PSYCHO-ONCOLOGY, Issue 2 2009
Suzanne K. Steginga
Abstract Objective: The present study prospectively assessed the influence of medical, socio-demographic, psychological, and lifestyle variables on physical, social/family, emotional, functional well-being and colorectal cancer-specific concerns in a population-based sample of colorectal cancer survivors. Methods: Participants (n=1822) were assessed at 6 and 24 months post-diagnosis. Predictor variables assessed at 6 months included socio-demographic and medical variables, symptoms/side-effects, body mass index, physical activity, optimism, social support, and cancer threat appraisal. Quality of life (QOL) was assessed at 6 and 24 months post-diagnosis using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C). Results: For each QOL subscale and for the overall FACT-C scale, 6 month scores were the strongest predictor of QOL scores at 24 months post-diagnosis (e.g. ,=0.447, p < 0.001 for overall QOL). Socio-demographic, medical, and psychosocial variables, but not lifestyle variables, differentially predicted domain specific QOL. Only cancer threat appraisal was associated with all five QOL domains. Conclusion: Cancer threat appraisal presents as a potentially modifiable variable for interventions seeking to improve QOL. Symptom management and lifestyle strategies to ameliorate the effects of co-morbidities, disease stage and troublesome symptoms such as faecal incontinence on QOL should also be included. Copyright © 2008 John Wiley & Sons, Ltd. [source]

HNF1B and JAZF1 genes, diabetes, and prostate cancer risk,

THE PROSTATE, Issue 6 2010
Victoria L. Stevens
Abstract BACKGROUND Epidemiologic studies have shown that men with type II diabetes have a lower risk of prostate cancer than non-diabetic men. Recently, common variants in two genes, HNF1B and JAZF1, were found to be associated with both of these diseases. METHODS We examined whether the relationship between HNF1B and JAZF1 variants and decreased prostate cancer risk may potentially be mediated through diabetes in two large prospective studies, the Cancer Prevention Study II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. RESULTS Three HNF1B SNPS, rs11649743, rs4430796, and rs7501939, were associated with decreased risk of prostate cancer and were also associated, with marginal statistical significance, with increased risk of diabetes. The JAZF1 SNPs rs6968704 and rs10486567 were associated with decreased risk of prostate cancer but were not associated with diabetes. All five SNP,prostate cancer relationships did not substantially differ when the analyses were stratified by diabetic status or when diabetic status was controlled for in the model. Furthermore, the association of diabetes with prostate cancer was not altered when the SNPs were included in the logistic model. CONCLUSIONS These findings indicate that the HNF1B variants are directly associated with both diabetes and prostate cancer, that diabetes does not mediate these gene variant,prostate cancer relationships, and the relationship between these diseases is not mediated through these gene variants. Prostate 70: 601,607, 2010. © 2009 Wiley-Liss, Inc. [source]

Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate carcinoma

THE PROSTATE, Issue 6 2010
Jessica Lubahn
Abstract BACKGROUND Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. METHODS We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. RESULTS The H allele was associated with a reduced risk of aggressive PCa (ORper allele,= 0.67, 95% CI: 0.54,0.83, Ptrend,=,0.0003). The results were similar for European-Americans (ORper allele,=,0.68; 95% CI: 0.54,0.86) and African-Americans (ORper allele,=,0.61; 95% CI: 0.34,1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases ORper allele,=,0.94; 95% CI: 0.79,1.11; localized, low-grade disease ORper allele,=,0.98; 95% CI: 0.79,1.23; and aggressive disease ORper allele,=,0.73; 95% CI: 0.50,1.07). CONCLUSION These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype. Prostate 70: 646,653, 2010. © 2009 Wiley-Liss, Inc. [source]

Six of the Best, Colorectal 29,34

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue S1 2004
Article first published online: 3 JUN 200
No abstract is available for this article. [source]

Six of the Best, Colorectal 22,27

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue S1 2003
Article first published online: 1 MAY 200
No abstract is available for this article. [source]

Six of the Best, Colorectal 20

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue S1 2002
D.L. Francis
Aims: Surgical resection is the only potential cure for patients with colorectal liver metastases (CLM), but patient selection relies on accurate preoperative staging. The aim of this study was to assess the accuracy of routinely using whole-body FDG-PET (WBPET) for preoperative staging of patients being considered for resection of CLM. Methods: A prospective study of patients referred for possible hepatic resection was undertaken. Patients were initially staged by spiral CT and subsequently underwent WBPET. These modalities were considered independently before findings were compared and a decision regarding patient management was made. Accuracy of each modality was compared with histology, clinical/radiological follow-up or operative findings if appropriate. Results: Twenty-nine patients were recruited. Ten solitary CLM were correctly identified by both WBPET and CT. Nineteen patients had multiple CLM or extrahepatic disease, of these CT correctly staged seven patients (36 per cent), understaged 10 patients (53 per cent) and overstaged two (11 per cent). WBPET correctly staged 18 patients (95 per cent) and overstaged just one (5 per cent). WBPET was more sensitive and specific (100 and 92 per cent, respectively) for detecting multiple CLM and extrahepatic disease compared to CT (41 and 83 per cent). As a result of routine WBPET, patient management was altered in 10 patients (34 per cent), of whom four (14 per cent) avoided inappropriate surgery. Conclusions: WBPET is both more sensitive and specific in the preoperative staging of CLM, and we recommend its inclusion in the management algorithm of all patients being considered for hepatic resection. Altered patient management such as avoiding inappropriate laparotomy may also ultimately lead to financial savings. [source]

