/253 (40.7%), 154/461 (33.4%), 65/223 (29.1%); P = 0.025] and a lower 3-year overall survival (50.2%, 57.8%, 65.6%; P = 0.013), but with no difference in case-mix or deprivation levels. In adjusted analysis, this difference remained significant (advanced disease, OR 1.663, P = 0.011; 3-year hazard ratio 1.479, P = 0.010; comparing HV with LV). Conversely, elective suspected cancer referrals were less often used amongst diagnosed cancers [LV 136/223 (61.0%), MV 228/461 (49.5%), HV 114/253 (45.1%), P < 0.001] with limited evidence for a more selective approach in the use of the 2-week rule amongst all 2-week rule referrals [LV 136/2508 (5.4%); MV 228/4239 (5.4%); HV 115/1526 (7.8%); positive cancer diagnosis, P = 0.005]. Significant variability in emergency presentation of CRC requires local audit and examination of the reasons for delay in diagnosis and targeted measures to improve performance in non-emergency referral pathways. Colorectal Disease © 2016 The Association of Coloproctology of Great
Ströhle, Alexander; Maike, Wolters; Hahn, Andreas
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
Mounce, Luke T A; Price, Sarah; Valderas, Jose M; Hamilton, William
Pre-existing non-cancer conditions may complicate and delay colorectal cancer diagnosis. Incident cases (aged ⩾40 years, 2007-2009) with colorectal cancer were identified in the Clinical Practice Research Datalink, UK. Diagnostic interval was defined as time from first symptomatic presentation of colorectal cancer to diagnosis. Comorbid conditions were classified as 'competing demands' (unrelated to colorectal cancer) or 'alternative explanations' (sharing symptoms with colorectal cancer). The association between diagnostic interval (log-transformed) and age, gender, consultation rate and number of comorbid conditions was investigated using linear regressions, reported using geometric means. Out of the 4512 patients included, 72.9% had ⩾1 competing demand and 31.3% had ⩾1 alternative explanation. In the regression model, the numbers of both types of comorbid conditions were independently associated with longer diagnostic interval: a single competing demand delayed diagnosis by 10 days, and four or more by 32 days; and a single alternative explanation by 9 days. For individual conditions, the longest delay was observed for inflammatory bowel disease (26 days; 95% CI 14-39). The burden and nature of comorbidity is associated with delayed diagnosis in colorectal cancer, particularly in patients aged ⩾80 years. Effective clinical strategies are needed for shortening diagnostic interval in patients with comorbidity.
In a randomized phase III trial, the addition of the targeted therapy cetuximab to oxaliplatin and fluoropyrimidine chemotherapy did not prolong survival or time to disease progression of patients with advanced colorectal cancer.
Guiriguet, Carolina; Muñoz-Ortiz, Laura; Burón, Andrea; Rivero, Irene; Grau, Jaume; Vela-Vallespín, Carmen; Vilarrubí, Mercedes; Torres, Miquel; Hernández, Cristina; Méndez-Boo, Leonardo; Toràn, Pere; Caballeria, Llorenç; Macià, Francesc; Castells, Antoni
Participation rates in colorectal cancer screening are below recommended European targets. To evaluate the effectiveness of an alert in primary care electronic medical records (EMRs) to increase individuals' participation in an organised, population-based colorectal cancer screening programme when compared with usual care. Cluster randomised controlled trial in primary care centres of Barcelona, Spain. Participants were males and females aged 50-69 years, who were invited to the first round of a screening programme based on the faecal immunochemical test (FIT) (n = 41 042), and their primary care professional. The randomisation unit was the physician cluster (n = 130) and patients were blinded to the study group. The control group followed usual care as per the colorectal cancer screening programme. In the intervention group, as well as usual care, an alert to health professionals (cluster level) to promote screening was introduced in the individual's primary care EMR for 1 year. The main outcome was colorectal cancer screening participation at individual participant level. In total, 67 physicians and 21 619 patients (intervention group) and 63 physicians and 19 423 patients (control group) were randomised. In the intention-to-treat analysis screening participation was 44.1% and 42.2% respectively (odds ratio 1.08, 95% confidence interval [CI] = 0.97 to 1.20, P = 0.146). However, in the per-protocol analysis screening uptake in the intervention group showed a statistically significant increase, after adjusting for potential confounders (OR, 1.11; 95% CI = 1.02 to 1.22; P = 0.018). The use of an alert in an individual's primary care EMR is associated with a statistically significant increased uptake of an organised, FIT-based colorectal cancer screening programme in patients attending primary care centres. © British Journal of General Practice 2016.
van Wyk, H C; Park, James; Roxburgh, Campbell; Horgan, Paul; Foulis, Alan; McMillan, Donald C
Tumour budding reflects a detachment of tumour cells at the invasive front of carcinomas and is presumed to be an early step in the metastatic process. Tumour budding has received some attention in colorectal cancer as it has been proposed as an additional prognostic factor in colorectal cancer that may stratify patients into risk categories. The purpose of the review was to examine (1): The different methods of detection using either routine stains (H&E) or immunohistochemistry; (2): to compare studies that examined the different methods used to identify tumour budding; and (3) to examine the impact of tumour budding on survival in primary operable colorectal cancer. Results from the present review suggest that tumour budding can be considered a promising and strong prognostic factor in colorectal cancer. However, the implementation of the assessment of tumour budding in routine pathological work will depend on a selected, internationally accepted scoring system and validation against other established prognostic factors in patients with colorectal cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.
Lao, Victoria Valinluck; Grady, William M.
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
Cejas, Paloma; López-Gómez, Miriam; Aguayo, Cristina; Madero, Rosario; de Castro Carpeño, Javier; Belda-Iniesta, Cristóbal; Barriuso, Jorge; Moreno García, Víctor; Larrauri, Javier; López, Rocío; Casado, Enrique; Gonzalez-Barón, Manuel; Feliu, Jaime
Background KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status. Methodology/Principal Findings KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006). Conclusions/Significance Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to
Triantafillidis, John K.; Vagianos, Constantine; Gikas, Aristofanis; Korontzi, Maria
In recent years, the role of primary care physicians (PCPs) in the diagnosis and management of gastrointestinal disorders, including screening for colorectal cancer (CRC), has been recognized as very important. The available data indicate that PCPs are not adequately following CRC screening guidelines because a number of factors have been identified as significant barriers to the proper application of CRC screening guidelines. These factors include lack of time, patient reluctance, and challenges related to scheduling colonoscopy. Further positive engagement of PCPs with CRC screening is required to overcome these barriers and reach acceptable levels in screening rates. To meet the expectations of modern medicine, PCPs should not only be able to recommend occult blood testing or colonoscopy but also, under certain conditions, able to perform colonoscopy. In this review, the authors aim to provide the current knowledge of the role of PCPs in increasing the rate and successfully implementing a screening program for CRC by applying the relevant international guidelines. PMID:27676092
Zauber, Ann G.; Levin, Theodore R; Jaffe, C. Carl; Galen, Barbara A.; Ransohoff, David F.; Brown, Martin L.
Colorectal cancer (CRC) screening reduces the risk of CRC mortality but is currently not well utilized, with adherence only 50% in the eligible U.S. population and rates that lag behind those for breast and cervical cancer. The primary care physician has the pivotal role of facilitating patient adherence to CRC screening by informed choice of the screening tests, follow up of positive tests, and coordination of medical resources when diagnostic intervention is required. Consequently, the primary care setting is where significant improvements can be made in CRC screening adherence. This article provides a summary of the newer CRC screening technologies that can be used by primary care physicians in shared decision making with their patients. There are now multiple CRC screening tests which vary in their ability to detect the different stages in the adenoma to carcinoma sequence. Current guidelines of the Multi-Society (Gastroenterology) Task Force (1997, 2003, 2006, 2008), the American Cancer Society (2001, 2003, 2007, 2008), and the United States Preventive Services Task Force (2002) recommend a menu of CRC screening options, including fecal occult blood tests (FOBT) (Hemoccult II, Hemoccult SENSA, fecal immunochemical tests (FIT)), double contrast barium enema (DCBE), flexible sigmoidoscopy with or without annual FOBT’s, and colonoscopy. In this report, we assess the options of fecal immunochemical tests, colonoscopy, CT-colonography (CTC or virtual colonoscopy), and fecal DNA tests. The tests are discussed with respect to the evidence in support of their use and within the context of how they could be managed and implemented in primary care practice. Primary care physicians will want to understand the tradeoffs among accuracy, costs, and patient preferences for the current and emerging CRC tests. PMID:18725826
Jung, Jiyoon; Kang, Youngjin; Lee, Yoo Jin; Kim, Eojin; Ahn, Bokyung; Lee, Eunjung; Kim, Joo Young; Lee, Jeong Hyeon; Lee, Youngseok; Kim, Chul Hwan; Chae, Yang-Seok
Background Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses. Methods In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC. PMID:28192899
Chen, Huanhuan Joyce; Sun, Jian; Huang, Zhiliang; Hou, Harry; Arcilla, Myra; Rakhilin, Nikolai; Joe, Daniel J.; Choi, Jiahn; Gadamsetty, Poornima; Milsom, Jeff; Nandakumar, Govind; Longman, Randy; Zhou, Xi Kathy; Edwards, Robert; Chen, Jonlin; Chen, Kai Yuan; Bu, Pengcheng; Wang, Lihua; Xu, Yitian; Munroe, Robert; Abratte, Christian; Miller, Andrew D.; Gümüş, Zeynep H.; Shuler, Michael; Nishimura, Nozomi; Edelmann, Winfried; Shen, Xiling; Lipkin, Steven M.
Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokine receptor CCR9 in CRC cell lines and patient-derived cells to create primary gastrointestinal (GI) tumors in immunodeficient mice by tail-vein injection rather than surgery. The tumors metastasize inducibly and robustly to the liver. Metastases have higher DKK4 and NOTCH signaling levels and are more chemoresistant than paired sub-cutaneous xenografts. Using this approach, we generated 17 chemokine-targeted mouse models (CTMMs) that recapitulate the majority of common human somatic CRC mutations. We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance. We expect that CTMMs will facilitate investigation of the biology of CRC metastasis and drug screening. PMID:26006007
Swets, Marloes; König, Marion H; Zaalberg, Anniek; Dekker-Ensink, Neeltje G; Gelderblom, Hans; van de Velde, Cornelis J H; van den Elsen, Peter J; Kuppen, Peter J K
De novo expression of HLA-G has been demonstrated in colorectal cancer. HLA-G, amongst others, inhibits natural killer cell function, contributing to host immune defense evasion. Another mechanism to escape anti-tumor immunity is loss of HLA class I. Therefore, we determined HLA-G and HLA class I expression on primary colorectal tumors and associated liver metastases, in order to get insight in the metastasizing process regarding escaping anti-tumor immunity. HLA-G expression was evaluated using three mAbs; 4H84, MEM-G/1 and MEM-G/2. In total 81 colorectal cancer patients were evaluated. Formalin-fixed paraffin-embedded tissue sections of primary tumors and associated liver metastases, were immunohistochemically stained. A concordance between expression or loss/downregulation in the primary tumor and associated liver metastasis regarding HLA class I expression was observed in 80% of the cases. In contrast with the hypothesis of escaping NK cell-killing, we demonstrated for each HLA-G detecting mAbs used in this study, that the majority of the primary tumors that positively stained for HLA-G did not express HLA-G in the associated liver metastasis. Furthermore, we revealed the existence of non-specific binding and in addition we found that the different epitopes of HLA-G detected by 4H84, MEM-G/1 and MEM-G/2 mAbs were expressed differentially in colorectal tumor tissues.
Yamashita, S; Odisio, B C; Huang, S Y; Kopetz, S E; Ahrar, K; Chun, Y S; Conrad, C; Aloia, T A; Gupta, S; Harmoush, S; Hicks, M E; Vauthey, J-N
In patients with primary colorectal cancer (CRC) or unresectable metastatic CRC, midgut embryonic origin is associated with worse prognosis. The impact of embryonic origin on survival after ablation of colorectal liver metastases (CLM) is unclear. We identified 74 patients with CLM who underwent percutaneous ablation during 2004-2015. Survival and recurrence after ablation of CLM from midgut origin (n = 18) and hindgut origin (n = 56) were analyzed. Prognostic value of embryonic origin was evaluated. Recurrence-free survival (RFS) and overall survival (OS) after percutaneous ablation were worse in patients from midgut origin (3-year RFS: 5.6% vs. 24%, P = 0.004; 3-year OS: 25% vs. 70%, P 0.001). In multivariable analysis, factors associated with worse OS were midgut origin (hazard ratio [HR] 4.87, 95% CI 2.14-10.9, P 0.001), multiple CLM (HR 2.35, 95% CI 1.02-5.39, P = 0.044), and RAS mutation (HR 2.78, 95% CI 1.25-6.36, P = 0.013). At a median follow-up of 25 months, 56 patients (76%) had developed recurrence, 16 (89%) with midgut origin and 40 (71%) with hindgut origin (P = 0.133). Recurrent disease was treated with local therapy in 20 patients (36%), 2 (13%) with midgut origin and 18 (45%) with hindgut origin (P = 0.022). Compared to CLM from hindgut origin tumors, CLM from midgut origin tumors were associated with worse survival after ablation, which was partly attributable to the fact that patients with hindgut origin were more frequently candidates for local therapy at recurrence. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Thorstensen, Lin; Qvist, Hanne; Heim, Sverre; Liefers, Gerrit-Jan; Nesland, Jahn M; Giercksky, Karl-Erik; Lothe, Ragnhild A
Abstract Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas have shown that loss of the distal part of chromosome arm 1p is common, particularly in tumors of the left colon. Because the importance of 1p loss in colorectal cancer metastases is unknown, we compared the frequency, exact site and extent of 1p deletions in primary carcinomas (n=28), local recurrences (n=19) and metastases (n=33) from 67 colorectal cancer patients using 14 markers in an allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas, 33% of the local recurrences, and 64% of the metastases, revealing a significant difference between the local recurrences and the metastases (P=.04). The smallest region of 1p deletion overlap (SRO) defined separately for each group of lesions had the region between markers D1S2647 and D1S2644, at 1p35–36, in common. The genes PLA2G2A (1p35.1–36) and TP73 (1p36.3) were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss. In the second part of the study, microdissected primary carcinomas and distant metastases from the same colorectal cancer patients (n=18) were analyzed, and the same 1p genotype was found in the majority of patients (12/18, 67%). The finding that primary carcinoma cells with metastatic ability usually contain 1p deletions, and that some cases lacking 1p alterations in the primary tumor acquire such changes during growth of a metastatic lesion, supports the notion that 1p loss may be important both early and late in colorectal carcinogenesis, with the apparent exception of local recurrences. PMID:11228544
Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7
Dignan, Mark; Shelton, Brent; Slone, Stacey A; Tolle, Cheri; Mohammad, Sohail; Schoenberg, Nancy; Pearce, Kevin; Van Meter, Emily; Ely, Gretchen
This report describes findings from a randomized controlled trial of an intervention to increase colorectal cancer (CRC) screening in primary care practices in Appalachian Kentucky. Sixty-six primary care practices were randomized to early or delayed intervention groups. The intervention was provided at practices using academic detailing, a method of education where providers receive information on a specific topic through personal contact. Data were collected in cross-sectional surveys of medical records at baseline and six months post-intervention. A total of 3844 medical records were reviewed at baseline and 3751 at the six-month follow-up. At baselines, colonoscopy was recommended more frequently (43.4%) than any other screening modality, followed by fecal occult blood testing (18.0%), flexible sigmoidoscopy (0.4%), and double-contrast barium enema (0.3%). Rates of documented screening results were higher for all practices at the six-month follow-up for colonoscopy (31.8% vs 29.6%) and fecal occult blood testing (12.2% vs 11.2%). For early intervention practices that recommended screening, colonoscopy rates increased by 15.7% at six months compared to an increase of 2.4% in the delayed intervention practices (p=.01). Using academic detailing to reach rural primary care providers with a CRC screening intervention was associated with an increase in colonoscopy. Copyright © 2013 Elsevier Inc. All rights reserved.
LANGMAN, M; BOYLE, P
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
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.
Kahlert, C; Pecqueux, M; Halama, N; Dienemann, H; Muley, T; Pfannschmidt, J; Lasitschka, F; Klupp, F; Schmidt, T; Rahbari, N; Reissfelder, C; Kunz, C; Benner, A; Falk, C; Weitz, J; Koch, M
Tumour-associated stroma has a critical role in tumour proliferation. Our aim was to determine a specific protein expression profile of stromal angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential biomarkers or new therapy targets. Frozen tissue of primary colorectal cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein expression of nine angiogenic cytokines and eight MMPs was analysed using a multiplex-based protein assay. We found a differential expression of several MMPs and angiogenic cytokines in tumour cells compared with adjacent tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal expression of MMPs and angiogenic cytokines. Univariate analysis identified stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung metastases. Expression of MMPs and angiogenic cytokines in tumour cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can be helpful to identify new agents for a targeted therapy in patients with colorectal cancer.
Spruce, Lisa R; Sanford, Julie Tanner
The purpose of this project was to increase colorectal cancer screening (CRC) rates in the state of Nevada. Research has shown that there are several interventions for providers to use to increase CRC screening rates in practice. The Nevada Colon Cancer Partnership (NCCP) has created a toolkit to assist providers to implement these interventions in practice. Research has repeatedly shown that CRC screening has a great impact on the morbidity and mortality of CRC. Studies have shown that a fecal occult blood test can detect 60-85% of CRCs and a colonoscopy with polyp removal can reduce mortality by 60-90%. Multiple studies have shown that a provider's recommendation is the most consistently influential factor in cancer screening. Furthermore, offering patients a choice and encouraging active participation in health care decision making has proven to increase CRC screening rates. The NCCP has collaborated with the American Cancer Society to create a web based toolkit for use by providers to change practice and screen all eligible patients for CRC. The toolkit is designed to encourage providers to decrease the morbidity and mortality of CRC and other cancers. The toolkit is useful to facilitate efforts of office-based clinicians to reduce disparities by applying screening guidelines on a universal basis to the age-appropriate population. A team approach to screening is encouraged to promote an opportunistic or global approach to assure all eligible patients are reached. As healthcare reform continues to evolve, Nurse Practitioners (NPs) will assume much of the primary care needs of our country. A preventive care model is an important aspect of the future of healthcare. NPs are in a perfect position to change the health of patients in a global way. The strategies and tools presented in this toolkit are designed to improve preventive care and assist the NP in assuring that every eligible patient receives the screening tests they need. ©2012 The Author(s) Journal
Charalampoudis, Petros; Kykalos, Stylianos; Stamopoulos, Paraskevas; Kouraklis, Gregory
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
Nanji, Sulaiman; Mackillop, William J.; Wei, Xuejiao; Booth, Christopher M.
Background Simultaneous resection of primary colorectal cancer (CRC) and synchronous liver metastases (LM) is gaining interest. We describe management and outcomes of patients undergoing simultaneous resection in the general population. Methods All patients with CRC who underwent surgical resection of LM between 2002 and 2009 were identified using the population-based Ontario Cancer Registry and linked electronic treatment records. Synchronous disease was defined as having resection of CRCLM within 12 weeks of surgery for the primary tumour. Results During the study period, 1310 patients underwent resection of CRCLM. Of these, 226 (17%) patients had synchronous disease; 100 (44%) had a simultaneous resection and 126 (56%) had a staged resection. For the simultaneous and the staged groups, the mean number of liver lesions resected was 1.6 and 2.3, respectively (p < 0.001); the mean size of the largest lesion was 3.1 and 4.8 cm, respectively (p < 0.001); and the major hepatic resection rate was 21% and 79%, respectively (p < 0.001). Postoperative mortality for simultaneous cases at 90 days was less than 5%. Five-year overall survival and cancer-specific survival for patients with simultaneous resection was 36% (95% confidence interval [CI] 26%–45%) and 37% (95% CI 25%–50%), respectively. Simultaneous resections are common in the general population. A more conservative approach is being adopted for simultaneous resections by limiting the extent of liver resection. Postoperative mortality and long-term survival in this patient population is similar to that reported in other contemporary series. Conclusion Compared with a staged approach, patients undergoing simultaneous resections had fewer and smaller liver metastases and underwent less aggressive resections. One-third of these patients achieved long-term survival. PMID:28234215
Della Vittoria Scarpati, Giuseppina; Troncone, Giancarlo; Pepe, Stefano; De Placido, Sabino; D'Incalci, Maurizio
Microarray technology was used to profile miRNA expression in primary tumor and stromal tissue from paraffin embedded material of 51 patients with colorectal cancer. 26 miRNAs resulted differentially expressed with at least 2-fold change in tumor tissue with respect to stroma (16 more expressed in the tumor and 10 more expressed in the stroma). 10/26 were confirmed as differentially expressed at qRTPCR: miR-200c-3p, miR-141-3p, miR-200b-3p, miR-200a-3p, miR-1246, miR-92a-3p, miR-194-5p, miR-192-5p, miR-3651-5p, and miR-574-3p. No significant association was found between miRNA expressions and stage at diagnosis, site of primary tumor, first site of metastasis, progression-free, or overall survival. PMID:25143946
Della Vittoria Scarpati, Giuseppina; Calura, Enrica; Di Marino, Mariacristina; Romualdi, Chiara; Beltrame, Luca; Malapelle, Umberto; Troncone, Giancarlo; De Stefano, Alfonso; Pepe, Stefano; De Placido, Sabino; D'Incalci, Maurizio; Marchini, Sergio; Carlomagno, Chiara
Microarray technology was used to profile miRNA expression in primary tumor and stromal tissue from paraffin embedded material of 51 patients with colorectal cancer. 26 miRNAs resulted differentially expressed with at least 2-fold change in tumor tissue with respect to stroma (16 more expressed in the tumor and 10 more expressed in the stroma). 10/26 were confirmed as differentially expressed at qRTPCR: miR-200c-3p, miR-141-3p, miR-200b-3p, miR-200a-3p, miR-1246, miR-92a-3p, miR-194-5p, miR-192-5p, miR-3651-5p, and miR-574-3p. No significant association was found between miRNA expressions and stage at diagnosis, site of primary tumor, first site of metastasis, progression-free, or overall survival.
... 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 ...
Background Long interspersed nucleotide element 1 (LINE-1) hypomethylation is suggested to play a role in the progression of colorectal cancer (CRC). To assess intra-patient heterogeneity of LINE-1 methylation in CRC and to understand its biological relevance in invasion and metastasis, we evaluated the LINE-1 methylation at multiple tumor sites. In addition, the influence of stromal cell content on the measurement of LINE-1 methylation in tumor tissue was analyzed. Methods Formalin-fixed paraffin-embedded primary tumor tissue was obtained from 48 CRC patients. Matched adjacent normal colon tissue, lymph node metastases and distant metastases were obtained from 12, 18 and 7 of these patients, respectively. Three different areas were microdissected from each primary tumor and included the tumor center and invasive front. Normal mucosal and stromal cells were also microdissected for comparison with the tumor cells. The microdissected samples were compared in LINE-1 methylation level measured by multicolor MethyLight assay. The assay results were also compared between microdissected and macrodissected tissue samples. Results LINE-1 methylation within primary tumors showed no significant intra-tumoral heterogeneity, with the tumor center and invasive front showing identical methylation levels. Moreover, no difference in LINE-1 methylation was observed between the primary tumor and lymph node and distant metastases from the same patient. Tumor cells showed significantly less LINE-1 methylation compared to adjacent stromal and normal mucosal epithelial cells. Consequently, LINE-1 methylation was significantly lower in microdissected samples compared to macrodissected samples. A trend for less LINE-1 methylation was also observed in more advanced stages of CRC. Conclusions LINE-1 methylation shows little intra-patient tumor heterogeneity, indicating the suitability of its use for molecular diagnosis in CRC. The methylation is relatively stable during CRC progression
... 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 ...
Bouvier, Anne-Marie; Launoy, Guy
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.
Edwardson, Nicholas; Bolin, Jane N; McClellan, David A; Nash, Philip P; Helduser, Janet W
Demand for a wide array of colorectal cancer screening strategies continues to outpace supply. One strategy to reduce this deficit is to dramatically increase the number of primary care physicians who are trained and supportive of performing office-based colonoscopies or flexible sigmoidoscopies. This study evaluates the clinical and economic implications of training primary care physicians via family medicine residency programs to offer colorectal cancer screening services as an in-office procedure. Using previously established clinical and economic assumptions from existing literature and budget data from a local grant (2013), incremental cost-effectiveness ratios are calculated that incorporate the costs of a proposed national training program and subsequent improvements in patient compliance. Sensitivity analyses are also conducted. Baseline assumptions suggest that the intervention would produce 2394 newly trained residents who could perform 71,820 additional colonoscopies or 119,700 additional flexible sigmoidoscopies after ten years. Despite high costs associated with the national training program, incremental cost-effectiveness ratios remain well below standard willingness-to-pay thresholds under base case assumptions. Interestingly, the status quo hierarchy of preferred screening strategies is disrupted by the proposed intervention. A national overhaul of family medicine residency programs offering training for colorectal cancer screening yields satisfactory incremental cost-effectiveness ratios. However, the model places high expectations on primary care physicians to improve current compliance levels in the US. Copyright © 2016 Elsevier Inc. All rights reserved.
Na, Soo-Young; Myung, Seung-Jae
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.
Otani, Kensuke; Ishihara, Soichiro; Yamaguchi, Hironori; Murono, Koji; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki
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.
Wu, Charlotte A; Mulder, Amara L; Zai, Adrian H; Hu, Yuanshan; Costa, Manuela; Tishler, Lori Wiviott; Saltzman, John R; Ellner, Andrew L; Bitton, Asaf
Provision of colorectal cancer (CRC) screening in primary care is suboptimal; failure to observe screening guidelines poses unnecessary risks to patients and doctors. Implement a population management system for CRC screening; evaluate impact on compliance with evidence-based guidelines. A quasi-experimental, prospective quality improvement study design using pre-post-analyses with concurrent controls. Six suites within an academic primary care practice. 5320 adults eligible for CRC screening treated by 70 doctors. In three intervention suites, doctors reviewed real-time rosters of patients due for CRC screening and chose practice delegate outreach or default reminder letter. Delegates tracked overdue patients, made outreach calls, facilitated test ordering, obtained records and documented patient deferral, exclusion or decline. In three control suites, doctors followed usual preventive care practices. CRC screening compliance (including documented decline, deferral or exclusion) and CRC screening completion rates over 5 months. At baseline, there was no significant difference in CRC screening compliance (I: 80.4% and C: 79.6%, P = 0.439) and CRC screening completion rates (I: 78.3% and C: 77.3%, P = 0.398) between intervention and control groups. Post-intervention, compliance rates (I: 88.1% and C: 80.5%, P < 0.01) and completion rates (I: 81.0% and C: 78.1%, P < 0.05) were significantly higher in the intervention group. A population management system using closed-loop communication may improve CRC screening compliance and completion rates within academic primary care practices. Team-based care using well-designed IT systems can enable sharing of patient care responsibilities and improve patient outcomes. © 2015 John Wiley & Sons, Ltd.
Pickhardt, Perry J.; Schumacher, Jessica R.; Potvien, Aaron; Kim, David H.; Pfau, Patrick R.; Jacobs, Elizabeth A.; Smith, Maureen A.
Aims. Colorectal cancer (CRC) screening is underutilized. Increasing CRC screening rates requires interventions targeting multiple barriers at each level of the healthcare organization (patient, provider, and system). We examined groups of primary care providers (PCPs) based on perceptions of screening barriers and the relationship to CRC screening rates to inform approaches for conducting barrier assessments prior to designing and implementing quality improvement interventions. Methods. We conducted a retrospective cohort study linking EHR and survey data. PCPs with complete survey responses for questions addressing CRC screening barriers were included (N = 166 PCPs; 39,430 patients eligible for CRC screening). Cluster analysis identified groups of PCPs. Multivariate logistic regression estimated odds ratios and 95% confidence intervals for predictors of membership in one of the PCP groups. Results. We found two distinct groups: (1) PCPs identifying multiple barriers to CRC screening at patient, provider, and system levels (N = 75) and (2) PCPs identifying no major barriers to screening (N = 91). PCPs in the top half of CRC screening performance were more likely to identify multiple barriers than the bottom performers (OR, 4.14; 95% CI, 2.43–7.08). Conclusions. High-performing PCPs can more effectively identify CRC screening barriers. Targeting high-performers when conducting a barrier assessment is a novel approach to assist in designing quality improvement interventions for CRC screening. PMID:28163715
Weiss, Jennifer M; Pickhardt, Perry J; Schumacher, Jessica R; Potvien, Aaron; Kim, David H; Pfau, Patrick R; Jacobs, Elizabeth A; Smith, Maureen A
Aims. Colorectal cancer (CRC) screening is underutilized. Increasing CRC screening rates requires interventions targeting multiple barriers at each level of the healthcare organization (patient, provider, and system). We examined groups of primary care providers (PCPs) based on perceptions of screening barriers and the relationship to CRC screening rates to inform approaches for conducting barrier assessments prior to designing and implementing quality improvement interventions. Methods. We conducted a retrospective cohort study linking EHR and survey data. PCPs with complete survey responses for questions addressing CRC screening barriers were included (N = 166 PCPs; 39,430 patients eligible for CRC screening). Cluster analysis identified groups of PCPs. Multivariate logistic regression estimated odds ratios and 95% confidence intervals for predictors of membership in one of the PCP groups. Results. We found two distinct groups: (1) PCPs identifying multiple barriers to CRC screening at patient, provider, and system levels (N = 75) and (2) PCPs identifying no major barriers to screening (N = 91). PCPs in the top half of CRC screening performance were more likely to identify multiple barriers than the bottom performers (OR, 4.14; 95% CI, 2.43-7.08). Conclusions. High-performing PCPs can more effectively identify CRC screening barriers. Targeting high-performers when conducting a barrier assessment is a novel approach to assist in designing quality improvement interventions for CRC screening.
van Wyk, Hester C; Park, James H; Edwards, Joanne; Horgan, Paul G; McMillan, Donald C; Going, James J
Tumour budding has been reported to reflect invasiveness, metastasis and unfavourable prognosis in colorectal cancer. The aim of the study was to examine the relationship between tumour budding and clinicopathological characteristics, tumour microenvironment and survival in patients with primary operable colorectal cancer. A total of 303 patients from a prospective data set of patients with primary operable colorectal cancer were included in the study. The presence of budding was determined through assessment of all tumour-containing H&E slides and the number of tumour buds was counted using a 10 high-powered field method. Routine pathologic sections were used to assess: tumour necrosis, the tumour inflammatory cell infiltrate using Klintrup-Makinen (KM) grade and tumour stroma percentage (TSP) combined as the Glasgow Microenvironment Score (GMS). High-grade tumour budding was present in 39% of all tumours and in 28% of node-negative tumours respectively. High-grade budding was significantly associated with T stage (P<0.001), N stage (P<0.001), TNM stage (P<0.001), serosal involvement (P<0.001), venous invasion (P<0.005), KM grade (P=0.022), high tumour stroma (P<0.001) and GMS (P<0.001). Tumour budding was associated with reduced cancer-specific survival (CSS) (HR=4.03; 95% confidence interval (CI), 2.50-6.52; P<0.001), independent of age (HR=1.47; 95% CI, 1.13-1.90; P=0.004), TNM stage (HR=1.52; 95% CI, 1.02-2.25; P=0.040), venous invasion (HR=1.73; 95% CI, 1.13-2.64; P=0.012) and GMS (HR=1.54; 95% CI, 1.15-2.07; P=0.004). The presence of tumour budding was associated with elements of the tumour microenvironment and was an independent adverse prognostic factor in patients with primary operable colorectal cancer. Specifically high tumour budding stratifies effectively the prognostic value of tumour stage, venous invasion and GMS. Taken together, tumour budding should be assessed routinely in patients with primary operable colorectal cancer.
van Wyk, Hester C; Park, James H; Edwards, Joanne; Horgan, Paul G; McMillan, Donald C; Going, James J
Background: Tumour budding has been reported to reflect invasiveness, metastasis and unfavourable prognosis in colorectal cancer. The aim of the study was to examine the relationship between tumour budding and clinicopathological characteristics, tumour microenvironment and survival in patients with primary operable colorectal cancer. Methods: A total of 303 patients from a prospective data set of patients with primary operable colorectal cancer were included in the study. The presence of budding was determined through assessment of all tumour-containing H&E slides and the number of tumour buds was counted using a 10 high-powered field method. Routine pathologic sections were used to assess: tumour necrosis, the tumour inflammatory cell infiltrate using Klintrup–Makinen (KM) grade and tumour stroma percentage (TSP) combined as the Glasgow Microenvironment Score (GMS). Results: High-grade tumour budding was present in 39% of all tumours and in 28% of node-negative tumours respectively. High-grade budding was significantly associated with T stage (P<0.001), N stage (P<0.001), TNM stage (P<0.001), serosal involvement (P<0.001), venous invasion (P<0.005), KM grade (P=0.022), high tumour stroma (P<0.001) and GMS (P<0.001). Tumour budding was associated with reduced cancer-specific survival (CSS) (HR=4.03; 95% confidence interval (CI), 2.50–6.52; P<0.001), independent of age (HR=1.47; 95% CI, 1.13–1.90; P=0.004), TNM stage (HR=1.52; 95% CI, 1.02–2.25; P=0.040), venous invasion (HR=1.73; 95% CI, 1.13–2.64; P=0.012) and GMS (HR=1.54; 95% CI, 1.15–2.07; P=0.004). Conclusions: The presence of tumour budding was associated with elements of the tumour microenvironment and was an independent adverse prognostic factor in patients with primary operable colorectal cancer. Specifically high tumour budding stratifies effectively the prognostic value of tumour stage, venous invasion and GMS. Taken together, tumour budding should be assessed routinely in patients with
Schiff, Gordon D; Bearden, Trudy; Hunt, Lindsay Swain; Azzara, Jennifer; Larmon, Jay; Phillips, Russell S; Singer, Sara; Bennett, Brandon; Sugarman, Jonathan R; Bitton, Asaf; Ellner, Andrew
Colorectal cancer (CRC) is a leading cause of cancer death, reducible by screening and early diagnosis, yet many patients fail to receive recommended screening. As part of an academic improvement collaborative, 25 primary care practices worked to improve CRC screening and diagnosis. The project featured triannual learning sessions, monthly conference calls, practice coach support, and monthly reporting. The project phases included literature review and interviews with national leaders/organizations, development of driver diagrams to identify key factors and change ideas, project launch and practice team planning, and a practice improvement phase. The project activities included (1) inventory of barriers and best practices, (2) driver diagram to drive improvements, (3) list of changes to try, (4) compilation of lessons learned, and (5) five key changes to optimize screening and follow-up. Practices leveraged prior transformation efforts to track patients for screening and follow-up during and between office visits. By mapping processes, testing changes, and collecting data, sites targeted opportunities to improve quality, safety, efficiency, and patient and care team experience. Successful change interventions centered around partnering with gastroenterology, engaging leadership, leveraging registries and health information technology, promoting alternative screening options, and partnering with and supporting patients. Several practices achieved improvement in screening rates, while others demonstrated no change from baseline during the 10-month testing and implementation phase (July 2014-April 2015). The collaborative effectively engaged teams in a broad set of process improvements with key lessons learned related to barriers, information technology challenges, outreach challenges/strategies, and importance of stakeholder and patient engagement. Copyright © 2017 The Joint Commission. Published by Elsevier Inc. All rights reserved.
Marley, Andrew R; Nan, Hongmei
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
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Bardou, Marc; Barkun, Alan N; Martel, Myriam
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?
Jellema, Petra; van der Windt, Daniëlle A W M; Bruinvels, David J; Mallen, Christian D; van Weyenberg, Stijn J B; Mulder, Chris J
Objective To summarise available evidence on diagnostic tests that might help primary care physicians to identify patients with an increased risk for colorectal cancer among those consulting for non-acute lower abdominal symptoms. Data sources PubMed, Embase, and reference screening. Study eligibility criteria Studies were selected if the design was a diagnostic study; the patients were adults consulting because of non-acute lower abdominal symptoms; tests included signs, symptoms, blood tests, or faecal tests. Study appraisal and synthesis methods Two reviewers independently assessed quality with a modified version of the QUADAS tool and extracted data. We present diagnostic two by two tables and pooled estimates of sensitivity and specificity. We refrained from pooling when there was considerable clinical or statistical heterogeneity. Results 47 primary diagnostic studies were included. Sensitivity was consistently high for age ≥50 (range 0.81-0.96, median 0.91), a referral guideline (0.80-0.94, 0.92), and immunochemical faeces tests (0.70-1.00, 0.95). Of these, only specificity of the faeces tests was good. Specificity was consistently high for family history (0.75-0.98, 0.91), weight loss (0.72-0.96, 0.89), and iron deficiency anaemia (0.83-0.95, 0.92), but all tests lacked sensitivity. None of these six tests was (sufficiently) studied in primary care. Conclusions Although combinations of symptom and results of immunochemical faeces tests showed good diagnostic performance for colorectal cancer, evidence from primary care is lacking. High quality studies on their role in the diagnostic investigation of colorectal cancer in primary care are urgently needed. PMID:20360221
Aleksandrova, Krasimira; Nimptsch, Katharina; Pischon, Tobias
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.
Geller, Berta M; Skelly, Joan M; Dorwaldt, Anne L; Howe, Kathleen D; Dana, Greg S; Flynn, Brian S
Rural populations as well as less educated people in the United States are less likely to receive colorectal cancer (CRC) screening than people living in urban areas and more educated people. We tested a computer tablet, Patient/Provider Communication Assistant (PPCA), which collected data, educated patients, and printed personalized notes to patients and providers encouraging conversation about CRC screening. Mixed model analyses using a prepost quasi-experimental design compared patient results during the comparison and intervention periods in 5 rural primary care practices on provider discussion about CRC screening, provider recommendation, and patient intention to be screened. Models including age, education, and literacy measures as covariates were examined. Providers talked with patients about CRC screening in general, and colonoscopy specifically more frequently after the PPCA than with the comparison group (P values = 0.04 and 0.01, respectively). Providers recommended CRC screening more often to patients in the intervention group than to the comparison group (P = 0.02). Patients planned to be screened, specifically with colonoscopy, more frequently after the intervention than in the comparison group (P = 0.003). There were no interactions between group and any of the covariates. Ninety-five percent of the patients, regardless of age or education, found the PPCA easy to use. Results indicated increased provider discussion and recommendation, and patients' intentions to obtain CRC screening, and in particular colonoscopy, for patients exposed to the intervention, regardless of the patients' age or literacy levels. The PPCA is a promising intervention method that is acceptable to rural patients.
Peters, H Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A; Tan, Sanda A
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.
