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[Programmed screening of the adult population in cancer detection].

Methods of examination aimed at early detection of neoplasms of main localizations (pulmonary, gastric and breast cancer, tumors of the colon, rectum and thyroid gland) are suggested. In 1982, the following percentage of malignancies was detected as a result of follow-up: stomach--66.0, colon--55.5, rectum--83.3, lung--62.8, breast--67.1, and thyroid gland--63.6%.

Adult↗

Malignancy associated changes in epithelial cells of buccal mucosa: a potential cancer detection test.

OBJECTIVE: To analyze the presence of malignancy associated changes (MACs) in normal buccal mucosa cells of lung and breast cancer patients and their relationship to tumor subtype, stage and size. STUDY DESIGN: Buccal mucosa smears of 107 lung cancer and 100 breast cancer patients and corresponding healthy subjects were collected, stained by the DNA-specific Feulgen-thionin method and scanned using an automated high-resolution cytometer. Nuclear texture features of a minimum of 500 nuclei per slide were calculated, and statistical classifiers using Gaussian models of class-probability distribution were designed, trained and tested in 3 parts: (1) ability to separate cancer patient samples from controls, (2) cross-validation of classifiers for different cancer types, and (3) correlation of MAC expression with tumor subtype, stage and size. RESULTS: Lung and breast cancer induce MACs in normal buccal mucosa cells. The classifiers based on the selected nuclear features correctly recognized >80% of lung and breast cancer cases. The results indicate that MAC detection is not dependent on the tumor subtype, stage or size. CONCLUSION: The presence of MACs in buccal mucosa cells offers the potential for developing a new noninvasive cancer screening test.

Adult↗

Caveolins as tumour markers in lung cancer detected by combined use of cDNA and tissue microarrays.

To identify new potential diagnostic markers for lung cancer, the expression profiles of 37 lung tumours were analysed using cDNA arrays. Seven samples were from small-cell lung cancer (SCLC), two from large-cell neuroendocrine tumours (LCNEC), and 28 from other non-small-cell lung cancers (mainly squamous cell cancer and adenocarcinoma). Principal component analysis and the permutation test were used to detect differences in the gene expression profiles and a set of genes was found that distinguished high-grade neuroendocrine carcinomas (SCLC and LCNEC) from other lung cancers. In addition, several genes, such as caveolin-1 (CAV1) and caveolin-2 (CAV2), were constantly deregulated in all types of tumour sample, compared with normal tissue. The expression of these two genes was investigated further at the protein level on a tissue microarray containing tumours from 161 patients and normal tissues. Immunostaining for CAV1 was negative in 48% of tumours, whereas 28% of the tumours did not express CAV2. Lack of CAV1 protein expression was not caused by methylation or mutation. In stage I adenocarcinomas, CAV2 protein expression correlated with shorter survival. In conclusion, the present study was able to identify genes that have not previously been implicated in lung cancer by the combined use of two different array techniques. Some of these genes may provide novel diagnostic markers for lung cancer.

Adenocarcinoma↗

Seasonal variation in breast cancer detection: correlation with tumour progesterone receptor status.

A significant circannual variation of the month in which patients detect the first sign or symptom of tumour has been defined in 1413 patients with breast cancer. The months of highest detection were in the late spring-early summer, and lowest detection was in late autumn-early winter. Analysis of subgroups indicates that this cyclic trend was most significant in younger women with small or moderate-sized tumours containing steroid hormone receptors, particularly progesterone receptors. It seems likely that this variation is related to the effect of cyclic hormonal changes on tumour growth, possibly mediated through the pineal.

Adult↗

DNA aberrations in urinary bladder cancer detected by flow cytometry and FISH: prognostic implications.

We evaluated the genetic changes in bladder cancer biopsy by fluorescence in situ hybridization (FISH) and related them to stage and grade of the tumor, ploidy (FCM) and clinical outcome, to determine a simple method to identify tumors with a poorer prognosis. Using FISH the numerical aberrations of chromosomes 1, 7, 9, 17 in tumor's imprints of 70 patients with transitional cell cancer (TCC) were determined. First of all, the data demonstrated that the sensitivity of FISH in detecting quantitative DNA aberrations exceeds FCM's sensitivity. The frequency of chromosome 1 and 9 aberrations did not show significant differences in diploid and aneuploid tumors in different stage and grade. On the contrary, the chromosome 7 and 17 aneusomy showed greater differences between pT1 and pT2-3 tumors (p<0.032 and p<0.0006, respectively) than between stage pTa and pT1. In our investigation, an increasing number of aberrations was observed in all chromosomes examined in tumors of patients who afterwards underwent cystectomy and/or had recurrent tumors. These results suggest that chromosome 7 and 17 aneusomy could be predictive of adverse outcome in a subgroup of patients with superficial tumors at presentation.

