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Predictive value of alarm features in a rapid access upper gastrointestinal cancer service.

AIMS: (i) To determine the value of individual alarm features for predicting cancer in subjects referred to a rapid access upper gastrointestinal cancer service; and (ii) to develop a clinical prediction model for cancer and to prospectively validate this model in a further patient cohort. METHODS: Patient demographics, referral indications, and subsequent diagnosis were recorded prospectively. Logistic regression analyses were employed to determine the predictive value of individual alarm features in an evaluation cohort of 1852 consecutive cases. The potential impact of applying a modified set of referral criteria was then examined in a validation cohort of 1785 patients. RESULTS: Evaluation cohort: mean age was 59 years; cancer prevalence 3.8%; and serious benign pathology 12.8%. Dysphagia (odds ratio (OR) 3.1), weight loss (OR 2.6), and age >55 years (OR 9.5) were found to be significant predictive factors for cancer but the value of other accepted alarm features was more limited. In particular, uncomplicated dyspepsia in those over 55 years was a negative predictive factor for cancer within this high risk cohort (OR 0.1). Validation cohort: the clinical prediction model would have selected 92% of cancer patients for fast track investigation while reducing the "two week rule" workload by 572 cases (31%). CONCLUSIONS: Fast track endoscopy in subjects fulfilling current criteria for suspected upper gastrointestinal malignancy results in a significant yield of cancer ( approximately 4%) and serious benign diseases such as peptic ulceration, strictures, and severe oesophagitis (13%). However, the predictive value of individual features for cancer varies widely. Uncomplicated dyspepsia in older subjects was a poor predictor of cancer. Application of narrower referral criteria for accessing fast track services may reduce pressures while retaining high sensitivity for cancer.

Adolescent↗

High-grade dysplasia in Barrett's oesophagus: natural history and review of clinical practice.

BACKGROUND: Management of high-grade dysplasia in Barrett's oesophagus is controversial: surgery carries an appreciable morbidity/mortality, high-grade dysplasia may not progress to cancer and endoscopic ablation is an emerging option. AIM: To review Barrett's oesophagus-related high-grade dysplasia management and outcome over a 10-year period. METHODS: This was a retrospective case note review of 36 patients identified from a pathology database. RESULTS: There were 31 men of mean age 67 years. Endoscopic surveillance identified nine. Median follow-up was 21 months. Seven patients had no further intervention because of age/comorbidity. The other 29 had repeat endoscopic biopsies, nine showing cancer (six oesophagectomized). Of the 20 remaining patients with persisting high-grade dysplasia, eight had surgery (histology showed cancer in six), seven continued endoscopic surveillance (high-grade dysplasia regressed in four) and five had 'curative' argon ablation. An intensive biopsy protocol was not followed in 55% of endoscopies. Prevalent cancers occurred in 44% with an annual incidence of 5% over 5 years. All cause mortality was 39% (14 of 36, eight of 14 from cancer). CONCLUSIONS: Management of high-grade dysplasia was not uniform. Unsuspected cancer was common in high-grade dysplasia patients undergoing surgery but 13% regressed under surveillance. High-grade dysplasia patients have a high mortality but 43% did not die from cancer.

Adenocarcinoma↗

Mammographic screening: significance of minimal breast cancers.

Analysis of cancers occurring during an aggressively performed screening program indicates: (1) In this study, during 3 years of active incidence screening of women under age 50, 24 cancers occurred, 14 of which were minimal. In the 3 years of very limited screening, 23 cancers occurred, ony five of which were minimal (P = 0.02393). (2) It was projected that 110 breast cancers should have occurred in the incidence years of observation of this self-selected population of 10,531 women. In the screened population, 124 cancers occurred. This is not significantly different from the expected number. (3) In a similar period of observation of a similar sized screened population in Louisville, Ky., there were 112 cancers, and during a similar period in Seattle, Wash., 113. There is no significant difference from the 124 reported in Cincinnati, Ohio, or the 110 expected. However of all the cancers (prevalent, incident, interval) in Cincinnati, 67 were minimal; in Louisville, 35; and in Seattle, 23 (P less tha 0.0001). All in all, these data support the concept that screening for breast cancer does not in any significant way increase the number of cancers detected; it only lowers the stage of detection. The data also suggest that, for an aggressive screen, length-biased sampling does not seem to be insurmountable obstacle.