Maxwell-Armstrong, C A; Durrant, L G; Robins, R A; Galvin, A M; Scholefield, J H; Hardcastle, J D
The anti-idiotypic monoclonal antibody 105AD7 mimics the tumour associated antigen 791Tgp72, expressed on 70-80% of colorectal cancers. Phase I studies have shown that the vaccine is non-toxic, and a number of patients have been immunised prior to resection of their primary tumours. To assess lymphocyte activation at the tumour site by measuring expression of the alpha subunit of the interleukin 2 receptor (CD25). Nineteen patients with primary colorectal cancer were immunised with varying doses of 105AD7 prior to resection of their primary tumours. Samples of normal bowel and tumour edge/centre from 16 patients were available for immunohistochemical staining with a monoclonal antibody against CD25. Samples from a matched control group were also stained. Fresh tumours from 14 immunised patients and 31 unimmunised control patients were disaggregated, and the lymphocytes obtained labelled for CD25. Samples were analysed blindly by flow cytometry. Median infiltration of lymphocytes expressing CD25, measured immunohistochemically, was higher in trial patients, as was the ratio of tumour to normal bowel infiltration. Flow cytometric analysis of fresh tumour from immunised patients showed a significantly higher percentage of lymphocytes expressing CD25 tumour infiltrating lymphocytes than their matched and unmatched controls. The alpha subunit of the interleukin 2 receptor is increased on tumour infiltrating lymphocytes, in patients immunised with the colorectal cancer vaccine 105AD7. This suggests a population of activated lymphocytes capable of targeting 791Tgp72 expressing tumour cells, such as circulating micrometastases. 105AD7 may have a role as adjuvant therapy in early stage disease.
Redaniel, Maria Theresa; Ridd, Matthew; Martin, Richard M; Coxon, Fareeda; Jeffreys, Mona; Wade, Julia
Objectives To ascertain the challenges associated with implementation of the 2-week wait referral criteria and waiting time targets for colorectal cancer and to identify recommendations for improvements to the pathway. Design Qualitative research using semistructured interviews and applying thematic analysis using the method of constant comparison. Setting 10 primary care surgeries and 6 secondary care centres from 3 geographical areas in the England. Participants Purposive sample of 24 clinicians (10 general practitioners (GPs), 7 oncologists and 7 colorectal surgeons). Results GPs and specialists highlighted delays in patient help-seeking, difficulties applying the colorectal cancer referral criteria due to their low predictive value, and concerns about the stringent application of targets because of potential impact on individual care and associated penalties for breaching. Promoting patient awareness and early presentation, clarifying predictive symptoms, allowing flexibility, optimising resources and maximising care coordination were suggested as improvements. Conclusions Challenges during diagnosis and treatment persist, with guidelines and waiting time targets producing the perception of unintended harms at individual and organisational levels. This has led to variations in how guidelines are implemented. These require urgent evaluation, so that effective practices can be adopted more widely. PMID:26493457
Meenan, Richard T.; Anderson, Melissa L.; Chubak, Jessica; Vernon, Sally W.; Fuller, Sharon; Wang, Ching-Yun; Green, Beverly B.
Introduction Recent colorectal cancer screening studies focus on optimizing adherence. This study evaluated the cost effectiveness of interventions using electronic health records (EHRs), automated mailings, and stepped support increases to improve 2-year colorectal cancer screening adherence. Methods Analyses were based on a parallel-design, randomized trial in which three stepped interventions (EHR-linked mailings [“automated”], automated plus telephone assistance [“assisted”], or automated and assisted plus nurse navigation to testing completion or refusal [navigated”]) were compared to usual care. Data were from August 2008–November 2011 with analyses performed during 2012–2013. Implementation resources were micro-costed; research and registry development costs were excluded. Incremental cost-effectiveness ratios (ICERs) were based on number of participants current for screening per guidelines over 2 years. Bootstrapping examined robustness of results. Results Intervention delivery cost per participant current for screening ranged from $21 (automated) to $27 (navigated). Inclusion of induced testing costs (e.g., screening colonoscopy) lowered expenditures for automated (ICER=−$159) and assisted (ICER=−$36) relative to usual care over 2 years. Savings arose from increased fecal occult blood testing, substituting for more expensive colonoscopies in usual care. Results were broadly consistent across demographic subgroups. More intensive interventions were consistently likely to be cost effective relative to less intensive interventions, with willingness to pay values of $600–$1,200 for an additional person current for screening yielding ≥80% probability of cost effectiveness. Conclusions Two-year cost effectiveness of a stepped approach to colorectal cancer screening promotion based on EHR data is indicated, but longer-term cost effectiveness requires further study. PMID:25998922
Nemecek, Radim; Berkovcova, Jitka; Radova, Lenka; Kazda, Tomas; Mlcochova, Jitka; Vychytilova-Faltejskova, Petra; Slaby, Ondrej; Svoboda, Marek
Although several molecular markers predicting resistance to cetuximab- or panitumumab-based therapy of metastatic colorectal cancer were described, mutations in RAS proto-oncogenes remain the only predictors being used in daily clinical practice. However, 35%-45% of wild-type RAS patients still do not respond to this anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody-based therapy, and therefore the definition of other predictors forms an important clinical need. The aim of the present retrospective single-institutional study was to evaluate potential genes responsible for resistance to anti-EGFR therapy in relation to mutational analysis of primary versus metastatic lesions. Twenty-four paired primary and corresponding metastatic tissue samples from eight nonresponding and four responding metastatic colorectal cancer patients treated with cetuximab-based therapy were sequenced using a next-generation sequencing panel of 26 genes involved in EGFR signaling pathway and colorectal carcinogenesis. Mutational status of primary tumors and metastatic lesions was highly concordant in TP53, APC, CTNNB1, KRAS, PIK3CA, PTEN, and FBXW7 genes. Metastatic samples harbor significantly more mutations than primary tumors. Potentially negative predictive value of FBXW7 mutations in relationship to anti-EGFR treatment outcomes was confirmed. Finally, new occurrences of activating KRAS mutations were identified in a group of patients initially determined as wild-type RAS by routinely used qPCR-based RAS mutational tests. All newly detected activating KRAS mutations most likely led to cetuximab treatment failure. The results of the present study suggest a need of careful consideration of previously published results of anti-EGFR-targeted therapy with regard to potentially inaccurate diagnostic tools used in the past. Based on our findings, we recommend more extensive use of next-generation sequencing testing in daily clinical practice, as it brings a significant
Pestalozzi, B C; Jäger, D; Knuth, A
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.
... 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)
... 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)
Byun, Ju-Young; Yoon, Seok-Jun; Oh, In-Hwan; Kim, Young Ae; Seo, Hye-Young; Lee, Yo-Han
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.
Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H
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
Zanardelli, Matteo; Micheli, Laura; Nicolai, Raffaella; Failli, Paola; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo
Oxaliplatin-based chemotherapy improves the outcomes of metastatic colorectal cancer patients. Its most significant and dose-limiting side effect is the development of a neuropathic syndrome. The mechanism of the neurotoxicity is unclear. The limited knowledge about differences existing between neurotoxic and antitumor effects hinders the discovery of effective and safe adjuvant therapies. In vitro, we suggested cell-specific activation apoptotic pathways in normal nervous cells (astrocytes) vs. colon-cancer cells (HT-29). In the present research we compared the apoptotic signals evoked by oxaliplatin in astrocytes and HT-29 analyzing the intrinsic and extrinsic apoptotic pathways. In astrocytes, oxaliplatin induced a mitochondrial derangement measured as cytosolic release of cytochrome C, increase in superoxide anion levels and decreased expression of the antiapoptotic protein Bcl-2. Caspase-8, a main initiator of the extrinsic process remained unaltered. On the contrary, in HT-29 oxaliplatin increased caspase-8 activity and Bid expression, thus activating the extrinsic apoptosis, while the Bcl-2 increased expression blocked the mitochondrial damage. Data suggest the preferred activation of the intrinsic apoptosis as oxaliplatin damage signaling in normal nervous cells. The extrinsic pathway prevails in tumor cells indicating a possible strategy for planning new molecules to treat oxaliplatin-dependent neurotoxicity without negatively influence chemotherapy. PMID:25761243
Fujiyoshi, Kenji; Yamamoto, Gou; Takahashi, Akemi; Arai, Yoshiko; Yamada, Mina; Kakuta, Miho; Yamaguchi, Kensei; Akagi, Yoshito; Nishimura, Yoji; Sakamoto, Hirohiko; Akagi, Kiwamu
Genetic testing is needed for the treatment of colorectal cancer (CRC), especially molecular-targeted therapy. The effects of anti-EGFR therapy and prognosis are affected by the presence of KRAS mutations. However, whether primary CRC or metastatic tissues are appropriate in the analysis is still unclear. In the present study, we assessed the concordance of KRAS/BRAF mutation status and microsatellite instability (MSI) in primary CRC and corresponding metastases. This study enrolled 457 patients with surgically resected primary and corresponding metastatic CRC (499 synchronous metastases and 57 metachronous metastases) and seven local recurrences, and KRAS/BRAF mutation and MSI status were analysed for these tumours. The concordance rates of KRAS mutation, BRAF mutation, wild-type, MSI-H and MSS between primary CRC and corresponding metastases were 93.9% (214/228), 100% (30/30), 99.3% (304/306), 87.5% (21/24) and 100% (137/137), respectively. These high concordance rates were not different between synchronous and metachronous metastases. In conclusion, a high concordance of KRAS/BRAF mutation status and MSI status was observed between primary CRC and corresponding metastases in this study. Either primary CRC or metastatic tissues can be used for testing KRAS/BRAF mutation status and MSI status.
Guenther, U; Herbst, H; Bauer, M; Isbert, C; Buhr, H-J; Riecken, E-O; Schuppan, D
Collagen type XVIII (C18) is a nonfibrillar collagen of basement membranes. Its C-terminal fragment, endostatin, has been identified as an inhibitor of angiogenesis. C18 is predominantly expressed by hepatocytes of normal, cirrhotic and neoplastic liver. We compared the patterns of C18 RNA-expression in colonic adenocarcinoma metastases, which represent the most frequently occurring liver tumours, to normal colon mucosa, to primary colon cancers and to ovarian cancers which are often morphologically similar to colonic cancer or metastasis. Two C18-specific RNA-probes were generated to perform in situ hybridization combined with immunohistochemistry for cytokeratin, vimentin and the endothelial marker CD31, in order to characterize the C18-expressing cells. C18/endostatin protein was localized by immunohistology. In colorectal carcinomas and their liver metastases high levels of C18 transcripts were observed in endothelial cells and fibroblasts/myofibroblasts, whereas C18 RNA was virtually absent from carcinoma cells. Ovarian carcinomas displayed high C18 RNA expression both in carcinoma and stromal cells, indicating that induction of C18 transcription in tumour stromal cells is independent of the ability of carcinoma cells to express C18. While the role of tumour cell derived C18 in cancer growth regulation remains unknown, stimulation of proteolysis of the locally strongly expressed C18 to endostatin could offer an attractive approach for a targeted antineoplastic therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11720442
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.
Yang, Jiao; Li, Shuting; Lv, Meng; Wu, Yinying; Chen, Zheling; Shen, Yanwei; Wang, Biyuan; Chen, Ling; Yi, Min; Yang, Jin
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
Borresen, Erica C; Gundlach, Kerry A; Wdowik, Melissa; Rao, Sangeeta; Brown, Regina J; Ryan, Elizabeth P
Introduction: Emerging evidence supports that increased consumption of dry beans (Phaseolus vulgaris L.) reduces both the incidence and recurrence of adenomatous polyps or precancerous growths. Navy beans have been studied for dietary colorectal cancer (CRC) chemoprevention in animal models. Our main objectives were to assess the feasibility of increased navy bean consumption in adults with and without history of CRC and to achieve intake amounts associated with chemoprevention. Methods: Seven meals and six snacks were developed for both the absence and inclusion of cooked navy bean powder (35grams/day). Sixteen healthy adults (7 non-cancer and 9 CRC survivors) completed the placebo-controlled, randomized, single-blinded dietary intervention trial. Participants consumed one study-provided meal and snack daily for 28 days, which accounted for approximately one-third of their total recommended caloric intake (meals = 202-483 kcal and snacks = 194-401 kcal). Participants also recorded three-day dietary food logs each week. Results: The addition of 35g of cooked navy bean powder (NBP) into foods provided 5-8% daily caloric intake. The compliance to the meal and snack intervention ranged from 89-100%. Non-cancer participants in the NBP group had a significant decrease in total caloric intake after week 4 (p≤0.0001). CRC survivors in the NBP group significantly increased total fiber intake by week 4 (p≤0.0001). Conclusions: NBP are feasible to include in meals for increased total fiber intake and for consuming the amount that is associated with CRC chemoprevention outcomes. These findings warrant further evaluation of NBP consumption in clinical nutrition trials for CRC control and prevention. PMID:25009453
He, Wen-Zhuo; Liao, Fang-Xin; Jiang, Chang; Kong, Peng-Fei; Yin, Chen-Xi; Yang, Qiong; Qiu, Hui-Juan; Zhang, Bei; Xia, Liang-Ping
Background: Published papers reported contradictory results about the correlation between bevacizumab effectiveness and primary tumor location of metastatic colorectal cancer (mCRC). Methods: 740 mCRC patients treated with chemotherapy (CT group) and 244 patients treated with bevacizumab plus chemotherapy as first-line setting (CT + B group) were included. Propensity score analyses were used for patients' stratification and matching. Kaplan-Meier curves with log-rank tests were used to detect different overall survival (OS). Results: Patients in CT + B group had similar OS comparing with CT group only when the primary tumor located at right-side colon (20.2 for CT + B versus 19.7 months for CT group, p = 0.269). For left-side colon and rectal cancer patients, significantly longer OS were observed in CT + B than CT group. Conclusion: Our data suggested only patients with left-side colon or rectal cancer could get survival benefit from the addition of bevacizumab to first-line chemotherapy. PMID:28261339
Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos
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
Bessa Caserras, Xavier
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 Â© 2016 Elsevier España, S.L.U. All rights reserved.
Banks, Jon; Walter, Fiona M; Hall, Nicola; Mills, Katie; Hamilton, William; Turner, Katrina M
The challenge for GPs when assessing whether to refer a patient for cancer investigation is that many cancer symptoms are also caused by benign self-limiting illness. UK National Institute for Health and Care Excellence (NICE) referral guidelines emphasise that the patient should be involved in the decision-making process and be informed of the reasons for referral. Research to date, however, has not examined the extent to which these guidelines are borne out in practice. To assess the degree to which patients are involved in the decision to be referred for investigation for symptoms associated with cancer and their understanding of the referral. Qualitative interview study of patients referred to secondary care for symptoms suspicious of lung and colorectal cancer. Patients were recruited from two regions of England using maximum variation sampling. Transcribed interviews were analysed thematically. The analysis was based on 34 patient interviews. Patients in both symptom pathways reported little involvement in the decision to be referred for investigation. This tended to be accompanied by a patient expectation for referral, however, to explain ongoing and un-resolving symptoms. It was also found that reasons for referral tended to be couched in non-specific terms rather than cancer investigation, even when the patient was on a cancer-specific pathway. GPs should consider a more overt discussion with patients when referring them for further investigation of symptoms suspicious of cancer. This would align clinical practice with NICE guidelines and encourage more open discussion between GPs and primary care patients around cancer. © British Journal of General Practice 2014.
Pereyra, Lisandro; Gómez, Estanislao J; Mella, José M; Cimmino, Daniel G; Boerr, Luis A
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.
Ng, Siew C; Wong, Sunny H
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.
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
Pucciarelli, S; Chiappetta, A; Giacomazzo, G; Barina, A; Gennaro, N; Rebonato, M; Nitti, D; Saugo, M
The aim of this study was to evaluate the impact of Surgical Unit volume on the 30-day reoperation rate in patients with CRC. Data were extracted from the regional Hospital Discharge Dataset and included patients who underwent elective resection for primary CRC in the Veneto Region (2005-2013). The primary outcome measure was any unplanned reoperation performed within 30 days from the index surgery. Independent variables were: age, gender, comorbidity, previous abdominal surgery, site and year of the resection, open/laparoscopic approach and yearly Surgical Unit volume for colorectal resections as a whole, and in detail for colonic, rectal and laparoscopic resections. Multilevel multivariate regression analysis was used to evaluate the impact of variables on the outcome measure. During the study period, 21,797 elective primary colorectal resections were performed. The 30-day reoperation rate was 5.5% and was not associated with Surgical Unit volume. In multivariate multilevel analysis, a statistically significant association was found between 30-day reoperation rate and rectal resection volume (intermediate-volume group OR 0.75; 95% CI 0.56-0.99) and laparoscopic approach (high-volume group OR 0.69; 95% CI 0.51-0.96). While Surgical Unit volume is not a predictor of 30-day reoperation after CRC resection, it is associated with an early return to the operating room for patients operated on for rectal cancer or with a laparoscopic approach. These findings suggest that quality improvement programmes or centralization of surgery may only be required for subgroups of CRC patients.
Jang, Hyun Seok; Kim, Chang Hyun; Lee, Soo Young; Kim, Hyeong Rok; Kim, Young Jin
Purpose The aim of this study was to evaluate the impact of extended resection of primary tumor on survival outcome in unresectable colorectal cancer (UCRC). Methods A retrospective analysis was conducted for 190 patients undergoing palliative surgery for UCRC between 1998 and 2007 at a single institution. Variables including demographics, histopathological characteristics of tumors, surgical procedures, and course of the disease were examined. Results Kaplan-Meier survival curve indicated a significant increase in survival times in patients undergoing extended resection of the primary tumor (P < 0.001). Multivariate analysis showed that extra-abdominal metastasis (P = 0.03), minimal resection of the primary tumor (P = 0.034), and the absence of multimodality adjuvant therapy (P < 0.001) were significantly associated poor survival outcome. The histological characteristics were significantly associated with survival times. Patients with well to moderate differentiation tumors that were extensively resected had significantly increased survival time (P < 0.001), while those with poor differentiation tumors that were extensively resected did not have increase survival time (P = 0.786). Conclusion Extended resection of primary tumors significantly improved overall survival compared to minimal resection, especially in well to moderately differentiated tumors (survival time: extended resection, 27.8 ± 2.80 months; minimal resection, 16.5 ± 2.19 months; P = 0.002). PMID:27757394
Nakayama, N; Yamashita, K; Tanaka, T; Kawamata, H; Ooki, A; Sato, T; Nakamura, T; Watanabe, M
PRL-3 genomic copy number is increased in colorectal cancer (CRC), and PRL-3 expression is closely associated with lymph node and liver metastasis of CRC. However, the clinical significance of PRL-3 genomic gain for CRC remains obscure. Here, PRL-3 genomic status in 109 primary CRC tumors and in 44 CRC tumors that had metastasized to the liver, was quantified using real time PCR. Association of PRL-3 genomic status with clinicopathological factors and prognosis was assessed in detail. PRL-3 genomic gain was identified in 31 primary CRC (27.4 %) and was more frequently seen in stage III than in stage II (p = 0.025). Among the clinicopathological factors assessed, PRL-3 genomic gain was significantly associated with poorly differentiated histology (p = 0.0039). Moreover, CRC patients with PRL-3 genomic gain exhibited poorer prognosis than those with no gain in stage II-IV CRC (p = 0.017). PRL-3 genomic gain was identified in 18 (41 %) of the liver metastasis tumors, and this frequency of gain was significantly increased as compared to that of the corresponding primary CRCs (11 %) (p = 0.001). Our findings suggested that PRL-3 genomic gain may represent an aggressive phenotype of primary CRC, and may associate with liver metastasis.
Background Primary health care (PHC) professionals play a key role in population screening of colorectal cancer. The purposes of the study are: to assess knowledge and attitudes among PHC professionals with regard to colorectal cancer screening, as well as the factors that determine their support for such screening. Methods Questionnaire-based survey of PHC physicians and nurses in the Balearic Islands and in a part of the metropolitan area of Barcelona. Results We collected 1,219 questionnaires. About 84% of all professionals believe that screening for colorectal cancer by fecal occult blood test (FOBT) is effective. Around 68% would recommend to their clients a colorectal cancer screening program based on FOBT and colonoscopy. About 31% are reluctant or do not know. Professionals perceive the fear of undergoing a colonoscopy as the main obstacle in getting patients to participate, and the invasive nature of this test is the main reason behind their resistance to this program. The main barriers to support the screening program among PHC professionals are lack of knowledge (nurses) and lack of time (physicians). On multivariate analysis, the factors associated with reluctance to recommend colorectal cancer screening were: believing that FOBT has poor sensitivity and is complicated; that colonoscopy is an invasive procedure; that a lack of perceived benefit could discourage client participation; that only a minority of clients would participate; thinking that clients are fed up with screening tests and being unaware if they should be offered something to ensure their participation in the programme. Conclusions Two in every three PHC professionals would support a population screening program for colorectal cancer screening. Factors associated with reluctance to recommend it were related with screening tests characteristics as sensitivity and complexity of FOBT, and also invasive feature of colonoscopy. Other factors were related with patients' believes. PMID:20854679
Mandel, Jack S
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.
May, Folasade P; Yano, Elizabeth M; Provenzale, Dawn; Neil Steers, W; Washington, Donna L
Colorectal cancer (CRC) is a deadly but largely preventable disease. Screening improves outcomes, but screening rates vary across healthcare coverage models. In the Veterans Health Administration (VA), screening rates are high; however, it is unknown how CRC screening rates compare for Veterans with other types of healthcare coverage. To determine whether Veterans with Veteran-status-related coverage (VA, military, TRICARE) have higher rates of CRC screening than Veterans with alternate sources of healthcare coverage. We conducted a cross-sectional analysis of Veterans 50-75 years from the 2014 Behavioral Risk Factor Surveillance System survey. We examined CRC screening rates and screening modalities. We performed multivariable logistic regression to identify the role of coverage type, demographics, and clinical factors on screening status. The cohort included 22,138 Veterans. Of these, 76.7% reported up-to-date screening. Colonoscopy was the most common screening modality (83.7%). Screening rates were highest among Veterans with Veteran-status-related coverage (82.3%), as was stool-based screening (10.8%). The adjusted odds of up-to-date screening among Veterans with Veteran-status-related coverage were 83% higher than among Veterans with private coverage (adjusted OR = 1.83, 95% CI = 1.52-2.22). Additional predictors of screening included older age, black race, high income, access to medical care, frequent medical visits, and employed or married status. CRC screening rates were highest among Veterans with Veteran-status-related coverage. High CRC screening rates among US Veterans may be related to system-level characteristics of VA and military care. Insight to these system-level characteristics may inform mechanisms to improve CRC screening in non-VA settings.
Hope, Nicholas R; Murray, Graeme I
The heterogeneous nuclear ribonucleoproteins are a group of RNA-binding proteins with a range of key cellular functions, which are dysregulated in tumorigenesis including regulation of translational and RNA processing. The aims of this study were to define the heterogeneous nuclear ribonucleoprotein expression profile in primary and metastatic colorectal cancer and to establish the clinicopathologic significance of this expression. A tissue microarray containing 515 primary colorectal cancers, 224 lymph node metastasis of colorectal cancer, and 50 normal colon samples was immunostained for 6 heterogeneous nuclear ribonucleoproteins. Heterogeneous nuclear ribonucleoprotein I, heterogeneous nuclear ribonucleoprotein K, and heterogeneous nuclear ribonucleoprotein L displayed the most frequent strong immunoreactivity in primary colorectal tumor samples. Heterogeneous nuclear ribonucleoprotein A1 (P < .001) and heterogeneous nuclear ribonucleoprotein U (P = .003) showed significant alterations in nuclear expression in tumors compared with normal colonic epithelium, whereas heterogeneous nuclear ribonucleoprotein A1 (P = .001), heterogeneous nuclear ribonucleoprotein I (P < .001), and heterogeneous nuclear ribonucleoprotein K (P < .001) all showed significant aberrant cytoplasmic immunoreactivity in tumor cells. There were also significant differences in cytoplasmic immunoreactivity between the primary tumor and the corresponding lymph node metastasis for heterogeneous nuclear ribonucleoprotein A1 (P = .001), heterogeneous nuclear ribonucleoprotein I (P < .001), and heterogeneous nuclear ribonucleoprotein K (P = .001). Nuclear heterogeneous nuclear ribonucleoprotein H (χ(2) = 72.1; P < .001), cytoplasmic heterogeneous nuclear ribonucleoprotein I (χ(2) = 28.1; P < .001), and cytoplasmic heterogeneous nuclear ribonucleoprotein K (χ(2) = 13.2; P = .04) all showed significant associations with tumor stage. There was a significant relationship between strong nuclear
Lynch, Henry T; Shaw, Trudy G
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
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.
Peters, H. Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A.
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
Mao, Chen; Wu, Xin-Yin; Yang, Zu-Yao; Threapleton, Diane Erin; Yuan, Jin-Qiu; Yu, Yuan-Yuan; Tang, Jin-Ling
Current data on the concordance of KRAS, BRAF, PIK3CA mutation status or PTEN expression status between primary tumors and metastases in colorectal cancer (CRC) are conflicting. We conducted a systematic review and meta-analysis to examine concordance and discordance of the status of these four biomarkers between primary tumors and corresponding metastases in CRC patients. The biomarker status in primary tumors was used as the reference standard. Concordance data for KRAS, BRAF, PIK3CA and PTEN were provided by 43, 16, 9 and 7 studies, respectively. The pooled concordance rate was 92.0% (95% CI: 89.7%–93.9%) for KRAS, 96.8% (95% CI: 94.8%–98.0%) for BRAF, 93.9% (95% CI: 89.7%–96.5%) for PIK3CA and 71.7% (95% CI: 57.6%–82.5%) for PTEN. The pooled false positive and false negative rates for KRAS were 9.0% (95% CI: 6.5%–12.4%) and 11.3% (95% CI: 8.0%–15.8%), respectively. KRAS, BRAF and PIK3CA mutations are highly concordant between primary tumors and corresponding metastases in CRC, but PTEN loss is not. Nine percent of patients with wild-type KRAS in primary tumors who received anti-EGFR treatment had mutant KRAS in metastases, while 11.3% patients with mutant KRAS primary tumors had wild-type KRAS in the metastases. These 11.3% patients currently do not receive potentially beneficial anti-EGFR treatment. PMID:25639985
Lee, Ko-Chao; Ou, Yu-Che; Hu, Wan-Hsiang; Liu, Chia-Cheng; Chen, Hong-Hwa
Background Colorectal cancer is the third leading cause of death worldwide. Currently, novel chemotherapeutic agents are first-line therapy for unresectable stage IV colorectal cancer, while benefits of noncurative primary tumor resection in advanced disease remain debatable. Objective This meta-analysis evaluated outcomes of patients with unresectable stage IV colorectal cancer receiving systemic chemotherapy with or without primary tumor resection. Materials and methods A database search of PubMed and Cochrane Library databases identified 167 studies that were screened for relevance. After 119 were excluded, 48 were assessed for eligibility and 26 were included for meta-analysis, including 24 retrospective studies, one prospective study, and one randomized, controlled trial. Extracted data included patient demographics (age, sex), clinical data (tumor stage, metastasis), targeted therapy agents, and surgical data (with/without tumor resection). Patients’ overall and progression-free survival was compared between groups with/without primary tumor resection. Results The 26 studies included 43,903 patients with colorectal cancer, with 29,639 receiving chemotherapy/radiotherapy plus primary tumor resection, and 14,264 managed medically with chemotherapy/chemoradiotherapy alone without primary tumor resection. Patients receiving primary tumor resection plus chemotherapy/radiotherapy had longer overall survival (hazard ratio [HR 0.59], 95% confidence interval [CI] 0.51–0.68; P<0.001), with significant differences in overall survival between patients with and without primary tumor resection (HR 0.58, 95% CI 0.49–0.68; P<0.001). Longer overall survival was also found among patients receiving primary tumor resection who were treated with bevacizumab/cetuximab targeted therapy agents (HR 0.63, 95% CI 0.46–0.86; P=0.003). Patients from three studies who received primary tumor resection had longer progression-free survival (HR 0.73, 95% CI 0.58–0.91; P=0
Brenner, Alison Tytell; Ko, Linda K; Janz, Nancy; Gupta, Shivani; Inadomi, John
Colorectal cancer (CRC) is an important cause of cancer death in adults in the U.S.; screening is effective but underutilized, particularly among minorities. The purpose of this paper was to explore whether health belief model (HBM) constructs pertaining to CRC screening differ by race/ethnicity and primary language. Data were from the baseline surveys of 933 participants (93.5%) in a randomized trial promoting CRC screening in San Francisco. Composite scores for each construct were created from multiple items, dichotomized for analysis, and analyzed using multivariate logistic regression. Most participants were Asian (29.7%) or Hispanic (34.3%), and many were non-English speakers. Non-English speaking Hispanics (p<.001) and English-speaking Asians (p=.002) reported lower perceived susceptibility than non-Hispanic Whites (NHW). Non-English speaking Hispanics reported more and non-English speaking Asians fewer perceived barriers (psychological and structural) than NHW. Understanding how different populations think about CRC screening may be critical in promoting screening in diverse populations.
... 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 ...
Onstenk, Wendy; Sieuwerts, Anieta M.; Mostert, Bianca; Lalmahomed, Zarina; Bolt-de Vries, Joan B.; van Galen, Anne; Smid, Marcel; Kraan, Jaco; Van, Mai; de Weerd, Vanja; Ramírez-Moreno, Raquel; Biermann, Katharina; Verhoef, Cornelis; Grünhagen, Dirk J.; IJzermans, Jan N.M.; Gratama, Jan W.; Martens, John W.M.; Foekens, John A.; Sleijfer, Stefan
Background CTCs are a promising alternative for metastatic tissue biopsies for use in precision medicine approaches. We investigated to what extent the molecular characteristics of circulating tumor cells (CTCs) resemble the liver metastasis and/or the primary tumor from patients with metastatic colorectal cancer (mCRC). Results The CTC profiles were concordant with the liver metastasis in 17/23 patients (74%) and with the primary tumor in 13 patients (57%). The CTCs better resembled the liver metastasis in 13 patients (57%), and the primary tumor in five patients (22%). The strength of the correlations was not associated with clinical parameters. Nine genes (CDH1, CDH17, CDX1, CEACAM5, FABP1, FCGBP, IGFBP3, IGFBP4, and MAPT) displayed significant differential expressions, all of which were downregulated, in CTCs compared to the tissues in the 23 patients. Patients and Methods Patients were retrospectively selected from a prospective study. Using the CellSearch System, CTCs were enumerated and isolated just prior to liver metastasectomy. A panel of 25 CTC-specific genes was measured by RT-qPCR in matching CTCs, primary tumors, and liver metastases. Spearman correlation coefficients were calculated and considered as continuous variables with r=1 representing absolute concordance and r= -1 representing absolute discordance. A cut-off of r>0.1 was applied in order to consider profiles to be concordant. Conclusions In the majority of the patients, CTCs reflected the molecular characteristics of metastatic cells better than the primary tumors. Genes involved in cell adhesion and epithelial-to-mesenchymal transition were downregulated in the CTCs. Our results support the use of CTC characterization as a liquid biopsy for precision medicine. PMID:27340863
Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H
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
Cox, Thomas R; Erler, Janine T
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.
Wang, Judy Huei-yu; Liang, Wenchi; Ma, Grace X; Gehan, Edmund; Wang, Haoying Echo; Ji, Cheng-Shuang; Tu, Shin-Ping; Vernon, Sally W; Mandelblatt, Jeanne S
Chinese Americans underutilize colorectal cancer screening. This study evaluated a physician-based intervention guided by social cognitive theory (SCT) to inform future research involving minority physicians and patients. Twenty-five Chinese-speaking primary care physicians were randomized into intervention or usual care arms. The intervention included two 45-minute in-office training sessions paired with a dual-language communication guide detailing strategies in addressing Chinese patients' screening barriers. Physicians' feedback on the intervention, their performance data during training, and pre-post intervention survey data were collected and analyzed. Most physicians (~85%) liked the intervention materials but ~84% spent less than 20 minutes reading the guide and only 46% found the length of time for in-office training acceptable. Despite this, the intervention increased physicians' perceived communication self-efficacy with patients (p<.01). This study demonstrated the feasibility of enrolling and intervening with minority physicians. Time constraints in primary care practice should be considered in the design and implementation of interventions.
Goel, Ajay; Boland, C Richard
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.
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.
Lung, M S; Trainer, A H; Campbell, I; Lipton, L
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.
Zhu, Bo; Li, Yongsheng
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
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
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?
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.
Balogh, A; Kahán, Z; Maráz, A; Mikó, T; Nagy, F; Palkó, A; Thurzó, L; Tiszlavicz, L
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.
Boland, C. Richard; Goel, Ajay
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
Lairson, David R; Dicarlo, Melissa; Deshmuk, Ashish A; Fagan, Heather B; Sifri, Randa; Katurakes, Nora; Cocroft, James; Sendecki, Jocelyn; Swan, Heidi; Vernon, Sally W; Myers, Ronald E
Colorectal cancer (CRC) screening is cost-effective but underused. The objective of this study was to determine the cost-effectiveness of a mailed standard intervention (SI) and tailored navigation interventions (TNIs) to increase CRC screening use in the context of a randomized trial among primary care patients. Participants (n = 945) were randomized either to a usual care control group (n = 317), to an SI group (n = 316), or to a TNI group (n = 312). The SI group was sent both colonoscopy instructions and stool blood tests irrespective of baseline preference. TNI group participants were sent instructions for scheduling a colonoscopy, a stool blood test, or both based on their test preference, as determined at baseline; then, they received a navigation telephone call. Activity cost estimation was used to determine the cost of each intervention and to compute incremental cost-effectiveness ratios. Statistical uncertainty within the base case was assessed with 95% confidence intervals derived from net benefit regression analysis. The effects of uncertain parameters, such as the cost of planning, training, and involvement of those receiving "investigator salaries," were assessed with sensitivity analyses. Program costs of the SI were $167 per participant. The average cost of the TNI was $289 per participant. The TNI was more effective than the SI but substantially increased the cost per additional individual screened. Decision-makers need to consider cost structure, level of planning, and training required to implement these 2 intervention strategies and their willingness to pay for additional individuals screened to determine whether a tailored navigation would be justified and feasible. © 2013 American Cancer Society.
Sehdev, Amikar; Shih, Ya-Chen T; Vekhter, Benjamin; Bissonnette, Marc B; Olopade, Olufunmilayo I; Polite, Blase N
Emerging evidence from observational studies has suggested that metformin may be beneficial in the primary prevention of colorectal cancer (CRC). However, to the authors' knowledge, none of these studies was conducted in a US population. Because environmental factors such as Western diet and obesity are implicated in the causation of CRC, a large case-control study was performed to assess the effects of metformin on the incidence of CRC in a US population. MarketScan databases were used to identify diabetic patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to 2 controls matched for age, sex, and geographical region were selected for each case. Metformin exposure was assessed by prescription tracking within the 12-month period before the index date. Conditional logistic regression was used to adjust for multiple potential confounders and to calculate adjusted odds ratios (AORs). The mean age of the study participants was 55 years and 57 years, respectively, in the control and case groups (P = 1.0). Approximately 60% of the study participants were male and 40% were female in each group. In the multivariable model, any metformin use was associated with a 15% reduction in the odds of CRC (AOR, 0.85; 95% confidence interval, 0.76-0.95 [P = .007]). After adjusting for health care use, the beneficial effect of metformin was reduced to 12% (AOR, 0.88; 95% confidence interval, 0.77-1.00 [P = .05]). The dose-response analyses demonstrated no significant association with metformin dose, duration, or total exposure. Metformin use appears to be associated with a reduced risk of developing CRC among diabetic patients in the United States. © 2014 American Cancer Society.
Johnson, Robert L.; Fleet, James C.
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
Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro; Ishigamori, Rikako
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
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.
Kreisler, Esther; Biondo, Sebastiano; Martí-Ragué, Joan
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.
Yee, Judy; Kim, David H; Rosen, Max P; Lalani, Tasneem; Carucci, Laura R; Cash, Brooks D; Feig, Barry W; Fowler, Kathryn J; Katz, Douglas S; Smith, Martin P; Yaghmai, Vahid
Colorectal cancer is the third leading cause of cancer deaths in the United States. Most colorectal cancers can be prevented by detecting and removing the precursor adenomatous polyp. Individual risk factors for the development of colorectal cancer will influence the particular choice of screening tool. CT colonography (CTC) is the primary imaging test for colorectal cancer screening in average-risk individuals, whereas the double-contrast barium enema (DCBE) is now considered to be a test that may be appropriate, particularly in settings where CTC is unavailable. Single-contrast barium enema has a lower performance profile and is indicated for screening only when CTC and DCBE are not available. CTC is also the preferred test for colon evaluation following an incomplete colonoscopy. Imaging tests including CTC and DCBE are not indicated for colorectal cancer screening in high-risk patients with polyposis syndromes or inflammatory bowel disease. This paper presents the updated colorectal cancer imaging test ratings and is the result of evidence-based consensus by the ACR Appropriateness Criteria Expert Panel on Gastrointestinal Imaging. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Siegel, Rebecca L; Miller, Kimberly D; Fedewa, Stacey A; Ahnen, Dennis J; Meester, Reinier G S; Barzi, Afsaneh; Jemal, Ahmedin
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
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
Degrolard-Courcet, Emilie; Sokolowska, Joanna; Padeano, Marie-Martine; Guiu, Séverine; Bronner, Myriam; Chery, Carole; Coron, Fanny; Lepage, Côme; Chapusot, Caroline; Loustalot, Catherine; Jouve, Jean-Louis; Hatem, Cyril; Ferrant, Emmanuelle; Martin, Laurent; Coutant, Charles; Baurand, Amandine; Couillault, Gérard; Delignette, Alexandra; El Chehadeh, Salima; Lizard, Sarab; Arnould, Laurent; Fumoleau, Pierre; Callier, Patrick; Mugneret, Francine; Philippe, Christophe; Frebourg, Thierry; Jonveaux, Philippe; Faivre, Laurence
Fanconi anaemia (FA) is characterized by progressive bone marrow failure, congenital anomalies, and predisposition to malignancy. In a minority of cases, FA results from biallelic FANCD1/BRCA2 mutations that are associated with early-onset leukaemia and solid tumours. Here, we describe the clinical and molecular features of a remarkable family presenting with multiple primary colorectal cancers (CRCs) without detectable mutations in genes involved in the Mendelian predisposition to CRCs. We unexpectedly identified, despite the absence of clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2 corresponding to a frameshift alteration (c.1845_1846delCT, p.Asn615Lysfs*6) and a missense mutation (c.7802A>G, p.Tyr2601Cys). The diagnosis of FA was confirmed by the chromosomal analysis of lymphocytes. Reverse transcriptase (RT)-PCR analysis revealed that the c.7802A>G BRCA2 variation was in fact a splicing mutation that creates an aberrant splicing donor site and results partly into an aberrant transcript encoding a truncated protein (p.Tyr2601Trpfs*46). The atypical FA phenotype observed within this family was probably explained by the residual amount of BRCA2 with the point mutation c.7802A>G in the patients harbouring the biallelic FANCD1/BRCA2 mutations. Although this report is based in a single family, it suggests that CRCs may be part of the tumour spectrum associated with FANCD1/BRCA2 biallelic mutations and that the presence of such mutations should be considered in families with CRCs, even in the absence of cardinal features of FA.
Lairson, David; DiCarlo, Melissa; Deshmuk, Ashish A.; Fagan, Heather B.; Sifri, Randa; Katurakes, Nora; Cocroft, James; Sendecki, Jocelyn; Swan, Heidi; Vernon, Sally W.; Myers, Ronald E.
