[Lung cancer: Progress in diagnosis and treatment. II. Diagnostic imaging: 4. Radioisotope diagnosis of lung cancer].
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Animals↗
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Supporting women during breast diagnostics.
Breast cancer is the most frequently diagnosed cancer among Canadian women. It is estimated that, in 1997, there will be 18,400 new cases of breast cancer and 5,100 breast cancer deaths among Canadian women; one in nine Canadian women will develop breast cancer at some time in their lives.
Breast Neoplasms↗
Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy.
The diagnosis of prostate cancer on needle biopsy is based on a constellation of histologic features. There are, however, three histologic findings that are diagnostic of prostate carcinoma: perineural invasion (PNI), mucinous fibroplasia, and glomerulations. We prospectively identified core needle biopsies during a 5-month period in which one of these three entities was the key diagnostic feature of carcinoma within the biopsy specimen. Of 1480 consult cases reviewed, the following were key features to the diagnosis of very limited carcinoma: PNI (n = 9; 0.6%), mucinous fibroplasia (n = 2; 0.1%), and glomerulations (n = 0). To assess the incidence of PNI as the key feature, we also analyzed reports from Dianon during a 1-year period. Of approximately 16,300 Dianon needle biopsies with cancer, 12(0.07%) cases had PNI as the key diagnostic feature. Six of these 12 cases were also consult cases. Of the total of 15 cases with PNI, cancer was limited with 11 of the cases showing involvement of only one nerve. The median number of glands per nerve was five (range, 1-15). In addition to PNI, malignant cytologic features included amphophilic cytoplasm in 11 of 11 assessable cases and nuclear enlargement and hyperchromasia in 11 of 15 cases. Other malignant features were limited. Twelve cases showed rare to no visible nucleoli. Two cases had eosinophilic intraluminal debris. Blue mucin, crystalloids, and mitoses were absent in all cases. Nine of the 15 cases of PNI and the two cases of mucinous fibroplasia were verified as carcinoma with immunohistochemistry using high molecular weight cytokeratin. In rare cases, PNI is virtually the sole finding necessary to establish the diagnosis of carcinoma on needle biopsy. Although mucinous fibroplasia and glomerulations are also considered diagnostic of carcinoma, their occurrence alone without more conventional forms of carcinoma is even more rare.
Adenocarcinoma↗
Ten years of respiratory cytopathology at Duke University Medical Center. I. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, noting the significance of specimen number and type.
In 1975 at Duke University Medical Center, a retrospective and prospective survey of respiratory cytopathologic specimens was undertaken for the ten-year period 1970 to 1979. The purpose of this study was to document the role of cytopathology in the diagnosis of lung cancer at this institution. This paper, the first of a series on the subject, presents the relationship between the number of cytopathologic specimens examined, the types of respiratory cytopathologic specimens examined and the cytopathologic diagnosis of lung cancer during the first five years of the study. Of the total, 363 patients had respiratory cytopathologic specimens that were interpreted as being diagnostic of cancer. Among those patients with cytopathology diagnostic of cancer, a diagnosis was made with five satisfactory specimens in 86.6%. Sputum only revealed neoplastic cells in 47.1% of the cases, bronchial material only in 26.0% and both sputum and bronchial material in 26.9%. Among the total number of primary lung cancers seen during this five-year period, a definitive cytopathologic diagnosis of cancer was made in approximately 50% of cases.
Bronchi↗
Diagnostic significance of cancer-associated carbohydrate antigen (CA19-9) concentrations in pancreatic juice: analysis in pure pancreatic juice collected by endoscopic aspiration and immunohistochemical study in chronic pancreatitis.
This study evaluated the diagnostic significance of concentrations of the cancer-associated carbohydrate antigen CA19-9 in pure pancreatic juice (PPJ) collected by endoscopic cannulation. We also attempted to elucidate the features and source of the increased CA19-9 concentration found in the pancreatic juice of patients with chronic pancreatitis (CP) by means of immunohistochemical staining. The mean output as well as the mean concentration of CA19-9 in each of the four fractions collected was highest in patients with pancreatic cancer (PC) and also was elevated significantly in patients with CP compared with controls. However, CA19-9 concentrations were not elevated in patients with cholecystolithiasis. When the cutoff value was set as the mean concentration + 2SD of the controls, significantly elevated concentrations of CA19-9 were found in the third fraction (secretory phase) in 90% of the patients with PC and 66% of the patients with CP. Immunohistochemical staining revealed that CA19-9 was expressed more widely in the ductal cells of CP tissues than in those of normal pancreatic (NP) tissues, with CP tissue showing more CA19-9-positive ductal cells per area than NP tissues. In NP tissue, CA19-9 was localized to the apical surface and supranuclear regions (apical type) in all the ductal cells stained by the antigen, while approximately 50% of cases with CP exhibited a cytoplasmic pattern showing a loss of polarity of the antigen expression. Moreover, this cellular localization pattern was more pronounced in the small ducts that had proliferated and aggregated following the destruction of lobules in CP.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, Tumor-Associated, Carbohydrate↗
[THE ACTIVITY OF PHOSPHO-6-GLUCONATE DEHYDROGENASE IN THE VAGINAL FLUID: NEW DIAGNOSTIC TEST FOR GENITAL CANCER].