Six of the Best, Colorectal 21

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue S1 2002
I. Taylor
Aims: Intrahepatic arterial (IHA) therapy should deliver higher doses of drug to the liver with reduced overall systemic exposure. An IHA regimen was designed which used the same drugs and schedule, and achieved similar toxicity and steady-state venous 5FU levels as the standard de Gramont IV regimen. Patients with advanced colorectal liver metastases were randomized to either IV or IHA. Methods: In total 290 patients were randomized from 16 centres in 6 years. The median age was 62 years, 70 per cent were male, 68 per cent had colon cancer. Of the 145 patients allocated to IV, 14 per cent did not receive any allocated therapy, but 78 per cent received six cycles of chemotherapy. Of the 145 IHA patients, 37 per cent did not start and only 35 per cent received six cycles. The additional problems in the IHA group were inability to insert the catheter, or infected, leaking, or blocked catheters. Of the patients who did not receive six cycles of IHA therapy, 52 per cent switched to IV therapy. Similar levels of toxicity and quality of life were reported in both arms. Results: There was no clear evidence of a difference in progression-free survival (HR 0.90, 95 per cent CI: 0.71,1.16; P = 0.42) or overall survival (HR 1.03, 95 per cent CI: 0.79,1.33; P = 0.85). From randomization median, and estimated 1- and 2-year survival were 14.1 months in both groups, and 60 and 57 per cent, and 26 and 22 per cent for IV and IHA, respectively. Conclusions: This trial suggests that there is no obvious role for this IHA regimen in the management of hepatic metastatic colorectal cancer. [source]

Cancer patients' satisfaction with communication, information and quality of care in a UK region

EUROPEAN JOURNAL OF CANCER CARE, Issue 1 2005
R. DAVIDSON bsc, abps. consultant clinical psychologist , dphil., msc (clin. psych.)
Effective patient,professional communication can be of crucial importance to long-term psycho-social outcomes in patients with cancer. This study identifies patient satisfaction with regard to various aspects of communication and perceived quality of care. A well-validated questionnaire was administered to 435 cancer patients throughout Northern Ireland during a 3-month period. Northern Ireland can be regarded as a typical UK region in terms of cancer service configuration. The cohort consisted of patients with breast, colorectal, lung, prostate, gynaecological and gastric cancers. There was a 78% response rate. Satisfaction scores were individually calculated for various aspects of care, particularly diagnosis, treatment, follow-up and overall care. Non-parametric analysis examined the interaction between satisfaction scores and primary tumour site, age and gender. While overall satisfaction scores were relatively high, there was considerable variation. Of particular note was the interaction between perceived satisfaction and quality of care, communication, tumour site and age. Key findings are that there are a number of issues with regard to information and communication which can be clearly improved within Northern Ireland cancer services. The paper concludes that patient,professional communication should be tailored to meet individual need. [source]

Statistical behavior of complex cancer karyotypes

GENES, CHROMOSOMES AND CANCER, Issue 4 2005
Mattias Höglund
Epithelial tumors commonly show complex and variable karyotypes that obscure the identification of general patterns of the karyotypic evolution. To overcome some of these problems, we previously systematically analyzed the accumulated cytogenetic data from individual tumor types by using various statistical means. In the present study, we compare previous results obtained for nine tumor types and perform several meta-analyses of data obtained from a number of epithelial tumors, including head and neck, kidney, bladder, breast, colorectal, ovarian, and lung cancer, as well as from malignant melanoma and Wilms tumor, with the specific aim of discovering common patterns of karyotypic evolution. We show that these tumors frequently develop through a hypo- or a hyperdiploid pathway and progress by an increasing number of alternative imbalances through at least two karyotypic phases, Phases I and II, and possibly through a third, Phase III. During Phase I, the karyotypes exhibited a power law distribution of both the number of changes per tumor and the frequency distribution at which bands were involved in breaks. At the transition from Phase I to Phase II/III, the observed power law distributions were lost, indicating a transition from an ordered and highly structured process to a disordered and chaotic pattern. The change in karyotypic orderliness at the transition from Phase I to Phase II/III was also shown by a drastic difference in karyotypic entropy. © 2005 Wiley-Liss, Inc. [source]