Background Colorectal cancer (CRC) screening is cost-effective but underutilized. This study aimed to determine the cost-effectiveness of mailed standard intervention (SI) and tailored navigation interventions (TNI) to increase CRC screening use in the context of a randomized trial among primary care patients. Methods Participants (n=945) were randomized either to a usual care Control Group (n=317), SI Group (n=316), or TNI Group (n=312). The SI Group was sent both colonoscopy instructions and stool blood tests irrespective of baseline preference. TNI Group participants were sent instructions for scheduling a colonoscopy, a stool blood test, or both based on their test preference as determined at baseline, and then received a navigation telephone call. Activity cost estimation was used to determine the cost of each intervention and compute incremental cost-effectiveness ratios . Statistical uncertainty within the base case was assessed with 95 percent confidence intervals derived from net benefit regression analysis. Effects of uncertain parameters such as the cost of planning, training, and involvement of those receiving “investigator salaries” were assessed with sensitivity analyses. Results Program costs of the SI were $167 per participant. Average cost of the TNI was $289 per participant. Conclusion The TNI was more effective than the SI, but substantially increased the cost per additional person screened. Decision-makers need to consider cost structure, level of planning, and training required to implement these two intervention strategies, and their willingness to pay for additional persons screened, to determine whether tailored navigation would be justified and feasible. PMID:24435411
Sehdev, Amikar; Shih, Ya-Chen T.; Vekhter, Benjamin; Bissonnette, Marc; Olopade, Olufunmilayo I.; Polite, Blase
Background Emerging evidence from observational studies suggests that metformin may be beneficial in the primary prevention of colorectal cancer (CRC). However, none of these were conducted in a US population. Since environmental factors, such as Western diet and obesity, are implicated in the causation of CRC, we conducted a large case control study to assess the effects of metformin on CRC incidence in a US population. Methods MarketScan® databases were used to identify diabetic patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to two controls matched for age, sex and geographical region, were selected for each case. Metformin exposure was assessed by prescription tracking in the 12 months period prior to the index date. Conditional logistic regression was used to adjust for multiple potential confounders and to calculate adjusted odds ratios (AOR). Results The mean age of participants was 55 and 57 years in the control and case group, respectively (p=1.0). Sixty percent of the study participants were males and 40% were females in each group. In the multivariable model, any metformin use was associated with 15% reduced odds of CRC (AOR, 0.85, 95% confidence interval (CI), 0.76–0.95, p<0.007). After adjusting for health-care utilization the beneficial effect of metformin was reduced to 12% (AOR, 0.88, 95% CI, 0.77–1.00, p=0.05). The dose-response analyses showed no significant association with metformin dose, duration or total exposure. Conclusions Metformin use is associated with reduced risk of developing CRC among diabetic patients in the US population. PMID:25424411
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
Liedtke, Cornelia; Kolberg, Hans-Christian
Summary Background (Metastatic) breast cancer is a heterogeneous entity in which every disease subtype requires an individualized systemic treatment approach. Methods We reviewed the currently available data regarding systemic therapy of breast cancer and present a review of historical and current treatment approaches, with the publications cited covering a time span from 1896 to the last ASCO 2015. Results Systemic therapy of metastatic breast cancer may include chemotherapy, endocrine therapy, and targeted therapies (e.g. antibody-based approaches). Based on the patient's breast cancer subtype, these agents may be employed alone or in combination. Therefore, characterization of the phenotype of the disease is necessary and may include biopsy of the metastatic site. Novel therapeutic approaches include immunologic therapies as well as PARP, PI3K and CDK 4/6 inhibitors, which are currently under investigation in clinical trials. Conclusion Systemic therapy of metastatic breast cancer requires complex and individualized treatment approaches that are best offered in an interdisciplinary setting. PMID:26889146
Gillen, C D; Andrews, H A; Prior, P; Allan, R N
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
Guiriguet-Capdevila, Carolina; Muñoz-Ortiz, Laura; Rivero-Franco, Irene; Vela-Vallespín, Carme; Vilarrubí-Estrella, Mercedes; Torres-Salinas, Miquel; Grau-Cano, Jaume; Burón-Pust, Andrea; Hernández-Rodríguez, Cristina; Fuentes-Peláez, Antonio; Reina-Rodríguez, Dolores; De León-Gallo, Rosa; Mendez-Boo, Leonardo; Torán-Monserrat, Pere
Colorectal cancer is an important public health problem in Spain. Over the last decade, several regions have carried out screening programmes, but population participation rates remain below recommended European goals. Reminders on electronic medical records have been identified as a low-cost and high-reach strategy to increase participation. Further knowledge is needed about their effect in a population-based screening programme. The main aim of this study is to evaluate the effectiveness of an electronic reminder to promote the participation in a population-based colorectal cancer screening programme. Secondary aims are to learn population's reasons for refusing to take part in the screening programme and to find out the health professionals' opinion about the official programme implementation and on the new computerised tool. This is a parallel randomised trial with a cross-sectional second stage. all the invited subjects to participate in the public colorectal cancer screening programme that includes men and women aged between 50-69, allocated to the eleven primary care centres of the study and all their health professionals. The randomisation unit will be the primary care physician. The intervention will consist of activating an electronic reminder, in the patient's electronic medical record, in order to promote colorectal cancer screening, during a synchronous medical appointment, throughout the year that the intervention takes place. A comparison of the screening rates will then take place, using the faecal occult blood test of the patients from the control and the intervention groups. We will also take a questionnaire to know the opinions of the health professionals. The main outcome is the screening status at the end of the study. Data will be analysed with an intention-to-treat approach. We expect that the introduction of specific reminders in electronic medical records, as a tool to facilitate and encourage direct referral by physicians and nurse
Background Colorectal cancer is an important public health problem in Spain. Over the last decade, several regions have carried out screening programmes, but population participation rates remain below recommended European goals. Reminders on electronic medical records have been identified as a low-cost and high-reach strategy to increase participation. Further knowledge is needed about their effect in a population-based screening programme. The main aim of this study is to evaluate the effectiveness of an electronic reminder to promote the participation in a population-based colorectal cancer screening programme. Secondary aims are to learn population’s reasons for refusing to take part in the screening programme and to find out the health professionals’ opinion about the official programme implementation and on the new computerised tool. Methods/Design This is a parallel randomised trial with a cross-sectional second stage. Participants: all the invited subjects to participate in the public colorectal cancer screening programme that includes men and women aged between 50–69, allocated to the eleven primary care centres of the study and all their health professionals. The randomisation unit will be the primary care physician. The intervention will consist of activating an electronic reminder, in the patient’s electronic medical record, in order to promote colorectal cancer screening, during a synchronous medical appointment, throughout the year that the intervention takes place. A comparison of the screening rates will then take place, using the faecal occult blood test of the patients from the control and the intervention groups. We will also take a questionnaire to know the opinions of the health professionals. The main outcome is the screening status at the end of the study. Data will be analysed with an intention-to-treat approach. Discussion We expect that the introduction of specific reminders in electronic medical records, as a tool to facilitate
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.
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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.
Kim, Sung-Hyun; Choi, So-Jung; Park, Joon Suk; Lee, Jinseon; Cho, Yong Beom; Kang, Min-Woong; Lee, Woo Yong; Choi, Yong Soo; Kim, Hong Kwan; Han, Joungho; Chun, Ho-Kyung; Kim, Jhingook
In metastatic colorectal cancers, tumor cells are disseminated prior to surgical resection of the primary tumor but remain dormant until proper colonization mechanisms are activated. To identify the colonization mechanisms of the metastatic tumors, we conducted a pairwise comparison between primary colorectal cancers and metastatic tumors (n=12 pairs), including six hepatic pairs and six pulmonary pairs. The mRNA levels of 224 genes previously reported to be associated with metastasis, cytokines and angiogenesis were quantitatively determined by PCR arrays. Among them, 27 genes were duplicated or triplicated to show consistent expression. Unsupervised hierarchical clustering of the Ct values of metastasis-related genes revealed that liver metastases were indistinguishable from primary colorectal cancers (n=5/6), whereas lung metastases were highly diversified from one another and from the primary tumors (n=6/6). Cytokines and receptor gene expression array data also confirmed the divergence of pulmonary metastases from primary colorectal cancers (n=6/6). Heat map analyses of ΔCt values of the metastasis-related genes identified a 17-gene tropism signature that was sufficient not only to distinguish liver and the lung metastases, but also reconstituted the clustering of primary tumors with the hepatic metastases (n=17/18). In this pilot experiment, pulmonary metastases were significantly diverged from hepatic metastases that were indistinguishable from primary colorectal cancers. Further genomic and clinical studies are in progress to evaluate the potential of the tropism signature as a therapeutic target to inhibit the colonization of metastatic colorectal cancers.
Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu
Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m2, twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer. PMID:27920486
Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu
Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m(2), twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer.
Coughlin, Steven S; Blumenthal, Daniel S; Seay, Shirley Jordan; Smith, Selina A
In the USA, race and socioeconomic status are well-known factors associated with colorectal cancer incidence and mortality rates. These are higher among blacks than whites and other racial/ethnic groups. In this article, we review opportunities to address disparities in colorectal cancer incidence, mortality, and survivorship among African Americans. First, we summarize the primary prevention of colorectal cancer and recent advances in the early detection of the disease and disparities in screening. Then, we consider black-white disparities in colorectal cancer treatment and survival including factors that may contribute to such disparities and the important roles played by cultural competency, patient trust in one's physician, and health literacy in addressing colorectal cancer disparities, including the need for studies involving the use of colorectal cancer patient navigators who are culturally competent. To reduce these disparities, intervention efforts should focus on providing high-quality screening and treatment for colorectal cancer and on educating African Americans about the value of diet, weight control, screening, and treatment. Organized approaches for delivering colorectal cancer screening should be accompanied by programs and policies that provide access to diagnostic follow-up and treatment for underserved populations.
Blumenthal, Daniel S.; Seay, Shirley Jordan; Smith, Selina A.
Background In the USA, race and socioeconomic status are well-known factors associated with colorectal cancer incidence and mortality rates. These are higher among blacks than whites and other racial/ethnic groups. Methods In this article, we review opportunities to address disparities in colorectal cancer incidence, mortality, and survivorship among African Americans. Results First, we summarize the primary prevention of colorectal cancer and recent advances in the early detection of the disease and disparities in screening. Then, we consider black-white disparities in colorectal cancer treatment and survival including factors that may contribute to such disparities and the important roles played by cultural competency, patient trust in one’s physician, and health literacy in addressing colorectal cancer disparities, including the need for studies involving the use of colorectal cancer patient navigators who are culturally competent. Conclusion To reduce these disparities, intervention efforts should focus on providing high-quality screening and treatment for colorectal cancer and on educating African Americans about the value of diet, weight control, screening, and treatment. Organized approaches for delivering colorectal cancer screening should be accompanied by programs and policies that provide access to diagnostic follow-up and treatment for underserved populations. PMID:27294749
Zheng, Yu-Fang; Yang, Jun; Zhao, Xin-Jie; Feng, Bo; Kong, Hong-Wei; Chen, Ying-Jie; Lv, Shen; Zheng, Min-Hua; Xu, Guo-Wang
AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer. METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10 patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method. RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%). Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke’s stages of colorectal cancer. When monitoring the changes in urinary nucleoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32) and 91% (10/11) in response group and progressive group, respectively. CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer. PMID:15991285
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
El-Tawil, Ahmed Mahmoud
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.
El-Tawil, Ahmed Mahmoud
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
Gervaz, Pascal; Rubbia-Brandt, Laura; Andres, Axel; Majno, Pietro; Roth, Arnaud; Morel, Philippe; Mentha, Gilles
We report the histopathological results of a novel "inversed" strategy designed to manage patients with colorectal cancer (CRC) who have synchronous liver metastases by using chemotherapy first, liver surgery second, and resection of the primary tumor as a final step. This study was designed to compare the response to chemotherapy in liver metastases, primary tumors, and locoregional lymph nodes. Twenty-nine patients with stage IV CRC received a combination of oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin (OCFL) for 3-4 months. Histological response to chemotherapy was assessed by using a tumor regression grading (TRG) score based on presence of residual tumor cells and extent of fibrosis. Median age of patients was 56 (range, 37-69) years. Primary tumor location was right colon (n = 5), left colon (n = 7), and rectum (n = 17 patients). TRG scores correlated across disease sites (Spearman correlation coefficients for TRG in the primary tumor and lymph nodes was 0.59 [P = 0.005]; for the primary tumor and metastases 0.44 [P = 0.021]; and for lymph nodes and metastases 0.58 [P = 0.006]). Complete absence or poor tumor response (TRG4/5) was significantly more frequent in primary tumors (35.7%) and locoregional lymph nodes (38%) than in liver metastases (6.9%; McNemar test, P = 0.02). Two patients had a complete pathologic response (pT0N0M0). In patients with stage IV colorectal cancer, liver metastases exhibit a better histological response than primary tumors to OCFL neoadjuvant chemotherapy.
Song, Mingyang; Garrett, Wendy S; Chan, Andrew T
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.
Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.
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
Ji, Hong; Greening, David W; Barnes, Thomas W; Lim, Justin W; Tauro, Bow J; Rai, Alin; Xu, Rong; Adda, Christopher; Mathivanan, Suresh; Zhao, Wei; Xue, Yanhong; Xu, Tao; Zhu, Hong-Jian; Simpson, Richard J
Exosomes are small extracellular 40-100 nm diameter membrane vesicles of late endosomal origin that can mediate intercellular transfer of RNAs and proteins to assist premetastatic niche formation. Using primary (SW480) and metastatic (SW620) human isogenic colorectal cancer cell lines we compared exosome protein profiles to yield valuable insights into metastatic factors and signaling molecules fundamental to tumor progression. Exosomes purified using OptiPrep™ density gradient fractionation were 40-100 nm in diameter, were of a buoyant density ~1.09 g/mL, and displayed stereotypic exosomal markers TSG101, Alix, and CD63. A major finding was the selective enrichment of metastatic factors (MET, S100A8, S100A9, TNC), signal transduction molecules (EFNB2, JAG1, SRC, TNIK), and lipid raft and lipid raft-associated components (CAV1, FLOT1, FLOT2, PROM1) in exosomes derived from metastatic SW620 cells. Additionally, using cryo-electron microscopy, ultrastructural components in exosomes were identified. A key finding of this study was the detection and colocalization of protein complexes EPCAM-CLDN7 and TNIK-RAP2A in colorectal cancer cell exosomes. The selective enrichment of metastatic factors and signaling pathway components in metastatic colon cancer cell-derived exosomes contributes to our understanding of the cross-talk between tumor and stromal cells in the tumor microenvironment.
... 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 ...
Pestalozzi, B C; Jäger, D; Knuth, A
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.
Zhang, Ya-Li; Zhang, Zhen-Su; Wu, Ba-Ping; Zhou, Dian-Yuan
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
Centelles, Josep J.
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
Centelles, Josep J
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.
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
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
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.
Armbrust, Thomas; Sobotta, Michael; Füzesi, Laszlo; Grabbe, Eckhardt; Ramadori, Giuliano
Although modern chemotherapy of stage IV advanced colorectal cancer (CRC) has impressively improved overall survival, the response of the primary tumor has not been studied because surgical resection of the primary continues to be the standard procedure in stage IV CRC. Long-term follow-up of the primary in patients with stage IV CRC under chemotherapy. Here we report on the histological changes in the primary tumor in four patients suffering from stage IV CRC. Systemic chemotherapy was started immediately after endoscopic tumor debulking in three cases. In one case no endoscopic intervention was performed before chemotherapy. Neither macroscopic nor histological evidence for malignant tumor growth was found at the former site of the primary after 6, 23, 26 or 48 months, respectively. Two patients had a complete suppression of the primary, two patients had an adenoma at the former site of the primary. To date, three patients have died because of progression of liver metastases and one patient is still alive with no signs of tumor growth. The four cases illustrate that today's chemotherapy may effectively induces suppression of the primary in CRC. The development of CRC may follow different pathways.
Yoshida, Yoichiro; Hoshino, Seiichiro; Aisu, Naoya; Naito, Masayasu; Miyake, Toru; Tanimura, Syu; Yamashita, Yuichi
The start of chemotherapy usually requires a delay of about 4 weeks after surgical resection of colorectal cancer. However, there is no evidence for the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. We therefore conducted a pilot study to determine the safety and feasibility of an early start of chemotherapy after the resection of colorectal cancer with distant metastases. Five patients were enrolled. They received XELOX therapy (130 mg/m2 of oxaliplatin on day 1 plus 1,000 mg/m2 of capecitabine twice daily on days 1 to 14) on the 7th postoperative day and XELOX + bevacizumab (7.5 mg/kg of bevacizumab on day 1) after the 2nd cycle of chemotherapy. Five patients underwent open surgery. The procedures included right hemicolectomy in 1 patient, sigmoidectomy in 2 patients, high anterior resection in 1 patient, and Hartmann procedure in 1 patient. All patients started chemotherapy on postoperative day 7. The median number of cycles of chemotherapy was 11 (8 to 22). No postoperative complications were observed. The tumor reduction rate was 44.3% (32.0 to 66.6%). Progression-free survival was 10.3 months. An early start of chemotherapy after surgery is feasible and safe. These findings suggest possible changes in the start time of chemotherapy after surgery in the future. We have already started a new phase II trial to confirm the effects of the early start of chemotherapy after surgery. UMIN000004361.
Bronte, Giuseppe; Silvestris, Nicola; Castiglia, Marta; Galvano, Antonio; Passiglia, Francesco; Sortino, Giovanni; Cicero, Giuseppe; Rolfo, Christian; Peeters, Marc; Bazan, Viviana; Fanale, Daniele; Giordano, Antonio; Russo, Antonio
Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid biopsy, which helps to isolate circulating tumor DNA, is an innovative method to study both primary and acquired resistance to anti-EGFR monoclonal antibodies. However, high-sensitivity techniques should be used to enable the identification of a wide set of gene mutations related to resistance.
Castiglia, Marta; Galvano, Antonio; Passiglia, Francesco; Sortino, Giovanni; Cicero, Giuseppe; Rolfo, Christian; Peeters, Marc; Bazan, Viviana; Fanale, Daniele; Giordano, Antonio; Russo, Antonio
Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid biopsy, which helps to isolate circulating tumor DNA, is an innovative method to study both primary and acquired resistance to anti-EGFR monoclonal antibodies. However, high-sensitivity techniques should be used to enable the identification of a wide set of gene mutations related to resistance. PMID:26318427
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Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomised trials.
Faron, Matthieu; Pignon, Jean-Pierre; Malka, David; Bourredjem, Abderrahmane; Douillard, Jean-Yves; Adenis, Antoine; Elias, Dominique; Bouché, Olivier; Ducreux, Michel
To evaluate the impact on survival of primary tumour resection in patients with unresectable synchronous metastases from colorectal cancer (CRC). Primary tumour resection in this setting remains controversial. We retrieved individual data of 1155 patients with metastatic CRC included in four first-line chemotherapy trials: Fédération Francophone de Cancérologie Digestive (FFCD)-9601, FFCD-2000-05, Actions Concertées dans les cancers COloRectaux et Digestifs (ACCORD)-13, and ML-16987. Patients with unresectable synchronous metastases were eligible for this study. We used univariate and multivariate analyses (Cox models stratified on the trial) to assess the impact of primary tumour resection and other potential prognostic variables on overall survival (OS) (the primary endpoint). Amongst the 1155 patients, 810 patients met the inclusion criteria and 59% (n = 478) underwent resection of their primary tumour, prior to trial entry (resection group). Compared to patients in the non-resection group (n =3 32 [41%]), those in the resection group were more likely to have a colonic primary, lower baseline carcinoembryonic antigen (CEA) and alkaline phosphatase levels, and normal white-blood-cell count (p < 0.001 each). Primary tumour resection was independently associated to better OS in multivariate analysis (hazard ratio (HR), 0.63 [0.53-0.75]; p < 0.001, with a more favourable impact of resection on OS in case of rectal primary and low CEA level. Primary tumour resection was also independently associated to a better progression-free survival in multivariate analysis (HR, 0.82 [0.70-0.95]; p < 0.001). Primary tumour resection was independently associated to a better OS in patients with CRC and unresectable synchronous metastases. Copyright © 2014 Elsevier Ltd. All rights reserved.
Zhou, Min-Wei; Gu, Xiao-Dong; Xiang, Jian-Bin; Chen, Zong-You
This study was performed to compare the clinical safety and outcomes of laparoscopic versus open surgery for primary tumors in patients with stage IV colorectal cancer. Pertinent studies were selected from the MEDLINE, EMBASE, and Cochrane Library databases; references from published articles; and reviews. Both prospective and retrospective studies were included for the meta-analysis. Clinical outcomes included safety, complications, mortality, and survival. Six trials involving 1802 patients were included. The operative time was longer for laparoscopic than for open surgery (mean difference (MD) = 44.20, 95 % confidence interval (CI) 17.31-71.09, Z = 3.22, P = 0.001). Laparoscopic surgery was also associated with fewer postoperative complications (odds ratio 0.53, 95 % CI 0.37-0.78, Z = 3.29, P = 0.001) and less operative blood loss (MD = -65.40, 95 % CI -102.37 to -28.42, Z = 3.47, P = 0.0005). Median survival ranged from 11.4 to 30.1 months. The total hospital stay was 1.68 days shorter for laparoscopic than for open surgery (95 % CI -1.83 to -1.53, Z = 21.64, P < 0.00001). Laparoscopic surgery for palliative resection of stage IV colorectal cancer is associated with better perioperative outcomes than open surgery.
Christy, Shannon M.; Perkins, Susan M.; Tong, Yan; Krier, Connie; Champion, Victoria L.; Skinner, Celette Sugg; Springston, Jeffrey K.; Imperiale, Thomas F.; Rawl, Susan M.
Background Provider recommendation is a predictor of colorectal cancer (CRC) screening. Purpose To compare the effects of two clinic-based interventions on patient–provider discussions about CRC screening. Design Two-group RCT with data collected at baseline and 1 week post-intervention. Participants/setting African-American patients that were non-adherent to CRC screening recommendations (n=693) with a primary care visit between 2008 and 2010 in one of 11 urban primary care clinics. Intervention Participants received either a computer-delivered tailored CRC screening intervention or a nontailored informational brochure about CRC screening immediately prior to their primary care visit. Main outcome measures Between-group differences in odds of having had a CRC screening discussion about a colon test, with and without adjusting for demographic, clinic, health literacy, health belief, and social support variables, were examined as predictors of a CRC screening discussion using logistic regression. Intervention effects on CRC screening test order by PCPs were examined using logistic regression. Analyses were conducted in 2011 and 2012. Results Compared to the brochure group, a greater proportions of those in the computer-delivered tailored intervention group reported having had a discussion with their provider about CRC screening (63% vs 48%, OR=1.81, p<0.001). Predictors of a discussion about CRC screening included computer group participation, younger age, reason for visit, being unmarried, colonoscopy self-efficacy, and family member/friend recommendation (all p-values <0.05). Conclusions The computer-delivered tailored intervention was more effective than a nontailored brochure at stimulating patient–provider discussions about CRC screening. Those who received the computer-delivered intervention also were more likely to have a CRC screening test (fecal occult blood test or colonoscopy) ordered by their PCP. Trial registration This study is registered at www
Takata, Yumie; Kristal, Alan R.; King, Irena B.; Song, Xiaoling; Diamond, Alan M.; Foster, Charles B.; Hutter, Carolyn M.; Hsu, Li; Duggan, David J.; Langer, Robert D.; Petrovitch, Helen; Shikany, James M.; Vaughan, Thomas L.; Lampe, Johanna W.; Prentice, Ross L.; Peters, Ulrike
Background Selenium may prevent colorectal cancer. However, several previous studies are small and few investigated the associations between selenium and colorectal cancer among women, whose selenium metabolism may differ from men. Methods This nested case-control study investigated whether serum selenium concentration and genetic variants in five selenoenzymes (glutathione peroxidase 1-4 and selenoprotein P) were associated with colorectal cancer risk in 804 colorectal cancer cases and 805 matched controls from the Women’s Health Initiative (WHI) Observational Study. A meta-analysis was conducted to compare the WHI result with previous studies including 12 observational studies and two clinical trials on selenium. Results Within the WHI, selenium concentrations were relatively high (mean = 135.6 μg/L) and were not associated with colorectal cancer risk (p for trend = 0.10); the adjusted odds ratio (OR) comparing the fifth with first quintile was 1.26 [95% confidence intervals (CI) = 0.91-1.73]. Moreover, genetic variants in selenoenzymes were not significantly associated with colorectal cancer risk. Consistent with the finding in WHI, our meta-analysis showed no association between selenium and colorectal tumor risk in women (OR = 0.97, 95% CI = 0.79-1.18 comparing the highest quantile with the lowest); however, in men, there was a significant inverse association (OR = 0.68, 95% CI = 0.57-0.82) (p = 0.01). Conclusion Consistent with previous studies, we observed no protective effect of selenium on colorectal cancer among women. Impact Our analyses suggest a population with relatively high selenium concentrations, especially women, would not benefit from increasing selenium intake. PMID:21765007
Ahmad, Muayyad M; Dardas, Latefa; Dardas, Lubna; Ahmad, Huthaifa
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.
Underhill, Meghan L; Germansky, Katharine A; Yurgelun, Matthew B
Innovations in genetic medicine have led to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer. This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer. This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of new genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed. Given the availability of new diagnostic, risk-reducing, and therapeutic strategies that exist for patients with hereditary risk of colorectal or pancreatic cancer, it is imperative that clinicians be vigilant about evaluating patients for hereditary cancer syndromes. Continuing to advance genetics research in hereditary gastrointestinal cancers will allow for more progress to be made in personalized medicine and prevention. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.
Background Little data exists on the factors associated with health care seeking behaviour for primary symptoms of colorectal cancer (CRC). This study aimed to identify individual, provider and psychosocial factors associated with (i) ever seeking medical advice and (ii) seeking early medical advice for primary symptoms of colorectal cancer (CRC). Methods 1592 persons aged 56–88 years randomly selected from the Hunter Community Study (HCS) were sent a questionnaire. Results Males and those who had received screening advice from a doctor were at significantly higher odds of ever seeking medical advice for rectal bleeding. Persons who had private health coverage, consulted a doctor because the ‘symptom was serious’, or who did not wait to consult a doctor for another reason were at significantly higher odds of seeking early medical advice (< 2 weeks). For change in bowel habit, persons with lower income, within the healthy weight range, or who had discussed their family history of CRC irrespective of whether informed of ‘increased risk’ were at significantly higher odds of ever seeking medical advice. Persons frequenting their GP less often and seeing their doctor because the symptom persisted were at significantly higher odds of seeking early medical advice (< 2 weeks). Conclusions The seriousness of symptoms, importance of early detection, and prompt consultation must be articulated in health messages to at-risk persons. This study identified modifiable factors, both individual and provider-related to consultation behaviour. Effective health promotion efforts must heed these factors and target sub-groups less likely to seek early medical advice. PMID:22862960
Luo, Yanxin; Tsuchiya, Karen D.; Park, Dong Il; Fausel, Rebecca; Kanngurn, Samornmas; Welcsh, Piri; Dzieciatkowski, Slavomir; Wang, Jianping; Grady, William M.
Cancer arises as the consequence of mutations and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. Through a genome-wide screen for methylated genes in colon neoplasms, we identified aberrantly methylated RET in colorectal cancer. RET, a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, was one of the first oncogenes to be identified and has been shown to be an oncogene in thyroid cancer and pheochromocytoma. However, unexpectedly, we found RET is methylated in 27% of colon adenomas and in 63% of colorectal cancers, and now provide evidence that RET has tumor suppressor activity in colon cancer. The aberrant methylation of RET correlates with decreased RET expression, whereas the restoration of RET in colorectal cancer cell lines results in apoptosis. Furthermore, in support of a tumor suppressor function of RET, mutant RET has also been found in primary colorectal cancer. We now show that these mutations inactivate RET, which is consistent with RET being a tumor suppressor gene in the colon. These findings suggest that the aberrant methylation of RET and the mutational inactivation of RET promote colorectal cancer formation and that RET can serve as a tumor suppressor gene in the colon. Moreover, the increased frequency of methylated RET in colon cancers compared to adenomas suggests RET inactivation is involved in the progression of colon adenomas to cancer. PMID:22751117
Aykan, Nuri Faruk
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.
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
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
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.
Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas
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…
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.
Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas
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…
Weinrich, S P; Weinrich, M C; Boyd, M D; Johnson, E; Frank-Stromborg, M
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].
Murage, Peninah; Murchie, Peter; Bachmann, Max; Crawford, Michael; Jones, Andy
Several studies have reported a survival disadvantage for rural dwellers who develop colorectal cancer, but the underlying mechanisms remain obscure. Delayed presentation to GPs may be a contributory factor, but evidence is lacking. To examine the association between rurality and travel time on diagnosis and survival of colorectal cancer in a cohort from northeast Scotland. The authors used a database linking GP records to routine data for patients diagnosed between 1997 and 1998, and followed up to 2011. Primary outcomes were alarm symptoms, emergency admissions, stage, and survival. Travel time in minutes from patients to GP was estimated. Logistic and Cox regression were used to model outcomes. Interaction terms were used to determine if travelling time impacted differently on urban versus rural patients. Rural patients and patients travelling farther to the GP had better 3-year survival. When the travel outcome associations were explored using interaction terms, the associations differed between rural and urban areas. Longer travel in urban areas significantly reduced the odds of emergency admissions (odds ratio [OR] 0.62, P<0.05), and increased survival (hazard ratio 0.75, P<0.05). Longer travel also increased the odds of presenting with alarm symptoms in urban areas; this was nearly significant (OR 1.34, P = 0.06). Presence of alarm symptoms reduced the likelihood of emergency admissions (OR 0.36, P<0.01). Living in a rural area, and travelling farther to a GP in urban areas, may reduce the likelihood of emergency admissions and poor survival. This may be related to how patients present with alarm symptoms. © British Journal of General Practice 2017.
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Franceschi, S; Gallus, S; Talamini, R; Tavani, A; Negri, E; Vecchia, C La
Post-menopausal women who have never used hormone replacement therapy have a higher risk of colon, but not rectal, cancer than do premenopausal women of the same age, socio-cultural class and dietary habits. Such risk increase seems to last about 10 years and to be restricted to lean women, a group who have lower levels of oestradiol after ovarian function ceases after menopause. © 2000 Cancer Research Campaign PMID:10839302
Orlich, Michael J; Singh, Pramil N; Sabaté, Joan; Fan, Jing; Sveen, Lars; Bennett, Hannelore; Knutsen, Synnove F; Beeson, W Lawrence; Jaceldo-Siegl, Karen; Butler, Terry L; Herring, R Patti; Fraser, Gary E
Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96,354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77,659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64-0.95) for all colorectal cancers, 0.81 (95% CI, 0.65-1.00) for colon cancer, and 0.71 (95% CI, 0.47-1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59-1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65-1.02); in pescovegetarians, 0.57 (95% CI, 0.40-0.82); and in semivegetarians, 0.92 (95% CI, 0.62-1.37) compared with nonvegetarians. Effect estimates were similar for men and women and for black and nonblack individuals. Vegetarian diets are
Orlich, Michael J.; Singh, Pramil N.; Sabaté, Joan; Fan, Jing; Sveen, Lars; Bennett, Hannelore; Knutsen, Synnove F.; Beeson, W. Lawrence; Jaceldo-Siegl, Karen; Butler, Terry L.; Herring, R. Patti; Fraser, Gary E.
IMPORTANCE Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. DESIGN, SETTING, AND PARTICIPANTS The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96 354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77 659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. EXPOSURES Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. MAIN OUTCOMES AND MEASURES The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. RESULTS During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64–0.95) for all colorectal cancers, 0.81 (95%CI, 0.65–1.00) for colon cancer, and 0.71 (95% CI, 0.47–1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59–1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65–1.02); in pescovegetarians, 0.57 (95% CI, 0.40–0.82); and in semivegetarians, 0.92 (95% CI, 0.62–1.37) compared with
Background The wnt/β-catenin signaling pathway is known to affect in cancer oncogenesis and progression by interacting with the tumor microenvironment. However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been thoroughly studied. In the present study, we investigated the expression of wnt protein and the concordance rate in primary tumor and metastatic sites in CRC. To determine the relationship of wnt proteins with invasion related protein, we also analyzed the association between wnt protein expression and the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2). Methods Tumor tissue was obtained from eighty-three paraffin- embedded blocks which were using resected tissue from both the primary tumor and metastatic sites for each patient. We performed immunohistochemical staining for wnt3a, wnt5a, β-catenin, MMP-9 and VEGFR-2. Results Wnt3a, wnt5a, β-catenin, and MMP-9 expression was high; the proteins were found in over 50% of the primary tumors, but the prevalence was lower in tissue from metastatic sites. The concordance rates between the primary tumor and metastatic site were 76.2% for wnt5a and 79.4% for wnt3a and β-catenin, but VEGFR-2 was expressed in 67.4% of the metastatic sites even when not found in the primary tumor. Wnt3a expression in primary tumors was significantly associated with lymph node involvement (p = 0.038) and MMP-9 expression in the primary tumor (p = 0.0387), mesenchyme adjacent to tumor (p = 0.022) and metastatic site (p = 0.004). There was no other relationship in the expression of these proteins. Vascular invasion in primary tumor tissue may be a potential prognostic marker for liver metastasis, but no significant association was observed among the wnt protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, β-catenin expression was significantly correlated with overall survival (p = 0.05). Conclusions Wnt3a and wnt5a
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
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
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
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
Anal Cancer; Carcinoma of the Appendix; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Liver Cancer; Nausea and Vomiting; Pancreatic Cancer; Primary Peritoneal Cavity Cancer; Small Intestine Cancer
Obuch, Joshua C; Ahnen, Dennis J
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.
Yao, Caroline; Nash, Guy F; Hickish, Tamas
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
Salama, Paul; Platell, Cameron
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.
Lemon, Stephenie C; Zapka, Jane G; Estabrook, Barbara; Erban, Stephen; Luckmann, Roger
The aim of this study was to assess knowledge, beliefs, and practices of primary care clinicians regarding colorectal cancer screening. We surveyed 77 primary care providers in six clinics in central Massachusetts to evaluate several factors related to colorectal cancer screening. Most agreed with guidelines for fecal occult blood test (97%) and sigmoidoscopy (87%), which were reported commonly as usual practice. Although the majority (86%) recommended colonoscopy as a colorectal cancer screening test, it was infrequently reported as usual practice. Also, 36% considered barium enema a colorectal cancer screening option, and it was rarely reported as usual practice. Despite lack of evidence supporting effectiveness, digital rectal examinations and in-office fecal occult blood test were commonly reported as usual practice. However, these were usually reported in combination with a guideline-endorsed testing option. Although only 10% reported that fecal occult blood test/home was frequently refused, 60% reported sigmoidoscopy was. Frequently cited patient barriers to sigmoidoscopy compliance included fear the procedure would hurt and that patients assume symptoms occur if there is a problem. Perceptions of health systems barriers to sigmoidoscopy were less strong. Most providers recommended guideline-endorsed colorectal cancer screening. However, patient refusal for sigmoidoscopy was common. Results indicate that multiple levels of intervention, including patient and provider education and systems strategies, may help increase prevalence.
Offerhaus, G. Johan A.
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. Each year more than 140,000 new patients are diagnosed. About 30% of patients with CRC report a family history of CRC. However, only 5% of colorectal cancers arise in the setting of a well-established Mendelian inherited disorder such as Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, juvenile polyposis, hereditary mixed polyposis, or Peutz-Jeghers. In addition, serrated polyposis is a clinically defined syndrome with multiple serrated polyps in the colorectum and an increased CRC risk for which the genetics are unknown. The majority of familial colorectal cancers arise as so called non-syndromic familial colorectal cancer and likely have a more complex multigenetic cause. This review focuses on genetic and clinical aspects of Lynch syndrome, familial adenomatous polyposis and MUTYH-associated polyposis. PMID:26315524
Rawl, Susan M.; Christy, Shannon M.; Monahan, Patrick O.; Ding, Yan; Krier, Connie; Champion, Victoria L.; Rex, Douglas
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
Bessa Caserras, Xavier
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.
Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía
Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca(2+) stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca(2+)-release activated Ca(2+) channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca(2+) stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity. Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca(2+) remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca(2+) entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca(2+) homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin
Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Papa, Gennaro; Piepoli, Ada
Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer. PMID:24764658
Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Papa, Gennaro; Piepoli, Ada
Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.
Johnston, S J; Ridge, S A; Cassidy, J; McLeod, H L
Dihydropyrimidine dehydrogenase (DPD) is responsible for degradation of the pyrimidines uracil and thymine and the inactivation of the chemotherapeutic agent 5-fluorouracil. DPD activity is highly variable in cancer populations, and this variation may influence the antitumor efficacy of 5-fluorouracil. However, little is known about the regulation of DPD mRNA expression in any tissues. Using a reverse transcription competitive PCR assay, we quantified DPD mRNA levels in 10 matched colorectal tumors and adjacent normal mucosae and 7 colorectal liver metastases and adjacent normal livers. Lower levels of DPD mRNA expression were observed in colorectal tumor compared with adjacent normal colon mucosa (median, 0.01 versus 0.37 amole/microg total RNA, P = 0.02). DPD mRNA expression was also lower in metastases than adjacent normal liver tissue (median, 0.11 versus 1.17 amole/microg total RNA, P = 0.001). DPD mRNA expression was higher in normal liver than normal colonic mucosa (median, 1.17 versus 0.37 amole/microg total RNA, P = 0.02). A significant relationship was observed between DPD mRNA and catalytic activity (r(s) = 0.66, P<0.001). The tumor:normal ratio for DPD mRNA, protein, and activity was relatively stable in liver (0.25, 0.55, and 0.51, respectively) but varied considerably in colon (0.085, 0.9, and 1.25, respectively), consistent with enhanced translation of DPD transcript in primary colorectal tumor. This suggests that DPD can be regulated at the levels of both transcription and translation.
Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord
In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; P<0.001) and with the intensity of the overall inflammatory cell reaction (R=0.318; P<0.001). Both increasing peri- and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients
Vogelaar, F J; van Pelt, G W; van Leeuwen, A M; Willems, J M; Tollenaar, R A E M; Liefers, G J; Mesker, W E
Current TNM staging does not appropriately identify high-risk colorectal cancer (CRC) patients. The aim of this study was to evaluate whether the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) and the presence of stroma in the primary tumor, i.e., the tumor-stroma ratio (TSR), in patients undergoing surgical resection of primary CRC provides information relevant for disease outcome. Patients with primary CRC (n = 125), consecutively admitted for curative resection between 2001 and 2007, were included in the study. All patients underwent BM aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC). The TSR was determined on diagnostic H&E stained sections of primary tumors. DTCs were detected in the BM of 23/125 patients (18 %). No association was found between BM status and overall survival (HR 0.97 (95 % CI 0.45-2.09), p = 0.93). Also, no significant difference was found in their 5-year survival rate (resp. 72 % and 68 % for BM-positive versus BM-negative patients). The TSR was found to be associated with a worse overall survival (HR 2.16, 95 % CI 1.02-4.57, p = 0.04) with 5-year survival rates of 84 % versus 62 % for stroma-low and stroma-high patients, respectively. No relation was found between the presence of DTCs and TSR. Our data indicate that the presence of DTCs in the BM of CRC patients is not associated with disease outcome. The TSR was, however, found to be associated with a worse overall survival, which indicates that for CRC the tumor microenvironment plays an important role in its behavior and prognosis.
