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PubMed2001

Microsatellite instability as a tool for the classification of gastric cancer.

Microsatellite instability (MSI) is a common feature of gastric cancers that reflects underlying mismatch-repair deficiency in the tumor, caused most frequently by methylation of the hMLH1 promoter. Tumors with MSI have been found to inactivate certain target genes by permitting an increased frequency of mutations in mononucleotide runs in their coding regions. Gastric tumors with MSI have a distinct clinicopathological profile with a relatively good prognosis. Using the simple and robust methodologies available, MSI detection in gastrointestinal tumors promises to be one of the first widely used molecular prognostic tests for human cancer. Here, we review the molecular context of this exciting prospect with respect to one of the world's most prevalent cancers, that of the stomach.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to cholangiocarcinoma.

Human CYP1A2 and arylamine N-acetyltransferases, which are encoded by the polymorphic CYP1A2 and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between CYP1A2, NAT1 and NAT2 polymorphisms and cholangiocarcinoma (CCA), the most prevalent cancer in the north-east of Thailand. A total of 216 CCA patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two CYP1A2 alleles (CYP1A2*1A wild-type and *1F), six NAT1 alleles (NAT1*4 wild-type, *3, *10, *11, *14A and *14B) and seven NAT2 alleles (NAT2*4 wild-type, *5, *6A, *6B, *7A, *7B and *13), which are the major alleles found in most populations, were analysed. Although CYP1A2*1A allele, NAT1*10 allele, and the NAT2 slow acetylator alleles were not associated with CCA risk, among the male subjects, the genotype CYP1A2*1A/*1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with CYP1A2*1F/1*F. Frequency distributions of rapid NAT2*13 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower CCA risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the NAT2 polymorphism may be a modifier of individual risk to CCA.

Adult↗

PubMed1987

[Comparison of gastric mucosal lesions in high and low incidence areas of gastric cancer--analysis of 3146 operated gastric specimens and 112 autopsied samples. National Gastric Cancer Pathology Cooperative Group].

Gastric mucosal lesions, including 3146 gastric specimens resected for various benign diseases and 112 autopsied samples, in both high and low incidence areas of gastric cancer in China were analysed and compared. The results showed that, in high and low incidence areas of gastric cancer, the detection rate was 59.96% and 52.02% for chronic atrophic gastritis, 60.60% and 52.76% for intestinal metaplasia, 37.60% and 22.97% for atypical hyperplasia, 0.44% and 0.13% for microcarcinoma and small carcinoma of the stomach, 2.52% and 0.79% for gastric polyp. The data suggest that a positive correlation be present between the gastric mucosal lesions and gastric cancer. Prevalence of the gastric mucosal lesions in an area may be regarded as an indication of incidence of the gastric cancer. Microcarcinoma and small carcinoma of the stomach were 0.44% of the gastric specimens resected for benign diseases in high incidence area of gastric cancer, which indicates that more tissue sections will have to be taken for examination in order to avoid missing the early carcinoma.

Adolescent↗

PubMedDate not supplied

Human papillomavirus and cervical cancer from a prospective study in Khon Kaen, Northeast Thailand.

The risk of developing carcinoma of the cervix in women infected with human papillomavirus (HPV) was estimated in a nested case-control analysis of 33 cancers (invasive and in situ) and 113 controls, matched by age and sex, from an ongoing cohort study of lifestyle and cancer in a rural population of Northeast Thailand. Oncogenic HPV types were present in 10.8% of control women and in 31/33 of the carcinoma cases, corresponding to an odds ratio of 130.6 (95% CI 11.7-1457.0). There was no significant difference in risk between prevalent cancer cases (diagnosed less than 3 months after HPV testing) and incident cases (diagnosed an average of 2.1 years later). HPV 16 and 18 were the most prevalent oncogenic HPV types present. The results confirm that some two of three of cervical cancer cases in this population of Northeast Thailand are caused by HPV 16 and 18.

Adult↗

PubMed2000

Symposium overview: estrogens and antiestrogens in managing the patient with breast cancer.