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Alcohol Oxidoreductases↗
Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography.
Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are sophisticated modalities typically used in the second-line diagnosis following routine clinical practice. Among them, CT is regarded as the standard imaging in diagnosing pancreatic cancer at present in Japan due to its popularity and reasonable reliability in wide-ranging diagnostic ability. However, even with multidetector row CT (MDCT), the demonstration of pancreatic cancer less than 1 cm in size remains nearly impossible. CT staging is considered accurate in one-half to two-thirds of patients, but limitations in the imaging of peripancreatic microinvasion and nodal or hepatic micrometastases still have a tendency to underestimate tumor extension. With recent advancement in imaging techniques, MRI has proven to be equal or superior to other imaging modalities in diagnosing pancreatic cancer. Most of all, it is expected that MRCP will become as effective an instrument as ultra-sonography (US) in the screening of pancreatic cancer. Functional imaging with PET using the glucose analog FDG can be used in the diagnosis of pancreatic cancer, but systemic or local disturbance of glucose metabolism may result in an incorrect diagnosis. The usefulness of PET is now considered in assessing tumor viability, monitoring tumor response to treatment, and detecting distant metastases.
Carcinoma↗
Quality control of mammography screening in the Veneto Region. Evaluation of four programs at a local health unit level--analysis of the frequency and diagnostic pattern of interval cancers.
AIMS AND BACKGROUND: Service mammography screening has been reported to have suboptimal performance compared to controlled trials. The aim of this study was to evaluate the sensitivity of the mammography screening program in four Local Health Units (ASL) and the possible causes of diagnostic error in cases further surfacing as interval cancers. MATERIAL AND METHODS: Interval cancers were identified by cross checking of screened women databases with hospital discharge records reporting breast cancer. Proportional interval cancer incidence (observed interval cancers/expected invasive cancers) was determined by matching the database of women screened during 1999-2002 to the hospital discharge records databases during 1999-2003. The ratio of observed interval cancer rate to underlying incidence was compared to international standards and with literature data. Screening mammograms reported as negative and followed by interval cancers were randomly mixed with true-negative controls, and the resulting set underwent blind review by an external radiologist who applied the conventional criteria recommended for the classification of the type of diagnostic error (occult, minimal signs, screening error). RESULTS: Matching of screening archives with the hospital discharge records databases allowed for the identification of 154 invasive interval cancers compared to 480 expected. The proportional observed/expected interval cancer incidence in the first and second year of the interval was 21% and 46%, respectively (ASL 1 = 14% or 38%, ASL 2 = 19% or 48%, ASL 3 = 30% or 53%, ASL 4 = 25% or 49%). Radiological review included 38 further interval cancer cases, identified after the time limits defined for proportional interval cancer incidence assessment, and could not include 18 interval cancers, not retrieved from ASL 4 archives: overall, 174 interval cancers were reviewed, of which 135 were classified as occult (77.3%) (ASL 1 = 83.3%, ASL 2 = 71.1%, ASL 3 = 78.6%, ASL 4 = 75%), 12 (6.9%) as minimal signs (ASL 1 = 6.6%, ASL 2 = 11.5%, ASL 3 = 2.4%, ASL 4 = 5%), and 27 (15.5%) as screening error (ASL 1 = 8.3%, ASL 2 = 17.3%, ASL 3 = 19.0%, ASL 4 = 25%). CONCLUSIONS: Observed proportional interval cancer incidence was lower than commonly reported for service screening programs and currently recommended (< 30% in the first, < 50% in the second year of the interval). The analysis of interval cancer causes showed a screening error rate below the maximum acceptable standard (< 20% of interval cancers should be classified as screening error) in three of four programs and in average figures. Substantial differences observed among single programs (one did not comply to recommended standards) suggest that space is available for the improvement of overall performance by optimizing program organization and by further training of radiologists. Overall, the analysis showed a good sensitivity of the screening program in the Veneto Region, although the performance was inferior to that of excellence centers, and further action to improve it is possible. Assessment and review of interval cancers is an early indicator of screening efficacy which has not yet been fully adopted in Italian screening programs. Although using hospital discharge records to identify interval cancers may be affected by limited errors, such a procedure is particularly convenient, as data from hospital discharge records are available much in advance compared to cancer registries and are the most reliable source of information for areas uncovered by a cancer registry. Hospital discharge records-based procedures for interval cancers assessment should be employed routinely in screening programs.