Spreadborough, P; Doran, C
Colorectal cancer (CRC) is the fourth most common cancer in the UK and the incidence has increased over recent decades. Although only 1.5% of cases are diagnosed in those aged under 40 years, it remains an important condition to be aware of in the military population. Patients who are genetically predisposed can have a lifetime risk of 80-100% of developing CRC and are likely to develop symptoms during their service. 20% of patients will present with metastatic disease. While surgical and oncological treatments have improved outcomes, early diagnosis of CRC is essential to reducing mortality. This paper provides an overview of the aetiology, investigations and treatment options for CRC. Explanation of primary surgical options and the principles of adjuvant therapies are included to aid informed discussions with patients.
Veettil, Sajesh K; Lim, Kean Ghee; Chaiyakunapruk, Nathorn; Ching, Siew Mooi; Abu Hassan, Muhammad Radzi
This study aims to provide an analytical overview of the changing burden of colorectal cancer and highlight the implementable control measures that can help reduce the future burden of colorectal cancer in Malaysia. We performed a MEDLINE search via OVID with the Medical Subject Headings (MeSH) terms "Colorectal Neoplasms"[Mesh] and "Malaysia"[Mesh], and PubMed with the key words "colorectal cancer" and "Malaysia" from 1990 to 2015 for studies reporting any clinical, societal, and economical findings associated with colorectal cancer in Malaysia. Incidence and mortality data were retrieved from population-based cancer registries/databases. In Malaysia, colorectal cancer is the second most common cancer in males and the third most common cancer in females. The economic burden of colorectal cancer is substantial and is likely to increase over time in Malaysia owing to the current trend in colorectal cancer incidence. In Malaysia, most patients with colorectal cancer have been diagnosed at a late stage, with the 5-year relative survival by stage being lower than that in developed Asian countries. Public awareness of the rising incidence of colorectal cancer and the participation rates for colorectal cancer screening are low. The efficiency of different screening approaches must be assessed, and an organized national screening program should be developed in a phased manner. It is essential to maintain a balanced investment in awareness programs targeting general population and primary care providers, focused on increasing the knowledge on symptoms and risk factors of colorectal cancer, awareness on benefits of screening, and promotion of healthy life styles to prevent this important disease. Copyright © 2016. Published by Elsevier Taiwan.
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Rothenberger, David A; Dalberg, Deanna L; Leininger, Anna
The aim of the Minnesota Colorectal Cancer Initiative is to implement risk-specific interventions to decrease colorectal cancer morbidity and mortality by 1) assisting clinicians to identify and educate individuals and families at high and increased risk for colorectal cancer; 2) providing professional and community education; 3) maintaining a database to evaluate the effectiveness of preventive intervention strategies; and 4) facilitating colorectal cancer research. Two physician groups and the University Cancer Center founded the Minnesota Colorectal Cancer Initiative as a not-for-profit organization. Health care organizations, pharmaceutical companies, a consulting firm, and other practice groups provide continuing financial and other support. A database registry, risk-assessment survey, and consent document were developed and then were approved by an institutional review board. A trial enrollment was conducted. Minnesota Colorectal Cancer Initiative services are available to the public. Participants are actively recruited through member organizations. Minnesota Colorectal Cancer Initiative assesses hereditary risk and will document family history in the medical record on request. A personally targeted reply letter reviews risk factors and recommends specific screening and surveillance strategies for participants and their family members, and when appropriate, provides information regarding genetic counseling and testing services. Minnesota Colorectal Cancer Initiative services are free to participants. Since 1999, Minnesota Colorectal Cancer Initiative has sent individually tailored reply letters providing risk-specific information about colorectal cancer to 717 participants and more than 3200 of their first-degree and second-degree relatives. More than 200 families, previously unidentified as having histories suggestive of hereditary colorectal cancer (attenuated familial polyposis and hereditary nonpolyposis colorectal cancer), have been identified; genetic
Samalavicius, Narimantas E.; Baltruskeviciene, Edita; Smailyte, Giedre; Skuciene, Marija; Mikelenaite, Rasa; Venslovaite, Rasa; Aleknavicius, Eduardas; Samalavicius, Almantas; Lunevicius, Raimundas
Introduction The role of the resection of asymptomatic primary colorectal cancer in patients with incurable disease is questionable. Aim To evaluate the impact of the resection of asymptomatic primary tumour on overall survival in patients with unresectable distant metastases. Material and methods Patients treated in the National Cancer Institute, Lithuania, in the period 2008–2012, were selected retrospectively. The main inclusion criteria were: metastatic colorectal cancer (mCRC), endoscopically and histologically confirmed adenocarcinoma, without any symptoms for urgent operation, and at least one cycle of palliative chemotherapy administered. Information on patients’ age, gender, tumour histology, localization of the tumour, regional lymph node involvement, number of metastatic sites, surgery and systemic treatment was collected prospectively. Eligible patients for the study were divided into two groups according to the initial treatment – surgery (patients who underwent primary tumour resection) and chemotherapy (patients who received chemotherapy without surgery). The impact of initial treatment strategy, tumour size and site, regional lymph nodes, grade of differentiation of adenocarcinoma and application of biotherapy on overall cumulative survival was estimated using the Kaplan-Meier method. To compare survival between groups the log-rank test was used. Cox regression analysis was employed to assess the effects of variables on patient survival. Results The study group consisted of 183 patients: 103 men and 80 women. The median age was 66 years (range: 37–91). There were no notable imbalances with regard to age, gender, number of metastatic sites, metastases (such as pulmonary, peritoneal, liver, metastases into non-regional lymph nodes and other metastases), the number of received cycles of chemotherapy, first line chemotherapy type or biological therapy. Only 27 (14.8%) patients received biological therapy and the majority of them (n = 25, 92
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
Louvet, Christophe; de Gramont, Aimery
Pemetrexed (Alimta) shows single-agent activity in advanced colorectal cancer. In two phase II studies in which patients received pemetrexed at 600 mg/m2 or 500 mg/m2 as first-line treatment for metastatic disease, objective response rates were 15.4% and 17.2%. These trials were conducted prior to supplementation with folic acid and vitamin B12, which markedly decreased the frequency of hematologic toxicities of pemetrexed; routine supplementation is now included in all clinical trials of the agent. The marked improvement in toxicity and tolerance with vitamin supplementation suggests the need to reexamine optimal dosing in pemetrexed combination schedules. In a National Surgical Adjuvant Breast and Bowel Project phase II trial in 54 patients with previously untreated advanced colorectal cancer, pemetrexed at 500 mg/m2 plus oxaliplatin (Eloxatin) at 120 mg/m2 every 21 days with folic acid/vitamin B12 supplementation resulted in an objective response of 23%. Three additionalpatients (5.6%) had unconfirmed partial response (partial response at one visit), and 27 patients (50%) had stable disease. Median progression-free survival was 5.3 months and median duration of response was 5.7 months; median overall survival was approximately 11.05 months. Grade 3/4 neutropenia was observed in only 17% of patients and treatment was well tolerated. A phase I/II study is under way to identify and assess the optimal combination of pemetrexed/irinotecan in second-line treatment of advanced colorectal cancer. Planned studies include a phase I study examining the combination of pemetrexed and oxaliplatin given every 2 weeks as first-line treatment, and a phase I/II trial to identify the optimal pemetrexed/ oxaliplatin dose in a 21-day schedule and to compare pemetrexed/ oxaliplatin with FOLFOX4 in first-line treatment of metastatic disease. All of these trials include vitamin supplementation. A phase III trial comparing the every-3-week pemetrexed/oxaliplatin regimen with FOLFOX4 as
Baldwin, Graham S
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.
Tashiro, Takahiro; Okuyama, Hiroaki; Endo, Hiroko; Kawada, Kenji; Ashida, Yasuko; Ohue, Masayuki; Sakai, Yoshiharu; Inoue, Masahiro
In clinic, cetuximab, an anti-EGFR antibody, improves treatment outcomes in colorectal cancer (CRC). KRAS-mutant CRC is generally resistant to cetuximab, although difference of the sensitivity among KRAS-mutants has not been studied in detail. We previously developed the cancer tissue-originated spheroid (CTOS) method, a primary culture method for cancer cells. We applied CTOS method to investigate whether ex vivo cetuximab sensitivity assays reflect the difference in sensitivity in the xenografts. Firstly, in vivo cetuximab treatment was performed with xenografts derived from 10 CTOS lines (3 KRAS-wildtype and 7 KRAS mutants). All two CTOS lines which exhibited tumor regression were KRAS-wildtype, meanwhile all KRAS-mutant CTOS lines grew more than the initial size: were resistant to cetuximab according to the clinical evaluation criteria, although the sensitivity was quite diverse. We divided KRAS-mutants into two groups; partially responsive group in which cetuximab had a substantial growth inhibitory effect, and resistant group which exhibited no effect. The ex vivo signaling assay with EGF stimulation revealed that the partially responsive group, but not the resistant group, exhibited suppressed ERK phosphorylation ex vivo. Furthermore, two lines from the partially responsive group, but none of the lines in the resistant group, exhibited a combinatory effect of cetuximab and trametinib, a MEK inhibitor, ex vivo and in vivo. Taken together, the results indicate that ex vivo signaling assay reflects the difference in sensitivity in vivo and stratifies KRAS mutant CTOS lines by sensitivity. Therefore, coupling the in vivo and ex vivo assays with CTOS can be a useful platform for understanding the mechanism of diversity in drug sensitivity. PMID:28301591
... genetic condition called Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer or HNPCC. About 3% (1 ... early if you get it. Lynch syndrome is hereditary, meaning that it is caused by an inherited ...
Kalady, Matthew F.; Heald, Brandie
Approximately 5 to 10% of colorectal cancers develop within a known hereditary syndrome. Specific underlying genetic mutations drive the clinical phenotype and it is imperative to determine the genetic etiology to provide meaningful surveillance and intervention. Recognizing potential patients and families with a hereditary predisposition is the first step in management. Syndromes can be categorized according to polyp burden as polyposis or nonpolyposis. Clinical assessment should start with a personal and family medical history, physical examination, and evaluation for the presence and type of colorectal polyps or cancers. Key information is gained from these simple steps and should guide the specific genetic analysis for diagnosis. Genetic counseling is a critical component to any hereditary colorectal cancer program and should be conducted before genetic testing to provide education about the implications of test results. This review focuses on the thought process that drives initial clinical evaluation and guides genetic testing for patients with suspected hereditary colorectal cancer syndromes. PMID:26664327
Kalady, Matthew F; Heald, Brandie
Approximately 5 to 10% of colorectal cancers develop within a known hereditary syndrome. Specific underlying genetic mutations drive the clinical phenotype and it is imperative to determine the genetic etiology to provide meaningful surveillance and intervention. Recognizing potential patients and families with a hereditary predisposition is the first step in management. Syndromes can be categorized according to polyp burden as polyposis or nonpolyposis. Clinical assessment should start with a personal and family medical history, physical examination, and evaluation for the presence and type of colorectal polyps or cancers. Key information is gained from these simple steps and should guide the specific genetic analysis for diagnosis. Genetic counseling is a critical component to any hereditary colorectal cancer program and should be conducted before genetic testing to provide education about the implications of test results. This review focuses on the thought process that drives initial clinical evaluation and guides genetic testing for patients with suspected hereditary colorectal cancer syndromes.
A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati
A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati
Update of the 2009 USPSTF recommendation on aspirin use to prevent cardiovascular disease (CVD) events and the 2007 recommendation on aspirin and nonsteroidal anti-inflammatory drug use to prevent colorectal cancer (CRC). The USPSTF reviewed 5 additional studies of aspirin for the primary prevention of CVD and several additional analyses of CRC follow-up data. The USPSTF also relied on commissioned systematic reviews of all-cause mortality and total cancer incidence and mortality and a comprehensive review of harms. The USPSTF then used a microsimulation model to systematically estimate the balance of benefits and harms. This recommendation applies to adults aged 40 years or older without known CVD and without increased bleeding risk. The USPSTF recommends initiating low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. (B recommendation) The decision to initiate low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 60 to 69 years who have a 10% or greater 10-year CVD risk should be an individual one. Persons who are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years are more likely to benefit. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin. (C recommendation) The current evidence is insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults younger than 50 years. (I statement) The current evidence is insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults aged 70 years or older. (I
Guend, Hamza; Patel, Sunil
Patients with peritoneal metastasis from colorectal cancer represent a distinct subset with regional disease rather than systemic disease. They often have poorer survival outcomes with systemic chemotherapy. Optimal cytoreductive surgery and intraperitoneal chemotherapy (IPC) offers such patients a more directed therapy with improved survival. In this review, we discuss the diagnosis, evaluation and classification, as well as rational for treatment of peritoneal carcinomatosis (PC) secondary to colorectal cancer. PMID:26697203
Ngune, I; Jiwa, M; McManus, A; Parsons, R; Hodder, R
Patients treated for colorectal cancer (CRC) experience considerable physical, social and psychological morbidity. In this study, 66 participants with stages I-III CRC were enrolled in this study. Participants completed the self-assessment tool for patients (SATp) over a 5-month period and visited a general practitioner with a copy of their SATp to assist in the management of any problems associated with CRC treatment. General practitioners' notes were reviewed for management actions. Of the 66 participants, 57 visited a general practitioner over the 5-month study period. A total of 547 problems were identified (median 7; IQR: 3-12.25). Participants with physical problems were more likely to consult their general practitioner (OR: 1.84, CI: 1.05-3.21, P = 0.03) compared to those with psychological problems. The number of problems experienced by participants did not have any influence on the decision to visit a general practitioner. Psychological problems (P < 0.01) significantly reduced over the 5-month study period. Regular use of the SATp facilitates the identification of long-term CRC treatment-related problems. Some of these problems could then be addressed in primary care. © 2015 John Wiley & Sons Ltd.
Duncan, R; Carpenter, B; Main, L C; Telfer, C; Murray, G I
The annexins are family of calcium-regulated phospholipid-binding proteins with diverse roles in cell biology. Individual annexins have been implicated in tumour development and progression, and in this investigation a range of annexins have been studied in colorectal cancer. Annexins A1, A2, A4 and A11 were identified by comparative proteomic analysis to be overexpressed in colorectal cancer. Annexins A1, A2, A4 and A11 were further studied by immunohistochemistry with a colorectal cancer tissue microarray containing primary and metastatic colorectal cancer and also normal colon. There was significant increase in expression in annexins A1 (P=0.01), A2 (P<0.001), A4 (P<0.001) and A11 (P<0.001) in primary tumours compared with normal colon. There was increasing expression of annexins A2 (P=0.001), A4 (P=0.03) and A11 (P=0.006) with increasing tumour stage. An annexin expression profile was identified by k-means cluster analysis, and the annexin profile was associated with tumour stage (P=0.01) and also patient survival. Patients in annexin cluster group 1 (low annexin expression) had a better survival (log rank=5.33, P=0.02) than patients in cluster group 2 (high annexins A4 and A11 expression). In conclusion, this study has shown that individual annexins are present in colorectal cancer, specific annexins are overexpressed in colorectal cancer and the annexin expression profile is associated with survival.
Locker, Gershon Y; Kaul, Karen; Weinberg, David S; Gatalica, Zoran; Gong, Gordon; Peterman, Amy; Lynch, Jane; Klatzco, Lucy; Olopade, Olufunmilayo I; Bomzer, Charles A; Newlin, Anna; Keenan, Eileen; Tajuddin, Mohammed; Knezetic, Joseph; Coronel, Stephanie; Lynch, Henry T
Colorectal cancer is common in Ashkenazi Jews. The I1307K APC mutation occurs in 6-7% of Ashkenazi Jews and increases the risk of colorectal cancer. This study aimed to describe the clinical, pathologic and epidemiologic features of colorectal cancer in I1307K carriers to determine whether there were any features which might warrant individual screening for the mutation. In all, 215 Ashkenazi Jews with a personal history of colorectal cancer were enrolled. Clinical and family history, pathology reports, and slides were obtained and blood drawn for I1307K determination. The presence of the mutation was determined by PCR from white blood cell DNA. Colorectal cancer pathology slides were read in a blinded fashion. Of the 215 enrolled patients, 26 (12.1%) tested positive for I1307K. There was no difference in the pathologic features between colorectal cancers in Ashkenazi carriers compared to noncarriers. There was no difference in the age at diagnosis or history of second or other primaries. Carriers had an increased likelihood of having a first-degree relative with colorectal cancer (50%) compared to noncarriers (28%, P < 0.04). We could find no distinguishing feature other than family history that characterizes I1307K positive colorectal cancers. We could find no group of Ashkenazi Jews with colorectal cancer for whom screening for I1307K would be clinically useful.
Yabana, Takashi; Goto, Akira; Yamamoto, Motohisa; Ishimine, Yu; Yajima, Hidenori; Nakagaki, Suguru; Adachi, Takeya; Kondo, Yoshihiro
An 82-year-old woman presented with hematochezia and was diagnosed with resectable colon cancer. Laboratory analysis revealed prolonged activated partial thromboplastin time and false-positive reactions in serological tests for syphilis; results that were subsequently found to be caused by the presence of antiphospholipid antibody. Because she had no history of thrombotic events or pregnancy morbidity, she was considered to be an asymptomatic antiphospholipid antibody carrier (aaPL carrier). Throughout the perioperative period, anticoagulation was performed without complications, including thrombosis. aaPL carriers are not uncommon in clinical practice, and the attending gastroenterologist should assess the risk of future thrombotic events and the most effective means of preventing thrombosis. However, there are few evidence-based recommendations for primary thrombosis prevention in aaPL carriers over the long-term and in high-risk periods, such as the perioperative period. Here, we discuss aaPL carrier management with a focus on the perioperative period together with a review of the literature.
Forte, Angelo; De Sanctis, Rita; Leonetti, Giovanni; Manfredelli, Simone; Urbano, Vincenzo; Bezzi, Marcello
Colorectal cancer is the second cause of morbidity and death in Italy. Genetic and environmental factors, i.e. inappropriate nutrition, are strongly involved in the aetiology of colon cancer. In the present review the authors analyze the possible mechanisms by which certain nutritive factors may interfere with the complex process of carcinogenesis. The authors identify studies by a literature search of Medline from January 1, 1970, through December 31, 2006. The mechanism of every protective compound is detailed, in particular the impact of antioxidant vitamins and minerals on tumor development. At present, the data suggest that vegetables are associated with lower risk and that their fbre content alone does not account for this association. Further, meat consumption is associated with an increased risk but this, too, is not explained solely by its fat content. Several microconstituents of the diet may be associated with reduced risk, including folate, methionine, calcium and vitamin D. Short chain fatty acids also contribute to colonic health. Nevertheless agricultural products contain several dangerous pesticides. Mutagenic compounds, particularly heterocyclic amines, produced when protein is cooked, plausibly explain the meat association. Healthy nutrition is a necessary but not sufficient condition for colon cancer prevention: accepted the feasibility of an accurate control on every patient's diet, fequently the difficulty encountered in nutritional chemoprevention is to establish individual metabolic profiles.
Sandouk, Fayez; Al Jerf, Feras; Al-Halabi, M. H. D. Bassel
Colorectal cancer (CRC) is the third most common cause of cancer death in the world. The incidence rate (ASR) and age distribution of this disease differ between most of African-Middle-Eastern (AMAGE) and North America and Europe for many reasons. However, in all areas, “CRC” is considered as one of the most preventable cancers, because it might develop from variant processes like polyps and IBD in addition to the genetic pathogenesis which became very well known in this disease. We tried in this paper to review all the possible reasons of the differences in incidence and age between the west and AMAGE. Also we reviewed all the mutations that lead to the hereditary and familiar clustering of this disease with the correlations with the surrounding food and environment of different areas. Then, we focused on the precancerous pathology of this disease with special focusing on early detection depending on new endoscopy technology and most important genetic studies. We lastly reviewed the evidence of some of the surveillance and put suggestions about future surveillance programs and how important those programs are on the psychological aspect of the patients and their families. PMID:23737765
Lopes, Joana Pedro; de Castro Cardoso Pereira, Paula Manuela; dos Reis Baltazar Vicente, Ana Filipa; Bernardo, Alexandra; de Mesquita, María Fernanda
The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery procedure. The sample was divided between convention and fast-track procedures. Most of the individuals were overweight or obese but had lost weight on the past six months. Despite mild, there were signs of malnutrition in this sample with high losses of fat free mass, weight and also fat mass during the hospitalization period. These results reinforce the importance of malnutrition assessment in colorectal patients as well as consider weight loss on the past months and body composition in order to complement nutritional status evaluation.
Expert-reviewed information summary about the genetics of colorectal cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for colorectal cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary colorectal cancer syndrome are also discussed.
Expert-reviewed information summary about the genetics of colorectal cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for colorectal cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary colorectal cancer syndrome are also discussed.
Iacopetta, Barry; Grieu, Fabienne; Amanuel, Benhur
Approximately 20 percent of right-sided colon cancers and 5 percent of left-sided colon and rectal cancers have a deficient DNA mismatch repair system. This results in the widespread accumulation of mutations to nucleotide repeats, some of which occur within the coding regions of cancer-related genes such as TGFβRII and BAX. A standardized definition for microsatellite instability (MSI) based on the presence of deletions to mononucleotide repeats is gaining widespread acceptance in both research and the clinic. Colorectal cancer (CRC) with MSI are characterized histologically by an abundance of tumor-infiltrating lymphocytes, poor differentiation and a signet ring or mucinous phenotype. In younger patients these tumors usually develop along the chromosomal instability pathway, in which case the mismatch repair genes are inactivated by germline mutation, somatic mutation and loss of heterozygosity. In older patients MSI CRC usually develops against a background of widespread hypermethylation that includes methylation-induced silencing of the mismatch repair gene MLH1. The overall biological and clinical phenotype of MSI CRC that arise in these two pathways is likely to be different and may account for some of the discordant results reported in the literature relating to the clinical properties of these tumors. The available evidence indicates that MSI is unlikely to be a clinically useful marker for the prognostic stratification of early-stage CRC. The predictive value of MSI for response to 5-fluorouracil-based chemotherapy remains controversial, while for other agents the predictive value is difficult to assess because they are used in combination regimens. The MSI phenotype is being actively investigated for novel therapeutic approaches based on the principle of synthetic lethality. Finally, the MSI status of CRC is an extremely useful marker for population-based screening programs that aim to identify individuals and families with the hereditary cancer
Inoue, Yasuhiro; Ishida, Hideyuki; Ueno, Hideki; Kobayashi, Hirotoshi; Yamaguchi, Tatsuro; Konishi, Tsuyoshi; Tomita, Naohiro; Matsubara, Nagahide; Ishida, Fumio; Hinoi, Takao; Kanemitsu, Yukihide; Watanabe, Toshiaki; Sugihara, Kenichi
Colorectal cancer is a major cause of death in patients with familial adenomatous polyposis. Despite evidence for prophylactic colectomy, there is no ideal therapy for patients with coexisting familial adenomatous polyposis and colorectal cancer. We evaluated the correlation between surgery for familial adenomatous polyposis and multimodal treatment for colorectal cancer, and clarified prognosis of Japanese patients with familial adenomatous polyposis and colorectal cancer. We retrospectively reviewed data from 303 patients who underwent colorectal surgery for familial adenomatous polyposis between 2000 and 2012. Overall, 172 patients had colorectal cancer. The most common procedure for familial adenomatous polyposis was restorative proctocolectomy with ileal pouch anal anastomosis, irrespective of colorectal cancer. Partial colectomy was more frequent in patients with than without colorectal cancer (8.7% and 0%, respectively). Ileal pouch anal anastomosis was frequently (60.6%) performed in patients with Stage I-III colorectal cancer. Overall, 12 of 20 patients with Stage IV colorectal cancer underwent metastasectomy; six patients simultaneously and six metachronously. There were fewer cases of ileal pouch anal anastomosis, but more total colectomy with ileorectal anastomosis was performed metachronously, compared with simultaneous metastasectomy (P = 0.006). More cytotoxic (P = 0.006) and molecular (P = 0.03) agents were administered to the ileorectal anastomosis/partial colectomy patients, compared with total proctocolectomy/ileal pouch anal anastomosis patients. A 5-year overall survival was 100% in Stage 0/I, 89.8% in Stage II, 87.9% in Stage III and 48.4% in Stage IV. In patients with familial adenomatous polyposis and colorectal cancer, primary surgery, metastasectomy and chemotherapy could be compatible with standard surgical approaches for familial adenomatous polyposis . However, modifying surgical procedures for familial adenomatous polyposis might help
Lee, Bo-In; Hong, Sung Pil; Kim, Seong-Eun; Kim, Se Hyung; Hong, Sung Noh; Yang, Dong-Hoon; Shin, Sung Jae; Lee, Suck-Ho; Park, Dong Il; Kim, Young-Ho; Kim, Hyun Jung; Yang, Suk-Kyun; Kim, Hyo Jong; Jeon, Hae Jeong
Now colorectal cancer is the second most common cancer in males and the fourth most common cancer in females in Korea. Since most of colorectal cancers occur after the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are one of the most effective methods to prevent colorectal cancer. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish Korean guideline for colorectal cancer screening and polyp detection. The guideline was developed by the Korean Multi-Society Take Force and we tried to establish the guideline by evidence-based methods. Parts of the statements were draw by systematic reviews and meta-analyses. Herein we discussed epidemiology of colorectal cancers and adenomas in Korea and optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations. PMID:22741131
Homan, Sherri G.; Yun, Shumei; Stewart, Bob R.; Armer, Jane M.
Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC) is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups’ questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02) and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003). The most cited barrier was the complexity of preparation for colonoscopy. PMID:26258794
Homan, Sherri G; Yun, Shumei; Stewart, Bob R; Armer, Jane M
Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC) is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups' questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02) and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003). The most cited barrier was the complexity of preparation for colonoscopy.
Favoriti, Pasqualino; Carbone, Gabriele; Greco, Marco; Pirozzi, Felice; Pirozzi, Raffaele Emmanuele Maria; Corcione, Francesco
Colorectal cancer is a major public health problem, being the third most commonly diagnosed cancer and the fourth cause of cancer death worldwide. There is wide variation over time among the different geographic areas due to variable exposure to risk factors, introduction and uptake of screening as well as access to appropriate treatment services. Indeed, a large proportion of the disparities may be attributed to socioeconomic status. Although colorectal cancer continues to be a disease of the developed world, incidence rates have been rising in developing countries. Moreover, the global burden is expected to further increase due to the growth and aging of the population and because of the adoption of westernized behaviors and lifestyle. Colorectal cancer screening has been proven to greatly reduce mortality rates that have declined in many longstanding as well as newly economically developed countries. Statistics on colorectal cancer occurrence are essential to develop targeted strategies that could alleviate the burden of the disease. The aim of this paper is to provide a review of incidence, mortality and survival rates for colorectal cancer as well as their geographic variations and temporal trends.
Viloria, Cristina G; Obaya, Alvaro J; Moncada-Pazos, Angela; Llamazares, María; Astudillo, Aurora; Capellá, Gabriel; Cal, Santiago; López-Otín, Carlos
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.
The NCI CRCHD launches National Screen to Save Colorectal Cancer Outreach and Screening Initiative which aims to increase colorectal cancer screening rates among racially and ethnically diverse and rural communities.
Białek, Andrzej; Homa, Katarzyna; Marlicz, Krzysztof
Colorectal cancer is one of the most common neoplasms that often occurs in several members of family. In this communication we present the case of synchronous colorectal cancers with similar localization and similar clinical course in monozygotic twins.
Lechner, P; Lind, P; Snyder, M; Haushofer, H
Anti-CEA-scintigraphy turned out to be very reliable in detecting primary and recurrent colorectal cancer, its overall accuracy being more than 90%. The intraoperative application of this technology should provide similar results when focussing at extrahepatic tumor deposits, for example in lymph nodes, thus allowing accurate staging of the underlying disease. To test this hypothesis we launched the following feasibility study the results of which are compared to those reported in the recent literature. We investigated 20 patients, six with rectum and 14 with colon cancer. 24 hours before surgery they were intravenously given 1 ml of a fab'-fragment-antibody to CEA, labeled with 25 mCi of 99mTc (CEA-Scan). During surgery the radioactivity in lymph glands regional to the tumors was measured and compared to the much lower activity in healthy nodes. For this we used a scintillation probe (C-Trak, Care Wise, Inc., Morgan Hill, CA). All lymph nodes of interest were then excised and submitted to frozen section pathology. In 7 out of 20 cases scintimetry led to an up-staging of the disease. In addition we found metastatic spread to lymph nodes that were basically not regional to the primary tumor (retroperitoneum, renal hilum etc.). Scintimetry can precisely identify even very small tumor deposits. So it leads to accurate staging while surgery is still ongoing. In a further step the concept of sentinel node diagnosis, which is right now being clinically evaluated, may some day be applied in colorectal surgical oncology.
Honein-AbouHaidar, Gladys N; Kastner, Monika; Vuong, Vincent; Perrier, Laure; Daly, Corinne; Rabeneck, Linda; Straus, Sharon; Baxter, Nancy N
Screening reduces the incidence, morbidity, and mortality of colorectal cancer, yet participation tends to be low. We undertook a systematic review and meta-study synthesis of qualitative studies to identify facilitators and barriers to colorectal cancer screening participation. We searched major bibliographic databases for records published in all languages from inception to February 2015. Included primary studies that elicited views and perceptions towards colorectal cancer screening were appraised for relevance and quality. We used a two-stage synthesis to create an interpretation of colorectal cancer screening decisions grounded in primary studies; a thematic analysis to group themes and systematically compare studies and a meta-synthesis to generate an expanded theory of colorectal cancer screening participation. Ninety-four studies were included. The decision to participate in colorectal cancer screening depended on an individual's awareness of colorectal cancer screening. Awareness affected views of cancer, attitudes towards colorectal cancer screening modalities, and motivation for screening. Factors mediating awareness included public education to address misconceptions, primary care physician efforts to recommend screening, and the influence of friends and family. Specific barriers to participation in populations with lower participation rates included language barriers, logistical challenges to attending screening tests, and cultural beliefs. This study identifies key barriers, facilitators, and mediators to colorectal cancer screening participation. Cancer Epidemiol Biomarkers Prev; 25(6); 907-17. ©2016 AACR. ©2016 American Association for Cancer Research.
Lam, Alfred King-Yin; Gopalan, Vinod; Nassiri, Mohammad Reza; Kasim, Kais; Dissanayake, Jayampathy; Tang, Johnny Chuek-On; Smith, Robert Anthony
JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer.
Vaksman, Zalman; Garner, Harold R.
Microsatellites (MSTs) are short tandem repeated genetic motifs that comprise ~3% of the genome. MST instability (MSI), defined as acquired/lost primary alleles at a small subset of microsatellite loci (e.g. Bethesda markers), is a clinically relevant marker for colorectal cancer. However, these markers are not applicable to other types of cancers, specifically, for liver cancer which has a high mortality rate. Here we show that somatic MST variability (SMV), defined as the presence of additional, non-primary (aka minor) alleles at MST loci, is a complementary measure of MSI, and a genetic marker for colorectal and liver cancer. Re-analysis of Illumina sequenced exomes from The Cancer Genome Atlas indicates that SMV may distinguish a subpopulation of African American patients with colorectal cancer, which represents ~33% of the population in this study. Further, for liver cancer, a higher rate of SMV may be indicative of an earlier age of onset. The work presented here suggests that classical MSI should be expanded to include SMV, going beyond alterations of the primary alleles at a small number of microsatellite loci. This measure of SMV may represent a potential new diagnostic for a variety of cancers and may provide new information for colorectal cancer patients. PMID:25691061
Rama, A. R.; Aguilera, A.; Melguizo, C.; Caba, O.; Prados, J.
Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment. PMID:26648599
Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde
The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603
Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde
The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.
El-Shami, Khaled; Oeffinger, Kevin C; Erb, Nicole L; Willis, Anne; Bretsch, Jennifer K; Pratt-Chapman, Mandi L; Cannady, Rachel S; Wong, Sandra L; Rose, Johnie; Barbour, April L; Stein, Kevin D; Sharpe, Katherine B; Brooks, Durado D; Cowens-Alvarado, Rebecca L
Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer death in both men and women and second leading cause of cancer death when men and women are combined in the United States (US). Almost two-thirds of CRC survivors are living 5 years after diagnosis. Considering the recent decline in both incidence and mortality, the prevalence of CRC survivors is likely to increase dramatically over the coming decades with the increase in rates of CRC screening, further advances in early detection and treatment and the aging and growth of the US population. Survivors are at risk for a CRC recurrence, a new primary CRC, other cancers, as well as both short-term and long-term adverse effects of the CRC and the modalities used to treat it. CRC survivors may also have psychological, reproductive, genetic, social, and employment concerns after treatment. Communication and coordination of care between the treating oncologist and the primary care clinician is critical to effectively and efficiently manage the long-term care of CRC survivors. The guidelines in this article are intended to assist primary care clinicians in delivering risk-based health care for CRC survivors who have completed active therapy.
Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers
Vogtmann, Emily; Corley, Douglas A; Almers, Lucy M; Cardwell, Chris R; Murray, Liam J; Abnet, Christian C
Use of oral bisphosphonates has been associated with a decreased risk of colorectal cancer (CRC), but the association may be related to residual confounding by healthy lifestyle or body mass index (BMI). Therefore, we conducted a prospective nested case-control study within the Kaiser Permanente, Northern California health system cohort. In total, 12,505 CRC cases were individually matched to 599,534 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression models with adjustment for important covariates extracted from the database. Participants who had ever used oral bisphosphonates were less likely than non-users to be diagnosed with CRC (OR 0.82; 95% CI: 0.74, 0.89). Colon and rectum site-specific associations were similar to the overall association. A stronger inverse association for ever use of bisphosphonates was observed for men (OR 0.63; 95% CI: 0.47, 0.85), however when stratified by previous lower endoscopy, the association was only observed in the participants who did not have a previous lower endoscopy (OR 0.73 (0.64, 0.83)). In conclusion, we found that oral bisphosphonate use was associated with a decreased odds of CRC, however this association may be due to residual confounding by BMI or another confounder.
The incidence of colorectal cancer (CRC) has been increasing during the past decades, and the lifetime risk for CRC in industrialised countries is about 5%. CRC is a good candidate for screening, because it is a disease with high prevalence, has recognised precursors, and early treatment is beneficial. This paper outlines the evidence for efficacy from randomised trials for the most commonly used CRC screening tests to reduce CRC incidence and mortality in the average-risk population. Four randomised trials have investigated the effect of guaiac-based fecal occult blood screening on CRC mortality, with a combined CRC mortality risk reduction of 15-17% in an intention-to-screen analysis, and 25% for those people who attended screening. Flexible sigmoidoscopy screening has been evaluated in three randomised trials. The observed reduction in CRC incidence varied between 23 and 80%, and between 27 and 67% for CRC mortality, respectively (intention-to-screen analyses) in the trials with long follow-up time. No randomised trials exist in other CRC screening tools, included colonoscopy screening. FOBT and flexible sigmoidoscopy are the two CRC screening methods which have been tested in randomised trials and shown to reduce CRC mortality. These tests can be recommended for CRC screening. Copyright © 2010 Elsevier Ltd. All rights reserved.
Vogtmann, Emily; Corley, Douglas A.; Almers, Lucy M.; Cardwell, Chris R.; Murray, Liam J.; Abnet, Christian C.
Use of oral bisphosphonates has been associated with a decreased risk of colorectal cancer (CRC), but the association may be related to residual confounding by healthy lifestyle or body mass index (BMI). Therefore, we conducted a prospective nested case-control study within the Kaiser Permanente, Northern California health system cohort. In total, 12,505 CRC cases were individually matched to 599,534 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression models with adjustment for important covariates extracted from the database. Participants who had ever used oral bisphosphonates were less likely than non-users to be diagnosed with CRC (OR 0.82; 95% CI: 0.74, 0.89). Colon and rectum site-specific associations were similar to the overall association. A stronger inverse association for ever use of bisphosphonates was observed for men (OR 0.63; 95% CI: 0.47, 0.85), however when stratified by previous lower endoscopy, the association was only observed in the participants who did not have a previous lower endoscopy (OR 0.73 (0.64, 0.83)). In conclusion, we found that oral bisphosphonate use was associated with a decreased odds of CRC, however this association may be due to residual confounding by BMI or another confounder. PMID:28281559
Peters, Ulrike; Bien, Stephanie; Zubair, Niha
Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3–5%) of cases arises from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well-defined genes. In contrast, CRC is predominantly a late-onset “sporadic” disease, developing in individuals with no obvious hereditary syndrome. In recent years genome-wide association studies have discovered over 40 genetic regions to be associated with weak effects on sporadic CRC and it has been estimated that increasingly large genome-wide scans will identify many additional novel genetic regions. Subsequent experimental validations have identified the causally related variant(s) in a limited number of these genetic regions. Further biological insight could be obtained through ethnically diverse study populations, larger genetic sequencing studies, and development of higher-throughput functional experiments. Along with inherited variation, integration of the tumour genome may shed light on the carcinogenic processes in CRC. In addition to summarizing the genetic architecture of CRC, this review discusses genetic factors that modify environmental predictors of CRC, as well as examples of how genetic insight has improved clinical surveillance, prevention, and treatment strategies. In summary, substantial progress has been made in uncovering the genetic architecture of CRC and continued research efforts are expected to identify additional genetic risk factors that further our biological understanding of this disease. PMID:26187503
Wolf, Michael S.; Baker, David W.
Background Despite the documented benefits of colorectal cancer screening, patient participation rates remain low. Physician recommendation has been identified as a significant predictor of screening completion. Objective The aim of this study is to investigate how primary care physicians perceive colorectal cancer screening communication tasks, as well as to explore the form and content of actual screening discussions. Design The research design includes a mailed physician survey and a separate observational study in a sample of videotaped medical encounters. Participants and Data Sources The participants were 270 primary care physicians who completed a mailed questionnaire (57.9% response rate) and 18 physician–patient encounters that included discussions of colorectal cancer screening. Measurement The questionnaire focused on perceived importance and accomplishment of communication tasks relevant to colorectal cancer screening. Two of the authors reviewed transcripts of videotaped physician encounters to determine whether the same communication tasks assessed in the survey were accomplished. Interrater reliability was high across all of the mutually exclusive coding categories (Kappa > .90). Results Physicians rated colonoscopy as the most important screening option to discuss; self-reports indicate that colonoscopy (84.8%) is more frequently mentioned than fecal occult blood test (FOBT; 49.4%), flexible sigmoidoscopy (34.1%), or computed tomography (CT) imaging (18.1%). Explaining benefits and risks, describing test procedure and frequency, eliciting patient preferences, and making a plan for screening were all viewed as very important. Self-reported accomplishment of these communication tasks was considerably higher than that observed in our separate videotape sample. Conclusion Most physicians recognize and espouse the importance of recommending colorectal cancer screening to eligible patients. However, findings from both the physician survey and
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
Wang, Zhenjie; Uchida, Kazuhiro; Ohnaka, Keizo; Morita, Makiko; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
A diet high in sugars may promote colorectal carcinogenesis, but it remains uncertain whether high intake of sugars or sucrose confers increased risk of colorectal cancer. The authors investigated the associations of sugars and sucrose intake with colorectal cancer risk in a community-based case-control study in Japan. The study subjects comprised 816 incident cases of colorectal cancer and 815 community controls. Consumption frequencies and portion sizes of 148 food and beverage items were ascertained by a computer-assisted interview. The authors used the consumption of 29 food items to estimate sugars and sucrose intake. The odds ratios of colorectal cancer risk according to intake categories were obtained using a logistic regression model with adjustment for potential confounding variables. Overall, intakes of sugars and sucrose were not related to colorectal cancer risk either in men or women. The association between sugars intake and colorectal cancer risk differed by smoking status and alcohol use in men, but not in women. In men, sugars intake tended to be associated with colorectal cancer risk inversely among never-smokers and positively among male ever-smokers (interaction p=0.01). Sugars intake was associated with an increased risk among men with no alcohol consumption, but was unrelated to the risk among male alcohol drinkers (interaction p=0.02). Body mass index did not modify the association with sugars intake in either men or women. Sugars intake was associated with increased risk of colorectal cancer among smokers and non-alcohol drinkers in men selectively.