Preventive medicine beyond 65

GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2 2006
Lionel S. Lim
Preventive health care in adults aged 65 and older is essential to ensure that quality of life is maintained with longevity. The first half of this article will focus on the two major causes of mortality in the US adult population: cancer and cardiovascular disease. We will address current screening and chemoprevention issues pertaining to breast, cervical, colorectal, prostate and skin cancer. For cardiovascular disease prevention, we will discuss the importance of screening for and treating hypertension, hyperlipidemia, diabetes mellitus, and the use of aspirin chemoprophylaxis and angiotensin-converting enzyme inhibition. In the latter half, we will discuss other aspects of preventive health care including fall prevention, motor vehicle safety, immunizations and screening issues. Health screening can help detect conditions like osteoporosis, subclinical thyroid disease, hearing impairment, nutritional status, and oral and dental problems. Finally, we will also address psychosocial health issues that affect older people including dementia, depression, elder abuse, lifestyle habits and advanced directives. Our recommendations are based on the latest available evidence and include the US Preventive Services Task Force and other leading health professional organizations. [source]

Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas

HISTOPATHOLOGY, Issue 1 2010
Michael G A Norwood
Norwood M G A, Bailey N, Nanji M, Gillies R S, Nicholson A, Ubhi S, Darnton J J, Steyn R S, Womack C, Hughes A, Hemingway D, Harrison R, Waters R & Jankowski J A (2010) Histopathology,57, 101,111 Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas Aims:, ,-Catenin is an important molecule in cancer biology. Membranous ,-catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. Methods and results:, Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess ,-catenin expression. Increasing ,-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of ,-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer. Conclusions:, This is one of the largest prognostic studies of ,-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic ,-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic ,-catenin could be used as a prognostic marker for less aggressive disease. [source]

Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease

INFLAMMATORY BOWEL DISEASES, Issue 9 2010
Udayakumar Navaneethan MD
Abstract Abstract: Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated. (Inflamm Bowel Dis 2010) [source]

Multiple serological biomarkers for colorectal cancer detection

INTERNATIONAL JOURNAL OF CANCER, Issue 7 2010
Chung-Chuan Chan
Abstract The aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumor-associated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor-associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme-linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY-CO-16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (,5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early-stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer-associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor-associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early-stage patients. [source]

Cancer survival in Germany and the United States at the beginning of the 21st century: An up-to-date comparison by period analysis

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2007
Adam Gondos
Abstract Transatlantic cancer survival comparisons are scarce and involve mostly aggregate European data from the late 1980s. We compare the levels of cancer patient survival achieved in Germany and the United States (US) by the beginning of the 21st century, using data from the Cancer Registry of Saarland/Germany and the SEER Program of the US. Age-adjusted 5- and 10-year relative survival for 23 common forms of cancer derived by period analysis for the 2000,2002 period were calculated, with additional detailed age- and stage-specific analyses for cancers with the highest incidence. Among the 23 cancer sites, 5 (10) year relative survival was significantly higher for 1 (2) and 8 (5) cancers in Germany and the US, respectively. In Germany, survival was significantly higher for patients with stomach cancer, whereas survival was higher in the US for patients with breast, cervical, prostate, colorectal and oral cavity cancer. Among the most common cancers, age-specific survival differences were particularly pronounced for older patients with breast, colorectal and prostate cancer. Survival advantages of breast cancer patients in the US were mainly due to more favorable stage distributions. This comprehensive survival comparison between Germany and the US suggests that although survival was similar for the majority of the compared cancer sites, long-term prognosis of patients continues to be better in the US for many of the most common forms of cancer. Among these, differences between patients with breast and prostate cancer are probably due to more intensive screening activities. © 2007 Wiley-Liss, Inc. [source]

A history of cancer in the husband does not increase the risk of breast cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2006
Eva Negri
Abstract Spouses share the home environment, and dietary and other lifestyle habits. Furthermore, a cancer diagnosis in the husband is a stressful event for the wife also. Thus, a history of cancer in the husband may be an indicator of breast cancer risk. We investigated the issue in a large Italian multicentric case-control study on 2,588 women with incident breast cancer and 2,569 female hospital controls, admitted for acute, non neoplastic diseases. The adjusted odds ratio (OR) was 1.0 (95% confidence interval, CI, 0.7,1.4) for a history of any type of cancer in the husband, 1.0 (95% 0.4,2.7) for stomach, 0.7 (95% 0.2,2.3) for intestinal (chiefly colorectal), 0.9 (95% CI 0.5,1.7) for lung, and 1.3 (95% CI 0.4,4.3) for prostate cancer. The OR was close to unity also when data were analyzed in separate strata of patient's or husband's age, patient's education, or vital status of the husband. This study suggests that women whose husband had a diagnosis of cancer are not at increased risk of breast cancer, although results for individual cancer sites should be interpreted with caution, due to small numbers. © 2006 Wiley-Liss, Inc. [source]