Breast Neoplasms↗
Diagnostic potential in bladder cancer of a panel of tumor markers (calreticulin, gamma -synuclein, and catechol-o-methyltransferase) identified by proteomic analysis.
Using proteomic analysis, we previously identified calreticulin (CRT) as a potentially useful urinary marker for bladder cancer. Now, we have also identified gamma -synuclein (SNCG) and a soluble isoform of catechol-o-methyltransferase (s-COMT) as novel candidates for tumor markers in bladder cancer, by means of proteomic analysis. In the process of establishing a superior tumor marker system, we investigated the diagnostic value of a combination assay of these three proteins. Voided urine samples were obtained from 112 bladder cancer and 230 control patients. Urinary CRT, SNCG, and s-COMT were measured as a combined marker by quantitative western blot analysis. Relative concentration of each protein was calculated and the diagnostic value of a concomitant examination of these markers was evaluated by receiver operator characteristic analysis. With the best diagnostic cutoff, the overall sensitivity of the combined markers was 76.8% (95% confidence interval, 69-81%) with a specificity of 77.4% (72-80%), while those of a single use of CRT were 71.4% and 77.8%, respectively. When evaluated in relation to tumor characteristics, such as grade, stage, size, and outcome of urinary cytology, the diagnostic capacity of the combined markers was equal to or better than that of CRT in all categories. Concomitant use of CRT, SNCG, and s-COMT had higher sensitivity for detection of bladder cancer than did single use of CRT. Our study suggests that use of this panel of markers will improve the diagnosis of bladder cancer and may allow the development of a protein microarray assay or multi-channel enzyme-linked immunosorbent assay.
Aged↗
[Molecular diagnostic techniques in gynaecologic cancer].
BACKGROUND: Our understanding of the genetic basis of gynaecologic cancer has increased. Still this is a major cause of death. Based on a review of the literature, we present molecular diagnostic tools no available for the prevention and characterisation of cancers in the ovaries, uterus and cervix. MATERIALS AND METHODS: The presentation is based on a limited literature search in PubMed, Medline, Cochrane, internet addresses for treatment protocols, and our own experiences. RESULTS: The cause of endometrial and ovarian cancer is mainly unknown. Around 5% of the cases are caused by inherited mutations in the BRCA1, BRCA2 or DNA repair genes. Special follow up is recommended for carriers of these mutations. Human papillomavirus (HPV) is the main cause of cervical cancer. Determination of the HPV type can contribute to a diagnosis, but it is not part of the screening programme. A more precise molecular diagnosis in endometrial and ovarian cancer can lead to development of new targeted therapy and tests for prediction of treatment response. Preliminary studies have given promising results, including studies of papillomavirus vaccines. INTERPRETATION: Detection of susceptibility genes, oncogenic viruses and prognostic markers are now useful tools in the prevention, diagnosis and treatment of gynaecologic cancer. Studies of the molecular tumour profile have shown promise for the development of new treatment strategies.
Endometrial Neoplasms↗
Cancer incidence among medical diagnostic X-ray workers in China, 1950 to 1985.