Westwood, Marie; Corro Ramos, Isaac; Lang, Shona; Luyendijk, Marianne; Zaim, Remziye; Stirk, Lisa; Al, Maiwenn; Armstrong, Nigel; Kleijnen, Jos
Colorectal cancer (CRC) is the third most common cancer in the UK. Presenting symptoms that can be associated with CRC usually have another explanation. Faecal immunochemical tests (FITs) detect blood that is not visible to the naked eye and may help to select patients who are likely to benefit from further investigation. To assess the effectiveness of FITs [OC-Sensor (Eiken Chemical Co./MAST Diagnostics, Tokyo, Japan), HM-JACKarc (Kyowa Medex/Alpha Laboratories Ltd, Tokyo, Japan), FOB Gold (Sentinel/Sysmex, Sentinel Diagnostics, Milan, Italy), RIDASCREEN Hb or RIDASCREEN Hb/Hp complex (R-Biopharm, Darmstadt, Germany)] for primary care triage of people with low-risk symptoms. Twenty-four resources were searched to March 2016. Review methods followed published guidelines. Summary estimates were calculated using a bivariate model or a random-effects logistic regression model. The cost-effectiveness analysis considered long-term costs and quality-adjusted life-years (QALYs) that were associated with different faecal occult blood tests and direct colonoscopy referral. Modelling comprised a diagnostic decision model, a Markov model for long-term costs and QALYs that were associated with CRC treatment and progression, and a Markov model for QALYs that were associated with no CRC. We included 10 studies. Using a single sample and 10 µg Hb/g faeces threshold, sensitivity estimates for OC-Sensor [92.1%, 95% confidence interval (CI) 86.9% to 95.3%] and HM-JACKarc (100%, 95% CI 71.5% to 100%) indicated that both may be useful to rule out CRC. Specificity estimates were 85.8% (95% CI 78.3% to 91.0%) and 76.6% (95% CI 72.6% to 80.3%). Triage using FITs could rule out CRC and avoid colonoscopy in approximately 75% of symptomatic patients. Data from our systematic review suggest that 22.5-93% of patients with a positive FIT and no CRC have other significant bowel pathologies. The results of the base-case analysis suggested minimal difference in QALYs between all of the
Grady, William M.; Pritchard, Colin C.
The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577
Goel, Vivek; Gray, Ross; Chart, Pam; Fitch, Marg; Saibil, Fred; Zdanowicz, Yola
Abstract Objective To assess attitudes and acceptability of Ontario consumers and doctors towards colorectal screening with faecal occult blood testing (FOBT) and colonoscopy. Design, setting and participants Focus groups with gender‐specific samples of the population, high‐risk gastroenterology patients and family doctors. Method Semi‐structured interview guides used by facilitator to lead groups through knowledge of risk factors and prevention of colorectal cancer, the screening modalities, requirements for implementing screening programmes, barriers to screening and preferences towards screening. Main findings There were low levels of knowledge about colorectal cancer and its prevention in the general population. FOBT was an acceptable screening modality, but considerable education about its use and benefits would be necessary to implement a screening programme. Colonoscopy was not perceived to be a good choice for a primary screen in the general population. The high‐risk group supported use of FOBT in the general population and emphasized the need for education. The doctors were more reluctant about screening, requesting clear guidelines. They also identified the time and resources that would be required if a screening programme were initiated. Conclusion While colorectal screening is acceptable in this sample, information and decision aids are required to enable consumers and providers to make effective decisions. Implementation of colorectal screening programmes requires substantial educational efforts for both consumers and doctors. PMID:14982499
Carney, Patricia A; O'Malley, Jean P; Gough, Andrea; Buckley, David I; Wallace, James; Fagnan, Lyle J; Morris, Cynthia; Mori, Motomi; Heintzman, John D; Lieberman, David
Previous research on ascertainment of cancer family history and cancer screening has been conducted in urban settings. To examine whether documented family history of breast or colorectal cancer is associated with breast or colorectal cancer screening. Medical record reviews were conducted on 3433 patients aged 55 and older from four primary care practices in two rural Oregon communities. Data collected included patient demographic and risk information, including any documentation of family history of breast or colorectal cancer, and receipt of screening for these cancers. A positive breast cancer family history was associated with an increased likelihood of being up-to-date for mammography screening (OR 2.09, 95% CI 1.45-3.00 relative to a recorded negative history). A positive family history for colorectal cancer was associated with an increased likelihood of being up-to-date with colorectal cancer screening according to U.S. Preventive Services Task Force low risk guidelines for males (OR 2.89, 95% CI 1.15-7.29) and females (OR 2.47, 95% CI 1.32-4.64) relative to a recorded negative family history. The absence of any recorded family cancer history was associated with a decreased likelihood of being up-to-date for mammography screening (OR 0.70, 95% CI 0.56-0.88 relative to recorded negative history) or for colorectal cancer screening (OR 0.75, 95% CI 0.60-0.96 in females, OR 0.68, 95% CI 0.53-0.88 in males relative to recorded negative history). Further research is needed to determine if establishing routines to document family history of cancer would improve appropriate use of cancer screening. © 2013.
Ruiz, Eloy; Celis, Juan; Berrospi, Francisco; Payet, Eduardo
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.
Cernat, Laura; Blaj, Cristina; Jackstadt, Rene; Brandl, Lydia; Engel, Jutta; Hermeking, Heiko; Jung, Andreas; Kirchner, Thomas; Horst, David
Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes. PMID:25111606
Obstein, Keith L; Valdastri, Pietro
Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation.
Obstein, Keith L; Valdastri, Pietro
Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation. PMID:23382621
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.
... 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 ...
Kreso, Antonija; van Galen, Peter; Pedley, Nicholas M; Lima-Fernandes, Evelyne; Frelin, Catherine; Davis, Thomas; Cao, Liangxian; Baiazitov, Ramil; Du, Wu; Sydorenko, Nadiya; Moon, Young-Choon; Gibson, Lianne; Wang, Yadong; Leung, Cherry; Iscove, Norman N; Arrowsmith, Cheryl H; Szentgyorgyi, Eva; Gallinger, Steven; Dick, John E; O'Brien, Catherine A
Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, more specifically, human colorectal CIC function are dependent on the canonical self-renewal regulator BMI-1. Downregulation of BMI-1 inhibits the ability of colorectal CICs to self-renew, resulting in the abrogation of their tumorigenic potential. Treatment of primary colorectal cancer xenografts with a small-molecule BMI-1 inhibitor resulted in colorectal CIC loss with long-term and irreversible impairment of tumor growth. Targeting the BMI-1-related self-renewal machinery provides the basis for a new therapeutic approach in the treatment of colorectal cancer.
Benson, Victoria S; Atkin, Wendy S; Green, Jane; Nadel, Marion R; Patnick, Julietta; Smith, Robert A; Villain, Patricia
The International Colorectal Cancer Screening Network was established in 2003 to promote best practice in the delivery of organized colorectal cancer screening programs. To facilitate evaluation of such programs, we defined a set of universally applicable colorectal cancer screening measures and indicators. To test the feasibility of data collection, we requested data on these variables and basic program characteristics from 26 organized full programs and 9 pilot programs in 24 countries. The size of the target population for each program varied considerably from a few thousand to 36 million. The majority of programs used fecal occult blood tests for primary screening, with more using guaiac than immunochemical tests. There was wide variation in the ability of screening programs to report the requested measures and in the values reported. In general, pilot programs were more likely to provide screening measure values than were full programs. As expected, detection rates for polyps and neoplasia were substantially higher in programs screening with endoscopy than in those using fecal occult blood tests. It is hoped that the screening measures and indicators, once revised in the light of this survey, will be adopted and used by existing programs and those in the early planning stages, allowing international comparison with the goal of improved colorectal cancer screening quality. Copyright © 2011 UICC.
Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Àlex; Medina-Hayas, Manuel
Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy
Preisich, P; Siba, S; Szakátsy, E
Haemoccult screening for colorectal tumours was carried out in Hungary in small cities and villages around Budapest. Haemoccult slides were supplied to 17,662 individuals over 40 years of age, and 15,431 (87%) were returned. Of these, 346 (2.2%) were positive and 18 colorectal carcinomas were detected. Additionally, 24 patients with one or more polyps greater than 1 cm diameter were found. Of the screened cases of cancer 39% were in Dukes' stage A and B, a rate twice as good as when screening was not done. The cost per tumour detected amounted to about three times more than one monthly income, indicating that the costs of screening for colorectal cancer are relatively much higher in Hungary than in Western countries. All expenses were met from state funds. PMID:3625689
Hiraide, Takanori; Ikegami, Koji; Sakaguchi, Takanori; Morita, Yoshifumi; Hayasaka, Takahiro; Masaki, Noritaka; Waki, Michihiko; Sugiyama, Eiji; Shinriki, Satoru; Takeda, Makoto; Shibasaki, Yasushi; Miyazaki, Shinichiro; Kikuchi, Hirotoshi; Okuyama, Hiroaki; Inoue, Masahiro; Setou, Mitsutoshi; Konno, Hiroyuki
Accumulating evidence indicates that cancer cells show specific alterations in phospholipid metabolism that contribute to tumour progression in several types of cancer, including colorectal cancer. Questions still remain as to what lipids characterize the outer edge of cancer tissues and whether those cancer outer edge-specific lipid compositions emerge autonomously in cancer cells. Cancer tissue-originated spheroids (CTOSs) that are composed of pure primary cancer cells have been developed. In this study, we aimed to seek out the cancer cell-autonomous acquisition of cancer outer edge-characterizing lipids in colorectal cancer by analysing phospholipids in CTOSs derived from colorectal cancer patients with matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS). A signal at m/z 885.5 in negative ion mode was detected specifically at the surface regions. The signal was identified as an arachidonic acid (AA)-containing phosphatidylinositol (PI), PI(18:0/20:4), by tandem mass spectrometry analysis. Quantitative analysis revealed that the amount of PI(18:0/20:4) in the surface region of CTOSs was two-fold higher than that in the medial region. Finally, PI(18:0/20:4) was enriched at the cancer cells/stromal interface in colorectal cancer patients. These data imply a possible importance of AA-containing PI for colorectal cancer progression, and suggest cells expressing AA-containing PI as potential targets for anti-cancer therapy. PMID:27435310
Colorectal cancer (CRC) cells express renin and chymase through which they can activate angiotensin. Renin expression is induced by hyperglycemic conditions. As angiotensinogen is produced in the liver, CRC cells that can activate angiotensin have an enhanced ability to metastasize to this organ. In human CRC cases, patients with diabetes have higher activities of rennin and angiotensin-II in primary tumors, and on average, have a more progressed disease stage, especially with respect to liver metastasis. These patients exhibit a stronger association with Hemoglobin A1c levels and metastasis compared to patients without diabetes. In a combined diabetes/CRC liver metastasis mouse model, concurrent treatment with anti-angiotensin and hypoglycemic agents shows a synergic effect in terms of reduced liver metastasis and improved survival. The effect of anti-angiotensin treatment and blood sugar control as a baseline management for colon cancer patients with diabetes needs to be examined in clinical trials to establish whether it can prevent liver metastasis. PMID:23293754
Kang, Wonmo; Lee, Sujin; Jeon, Eunyi; Yun, Ye-Rang; Kim, Kook-Hyun; Jang, Jun-Hyeog
Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D(3) reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer.
Lynch, H T; Watson, P; Lanspa, S J; Marcus, J; Smyrk, T; Fitzgibbons, R J; Kriegler, M; Lynch, J F
Approximately 5 to 6 percent of the total colorectal cancer burden is accounted for by hereditary nonpolyposis colorectal cancer (HNPCC). Because clinical premonitory signs such as those seen in familial polyposis coli (FPC) are lacking, the clinician must recognize clinical findings and family history typical of HNPCC. The authors have described colorectal cancer expression from a survey of ten HNPCC kindreds. Kindred members with colorectal cancer differed significantly (P less than .05) from patients with sporadic colorectal cancer: 1) mean age of initial colon cancer diagnosis was 44.6 years; 2) 72.3 percent of first colon cancers were located in the right colon, and only 25 percent were in the sigmoid colon and rectum; 3) 18.1 percent had synchronous colon cancers; and 4) 24.2 percent developed metachronous colon cancer, with a risk for metachronous lesions in ten years of 40 percent. Affecteds and their first-degree relatives should undergo early intensive education and surveillance. In families with an early age of onset, colonoscopy should begin at age 25, and biannually thereafter, with fecal occult blood testing of the stool semiannually. Third-party carriers must become more responsive to the costly surveillance measures required for these otherwise healthy patients.
Breast Cancer; Lung Cancer; Colorectal Cancer; Melanoma; Gynecological Cancer; Genitourinary Cancer; Pancreatobiliary Cancer; Gastrointestinal Cancer; Head and Neck Cancer; Rare Cancer; Unknown Primary Cancer
Palliative resection of the primary tumor is associated with improved overall survival in incurable stage IV colorectal cancer: A nationwide population-based propensity-score adjusted study in the Netherlands.
't Lam-Boer, Jorine; Van der Geest, Lydia G; Verhoef, Cees; Elferink, Marloes E; Koopman, Miriam; de Wilt, Johannes H
As the value of palliative primary tumor resection in stage IV colorectal cancer (CRC) is still under debate, the purpose of this population-based study was to investigate if palliative primary tumor resection as the initial treatment after diagnosis was associated with improved overall survival. All patients with stage IV colorectal adenocarcinoma (2008-2011) were selected from the Netherlands Cancer Registry, and patients undergoing treatment with curative intent (i.e., metastasectomy, radiofrequency ablation and/or hyperthermic intraperitoneal chemotherapy), or best supportive care were excluded. After propensity score matching, a multivariable Cox proportional hazard model was performed to determine the association between treatment strategy and mortality. From a total group of 10,371 patients with stage IV CRC, 2,746 patients (26%) underwent an elective palliative resection of the primary tumor, whether or not followed by systemic therapy, and 3,345 patients (32%) were initially treated with palliative systemic therapy. After propensity score matching, median overall survival in these groups was 17.2 months (95% CI 16.3-18.1) and 11.5 months (95% CI 11.0-12.0), respectively. In Cox regression analysis, primary tumor resection was significantly associated with improved overall survival (hazard ratio of death = 0.44 [95% CI 0.35-0.55], p < 0.001). This large population-based study shows an overall survival benefit for patients with incurable stage IV CRC who underwent primary tumor resection as the initial treatment after diagnosis, compared to patients who started systemic therapy with the primary tumor in situ. This result is an argument in favor of resection of the primary tumor, even when patients have little to no symptoms.
Povlow, Michael R
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
Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH) examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35%) pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) and 15 cases (1.73%) were suspected of HNPCC. In 69 cases (8%) with a cancer family aggregation (CFA) were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.
Park, Sang Min; Lee, Jongmog; Kim, Young Ae; Chang, Yoon Jung; Kim, Moon Soo; Shim, Young Mog; Zo, Jae Ill; Yun, Young Ho
Lung cancer survivors are more likely to develop colorectal and stomach cancer than the general population. However, little is known about the current status of gastrointestinal cancer screening practices and related factors among lung cancer survivors. We enrolled 829 disease-free lung cancer survivors ≥40 years of age, who had been treated at two hospitals from 2001 to 2006. The patients completed a questionnaire that included stomach and colorectal cancer screening after lung cancer treatment, as well as other sociodemographic variables. Among lung cancer survivors, correlations with stomach and colorectal screening recommendations were 22.7 and 25.8%, respectively. Of these, 40.7% reported receiving physician advice to screen for second primary cancer (SPC). Those who were recommended for further screening for other cancers were more likely to receive stomach cancer screening [adjusted odds ratios (aOR) = 1.63, 95% confidence interval (CI), 1.16-2.30] and colorectal cancer screening [aOR = 1.37, 95% CI, 0.99-1.90]. Less-educated lung cancer survivors were less likely to have stomach and colorectal cancer screenings. Lack of a physician's advice for SPC screening and lower educational status had negative impact on the gastrointestinal cancer screening rates of lung cancer survivors.
Baldwin, Laura-Mae; Cai, Yong; Larson, Eric H.; Dobie, Sharon A.; Wright, George E.; Goodman, David C.; Matthews, Barbara; Hart, L. Gary
Context: Cancer care requires specialty surgical and medical resources that are less likely to be found in rural areas. Purpose: To examine the travel patterns and distances of rural and urban colorectal cancer (CRC) patients to 3 types of specialty cancer care services--surgery, medical oncology consultation, and radiation oncology consultation.…
Baldwin, Laura-Mae; Cai, Yong; Larson, Eric H.; Dobie, Sharon A.; Wright, George E.; Goodman, David C.; Matthews, Barbara; Hart, L. Gary
Context: Cancer care requires specialty surgical and medical resources that are less likely to be found in rural areas. Purpose: To examine the travel patterns and distances of rural and urban colorectal cancer (CRC) patients to 3 types of specialty cancer care services--surgery, medical oncology consultation, and radiation oncology consultation.…
Rodrigues, Paulo; Macaya, Irati; Bazzocco, Sarah; Mazzolini, Rocco; Andretta, Elena; Dopeso, Higinio; Mateo-Lozano, Silvia; Bilić, Josipa; Cartón-García, Fernando; Nieto, Rocio; Suárez-López, Lucia; Afonso, Elsa; Landolfi, Stefania; Hernandez-Losa, Javier; Kobayashi, Kazuto; Cajal, Santiago Ramón y; Tabernero, Josep; Tebbutt, Niall C.; Mariadason, John M.; Schwartz, Simo; Arango, Diego
Activation of the small GTPase RHOA has strong oncogenic effects in many tumor types, although its role in colorectal cancer remains unclear. Here we show that RHOA inactivation contributes to colorectal cancer progression/metastasis, largely through the activation of Wnt/β-catenin signaling. RhoA inactivation in the murine intestine accelerates the tumorigenic process and in human colon cancer cells leads to the redistribution of β-catenin from the membrane to the nucleus and enhanced Wnt/β-catenin signaling, resulting in increased proliferation, invasion and de-differentiation. In mice, RHOA inactivation contributes to colon cancer metastasis and reduced RHOA levels were observed at metastatic sites compared to primary human colon tumors. Therefore, we have identified a new mechanism of activation of Wnt/β-catenin signaling and characterized the role of RHOA as a novel tumor suppressor in colorectal cancer. These results constitute a shift from the current paradigm and demonstrate that RHO GTPases can suppress tumor progression and metastasis. PMID:25413277
Sameer, Aga Syed; Nissar, Saniya
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.
Cézé, Nicolas; Charachon, Antoine; Locher, Christophe; Aparicio, Thomas; Mitry, Emmanuel; Barbieux, Jean-Pierre; Landi, Bruno; Dorval, Etienne; Moussata, Driffa; Lecomte, Thierry
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.
Richardson, Ann K; Potter, John D
Prostate cancer and colorectal cancer are the most commonly registered cancers in New Zealanders and among the five most commonly registered cancers worldwide, but the balance of benefits and harms, and therefore appropriate screening policies, for these cancers differ. We aimed to compare the potential benefits and harms of screening for prostate cancer and colorectal cancer to aid prioritisation in New Zealand. Relevant reports from randomised controlled trials and systematic reviews of prostate cancer and colorectal cancer screening were reviewed to obtain estimates of the potential benefits and harms of screening for prostate cancer and colorectal cancer. The balance of potential benefits and harms of screening is better for colorectal cancer screening than for prostate cancer screening. For colorectal cancer, the balance of benefits and harms is better for flexible sigmoidoscopy screening than for faecal occult blood screening. In New Zealand, colorectal cancer screening should be a priority. Challenges include colonoscopy capacity, and decisions about the most appropriate screening modality.
Levi, Fabio; Randimbison, Lalao; Blanc-Moya, Rafael; La Vecchia, Carlo
Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.
Morita, Makiko; Yin, Guang; Yoshimitsu, Shin-ichiro; Ohnaka, Keizo; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.
Lee, Kyung-Jae; Inoue, Manami; Otani, Tetsuya; Iwasaki, Motoki; Sasazuki, Shizuka; Tsugane, Shoichiro
To investigate prospectively the association between colorectal cancer screening and subsequent risk of colorectal cancer death in a large-scale population-based cohort study (the JPHC study) with a 13-year follow-up period in Japan. We analyzed data from a population-based cohort of 42,150 (20,326 men and 21,824 women) subjects. Subjects who had undergone fecal occult blood test (FOBT) screening during the preceding 12 months were defined as the screened group. A total of 132 colorectal cancer deaths and 597 cases of newly diagnosed colorectal cancer were identified during the follow-up period. We observed a nearly 70% decrease in colorectal cancer mortality in screened versus unscreened subjects (RR=0.28, 95% CI=0.13-0.61). Screening participation was associated with a 30% reduced risk of death from all causes other than colorectal cancer (RR=0.70, 95% CI=0.61-0.79). However, the extent of mortality reduction was greater for colorectal cancer than other causes. A significant decrease in the incidence of advanced colorectal cancer was seen in screened subjects (RR=0.41, 95% CI=0.27-0.63), although the overall incidence rate did not differ significantly between the screened and unscreened groups. Although self-selection bias could not be fully controlled, these findings suggest that colorectal cancer screening may be associated with a reduction in mortality from colorectal cancer in the Japanese population.
Colorectal cancer (CRC) is still one of the deadliest cancer-related diseases. About 10% of CRC patients are characterized by a mutation in the B-Raf proto-oncogene serine/threonine kinase (BRAF) gene resulting in a valine-to-glutamate change at the residue 600 (V600E). This mutation is also present in more than 60% of melanoma patients. BRAF inhibitors were developed and found to improve patient survival; however, most patients at the end of the track ultimately develop resistance to these inhibitors. Melanoma patients benefit from the combination of BRAF inhibitors with mitogen/extracellular signal-regulated kinase (MEK) inhibitors, among others. Unfortunately, colorectal patients do not respond much efficiently, which suggests different resistance mechanisms between the two cancer types. This review aims at shedding light on recent discoveries that improve our understanding of the BRAF mutation biology in CRC. PMID:26396549
El-Shami, Khaled; Oeffinger, Kevin C.; Erb, Nicole L.; Willis, Anne; Bretsch, Jennifer; Pratt-Chapman, Mandi L.; Cannady, Rachel; Wong, Sandra L.; Rose, Johnie; Barbour, April; Stein, Kevin; Sharpe, Katherine; Brooks, Durado D.; Cowens-Alvarado, Rebecca L.
Colorectal cancer (CRC) is the third most common malignant disease in the United States (U.S.). Almost two-thirds of CRC survivors are living 5 years following diagnosis. The prevalence of CRC survivors is likely to increase dramatically over the coming decades with further advances in early detection and treatment and the aging and growth of the U.S. population. Survivors are at risk for a CRC recurrence, a new primary CRC, other cancers, as well as both short and long-term adverse effects of the CRC and the modalities used to treat it. CRC survivors may also have psychological, reproductive, genetic, social, and employment concerns following treatment. Communication and coordination of care between the treating oncologist and the primary care clinician is critical to effectively and efficiently manage the long-term care of CRC survivors. The following guidelines are intended to assist primary care clinicians in delivering risk-based health care for CRC survivors who have completed active therapy. PMID:26348643
Panduro Cerda, A; Lima González, G; Villalobos, J J
Genetic and environmental aspects play an important role in the development of colorectal cancer. However, the common molecular alteration in both hereditary and sporadic colon cancer is localized in the APC gene. the APC gene maps in the long arm of chromosome 5 and was discovered in patients with familial adenomatous polyposis (FAP). The search for the APC gene led to the identification of restriction fragment length polymorphisms (RFLPs) in FAP patients. Using these RFLPs in relatives of FAP patients it is possible to make the presymptomatic and prenatal diagnosis. The FAP syndrome is an interesting model of carcinogenesis in vivo. Thus the different stages involved in the FAP syndrome which include hyperproliferative epithelium, adenoma, adenocarcinoma and metastases, have allowed the analysis of molecular alterations in oncogenes and tumor suppressor genes. The APC gene alteration if not inherited, occurs as the earliest molecular alteration in the development of colorectal cancer whereas structural alterations of the genes myc, ras, p53, MCC and DCC are considered to be late events. All these investigations have lead to 1) a better understanding of the ethiology of cancer and 2) early diagnosis of colorectal cancer in both the hereditary and sporadic forms of the disease.
Belov, Larissa; Zhou, Jerry; Christopherson, Richard I.
The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC. PMID:21339979
Kim, Karen; Chapman, Christopher; Vallina, Helen
The purpose of this study was to examine the factors determining fecal occult blood test (FOBT) uptake in Chinese American immigrants. This study used a prospective, cross-sectional design with convenience sampling. An educational session on colorectal cancer screening (CRS) was provided to the participants during a health fair, and each participant was offered a no-cost FOBT kit. Data was collected over two consecutive years during three different health fairs. A questionnaire was used to collect demographic data. A total of 113 participants were recruited and 72% of them returned the FOBT kit. There was a significant association between having a primary-care physician (PCP) and having CRS in the past, even after controlling for age, gender and the length of time in the US (P = .009). Participants who visited a doctor for health maintenance were less likely to participate in the FOBT, compared to participants who never visited a doctor or who only visited a doctor when they were sick (P = .001). The length of time in the US had a significant effect on having a PCP (P = .002). However, having a PCP or having CRS in the past was not associated with participating in the screening and so was feeling at risk for CRC. In fact, 49% of Chinese women and 45% of Chinese men felt no risk of CRC. Future research and interventions that address knowledge deficits and focus on recent immigrants and their access to health care may have the potential to increase CRS among Chinese American immigrants.
Brändstedt, Jenny; Wangefjord, Sakarias; Nodin, Björn; Eberhard, Jakob; Sundström, Magnus; Manjer, Jonas; Jirström, Karin
Obesity is a well-established risk factor for colorectal cancer (CRC), and accumulating evidence suggests a differential influence of sex and anthropometric factors on the molecular carcinogenesis of the disease. The aim of the present study was to investigate the relationship between height, weight, bodyfat percentage, waist- and hip circumference, waist-hip ratio (WHR), body mass index (BMI) and CRC risk according to KRAS and BRAF mutation status of the tumours, with particular reference to potential sex differences. KRAS and BRAF mutations were analysed by pyrosequencing in tumours from 494 incident CRC cases in the Malmö Diet and Cancer Study. Hazard ratios of CRC risk according to anthropometric factors and mutation status were calculated using multivariate Cox regression models. While all anthropometric measures except height were associated with an increased risk of KRAS-mutated tumours, only BMI was associated with an increased risk of KRAS wild type tumours overall. High weight, hip, waist, WHR and BMI were associated with an increased risk of BRAF wild type tumours, but none of the anthropometric factors were associated with risk of BRAF-mutated CRC, neither in the overall nor in the sex-stratified analysis. In men, several anthropometric measures were associated with both KRAS-mutated and KRAS wild type tumours. In women, only a high WHR was significantly associated with an increased risk of KRAS-mutated CRC. A significant interaction was found between sex and BMI with respect to risk of KRAS-mutated tumours. In men, all anthropometric factors except height were associated with an increased risk of BRAF wild type tumours, whereas in women, only bodyfat percentage was associated with an increased risk of BRAF wild type tumours. The results from this prospective cohort study further support an influence of sex and lifestyle factors on different pathways of colorectal carcinogenesis, defined by KRAS and BRAF mutation status of the tumours.
Chong, Dawn Q; Mehta, Raaj S; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A; Ng, Kimmie; Wu, Kana; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Chan, Andrew T
Circulating adiponectin is inversely related to the risk of colorectal cancer. However, its influence on colorectal cancer survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with colorectal cancer. We identified 621 incident colorectal cancer cases who provided blood specimens prior to diagnosis within the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to colorectal cancer. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21-2.97; P(trend) = 0.01) for colorectal cancer-specific mortality and 1.66 (95% CI, 1.15-2.39; P(trend) = 0.009) for overall mortality. The apparent increased risk in colorectal cancer-specific mortality was more pronounced in patients with metastatic disease (HR, 3.02: 95% CI, 1.50-6.08). Among patients with colorectal cancer, prediagnostic plasma adiponectin is associated with an increased risk of colorectal cancer-specific and overall mortality and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings.
Patel, K; Doulias, T; Hoad, T; Lee, C; Alberts, JC
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
Patel, K; Doulias, T; Hoad, T; Lee, C; Alberts, J C
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.
Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer; Small Intestine Cancer
Gross, Cary P; Guo, Zhenchao; McAvay, Gail J; Allore, Heather G; Young, Mary; Tinetti, Mary E
To ascertain the effect of common chronic conditions on mortality in older persons with colorectal cancer. Retrospective cohort study. Population-based cancer registry. Patients in the Surveillance Epidemiology and End Results-Medicare linked database who were aged 67 and older and had a primary diagnosis of Stage 1 to 3 colorectal cancer during 1993 through 1999. Chronic conditions were identified using claims data, and vital status was determined from the Medicare enrollment files. After estimating the adjusted hazard ratios for mortality associated with each condition using a Cox model, the population attributable risk (PAR) was calculated for the full sample and by age subgroup. The study sample consisted of 29,733 patients, 88% of whom were white and 55% were female. Approximately 9% of deaths were attributable to congestive heart failure (CHF; PAR = 9.4%, 95% confidence interval (CI) = 8.4-10.5%), more than 5% were attributable to chronic obstructive pulmonary disease (COPD; PAR = 5.3%, 95% CI = 4.7-6.6%), and nearly 4% were attributable to diabetes mellitus (PAR = 3.9%, 95% CI = 3.1-4.8%). The PAR associated with CHF increased with age, from 6.3% (95% CI = 4.4-8.8%) in patients aged 67 to 70 to 14.5% (95% CI = 12.0-17.5%) in patients aged 81 to 85. Multiple conditions were common. More than half of the patients who had CHF also had diabetes mellitus or COPD. The PAR associated with CHF alone (4.29%, 95% CI = 3.68-4.94%) was similar to the PAR for CHF in combination with diabetes mellitus (3.08, 95% CI = 2.60-3.61%) or COPD (3.93, 95% CI = 3.41-4.54%). A substantial proportion of deaths in older persons with colorectal cancer can be attributed to CHF, diabetes mellitus, and COPD. Multimorbidity is common and exerts a substantial effect on colorectal cancer survival.
Tape, Christopher J
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.
Brosens, Lodewijk A A; Offerhaus, G Johan A; Giardiello, Francis M
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. About 30% of patients with CRC report a family history of CRC. However, only 5% of CRCs arise in the setting of a well-established mendelian inherited disorder. In addition, serrated polyposis is a clinically defined syndrome with multiple serrated polyps in the colorectum and an increased CRC risk for which the genetics are unknown. This article focuses on genetic and clinical aspects of Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis. Copyright © 2015 Elsevier Inc. All rights reserved.
Millan, Monica; Merino, Sandra; Caro, Aleidis; Feliu, Francesc; Escuder, Jordi; Francesch, Tani
Colorectal cancer has a high incidence, and approximately 60% of colorectal cancer patients are older than 70, with this incidence likely increasing in the near future. Elderly patients (> 70-75 years of age) are a very heterogeneous group, ranging from the very fit to the very frail. Traditionally, these patients have often been under-treated and recruited less frequently to clinical trials than younger patients, and thus are under-represented in publications about cancer treatment. Recent studies suggest that fit elderly patients can be treated in the same way as their younger counterparts, but the treatment of frail patients with comorbidities is still a matter of controversy. Many factors should be taken into account, including fitness for treatment, the wishes of the patient and family, and quality of life. This review will focus on the existing evidence for surgical, oncologic, and palliative treatment in patients over 70 years old with colorectal cancer. Careful patient assessment is necessary in order to individualize treatment approach, and this should rely on a multidisciplinary process. More well-designed controlled trials are needed in this patient population. PMID:26483875
Body image is understood to be a person's perception of his or her own physical appearance although, as this article highlights, it embraces a greater range of bodily attributes than is often appreciated. It can be significantly affected by a diagnosis of colorectal cancer and subsequent treatment, which may modify the way the body looks, feels and functions. One of the major aesthetic and functional consequences of colorectal cancer surgery is the possibility of stoma formation, which is of particular concern to many. However, the range of other bodily effects following surgery should not be overlooked, not least because of they may result in distress. While concerns about changes in body image generally decrease over time, people recovering from cancer treatment often feel their relationship with their body has been permanently altered. Specialist support is often required when adjusting to any changes in bodily appearance and function. Care outcomes can be improved by having a sound understanding of the body image concerns likely to arise following treatment, as well as the skills to identify and support patients at risk of altered body image. This article provides guidance to nurses caring for individuals who may be experiencing distress over how their body is now perceived by themselves and others following colorectal cancer surgery.
Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real
Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as “hamartomatous polyposis syndromes”, “Peutz-Jeghers syndrome”, “juvenile polyposis syndrome”, “juvenile polyp”, and “PTEN hamartoma tumour syndrome” (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented. PMID:25848489
Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real
Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as "hamartomatous polyposis syndromes", "Peutz-Jeghers syndrome", "juvenile polyposis syndrome", "juvenile polyp", and "PTEN hamartoma tumour syndrome" (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented.
Thomas, Joe; Ohtsuka, Masahisa; Pichler, Martin; Ling, Hui
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.
Wang, Zhen-Jie; Ohnaka, Keizo; Morita, Makiko; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
AIM: To investigate the associations between dietary intake of polyphenols and colorectal cancer. METHODS: The study subjects were derived from the Fukuoka colorectal cancer study, a community-based case-control study. The study subjects were 816 cases of colorectal cancer and 815 community-based controls. The consumption of 148 food items was assessed by a computer-assisted interview. We used the consumption of 97 food items to estimate dietary intakes of total, tea and coffee polyphenols. The Phenol-Explorer database was used for 92 food items. Of the 5 foods which were not listed in the Phenol-Explorer Database, polyphenol contents of 3 foods (sweet potatoes, satoimo and daikon) were based on a Japanese study and 2 foods (soybeans and fried potatoes) were estimated by ORAC-based polyphenol contents in the United States Department of Agriculture Database. Odds ratios (OR) and 95%CI of colorectal cancer risk according to quintile categories of intake were obtained by using logistic regression models with adjustment for age, sex, residential area, parental history of colorectal cancer, smoking, alcohol consumption, body mass index 10 years before, type of job, leisure-time physical activity and dietary intakes of calcium and n-3 polyunsaturated fatty acids. RESULTS: There was no measurable difference in total or tea polyphenol intake between cases and controls, but intake of coffee polyphenols was lower in cases than in controls. The multivariate-adjusted OR of colorectal cancer according to quintile categories of coffee polyphenols (from the first to top quintile) were 1.00 (referent), 0.81 (95%CI: 0.60-1.10), 0.65 (95%CI: 0.47-0.89), 0.65 (95%CI: 0.46-0.89) and 0.82 (95%CI: 0.60-1.10), respectively (Ptrend = 0.07). Similar, but less pronounced, decreases in the OR were also noted for the third and fourth quintiles of total polyphenol intake. Tea polyphenols and non-coffee polyphenols showed no association with colorectal cancer risk. The site-specific analysis
Pericleous, Marinos; Mandair, Dalvinder
Background Colorectal cancer is the third commonest cancer and the third leading cause of cancer death among men and women. It has been proposed that dietary factors are responsible for 70-90% of colorectal cancer and diet optimization may prevent most cases. Aim To evaluate the role of dietary components and supplements in colorectal cancer. Methods Bibliographical searches were performed in Pubmed for the terms “diet and colorectal cancer”, “diet and colon cancer”, “diet and rectal cancer”, “nutrition and colorectal cancer”, “probiotics and colorectal cancer”, “prebiotics and colorectal cancer”, “alcohol and cancer” and “colorectal cancer epidemiology”. Results Consumption of processed or red meat, especially when cooked at high temperatures may be associated with increased risk of colorectal cancer. The evidence for dietary fibre is unclear but foods that contain high amounts of fibre are usually rich in polyphenols which have been shown to alter molecular processes that can encourage colorectal carcinogenesis. Meta-analyses provide evidence on the benefits of circulating, diet-derived and supplemented, vitamin D and Calcium. We also found that diets rich in Folate may prevent colorectal carcinoma. The evidence on dietary micronutrients such as Zinc and Selenium in association with colorectal cancer is not conclusive. It has been suggested that there may be a direct association between alcohol intake and colorectal cancer. In vitro and in vivo studies have highlighted a possible protective role of prebiotics and probiotics. Conclusions The lack of randomized trials and the presence of confounding factors including smoking, physical activity, obesity and diabetes may often yield inconclusive results. Carefully designed randomized trials are recommended. PMID:24294513
Migliore, Lucia; Migheli, Francesca; Spisni, Roberto; Coppedè, Fabio
Most of the colorectal cancer (CRC) cases are sporadic, only 25% of the patients have a family history of the disease, and major genes causing syndromes predisposing to CRC only account for 5-6% of the total cases. The following subtypes can be recognized: MIN (microsatellite instability), CIN (chromosomal instability), and CIMP (CpG island methylator phenotype). CIN occurs in 80–85% of CRC. Chromosomal instability proceeds through two major mechanisms, missegregation that results in aneuploidy through the gain or loss of whole chromosomes, and unbalanced structural rearrangements that lead to the loss and/or gain of chromosomal regions. The loss of heterozygosity that occur in the first phases of the CRC cancerogenesis (in particular for the genes on 18q) as well as the alteration of methylation pattern of multiple key genes can drive the development of colorectal cancer by facilitating the acquisition of multiple tumor-associated mutations and the instability phenotype. PMID:21490705
Houlston, Richard S.