Dietary acrylamide and human cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2006
Claudio Pelucchi
Abstract Low levels of acrylamide have been found in several foods cooked at high temperatures. While there is sufficient evidence for the carcinogenicity of acrylamide in experimental animals, the few epidemiologic studies conducted to date on occupational and dietary exposure to acrylamide have found no consistent evidence of association with human cancer risk. Using data from an integrated network of Italian and Swiss hospital-based case-control studies, we analyzed the relation between dietary acrylamide intake and cancers of the oral cavity and pharynx (749 cases, 1,772 controls), esophagus (395 cases, 1,066 controls), large bowel (1,394 cases of colon, 886 cases of rectal cancer, 4,765 controls), larynx (527 cases, 1,297 controls), breast (2,900 cases, 3,122 controls), ovary (1,031 cases, 2,411 controls) and prostate (1,294 cases, 1,451 controls). All the studies included incident, histologically confirmed cancer cases and controls admitted to the same network of hospitals for acute nonneoplastic conditions. We calculated odds ratios (ORs) using multivariate logistic regression models, adjusted for energy intake and other major covariates of interest. The ORs for the highest versus the lowest quintile of acrylamide intake were 1.12 (95% CI = 0.76,1.66) for cancer of the oral cavity/pharynx, 1.10 (95% CI = 0.65,1.86) for esophageal, 0.97 (95% CI = 0.80,1.18) for colorectal, 1.23 (95% CI = 0.80,1.90) for laryngeal, 1.06 (95% CI = 0.88,1.28) for breast, 0.97 (95% CI = 0.73,1.31) for ovarian and 0.92 (95% CI = 0.69,1.23) for prostate cancer. None of the trend in risk was significant. This uniquely large and comprehensive data set does not show any consistent association between intake of acrylamide and the risk of breast and several other common cancers. © 2005 Wiley-Liss, Inc. [source]

Anti-tumor efficacy of the nucleoside analog 1-(2-deoxy-2-fluoro-4-thio-,-D-arabinofuranosyl) cytosine (4,-thio-FAC) in human pancreatic and ovarian tumor xenograft models

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2005
Deborah A. Zajchowski
Abstract 1-(2-Deoxy-2-fluoro-4-thio-,- D -arabinofuranosyl) cytosine (4,-thio-FAC) is a deoxycytidine analog that has been shown previously to have impressive anti-proliferative and cytotoxic effects in vitro and in vivo toward colorectal and gastric tumors. In our present studies, the pharmacokinetic behavior in nude mice and the effectiveness of 4,-thio-FAC against human pancreatic and ovarian tumor growth were assessed in comparison with standard chemotherapeutic agents. Potent in vitro anti-proliferative effects were observed against pancreatic (Capan-1, MIA-PaCa-2, BxPC-3) and ovarian (SK-OV-3, OVCAR-3, ES-2) cancer cell lines with IC50 of 0.01,0.2 ,M. In vivo anti-tumor activity was evaluated in nude mice bearing subcutaneously (s.c.) implanted human pancreatic tumor xenografts or intraperitoneally (i.p.) disseminated human ovarian xenografted tumors. Oral daily administration of 4,-thio-FAC for 8,10 days significantly inhibited the growth of gemcitabine-resistant BxPC-3 pancreatic tumors and induced regression of gemcitabine-refractory Capan-1 tumors. 4,-Thio-FAC was also a highly effective inhibitor of ovarian peritoneal carcinomatosis. In the SK-OV-3 and ES-2 ovarian cancer models, 4,-thio-FAC prolonged survival to a greater extent than that observed with gemcitabine. Furthermore, the superiority of 4,-thio-FAC to carboplatin and paclitaxel was demonstrated in the ES-2 clear cell ovarian carcinoma model. Studies provide evidence that 4,-thio-FAC is a promising new alternative to gemcitabine and other chemotherapeutic drugs in the treatment of a variety of tumor indications, including pancreatic and ovarian carcinoma. © 2004 Wiley-Liss, Inc. [source]

SELECT shows no effect on prostate cancer prevention

INTERNATIONAL JOURNAL OF UROLOGICAL NURSING, Issue 1 2009
Lawrence Drudge-Coates
Abstract To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. Oral selenium (200 ,g/d from L -selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-, -tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. Number of men diagnosed with prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men. [source]

Statins, stem cells, and cancer

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009
Kalamegam Gauthaman
Abstract The statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) were proven to be effective antilipid agents against cardiovascular disease. Recent reports demonstrate an anticancer effect induced by the statins through inhibition of cell proliferation, induction of apoptosis, or inhibition of angiogenesis. These effects are due to suppression of the mevalonate pathway leading to depletion of various downstream products that play an essential role in cell cycle progression, cell signaling, and membrane integrity. Recent evidence suggests a shared genomic fingerprint between embryonic stem cells, cancer cells, and cancer stem cells. Activation targets of NANOG, OCT4, SOX2, and c-MYC are more frequently overexpressed in certain tumors. In the absence of bona fide cancer stem cell lines, human embryonic stem cells, which have similar properties to cancer and cancer stem cells, have been an excellent model throwing light on the anticancer affects of various putative anticancer agents. It was shown that key cellular functions in karyotypically abnormal colorectal and ovarian cancer cells and human embryonic stem cells are inhibited by the statins and this is mediated via a suppression of this stemness pathway. The strategy for treatment of cancers may thus be the targeting of a putative cancer stem cell within the tumor with specific agents such as the statins with or without chemotherapy. The statins may thus play a dual prophylactic role as a lipid-lowering drug for the prevention of heart disease and as an anticancer agent to prevent certain cancers. This review examines the relationship between the statins, stem cells, and certain cancers. J. Cell. Biochem. 106: 975,983, 2009. © 2009 Wiley-Liss, Inc. [source]

Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2002
Eugene P. Goldberg
The recent literature documents the growing interest in local intratumoral chemotherapy as well as systemic preoperative chemotherapy with evidence for improved outcomes using these therapeutic modalities. Nevertheless, with few exceptions, the conventional wisdom and standard of care for clinical and surgical oncology remains surgery followed by radiation and/or systemic chemotherapy, as deemed appropriate based on clinical findings. This, in spite of the fact that the toxicity of conventional systemic chemotherapy and immunotherapy affords limited effectiveness and frequently compromises the quality of life for patients. Indeed, with systemic chemotherapy, the oncologist (and the patient) often walks a fine line between attempting tumour remission with prolonged survival and damaging the patient's vital functions to the point of death. In this context, it has probably been obvious for more than 100 years, due in part to the pioneering work of Ehrlich (1878), that targeted or localized drug delivery should be a major goal of chemotherapy. However, there is still only limited clinical use of nonsystemic intratumoral chemotherapy for even those high mortality cancers which are characterized by well defined primary lesions i.e. breast, colorectal, lung, prostate, and skin. There has been a proliferation of intratumoral chemotherapy and immunotherapy research during the past two to three years. It is therefore the objective of this review to focus much more attention upon intratumoral therapeutic concepts which could limit adverse systemic events and which might combine clinically feasible methods for localized preoperative chemotherapy and/or immunotherapy with surgery. Since our review of intratumoral chemo-immunotherapy almost 20 years ago (McLaughlin & Goldberg 1983), there have been few comprehensive reviews of this field; only one of broad scope (Brincker 1993), three devoted specifically to gliomas (Tomita 1991; Walter et al. 1995; Haroun & Brem 2000), one on hepatomas (Venook 2000), one concerning veterinary applications (Theon 1998), and one older review of dermatological applications (Goette 1981). However, none have shed light on practical opportunities for combining intratumoral therapy with subsequent surgical resection. Given the state-of-the-art in clinical and surgical oncology, and the advances that have been made in intratumoral drug delivery, minimally invasive tumour access i.e. fine needle biopsy, new drugs and drug delivery systems, and preoperative chemotherapy, it is timely to present a review of studies which may suggest future opportunities for safer, more effective, and clinically practical non-systemic therapy. [source]

"Spontaneous," delayed colon and rectal anastomotic complications associated with bevacizumab therapy

JOURNAL OF SURGICAL ONCOLOGY, Issue 2 2008
David A. August MD
Abstract Bevacizumab, a humanized monoclonal antibody used to treat recurrent and metastatic colorectal cancer, targets the vascular endothelial growth factor (VEGF) molecule. It is hypothesized that bevacizumab works by both depriving tumors of the neovascularity they require to grow, and by improving local delivery of chemotherapy through alterations of tumor vasculature permeability and Starling forces. Complications of bevacizumab treatment include bowel ischemia and perforation, but to date, these complications have only rarely been described as occurring at the site of presumably healed anastomoses following surgery. We report two cases of delayed, "spontaneous" low anterior colorectal anastomotic dehiscence and one right colon anastomotic colocutaneous fistula associated with bevacizumab therapy. After seeing three patients with complications arising from apparently healed low anterior colorectal or right colon anastomoses following initiation of bevacizumab therapy for treatment of metastatic colorectal cancer, we reviewed the experience of The Cancer Institute of New Jersey (CINJ) with use of bevacizumab in approximately 50 patients between April 2004 and December 2006. The three index cases had been treated surgically at CINJ but received chemotherapy elsewhere. None of the 50 patients receiving bevacizumab at CINJ who had previous colon or rectal anastomoses were identified as having this complication. The medical records of the three index cases were reviewed and analyzed. Additionally, a Medline search was performed to identify other reports documenting similar cases. Two reports of related cases were found in the literature. In two of our index cases who underwent low anterior anastomoses, the patients had received preoperative pelvic irradiation before their initial low anterior resection. In one of the two cases, the initial resection was complicated by an anastomotic leak requiring proximal diversion and then subsequent stoma takedown. In both cases, the dehiscence occurred more than 1 year after anastomosis, and became evident 1,10 months following initiation of bevacizumab treatment. In the third index case, a colocutaneous fistula arising from the anastomotic site presented 5 months following right colon resection and 3 months after starting adjuvant systemic therapy with FOLFOX (5-fluorouracil (5-FU), leucovorin, and oxaliplatin) and bevacizumab. Delayed colorectal anastomotic complications may occur in association with bevacizumab therapy. Contributing factors may include anastomotic leak at the time of the original operation and history of anastomotic irradiation. Clinicians treating patients who receive bevacizumab following colectomy for colorectal cancer should be aware of this possible life-threatening complication. These findings may also be relevant to the design of trials of the use of bevacizumab for the postoperative adjuvant treatment of patients with colorectal cancer. J. Surg. Oncol. 2008;97:180,185. © 2007 Wiley-Liss, Inc. [source]