The prevalence of breast cancer (a hormonally driven neoplasm) in the United States, the potential health benefits of estrogen replacement therapy for postmenopausal women, and the burgeoning research focusing on selective estrogen receptor modulators (SERMs) have resulted in additional complexity in managing breast cancer. In an attempt to clarify existing data, the Society of Surgical Oncology sponsored a symposium entitled "Estrogens and Antiestrogens in Managing the Patient with Breast Cancer" at its 52nd Annual Cancer Symposium. This conference was held in March 1999 and was chaired by Dr. S. Eva Singletary, Professor of Surgery and Chief of the Surgical Breast Section at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. The following is a review of the material presented by the symposium participants.

Age Factors↗

PubMed1978

Mycosis fungoides, nitrogen mustard and skin cancer.

The prevalence of epithelial cancer was determined in 202 patients with mycosis fungoides and the Sézary syndrome and was found to be 10.5%. In an attempt to establish a possible association with topically applied nitrogen mustard, it was noted that 4.0% of these patients had lesions prior to nitrogen mustard therapy (although over half subsequently developed further lesions) and 6.5% of the patients developed them de novo after therapy. In two patients in this latter group, malignancies developed in are as not usually associated with solar-induced cancer. These findings indicate that epidermal neoplasia is not uncommon in these patients and that nitrogen mustard may function as a carcinogen or a co-carcinogen.

Administration, Topical↗

PubMed2005

Detection of lung cancer by sensor array analyses of exhaled breath.

RATIONALE: Electronic noses are successfully used in commercial applications, including detection and analysis of volatile organic compounds in the food industry. OBJECTIVES: We hypothesized that the electronic nose could identify and discriminate between lung diseases, especially bronchogenic carcinoma. METHODS: In a discovery and training phase, exhaled breath of 14 individuals with bronchogenic carcinoma and 45 healthy control subjects or control subjects without cancer was analyzed. Principal components and canonic discriminant analysis of the sensor data was used to determine whether exhaled gases could discriminate between cancer and noncancer. Discrimination between classes was performed using Mahalanobis distance. Support vector machine analysis was used to create and apply a cancer prediction model prospectively in a separate group of 76 individuals, 14 with and 62 without cancer. MAIN RESULTS: Principal components and canonic discriminant analysis demonstrated discrimination between samples from patients with lung cancer and those from other groups. In the validation study, the electronic nose had 71.4% sensitivity and 91.9% specificity for detecting lung cancer; positive and negative predictive values were 66.6 and 93.4%, respectively. In this population with a lung cancer prevalence of 18%, positive and negative predictive values were 66.6 and 94.5%, respectively. CONCLUSION: The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose. The results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer.

Adult↗

PubMed2005

Development of novel diagnostic and prognostic molecular markers for sporadic colon cancer.

Gene expression studies are informative about changes in colon cancer, increase understanding of the biology of tumorigenesis and aid in developing diagnostic and prognostic markers. In this review, expression techniques used to examine the multistage process of colon cancer are discussed. Many genes have been found to differ in expression between normal and tumorigenic states, as early as the seemingly normal colonic crypts. The clinical usefulness of markers varies with stage, ethnicity and anatomic location of colon cancer. Thus, combinations of markers can be used to develop an approach to molecularly screen and follow the progression of this prevalent cancer.

Biomarkers, Tumor↗

PubMed1990

Counting the costs of mammography screening: first year results from the Sydney study.

Population-based mammography screening is a highly specialized service which aims to improve the early detection of breast cancer. This is achieved through the installation of a dedicated mix of medical technology and professional skills. It is therefore a resource-intensive activity so the benefits foregone by deploying these resources for mammography screening ought to be determined to investigate the relative efficiency of such a commitment. This paper describes the costing methodology used in the evaluation of the Sydney Breast X-ray Programme and presents the health service costs for the first 12 months of operation. In the first year when attendance was under 5000 it cost $118.93 to screen a woman, $13,817 to detect a cancer and $18,720 to detect an impalpable cancer. However, costs are expected to fall in subsequent years as attendance reaches capacity level. The first screening round will detect prevalent cancers; costs will change with subsequent screening rounds as incident cancers are detected. We are cautious in extrapolating the costs of a national programme from these results. However, on the basis of our data and disregarding treatment costs, a national programme which screened 70% of all Australian women over the age of 45 years every two years would add between $60 million and $100 million to the national health bill each year.

Aged↗

PubMed1991

30-year cancer trends in Jamaica. Kingston & St. Andrew (1958-1987).

A total of 19,225 malignant neoplasms were recorded in Kingston & St. Andrew, Jamaica over the 30-year period 1958-1987. The most prevalent cancers in males were those of prostate (12.2%), stomach (10.9%) and lung (10.7%). In females 24.1% of cancers occurred in breast and 20% were recorded for invasive carcinoma of the cervix. There is a steady improvement in the diagnosis of in situ cervical lesions, and a relative decline in the incidence of invasive lesions. Lung cancer in women remains at a low level. A significant decline in cancer of the oesophagus and stomach in both sexes was noted, while neoplasms of colon and rectum maintained a stable pattern. The 30-year trends of lymphomas and leukaemias have shown no increase, although there are changes in classification patterns.

Adolescent↗

PubMed2005

Preservation of prostate during radical cystectomy: evaluation of prevalence of prostate cancer associated with bladder cancer.

OBJECTIVES: To estimate the frequency and characteristics of prostatic lesions discovered incidentally in radical cystoprostatectomy specimens and to determine whether any factors would allow for the detection of prostate cancer preoperatively. METHODS: A total of 100 radical cystoprostatectomy specimens with orthotopic bladder reconstruction were performed for malignant bladder disease between 1990 and 2000. The mean patient age at surgery was 62 +/- 8 years (range 32 to 75). Digital rectal examination and prostate-specific antigen (PSA) assay were done routinely before surgery. During the 10-year study period, the same pathologist examined the prostatic tissues from radical cystoprostatectomy specimens using McNeal's technique on fine slices every 2.5 mm. RESULTS: The overall incidence of prostate cancer discovered incidentally in radical cystoprostatectomy specimens was 51%, of which 29% were microcancers (volume less than 0.5 cm3) and 22% were significantly larger (volume 0.5 cm3 or more). The mean Gleason score was 6. Of the tumors, 24% could be considered "clinically nonsignificant" (less than 0.5 cm3 and Gleason score less than 7). The mean preoperative PSA level was 4.13 +/- 1.36 ng/mL. Of 66 patients with a PSA level of less than 4 ng/mL (mean PSA 1.5 +/- 0.8) and a normal digital rectal examination before surgery, 50% had prostate cancer, of which 69% were microcancers. CONCLUSIONS: The prevalence of prostate cancer (51%) in our series is among the highest in published reports. Furthermore, our results stress that currently no factors are available to enable the detection of "clinically significant" prostate cancer preoperatively.

Adult↗

PubMed2003

Measures of benefit for breast screening from the pathology database for Scotland, 1991-2001.

AIMS: To examine pathology characteristics of breast cancers detected by mammography screening over 10 years in Scotland, and compare the nature of cancer yields after different levels of very small invasive cancer at prevalence detection. METHODS: A pathology database of cancers from mammography screening of women aged 50-64 years invited every three years was used to assess the variation over time in annual yield of different invasive cancer sizes. Screening centres were compared for incidence screen yields, according to sizes, histological type, grade, and node status. RESULTS: There was a significant trend over time for increased detection of < 15 mm cancers among 2353 prevalence cancers, and a significant trend for increase in all size groups, < 10, 10-14, < 15, and >or= 15 mm, among 2245 incidence cancers. Based on individual screening centres, there was a significant negative relation between proportions of very small (< 10 mm) cancers at prevalence screens and of large (>or= 15 mm) cancers at incidence screens of the same "cohort" three years later. There was no significant relation on the same centre basis for worse pathology characteristics (histological no special type, high grade, and positive node status) in cancers detected in the same "cohort" three years later. CONCLUSIONS: Sensitive mammography screening has a significant effect on the nature of yields at subsequent screens. Length of screening interval and consistency in pathologist opinions are factors that account for lack of effect on incidence cancer qualitative pathology characteristics. These issues are relevant to the use of such characteristics as surrogate measures of service screening performance.

Breast Neoplasms↗

PubMed1999

Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice.

Dietary manipulations to prevent cancer and other diseases of aging have drawn broad public and scientific attention. One indicator of this interest is that dehydroepiandrosterone (DHEA) supplements are widely consumed by those who hope that this hormone may keep them "younger longer." However, key data to support this belief are lacking. For example, the influence of DHEA treatment on spontaneous cancer and life span in healthy, long-lived strains of mice or rats is unknown. This is in contrast to the situation for caloric restriction (CR), which is known to oppose cancer development and increase maximum life span in rodents. To address this issue, we assigned 300 middle age (12-month-old) male C57BL/6 mice to one of four groups (n = 75 for each group) and evaluated them for longevity and spontaneous disease patterns. Two groups were fed a normal diet (ND), and two others were fed a calorie-restricted diet (RD). One ND group and one RD group were also given 25 microg/ml DHEA sulfate (DHEAS) in their drinking water. Although urine samples from DHEAS-treated mice contained 10-fold more DHEA and DHEAS than did samples from unsupplemented mice, DHEAS administration did not affect body weight, life span, or cancer patterns. The RD lowered body weight by 26% and increased maximum life span by approximately 15%. The incidence of the most prevalent cancer, plasma cell neoplasm, was higher in RD mice (66%) than in ND mice (41%). Thus, DHEAS, as administered here, influenced neither cancer nor longevity at two caloric intakes. In contrast, CR from middle age increased longevity, the age at which tumor-bearing mice died, and the percentage of mice dying with cancers, suggesting that CR may retard promotion and/or progression of existing lymphoid cancers.

Age Factors↗

PubMed2004

[Home palliative care--2 case reports: a long-term cancer pain management with transdermal fentanyl].

Transdermal Fentanyl was released in March 2002 in Japan after the acceptance of the insurance under the office of public health. Transdermal therapy is especially effective for patients having difficulty of oral intakes, and for home care cancer patients who suffer from chronic pain only if the therapy is feasible on the long-term basis. We report our cases for long-term cancer pain management with transdermal fentanyl. A total of 52 long-term patients with chronic cancer pain (28 men and 24 women with an average age of 63.5 years, range 46-74 years) were evaluated. The most prevalent cancers were colorectum (n=14), stomach (n=10), breast (n=8), esophagus (n=6), pancreas (n=6), and others. The duration of the transdermal therapy varied from minimum of 2 days to maximum of 630 days. Two patients on this therapy were longer than 500 days. The transdermal therapy was discontinued 2-37 days for 8 patients due to uncontrolled pain relief. Case report 1: A 72-year-old woman suffering from a relapse of pancreatic cancer with chronic back pain experienced a good pain relief after switching from 60 mg/day sustained oral release morphine to 2.5 mg transdermal fentanyl. During the long-term treatment, the transdermal fentanyl dosage had to be increased. Transdermal therapy was continued until the patient's death on day 601. The last fentanyl dosage was 7.5 mg. Transdermal therapy was given 319/601 days at home and 282/601 days in the hospital. Meanwhile, a little rescue suppository morphine was used as an adjuvant during the duration of transdermal therapy. Case report 2: A 73-year-old man suffered a relapse of rectal cancer. He experienced adequate pain relief with 40 mg oral sustained release morphine, but he was switched to 2.5 mg transdermal fentanyl. Transdermal therapy was continued until today on day 630. At present, fentanyl dosage is 20 mg. The patient has been treated at home for 622/630 days. He was hospitalized only once for 8 days because of dehydrations, and has been treated at home. Only a little rescue powder morphine was needed as an adjuvant during the duration of transdermal therapy. In these 2 cases of long-term cancer pain management, transdermal therapy has resulted in good pain reduction and the side effects with transdermal therapy were not noted. Transdermal fentanyl can be recommended for treatment of palliative cancer pain at home.

Administration, Cutaneous↗

PubMed2006

Prostate cancer specific mortality in the Florence screening pilot study cohort 1992-1993.

The impact of screening on prostate cancer mortality is still unknown. A favourable impact is suggested by uncontrolled and possibly biased studies. Mortality from all causes and from prostate cancer was assessed in a cohort of 6,861 males aged 60-74 years, participants to a pilot screening study during 1991-1994. Observed/expected mortality was determined by linkage with cancer and mortality registries. Prostate cancer standardised mortality rate (SMR) in the overall series (751 subjects excluded by GPs for disabling illness or prostate cancer; 3,448 refusers, 2,662 attenders; 67,321.2 men-year) was 0.96 (95% confidence interval (CI)=0.74-1.22) when deaths from prevalent cancers diagnosed before screening were considered. Reduced prostate cancer mortality (SMR=0.48; 95% CI=0.26-0.83), persisting beyond five years after study entry (SMR=0.48; 95% CI=0.22-0.90), was observed in attenders and not in refusers (SMR=0.99; 95% CI=0.69-1.37). This finding might suggest a screening effect, but might also be ascribed to an healthy screening effect, and cannot be assumed as a reliable evidence of screening efficacy.

Aged↗

PubMed2003

Skin cancer and photoaging in ethnic skin.

Skin cancer prevalence in ethnic skin is low. Squamous cell carcinoma, hypopigmented mycosis fungoides, and acral lentiginous melanoma are the most serious types of skin cancer noted in the darker-skinned population. Photoaging occurs less frequently and is less severe in ethnic skin.

Adult↗

PubMed1994

Reproductive risk factors in a prospective study of breast cancer: the Nurses' Health Study.

A modification of the model of Pike et al. (Nature 1983;303: 767-70) was applied to 91,523 women in the Nurses' Health Study who did not report prevalent cancer initially and who were followed for 14 years (1,212,855 person-years and 2,341 incident breast cancers). The model took into account current age, age at all births, age at menopause, and age at menarche in predicting the annual and cumulative incidence of breast cancer. The authors found that ages both at first birth and at subsequent births have long-term influence on breast cancer incidence. The incidence density for parous women was greater than for nulliparous women for 20-30 years after the time of the first birth. However, cumulative incidence up to age 70 years was about 20% lower, 10% lower, or 5% higher for parous versus nulliparous women if their first birth was at age 20, 25, or 35 years, respectively. The authors also observed a significantly lower incidence after each additional birth as well as after menopause for women of the same age. Overall, the effect of reproductive factors (other than age at menarche) appears to influence cumulative incidence to age 70 years by a maximum of approximately 50% when women with multiple births with an early age at first birth are compared with women with a single birth at a late age.

Adult↗

PubMed1986

Randomized mammographic screening for breast cancer in Stockholm. Design, first round results and comparisons.

In March 1981 a randomized single-view mammographic screening for breast cancer was started in the south of Stockholm. The screened population in the first round numbered 40,318 women, and 20,000 women served as a well-defined control group. The age groups represented were 40-64 years, and 80.7% of the invited women participated in the study. The first round disclosed 128 breast cancers (113 invasive and 15 noninvasive), or 4.0 per 1,000 women. Mean tumour size was 14.1 mm and axillary lymph node metastases were found in 21.8%. Fifty-five per cent of the tumours were small (less than or equal to 10 mm) or non-invasive, and 71% were stage I. Participation rates are high in all Swedish trials. The present results differ only slightly from other screening programs; the percentages of patients with axillary metastases and stage II tumours are similar in the Stockholm, Malmö and Kopparberg/Ostergötland studies. Comparisons of cancer prevalence in the various Swedish screening trials show that, in comparable age groups, there are some differences, even when the differences in the natural cancer incidence are taken into account. A decreased mortality was found recently in a Swedish trial in ages above 50 years but not below. In the Stockholm study more than one-third of the participants were aged 40-49 years.

Adult↗