Many colorectal cancers (CRCs) develop in genetically susceptible individuals most of whom are not carriers of germ line mismatch repair or APC gene mutations and much of the heritable risk of CRC appears to be attributable to the co-inheritance of multiple low-risk variants. The accumulated experience to date in identifying this class of susceptibility allele has highlighted the need to conduct statistically and methodologically rigorous studies and the need for the multi-centre collaboration. This has been the motivation for establishing the COGENT (COlorectal cancer GENeTics) consortium which now includes over 20 research groups in Europe, Australia, the Americas, China and Japan actively working on CRC genetics. Here, we review the rationale for identifying low-penetrance variants for CRC and the current and future challenges for COGENT. PMID:22294761
Van Dam, Jacques
Premalignant diseases of the gastrointestinal tract, such as Barrett's esophagus, long-standing ulcerative colitis, and adenomatous polyps, have a significantly increased risk for development of adenocarcinoma, most often through an intermediate stage of dysplasia. Adenocarcinoma of the colon is the second most common cancer in the United States. Because patients with colorectal cancer often present with advanced disease, the outcomes are associated with significant morbidity and mortality. Effective methods of early detection are essential. As non-polypoid dysplasia is not visible using conventional endoscopy, surveillance of patients with Barrett's esophagus and ulcerative colitis is performed via a system in which multiple random biopsies are obtained at prescribed intervals. Sampling error and missed diagnoses occur frequently and render current screening methods inadequate. Also, the examination of a tissue biopsy is time consuming and costly, and significant intra- and inter-observer variation may occur. The newer methods discussed herein demonstrate the potential to solve these problems by early detection of disease with high sensitivity and specificity. Conventional endoscopy is based on the observation of white light reflected off the tissue surface. Subtle changes in color and shadow reveal structural changes. New developments in optical imaging go beyond white light, exploiting other properties of light. Several promising methods will be discussed at this meeting and shall be briefly discussed below. However, few such imaging modalities have arrived at our clinical practice. Some much more practical methods to improve colorectal cancer screening are currently being evaluated for their clinical impact. These methods seek to overcome limitations other than those of detecting dysplasia not visible under white light endoscopy. The current standard practice of colorectal cancer screening utilizes colonoscopy, an uncomfortable, sometimes difficult medical
Guillén-Ponce, C; Serrano, R; Sánchez-Heras, A B; Teulé, A; Chirivella, I; Martín, T; Martínez, E; Morales, R; Robles, L
Genetic mutations have been identified as the cause of inherited cancer risk in some colon cancer; these mutations are estimated to account for only 5-6 % of colorectal cancer (CRC) cases overall. Up to 25-30 % of patients have a family history of CRC that suggests a hereditary component, common exposures among family members, or a combination of both. Cancers in people with a hereditary predisposition typically occur at an earlier age than in sporadic cases. A predisposition to CRC may include a predisposition to other cancers, such as endometrial cancer. We describe genetics, current diagnosis and management of CRC hereditary syndromes pointing to a multidisciplinary approach to achieve the best results in patients and family outcomes.
Cohen, A.M.; Martin, E.W. Jr.; Lavery, I.; Daly, J.; Sardi, A.; Aitken, D.; Bland, K.; Mojzisik, C.; Hinkle, G. )
Preliminary data using B72.3 murine monoclonal antibody labeled with iodine 125 suggested that both clinically apparent as well as occult sites of colorectal cancer could be identified intraoperatively using a hand-held gamma detecting probe. We report the preliminary data of a multicenter trial of this approach in patients with primary or recurrent colorectal cancer. One hundred four patients with primary, suspected, or known recurrent colorectal cancer received an intravenous infusion of 1 mg of B72.3 monoclonal antibody radiolabeled with 7.4 x 10 Bq of iodine 125. Twenty-six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined. Using the gamma detecting probe, 78% of the patients had localization of the antibody in their tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor sites; 9.2% of all tumor sites identified represented occult sites detected only with the gamma detecting probe. The overall sensitivity was 77% and a predictive value of a positive detection was 78%. A total of 30 occult sites in 26 patients were identified. In patients with recurrent cancer, the antibody study provided unique data that precluded resection in 10 patients, and in another eight patients it extended the potentially curative procedure.
Wang, Yue; Duan, Boshi; Shen, Chunjian; Wu, Bo; Luo, Ji; Zhao, Guohua
The aim of this study was to identify the influencing factors related to outcome of patients of colorectal cancer with liver metastasis. From January 1999 to January 2009, 293 cases of colorectal cancer with liver metastasis undergoing surgery were analysised retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis. Results: The 1-, 3- and 5-year survival rates of patients after resection were 58.3%, 26.4%, and 11.3%, respectively. Univariate analysis showed that preoperative CEA level, degree of primary tumor differentiation, resection margin, number of liver metastases, resection of liver metastases were prognostic impacts. The difference was statistically significant (p<0.05). Cox multivariate analysis showed that preoperative CEA level, number of liver metastases, and resection of liver metastases are three separate prognostic factors. Racical resection is the key to improve the long-term survival rate of colorectal cancer with liver metastasis. Important predictive factors related to poor survival are preoperative CEA level and number of liver metastases.
McCafferty, Michael H
The purpose of this review is to provide the practicing surgeon with an outline of several significant developments in colorectal cancer treatment that have affected the care of patients. This review is not intended to report on every important publication of the past few years nor is it intended to be encyclopedic. The author simply hopes to provide a useful reference for surgeons in their daily practice.
Deckx, Laura; van Abbema, Doris L; van den Akker, Marjan; van den Broeke, Carine; van Driel, Mieke; Bulens, Paul; Tjan-Heijnen, Vivianne C G; Kenis, Cindy; de Jonge, Eric T; Houben, Bert; Buntinx, Frank
Although older cancer survivors commonly report psychosocial problems, the impact of both cancer and ageing on the occurrence of these problems remains largely unknown. The evolution of depression, cognitive functioning, and fatigue was evaluated in a group of older cancer patients in comparison with a group of younger cancer patients and older persons without cancer. Older (≥70 years) and younger cancer patients (50-69 years) with breast or colorectal cancer stage I-III, and older persons without cancer (≥70 years) were included. Data were collected at baseline and one year follow-up and were available for 536 persons. Depression was evaluated with the 15-item Geriatric Depression Scale. Cognitive functioning was measured with the cognitive functioning subscale of the European Organization for Research and Treatment of Cancer. Fatigue was measured with a Visual Analogue Scale. Risk factors for depression, cognitive functioning, and fatigue were analysed using multivariate logistic regression analyses. Risk factors included cancer- and ageing-related factors such as functional status, cancer treatment, and comorbidities. The evolution of psychosocial problems was similar for the group of older (N = 125) and younger cancer patients (N = 196): an increase in depression (p < 0.01), slight worsening in cognitive functioning (p = 0.01), and no clear change in fatigue. Also, compared to the group of people without cancer (N = 215), the differences were small and after one year of follow-up only depression was more frequent in older cancer patients compared to older persons without cancer (18% versus 9%, p = 0.04). In multivariate analyses the main risk factors for psychosocial problems after one year follow-up were changes in functional status and presence of baseline depression, fatigue, or cognitive impairment. Over the course of one year after a diagnosis of cancer, cancer patients face increasing levels of depression and increasing
Zöllner, Frank Gerrit; Schad, Lothar R.; Sinn, Hans-Peter; Marx, Alexander; Gaiser, Timo; Weis, Cleo-Aron
Blood vessels in cancer Intra-tumoral blood vessels are of supreme importance for tumor growth, metastasis and therapy. Yet, little is known about spatial distribution patterns of these vessels. Most experimental or theoretical tumor models implicitly assume that blood vessels are equally abundant in different parts of the tumor, which has far-reaching implications for chemotherapy and tumor metabolism. In contrast, based on histological observations, we hypothesized that blood vessels follow specific spatial distribution patterns in colorectal cancer tissue. We developed and applied a novel computational approach to identify spatial patterns of angiogenesis in histological whole-slide images of human colorectal cancer. A characteristic spatial pattern of blood vessels in colorectal cancer In 33 of 34 (97%) colorectal cancer primary tumors blood vessels were significantly aggregated in a sharply limited belt-like zone at the interface of tumor tissue to the intestinal lumen. In contrast, in 11 of 11 (100%) colorectal cancer liver metastases, a similar hypervascularized zone could be found at the boundary to surrounding liver tissue. Also, in an independent validation cohort, we found this vascular belt zone: 22 of 23 (96%) samples of primary tumors and 15 of 16 (94%) samples of liver metastases exhibited the above-mentioned spatial distribution. Summary and implications We report consistent spatial patterns of tumor vascularization that may have far-reaching implications for models of drug distribution, tumor metabolism and tumor growth: luminal hypervascularization in colorectal cancer primary tumors is a previously overlooked feature of cancer tissue. In colorectal cancer liver metastases, we describe a corresponding pattern at the invasive margin. These findings add another puzzle piece to the complex concept of tumor heterogeneity. PMID:28253263
Locker, Gershon Y; Lynch, Henry T
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.
Quintero, Enrique; Castells, Antoni; Bujanda, Luis; Cubiella, Joaquín; Salas, Dolores; Lanas, Ángel; Andreu, Montserrat; Carballo, Fernando; Morillas, Juan Diego; Hernández, Cristina; Jover, Rodrigo; Montalvo, Isabel; Arenas, Juan; Laredo, Eva; Hernández, Vicent; Iglesias, Felipe; Cid, Estela; Zubizarreta, Raquel; Sala, Teresa; Ponce, Marta; Andrés, Mercedes; Teruel, Gloria; Peris, Antonio; Roncales, María-Pilar; Polo-Tomás, Mónica; Bessa, Xavier; Ferrer-Armengou, Olga; Grau, Jaume; Serradesanferm, Anna; Ono, Akiko; Cruzado, José; Pérez-Riquelme, Francisco; Alonso-Abreu, Inmaculada; de la Vega-Prieto, Mariola; Reyes-Melian, Juana Maria; Cacho, Guillermo; Díaz-Tasende, José; Herreros-de-Tejada, Alberto; Poves, Carmen; Santander, Cecilio; González-Navarro, Andrés
Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).
Torino, Francesco; Bonmassar, Enzo; Bonmassar, Laura; De Vecchis, Liana; Barnabei, Agnese; Zuppi, Cecilia; Capoluongo, Ettore; Aquino, Angelo
The availability of sensitive methods has allowed the detailed study of circulating tumor cells only recently. Evolving evidence support the prognostic and predictive role of these cells in patients affected by several solid tumors, including colorectal cancer. Ongoing studies are aimed at confirming that the molecular characterization of circulating tumor cells in peripheral blood and in bone marrow of patients is a powerful tool to improve the patient risk-stratification, to monitor activity of the drugs, to develop more appropriate targeted therapies and tailored treatments. In parallel, results from these correlative studies promise to gain a better biological understanding of the metastatic process. The clinical utility of the detection of circulating tumor cells in patients affected by colorectal cancer is still hampered by a number of specific hurdles. Improvement in sensitivity and specificity of the available methods of detection, standardization of these methods and functional characterization of circulating tumor cells in well designed and statistically well powered studies are the key steps to reach these ambitious objectives in colorectal cancer patients as well. Copyright © 2013 Elsevier Ltd. All rights reserved.
Landi, Stefano; Gemignani, Federica; Bottari, Fabio; Gioia-Patricola, Lydie; Guino, Elisabet; Cambray, María; Biondo, Sebastiano; Capella, Gabriel; Boldrini, Laura; Canzian, Federico; Moreno, Victor
Background Chronic inflammation is a risk factor for colorectal cancer and polymorphisms in the inflammatory genes could modulate the levels of inflammation. We have investigated ten single nucleotide polymorphisms (SNPs) in the following inflammation-related genes: TLR4 (Asp299Gly), CD14 (-260 T>C), MCP1 (-2518 A>G), IL12A (+7506 A>T, +8707 A>G, +9177 T>A, +9508 G>A), NOS2A (+524T>C), TNF (-857C>T), and PTGS1 (V444I) in 377 colorectal (CRC) cancer cases and 326 controls from Barcelona (Spain). Results There was no statistically significant association between the SNPs investigated and colorectal cancer risk. Conclusion The lack of association may show that the inflammatory genes selected for this study are not involved in the carcinogenic process of colorectum. Alternatively, the negative results may derive from no particular biological effect of the analysed polymorphisms in relation to CRC. Otherwise, the eventual biological effect is so little to go undetected, unless analysing a much larger sample size. PMID:17062130
Kostakis, Ioannis D; Agrogiannis, George; Vaiopoulos, Aristeidis G; Mylona, Eleni; Patsouris, Efstratios; Kouraklis, Gregory; Koutsilieris, Michael
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.
Budhathoki, Sanjeev; Joshi, Amit Man; Ohnaka, Keizo; Yin, Guang; Toyomura, Kengo; Kono, Suminori; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji
It has been suggested that soy food and isoflavone intake may be protective against the risk of colorectal cancer. However, epidemiologic evidence remains sparse and inconsistent. We addressed this issue in the Fukuoka Colorectal Cancer Study. The study subjects were the 816 incident cases of histologically confirmed colorectal cancer and 815 community controls. Intakes of soy foods and isoflavones were assessed by in-person interview using a computer-assisted dietary method. Logistic regression analysis was applied to estimate odds ratio (OR) and 95% confidence interval (CI) of colorectal cancer with adjustment for dietary intakes of calcium and n-3 polyunsaturated fatty acids as well as for body mass index, physical activity, alcohol use, and other lifestyle factors. Energy-adjusted intakes of soy foods (dry weight) and isoflavones were inversely associated with colorectal cancer risk in men and postmenopausal women, but not in premenopausal women. The multivariate-adjusted OR for the highest versus lowest quintile was 0.65 (95% CI 0.41-1.03, p for trend = 0.03) for soy foods and 0.68 (95% CI 0.42-1.10, p for trend = 0.051) for isoflavones in men. The corresponding values for postmenopausal women were 0.60 (95% CI 0.29-1.25, p for trend = 0.053) and 0.68 (95% CI 0.33-1.40, p for trend = 0.049). The site-specific analysis showed inverse associations of soy foods (p for trend = 0.007) and isoflavones (p for trend = 0.02) with rectal cancer in men. The findings add to epidemiologic evidence for protective effects of soy foods and isoflavones in colorectal carcinogenesis.
Wang, Qinjun; Zhang, Hongchun; Shen, Xianjuan; Ju, Shaoqing
Objective The purpose of this study was to explore serum miR-135a-5p expression in colorectal cancer and examine the potential usefulness of this molecule as a biomarker for diagnosis in colorectal cancer. Methods Serum samples were collected from 60 patients with primary colorectal cancer, 40 patients with colorectal polyps and 50 healthy controls. Serum miR-135a-5p expression levels were detected by reverse transcription quantitative real-time quantitative polymerase chain reaction. Serum carcinoembryonic antigen and carbohydrate antigen 199 concentrations were detected by MODULAR ANALYTICS E170. Results The relative expression level of serum miR-135a-5p in colorectal cancer patients, colorectal polyps patients and healthy controls was 2.451 (1.107, 4.413), 0.946 (0.401, 1.942) and 0.949 (0.194, 1.415), respectively, indicating that it was significantly higher in colorectal cancer patients than that in the other two groups ( U = 351.0, 313.0, both P < 0.001). Additionally, it was significantly correlated with different degrees of tumour differentiation ( U = 215.0, P = 0.029) and different tumour stages ( U = 202.0, P = 0.013). There was no significant correlation between the relative expression of serum miR-135a-5p and carcinoembryonic antigen ( r(2 )= 0.023, P = 0.293) or carbohydrate antigen 199 ( r(2 )= 0.067, P = 0.068) in colorectal cancer patients. Compared with colorectal polyps group, AUC(ROC) of serum miR-135a-5p in colorectal cancer group was 0.832 with 95% CI 0.73-0.93; compared with healthy control group, AUC(ROC) was 0.875 with 95% CI 0.80-0.95. Conclusion Serum miR-135a-5p expression in colorectal cancer patients was higher than that in patients with colorectal polyps and healthy controls, suggesting that serum miR-135a-5p may prove to be an important biomarker for auxiliary diagnosis of colorectal cancer.
Mazzolini, Guillermo; Murillo, Oihana; Atorrasagasti, Catalina; Dubrot, Juan; Tirapu, Iñigo; Rizzo, Miguel; Arina, Ainhoa; Alfaro, Carlos; Azpilicueta, Arantza; Berasain, Carmen; Perez-Gracia, José L; Gonzalez, Alvaro; Melero, Ignacio
Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma. PMID:17990348
Cui, Ji; Cai, Yonghua; Hu, Ying; Huang, Zenghong; Luo, Yanxin; Kaz, Andrew M; Yang, Zihuan; Chen, Dianke; Fan, Xinjuan; Grady, William M; Wang, Jianping
Beta-tropomyosin (β-tropomyosin, TPM2) has been found to be downregulated in colorectal cancer (CRC) in previous studies. In this study, we aimed to investigate the mechanisms and potential biological consequences of the downregulation of TPM2 in colorectal cancer. TPM2 expression in colorectal cancer was assessed by qRT-PCR and immunostaining. The biological functions of TPM2 were assessed in cell lines either overexpressing or underexpressingTPM2. Aberrant DNA methylation in the promoter region is associated with suppression of TPM2 expression in primary colorectal cancer tissue samples. Treatment with the demethylation agent 5-AZA can induceTPM2 expression in colorectal cancer cell lines. Reconstitution of TPM2 suppresses cell proliferation and migration in colorectal cancer cell lines, whereas the loss of TPM2 expression is associated with increased tumor proliferation and migration in vitro, which was accompanied by RhoA activation. In summary, our findings indicate that TPM2 appears to be commonly silenced by aberrant DNA methylation in colon cancer. TPM2 loss is associated with RhoA activation and tumor proliferation.
Fedyanin, Mikhail; Anna, Popova; Elizaveta, Polyanskaya; Sergei, Tjulandin
In the last decade, an increasing number of studies on tumor stem cell theory stating that there is only a small fraction of tumor cells capable of inducing tumor growth have been published. These cells can not only differentiate into more mature tumor cells, but also can maintain their own pool, that is the capacity for self-renewal. There are distinct subpopulations of cells within a tumor that express different combinations of stem cell markers and have different functions. The following markers are typically considered as markers of colorectal adenocarcinoma stem cells: CD133, CD144, CD24, CD166, CD44, CD29, ALDH1, LGR5, and CXCR4. However, data on the role of cancer stem cells in the process of colorectal cancer progression, their prognostic and predictive role are lacking. Researches on the phenotype, molecular and functional properties of this tumor cell subpopulation in both primary site and metastases of colorectal cancer are of great interest because they can allow developing new diagnostic and therapeutic strategies in the future.
Guo, Chunguang; Liu, Qian; Dai, Min
Colorectal cancer (CRC) is the fourth most common cause of cancer death in China and the incidence has been increasing during the decades. It is reported to take decades for adenoma to transform to carcinoma, which is known as the main CRC pre-cancer lesion. It is important to carry out mass screening in the average risk populations to find the pre-cancer lesion and early cancer, which was the key approach to improve CRC survival. Fecal occult blood test and flexible sigmoidoscopy are the two CRC screening methods, which have been shown to reduce CRC mortality. It still needs to be confirmed in random clinical trials that the value of colonoscopy in CRC screening. In China, the most CRC screening experience was drawn from the works in Zhejiang province in 1970s. Consequently, the Chinese CRC treatment and guideline was founded to provide standard for the CRC screening project.
Pathak, S; Nunes, Q M; Daniels, I R; Smart, N J
With the advent of several different therapeutic strategies to manage the different stages of colorectal cancer, it would be beneficial to allow substratification of patients into groups who are most likely to benefit from costly interventions. The purpose of this review is to analyse the evidence from several retrospective studies examining the prognostic significance of C-reactive protein (CRP). A literature search was performed using PubMed, Embase, Cochrane Library, CINAHL and Google Scholar databases to identify studies that analysed CRP and its prognostic significance in all stages of operable colorectal cancer. The primary end-points of interest were overall survival and disease-free survival. In all, 205 studies were identified by the search. Twelve involving 1705 patients fulfilled the inclusion criteria and were included. Three of the included studies including 305 patients considered Stage IV colorectal cancer and the impact of CRP on survival. Overall survival and disease-free survival were shorter in the presence of an elevated preoperative CRP in local and advanced colorectal cancer. CRP may be useful for prognosis in patients with primary and metastatic colorectal cancer, but currently there is insufficient evidence to justify its routine use. Further well-designed prospective studies are needed to validate its role in substratification of patients for consideration of (neo)adjuvant therapies. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.
Sameer, Aga Syed; Nissar, Saniya
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
Nayani, Rahul; Ashktorab, Hassan; Brim, Hassan; Laiyemo, Adeyinka O.
African Americans suffer the highest burden from colorectal cancer (CRC) in the USA. Studies have suggested that healthcare access and poorer utilization of preventive services may be playing more of a role in this disparity. However, African Americans also tend to develop CRC at younger ages and are more likely to have proximal cancers. This raises the possibility of higher genetic predisposition to CRC among African Americans and this has not been well studied. In this article, we reviewed possible genetic basis underpinning biological differences in CRC burden in the USA. PMID:26997937
Norton, Samuel E; Ward-Hartstonge, Kirsten A; Taylor, Edward S; Kemp, Roslyn A
The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, particularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship between cancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment.
Brim, Hassan; Ashktorab, Hassan
Genome-wide studies are increasingly becoming a must, especially for complex diseases such as cancer where multiple genes and diverse molecular mechanisms are known to be involved in genes’ function alteration. In this review, we report our latest genomic and epigenomic findings in African-American colorectal cancer patients. This population suffers a higher burden of the disease and most investigators in this field are looking for the underlying genetic and epigenetic targets that might be responsible for this disparity. We here report genome-wide copy number variations, single nucleotide mutations and DNA methylation findings that might be specific to this population. PMID:27917406
DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain;numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |
Fanali, Caterina; Lucchetti, Donatella; Farina, Marisa; Corbi, Maddalena; Cufino, Valerio; Cittadini, Achille; Sgambato, Alessandro
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.
Yoshida, Naoya; Tamaoki, Yuka; Baba, Yoshifumi; Sakamoto, Yasuo; Miyamoto, Yuji; Iwatsuki, Masaaki; Shono, Takashi; Miyamoto, Hideaki; Imuta, Masanori; Kurashige, Junji; Sawayama, Hiroshi; Tokunaga, Ryuma; Watanabe, Masayuki; Sasaki, Yutaka; Yamashita, Yasuyuki; Baba, Hideo
The precise incidence rates of multiple primary colorectal cancers in esophageal cancer patients are unknown. In total, 480 consecutive patients with esophageal cancers surgically resected in the Kumamoto University Hospital received preoperative total colonoscopy for the assessment of colorectal disease between April 2005 and February 2016. We retrospectively investigated the occurrence of synchronous colorectal cancer with esophageal cancer. In addition, we examined the risk factors for the incidence of multiple primary colorectal cancers. Of the 480 patients, 14 (2.9 %) had synchronous colorectal cancers, 13 had well-differentiated tubular adenocarcinomas, and 1 had papillary adenocarcinoma. Other 14 patients had metachronous colorectal cancer. The current incidence rates of synchronous and total (both synchronous and metachronous) colorectal cancers outnumbered those in normal healthy population and those in esophageal cancer patients which previously reported by The Japan Esophageal Society. The age ≥70 years (hazard ratio 4.82, 95 % confidence interval 1.473-15.78; p = 0.009) and Brinkman index ≥800 (hazard ratio 3.47, 95 % confidence interval 1.056-11.37; p = 0.040) were the independent risk factors for the incidence of synchronous colorectal cancer. They were also the independent risk factors for the incidence of total colorectal cancer. The results of the present study suggested that pretreatment screening with total colonoscopy is meaningful for patients with esophageal cancer, because the frequency of synchronous colorectal cancer was not negligible. Particularly, in patients >70 years and with history of heavy smoking, pretreatment colonoscopy might be necessary.
Brenner, H; Hoffmeister, M
Colorectal cancer (CRC) is the second most common cancer among both men and women in Germany. Owing to its relatively slow growth, perspectives for effective early detection are much better than for other forms of cancer. To summarize the evidence on effectiveness and cost-effectiveness of CRC screening, and to provide an overview on the current state and perspectives for effective CRC screening. Summary and critical review of evidence from randomized trials and observational epidemiological studies. A reduction in CRC mortality by offering annual fecal occult blood tests or once-only flexible sigmoidoscopy has been demonstrated in randomized trials. Novel fecal immunochemical tests for hemoglobin in stool have been shown to be more sensitive than traditional fecal occult blood tests and could substantially improve noninvasive CRC screening. Epidemiological studies suggest that the majority of CRC cases and deaths could be prevented by colonoscopy and removal of colorectal adenomas. However, adherence to screening offered outside organized screening programs is low. The National Cancer Plan recommends an organized CRC screening program in Germany. The law on the early detection of cancer from April 2013 has paved the way for its implementation. The great potential for CRC prevention by early detection has so far only been realized to a very limited extent in Germany. Introduction of an organized screening program and the offer of enhanced noninvasive screening tests could strongly enhance the utilization and effectiveness of CRC screening in Germany. The political frame has been set, and timely quality-assured implementation is required.
Gao, Bo; Yu, Tian; Xue, Dongbo; Sun, Boshi; Shao, Qin; Choudhry, Hani; Marcus, Victoria; Ragoussis, Jiannis; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-Hua
Approximately 9% of cancer-related deaths are caused by colorectal cancer. Liver metastasis is a major factor for the high colorectal cancer mortality rate. However, the molecular mechanism underlying colorectal cancer liver metastasis remains unclear. Using a global and multidimensional integration approach, we studied sequencing data, protein-protein interactions, and regulation of transcription factor and non-coding RNAs in primary tumor samples and liver metastasis samples to unveil the potential bridging molecules and the regulators that functionally link different stages of colorectal cancer liver metastasis. Primary tumor samples and liver metastasis samples had modules with significant overlap and crosstalk from which we identified several bridging genes (e.g. KNG1 and COX5B), transcription factors (e.g. E2F4 and CDX2), microRNAs (e.g. miR-590-3p and miR-203) and lncRNAs (e.g. lincIRX5 and lincFOXF1) that may play an important role in the process of colorectal cancer liver metastasis. This study enhances our understanding of the genetic alterations and transcriptional regulation that drive the metastatic process, but also provides the methodology to guide the studies on other metastatic cancers.
Korpela, J T; Adlercreutz, H; Turunen, M J
Increased excretion and intestinal bacterial metabolism of bile acids and neutral sterols have been suggested to be associated with an increased risk of colorectal cancer. We determined fecal neutral sterol and bile acid profiles by new capillary column gas-liquid chromatographic methods in 18 patients with colorectal cancer, 10 omnivores, and 10 vegetarians. The methods also determine concentrations of esterified neutral sterols and saponifiable bile acids formed by intestinal bacterial action. Patients with colorectal cancer had the highest concentrations of neutral animal sterols, the lowest degree of esterification of neutral sterols, the lowest relative amount of saponifiable bile acids, and the highest concentrations of unconjugated primary bile acids. These differences were statistically significant (p less than 0.05) and more profound when the patients were compared with vegetarians than with omnivores. Since epidemiologic studies suggest that vegetarians have a lower risk of colorectal cancer than omnivores, these differences are discussed as possible risk factors for colorectal cancer.
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
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.
Lee, Sung Hwan; Kim, Sung Hyun; Lim, Jin Hong; Kim, Sung Hoon; Lee, Jin Gu; Kim, Dae Joon; Choi, Gi Hong; Choi, Jin Sub
Backgrounds/Aims Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. Methods Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. Results Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). Conclusions Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases. PMID:27621747
Patel, Sandip P; Osada, Takuya; Lyerly, H Kim; Morse, Michael A
Achieving long-term control of colorectal cancers with therapeutic vaccines that generate potent anti-tumor T cell and antibody responses has been a goal for more than two decades. To date, clinical trials of these vaccines have demonstrated induction of immune responses, but clinical benefit has been limited. Improved vector delivery systems with enhanced immunostimulatory properties, decreased immunogenicity against vector and improved antigen presentation are some of the key features of modern tumor vaccines. Furthermore, an improved understanding of the various immunosuppressive factors in the tumor microenvironment and regional lymph nodes, coupled with a burgeoning ability to impair inhibitory immune synapses, highlights a growing opportunity to induce beneficial antigen-specific responses against tumor. The combination of improved antigenic delivery systems, coupled with therapeutic immune activation, represents state-of-the-art colorectal vaccine design concepts with the goal of augmenting immune responses against tumor and improving clinical outcomes.
Fei, Weiqiang; Liu, Shuiping; Hu, Xiaotong
The human FAD-dependent oxidoreductase domain containing 1 (FOXRED1) protein is reported as an assembly factor which promotes the correct assembly and stability of mitochondrial Complex I (CI). Alterations of mitochondrial CI might cause tumorigenesis and metastasis, but it’s molecular mechanisms remain unclear. In this study, we selected 145 cases of colorectal cancer for immunohistochemistry to explore the role of FOXRED1 played in the tumor progression of colorectal cancer. The relationship between FOXRED1 expression and clinicopathological features of colorectal cancers was evaluated. FOXRED1 mainly localized in the cytoplasm in the colorectal cancer tissues, and had significant association with histopathological grading, depth of invasion, lymph node metastasis, distant metastasis and TNM stage (P<0.05 for each). However, age, gender and tumor location was not found to be associated with FOXRED1 expression. Colorectal cancer patients with higher expression of FOXRED1 had the higher 3 year survival rate (P=0.003). Moreover, FOXRED1 had potentiality to be an independent prognostic factor for survival in colorectal cancer (P=0.04). Low FOXRED1 expression correlated with poor prognosis of colorectal cancer and targeting this molecular will be a potential treatment strategy for colorectal cancer. PMID:27904784
Mulcahy, Hugh E; Hyland, John; O'Donoghue, Diarmuid P
The roots of colorectal cancer date back to antiquity. In this short history of colorectal cancer we trace its clinical and research origins from ancient times through the dark ages, middle ages, to the scientific and medical advances of the seventeenth to twentieth centuries and into the twenty-first century.
Enstrom, J. E.
Secular, socioeconomic and urban-rural gradients and geographical differences in beef and fat consumption within the United States of America are compared with corresponding data on colorectal cancer incidence and mortality rates. These results, together with the results of most previous epidemiological studies, appear to contradict the hypothesis that beef and fat consumption are involved in the aetiology of colorectal cancer. PMID:1212410
Study finds that flexible sigmoidoscopy is effective in reducing the rates of new cases and deaths due to colorectal cancer. Researchers found that overall colorectal cancer mortality was reduced by 26 percent and incidence was reduced by 21 percent as a
Vinson, Kaitlyn E; George, Dennis C; Fender, Alexander W; Bertrand, Fred E; Sigounas, George
Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem-cell-like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch-1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic.
Spiegelman, D; Wegman, D H
Several population data bases were used to generate hypotheses about associations between colorectal cancer and workplace exposures. The Third National Cancer Survey interview sample was used to select 343 male and 208 female cases and 626 male and 1,235 female cancer controls. Potential work exposures were assigned with the use of data from the National Institute for Occupational Safety and Health National Occupational Hazard Survey. Dietary factors were modeled from the National Health and Nutrition Examination Survey data. Work-related stress was considered with the use of a model based on the U.S. Department of Labor's Quality of Employment Survey. Other risk factors included age, race, ponderosity, and menopausal status. Logistic analysis yielded hypotheses for colon cancer risk in males with potentially high exposure to solvents, abrasives, and fuel oil and in those in jobs with high demand and low control (high "stress"). Hypotheses emerged for females with potentially high exposure to dyes, solvents, and grinding wheel dust.
Siriwardena, Ajith K; Mason, James M; Mullamitha, Saifee; Hancock, Helen C; Jegatheeswaran, Santhalingam
Up to a fifth of patients with colorectal cancer (CRC) present with synchronous hepatic metastases. In patients with CRC who present without intestinal obstruction or perforation and in whom comprehensive whole-body imaging confirms the absence of extrahepatic disease, evidence indicates a state of equipoise between several different management pathways, none of which has demonstrated superiority. Neoadjuvant systemic chemotherapy is advocated by current guidelines, but must be integrated with surgical management in order to remove the primary tumour and liver metastatic burden. Surgery for CRC with synchronous liver metastases can take a number of forms: the 'classic' approach, involving initial colorectal resection, interval chemotherapy and liver resection as the final step; simultaneous removal of the liver and bowel tumours with neoadjuvant or adjuvant chemotherapy; or a 'liver-first' approach (before or after systemic chemotherapy) with removal of the colorectal tumour as the final procedure. In patients with rectal primary tumours, the liver-first approach can potentially avoid rectal surgery in patients with a complete response to chemoradiotherapy. We overview the importance of precise nomenclature, the influence of clinical presentation on treatment options, and the need for accurate, up-to-date surgical terminology, staging tests and contemporary management options in CRC and synchronous hepatic metastatic disease, with an emphasis on multidisciplinary care.
Auman, J Todd; McLeod, Howard L
Clinically and histopathologically similar colorectal cancers exhibit considerable variability in their responses to chemotherapeutics. The advent of genomic technologies has enabled the unbiased determination of changes in DNA and RNA, alterations that may be responsible for, or predictive of the variability in response to chemotherapy. This review highlights several advances made in applying genomic tools toward colorectal cancer therapeutics. Progress has been made using gene expression profiling to identify which colorectal cancer patients would benefit most from adjuvant chemotherapy. In addition, advances have been made in colorectal cancer pharmacogenomics by identifying gene expression patterns associated with sensitivity to specific chemotherapeutic agents. Lastly, the use of genome-wide mutation screening of individual tumor samples to identify the profiles of mutated genes is explored. Future research toward integrating genomic information with clinical and histopathological data is expected to lead to improved therapeutic management of colorectal cancer.
Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang
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
Bretagne, Jean-François; Manfredi, Sylvain; Heresbach, Denis
Hemoccult II is the only method of screening for colorectal cancer whose effectiveness in reducing specific mortality has been proved by randomized controlled trials. The first experience of French districts based on this strategy reproduced on a population scale the results of the experimental studies. Expanding screening in France to the general public is a public health priority. Large-scale media campaigns, which currently do not exist, could then be launched, and prevention opportunities seized. Immunological tests identifying the presence of blood in the stool have better sensitivity than the guaiac smear tests, especially for the diagnosis of adenomas and to a lesser extent, for that of cancers as a whole. These tests may constitute an alternative to guaiac tests, but are more expensive. Total colonoscopy, proposed every 10 years from the age of 50 years or once in a lifetime around the age of 60 years, is not a realistic method because of its cost and its risks. Sigmoidoscopies are under evaluation in several countries in randomized controlled trials but do not seem appropriate to either the epidemiologic trends of colorectal cancer or to the practice of endoscopy in France. Virtual colonoscopy is an attractive alternative to searching for blood in stool. The evaluation now underway should not interfere with the broad expansion of methods of proven efficacy. Virtual colonoscopy may face competition from numerous emerging techniques of endoscopic exploration of the colon, including the video-capsule. To obtain widespread participation in colorectal cancer screening, policy-makers must take the opinions of healthcare professionals and of the public into account. The medicoeconomic data will be a decisive factor in the choice between these new strategies.
Boehm, Jennifer E; Rohan, Elizabeth A; Preissle, Judith; DeGroff, Amy; Glover-Kudon, Rebecca
In 2005, the Centers for Disease Control and Prevention (CDC) funded 5 sites as part of the Colorectal Cancer Screening Demonstration Program (CRCSDP) to provide colorectal cancer screening to low-income, uninsured, and underinsured individuals. Funded sites experienced unexpected challenges in recruiting patients for services. The authors conducted a longitudinal, qualitative case study of all 5 sites to document program implementation, including recruitment. Data were collected during 3 periods over the 4-year program and included interviews, document review, and observations. After coding and analyzing the data, themes were identified and triangulated across the research team. Patterns were confirmed through member checking, further validating the analytic interpretation. During early implementation, patient enrollment was low at 4 of the 5 CRCSDP sites. Evaluators found 3 primary challenges to patient recruitment: overreliance on in-reach to National Breast and Cervical Cancer Early Detection Program patients, difficulty keeping colorectal cancer screening and the program a priority among staff at partnering primary care clinics responsible for patient recruitment, and a lack of public knowledge about the need for colorectal cancer screening among patients. To address these challenges, site staff expanded partnerships with additional primary care networks for greater reach, enhanced technical support to primary care providers to ensure more consistent patient enrollment, and developed tailored outreach and education. Removing financial barriers to colorectal cancer screening was necessary but not sufficient to reach the priority population. To optimize colorectal cancer screening, public health practitioners must work closely with the health care sector to implement evidence-based, comprehensive strategies across individual, environmental, and systems levels of society. © 2013 American Cancer Society.
Sozucan, Y; Kalender, M E; Sari, I; Suner, A; Oztuzcu, S; Arman, K; Yumrutas, O; Bozgeyik, I; Cengiz, B; Igci, Y Z; Balakan, O; Camci, C
Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues.
Hyphantis, Thomas; Goulia, Panagiota; Zerdes, Ioannis; Solomou, Solomis; Andreoulakis, Elias; Carvalho, André F; Pavlidis, Nicholas
Sleep disturbances are common in cancer patients, but little is known about the complex interplay between the background psychological profile, coping with health stressors capacities and psychological distress in the formation of sleep difficulties in colorectal cancer. To study the course and to identify psychological predictors of sleep difficulties in early non-metastatic colorectal cancer patients over a one-year period. In this 1-year prospective study, we assessed in 84 early non-metastatic colorectal cancer patients the association of psychological distress (SCL-90-R), sense of coherence (SOC-29), and defense styles (Defense Style Questionnaire) with sleep difficulties (SCL-90-R) in multiple regression models. Eighty-two patients with breast cancer and 50 patients with cancer of unknown primary site served as disease controls, and 84 matched for age and sex alleged healthy individuals served as healthy controls. Colorectal cancer patients presented more sleep difficulties compared to healthy participants but fewer than patients with breast cancer and cancer of unknown primary site. Colorectal cancer patients' trouble falling asleep (p = 0.033) and wakening up early in the morning (p < 0.001) deteriorated over time. Sleep that was restless or disturbed was independently associated with low SOC (p = 0.046) and maladaptive defenses (p = 0.008). Anxiety symptoms (p < 0.001) predicted deterioration in trouble falling asleep, while depressive symptoms (p = 0.022) and self-sacrificing defense style (p = 0.049) predicted deterioration in wakening up early in the morning. Psychological parameters and coping with health stressors capacities are independently associated with sleep difficulties in colorectal cancer patients, indicating the need for psychological interventions aiming at improving adjustment to the disease.