Peritoneal carcinomatosis from colorectal or appendiceal origin: Correlation of preoperative CT with intraoperative findings and evaluation of interobserver agreement

JOURNAL OF SURGICAL ONCOLOGY, Issue 2 2004
Eelco de Bree MD
Abstract Background and Objectives In patients with colorectal cancer, it is important to diagnose peritoneal carcinomatosis as well as to detect location and size of peritoneal tumor dissemination in view of treatment planning. The aim of this study was to investigate the detection accuracy of computed tomography (CT). Methods Preoperative CT-scans from 25 consecutive patients with peritoneal carcinomatosis from colorectal or appendiceal origin were independently blindly reviewed by 2 radiologists. The presence and diameter of tumor deposits were noted in seven abdominopelvic areas. Intraoperative findings were regarded as the gold standard. Agreement was assessed using the Kappa index and the chi-square test. Results The presence of peritoneal carcinomatosis was detected in 60 and 76% of those patients by each of the radiologist. Detection of individual peritoneal implants was poor (,,=,0.11/0.23) and varied from 9.1%/24.3% for tumor size <1 cm to 59.3%/66.7% for tumor size >5 cm. Overall sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) for tumor involvement per area were 24.5%/37.3%, 94.5%/90.4%, 53.0%/60.0%, 86.2%/84.4%, and 47.3%/50.8%, respectively. Accuracy of tumor detection varied widely per anatomic site. Statistically significant interobserver differences were noted, specifically for tumor size of 1,5 cm (P,=,0.007) and localization on mesentery and small bowel (,,=,0.30, P,=,0.04). Conclusions In colorectal cancer, CT detection of peritoneal carcinomatosis is moderate and of individual peritoneal tumor deposits poor. Interobserver differences are statistically significant. Therefore, preoperative CT seems not to be a reliable tool for detection of presence, size, and location of peritoneal tumor implants in view of treatment planning in patients with colorectal cancer. J. Surg. Oncol. 2004;86:64,73. © 2004 Wiley-Liss, Inc. [source]

Maximum likelihood inference on a mixed conditionally and marginally specified regression model for genetic epidemiologic studies with two-phase sampling

JOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 2 2007
Nilanjan Chatterjee
Summary., Two-phase stratified sampling designs can reduce the cost of genetic epidemiologic studies by limiting expensive ascertainments of genetic and environmental exposure to an efficiently selected subsample (phase II) of the main study (phase I). Family history and some covariate information, which may be cheaply gathered for all subjects at phase I, can be used for sampling of informative subjects at phase II. We develop alternative maximum likelihood methods for analysis of data from such studies by using a novel regression model that permits the estimation of ,marginal' risk parameters that are associated with the genetic and environmental covariates of interest, while simultaneously characterizing the ,conditional' risk of the disease associated with family history after adjusting for the other covariates. The methods and appropriate asymptotic theories are developed with and without an assumption of gene,environment independence, allowing the distribution of the environmental factors to remain non-parametric. The performance of the alternative methods and of sampling strategies is studied by using simulated data involving rare and common genetic variants. An application of the methods proposed is illustrated by using a case,control study of colorectal adenoma embedded within the prostate, lung, colorectal and ovarian cancer screening trial. [source]

Serum bilirubin and colorectal cancer risk: a population-based cohort study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2006
G. N. IOANNOU
Summary Background Bilirubin has antioxidant properties and has been postulated to protect against the development of malignancies. Aim To investigate whether baseline serum bilirubin concentration predicts the incidence of colorectal cancer in a nationally representative sample of the US population. Methods Participants of the first National Health and Nutrition Examination Survey were divided into four groups based on quartiles of baseline serum bilirubin concentration in mg/dL: <0.38 (n = 1410), 0.38 to <0.5 (n = 1287), 0.5 to <0.6 (n = 1048) and ,0.6 (n = 1742). The incidence of colorectal cancer during the following 20 years was determined from hospitalization records and death certificates. Results 110 cases of colorectal cancer-related death or hospitalization were identified among 5487 participants during 88 339 person-years of follow-up (12 per 10 000 person-years). There was no association between baseline serum bilirubin concentration and the incidence of colorectal cancer either in unadjusted analyses or after adjusting for age, gender, ethnicity, smoking, body mass index, alcohol consumption and educational attainment. Conclusions Baseline serum bilirubin concentration did not predict the subsequent incidence of colorectal cancer in this population-based cohort study. [source]

Novel Types of Carborane-Carrier Hyaluronan Derivatives via "Click Chemistry",

MACROMOLECULAR BIOSCIENCE, Issue 7 2008
Chiara Di Meo
Abstract Two new HA derivatives bearing carborane rings were synthesized by click chemistry. The optimal conditions were assessed for the preparation of biocompatible boron carriers, potentially suitable for application in BNCT and capable of targeting the CD44 antigen. The new polymeric samples were characterized by means of NMR-spectroscopy techniques that gave degrees of 17 and 8% for HAAACB and HapACB, respectively. Both HAAACB and HApACB turned out to be nontoxic for colorectal, ovarian and bladder tumor cell lines, to disclose a specific interaction with the CD44 antigen as the native hyaluronan moiety, and to deliver boron-atom concentrations largely sufficient for BNCT therapy when accumulated in cancer cells. [source]