Adult↗

Intra-abdominal recurrence of colorectal cancer detected by radioimmunoguided surgery (RIGS system).

Since 1986, 32 patients with metastatic colorectal cancer have undergone second-look radioimmunoguided surgery (RIGS system). The primary tumor was located in the right and transverse colon in 11 patients, left and sigmoid colon in 16, and rectum in five. The carcinoembryonic antigen level was elevated in 30 patients (94%); all patients underwent a computed tomographic scan of the abdomen and pelvis. The overall sensitivity of the computed tomographic scan was 41% (abdomen other than liver, 27%; liver, 58%; and pelvis, 22%). The RIGS system identified recurrent tumor in 81% of the patients. The most common site of metastasis was the liver (41%), independent of the primary location. Local/regional recurrences alone accounted for 40% of all recurrences. In six patients (18%), recurrent tumor was found only with the RIGS system. The RIGS system is more dependable in localizing clinically obscure metastases than other methods, and carcinoembryonic antigen testing remains the most accurate preoperative method to indicate suspected recurrences.

Abdominal Neoplasms↗

Advanced endometrial cancer detected at 7 months after childbirth.

It is very rare to find endometrial cancers arising within a short period following childbirth, presumably because pregnancy has a protective effect against endometrial cancer mediated by elevated secretion of progesterone. We present the case of a 30-year-old Japanese woman with stage IIIC endometrial cancer that was found 7 months after childbirth. The patient was treated with surgery followed by 6 cycles of intravenous combination chemotherapy and oral administration of medroxyprogesterone acetate. Histopathological examination of surgical specimen revealed poorly differentiated adenosquamous carcinoma of the endometrium with deep myometrial invasion, cervical stromal involvement, and pelvic and paraaortic lymph node metastases. The disease progressed rapidly and the patient died of the disease.

Adult↗

Evaluation model of the Mexican national program for early cervical cancer detection and proposals for a new approach.

INTRODUCTION: An evaluation model on cervical cancer (CC) prevention in Mexico was carried out during 1990-95, using three observation units: women at risk, screening providers, and use of health services. METHODS: A diagnostic procedure of the pitfalls was applied to the following steps of the screening procedure: Pap sampling quality, cytological diagnosis validity, compliance of women, and determinants of nonparticipation. RESULTS: The low effectiveness of screening for CC is due principally to factors associated with quality and coverage. Quality of Pap is deficient; 64 percent of a random sample of specimens lacked endocervical cells. Reading centers presented false negative indices between 10 and 54 percent. Women seek screening in a late stage of disease (55 percent with CC seek care because they have symptoms). In addition, coverage is low; in women between 15 and 49 years of age in Mexico City, 64.2 percent have a history of Pap smears, compared with 30 percent in rural areas. Knowledge of what the Pap is used for strongly determines use of screening. In rural areas, only 40 percent know the purpose of the Pap. CONCLUSIONS: This information justifies an intervention to reorganize CC screening in Mexico, through strategies for improving compliance, quality, follow-up, and treatment for abnormal screens.

Adolescent↗

p53 aberrations in oral sub mucous fibrosis and oral cancer detected by immunohistochemistry.

Study of expression of p53 oncoprotein in several precancerous and cancer have been done, but only one literature is available regarding p53 expression in Oral Sub Mucous Fibrosis (OMSF), hence this study was taken up (i) to determine the expression of aberrant p53 in Oral Sub Mucous Fibrosis (OSMF) and Oral Squamous cell carcinoma (SCC) patients. (ii)To study correlation if any between p53 expression and degree of dysplasia in OSMF and SCC patients and (iii)To study correlation if any between p53 expression and habits in OSMF and SCC patients. Study Design consists of biopsy specimens of 38 cases of OSMF and 37 cases of Squamous cell carcinoma were subjected for staining by immunohistochemistry for p53 protein using LSAB visualization system kit. Clinical details along with habits were recorded and the data analyzed with t- test and chi- square test. Results of the study reveals 18 cases of OSMF and 26 cases of SCC were positive for p53 protein. Only 4 cases of SCC showed (++)grade and the rest all had (+)grade. Out of 75 patients, 65 had the habit of smoking and chewing, 4 patients history of habit was not known. Among patients with habits (65), 40 specimens were +ve for p53 stain and 2 out of 6 without history of habit, 2 out of 4 unknown history of habit took up p53 stain. To conclude study showed higher percentage of p53 positive cells in oral cancer cases when compared to oral sub mucous fibrosis cases. It suggests p53 expression may correlate with increase in dysplasia or malignant transformation. Both smoking and chewing habits had a significant role in p53 positive expression.

Adult↗

[Hilar and mediastinal lymph node metastases from lung cancer; detection with CT and MR imaging].

Sixty-one patients with primary lung cancer, who had CT and MR imaging before surgery, were studied. MR imaging used spin-echo sequences with T1 weighted image and T2 weighted image (C-MRI), and included STIR technique (Stir-MRI). The accuracy of diagnosis of mediastinal lymphadenopathy (regarding 10 mm or larger in short transverse diameter as positive) was 89% by CT, 84% by C-MRI and 89% by Stir-MRI. The accuracy of diagnosis of hilar lymphadenopathy was 42% by CT, 67% by C-MRI, and 75% by Stir-MRI. The accuracy of diagnosis of mediastinal lymph node metastases was 89% by CT, 94% by C-MRI and 96% by Stir-MRI. The accuracy of diagnosis of hilar lymph node metastases was 78% by CT, 87% by C-MRI and 89% by Stir-MRI. The possibility of enhancement of diagnostic accuracy of lymph node metastases from lung cancer was suggested by combining MR imaging included STIR technique with CT.

Adenocarcinoma↗

Characteristics of 108 thyroid cancers detected by screening in a population with a history of head and neck irradiation.

One hundred and eight cases of thyroid cancer have been discovered as a result of screening 1712 individuals from a well defined population known to be at high risk because of prior head or neck irradiation for benign conditions. Of these 198 cancers, 43 (39.8%) were palpable, 27 (25.0%) were detectable by means of thyroid scintigraphy alone, and 38 (35.2%), referred to as incidental carcinomas, were found when the patients were operated on for lesions which approved to be benign. The most striking feature of these cancers was the high frequency of multicentricity (55%) and bilaterality (36%). This high frequency was found in clinically apparent as well as incidental cancers, and could not be accounted for by the operative pathologic techniques of investigation. Of 42 subjects reevaluated at our institution after a mean time of 38 months, 2 had definite and 2 had probable recurrent or residual thyroid disease. The postoperative thyroglobulin levels in subjects with thyroid cancer were proportional to the amount of thyroid tissue remaining. Follow-up evaluation of the entire group did not disclose any differences in the behavior of these thyroid cancers compared to those not associated with radiation.

Chicago↗

Quantitative detection of methylated SOCS-1 , a tumor suppressor gene, by a modified protocol of quantitative real time methylation-specific PCR using SYBR green and its use in early gastric cancer detection.

Although methylation-specific PCR (MSP) is a sensitive technique in the detection of DNA hypermethylation, it is not quantitative. Here we described a modified PCR protocol to quantify methylated SOCS-1 gene by real time MSP using SYBR green, which involves an additional PCR step after the 72 degrees C extension step. This modified protocol is also useful in the quantitative detection of methylated SOCS-1 gene in serum samples of gastric cancer patients.

Adult↗

Multi-valued logic in breast cancer detection.

The aim of this paper is to determine the type of the breast cancer disease. The two classes of separation are malignant respectively benign. A multi-valued logic system (fuzzy system) was develop and applied in this classification. The system uses nine attributes as inputs that were scaled with an integer value in the range between 1 and 10. The attributes represent: 1. Clump Thickness, 2. Uniformity of Cell Size, 3. Uniformity of Cell Shape, 4. Marginal Adhesion, 5. Single Epithelial Cell Size, 6. Bare Nuclei, 7. Bland Chromatin, 8. Normal Nucleoli, 9. Mitoses. After training the system managed to get a good detection with an error less than 5%.

Algorithms↗

Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization.

Little is known about the genetic changes underlying invasive tumor growth in bladder cancer. Because alterations that are linked to invasive tumor growth may be detectable in minimally invasive (stage pT1) but not in noninvasive (stage pTa) tumors, we searched for genetic differences between 28 pTa and 28 papillary pT1 bladder tumors by comparative genomic hybridization. Losses of 9q (54%), 9p (39%), and Y (28%) and gains of 1q (14%) were most prevalent in pTa tumors. These changes may play a role in the initiation of noninvasive papillary bladder cancer. The total number of aberrations was higher in pT1 tumors (6.5 +/- 5.4) than in pTa tumors (2.3 +/- 2.1; P = 0.0003), suggesting an increased genetic instability at stage pT1. Specific alterations, which were significantly more frequent in pT1 than in pTa tumors (P < or = 0.05), included deletions at 2q (36% of pT1 tumors), 8p (32%), and 11p (21%) and gains at 1q (54%), 8q (32%), 3p, 3q, 5p, 6p, and 10p (18% each). These loci are candidates for carrying genes involved in invasive tumor growth in bladder cancer. High-level amplifications at 1q22-24, 3p24-25, 6p22, 8p12, 8q21-22, 10p12.1-14, 11q13, 12q15-21, 13q31-33, Xp11-13, and Xq21-22.2 may pinpoint the location of oncogenes with relevance for bladder cancer.

Chromosome Aberrations↗

Monitoring the serological proteome: the latest modality in prostate cancer detection.

PURPOSE: Various strategies have recently emerged to improve the diagnostic prediction of prostate cancer (CaP). One such strategy includes the mass profiling of serum protein fractions selectively adsorbed onto chemically modified probes. In the current study we further validated this approach, while offering a more versatile, less expensive and yet equally predictive alternative to existing technologies. MATERIALS AND METHODS: A solid core lipophilic C-18 resin was used to extract and enrich the low molecular weight protein fraction from patient serum for further analysis by mass spectrometry. Mass spectra generated from a 48 patient training set were data mined using multivariate analysis to identify diagnostically significant protein peaks. These peaks were then used to test a blinded study set comprising 168 patients with common statistical algorithms and commercially available software packages. RESULTS: A total of 36 peaks generated from the training set were used to test the combined set of 168 serum samples obtained from 98 healthy individuals and 70 patients with CaP. We report a sensitivity of 94.1% and a specificity of 99.0% with 1 false-positive, 4 false-negative and 5 nondiagnosed cases. CONCLUSIONS: Our results further indicate that mass profiling of serological proteins provides a means for the accurate detection of CaP. In addition, our approach was found to be superior to chip based protocols, generating rich, sharp, highly reproducible spectra attainable in a high throughput manner and at minimal cost. This technique is also scaleable for subsequent protein characterization using multidimensional protein identification technologies. Finally, analyses of mass spectra with commercially available statistical applications was found to be highly effective in generating highly discriminatory m/z values for CaP diagnosis.

Biomarkers, Tumor↗

[Positive and negative false diagnosis of cancer detected by autopsy (author's transl)].

1. Among autopsied cases every third case of cancer is only discovered by autopsy or correctly diagnosed with regard to his localization or structure. 2. 90% and more of all cancer of the breast, the skin, the upper alimentary and aerial tract, of the uterus and the vagina and vulva are clinical correctly diagnosed, but only 70% of malignant lymphomas and cancers of the lung, the stomach, the bowel and the ovary. More than 50% of all cancers of the prostata gland, the urinary tract and the pancreas are exactly clinical diagnosed, but the diagnosis of tumours of the brain, the biliary tract and the liver is worse. 3. In about 10% of all clinically diagnosed cancers any cancer does not exist and 10% have another cancer than expected. The clinical and the epidemiological aspect of such cancers is perturbed by these positive false diagnoses. 4. The group of negative false diagnoses descends only from deaths without suspicion for cancer. If cancer cases are more often autopsied than other deaths, the percentage of negatives erroneous diagnoses decreases in spite of the number of unknown unautopsied cancer cases increases. 5. Among the present autopsy rates about 10% (or more) of all cancer cases are not included in medical statistics.

Adult↗

Analysis of 172 subtle findings on prior normal mammograms in women with breast cancer detected at follow-up screening.

PURPOSE: To retrospectively review nonspecific findings on prior screening mammograms to determine what features were most often deemed normal or benign despite the development of breast cancer in the same location detected at follow-up screening. MATERIALS AND METHODS: Four hundred ninety-three pairs of consecutive mammographic findings were collected from 13 institutions, consisting of initial normal screening findings and a subsequent finding of cancer at screening (mean interval between examinations, 14.6 months). One designated radiologist reviewed each pair of mammograms and determined that 286 findings were judged visible at prior examination in locations where cancer later developed. Five blinded radiologists independently reviewed the prior findings in these 286 cases, identifying 169 mammograms (172 cancers) with findings so subtle that none or only one or two of the five radiologists recommended screening recall. Two unblinded radiologists reviewed the initial and subsequent findings and recorded descriptors and assessments for each finding and subjective factors influencing why, although the lesion was perceptible, it might have been undetected or not recalled. RESULTS: Of 172 cancers, 129 (75%) were invasive (112 T1 tumors and 17 T2 tumors or higher; median diameter, 10 mm), and 43 (25%) were ductal carcinoma in situ (median size, 10 mm). On the prior mammograms, 80% (137 of 172) of these cancers had subtle nonspecific findings where cancer later developed, and most were assessed as being normal or benign in appearance. CONCLUSION: There is a subset of cancers that display perceptible but nonspecific mammographic findings that do not warrant recall, as judged by both a majority of blinded radiologists and by unblinded reviewers. We believe failure to act on these nonspecific findings prospectively does not necessarily constitute interpretation below a reasonable standard of care.

Adult↗