Adult↗

[On the epidemiology of malignant neoplasms in the German Democratic Republic in the period of 1962 to 1972 (author's transl)].

On the basis of the model for the evaluation of mass attendance, described in (2), a first survey is given on the epidemiology of malignant neoplasms (sum of all diagnoses 140-209 ICD, 8. Rev.) from 1962 to 1972. The development of prevalence in male and female populations is about the same (a clear increase during 1967 and 1969). In spite of a lower incidence of care by women than by men, the mass attendence of women is clearly greater than of men, because the prognosis for women is better than for men. The 5-years-survival rates are for women about 38% and for men only 14%. The cancer prevalence in the GDR (population about 17 Mio.) is nearly 400000, supposed that medical care for cancer patients ends only by death of the patient. An analysis of single diagnosis is not given in this paper.

Adolescent↗

Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.

BACKGROUND: The optimal upper limit of the normal range for prostate-specific antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less. METHODS: Of 18,882 men enrolled in the prevention trial, 9459 were randomly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination. Among these 9459 men, 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination, had a final PSA determination, and underwent a prostate biopsy after being in the study for seven years. RESULTS: Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed in 449 (15.2 percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of 7 or higher. The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter, 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter, 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter, and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter. The prevalence of high-grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter. CONCLUSIONS: Biopsy-detected prostate cancer, including high-grade cancers, is not rare among men with PSA levels of 4.0 ng per milliliter or less--levels generally thought to be in the normal range.

Aged↗

Breast cancer screening: significance of minimal breast cancers.

Analysis of cancers occurring during an aggressive screening program indicates: (1) In our study, during 3 years of active incidence screening of women under the age of 50 years, 24 cancers occurred, 14 of which were minimal. In the 3 years that there has been very limited screening, 23 cancers occurred, only five of which were minimal (p = 0.02393). (2) We projected that 110 breast cancers should have occurred in the incidence years of observation of this self-selected population of 10,531 women. In our screened population, 124 cancers occurred. This is not significantly different from the expected number. (3) In a similar period of observation of a similar sized screened population 112 cancers occurred in Louisville and 113 cases of cancer occurred in Seattle. There is no significant difference from the 124 cases reported in Cincinnati nor from the 110 cases expected. However, of all forms of cancer (prevalent, incident, interval) in Cincinnati, 67 cases were minimal, as against 35 in Louisville and 23 in Seattle (p = less than 0.0001). All in all, these data supported the concept that screening for breast cancer does not in any significant way increase the number of cancer cases detected, it only advances the stage of detection. The data also suggest that, for an aggressive screen, length-biased sampling does not seem to be an insurmountable obstacle.

Adult↗

Cancer burden in the aged: an epidemiologic and demographic overview.

Sixty percent of all cancer occurs in persons aged > or =65 years. This article provides an overview of aspects of the burden of cancer in the elderly, highlighting certain demographic and epidemiologic data. It served as a frame of reference for participants in the Oncology Geriatric Education Retreat, San Juan, Puerto Rico, February 21-26, 1997. Information comes from several major sources: U. S. Bureau of the Census; National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program; National Center for Health Statistics; National Institute on Aging (NIA)/NCI SEER Study on Comorbidity and Cancer in the Elderly; and NCI cancer prevalence estimates. Data on the aging population demonstrate an unprecedented expansion of the segment of the population aged > or =65 years. By 2030, 1 in 5 Americans will be aged > or =65 years. Because cancer incidence and mortality rates are highest in persons aged > or =65 years, expansion of this age group takes on great importance for medical professionals who provide treatment to older aged cancer patients. In addition, older aged cancer patients are likely to have preexisting conditions at diagnosis, creating a special clinical challenge. There is an urgent need to better understand the influence of aging on the early detection, diagnosis, and treatment of cancer. Clinicians who treat older persons (geriatricians, oncologists, and other health professionals) can benefit from the integration of the knowledge and approaches of each others' fields. The foundation for this multidisciplinary effort is linked with the education and training of future clinicians.

Age Distribution↗

Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features.

The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.

Adult↗

Practice of opportunistic prostate-specific antigen screening in Italy: data from the Health Search database.