Cancer Pain: An Age-Based Analysis

PAIN MEDICINE, Issue 10 2010
Carmen R. Green MD
Abstract Objective., Although cancer pain (consistent and breakthrough pain [BTP; pain flares interrupting well-controlled baseline pain]) is common among cancer patients, its characteristics, etiology, and impact on health-related quality of life (HRQOL) across the lifespan are poorly understood. Design., This longitudinal study examines age-based differences and pain-related interference in young and old patients with cancer-related pain over 6 months. Patients in the community with stage III or IV breast, prostate, colorectal, or lung cancer, or stage II,IV multiple myeloma with BTP completed surveys (upon initial assessment, 3 and 6 months) assessing consistent pain, BTP, depressed affect, active coping ability, and HRQOL using previously validated measures. Results., Respondents (N = 96) were 70% white and 66% female, with a mean age of 57 ± 10 years. There were no significant differences in pain severity based upon age. However, the younger group experienced more pain flares with greater frequency (P = 0.05). The oldest group had better emotional functioning at baseline but worse physical functioning at 6 months. Younger groups also had worse cognitive functioning at 6 months (P = 0.03). Pain interference was independent of age. Conclusions., These data provide evidence for the significant toll of cancer pain on overall health and well-being of young and old adults alike but demonstrate an increased toll for younger adults (especially financially). Beyond race and gender disparities, further health care disparities in the cancer and cancer pain were identified by age, illustrating the need for additional research across the lifespan in diverse cancer survivors. [source]

Latest news and product developments

PRESCRIBER, Issue 20 2007
Article first published online: 26 NOV 200
GPs and pharmacists to work more closely Closer working between GPs and community and primary-care pharmacists ,could further improve prescribing quality and therapeutic outcomes for patients', according to a report by the London School of Pharmacy and Alliance Boots. The report suggests that the expansion of primary-care centres and the increasing complexity of care they offer mean that community pharmacists will increasingly need to take on some GP roles. It foresees an increase in shared premises and calls for closer interdisciplinary working between GPs, pharmacists and nurses. Variation in PCT commissioning of enhanced services from pharmacies has resulted in ,a fragmented system of postcode pharmaceutical care rationing'. Full read-write access to patients' records will be essential if the benefits of electronic prescribing are to be realised. How pharmacists can support commissioners The NHS Alliance and Primary Care Pharmacists' Association have published a guide for practice-based commissioners on making the most of primary-care pharmacists. Prescribing Support and Prescribing Advice for Practice Based Commissioners , A Guide for Commissioning Groups and GPs illustrates how pharmacists can support commissioners at all levels of medicines use. Copies are free to NHS Alliance members and cost £10 for others. Directory website aids diabetes management The National Diabetes Support Team is developing a website that brings together different datasets and tools for diabetes management. The Diabetes Data Directory (www.yhpho.org.uk/diabetesdatadirectory/introddd.asp) summarises what other online databases can provide and lists the tools that can be used to answer specific questions. The first edition is now online, providing direct links to the appropriate sites. Flu vaccine efficacy in older people challenged US reviewers have questioned the effectiveness of flu vaccine in older people (Lancet Infect Dis online: 24 September; doi: 10.1016/ S1473-3099(07)70236-0). They were unable to confirm a reduction in flu mortality since 1980, concluding that biased patient selection and nonspecific end-points such as all-cause mortality may have exaggerated the benefits of vaccination in clinical trials. The Department of Health is encouraging younger people in at-risk groups to be vaccinated against flu this winter; last year, 58 per cent of under-65s at risk were not vaccinated. OC cervical cancer risk probably overestimated Recent evidence that oral contraceptives may be associated with a small increase in the incidence of cervical cancer probably overestimates the risk, says the Clinical Effectiveness Unit of the Faculty of Family Planning and Reproductive Health Care (www.ffprhc.org.uk). A recent study in the BMJ reported a 12 per cent reduced overall risk of cancer associated with oral contraceptives but an increased risk of cervical cancer of 38 per 100 000 woman-years after at least eight years' use. The FFPRHC says this study was conducted before the UK cervical screening programme was established, and at a time when the average Inhaled insulin ,unlikely to be cost effective' Inhaled insulin (Exubera) is safe and effective but costs so much more than injected insulin that it is unlikely to be cost effective, according to a new Health Technology Assessment (2007;11:No.33.www.hta.nhsweb.nhs.uk). The review included nine trials (seven of Exubera), in which the only significant difference between inhaled and injected soluble insulin was in patient preference. However, most of the trials used syringes for insulin injection rather than pens. The extra cost of inhaled insulin is put at between £600 and £1000 per year. New topics for NICE The Secretary of State for Health has referred the novel antihypertensive aliskiren (Rasilez) for appraisal by NICE; aliskiren is the first direct renin inhibitor to be introduced. Other referrals to NICE include five clinical guidelines (multiple pregnancy, transient loss of consciousness, lower UTI in men, post-ITU rehabilitation and colorectal and anal cancer). Topics for technology appraisals include cetuximab (Erbitux) for colorectal and head and neck cancers. QOF statistics for 06/07 GPs in England averaged 96.3 per cent of the maximum points available for the clinical domain of the Quality and Outcomes Framework in 2006/07 compared with 97.1 per cent previously, official statistics show. Mean practice scores for most clinical areas were in the mid-90 per cent range, but highest for obesity (100 per cent) and lowest for depression (81 per cent), palliative care (90 per cent), mental health and epilepsy (<95 per cent). NICE consulting on type 2 diabetes guideline NICE is consulting on its draft clinical guideline for the management of type 2 diabetes. Comments should be submitted online by 22 November; publication is scheduled for April 2008. The drug of first choice for glycaemic control is metformin, which should be considered even for patients who are not overweight; a sulphonylurea is an alternative or adjunctive agent if glycaemic control is not achieved with metformin alone. If these regimens fail, a glitazone may be added. Exenatide (Byetta) is recommended only for obese patients for whom other oral treatments have failed. The guidance will update and replace clinical guidelines E, F, G and H, and technology appraisals 53, 60 and 63. Glitazones increase risk of HF but not CV death A new meta-analysis , this time of seven trials involving a total of 20 191 patients with type 2 diabetes or impaired glucose tolerance treated with a glitazone , has concluded that these agents are associated with an increased risk of heart failure but not cardiovascular death (Lancet 2007;370:1129,36). Compared with comparator drugs, glitazones were associated with an increased risk of congestive heart failure (2.3 vs 1.4 per cent; relative risk, RR, 1.72; number needed to harm over 30 months, 107). There was no heterogeneity between studies, showing that this is a class effect. However, the risk of cardiovascular death was not increased for either rosiglitazone (Avandia) or pioglitazone (Actos). Copyright © 2007 Wiley Interface Ltd [source]