De Angelis, Maria Laura; Zeuner, Ann; Policicchio, Eleonora; Russo, Giorgio; Bruselles, Alessandro; Signore, Michele; Vitale, Sara; De Luca, Gabriele; Pilozzi, Emanuela; Boe, Alessandra; Stassi, Giorgio; Ricci-Vitiani, Lucia; Amoreo, Carla Azzurra; Pagliuca, Alfredo; Francescangeli, Federica; Tartaglia, Marco
Colorectal cancer (CRC) therapy mainly relies on the use of conventional chemotherapeutic drugs combined, in a subset of patients, with epidermal growth factor receptor [EGFR]-targeting agents. Although CRC is considered a prototype of a cancer stem cell (CSC)-driven tumor, the effects of both conventional and targeted therapies on the CSC compartment are largely unknown. We have optimized a protocol for colorectal CSC isolation that allowed us to obtain CSC-enriched cultures from primary tumor specimens, with high efficiency. CSC isolation was followed by in vitro and in vivo validation, genetic characterization, and drug sensitivity analysis, thus generating panels of CSC lines with defined patterns of genetic mutations and therapy sensitivity. Colorectal CSC lines were polyclonal and maintained intratumor heterogeneity in terms of somatically acquired mutations and differentiation state. Such CSC-enriched cultures were used to investigate the effects of both conventional and targeted therapies on the CSC compartment in vivo and to generate a proteomic picture of signaling pathways implicated in sensitivity/resistance to anti-EGFR agents. We propose CSC lines as a sound preclinical framework to test the effects of therapies in vitro and in vivo and to identify novel determinants of therapy resistance. Significance Colorectal cancer stem cells (CSCs) have been shown to be responsible for tumor propagation, metastatic dissemination, and relapse. However, molecular pathways present in CSCs, as well as mechanisms of therapy resistance, are mostly unknown. Taking advantage of genetically characterized CSC lines derived from colorectal tumors, this study provides an extensive analysis of CSC response to EGFR-targeted therapy in vivo and an overview of factors implicated in therapy response or resistance. Furthermore, the implementation of a biobank of molecularly annotated CSC lines provides an innovative resource for future investigations in colorectal cancer. PMID
Boyle, T; Fritschi, L; Platell, C; Heyworth, J
Background: Aside from tumour stage and treatment, little is known about potential factors that may influence survival in colorectal cancer patients. The aim of this study was to investigate the associations between physical activity, obesity and smoking and disease-specific and overall mortality after a colorectal cancer diagnosis. Methods: A cohort of 879 colorectal cancer patients, diagnosed in Western Australia between 2005 and 2007, were followed up to 30 June 2012. Cox's regression models were used to estimate the hazard ratios (HR) for colorectal cancer-specific and overall mortality associated with self-reported pre-diagnosis physical activity, body mass index (BMI) and smoking. Results: Significantly lower overall and colorectal cancer-specific mortality was seen in females who reported any level of recent physical activity than in females reporting no activity. The colorectal cancer-specific mortality HR for increasing levels of physical activity in females were 0.34 (95% CI=0.15, 0.75), 0.37 (95% CI=0.17, 0.81) and 0.41 (95% CI=0.18, 0.90). Overweight and obese women had almost twice the risk of dying from any cause or colorectal cancer compared with women of normal weight. Females who were current smokers had worse overall and colorectal cancer-specific mortality than never smokers (overall HR=2.64, 95% CI=1.18, 5.93; colorectal cancer-specific HR=2.70, 95% CI=1.16, 6.29). No significant associations were found in males. Conclusion: Physical activity, BMI and smoking may influence survival after a diagnosis of colorectal cancer, with more pronounced results found for females than for males. PMID:23787918
Established in 1995, the Hereditary Gastrointestinal Cancer Registry aimed at cancer prevention due to hereditary colorectal cancer syndromes in Hong Kong through early detection, timely treatment, education and ongoing research. This article details the history, structure and work of the Registry. A summary is also provided on the results of various research work conducted by the Registry which facilitates the clinical management of hereditary colorectal cancer syndromes in Hong Kong Chinese families. PMID:20223041
Kaminski, Michal F; Wieszczy, Paulina; Rupinski, Maciej; Wojciechowska, Urszula; Didkowska, Joanna; Kraszewska, Ewa; Kobiela, Jaroslaw; Franczyk, Robert; Rupinska, Maria; Kocot, Bartlomiej; Chaber-Ciopinska, Anna; Pachlewski, Jacek; Polkowski, Marcin; Regula, Jaroslaw
The quality of endoscopists' colonoscopy performance is measured by adenoma detection rate (ADR). Although ADR is associated inversely with interval colorectal cancer and colorectal cancer death, the effects of an increasing ADR have not been shown. We investigated whether increasing ADRs from individual endoscopists is associated with reduced risks of interval colorectal cancer and subsequent death. We performed a prospective cohort study of individuals who underwent a screening colonoscopy within the National Colorectal Cancer Screening Program in Poland, from January 1, 2004, through December 31, 2008. We collected data from 146,860 colonoscopies performed by 294 endoscopists, with each endoscopist having participated at least twice in annual editions of primary colonoscopy screening. We used annual feedback and quality benchmark indicators to improve colonoscopy performance. We used ADR quintiles in the whole data set to categorize the annual ADRs for each endoscopist. An increased ADR was defined as an increase by at least 1 quintile category, or the maintenance of the highest category in subsequent screening years. Multivariate frailty models were used to evaluate the effects of increased ADR on the risk of interval colorectal cancer and death. Throughout the enrollment period, 219 endoscopists (74.5%) increased their annual ADR category. During 895,916 person-years of follow-up evaluation through the National Cancer Registry, we identified 168 interval colorectal cancers and 44 interval cancer deaths. An increased ADR was associated with an adjusted hazard ratio for interval colorectal cancer of 0.63 (95% confidence interval [CI], 0.45-0.88; P = .006), and for cancer death of 0.50 (95% CI, 0.27-0.95; P = .035). Compared with no increase in ADR, reaching or maintaining the highest quintile ADR category (such as an ADR > 24.56%) decreased the adjusted hazard ratios for interval colorectal cancer to 0.27 (95% CI, 0.12-0.63; P = .003), and 0.18 (95% CI, 0
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
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
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
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.
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
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.
The SCAN colorectal cancer systemic therapy workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for colorectal cancer in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated-those developed by the National Comprehensive Cancer Network for colon (2014) and rectal (2014) cancer, the European Society of Medical Oncology for advanced (2012) and early (2013) cancer and the National Institute of Clinical Excellence (2011). Recommendations on systemic therapy in colorectal cancer were produced. These adapted guidelines form the SCAN Guidelines 2015 for systemic therapy of colorectal cancer.
Fidler, Miranda M; Bray, Freddie; Vaccarella, Salvatore; Soerjomataram, Isabelle
Colorectal cancer incidence has paralleled increases in human development across most countries. Yet, marked decreases in incidence are now observed in countries that have attained very high human development. Thus, in this study, we explored the relationship between human development and colorectal cancer incidence, and in particular assessed whether national transitions to very high human development are linked to temporal patterns in colorectal cancer incidence. For these analyses, we utilized the Human Development Index (HDI) and annual incidence data from regional and national cancer registries. Truncated (30-74 years) age-standardized incidence rates were calculated. Yearly incidence rate ratios and HDI ratios, before and after transitioning to very high human development, were also estimated. Among the 29 countries investigated, colorectal cancer incidence was observed to decrease after reaching the very high human development threshold for 12 countries; decreases were also observed in a further five countries, but the age-standardized incidence rates remained higher than that observed at the threshold. Such declines or stabilizations are likely due to colorectal cancer screening in some populations, as well as varying levels of exposure to protective factors. In summary, it appears that there is a threshold at which human development predicts a stabilization or decline in colorectal cancer incidence, though this pattern was not observed for all countries assessed. Future cancer planning must consider the increasing colorectal cancer burden expected in countries transitioning towards higher levels of human development, as well as possible declines in incidence among countries reaching the highest development level. © 2017 UICC.
Ge, Yaorong; Vining, David J.; Ahn, David K.; Stelts, David R.
Early detection and removal of colorectal polyps have been proven to reduce mortality from colorectal carcinoma (CRC), the second leading cause of cancer deaths in the United States. Unfortunately, traditional techniques for CRC examination (i.e., barium enema, sigmoidoscopy, and colonoscopy) are unsuitable for mass screening because of either low accuracy or poor public acceptance, costs, and risks. Virtual colonoscopy (VC) is a minimally invasive alternative that is based on tomographic scanning of the colon. After a patient's bowel is optimally cleansed and distended with gas, a fast tomographic scan, typically helical computed tomography (CT), of the abdomen is performed during a single breath-hold acquisition. Two-dimensional (2D) slices and three-dimensional (3D) rendered views of the colon lumen generated from the tomographic data are then examined for colorectal polyps. Recent clinical studies conducted at several institutions including ours have shown great potential for this technology to be an effective CRC screening tool. In this paper, we describe new methods to improve bowel preparation, colon lumen visualization, colon segmentation, and polyp detection. Our initial results show that VC with the new bowel preparation and imaging protocol is capable of achieving accuracy comparable to conventional colonoscopy and our new algorithms for image analysis contribute to increased accuracy and efficiency in VC examinations.
Muzaffar, Mahvish; Irlam, John; Mohamed, Iman
Recent research has provided compelling evidence that a subset of hyperplastic polyps may be associated with a risk of colorectal cancer. Colorectal cancer with extracolonic manifestation is usually seen in a hereditary syndrome setting, but some association with meningioma has been reported. The association of colorectal cancer with hyperplastic polyposis and meningioma is extremely rare. This report in a 57-year-old female with no family history of colon cancer or polyps, could be the first case of hyperplastic polyposis syndrome, colorectal cancer and meningioma. Hyperplastic polyposis syndrome was diagnosed as per WHO criteria at the time of colon cancer diagnosis. Within 4 months of colon cancer diagnosis she developed seizures. Imaging of the brain revealed meningioma of the left cerebellopontine angle. The patient underwent surgery followed by chemotherapy.
Fletcher, Robert H; Colditz, Graham A; Pawlson, L Greg; Richman, Howard; Rosenthal, David; Salber, Patricia R
Colorectal cancer screening is advocated by expert groups based on strong evidence of effectiveness, yet only approximately 1 in 3 Americans are screened. For a screening program to be effective, it is necessary for providers to offer and patients to accept screening, insurers to pay for screening, and provider groups to have monitoring and reminder systems and the expertise and facilities to perform the tests well. Whether and when such screening programs become successful depends on the priorities of healthcare decision makers as much as on the efforts of individual physicians and patients. There are strong arguments for decision makers giving colorectal cancer screening programs high priority: it saves as many lives as other services now in common use; it is a good use of scarce resources, costing less than $20,000 per year of life saved; and members of insurance programs increasingly expect screening benefits and programs, and failure to offer them might lead to member dissatisfaction and malpractice claims. Screening is costly, however, taking into account the cost of screening, follow-up tests, and treatments, and the costs occur many years before the benefits. Programs that are promoted to members but not fully implemented could create disappointment and backlash. Also, this screening can cause medical complications. Nevertheless, successful programs have been developed, proving that they are feasible in today's cost-conscious environment. We believe that colorectal cancer screening programs are integral to any organization purporting to provide high-quality care. Organizations without such programs should give them high priority for implementation.
Boehm, Jennifer E.; Rohan, Elizabeth A.; Preissle, Judith; DeGroff, Amy; Glover-Kudon, Rebecca
BACKGROUND In 2005, the Centers for Disease Control and Prevention (CDC) funded 5 sites as part of the Colorectal Cancer Screening Demonstration Program (CRCSDP) to provide colorectal cancer screening to low-income, uninsured, and underinsured individuals. Funded sites experienced unexpected challenges in recruiting patients for services. METHODS The authors conducted a longitudinal, qualitative case study of all 5 sites to document program implementation, including recruitment. Data were collected during 3 periods over the 4-year program and included interviews, document review, and observations. After coding and analyzing the data, themes were identified and triangulated across the research team. Patterns were confirmed through member checking, further validating the analytic interpretation. RESULTS During early implementation, patient enrollment was low at 4 of the 5 CRCSDP sites. Evaluators found 3 primary challenges to patient recruitment: overreliance on in-reach to National Breast and Cervical Cancer Early Detection Program patients, difficulty keeping colorectal cancer screening and the program a priority among staff at partnering primary care clinics responsible for patient recruitment, and a lack of public knowledge about the need for colorectal cancer screening among patients. To address these challenges, site staff expanded partnerships with additional primary care networks for greater reach, enhanced technical support to primary care providers to ensure more consistent patient enrollment, and developed tailored outreach and education. CONCLUSIONS Removing financial barriers to colorectal cancer screening was necessary but not sufficient to reach the priority population. To optimize colorectal cancer screening, public health practitioners must work closely with the health care sector to implement evidence-based, comprehensive strategies across individual, environmental, and systems levels of society. PMID:23868486
Fornasarig, Mara; Minisini, Alessandro Marco; Clementi, Silvia; Bidoli, Ettore; Viel, Alessandra; Cannizzaro, Renato; Campagnutta, Elio; Boz, Gianni; Libra, Massimo
Endometrial carcinoma (EC) and colorectal cancer (CRC) are closely linked in a well-documented, predominantly inherited cancer syndrome known as hereditary non-polyposis colorectal cancer (HNPCC). Epidemiological studies report that women with EC have a 1.5- to 3-fold increased risk of developing CRC. However, this elevated risk could be the consequence of genetic confounding. In order to plan a proper CRC prevention program, we sought to verify and quantify this risk, first estimating it in 697 women with EC who received treatment and follow-up in one health care district between 1986 and 2000. The standardised incidence ratio (SIR), which compares observed with expected cases of CRC in the general population, was calculated. Multiple logistic regression analysis was used to estimate the odds ratio and 95% confidence interval of a dependent variable, second primary CRC, as a function of clinical and pathological features. Multiple primary tumours were observed in 6.7% of the patients, with CRC being the second most frequently occurring type of cancer. The estimated overall risk for CRC was slightly higher than that observed in the general population, but was nonetheless not statistically significant. Multivariate analysis revealed a family history of CRC to be a risk factor for developing the disease as a second primary cancer. A BMI ≤25 and the pathological spectrum of EC were clinical and pathological features associated with CRC development, but were without statistical significance. MSH2 and MLH1 mutational screening confirmed genetic involvement in most of the CRCs observed in the cohort. Overall, the data show that women with EC have a CRC risk similar to that of the general population, and should therefore be screened on the basis of risk factors for CRC.
Fakih, Marwan G.; Trump, Donald L.; Johnson, Candace S.; Tian, Lili; Muindi, Josephia; Sunga, Annette Y.
Background Preclinical and clinical evidence support an association between vitamin D deficiency and an increased risk of colorectal cancer. Normal vitamin D status has been linked to favorable health outcomes ranging from decreased risk of osteoporosis to improved cancer mortality. We performed a retrospective study to assess the impact of metastatic disease and chemotherapy treatment on vitamin D status in patients with colorectal cancer residing in Western New York. Materials and methods Patients, 315, with colorectal cancer treated in a single institute were assayed for 25-OH vitamin D. The association of age, gender, primary disease site and stage, body mass index, and chemotherapy with vitamin D status was investigated. Results Vitamin D deficiency was common among participants with a median 25-OH vitamin D level of 21.3 ng/ml (optimal range 32–100 ng/ml). Primary site of disease and chemotherapy status were associated with very low 25-OH vitamin D levels (≤15 ng/ml) on multivariate analysis. Patients receiving chemotherapy and patients with a rectal primary were fourfold and 2.6-fold more likely to have severe vitamin D deficiency on multivariate analysis than nonchemotherapy patients and colon cancer primary patients, respectively. Conclusions Chemotherapy is associated with a significant increase in the risk of severe vitamin D deficiency. Patients with colorectal cancer, especially those receiving chemotherapy, should be considered for aggressive vitamin D replacement strategies. PMID:18830610
Patai, Árpád V; Molnár, Béla; Tulassay, Zsolt; Sipos, Ferenc
Serrated polyps have been an area of intense focus for gastroenterologists over the past several years. Contrary to what was thought before, a growing body of literature indicates that these polyps can be precursors of colorectal cancer (CRC). Most of these lesions, particularly those in the proximal colon, have so far been under-recognized and missed during colonoscopy, qualifying these lesions to be the main cause of interval cancers. It is estimated that 10%-20% of CRCs evolve through this alternative, serrated pathway, with a distinct genetic and epigenetic profile. Aberrant DNA methylation plays a central role in the development of this CRC subtype. This characteristic molecular background is reflected in a unique pathological and clinical manifestation different from cancers arising via the traditional pathway. In this review we would like to highlight morphological, molecular and clinical features of this emerging pathway that are essential for gastroenterologists and may influence their everyday practice. PMID:23431044
Atkin, Wendy S; Edwards, Rob; Kralj-Hans, Ines; Wooldrage, Kate; Hart, Andrew R; Northover, John M A; Parkin, D Max; Wardle, Jane; Duffy, Stephen W; Cuzick, Jack
Colorectal cancer is the third most common cancer worldwide and has a high mortality rate. We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 years of age can substantially reduce colorectal cancer incidence and mortality. This randomised controlled trial was undertaken in 14 UK centres. 170 432 eligible men and women, who had indicated on a previous questionnaire that they would accept an invitation for screening, were randomly allocated to the intervention group (offered flexible sigmoidoscopy screening) or the control group (not contacted). Randomisation by sequential number generation was done centrally in blocks of 12, with stratification by trial centre, general practice, and household type. The primary outcomes were the incidence of colorectal cancer, including prevalent cases detected at screening, and mortality from colorectal cancer. Analyses were intention to treat and per protocol. The trial is registered, number ISRCTN28352761. 113 195 people were assigned to the control group and 57 237 to the intervention group, of whom 112 939 and 57 099, respectively, were included in the final analyses. 40 674 (71%) people underwent flexible sigmoidoscopy. During screening and median follow-up of 11.2 years (IQR 10.7-11.9), 2524 participants were diagnosed with colorectal cancer (1818 in control group vs 706 in intervention group) and 20 543 died (13 768 vs 6775; 727 certified from colorectal cancer [538 vs 189]). In intention-to-treat analyses, colorectal cancer incidence in the intervention group was reduced by 23% (hazard ratio 0.77, 95% CI 0.70-0.84) and mortality by 31% (0.69, 0.59-0.82). In per-protocol analyses, adjusting for self-selection bias in the intervention group, incidence of colorectal cancer in people attending screening was reduced by 33% (0.67, 0.60-0.76) and mortality by 43% (0.57, 0.45-0.72). Incidence of distal colorectal cancer (rectum and sigmoid colon) was reduced by 50% (0.50, 0.42-0.59; secondary
Background Health behaviors are known risk factors for colorectal cancer and are more common in low socioeconomic status (SES) populations. We evaluated the extent to which behavioral risk factors and body mass index (BMI) explain SES disparities in colorectal cancer incidence, overall and by tumor location. Methods We analyzed prospective National Institutes of Health-AARP Diet and Health Study data on 506 488 participants who were recruited in 1995–1996 from six US states and two metropolitan areas and followed through 2006. Detailed baseline data on risk factors for colorectal cancer, including health behaviors, were obtained using questionnaires. SES was measured by self-reported education and census-tract data. The outcome was primary incident invasive colorectal adenocarcinoma. Poisson regression was used to estimate the association between SES and risk of incident colorectal cancer, with adjustment for age, sex, race and ethnicity, family history, and state of residence. The model estimates were used to derive percentage mediation by behavioral risk factors; bias-corrected 95% confidence intervals were obtained through bootstrap techniques. Results Seven-thousand six-hundred seventy-six participants developed colorectal cancer during follow-up. SES differences in prevalence of physical inactivity, unhealthy diet, smoking, and unhealthy weight each explained between 11.3% (BMI) and 21.6% (diet) of the association between education and risk of colorectal cancer and between 8.6% (smoking) and 15.3% (diet) of the association between neighborhood SES and risk of colorectal cancer. Health behaviors and BMI combined explained approximately 43.9% (95% CI = 35.1% to 57.9%) of the association of education and 36.2% (95% CI = 28.0% to 51.2%) of the association of neighborhood SES with risk of colorectal cancer. The percentage explained by all factors and BMI combined was largest for right colon cancers and smallest for rectal cancers. Conclusion A substantial
Hubbard, Joleen M
Treatment for colorectal cancer should not be based on age alone. Pooled analyses from clinical trials show that fit older adults are able to tolerate treatment well with similar efficacy as younger adults. When an older adult is considered for treatment, the clinical encounter must evaluate for deficits in physical and cognitive function, and assess comorbidities, medications, and the degree of social support, all which have may affect tolerance of treatment. Based on the degree of fitness of the patient, multiple alternatives to aggressive treatment regimens and strategies exist to minimize toxicity and preserve quality of life during treatment.
Palmieri, Valentina; Lucchetti, Donatella; Maiorana, Alessandro; Papi, Massimiliano; Maulucci, Giuseppe; Ciasca, Gabriele; Svelto, Maria; De Spirito, Marco; Sgambato, Alessandro
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.
Yang, Meng; Hu, Frank B.; Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.; Fuchs, Charles S.; Wu, Kana; Bao, Ying
Background/Objectives Increasing nut consumption has been associated with reduced risk of obesity and type II diabetes, which are risk factors for colorectal cancer. However, the association between nut consumption and colorectal cancer risk is unclear. We aimed to examine the association of long-term nut consumption with risk of colorectal cancer. Subjects/Methods We prospectively followed 75,680 women who were free of cancer at baseline in the Nurses’ Health Study, and examined the association between nut consumption and colorectal cancer risk. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results During 2,103,037 person-years of follow-up, we identified 1,503 colorectal cancer cases. After adjustment for other known or suspected risk factors, women who consumed nuts 2 or more times per week (i.e., ≥56 grams per week) had a 13% lower risk of colorectal cancer compared to those who rarely consumed nuts, but the association was not statistically significant (RR: 0.87; 95% CI: 0.72, 1.05; P trend: 0.06). No association was observed for peanut butter. Conclusions In this large prospective cohort of women, frequent nut consumption was not significantly associated with colorectal cancer risk after adjusting for other risk factors. PMID:25944181
To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.
Lewis, Maria; Goh, Vicky; Beggs, Shaun; Bridges, Andrew; Clewer, Philip; Davis, Anne; Foy, Trevelyan; Fuller, Karen; George, Jennifer; Higginson, Antony; Honey, Ian; Iball, Gareth; Mutch, Steve; Neil, Shellagh; Rivett, Cat; Slater, Andrew; Sutton, David; Weir, Nick; Wayte, Sarah
To assess the cross-centre consistency of iodine enhancement, contrast-to-noise ratio and radiation dose in a multicentre perfusion CT trial of colorectal cancer. A cylindrical water phantom containing different iodine inserts was examined on seven CT models in 13 hospitals. The relationship between CT number (Hounsfield units, HU) and iodine concentration (milligrams per millilitre) was established and contrast-to-noise ratios (CNRs) calculated. Radiation doses (CTDIvol, DLP) were compared across all sites. There was a linear relationship between CT number and iodine density. Iodine enhancement varied by a factor of at most 1.10, and image noise by at most 1.5 across the study sites. At an iodine concentration of 1 mg ml(-1) and 100 kV, CNRs ranged from 3.6 to 4.8 in the 220-mm phantom and from 1.4 to 1.9 in the 300-mm phantom. Doses varied by a factor of at most 2.4, but remained within study dose constraints. Iterative reconstruction algorithms did not alter iodine enhancement but resulted in reduced image noise by a factor of at most 2.2, allowing a potential dose decrease of at most 80% compared to filtered back projection (FBP). Quality control of CT performance across centres indicates that CNR values remain relatively consistent across all sites, giving acceptable image quality within the agreed dose constraints. Quality control is essential in a multicentre setting to enable CT quantification. CNRs in a body-sized phantom had the recommended value of at least 1.5. CTDIs and DLPs varied by factors of 1.8 and 2.4 respectively.
Takahashi, Kazuto; Hosokawa, Masashi; Kasajima, Hiroyuki; Hatanaka, Kazuteru; Kudo, Kazuhiro; Shimoyama, Norihiko; Miyashita, Kazuo
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.
Shabo, Ivan; Olsson, Hans; Elkarim, Rihab; Sun, Xiao-Feng; Svanvik, Joar
The scavenger receptor, CD163, is a macrophage-specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression as a macrophage trait in cancer cells, and macrophage infiltration and its clinical significance in colorectal cancer. Immunostaining of CD163 and macrophage infiltration were evaluated in paraffin-embedded specimens, earlier analyzed for CD31, D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 75 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data. CD163 expression was positive in cancer cells in 20 % of colorectal cancer patients and was related to advanced tumor stages (P = 0.008) and unfavorable prognosis (p = 0.001). High macrophage infiltration was related to shorter survival and positive CD163 expression in tumor cells. The prognostic impact of macrophage infiltration was independent of tumor stage and CD163 expression in cancer cells (p = 0.034). The expression of macrophage phenotype in colorectal cancer cells is associated with macrophage density in tumor stroma and lower survival rates. Macrophage infiltration has an independent prognostic impact on mortality in colorectal cancer. In accordance with previous experimental studies, these findings provide new insights into the role of macrophages in colorectal cancer.
Levi, F; Pasche, C; La Vecchia, C; Lucchini, F; Franceschi, S
Most studies of diet and colorectal cancer have considered nutrients and micronutrients, but the role of foods or food groups remains open to debate. To elucidate the issue, we examined data from a case–control study conducted between 1992 and 1997 in the Swiss canton of Vaud. Cases were 223 patients (142 men, 81 women) with incident, histologically confirmed colon (n = 119) or rectal (n = 104) cancer (median age 63 years), linked with the Cancer Registry of the Swiss Canton of Vaud, and controls were 491 subjects (211 men, 280 women, median age 58 years) admitted to the same university hospital for a wide spectrum of acute non-neoplastic conditions unrelated to long-term modifications of diet. Odds ratios (OR) were obtained after allowance for age, sex, education, smoking, alcohol, body mass index, physical activity and total energy intake. Significant associations were observed for refined grain (OR = 1.32 for an increase of one serving per day), and red meat (OR = 1.54), pork and processed meat (OR = 1.27), alcohol (OR = 1.28), and significant protections for whole grain (OR = 0.85), raw (OR = 0.85) and cooked vegetables (OR = 0.69), citrus (OR = 0.86) and other fruits (OR = 0.85), and for coffee (OR = 0.73). Garlic was also protective (OR = 0.32 for the highest tertile of intake). These findings in a central European population support the hypothesis that a diet rich in refined grains and red meat increases the risk of colorectal cancer; they, therefore, support the recommendation to substitute whole grains for refined grain, to limit meat intake, and to increase fruit and vegetable consumption. © 1999 Cancer Research Campaign PMID:10098773
Ho, Gloria Y F; Wang, Tao; Gunter, Marc J; Strickler, Howard D; Cushman, Mary; Kaplan, Robert C; Wassertheil-Smoller, Sylvia; Xue, Xiaonan; Rajpathak, Swapnil N; Chlebowski, Rowan T; Vitolins, Mara Z; Scherer, Philipp E; Rohan, Thomas E
Mechanistic associations between obesity and colorectal cancer remain unclear. In this study, we investigated whether adipokines are risk factors for colorectal cancer and whether they may mediate its association with obesity. In a case-cohort study nested within the Women's Health Initiative cohort of postmenopausal women, baseline plasma samples from 457 colorectal cancer cases and 841 subcohort subjects were assayed for seven adipokines-adiponectin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, hepatocyte growth factor, interleukin-6 (IL-6), and TNF-α. Serum insulin and estradiol values measured previously were also available for data analysis. After adjusting for age, race, smoking, colonoscopy history, and estrogen level, a low level of anti-inflammatory adiponectin and high levels of proinflammatory leptin, PAI-1, and IL-6 were associated with increased colorectal cancer risk, though only leptin remained significant after further adjustment for insulin [HRs comparing extreme quartiles (HR(Q4-Q1)), 1.84; 95% CI, 1.17-2.90]. Mediation analyses showed that leptin and insulin partially explained the association between waist circumference and colorectal cancer and attenuated it by 25% and 37%, respectively, with insulin being a significant mediator (P = 0.041). Our findings support the conclusion that adipokines involved in inflammation are associated with colorectal cancer risk, but that their effects may be mediated mostly by insulin, with leptin exerting an independent effect. Hyperinsulinemia and hyperleptinemia may therefore partially explain the adiposity association with colorectal cancer in postmenopausal women.
Yu, TaChung; Guo, Fangfang; Yu, Yanan; Sun, Tiantian; Ma, Dan; Han, Jixuan; Qian, Yun; Kryczek, Ilona; Sun, Danfeng; Nagarsheth, Nisha; Chen, Yingxuan; Chen, Haoyan; Hong, Jie; Zou, Weiping; Fang, Jing-Yuan
Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.
Ho, Gloria Y.F.; Wang, Tao; Gunter, Marc J.; Strickler, Howard D.; Cushman, Mary; Kaplan, Robert C.; Wassertheil-Smoller, Sylvia; Xue, Xiaonan; Rajpathak, Swapnil N.; Chlebowski, Rowan T.; Vitolins, Mara Z.; Scherer, Philipp E.; Rohan, Thomas E.
Mechanistic associations between obesity and colorectal cancer remain unclear. In this study, we investigated whether adipokines are risk factors for colorectal cancer and whether they may mediate its association with obesity. In a case–cohort study nested within the Women’s Health Initiative cohort of postmenopausal women, baseline plasma samples from 457 colorectal cancer cases and 841 subcohort subjects were assayed for seven adipokines—adiponectin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, hepatocyte growth factor, interleukin-6 (IL-6), and TNF-α. Serum insulin and estradiol values measured previously were also available for data analysis. After adjusting for age, race, smoking, colonoscopy history, and estrogen level, a low level of antiinflammatory adiponectin and high levels of proinflammatory leptin, PAI-1, and IL-6 were associated with increased colorectal cancer risk, though only leptin remained significant after further adjustment for insulin [HRs comparing extreme quartiles (HRQ4–Q1), 1.84; 95% CI, 1.17–2.90]. Mediation analyses showed that leptin and insulin partially explained the association between waist circumference and colorectal cancer and attenuated it by 25% and 37%, respectively, with insulin being a significant mediator (P = 0.041). Our findings support the conclusion that adipokines involved in inflammation are associated with colorectal cancer risk, but that their effects may be mediated mostly by insulin, with leptin exerting an independent effect. Hyperinsulinemia and hyperleptinemia may therefore partially explain the adiposity association with colorectal cancer in postmenopausal women. PMID:22511581
Feng, Zhe; Chen, Ji-Wei; Feng, Jian-Hua; Shen, Fei; Cai, Wen-Song; Cao, Jie; Xu, Bo
There are conflicting reports on the correlation between serum levels of ferritin with colorectal cancer. The purpose of the present study is to clarify the association between serum ferritin with colorectal cancer using a meta-analysis approach. We searched articles indexed in Pubmed published as of July 2015 that met our predefined criteria. Six eligible articles involving 927 subjects were identified. Overall, pooled analysis indicated that subjects with colorectal cancer had lower serum level of ferritin than the healthy controls (SMD=-1.569, 95% CI=[-2.718, -0.420], P= 0.007). Further subgroup analysis found lower serum level of ferritin among patients with colorectal cancer in eastern country (SMD=-1.956, 95% CI=[-3.750, -0.162], P=0.033), but not in western country (SMD=-1.285, 95% CI=[-2.778, 0.207], P=0.091). In conclusion, this meta-analysis supports a significant association between serum ferritin with colorectal cancer. However, the subgroup analysis found that there was significant effect modification of ferritin level by ethnic. Thus this finding needs further confirmation by trans-regional multicenter, long-term observation in a cohort design to obtain better understanding of causal relationships between serum ferrintin levels and colorectal cancer, through measuring ferritin at baseline to investigate whether the highest ferritin category versus lowest is associated with colorectal cancer risk.
The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.
The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.
Attiê, Regina; Chinen, Ludmilla Thomé Domingos; Yoshioka, Eliane Muta; Silva, Michele Cristina F; de Lima, Vladmir Cláudio Cordeiro
To assess the impact of bacterial infections on cancer-specific survival in patients with colorectal cancer. This was a retrospective cohort study of colorectal cancer patients treated at the A.C. Camargo Cancer Center between January 2006 and April 2010. The presence of bacterial infection during cancer treatment, or up to one year after, was confirmed by laboratory tests or by the physician. Infections of the urinary, respiratory or digestive tracts, bloodstream, skin or surgical site were defined by testing within a single laboratory. Criteria for exclusion from the study were: chronically immunosuppressed patients; transplant patients (due to chronic immunosuppression); human immunodeficiency virus carriers; chronic use of corticosteroids or other immunosuppressive drugs; patients with autoimmune disease or primary immunodeficiency; known viral or parasitic infections. Patients with infections that did not require hospitalization were not included in the study because of the difficulty of collecting and tracking data related to infectious processes. In addition, patients hospitalized for pulmonary thromboembolism, stroke, acute myocardial infarction, uncontrolled diabetes, malignant hypercalcemia or other serious non-infectious complications not directly related to infection were also excluded. Survival curves were plotted using the Kaplan-Meier method, and log-rank tests (univariate analysis) and a Cox test assuming a proportional hazards model (multivariate analysis) were performed to examine associations between clinical history and characteristics of infection with cancer-specific survival. One-hundred and six patients with colorectal cancer were divided into two groups based on the presence or absence of bacterial infection. Patient ages ranged from 23 to 91 years, with a median of 55 years. The majority of patients were male (57/106, 53.77%) with stage III colorectal cancer (45/106, 44.11%). A total of 86 bacteriologic events were recorded. Results
Wei, Xiao-Li; Wang, De-Shen; Xi, Shao-Yan; Wu, Wen-Jing; Chen, Dong-Liang; Zeng, Zhao-Lei; Wang, Rui-Yu; Huang, Ya-Xin; Jin, Ying; Wang, Feng; Qiu, Miao-Zhen; Luo, Hui-Yan; Zhang, Dong-Sheng; Xu, Rui-Hua
To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer. We retrospectively collected clinicopathologic data and archived paraffin-embedded primary colorectal cancer samples from 209 patients, including 111 patients with colon cancer and 98 patients with rectal cancer. The tumor stage ranged from stage I to stage IV according to the 7(th) edition of the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. All patients underwent resection of primary colorectal tumors. The expression of ARID1A protein in primary colorectal cancer tissues was examined by immunohistochemical staining. The clinicopathologic association and survival relevance of ARID1A protein loss in colorectal cancer were analyzed. ARID1A loss by immunohistochemistry was not rare in primary colorectal cancer tumors (25.8%). There were 7.4%, 24.1%, 22.2% and 46.3% of patients with ARID1A loss staged at TNM stage I, II, III and IV, respectively, compared with 20.0%, 22.6%, 27.7% and 29.7% of patients without ARID1A loss staged at TNM stage I, II, III and IV, respectively. In patients with ARID1A loss, the distant metastasis rate was 46.3%. However, only 29.7% of patients without ARID1A loss were found to have distant metastasis. In terms of pathologic differentiation, there were 25.9%, 66.7% and 7.4% with poorly, moderately and well differentiated tumors in patients with ARID1A loss, and 14.2%, 72.3% and 13.5% with poorly, moderately and well differentiated tumors in patients without ARID1A loss, respectively. ARID1A loss was associated with late TNM stage (P = 0.020), distant metastasis (P = 0.026), and poor pathological classification (P = 0.035). However, patients with positive ARID1A had worse overall survival compared to those with negative ARID1A in stage IV colorectal cancer (HR = 2.49, 95%CI: 1.13-5.51). ARID1A protein loss is
Woo, Hae Dong; Kim, Jeongseon
Stomach and colorectal cancers are common cancers and leading causes of cancer deaths. Because the alimentary tract can interact directly with dietary components, stomach and colorectal cancer may be closely related to dietary intake. We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30, 2012. Twenty-three studies out of 209 identified articles were finally selected for the analysis. Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies. Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio (OR) (95%CI) = 1.00 (0.90-1.11) and 1.07 (0.70-1.61), respectively]. Among flavonoid subclasses, the intake of flavonols, flavan-3-ols, anthocyanidins, and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR (95%CI) = 0.71 (0.63-0.81), 0.88 (0.79-0.97), 0.68 (0.56-0.82), and 0.72 (0.61-0.85), respectively]. A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR (95%CI) = 0.68 (0.46-0.99)]. In the summary estimates from case-control studies, all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk, whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies. The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design. There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer. PMID:23467443
Woo, Hae Dong; Kim, Jeongseon
Stomach and colorectal cancers are common cancers and leading causes of cancer deaths. Because the alimentary tract can interact directly with dietary components, stomach and colorectal cancer may be closely related to dietary intake. We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30, 2012. Twenty-three studies out of 209 identified articles were finally selected for the analysis. Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies. Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio (OR) (95%CI) = 1.00 (0.90-1.11) and 1.07 (0.70-1.61), respectively]. Among flavonoid subclasses, the intake of flavonols, flavan-3-ols, anthocyanidins, and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR (95%CI) = 0.71 (0.63-0.81), 0.88 (0.79-0.97), 0.68 (0.56-0.82), and 0.72 (0.61-0.85), respectively]. A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR (95%CI) = 0.68 (0.46-0.99)]. In the summary estimates from case-control studies, all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk, whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies. The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design. There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer.
Bujanda, Luis; Sarasqueta, Cristina; Hijona, Elisabeth; Hijona, Lander; Cosme, Angel; Gil, Ines; Elorza, Jose Luis; Asensio, Jose I; Larburu, Santiago; Enríquez-Navascués, José M; Jover, Rodrigo; Balaguer, Francesc; Llor, Xavier; Bessa, Xavier; Andreu, Montserrat; Paya, Artemio; Castells, Antoni; Association, Gastrointestinal Oncology Group of the Spanish Gastroenterological
AIM: To evaluate changes in colorectal cancer (CRC) survival over the last 20 years. METHODS: We compared two groups of consecutive CRC patients that were prospectively recruited: Group I included 1990 patients diagnosed between 1980 and 1994. Group II included 871 patients diagnosed in 2001. RESULTS: The average follow up time was 21 mo (1-229) for Group I and 50 mo (1-73.4) for Group II. Overall median survival was significantly longer in Group II than in Group I (73 mo vs 25 mo, P < 0.001) and the difference was significant for all tumor stages. Post surgical mortality was 8% for Group Iand 2% for Group II (P < 0.001). Only 17% of GroupI patients received chemotherapy compared with 50% of Group II patients (P < 0.001). CONCLUSION: Survival in colorectal cancer patients has doubled over the past 20 years. This increase seems to be partly due to the generalization in the administration of chemotherapy and to the decrease of post surgical mortality. PMID:20143465
Van Blarigan, Erin L.; Meyerhardt, Jeffrey A.
This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. PMID:25918293
Van Blarigan, Erin L; Meyerhardt, Jeffrey A
This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. © 2015 by American Society of Clinical Oncology.
Rafiemanesh, Hosein; Pakzad, Reza; Abedi, Mehdi; Kor, Yones; Moludi, Jalal; Towhidi, Farhad; Reza Makhsosi, Behnam; Salehiniya, Hamid
Colorectal cancer is one of the most prevalent cancers in different countries, including Iran. No comprehensive study has been done in the country for colorectal cancer, but information on the incidence and trends is essential to planning. This study aimed to evaluate the occurrence and morphology of colorectal cancer and its trend in Iran. This study was conducted using data from the national cancer registry system in Iran from 2003-2008. We used joinpoint regression analysis for assessing incidence time trends and morphology change percentage. Of all cases of colorectal cancer, 61.83 % were colon cancer, 27.54 % rectal cancer, 7.46 % rectosigmoid cancer, and 3.10 anal cancer. The most common histological types with the frequencies of 80.85 % was related to adenocarcinoma, NOS. The Annual percentage changes (APC) in ASIR for colorectal cancer significantly increased in both men and women. APC in ASIR was 13.7 (CI: 10.5-17.1) in women and 16.4 (CI: 12.4-20.5) in men. APC of adenocarcinoma in villous adenoma showed significant declining trend (p<0.05), while APC of adenocarcinoma, NOS had a constant trend. The incidence of the cancer in recent years has increased in Iran because of changes in lifestyle and diet. Therefore, further studies are necessary to detect the cause of this cancer and perform preventive measures. PMID:28337105
Sun, Jun; Kato, Ikuko
Although genes contribute to colorectal cancer, the gut microbiota are an important player. Accumulating evidence suggests that chronic infection and the ensuing inflammation contributes to tumor initiation and tumor progression. A variety of bacterial species and tumor-promoting virulence mechanisms have been investigated. Significant advances have been made in understanding the composition and functional capabilities of the gut microbiota and its roles in cancer. In the current review, we discuss the novel roles of microbiota in the progression of colon cancer. Although microbiota technically include organisms other than bacteria e.g., viruses and fungi, this review will primarily focus on bacteria. We summarize epidemiological studies of human microbiome and colon cancer. We discuss the progress in the scientific understanding of the interplay between the gut microbiota, barrier function, and host responses in experimental models. Further, we discuss the potential application in prevention, diagnosis, and therapy of colon cancer by targeting microbiota. We discuss the challenges lie ahead and the future direction in studying gut microbiome in colon cancer to close the gap between the basic sciences and clinical application. PMID:28078319
Koshkin, Sergey; Danilova, Anna; Raskin, Grigory; Petrov, Nikolai; Bajenova, Olga; O'Brien, Stephen J; Tomilin, Alexey; Tolkunova, Elena
The principal cause of death in cancer involves tumor progression and metastasis. Since only a small proportion of the primary tumor cells, cancer stem cells (CSCs), which are the most aggressive, have the capacity to metastasize and display properties of stem cells, it is imperative to characterize the gene expression of diagnostic markers and to evaluate the drug sensitivity in the CSCs themselves. Here, we have examined the key genes that are involved in the progression of colorectal cancer and are expressed in cancer stem cells. Primary cultures of colorectal cancer cells from a patient's tumors were studied using the flow cytometry and cytological methods. We have evaluated the clinical and stem cell marker expression in these cells, their resistance to 5-fluorouracil and irinotecan, and the ability of cells to form tumors in mice. The data shows the role of stem cell marker Oct4 in the resistance of primary colorectal cancer tumor cells to 5-fluorouracil.
