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[A pilot study with lung-cancer screening CT (LSCT) at the secondary screening for lung cancer detection].

We have developed computed tomography (CT) equipment for lung-cancer screening (named LSCT) that can be used exclusively for lung-cancer screening with spiral volumetric CT and is available on a screening car. A pilot study with LSCT was performed from November 1992 to January 1993 on 118 screenees at the secondary examination of lung-cancer screening. Scan parameters were as follows: 120 kVp, 50 mA, slice thickness 10 mm, table feed 10 mm/sec, scan time 2 sec/rotation. All the screenees were scanned under quiet respiration instead of the breath-hold technique. Under these scan parameters, LSCT images were almost free from respiratory motion artifacts even at the lung base. Continuity of the bronchial tree and vessels was well maintained in consecutive slices. Pulmonary nodules approximately 5 mm in diameter were clearly depicted. By LSCT, 43 of 118 screenees were diagnosed to need further examinations. And 33 out of 43 screenees underwent detailed examinations. Finally, 16 lung cancers were confirmed. Ten of 16 patients with lung cancer underwent surgery; nine were in stage I and one in stage IIIA. LSCT was considered to be useful in lung-cancer screening.

Adult↗

Outcome of 51 patients with roentgenographically occult lung cancer detected by sputum cytologic testing: a community hospital program.

BACKGROUND: Lung cancer is the most common fatal malignant neoplasm of both men and women. It is usually caused by tobacco smoke. However, at present there is no systematic approach to early diagnosis. The diagnosis of lung cancer is usually made by standard chest roentgenograms and biopsy by bronchoscopy or surgery. Survival rates at 5 years have remained 10% to 15% for the past 30 years with this conventional approach to diagnosis. METHODS: Fifty-one men and women, aged 46 to 81 years (mean age, 64.2 years), with roentgenographically occult cancer were identified in one community hospital by means of sputum cytologic testing. Cancers were diagnosed by means of one or more standard light fiberoptic bronchoscopic procedures with biopsies. RESULTS: Forty-four squamous cell carcinomas, three adenocarcinomas, two large-cell carcinomas, and two undifferentiated carcinomas were found. Forty-five (86%) were stage 0 or 1. Surgical cure was attempted in 27 patients, and there were three actuarial cancer deaths at 5 years and a total of nine deaths. Additionally, 19 patients received attempts at curative radiation therapy for various reasons, which were usually poor pulmonary or cardiac function or advanced age. Of both the 27 patients who underwent surgery and the 19 who were treated with radiation therapy (total, 46), the actuarial results by the life-table method included nine lung cancer deaths in 5 years and 21 deaths from all causes, giving an actuarial survival, including deaths from all causes, of 55%. CONCLUSION: Roentgenographically occult lung cancer can be found by sputum cytologic testing followed by fiberoptic bronchoscopy and biopsy at a time when cure is more likely than when it is diagnosed by conventional roentgenographic techniques (ie, 55% survival vs 10% to 15% survival). Sputum cytologic testing should be used as a case-finding tool, particularly in heavy smokers and those with occupational risks. This diagnostic approach to earlier diagnosis and intervention can be successful in a small community hospital.

Aged↗

Hospital-based cancer detection programs for the community.

Experimental screening programs have demonstrated the efficacy of screening procedures for cervical, breast, and colorectal cancers but there has not been widespread application of such screening projects to programs suited to community health care facilities. Here, we illustrate how this may be accomplished by use of outpatient facilities, cancer screening clinics in hospitals, or periodic short-term community screening programs. The objective is cancer control through screening and detection programs characterized by application of demonstrated detection procedures, reliance on existing hospital resources, use of minimally invasive screening procedures, promotion targeted to high-risk groups, collaboration with community volunteer organizations, and emphasis on serving persons not already receiving such routine detection services. This paper presents results on the hospital monitoring of Pap smear screening of outpatients and the yield from experience with the community screening program. It also describes the various cancer control activities of an ongoing hospital-based cancer screening clinic.

Adult↗

The potential role of dynamic thermal analysis in breast cancer detection.