Physical activity in cancer survivors: a field in motion

PSYCHO-ONCOLOGY, Issue 4 2009
Kerry S. Courneya
Abstract Physical activity (PA) is an important health behavior in almost any population but it may be particularly helpful for cancer survivors. Objective: To introduce this special issue on PA in cancer survivors and to provide a summary of its important contributions to the field. Methods: A brief historical review of PA research in cancer survivors followed by a narrative review of the articles published in this special issue. Results: This special issue contains 13 original articles reporting 15 studies on PA in cancer survivors. Just over half of the studies focus on breast cancer survivors, whereas the remainder focus on understudied cancer survivor groups such as lung, ovarian, colorectal, prostate, hematologic, and pediatric. Moreover, a majority of the studies focus on the survivorship phase of the cancer continuum. Perhaps the most distinctive feature of this special issue is the number of studies focusing on the determinants of PA. Taken together, the 13 articles make significant contributions in four areas: (1) randomized controlled trials of PA interventions with supportive care endpoints, (2) observational studies on the determinants of PA, (3) observational studies on the ,determinants of PA determinants', and (4) studies on methodological and feasibility issues related to conducting PA trials. Conclusions: PA research is making an important contribution to the health and well-being of cancer survivors across the entire cancer control continuum. This special issue builds on this momentum and provides the single largest collective contribution of knowledge to date in the field of PA in cancer survivors. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Psychosocial issues in genetic testing for familial adenomatous polyposis: a review of the literature

PSYCHO-ONCOLOGY, Issue 8 2008
K. F. L. Douma
Abstract Objectives: Familial adenomatous polyposis (FAP) is characterized by the development of multiple adenomas in the colon that can lead to colorectal cancer. Being a carrier for FAP is hypothesized to have a negative impact on psychosocial well-being. This paper reviews the current literature on the psychosocial aspects of FAP. Methods: Four literature databases were used to identify all papers published between 1986 and 2007 about psychosocial and behavioral issues in FAP related to genetic testing. The following topics were reviewed: uptake and psychosocial impact of genetic testing, endoscopic screening behavior and psychosocial well-being in general. Results: Seventeen papers were identified. Across studies, genetic test uptake varied between 62 and 97%. Two out of three studies showed clinical levels of anxiety and/or depression after genetic testing. A minority of individuals were not reassured by a negative test result, and intended to continue endoscopic surveillance. Well-being (e.g. quality of life, family functioning) was found to be lower in some studies, while comparable to the general population in other studies. The studies had several shortcomings, such as mixed patient population (e.g. colorectal and breast cancer) and small sample sizes, and provided no information on other potentially important issues, such as psychosexual development. Conclusions: Future studies should employ larger sample sizes and standardized measurements. Additionally, future studies should address the long-term consequences of genetic testing for FAP, psychosexual development and consequences of FAP for the family as a whole. Copyright © 2008 John Wiley & Sons, Ltd. [source]