The effectiveness of prostate-specific antigen (PSA) testing for opportunistic screening of prostate cancer is not yet well established, although this practice seems to be widely accepted. To estimate the opportunistic use of PSA by general practitioners (GPs) in Italy, we conducted a survey by querying the Health Search (HS) database, which collects clinical records from a representative sample of the Italian population. Clinical computerized data from 320 GPs and 221,557 male patients were analysed. Among total requests for PSA, 3% were linked to prostate cancer, 18% to a urological disease or symptom and 79% were not linked to any urological condition (opportunistic screening). Opportunistic screening was used for 31.4% of subjects over 50 with a significant (P<0.0001) difference between geographical areas (36.4% north, 33.5% central regions, 22.9% south and isles). This distribution was very similar to prostate cancer prevalence as it resulted from the HS data. PSA testing practice showed an increase over the years (12.7% of men over 50 in 2000, 14.3% in 2001 and 15.9% in 2002). In conclusion, the practice of opportunistic screening of prostate cancer seems to be extensively adopted by Italian GPs and is becoming more and more popular, although to date it is not supported by strong scientific evidence.

Adult↗

Aggregation of lung cancer in families: results from a population-based case-control study in Germany.

The authors investigated familial aggregation of lung cancer by means of a population-based case-control study, conducted in Germany between 1988 and 1993. They compared lung cancer prevalence in first degree relatives of 945 patients and 983 controls, accounting for various potential risk factors using logistic regression and generalized estimating equations. Some 83% of the study participants were male, and about 14% were below age 51 (young age group). Overall, lung cancer in parents or siblings was associated with a 1.67-fold (95% confidence interval (CI): 1.11, 2.52) increase in lung cancer risk. For the young participants, this risk was 4.75 (95% CI: 1.20, 18.77). Having multiple affected relatives (two or more) was related to a threefold risk elevation (odds ratio (OR) = 2.99, 95% CI: 0.32, 27.55). Paternal (OR = 1.64, 95% CI: 0.91, 2.96) but not maternal (OR = 0.91, 95% CI: 0.32, 2.61) lung cancer was associated with an increased risk of the disease. Lung cancer risk from smoking was particularly pronounced in the parents of cases (OR = 12.20, 95% CI: 3.34, 44.62 vs. OR = 7.93, 95% CI: 2.43, 25.91 in parents of controls). No risk elevation was detected for other smoking-related and other cancers in general. Results confirm previous findings and support the etiologic role of a genetic predisposition to lung cancer.

Adult↗

Familial aggregation of lung cancer in a high incidence area in China.

To investigate whether lung cancer clusters in families in a high incidence county of China, an analysis was conducted using data on domestic fuel history and tobacco use for family members of 740 deceased lung cancer probands and 740 controls (probands' spouses). Lung cancer prevalence was compared among first-degree relatives of probands and of controls, taking into account various factors using logistic regression and generalised estimating equations. First-degree relatives of probands, compared with those of controls, showed an excess risk of lung cancer (odds ratio (OR)=2.05, 95% confidence interval (CI): 1.68-2.53). Overall, female relatives of probands had a greater risk than did their male counterparts, and the risk was 2.90-fold for parents of probands as compared with parents of spouses. Female relatives of probands had 2.67-fold greater risk than female controls. Lung cancer risk was particularly marked among mothers (OR=3.78, 95% CI: 2.03-7.12). Having two or more affected relatives was associated with a 2.69-5.40-fold risk increase. The risk elevation was also found for other cancers overall. Results confirm previous findings of a genetic predisposition to lung cancer, and also imply that lung cancer may share a genetic background with other cancers.

Adult↗

Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells.

PURPOSE: Prostate cancer is the second most common cancer that leads to death in elderly men. The risk of prostate cancer prevalence is often associated with the elevated level of insulin-like growth factor-I (IGF-I) and decreased level of IGF-binding protein 3 (IGFBP-3). Lycopene, a carotenoid, reduces the proliferation of cancer cells and induces apoptosis. Hence, higher intake of lycopene can be associated with the lower risk of prostate cancer. However, the mechanism of action of lycopene in the prevention of prostate cancer is still unclear. The present study was carried out to study the effects of lycopene on the components of IGF system and apoptosis in androgen-independent prostate cancer cells (PC-3 cells). METHODS: PC-3 cells were treated with various concentrations of lycopene, (20, 40 and 60 microM) for 24, 48, 72 and 96 h. IGF-I, IGFBP-3 and IGF-I receptor (IGF-IR) levels in lycopene-treated cells were evaluated. Annexin V and propidium iodide (PI) binding studies were done to assess apoptosis. RESULTS: PC-3 cells treated with lycopene showed a significant decrease in cell proliferation. Lycopene, at a dose of 40 microM, significantly increased the level of IGFBP-3. Lycopene-induced apoptosis was confirmed by annexin V and PI binding. Lycopene-induced DNA fragmentation was absent after 24 h treatment whereas the same was observed after 48 h treatment. There was a significant decrease in the IGF-IR expression after the cells were treated with lycopene and IGF-I. CONCLUSION: The data obtained suggest that the components of the IGF system may act as a positive regulator of lycopene-induced apoptosis in PC-3 cells. Thus, the observed lycopene-induced biological effects and their associated mechanisms are encouraging and may lead to the development of a highly successful drug for the treatment of prostate cancer.

Annexin A5↗

The demography of primary biliary cirrhosis in Ontario, Canada.

The demographics of primary biliary cirrhosis in Ontario, Canada, are described. Two hundred and twenty-five primary biliary cirrhosis patients were identified by 85 of 502 gastroenterologists (or internists) practicing in Ontario acute care hospitals that have 150 or more beds. Two hundred and six patients were verified as being antimitochondrial antibody-positive, resulting in an incidence of 3.26 per million per year and a prevalence of 22.39 per million. Questionnaire data were obtained on 88.5% of these patients. Twenty-nine percent of the patients were found to be asymptomatic. Geographical clustering and racial predisposition were not seen. No increase in breast cancer prevalence was noted. By the time the diagnosis of primary biliary cirrhosis was established, the patients had consulted a median number of 3.5 physicians. Fatigue was reported as the most disabling symptom. The diagnosis of primary biliary cirrhosis in patients referred from across the province of Ontario was independently confirmed by us, using standard criteria (antimitochondrial antibody testing and liver biopsy), and was found to be reliable.

Autoantibodies↗

Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.

UNLABELLED: Breast and prostate cancers are both hormone-driven adenocarcinomas that undergo analogous invasion programs. Using lightsheet microscopy on intact tumors, we identified transitional junctions between precancerous and invasive regions. We then developed a multimodal serial-section workflow integrating volumetric reconstruction with spatial transcriptomics. Analysis of 319 spatial assays from 51 cases revealed gene expression features and novel structural insights defining the shift from precancer to invasive disease. In breast cancer, loss of MGP and PLAT was associated with invasive transition and promoted tumorigenesis in functional assays. In prostate cancer, GDF15, ALDH1A3, ANPEP, and FASN were upregulated along invasive progression, and their knockdown in PC-3 cells suppressed proliferation and migration. Enrichment of tumor-associated macrophages (SPP1+ and MS4A6A+) along non-triple-negative breast cancer breast cancer transitions highlights immune involvement as a potential driver of invasiveness. SIGNIFICANCE: Our method of defining precise spatial locations of invasive transition allows for the direct interrogation of transition drivers, presenting new therapeutic targets for the two most prevalent cancers and providing a framework for studying spatially defined mechanisms of tumor progression. See related commentary by Jing and Li, p. 1720.

Humans↗

The prevalence of prostate cancer screening in Thai elderly.

PROBLEM: Prostate cancer is the most common cancer in elderly men in Western countries. In the future, it may be an important problem in Thailand. At present, there is no evidence about the prevalence and the outcome of screening in this disease. OBJECTIVES: To determine the prevalence of prostate cancer in elderly Thai men and to identify the most appropriate screening method for detection of prostate cancer in Thailand. MATERIAL AND METHOD: 928 elderly men from communities around Siriraj Hospital were evaluated for prostate cancer by Digital Rectal Examination (DRE) and/or Prostate Specific Antigen (PSA). Transrectal ultrasound guided biopsy (TRUS-Bx) which is the gold standard for definitive diagnosis was performed in cases with an abnormal DRE and/or PSA. If biopsy could not be performed, intermittent follow-up with DRE and/or PSA were recommended. RESULT: The prevalence of prostate cancer in Thai elderly men in the urban community was more than 0.75 per cent and the prevalence of abnormal DRE and PSA was 8.7 and 17.3 per cent respectively. The Positive Predictive Value (PPV) of both tests was 60 per cent and higher than the PPV of an individual test. A screening program for prostate cancer starting with DRE may be more cost effective. CONCLUSION: The prevalence of prostate cancer, abnormal DRE and abnormal PSA in Thai elderly men were more than 0.75, 8.7 and 17.3 per cent respectively which are comparable to the prevalence in Western countries. It is important that we take an interest in this disease.

Humans↗

New Mexico's capacity for increasing the prevalence of colorectal cancer screening with screening colonoscopies.

INTRODUCTION: Colorectal cancer screening rates are low throughout the United States. Colonoscopy has been recommended as a cost-effective strategy for colorectal cancer screening and prevention. We evaluated New Mexico's capacity to increase the prevalence of colorectal cancer screening using colonoscopy. METHODS: We identified New Mexican gastroenterologists from state licensing data and from endoscopic manufacturers. We surveyed gastroenterologists on their weekly number of colonoscopies, capacity for additional screening colonoscopies, and barriers to increasing capacity. We used census data, published data on the yield of screening colonoscopy, and professional society guidelines for cancer/polyp surveillance to estimate the additional colonoscopies required to increase the state's prevalence of endoscopic screening. RESULTS: Forty gastroenterologists, representing all 11 group practices in the state, and nine of 12 solo practitioners responded. They estimated that their weekly procedure capacity could be increased by 41%, from 832 to 1174 colonoscopies. We estimated an annual capacity increase of 14,880 procedures, which could increase the prevalence of endoscopic colorectal cancer screening from the current 35% to about 50% over five years. Lack of support staff, space, and physicians were barriers to increasing screening. CONCLUSION: Implementing a screening colonoscopy strategy could achieve the goal of a higher level of colorectal screening. However, achieving more universal screening would require additional testing modalities.

Colonoscopy↗

The role of Raf kinases in malignant transformation.

The Raf kinases are proto-oncogenes that work at the entry point of the mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway, a signalling module that connects cell-surface receptors and Ras proteins to nuclear transcription factors. The pathway impinges on all the functional hallmarks of cancer cells: immortalisation, growth-factor-independent proliferation, insensitivity to growth-inhibitory signals, ability to invade and metastasise, ability to attract blood vessels, and evasion of apoptosis. Indeed, the pathway is hyperactivated in 30% of all human tumours including prevalent cancers of the colon and lung. The molecular mechanisms underlying the role of Raf kinase in tumourigenesis and the opportunities for therapeutic intervention are reviewed in this article.

Animals↗

Post-transplant malignancies in minority populations.

Post-transplant malignancy (PTM), is emerging as an important cause of early morbidity and mortality following transplantation (TX). Unfortunately its prevalence in minorities (African-Americans, AA; Native Americans, NA; Asian Pacific Islanders, AP; American Indians, AI; Latino-Hispanics, LH) in the United States, though important, remains unknown. Published reports of prevalence rates by different centers, including the Cincinnati Transplant Tumor Registry (CITTR) of about 4%-18% though informative, remain of little help. These reports erroneously assume a homogeneity in population, uniformity in the impact and spread of the determinants of this disease, and equal access to health for all patients. Data from AA, the only minority group studied by the Howard University Hospital Transplant Center (HUHTC) group, in Washington, D.C.; revealed a cancer occurrence of 3% in 339 TX patients. It is important to note that unlike the CITTR data base, the HUHTC cancer database is smaller. Nevertheless, a comparative analysis was revealing. Skin/lymphoid cancers had a lower occurrence (20% versus 54%), while head and neck tumors had a higher occurrence (30% versus 3%) as were genitourinary cancers (30% versus 8%) in AA as compared to the general population. Since minorities as a group are prone to higher cancer prevalence and mortality rates, and because patterns of PTM may differ among groups, studies to analyze PTM and other factors that may further escalate cancer rates in minorities deserve greater impetus.

Female↗