BACKGROUND: It is presently well accepted that the breast exhibits a circadian rhythm reflective of its physiology. There is increasing evidence that rhythms associated with malignant cells proliferation are largely non-circadian. Cancer development appears to generate its own thermal signatures and the complexity of these signatures may be a reflection of its degree of development. The limitations of mammography as a screening modality especially in young women with dense breasts necessitated the development of novel and more effective screening strategies with a high sensitivity and specificity. The aim of this prospective study was to evaluate the feasibility of dynamic thermal analysis (DTA) as a potential breast cancer screening tool. METHODS: 173 women undergoing mammography as part of clinical assessment of their breast symptoms were recruited prior to having a biopsy. Thermal data from the breast surface were collected every five minutes for a period of 48 hours using eight thermal sensors placed on each breast surface [First Warning System (FWS), Lifeline Biotechnologies, Florida, USA]. Thermal data were recorded by microprocessors during the test period and analysed using specially developed statistical software. Temperature points from each contra-lateral sensor are plotted against each other to form a thermal motion picture of a lesion's physiological activity. DTA interpretations [positive (abnormal thermal signature) and negative (normal thermal signature)] were compared with mammography and final histology findings. RESULTS: 118 (68%) of participating patients, were found to have breast cancer on final histology. Mammography was diagnostic of malignancy (M5) in 55 (47%), indeterminate (M3, M4) in 54 (46%) and normal/benign (M1, M2) in 9 (8%) patients. DTA data was available on 160 (92.5%) participants. Using our initial algorithm, DTA was interpreted as positive in 113 patients and negative in 47 patients. Abnormal thermal signatures were found in 76 (72%) out of 105 breast cancer patients and 37 of the 55 benign cases. Then we developed a new algorithm using multiple-layer perception and SoftMax output artificial neural networks (ANN) on a subgroup (n = 38) of recorded files. The sensitivity improved to 76% (16/21) and false positives decreased to 26% (7/27) CONCLUSION: DTA of the breast is a feasible, non invasive approach that seems to be sensitive for the detection of breast cancer. However, the test has a limited specificity that can be improved further using ANN. Prospective multi-centre trials are required to validate this promising modality as an adjunct to screening mammography especially in young women with dense breasts.

Journal Article↗

der(16)t(1;16)/der(1;16) in breast cancer detected by fluorescence in situ hybridization is an indicator of better patient prognosis.

By two-color fluorescence in situ hybridization (FISH), der(16)t(1;16) or der(1;16) was frequently detected in low-grade papillary carcinoma but not in benign intraductal papilloma of the breast. In order to clarify the incidence and clinicopathological significance of der(16)t(1;16)/der(1;16) in common breast cancers, der(16)t(1;16)/der(1;16) was examined by two-color FISH in breast cancers resected from 51 patients by using DNA probes for 16cen, 16q11.2, and 1q12 labeled with biotin or digoxigenin. der(16)t(1;16)/der(1;16) was clonally detected in 16 cancers (31%), being more frequent in ductal carcinomas of lower grade and invasive lobular carcinoma than in high-grade invasive ductal carcinoma (P<0.001). der(16)t(1;16)/der(1;16) was also correlated with a higher amount of hormone receptors in the tumor (P<0.05). Disease-free and overall survival rates of the patient group with der(16)t(1;16)/der(1;16)-positive cancer were higher (88% and 94%) than those of the group with der(16)t(1;16)/der(1; 16)-negative cancer (39% and 68%) (P<0.05). Among the 16 patients with lymph node metastasis who received one of two similar forms of postsurgical adjuvant chemo-endocrine therapy, the prognosis of those with der(16)t(1;16)/der(1;16)-positive cancer was better than that of those with der(16)t(1;16)/der(1;16)-negative cancer (P<0.05). der(16)t(1;16)/der(1;16) detected by FISH is considered helpful in identifying patients with a better prognosis and for stratification of patients in randomized clinical trials of adjuvant chemo-endocrine therapies.

Breast Neoplasms↗

Liver metastases from colorectal cancers: detection with CT during arterial portography.