Aronson, Melyssa; Holter, Spring; Semotiuk, Kara; Winter, Laura; Pollett, Aaron; Gallinger, Steven; Cohen, Zane; Gryfe, Robert
The treatment of colorectal cancer in young patients involves both management of the incident cancer and consideration of the possibility of Lynch syndrome and the development of metachronous colorectal cancers. This study aims to assess the prognostic role of DNA mismatch repair deficiency and extended colorectal resection for metachronous colorectal neoplasia risk in young patients with colorectal cancer. This is a retrospective review of 285 patients identified in our GI cancer registry with colorectal cancer diagnosed at 35 years or younger in the absence of polyposis. Using univariate and multivariate analysis, we assessed the prognostic role of mismatch repair deficiency and standard clinicopathologic characteristics, including the extent of resection, on the rate of developing metachronous colorectal neoplasia requiring resection. Mismatch repair deficiency was identified in biospecimens from 44% of patients and was significantly associated with an increased risk for metachronous colorectal neoplasia requiring resection (10-year cumulative risk, 13.5% ± 4.2%) compared with 56% of patients with mismatch repair-intact colorectal cancer (10-year cumulative risk, 5.8% ± 3.3%; p = 0.011). In multivariate analysis, mismatch repair deficiency was associated with a HR of 3.65 (95% CI, 1.44-9.21; p = 0.006) for metachronous colorectal neoplasia, whereas extended resection with ileorectal or ileosigmoid anastomosis significantly decreased the risk of metachronous colorectal neoplasia (HR, 0.21; 95% CI, 0.05-0.90; p = 0.036). This study had a retrospective design, and, therefore, recommendations for colorectal cancer surgery and screening were not fully standardized. Quality of life after colorectal cancer surgery was not assessed. Young patients with colorectal cancer with molecular hallmarks of Lynch syndrome were at significantly higher risk for the development of subsequent colorectal neoplasia. This risk was significantly reduced in those who underwent extended
Ambalam, Padma; Raman, Maya; Purama, Ravi Kiran; Doble, Mukesh
Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention.
Dulal, Santosh; Deveaux, April; Jovov, Biljana; Han, Xuesong
The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation. PMID:25540232
Keku, Temitope O; Dulal, Santosh; Deveaux, April; Jovov, Biljana; Han, Xuesong
The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation.
Li, Yu-Hua; Niu, Yin-Bo; Sun, Yang; Zhang, Feng; Liu, Chang-Xu; Fan, Lei; Mei, Qi-Bing
Although the incidence of colorectal cancer (CRC) has been declining in recent decades, it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone for this disease. Extensive study has demonstrated that a diet containing fruits, vegetables, and spices has the potential to prevent CRC. The specific constituents in the dietary foods which are responsible for preventing CRC and the possible mechanisms have also been investigated extensively. Various phytochemicals have been identified in fruits, vegetables, and spices which exhibit chemopreventive potential. In this review article, chemopreventive effects of phytochemicals including curcumin, polysaccharides (apple polysaccharides and mushroom glucans), saponins (Paris saponins, ginsenosides and soy saponins), resveratrol, and quercetin on CRC and the mechanisms are discussed. This review proposes the need for more clinical evidence for the effects of phytochemicals against CRC in large trials. The conclusion of the review is that these phytochemicals might be therapeutic candidates in the campaign against CRC.
Tariq, Kanwal; Ghias, Kulsoom
Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men globally. CRC arises from one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. Non-coding RNAs, more importantly microRNAs and long non-coding RNAs have also been implicated at various CRC stages. Understanding the specific mechanisms of tumorigenesis and the underlying genetic and epigenetic traits is critical in comprehending the disease phenotype. This paper reviews these mechanisms along with the roles of various non-coding RNAs in CRCs.
Manzano, A.; Pérez-Segura, P.
Colorectal cancer (CRC) is presently one of the most common causes of cancer-related death in our setting and affects a great number of people each year. Screening strategies are commonly used but they do not seem enough to avoid CRC development or prevent completely its mortality. Because of this fact other prevention strategies have gained interest in recent years. Chemoprevention seems to be an attractive option in this setting and several drugs have been studied in this field. This review is focused on salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs) and cycloxygenase-2 inhibitors (COXIBs), whose mechanism of action could be directly related to colon cancer chemoprevention. PMID:22649288
Zhang, Wen; Tong, Duo; Liu, Fei; Li, Dawei; Li, Jiajia; Cheng, Xi; Wang, Ziliang
Ribosomal protein S7 (RPS7) acts as a tumor suppressor in primary tumorigenesis but its role in cancer metabolism remains unclear. In this study, we demonstrate that RPS7 inhibits the colorectal cancer (CRC) cell glycolysis by suppressing the expression of hypoxia-inducible transcription factor-1α (HIF-1α) and the metabolic promoting proteins glucose transporter 4 (GLUT4) and lactate dehydrogenase B (LDHB). Further study found that the enhanced expression of HIF-1α abrogates the overexpression effects of RPS7 on CRC. In vivo assays also demonstrate that RPS7 suppresses colorectal cancer tumorigenesis and glycolysis. Clinically, the tissue microarray (TMA) analysis discloses the negative regulatory association between RPS7 and HIF-1α in colorectal cancer. Meanwhile, overexpression of RPS7 in colorectal cancer tissues predicts good overall survival and progression-free survival, but high expression level of HIF-1α indicates poor overall survival and progression-free survival. Overall, we reveal that RPS7 inhibits colorectal cancer glycolysis through HIF-1α-associated signaling and may be a promising biomarker for prognosis prediction and a potential target for therapeutic treatment.
Li, Dawei; Li, Jiajia; Cheng, Xi; Wang, Ziliang
Ribosomal protein S7 (RPS7) acts as a tumor suppressor in primary tumorigenesis but its role in cancer metabolism remains unclear. In this study, we demonstrate that RPS7 inhibits the colorectal cancer (CRC) cell glycolysis by suppressing the expression of hypoxia-inducible transcription factor-1α (HIF-1α) and the metabolic promoting proteins glucose transporter 4 (GLUT4) and lactate dehydrogenase B (LDHB). Further study found that the enhanced expression of HIF-1α abrogates the overexpression effects of RPS7 on CRC. In vivo assays also demonstrate that RPS7 suppresses colorectal cancer tumorigenesis and glycolysis. Clinically, the tissue microarray (TMA) analysis discloses the negative regulatory association between RPS7 and HIF-1α in colorectal cancer. Meanwhile, overexpression of RPS7 in colorectal cancer tissues predicts good overall survival and progression-free survival, but high expression level of HIF-1α indicates poor overall survival and progression-free survival. Overall, we reveal that RPS7 inhibits colorectal cancer glycolysis through HIF-1α-associated signaling and may be a promising biomarker for prognosis prediction and a potential target for therapeutic treatment. PMID:26735579
Dowswell, George; Ismail, Tariq; Clifford, Sue; Hancock, Beverley; Wilson, Sue
Objectives To examine the experiences of men after treatment for colorectal cancer, identify barriers to accessing services, and suggest improvements to providing information in primary and secondary care. Design Semistructured, qualitative interview study with purposive sampling and thematic analysis. Participants 28 patients treated for colorectal cancer. Setting West Midlands. Results Most men treated for colorectal cancer experience erectile dysfunction as a consequence. Not all, however, want the same response from health professionals. Although, erectile dysfunction is profoundly stressful for most men, affecting self image, behaviour, and relationships, some do not regard it as a health priority. Many of the men were uninformed about erectile dysfunction and were unprepared for it, and the majority neither helped themselves nor asked for help. Almost none were receiving adequate, effective, and affordable care. Evidence of ageism was strong. Conclusions Unlike patients with prostate cancer, men with colorectal cancer are not routinely offered information and treatment for erectile dysfunction. Greater coordination of care and consistent strategies are needed to tackle the unmet needs of this widely diverse patient group. Currently, clinicians are inadvertently neglecting, misleading, and offending such patients; better training could improve this situation, as might the reorganisation of services. Further research is needed to determine whether trained clinical nurse specialists in colorectal cancer units could coordinate ongoing care. PMID:22010127
Heitman, Steven J.; Manns, Braden J.; Hilsden, Robert J.; Fong, Andrew; Dean, Stafford; Romagnuolo, Joseph
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
Pritchard, Colin C.; Grady, William M.
The promise of personalized medicine is now a clinical reality, with colorectal cancer genetics at the forefront of this next major advance in clinical medicine. This is no more evident than in the recent advances in testing of colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we examine genetic mechanisms of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:20921207
Bazzocco, Sarah; Dopeso, Higinio; Carton-Garcia, Fernando; Macaya, Irati; Andretta, Elena; Chionh, Fiona; Rodrigues, Paulo; Garrido, Miriam; Alazzouzi, Hafid; Nieto, Rocio; Sanchez, Alex; Schwartz, Simo; Bilic, Josipa; Mariadason, John M; Arango, Diego
The clinical management of colorectal cancer patients has significantly improved because of the identification of novel therapeutic targets such as EGFR and VEGF. Because rapid tumor proliferation is associated with poor patient prognosis, here we characterized the transcriptional signature of rapidly proliferating colorectal cancer cells in an attempt to identify novel candidate therapeutic targets. The doubling time of 52 colorectal cancer cell lines was determined and genome-wide expression profiling of a subset of these lines was assessed by microarray analysis. We then investigated the potential of genes highly expressed in cancer cells with faster growth as new therapeutic targets. Faster proliferation rates were associated with microsatellite instability and poorly differentiated histology. The expression of 1,290 genes was significantly correlated with the growth rates of colorectal cancer cells. These included genes involved in cell cycle, RNA processing/splicing, and protein transport. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protoporphyrinogen oxidase (PPOX) were shown to have higher expression in faster growing cell lines and primary tumors. Pharmacologic or siRNA-based inhibition of GAPDH or PPOX reduced the growth of colon cancer cells in vitro. Moreover, using a mouse xenograft model, we show that treatment with the specific PPOX inhibitor acifluorfen significantly reduced the growth of three of the seven (42.8%) colon cancer lines investigated. We have characterized at the transcriptomic level the differences between colorectal cancer cells that vary in their growth rates, and identified novel candidate chemotherapeutic targets for the treatment of colorectal cancer. ©2015 American Association for Cancer Research.
Green, Chadwick John; de Dauwe, Palina; Boyle, Terry; Tabatabaei, Seyed Mehdi; Fritschi, Lin; Heyworth, Jane Shirley
Data regarding the effects of tea, coffee, and milk on the risk of colorectal cancer are inconsistent. We investigated associations of tea, coffee, and milk consumption with colorectal cancer risk and attempted to determine if these exposures were differentially associated with the risks of proximal colon, distal colon, and rectal cancers. Data from 854 incident cases and 948 controls were analyzed in a case-control study of colorectal cancer in Western Australia during 2005-07. Multivariable logistic regression was used to analyze the associations of black tea (with and without milk), green tea, herbal tea, hot coffee, iced coffee, and milk with colorectal cancer. Consumption of 1 or more cups of herbal tea per week was associated with a significantly decreased risk of distal colon cancer (adjusted odds ratio, 0.37; 95% CI, 0.16-0.82; PTrend = 0.044), and consumption of 1 or more cups of iced coffee per week was associated with increased risk of rectal cancer (adjusted odds ratio, 1.52; 95% CI, 0.91-2.54; PTrend = 0.004). Neither herbal tea nor iced coffee was associated with the risk of proximal colon cancer. Hot coffee was associated with a possible increased risk of distal colon cancer. Black tea (with or without milk), green tea, decaffeinated coffee, and milk were not significantly associated with colorectal cancer risk. Consumption of herbal tea was associated with reduced risk of distal colon cancer, and consumption of iced coffee was associated with increased rectal cancer risk.
Abraha, Aman M; Ketema, Ezra B
Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment.
Devoto, Laurence; Celentano, Valerio; Cohen, Richard; Khan, Jim; Chand, Manish
Colorectal cancer is the second most common cause of death from neoplastic disease in men and third in women of all ages. Globally, life expectancy is increasing, and consequently, an increasing number of operations are being performed on more elderly patients with the trend set to continue. Elderly patients are more likely to have cardiovascular and pulmonary comorbidities that are associated with increased peri-operative risk. They further tend to present with more locally advanced disease, more likely to obstruct or have disseminated disease. The aim of this review was to investigate the feasibility of laparoscopic colorectal resection in very elderly patients, and whether there are benefits over open surgery for colorectal cancer. A systematic literature search was performed on Medline, Pubmed, Embase and Google Scholar. All comparative studies evaluating patients undergoing laparoscopic versus open surgery for colorectal cancer in the patients population over 85 were included. The primary outcomes were 30-day mortality and 30-day overall morbidity. Secondary outcomes were operating time, time to oral diet, number of retrieved lymph nodes, blood loss and 5-year survival. The search provided 1507 citations. Sixty-nine articles were retrieved for full text analysis, and only six retrospective studies met the inclusion criteria. Overall mortality for elective laparoscopic resection was 2.92% and morbidity 23%. No single study showed a significant difference between laparoscopic and open surgery for morbidity or mortality, but pooled data analysis demonstrated reduced morbidity in the laparoscopic group (p = 0.032). Patients undergoing laparoscopic surgery are more likely to have a shorter hospital stay and a shorter time to oral diet. Elective laparoscopic resection for colorectal cancer in the over 85 age group is feasible and safe and offers similar advantages over open surgery to those demonstrated in patients of younger ages.
Rawl, S M; Menon, U; Champion, V L; Foster, J L; Skinner, C S
The purpose of this paper is to describe the perceived benefits and barriers to colorectal cancer screening reported by first-degree relatives of colorectal cancer patients. In this study, the authors used focus groups to identify perceived benefits and barriers to colorectal cancer screening among parents and children of colorectal cancer patients. Four focus groups were conducted with relatives of colorectal cancer patients seen at two university medical centers in the Midwest. The groups ranged in size from five to eight members each and were stratified by gender. Four benefits of colorectal cancer screening were identified by participants: finding colorectal cancer early, decreasing the chances of dying from colorectal cancer, freedom from worry about colorectal cancer, and reassurance that one was cancer-free. Four main barriers were identified that applied to all four types of colorectal cancer screening or to colorectal cancer screening in general. These included inadequate public awareness of colorectal cancer, inconsistent recommendations from healthcare providers, concerns about the efficacy of screening tests, and embarrassment. Barriers unique to each screening test also were identified. Understanding individual beliefs about the benefits and barriers to colorectal cancer screening will allow clinicians and researchers to develop effective interventions to increase screening. Results from the focus groups have been used to develop an instrument to measure benefits and barriers to colorectal cancer screening, which now needs to be tested with more culturally and socioeconomically diverse groups.
Couch, D G; Murphy, J H; Boyle, K M; Hemingway, D M
The 2-week wait pathway was designed to decrease the time from presentation to primary care of patients with 'red flag' symptoms of suspected cancer for review by a specialist for the diagnosis or exclusion of cancer. In our tertiary referral centre we have found that 968 colonoscopies per year are required to satisfy the demand for the 2-week wait, leading to limited colonoscopy availability for other services. We sought to determine the yield of colorectal cancer found at colonoscopy referred via the 2-week wait and referenced to the original red flag symptoms. This was in order to select the most efficacious alternative primary investigation based upon presenting symptoms. Electronic records were retrospectively analysed. All patients who went through the 2-week wait for suspicion of colorectal cancer in 2013 and were found to have colorectal cancer on colonoscopy were included. Patients not undergoing colonoscopy as the first investigation were excluded. The splenic flexure was deemed to be within the range of a flexible sigmoidoscope. In all, 2950 referrals were made. 968 colonoscopies were performed as the primary investigation of which 35 were found to have colorectal cancer. No patients referred with rectal bleeding and another symptom had a tumour more proximal to the range of flexible sigmoidoscopy. 80% of tumours proximal to the splenic flexure were suitable for CT diagnosis alone. Our data support the use of flexible sigmoidoscopy alone as an initial investigation for patients presenting with rectal bleeding with or without additional colorectal symptoms. Patients with anaemia (without bleeding) or change in bowel habit (without bleeding) may be investigated with CT colonography alone; colonoscopy may then be used selectively prior to surgery. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.
The NCCN has recently released its 2017 version 1.0 guideline for colorectal cancer. There are several updates from this new version guideline which are believed to change the current clinical practice. Update one, low-dose aspirin is recommended for patients with colorectal cancer after colectomy for secondary chemoprevention. Update two, biological agents are removed from the neoadjuvant treatment regimen for resectable metastatic colorectal cancer (mCRC). This update is based on lack of evidence to support benefits of biological agents including bevacizumab and cetuximab in the neoadjuvant setting. Both technical criteria and prognostic information should be considered for decision-making. Currently biological agents may not be excluded from the neoadjuvant setting for patients with resectable but poor prognostic disease. Update three, panitumumab and cetuximab combination therapy is only recommended for left-sided tumors in the first line therapy. The location of the primary tumor can be both prognostic and predictive in response to EGFR inhibitors in metastatic colorectal cancer. Cetuximab and panitumumab confer little benefit to patients with metastatic colorectal cancer in the primary tumor originated on the right side. On the other hand, EGFR inhibitors provide significant benefit compared with bevacizumab-containing therapy or chemotherapy alone for patients with left primary tumor. Update four, PD-1 immune checkpoint inhibitors including pembrolizumab or nivolumab are recommended as treatment options in patients with metastatic deficient mismatch repair (dMMR) colorectal cancer in second- or third-line therapy. dMMR tumors contain thousands of mutations, which can encode mutant proteins with the potential to be recognized and targeted by the immune system. It has therefore been hypothesized that dMMR tumors may be sensitive to PD-1 inhibitors.
Marin, Jose J G; Sanchez de Medina, Fermin; Castaño, Beatriz; Bujanda, Luis; Romero, Marta R; Martinez-Augustin, Olga; Moral-Avila, Rosario Del; Briz, Oscar
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.
Okugawa, Yoshinaga; Grady, William M.; Goel, Ajay
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the fundamental processes driving the initiation and progression of CRC is the accumulation of a variety of genetic and epigenetic changes in colon epithelial cells. Over the past decade, major advances have been made in our understanding of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA (miRNA) and noncoding RNA deregulation, and alterations in histone modification states. Assessment of the colon cancer “epigenome” has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression. The average CRC methylome has hundreds to thousands of abnormally methylated genes and dozens of altered miRNAs. As with gene mutations in the cancer genome, a subset of these epigenetic alterations, called driver events, is presumed to have a functional role in CRC. In addition, the advances in our understanding of epigenetic alterations in CRC have led to these alterations being developed as clinical biomarkers for diagnostic, prognostic and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC. PMID:26216839
Tuncer, Sinem; Banerjee, Sreeparna
Enzymatic metabolism of the 20C polyunsaturated fatty acid (PUFA) arachidonic acid (AA) occurs via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and leads to the production of various bioactive lipids termed eicosanoids. These eicosanoids have a variety of functions, including stimulation of homeostatic responses in the cardiovascular system, induction and resolution of inflammation, and modulation of immune responses against diseases associated with chronic inflammation, such as cancer. Because chronic inflammation is essential for the development of colorectal cancer (CRC), it is not surprising that many eicosanoids are implicated in CRC. Oftentimes, these autacoids work in an antagonistic and highly temporal manner in inflammation; therefore, inhibition of the pro-inflammatory COX-2 or 5-LOX enzymes may subsequently inhibit the formation of their essential products, or shunt substrates from one pathway to another, leading to undesirable side-effects. A better understanding of these different enzymes and their products is essential not only for understanding the importance of eicosanoids, but also for designing more effective drugs that solely target the inflammatory molecules found in both chronic inflammation and cancer. In this review, we have evaluated the cancer promoting and anti-cancer roles of different eicosanoids in CRC, and highlighted the most recent literature which describes how those molecules affect not only tumor tissue, but also the tumor microenvironment. Additionally, we have attempted to delineate the roles that eicosanoids with opposing functions play in neoplastic transformation in CRC through their effects on proliferation, apoptosis, motility, metastasis, and angiogenesis. PMID:26557000
Kim, Jung Han
Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the elderly. However, elderly patients with CRC tend to be under-presented in clinical trials and undertreated in clinical practice. Advanced age alone should not be the only criteria to preclude effective therapy in elderly patients with CRC. The best guide about optimal cancer treatment can be provided by comprehensive geriatric assessment. Elderly patients with stage III colon cancer can enjoy the same benefit from adjuvant chemotherapy with 5-fluorouracil/leucovorin or capecitabine as younger patients, without a substantial increase in toxicity. With conflicting results of retrospective studies and a lack of data available from randomized studies, combined modality treatment should be used with great caution in elderly patients with locally advanced rectal cancer. Combination chemotherapy can be considered for older patients with metastatic CRC. For elderly patients who are frail or vulnerable, however, monotherapy or a stop-and-go strategy may be desirable. The use of targeted therapies in older patients with metastatic CRC appears to be promising in view of their better efficacy and toxicity. Treatment should be individualized based on the nature of the disease, the physiologic or functional status, and the patient's preference.
Gao, Zhiguang; Guo, Bomin; Gao, Renyuan; Zhu, Qingchao; Qin, Huanlong
The dysbiosis of the human intestinal microbiota is linked to sporadic colorectal carcinoma (CRC). The present study was designed to investigate the gut microbiota distribution features in CRC patients. We performed pyrosequencing based analysis of the 16S rRNA gene V3 region to investigate microbiota of the cancerous tissue and adjacent non-cancerous normal tissue in proximal and distal CRC samples. The results revealed that the microbial structures of the CRC patients and healthy individuals differed significantly. Firmicutes and Fusobacteria were over-represented whereas Proteobacteria was under-represented in CRC patients. In addition, Lactococcus and Fusobacterium exhibited a relatively higher abundance while Pseudomonas and Escherichia-Shigella was reduced in cancerous tissues compared to adjacent non-cancerous tissues. Meanwhile, the overall microbial structures of proximal and distal colon cancerous tissues were similar; but certain potential pro-oncogenic pathogens were different. These results suggested that the mucosa-associated microbiota is dynamically associated with CRC, which may provide evidences for microbiota-associated diagnostic, prognostic, preventive, and therapeutic strategies for CRC.
Simon, Michael S.; Chlebowski, Rowan T.; Wactawski-Wende, Jean; Johnson, Karen C.; Muskovitz, Andrew; Kato, Ikuko; Young, Alicia; Hubbell, F. Allan; Prentice, Ross L.
Purpose During the intervention phase in the Women's Health Initiative (WHI) clinical trial, use of estrogen plus progestin reduced the colorectal cancer diagnosis rate, but the cancers were found at a substantially higher stage. To assess the clinical relevance of the findings, analyses of the influence of combined hormone therapy on colorectal cancer incidence and colorectal cancer mortality were conducted after extended follow-up. Patients and Methods The WHI study was a randomized, double-blind, placebo-controlled clinical trial involving 16,608 postmenopausal women with an intact uterus who were randomly assigned to daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or matching placebo (n = 8,102). Colorectal cancer diagnosis rates and colorectal cancer mortality were assessed. Results After a mean of 5.6 years (standard deviation [SD], 1.03 years) of intervention and 11.6 years (SD, 3.1 years) of total follow-up, fewer colorectal cancers were diagnosed in the combined hormone therapy group compared with the placebo group (diagnoses/year, 0.12% v 0.16%; hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.94; P = .014). Bowel screening examinations were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (50.5% v 28.6%; P < .001) and were at higher stage (regional or distant, 68.8% v 51.4%; P = .003). Although not statistically significant, there was a higher number of colorectal cancer deaths in the combined hormone therapy group (37 v 27 deaths; 0.04% v 0.03%; HR, 1.29; 95% CI, 0.78 to 2.11; P = .320). Conclusion The findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer. PMID:23008295
Curtis, N. J.; Noble, E.; Cortina-Borja, M.; Salib, E.
Introduction. The developmental origins of health and disease hypothesis and season of birth have been linked to a wide variety of later life conditions including cancer. Whether any relationship between month and season of birth and colorectal cancer exists is unknown. Methods. A case-control study was performed with month of birth extracted from a dedicated colorectal cancer database. Age and gender matched patients were used as a control group. Generalised linear models were fitted with Poisson and negative binomial responses and logarithmic links. A forward stepwise approach was followed adding seasonal components with 6- and 12-month periods. Results. 1019 colorectal cancer patients and 1277 randomly selected age and gender matched controls were included. For both men and women there is an excess of colorectal cancer in those born in autumn and a corresponding reduction of risk among those born in spring (p = 0.026). For the identified September peak, the excess risk for colorectal cancer was 14.8% (95% CI 5.6–32.3%) larger than the spring trough. Conclusion. There is a seasonal effect in the monthly birth rates of people who are operated for colorectal cancer with a disproportionate excess of cancer in those born in September. Further large studies are required to validate these findings. PMID:28133478
Francis, N K; Curtis, N J; Noble, E; Cortina-Borja, M; Salib, E
Introduction. The developmental origins of health and disease hypothesis and season of birth have been linked to a wide variety of later life conditions including cancer. Whether any relationship between month and season of birth and colorectal cancer exists is unknown. Methods. A case-control study was performed with month of birth extracted from a dedicated colorectal cancer database. Age and gender matched patients were used as a control group. Generalised linear models were fitted with Poisson and negative binomial responses and logarithmic links. A forward stepwise approach was followed adding seasonal components with 6- and 12-month periods. Results. 1019 colorectal cancer patients and 1277 randomly selected age and gender matched controls were included. For both men and women there is an excess of colorectal cancer in those born in autumn and a corresponding reduction of risk among those born in spring (p = 0.026). For the identified September peak, the excess risk for colorectal cancer was 14.8% (95% CI 5.6-32.3%) larger than the spring trough. Conclusion. There is a seasonal effect in the monthly birth rates of people who are operated for colorectal cancer with a disproportionate excess of cancer in those born in September. Further large studies are required to validate these findings.
O'Dwyer, Donna; Ralton, Lynda D.; O'Shea, Aisling; Murray, Graeme I.
Colorectal cancer is one of the commonest types of cancer and there is requirement for the identification of prognostic biomarkers. In this study protein expression profiles have been established for colorectal cancer and normal colonic mucosa by proteomics using a combination of two dimensional gel electrophoresis with fresh frozen sections of paired Dukes B colorectal cancer and normal colorectal mucosa (n = 28), gel image analysis and high performance liquid chromatography–tandem mass spectrometry. Hierarchical cluster analysis and principal components analysis showed that the protein expression profiles of colorectal cancer and normal colonic mucosa clustered into distinct patterns of protein expression. Forty-five proteins were identified as showing at least 1.5 times increased expression in colorectal cancer and the identity of these proteins was confirmed by liquid chromatography–tandem mass spectrometry. Fifteen proteins that showed increased expression were validated by immunohistochemistry using a well characterised colorectal cancer tissue microarray containing 515 primary colorectal cancer, 224 lymph node metastasis and 50 normal colonic mucosal samples. The proteins that showed the greatest degree of overexpression in primary colorectal cancer compared with normal colonic mucosa were heat shock protein 60 (p<0.001), S100A9 (p<0.001) and translationally controlled tumour protein (p<0.001). Analysis of proteins individually identified 14-3-3β as a prognostic biomarker (χ2 = 6.218, p = 0.013, HR = 0.639, 95%CI 0.448–0.913). Hierarchical cluster analysis identified distinct phenotypes associated with survival and a two-protein signature consisting of 14-3-3β and aldehyde dehydrogenase 1 was identified as showing prognostic significance (χ2 = 7.306, p = 0.007, HR = 0.504, 95%CI 0.303–0.838) and that remained independently prognostic (p = 0.01, HR = 0.416, 95%CI 0.208–0.829) in a multivariate model. PMID
Kitahara, Cari M.; Berndt, Sonja I.; de González, Amy Berrington; Coleman, Helen G.; Schoen, Robert E.; Hayes, Richard B.; Huang, Wen-Yi
Purpose Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection. Methods We prospectively evaluated the association between baseline BMI and the risk of incident distal adenoma (1,213 cases), recurrent adenoma (752 cases), and incident colorectal cancer (966 cases) among men and women, ages 55 to 74 years, randomly assigned to receive flexible sigmoidoscopy screening as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We calculated odds ratios (ORs) and 95% CIs for adenoma incidence and recurrence, and hazard ratios (HRs) and 95% CIs for colorectal cancer incidence, using multivariable-adjusted models. Results Compared with normal-weight men (18.5 to 24.9 kg/m2), obese men (≥ 30 kg/m2) had significantly higher risk of incident adenoma (OR, 1.32; 95% CI, 1.06 to 1.65) and colorectal cancer (HR, 1.48; 95% CI, 1.16 to 1.89) and a borderline increased risk of recurrent adenoma (OR, 1.50; 95% CI, 0.98 to 2.30). No associations were observed for either adenoma or cancer in women. Conclusion Data from this large prospective study suggest that obesity is important throughout the natural history of colorectal cancer, at least in men, and colorectal cancer prevention efforts should encourage the achievement and maintenance of a healthy body weight in addition to regular screenings. PMID:23715565
Kitahara, Cari M; Berndt, Sonja I; de González, Amy Berrington; Coleman, Helen G; Schoen, Robert E; Hayes, Richard B; Huang, Wen-Yi
Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection. We prospectively evaluated the association between baseline BMI and the risk of incident distal adenoma (1,213 cases), recurrent adenoma (752 cases), and incident colorectal cancer (966 cases) among men and women, ages 55 to 74 years, randomly assigned to receive flexible sigmoidoscopy screening as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We calculated odds ratios (ORs) and 95% CIs for adenoma incidence and recurrence, and hazard ratios (HRs) and 95% CIs for colorectal cancer incidence, using multivariable-adjusted models. Compared with normal-weight men (18.5 to 24.9 kg/m(2)), obese men (≥ 30 kg/m(2)) had significantly higher risk of incident adenoma (OR, 1.32; 95% CI, 1.06 to 1.65) and colorectal cancer (HR, 1.48; 95% CI, 1.16 to 1.89) and a borderline increased risk of recurrent adenoma (OR, 1.50; 95% CI, 0.98 to 2.30). No associations were observed for either adenoma or cancer in women. Data from this large prospective study suggest that obesity is important throughout the natural history of colorectal cancer, at least in men, and colorectal cancer prevention efforts should encourage the achievement and maintenance of a healthy body weight in addition to regular screenings.
Knutsen, Turid; Padilla-Nash, Hesed M.; Wangsa, Danny; Barenboim-Stapleton, Linda; Camps, Jordi; McNeil, Nicole; Difilippantonio, Michael J.; Ried, Thomas
In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. We here present the results of a comprehensive investigation of 15 established colorectal cancer cell lines utilizing spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-1) are described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines, isochromosomes were the most common recurrent abnormalities, and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities result predominantly in copy number changes rather than specific chromosome or gene fusions, suggests this may be the major mechanism leading to carcinogenesis in colorectal cancer. PMID:19927377
Knutsen, Turid; Padilla-Nash, Hesed M; Wangsa, Danny; Barenboim-Stapleton, Linda; Camps, Jordi; McNeil, Nicole; Difilippantonio, Michael J; Ried, Thomas
In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. Here, we present the results of a comprehensive investigation of 15 established colorectal cancer cell lines using spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-1) is described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines; isochromosomes were the most common recurrent abnormalities; and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer.
Jarvandi, Soghra; Davidson, Nicholas O.; Schootman, Mario
Background Poor diet increases the risk of both colorectal cancer and type 2 diabetes. We investigated the role of diet in the association between diabetes and colorectal cancer. Methods We analyzed data from 484,020 individuals, aged 50–71 years who participated in the prospective National Institutes of Health-AARP Diet and Health Study and were cancer free at baseline (1995–1996). History of diabetes was self-reported. Diet quality was measured with the Healthy Eating Index-2005 (HEI-2005), using a self-administered food-frequency questionnaire. Cox regression models were constructed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of first primary incident colorectal cancer, overall and by anatomical location. Results During an average follow-up of 9.2 years, we identified 7,598 new cases of colorectal cancer. After controlling for non-dietary confounders, diabetes was associated with increased risk of colorectal cancer (HR 1.27, 95% CI: 1.18, 1.36). Further adjustment for diet quality did not attenuate this association. Diabetes was associated with a HR of 1.23 (95% CI: 1.07, 1.40) in individuals with good diet (quartile 4 of HEI-2005) and 1.58 (95% CI: 1.34, 1.86) in those with poor diet (quartile 1 of HEI-2005), compared to those with no diabetes and good diet. Moreover, diabetes was associated with a stronger risk of proximal than distal colon cancer (HR: 1.33 vs. HR: 1.20), while poor diet was associated with a weaker risk of proximal colon cancer (HR: 1.18 vs. HR: 1.46). Conclusion Diabetes and poor diet, independently and additively are associated with the increased risk of colorectal cancer. PMID:24069323
The Primary Study Objective is to Assess the Efficacy and; Safety of Extended 4-week Heparin Prophylaxis Compared to; Prophylaxis Given for 8±2 Days After Planned Laparoscopic; Surgery for Colorectal Cancer.; The Clinical Benefit Will be Evaluated as the Difference in; the Incidence of VTE or VTE-related Death Occurring Within 30 Days; From Surgery in the Two Study Groups.
Biswas, S; Holyoake, D; Maughan, T S
Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy. Copyright © 2015. Published by Elsevier Ltd.
Wang, Jun; Luo, Mao-Hong; Zhang, Zuo-Xing; Zhang, Pei-Da; Jiang, Xi-Li; Ma, Dong-Wang; Suo, Rong-Zeng; Zhao, Li-Zhong; Qi, Qing-Hui
AIM: To analyze the frequency of hereditary non-polyposis colorectal cancer (HNPCC) in Chinese colorectal cancer (CRC) patients, and to discuss the value of microsatellite instability (MSI) and/or immunohistochemistry (IHC) for MSH2/MLH1 protein analysis as pre-screening tests in China. METHODS: The Amsterdam criteriaIandII(clinical diagnosis) and/or germline hMLH1/hMSH2 mutations (genetic diagnosis) were used to classify HNPCC families. Genetic tests, including microsatellite instability, immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes, were performed in each proband. RESULTS: From July 2000 to June 2004, 1988 patients with colorectal cancer were analysed and 114 CRC patients (5.7%) from 48 families were categorized as having HNPCC, including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically. The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%, and 79% and 77%, respectively. CONCLUSION: The frequency of HNPCC is approximately 10% among all Chinese CRC cases. The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable pre-screening tests for hMLH1/hMSH2 germline mutations in families suspected of having HNPCC. PMID:17461458
Kovac, Suzana; Anderson, Gregory J; Baldwin, Graham S
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.
Nag, S. )
Radical surgical excision of locoregional recurrence of colorectal carcinoma usually produces the best survival and should be attempted whenever possible. However, recurrences are often unresectable; hence palliative local therapy may be indicated. There are several options for the radiation therapy of local, unresectable, recurrent, or metastatic colorectal cancer. Whole pelvis irradiation of 4,000-5,000 cGy followed by a coned-down boost of 1,000-1,500 cGy generally provides good symptomatic palliation in 80-90% of patients, but long-term control or cure is rarely achieved. External beam irradiation of 2,000-3,000 cGy to the whole liver with or without concurrent chemotherapy may be used for palliation of metastatic disease to the liver. A combination of intraoperative radiation therapy applied directly to the tumor bed and external beam irradiation may improve local control and survival rates. Multiple options are available for the intraoperative use of brachytherapy which can deliver high radiation doses to the residual tumor, or tumor bed, sparing normal tissue.
Kovac, Suzana; Anderson, Gregory J.; Baldwin, Graham S.
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
Bailey, James R; Aggarwal, Ashish; Imperiale, Thomas F
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.
There are five types of tests that are used to screen for colorectal cancer: fecal occult blood test, sigmoidoscopy, colonoscopy, virtual colonoscopy, and DNA stool test. Learn more about these and other tests in this expert-reviewed summary.
Passot, Guillaume; Mohkam, Kayvan; Cotte, Eddy; Glehen, Olivier
Free cancer cells can be detected in peritoneal fluid at the time of colorectal surgery. Peritoneal lavage in colorectal surgery for cancer is not used in routine, and the prognostic significance of intraperitoneal free cancer cells (IPCC) remains unclear. Data concerning the technique of peritoneal lavage to detect IPCC and its timing regarding colorectal resection are scarce. However, positive IPCC might be the first step of peritoneal spread in colorectal cancers, which could lead to early specific treatments. Because of the important heterogeneity of IPCC determination in reported studies, no treatment have been proposed to patients with positive IPCC. Herein, we provide an overview of IPCC detection and its impact on recurrence and survival, and we suggest further multi-institutional studies to evaluate new treatment strategies. PMID:24616569
Passot, Guillaume; Mohkam, Kayvan; Cotte, Eddy; Glehen, Olivier
Free cancer cells can be detected in peritoneal fluid at the time of colorectal surgery. Peritoneal lavage in colorectal surgery for cancer is not used in routine, and the prognostic significance of intraperitoneal free cancer cells (IPCC) remains unclear. Data concerning the technique of peritoneal lavage to detect IPCC and its timing regarding colorectal resection are scarce. However, positive IPCC might be the first step of peritoneal spread in colorectal cancers, which could lead to early specific treatments. Because of the important heterogeneity of IPCC determination in reported studies, no treatment have been proposed to patients with positive IPCC. Herein, we provide an overview of IPCC detection and its impact on recurrence and survival, and we suggest further multi-institutional studies to evaluate new treatment strategies.
An herbal extract used for centuries to prevent heart disease has now been shown to be effective against colorectal cancer when tested in laboratory cell cultures. From left to right: Weidong Li, principal investigator, China Academy of Chinese Medic
Formica, Vincenzo; Cereda, Vittore; Nardecchia, Antonella; Tesauro, Manfredi; Roselli, Mario
The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal