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Lung cancer diagnosis: evaluation of diagnostic techniques.

In 200 patients with histologically proven lung cancer, retrospective analysis of the relative diagnostic value of sputum cytology, bronchial washings cytology, bronchial biopsy, scalene node biopsy, mediastinoscopy and thoracotomy was undertaken. Bronchial biopsy proved positive in 80 percent of patients with central tumours (those lying between the origin of a main brochus and the origins of lobar segmental bronchi) against 35 percent of patients with peripheral tumours (those lying distal to the origins of the lobar segmental bronchi). Sputum cytology was positive in 27 percent of patients so investigated and bronchial washings cytology in 14 percent--both techniques being more effective with central tumours. Thoracotomy, as the sole method of obtaining histological confirmation of the clinical diagnosis, accounted for 20.5 percent of all cases, being used more often in patients with peripheral tumours. In 15 percent the first histologically positive result came from distal spread. The relative indications for needle biopsy and endobronchial fibroscopy are discussed.

Biopsy↗

Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays.

A noninvasive screening test would significantly facilitate early detection of epithelial ovarian cancer. This study used a combination of high-throughput selection and array-based serologic detection of many antigens indicative of the presence of cancer, thereby using the immune system as a biosensor. This high-throughput selection involved biopanning of an ovarian cancer phage display library using serum immunoglobulins from an ovarian cancer patient as bait. Protein macroarrays containing 480 of these selected antigen clones revealed 65 clones that interacted with immunoglobulins in sera from 32 ovarian cancer patients but not with sera from 25 healthy women or 14 patients having other benign or malignant gynecologic diseases. Sequence analysis data of these 65 clones revealed 62 different antigens. Among the markers, we identified some known antigens, including RCAS1, signal recognition protein-19, AHNAK-related sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic initiation factor 5A, and casein kinase II, as well as many previously uncharacterized antigenic gene products. Using these 65 antigens on protein microarrays, we trained neural networks on two-color fluorescent detection of serum IgG binding and found an average sensitivity and specificity of 55% and 98%, respectively. In addition, the top 6 of the most specific clones resulted in an average sensitivity and specificity of 32% and 94%, respectively. This global approach to antigenic profiling, epitomics, has applications to cancer and autoimmune diseases for diagnostic and therapeutic studies. Further work with larger panels of antigens should provide a comprehensive set of markers with sufficient sensitivity and specificity suitable for clinical testing in high-risk populations.

Antigens, Neoplasm↗

[Duration of the diagnostic process for lung cancer versus other solid tumors at the National Oncology Institute of Ecuador].

OBJECTIVE: To determine the duration of the outpatient diagnostic process for lung cancer in comparison to that of other solid organ tumors/all tumors at the National Oncology Institute-Society to Fight Cancer (ION-SOLCA) of Ecuador. PATIENTS AND METHODS: All patients with non-small cell lung cancer (NSCLC) seen between January 1 and December 31, 1995 at the ION-SOLCA, a specialized tertiary care hospital in Guayaquil, Ecuador, were studied. The duration of the patients' diagnostic process was compared to that of other patients with solid organ tumors (1 control per NSCLC patient). DESIGN: Retrospective study of health care services to measure the duration of each stage of the diagnostic process for cancer patients at the ION-SOLCA. MEASURES: The main variable was the duration of the diagnostic process. The duration of each phase of the process was also recorded. RESULTS: Results are given as means ( standard deviations, with standard errors between parentheses). The overall duration of the diagnostic process for all solid organ tumors (lung and others) at the ION-SOLCA was 54.5 days 62.3 (7.6). No differences were detected between the duration of diagnosis for lung and other tumors. The durations of the different phases of diagnosis were as follows: from the first pre-admission contact with the hospital until a visit with a specialist, 12.5 days 11.4 (1.4); from the visit with a specialist until a diagnostic procedure, 33.3 days 57 (7); and from the diagnostic procedure until the pathological diagnosis, 8.7 days 6.9 (0.8). CONCLUSIONS: Outpatient evaluation is an inefficient, slow and potentially dangerous process in cases in which the probability of a cancer diagnosis is high. A more interventionist process involving hospital admission may accelerate diagnosis in such cases.

Cancer Care Facilities↗

Diagnostic tests for lung cancer.