A total of 45 metastases to the liver from colorectal cancer were resected in 22 patients. The detectability of these lesions with the following modalities was determined: real-time ultrasound (US), computed tomography (CT), selective celiac arteriography (SCA), infusion hepatic angiography (IHA), CT during arterial portography (CTAP), and CT following intraarterial injection of iodized poppyseed oil (Lipiodol). The total detection rate (sensitivity) was 58% for US, 63% for CT, 27% for SCA, 50% for IHA, 84% for CTAP, and 38% for CT with iodized oil. Ten of 18 lesions less than 15 mm in largest diameter were demonstrated preoperatively by CTAP only. CTAP is useful in clarifying the locations of the lesions in the liver and should always be performed before liver metastases from colorectal cancer are resected.

Celiac Artery↗

[Diagnostic and treatment results in small-cell lung cancer detected during dispensary care].

The study was concerned with evaluating diagnosis and treatment for small-cell cancer of the lung in 75 patients who had been followed up for long periods of time before tumor detection. Methods of monitoring healthy populations as well as those at risk for lung cancer are discussed. Small-cell carcinoma was identified in 18.1%. Prophylactic fluorography of the chest conducted once a year was shown to fail to assure timely identification of small-cell cancer of the lung in most patients. An extra yearly X-ray examination of those at risk was followed by a rise in the percentage of actively--identifiable small-cell lung tumors to 66.7 while tumors detected on presentation--to 25%. Survival in small-cell lung cancer patients was studied and its median was established at 22 months in stage I--II patients given specialized antitumor treatment, 16 months in stage III and 7 months in stage IV.

Adult↗

Variation in management of small invasive breast cancers detected on screening in the former south east Thames region: observational study.

OBJECTIVE: To examine the variation in surgical and adjuvant treatment of breast cancer of known histology and detected on screening in a large cohort of patients treated by the surgeons of a health region. DESIGN: Part prospective, part retrospective observational study using the databases of a region's breast screening programme and of the cancer registry. SETTING: The former South East Thames region. SUBJECTS: 600 women aged 49-79 who presented during 1991-2 with invasive breast cancer up to 20 mm in diameter that had been detected on screening. These patients were treated by 35 surgeons. MAIN OUTCOME MEASURES: Mastectomy rate by surgeon and the use of adjuvant treatment (radiotherapy, tamoxifen, and chemotherapy) were compared with risk factors, tumour grade, resection margins, and axillary node status. RESULTS: The mastectomy rate varied between nil and 80%, although the numbers at these extremes were small (0/13 v 8/10). Surgeons operating on more than 20 such cases had a lower mastectomy rate (15%) than surgeons treating fewer cases (23%), but this difference was confounded by variation in casemix. There were also wide variations in mastectomy rates and in axillary sampling rates that were independent of casemix or caseload. There was broad agreement on the use of adjuvant tamoxifen (94%), but few patients received chemotherapy (2.5%). 78 patients (19%) did not receive radiotherapy, including 51 out of 317 patients with unfavourable tumours, and 26 patients did not receive tamoxifen. Whether the patient received adjuvant treatment was more dependent on referral by the surgeon than the risk factors for local recurrence and was independent of caseload. CONCLUSION: Mastectomy rates for similar tumours vary widely by surgeon independently of casemix or caseload, but surgeons with a higher caseload tend to have a lower mastectomy rate. Omission of postoperative radiotherapy or tamoxifen after conservative treatment is not related to risk factors for local recurrence or caseload. Confidential feedback of treatment profiles to individual surgeons has been used, but when benefit has been established treatment should be guided by evidence based protocol.

Aged↗

Promise and challenge: Markers of prostate cancer detection, diagnosis and prognosis.

Approximately 1 man in 6 will be diagnosed with prostate cancer during his life lifetime, and over 200,000 men in the U.S. are diagnosed with prostate cancer annually. Since the widespread adoption of PSA testing, about 60-70% of men at risk in the U.S. have had a blood test for prostate cancer. With this, prostate cancer death rates have decreased, yet only slightly. Thirty thousand men still die each year from this disease. PSA testing fails to identify a small but significant proportion of aggressive cancers, and only about 30% of men with a "positive" PSA have a positive biopsy. Additionally, of men who are treated for prostate cancer, about 25% require additional treatment, presumably due to disease recurrence. Also of concern is the growing evidence that there are some prostate cancers for which treatment may not be necessary. Very long-term studies from the U.S. and Europe, following men with prostate cancer have found that some tumors do not progress over time. In these individuals, prostate cancer treatment is unnecessary and harmful as these men do not benefit from treatment but will be at risk of treatment-related side effects and complications. They suggest a fundamental problem with prostate cancer: it is not possible, at this time, to predict the natural history of the disease. It is for these reasons that the most important challenge in prostate cancer today is the inability to predict the behavior of an individual tumor in an individual patient. Here we review issues related to performance and validation of biomarkers with a focus on "doing no harm", and bearing in mind that it is the ultimate goal of early detection to save lives. Improved diagnostic and prognostic biomarkers are needed for prostate cancer, and the use of these markers should ultimately translate into increased life span and quality of life. The ultimate goal would be to not only have accurate biomarkers suitable for early diagnosis, but also biomarkers that identify men at greatest risk of developing aggressive disease. Technology has been brought to bear on this problem, and the major approaches are genomics, expression analysis, and proteomics. Proteomics and DNA methylation assays may soon be used in sensitive and specific diagnostic testing of serum and tissues for cancer. Expression arrays may be used to establish both a more specific diagnosis and prognosis for a particular tumor. The proteome is only beginning to be understood, and alternative splicing and post-translational modifications of proteins such as glycosylation and phosphorylation are challenging areas of study. Finally, risk assessment and prognosis are being pursued through analysis of genomic polymorphisms (single nucleotide polymorphisms, SNPs). This huge task is only beginning, and requires the combined expertise of molecular epidemiologists, oncologists, surgeons, pathologists, and basic scientists.

Biomarkers, Tumor↗

Two-view mammography at the incident round has improved the rate of screen-detected breast cancer in Wales.

AIM: To investigate whether pre-invasive and invasive cancer detection rates were improved in Wales after the introduction of two views at incident screens. METHODS: The records of women attending follow-up screening for 2 years before and 2 years after the introduction of two-view incident screening were analysed. Cancer detection rates were compared before and after introduction of two view screening. RESULTS: At the incident round 98,752 women had one and 95,464 had two views. Five hundred and fifty-five cancers were detected with one view and 744 with two, an increased detection rate from 5.6 to 7.8 cancers per 1000 women screened (p=0.01). Two hundred and thirty-nine small cancers were detected with one view and 323 with two, increasing the detection rate from 2.4 to 3.4 per 1000 women screened (p=0.05). CONCLUSIONS: Two-view mammography at incident rounds detects more cancers and more favourable prognosis small cancers than single-view mammograms.

Breast Neoplasms↗

Tumour budding at the deepest invasive margin correlates with lymph node metastasis in submucosal colorectal cancer detected by anticytokeratin antibody CAM5.2.

In the past few years, tumour budding at the invasive margin has been reported as a new risk factor for lymph node metastasis in advanced colorectal cancers, but it is sometimes difficult to detect tumour budding in submucosal colorectal cancer by haematoxylin and eosin staining. We immunohistochemically examined tumour budding at the deepest invasive margin of 56 surgically resected submucosal colorectal carcinomas using anticytokeratin antibody CAM5.2, furthermore checked by AE1/AE3, and determined the relation between tumour budding and clinicopathological factors. Moreover, we used the monoclonal antibody D2-40 for immunohistochemistry to detect lymphatic involvement. Tumour budding was detected in 42 cases (75.0%), and the budding-positive group showed a significantly higher rate of lymph node metastasis (including isolated tumour cells) (16/42 vs 0/14; P=0.004) than the budding-negative group. The sensitivity and negative predictive value of tumour budding alone for lymph node metastasis were superior to those of lymphatic invasion alone. Furthermore, the specificity and positive predictive value of the combination of either lymphatic invasion or tumour budding were superior to those of lymphatic invasion alone. Tumour budding detected immunohistochemically by using CAM5.2 is a newly found risk factor for lymph node metastasis and may help to avoid oversurgery in the future.

Adenocarcinoma↗

[Clinical study on prostatic cancer detected incidentally by transurethral resection of the prostate].

Transurethral resection of the prostate (TUR-P) was performed on 463 consecutive patients with clinically diagnosed benign prostatic hyperplasia (BPH) between April 1994 and June 2000. Pathological examinations of resected prostatic tissues revealed prostatic cancer in 15 (3.2%) of them. Eight (53.3%) of them were in stage A1, and 7 (46.7%) in stage A2. Between 15 cases with prostatic cancer and those with BPH, clinical features including age, serum prostate specific antigen (PSA) levels, prostatic volume, PSA density (PSAD), and resected prostatic tissue weight were compared. As a result, age was the only parameter related with prostatic cancer with a statistically significant difference. The higher the age, prostate cancer was found more frequently. Postoperatively, radical prostatectomy and antiandrogen therapy were performed in 1 and 9 cases, respectively. The remaining 5 cases are being followed with no treatment for prostatic cancer, and have shown no findings suggesting recurrence. These 15 cases are all living disease-free at present. It seems of importance to explain preoperatively the possible detection of prostatic cancer in association with TUR-P, particularly for elderly patients aged 80 years or older.

Adenocarcinoma↗

Estrogen receptors in human breast cancer detected by the fluorescent estradiol histochemical and dextran coated charcoal techniques.

Surgical specimens from 60 Japanese women with breast cancer were studied histochemically to detect estrogen receptors (ER). Forty-six were analyzed in a double blind study designed to compare the histochemical method using fluorescent estradiol conjugate for detection of ER (FITC method) with findings in case of the currently employed dextran coated charcoal (DCC method) techniques. The ER test was positive in 39 (65 percent) of the 60 cases studied by FITC method. Of the 46 cases analysed in a double blind study, 41 (89.8 percent) showed the same results. Of the 5 with inconsistent test results, 2 showed positive DCC and negative FITC, and 3, negative DCC and positive FITC. According to the histologic type, the FITC method demonstrated a low positive ER response rate in scirrhous cases (57 per cent), whereas the positive rate was 67 percent among papillotubular-type cases and 65 percent among medullary tubular-type cases. In relation to menstrual status, the positive rates were 68 percent and 64 percent among premenopausal and postmenopausal women, respectively. However, in relation to tumor size, no difference was noted in the positive response rate by either method. Therefore, both the DCC and FITC methods are clinically useful to determine the indications for hormone therapy.

Breast Neoplasms↗

Bladder cancer detection and surveillance: carcinoembryonic antigen as a monitor of neoplastic transformation.

Routine cytopathology of exfoliated urothelial cells will identify only 70% of patients with transitional cell carcinoma (TCC) because most well-differentiated bladder tumors are not detected. Carcinoembryonic antigen (CEA) was identified on urothelial cancer cells from 66% of patients with grade I TCC, 65% with grade II TCC, 65% with grade III TCC, and 80% of patients with CIS. Immunoperoxidase labelling of CEA can enhance the sensitivity of exfoliative cytology.

Carcinoembryonic Antigen↗

Clinical usefulness of serum antip53 antibodies for prostate cancer detection: a comparative study with prostate specific antigen parameters.

PURPOSE: Alterations in the p53 tumor suppressor gene located on human chromosome 17p13.1 are currently the most common genetic abnormalities associated with many different types of human malignancies. Recently serum p53 antibodies (p53-Abs) have been detected in the serum of patients with various cancers. To evaluate the clinical usefulness of serum p53-Abs we compared p53-Abs with prostate specific antigen (PSA) parameters in patients with benign prostatic disease (BPD) and prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from 50 patients with BPD and 103 with histologically diagnosed prostate cancer, including T1c/2N0M0 in 50, T3N0M0 in 29 and TxNxM1 in 24. The serum p53-Abs titer was assessed by enzyme-linked immunoabsorbent assay using a MESCUP Kit II (Medical and Biological Laboratories Co., Ltd., Nagoya, Japan) antip53 test. Free and total PSA was measured using an Architect (Dinabott, Chicago, Illinois) PSA kit. The clinical values of p53-Abs were compared with total PSA, PSA density (PSAD), PSA density of the transition zone (PSATZD) and the free-to-total PSA ratio using ROC curves. RESULTS: All patients with prostate cancer had significantly higher total PSA, PSAD, PSATZD and p53-Abs than patients with BPD. While total PSA, PSAD, PSATZD and free-to-total PSA ratios were associated with stage progression, serum p53-Abs were not related to clinical stage. The Gleason sum 5 or less group had a higher level of p53-Abs than higher Gleason sum groups. Patients with T1c cancer had significantly higher p53-Abs than those with BPD. According to ROC curve analysis to distinguish prostate cancer from BPD the p53-Abs titer had the greatest AUC in the overall patient population and in patients without digital rectal examination findings. CONCLUSIONS: These results suggest that p53-Abs might be helpful in the clinical decision to perform prostate biopsy. In the current study the serum p53-Abs titer had the most useful validity in discriminating between prostate cancer and BPD in the overall patient population and in patients with normal digital rectal examination.

Aged↗

Loss of heterozygosity in ovarian cancer: detection by PCR and microsatellite polymorphism.

Loss of chromosome 6q was investigated in endometrial and ovarian carcinomas by a PCR based-microsatellite polymorphism analysis. Results obtained show that this technique is able to detect frequent loss of heterozygosity in the ovarian cancers (10/27) and only in the serous type (8/17). Then, this kind of analysis can contribute to the understanding of tumor development and progression of ovarian cancers with different histopathological features.

Base Sequence↗

Patterns of breast cancer detection in the United States.

The American College of Surgeons Commission on Cancer Short-term Survey of Breast Cancer in 12,315 patients showed that 73% of malignant tumors are found by patients, 23% by physicians, and 4% by mammography. It also indicated that younger women are more likely to discover tumors than older women, and that mammography is more likely to detect small tumors with negative axillary nodes. The effectiveness of mammography is most evident in women 50 to 74 years of age, although in women 45 to 49 years, the frequency of tumors detected by mammography nearly equals that for other groups. In black women, mammography may not be currently fully utilized. Analysis of the survey data would indicate that patients appear to demonstrate adequate skill in detecting tumors, as compared to physicians. A delay in diagnosis of longer than 3 months is associated with larger tumors and increased likelihood of axillary metastasis.

Adenocarcinoma↗

Multicenter evaluation of an artificial neural network to increase the prostate cancer detection rate and reduce unnecessary biopsies.

BACKGROUND: The percentage of free prostate-specific antigen (%fPSA) has been shown to improve specificity for the diagnosis of prostate cancer (PCa) over total PSA (tPSA). A multicenter study was performed to evaluate the diagnostic value of a %fPSA-based artificial neural network (ANN) in men with tPSA concentrations between 2 and 20 microg/L for detecting patients with increased risk of a positive prostate biopsy for cancer. METHODS: We enrolled 1188 men from six different hospitals with PCa or benign prostates between 1996 and 2001. We used a newly developed ANN with input data of tPSA, %fPSA, patient age, prostate volume, and digital rectal examination (DRE) status to calculate the risk for the presence of PCa within different tPSA ranges (2-4, 4.1-10, 2-10, 10.1-20, and 2-20 microg/L) at the 90% and 95% specificity or sensitivity cutoffs, depending on the tPSA concentration. ROC analysis and cutoff calculations were used to estimate the diagnostic improvement of the ANN compared with %fPSA alone. RESULTS: In the low tPSA range (2-4 microg/L), the ANN detected 72% and 65% of cancers at specificities of 90% or 95%, respectively. At 4-10 microg/L tPSA, the ANN detected 90% and 95% of cancers with specificities of 62% and 41%, respectively. Use of the ANN with 2-10 microg/L tPSA enhanced the specificity of %fPSA by 20-22%, thus reducing the number of unnecessary biopsies. CONCLUSIONS: Enhanced accuracy of PCa detection over that obtained using %fPSA alone can be achieved with a %fPSA-based ANN that also includes clinical information from DRE and prostate volume measurements.

Adult↗