Bronchogenic carcinoma is the leading cause of cancer death in both men and women in the United States. There has been little impact on the overall mortality from lung cancer in the past 20 years. Diagnostic tests such as routine chest x-ray and sputum cytology have proven to be ineffective in altering this mortality. The identification of risk factors, including obstructive lung disease and familial tendencies to develop lung cancer, may allow for specific strategies that will impact this mortality. Additionally, biological markers are being identified in sputum specimens that may allow identification of premalignant changes prior to morphologic changes seen in sputum cytology. Radiologic testing such as CT scans with contrast enhancement and positive emission tomography may also aid in the early detection of peripheral lung nodules. It is through the development of these new technologies that we have an opportunity to alter overall lung cancer mortality. Here we review several articles reporting exciting new diagnostic technology.

Biomarkers, Tumor↗

Reducing diagnostic delay in breast cancer. Possible therapeutic implications. GIVIO (Interdisciplinary Group for Cancer Care Evaluation) Italy.

A detailed examination of the diagnostic process of 1110 newly diagnosed breast cancer patients first seen at 63 Italian general hospitals showed that 36% of them were diagnosed more than 3 months after the appearance of the first symptom. Whereas 17% (108/633) of the women with less than or equal to 3 months delay were Stage III and IV, the corresponding proportion among women with greater than 3 months delay was 32% (101/320), suggesting that 15% of advanced cases can be attributed to diagnostic delay. A 9% gain in survival at 5 years (66% vs. 57%) could be postulated if reported figures on mortality by stage are applied to our patients with less than or equal to 3 months delay compared to those with greater than 3 months. Moreover, examining the two components of delay (first symptom-first visit and first visit-final diagnosis) our data suggest that the potential benefits of timely presentation were, for some patients, cancelled by delays arising in the health care system. Breast self-examination (BSE) was practiced by 34% of the total population, but only 9% did it on a regular monthly basis. Although any type of BSE (regular and irregular) was associated with a smaller primary at presentation, a limited benefit of the procedure in terms of nodal involvement and pathologic stage of disease was evident only among regular BSE performers.

Breast Neoplasms↗

Hypertension and breast cancer risk in a 19-year follow-up study (the DOM cohort). Diagnostic investigation into mammarian cancer.

BACKGROUND: To investigate whether hypertension and the use of anti-hypertensive drugs are associated with breast cancer risk. METHODS: This was a prospective study of 11, 011 women living in Utrecht, the Netherlands, aged 50-65 years at enrolment in a breast cancer screening project (DOM cohort). Women attended screening rounds between 1974 and 1985 at which blood pressure was measured and information on drug use and breast cancer risk factors was ascertained. Since 1974 (median follow-up time 19 years), information on breast cancer occurrence and death has been registered. Hypertension was defined as a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 95 mmHg or current use of drugs for the indication hypertension. Cox's regression analysis was used to investigate the association between hypertension (treated or untreated) and subsequent breast cancer risk. Analyses were adjusted for age, body mass index, height, parity, familial breast cancer, smoking and oral contraceptive use. RESULTS: A total of 523 women were diagnosed with breast cancer. Hypertensive women experienced a statistically significant increased breast cancer risk of 23% (age-adjusted hazard ratio (HRa) = 1.23; 95% confidence interval (CI) 1.01 -1.49). After adjustment for all confounders, the increase was 14% (HR = 1.14; 95% CI 0.93-1.40). The decline in risk was mainly attributable to the effect of BMI. The risk was similar in treated (HR = 1.22; 95% CI 0.91-1.63) and untreated hypertensive women (HR = 1.13; 95% CI 0.91-1.40). CONCLUSION: These results do not support an association between hypertension and breast cancer, and if there is a link, it is likely to be positive and relatively small in size (+14%). This relation, if present, is not attributable to anti-hypertensive drugs, since the relation is also present in non-drug users.

Aged↗

The carcinoembryonic antigen test in urologic cancer.

The diagnostic value of the CEA test was evaluated in 2,029 blood and urine samples from 308 patients with urologic cancer, 13 with nonurologic cancer, 20 urologic patients with nonmalignant disease, and in 30 controls. The blood CEA test was positive in 50% of the patients with active urologic cancer and in 35% of those with inactive cancer. The urine CEA test was elevated only in patients with active bladder cancer, but most of these had concurrently infected urines. At the present time, the CEA test does not reflect the accuracy necessary for an acceptable diagnostic test for the detection of urologic cancer.

Carcinoembryonic Antigen↗

Comparison of telomerase activity and GSTP1 promoter methylation in ejaculate as potential screening tests for prostate cancer.

New diagnostic tools are needed for the early detection of prostatic cancer. The molecular detection of prostate cancer cells in ejaculates was evaluated using complementary PCR-based methods. LNCaP cells, a cell line derived from prostatic carcinoma, were spiked into normal seminal ejaculates and the prostatic epithelial component of the specimens was isolated by immunomagnetic bead sorting, using a monoclonal antibody to prostate-specific membrane antigen (PSMA). Ejaculates from nine patients with a recent diagnosis of prostate cancer were processed in a similar fashion, using LNCaP-spiked aliquots as an internal positive control. Telomerase expression was evaluated by the telomeric repeat amplification protocol (TRAP) and glutathione S-transferase gene promoter (GSTP1) hypermethylation was evaluated by methylation-sensitive restriction endonuclease digestion and PCR amplification. Telomerase activity was detected in LNCaP cells recovered from normal seminal ejaculates but was not found in all nine samples from patients with prostate cancer. The sensitivity of GSTP1 analysis was similar to telomerase analysis for the detection of LNCaP cells from normal ejaculate samples but was positive in ejaculates from four out of nine patients with prostate cancer. GSTP1 DNA methylation status is more sensitive than telomerase analysis for the detection of malignant cells in seminal ejaculates from patients with prostate cancer.

DNA Methylation↗

Tumour marker CA 50 levels compared to signs and symptoms in the diagnosis of pancreatic cancer.

The diagnostic merits of CA 50 and of symptoms indicating pancreatic cancer (pain, jaundice, weight loss, malabsorption) were compared prospectively in 512 consecutive patients. Among the final diagnoses were: exocrine pancreatic cancer, 175; periampullary cancer, 44; other gastrointestinal cancer, 45; and chronic pancreatitis, 64 cases. The suspected diagnoses based on symptoms and signs were correct in 80% of the patients with exocrine pancreatic cancer, in 78% with periampullary, in 76% with other gastrointestinal cancer and in 90% with chronic pancreatitis. CA 50 was pathological in 96% of the cases with exocrine pancreatic cancer, in 70% with periampullary, in 78% with other gastrointestinal malignancies and in 36% with chronic pancreatitis. The sensitivity was 96%, specificity 48%, positive prediction 49% and negative prediction 96%, depending on cut-off level. The single CA 50 value was comparable to symptoms and signs regarding sensitivity and negative prediction. In 28 of 42 cases incorrectly clinically classified, CA 50 alone indicated a benign or malignant diagnosis. If both the modalities 'signs and symptoms' and CA 50 were combined, the sensitivity was 91%, the specificity 92%, the positive prediction 86% and the negative prediction 95%. The initial CA 50 value can help to indicate in which patients a pancreatic malignancy should be suspected.

Adolescent↗

Fiberoptic colonoscopic examination in surgical patients with colorectal cancer.

A diagnostic and surveillance program using colonscopy in patients with colorectal cancer was established at North Carolina Memorial Hospital. The records of all patients who had preoperative or postoperative colonoscopic examination between 1976 and 1979 were reviewed. Fifty-five patients had colonscopic examination preoperatively. No additional disease was found in 39. In 15 patients, unsuspected additional disease was detected, and one patient had a suspected polyp ruled out by colonoscopic examination. One of these patients was found to have a synchronous primary cancer, not demonstrated by barium enema. Surgical treatment was modified in nine (16%) of these 55 patients by the preoperative colonoscopic findings. Sixty patients had colonoscopy six months to six years postoperatively. No additional disease was found in 47. Adenomatous polyps were found in eight. Two patients had recurrent cancer proved by colonoscopy, and three had a second primary cancer detected only by colonoscopy. Treatment was directly influenced by colonoscopy in eight (13.3%) of these 60 patients. These studies had a favorable cost/benefit ratio in patients with colorectal cancer and support a program of preoperative colonoscopy in patients with colorectal cancer and reexamination within two to three years after operation.

Colonic Neoplasms↗

Importance of early diagnosis in managing ovarian cancer.

Because of diagnostic difficulties, ovarian cancer is a disease that is characterised by disappointing survival rates and a very real risk of relapse. This article highlights the importance of early diagnosis, risk factors and screening for ovarian cancer and outlines the treatment options that are available.

Antineoplastic Agents↗

Detailed faecal bile acid profile: a diagnostic test for colorectal cancer?

Detailed profiles of bile acids in faeces were evaluated as a diagnostic test for colorectal cancer in rats. Twenty-seven bile acid peaks were measured using improved methods of extraction and separation followed by the sensitive and specific techniques of capillary column gas liquid chromatography and mass spectrometry. Colorectal cancer was induced in experimental animals (female Sprague-Dawley rats, n = 20) by subcutaneous injection of dimethylhydrazine (DMH) and faecal unconjugated bile acids compared with those in the control group (n = 20). The amount of total faecal unconjugated bile acids was lower in the animals administered DMH (255 mg/day vs 334 mg/day: (P = 0.04), and the excretion of seven individual bile acids was reduced when compared with those in the control group (P less than 0.01). In order to use the faecal bile acid profiles as a diagnostic test, linear discriminant analysis was performed. A discriminant score was derived which was applied to each profile, to determine to which group (control or DMH) each animal belonged retrospectively. All analyses were performed blind, and 90% of the animals were correctly assigned. In man, as in rats, the bile acid profile of faces is equally complex and the bile acid profile may be useful as a diagnostic test.

Animals↗

[Usefulness and limitation of digital rectal examination and imaging studies in staging prostate cancer].

The diagnostic usefulness of digital rectal examination (DRE), transrectal ultrasonography (TRUS), magnetic resonance imaging (MRI) and computed tomography (CT) was compared in the differentiation of stage B from stage C prostate cancer. Eighteen patients who had undergone radical retropubic prostatectomy were included in this study. Overall, the positive predictive values (PPV) for detecting extraprostatic disease (extracapsular extension, seminal vesicle invasion) were 100% for DRE, 88.9% for TRUS and 80.0% for MRI, respectively. Corresponding figures for accuracy in detecting extraprostatic spread were 55.6%, 66.7% and 61.1%, respectively. The PPV and accuracy for detecting extraprostatic disease in 13 patients with localized cancer (< stage B) were 75.0%, 53.8% for TRUS and 66.7%, 53.8% for MRI, respectively. Both of these examinations appeared to be superior to DRE alone. The PPV and accuracy increased when findings on TRUS and MRI coincided. Computed tomography was less accurate than MRI in diagnosing nodal involvement because of the higher incidence of false positives. Further efforts should be focused on enhancing preoperative diagnostic precision in staging prostate cancer because of the limited usefulness of the current imaging techniques. Development of more reliable diagnostic modalities or designing ideal combination of these studies are desperately needed.

Aged↗

Investigation of diagnostic criteria for cancer-related fatigue syndrome in patients with advanced cancer: a feasibility study.

The primary aim of this study was to explore the feasibility of applying diagnostic criteria for cancer-related fatigue syndrome (CRFS) in patients with advanced cancer. A secondary aim was to assess the use of screening instruments for fatigue and depression in this population. Patients with advanced cancer (n=16) were interviewed using the Diagnostic Interview for CRFS and a semi-structured psychiatric interview. Subjects also completed the Bi-dimensional Fatigue Scale (BFS) and the Edinburgh Postnatal Depression Scale (EPDS) as screening instruments. The prevalence of psychiatric disorders was 50% (8/16). The EPDS was found to have a sensitivity of 67% and a specificity of 100% for detecting depression. The prevalence of clinically significant fatigue symptoms was 62.5% (10/16). The BFS was found to have a sensitivity of 70% and a specificity of 64% for detecting clinically significant fatigue. The prevalence of CRFS was 12.5% (2/16).

Fatigue↗

Thyroid cancer in pregnant women: diagnostic and therapeutic management.

There is considerable literature on the effect of pregnancy on established thyroid cancer. In contrast, there are only isolated case reports of management of thyroid cancer diagnosed de novo during pregnancy. We describe four such patients. We recommend fine-needle aspiration biopsy (FNA) of solitary thyroid nodules found early in pregnancy. When the cytopathology is diagnostic of thyroid cancer, thyroidectomy under local or general anesthesia is advised. The patient should be given levothyroxine in a dose sufficient to keep serum thyroid-stimulating hormone (TSH) low. Serum thyroglobulin is a valuable noninvasive method of evaluating completeness of this therapy. The work-up of a nodule found late in pregnancy is best deferred until after delivery.

Adenocarcinoma, Papillary↗

Artificial neural network for prediction of lymph node metastases in gastric cancer: a phase II diagnostic study.

BACKGROUND: Extension of lymphadenectomy in gastric cancer is controversial, and preoperative diagnosis of lymph node metastases (LNM) is difficult. Therefore, knowledge-based systems such as the Maruyama computer program (MCP) are being developed. MCP shows good prognostic value for the compartments; however, for different lymph node groups (LNG) there are a large number of false positives. The aim of this study was to evaluate artificial neural networks (ANN) for predicting LNM in patients with gastric cancer and to compare the predictive power with that of MCP. METHODS: A total of 135 consecutive patients who underwent D2 gastrectomy were included. We applied a single-layer perceptron to the data of 4302 patients from the National Cancer Center, Tokyo, and compared the results with those from the MCP. RESULTS: Prediction of N(+) or N0 with ANN-1 (Borrmann classification, T category, and tumor size and location) had an accuracy of 79%. The predictive value for LNM in each of the LNG varied: ANN-1, 64% to 86%; MCP, 42% to 70%. We constructed another ANN by using the additional parameter of metastases in LNG 3 as an example of sentinel node. The accuracy of this ANN was 93%. CONCLUSIONS: Using an ANN, LNM in each LNG can be accurately predicted. Additional knowledge about one lymph node improves the results.

Adult↗

Prospective comparison of stereotactic core biopsy and surgical excision as diagnostic procedures for breast cancer patients.

OBJECTIVE: To determine whether stereotactic core biopsy (SCNB) is the diagnostic method of choice for all mammographic abnormalities requiring tissue sampling. SUMMARY BACKGROUND DATA: Stereotactic core needle biopsy decreases the cost of diagnosis, but its impact on the number of surgical procedures needed to complete local therapy has not been studied in a large, unselected patient population. METHODS: A total of 1,852 mammographic abnormalities in 1,550 consecutive patients were prospectively categorized for level of cancer risk and underwent SCNB or diagnostic needle localization and surgical excision. Diagnosis, type of cancer surgery, and number of surgical procedures to complete local therapy were obtained from surgical and pathology databases. RESULTS: The malignancy rate was 24%. Surgical biopsy patients were older, more likely to have cancer, and more likely to be treated with breast-conserving therapy than those in the SCNB group. For all types of lesions, regardless of degree of suspicion, patients diagnosed by SCNB were almost three times more likely to have one surgical procedure. However, for patients treated with lumpectomy alone, the number of surgical procedures and the rate of negative margins did not differ between groups. CONCLUSIONS: Stereotactic core needle biopsy is the diagnostic procedure of choice for most mammographic abnormalities. However, for patients undergoing lumpectomy without axillary surgery, it is an extra invasive procedure that does not facilitate obtaining negative margins.

Biopsy, Needle↗

Advances in diagnostic practices affect thyroid cancer incidence in France.

OBJECTIVE: To analyse trends in diagnostic practices of thyroid diseases and to relate them to the increase in thyroid cancer incidence in France over time. DESIGN: From 1980 to 2000, a French retrospective multicentric (three endocrinology and three nuclear medicine centres) study of thyroid diseases was conducted on 20 consecutive unselected patients' records, sampled every 5 years in each centre. METHODS: Characteristics of the population and diagnosis procedures (thyroid ultrasonography (US), radionuclide scan, cytology and hormonal measurements) were described over time. Changing trends in operated patients and in cancer prevalence were analysed as well as the impact of practices on cancer incidence. RESULTS: The study included 471 patients (82% female, mean age 46.7, range 9-84 years), referred for nodular thyroid diseases (66.7%) or thyroid dysfunctions (33.3%). A significant increase in US (3 to 84.8%) and cytological practices (4.5 to 23%), and a decrease (89.4 to 49.6%) in radionuclide scan procedures were observed over time. Although the proportion of patients undergoing surgery remained constant (24.8%), the prevalence of cancer increased among operated patients from 12.5 to 37% (P=0.006). In a Cox's proportional hazard model stratified on the clinical characteristics of patients, only the cytological practice, regardless of its results, was significantly associated with the occurrence of cancer: relative risk (RR)=4.4 (95% confidence interval (CI): 1.1-16; P=0.04). CONCLUSIONS: From 1980 to 2000, a major evolution in clinical practices has led to the increase in thyroid cancer reported in France. Such changes in medical, as well as in surgical and pathological, practices must be taken into account in incidence measurement.

Adolescent↗