A second follow-up of 27,011 diagnostic X-ray workers in China revealed a 21% greater incidence of cancer than expected based on the experience of 25,782 physicians who did not routinely use X-rays (RR = 1.21; 95% Cl: 1.08 to 1.35). This risk is lower than the 50% excess reported previously and reflects, in part, the reduced risk among workers first employed after 1965, when hospital exposures to radiation probably were lower than in earlier years. The X-ray workers were employed between 1950 and 1985 and followed for an average of 16.1 years. Significantly elevated risks were seen for leukemia (RR = 2.4, n = 34 cases), and cancers of the esophagus (RR = 5.2, n = 19), liver (RR = 1.8, n = 65), and skin (RR = 2.8, n = 9). Cancers of the breast (RR = 1.5, n = 20), thyroid (RR = 1.7, n = 8), and bone (RR = 7.6, n = 4) also occurred more often than expected. Non-significant deficits were observed for cancers of the oral cavity and pharynx (RR = 0.6, n = 16), colon and rectum (RR = 0.8, n = 20), stomach (RR = 0.8, n = 36), and lung (RR = 0.9, n = 45). Excess risks for leukemia and esophageal cancer were seen among men but not among women. The RR for leukemia was higher for X-ray workers who began employment before 1970 than for those who started more recently and also for those who were young when employment began. The patterns of risk associated with duration of work, and with age and calendar time of initial employment, suggest that the excesses of leukemia and skin cancer, and, possibly, cancers of the breast and thyroid, were due to occupational exposure to X-rays. However, there was little evidence that radiation contributed to the increased occurrences of liver or esophageal cancers.
Adult↗
Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets.
Monitoring human antibody recognition of tumor antigens could have potential diagnostic and prognostic significance. Serological analysis of recombinant cDNA expression libraries of human cancer has identified a number of immunogenic tumor antigens. To identify colon cancer antigens associated with a cancer-related serum IgG response, serum samples from 74 patients with colon cancer and 75 normal blood donors were screened for antibody reactivity to 77 serologically defined tumor antigens. The following 13 antigens reacted exclusively with sera from the colon cancer patients and not with sera from normal blood donors: p53, MAGEA3, SSX2, NY-ESO-1, HDAC5, MBD2, TRIP4, NY-CO-45, KNSL6, HIP1R, Seb4D, KIAA1416, and LMNA. Serum samples from 34 of 74 (46%) colon cancer patients detected 1 or more of these 13 antigens. Fifty-three of 74 colon cancer patients were of known clinicopathological stage. Analysis of antibody frequency showed that 5 of 7 (71%) stage I colon cancer patients, 4 of 11 (36%) stage II patients, 2 of 14 (14%) stage III patients, and 11 of 21 (52%) stage IV patients had serum IgG antibody that reacted with 1 or more of the 13 antigens. The mRNA expression patterns of 8 of these 13 antigens were altered in cancer. Three of the 13 antigens were cancer/testis antigens (MAGEA3, SSX2, and NY-ESO-1), which are expressed exclusively in normal gametogenic tissues and aberrantly expressed in a broad range of cancer types. Quantitative real-time reverse transcription-PCR showed that the mRNA expression levels of 2 antigens, HDAC5 and Seb4B, were down-regulated in colon cancer, 2 other antigens, KNSL6 and KIAA1416, were up-regulated, and another antigen, NY-CO-45, showed a variable level of mRNA expression in colon cancer. With regard to KNSL6 mRNA expression, only trace levels were detected in 15 different normal tissues with the exception of testis, which showed a high level of KNSL6 mRNA expression. In contrast, 9 of 9 colon cancer specimens showed overexpression of KNSL6 mRNA, ranging from 5 to 44 times the level detected in normal colon tissue, indicating that this antigen could also be a valuable therapeutic target.
Antibodies, Neoplasm↗
[Analysis of causes of diagnostic errors in gastric cancer at outpatient examinations].
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Adult↗
Electropotential measurements as a new diagnostic modality for breast cancer.
BACKGROUND: Proliferative changes in breast epithelium are an intrinsic aspect in the development of breast cancer, and result in regions of epithelial electrical depolarisation within the breast parenchyma, which can extend to the skin surface. Diagnostic information might be obtained from a non-imaging and non-invasive test based on skin-surface electropotentials. METHODS: In 661 women, scheduled for open biopsy at eight European centres, we studied whether measurements of breast electrical activity with surface sensors could distinguish benign from malignant breast disease. A depolarisation index was developed. RESULTS: We found a highly significant trend of progressive electrical changes according to the proliferative characteristics of the biopsied tissue. Discriminatory information was obtained in both premenopausal and postmenopausal women, and the index was not related to age. The best test performances were for women with palpable lesions. The median index was 0.398 for non-proliferative benign lesions, 0.531 for proliferative benign lesions, and 0.644 for cancer (ductal carcinoma-in-situ and invasive). A specificity of 55% was obtained at 90% sensitivity for women with palpable lesions when a discriminant based on age and the depolarisation index was used. INTERPRETATION: This new modality may have diagnostic value, especially in reducing the number of unnecessary diagnostic tests among women with inconclusive findings on physical examination. Understanding and control of the biological variability of these electrical phenomena will be important in the improvement of this test. Studies in populations with a lower cancer prevalence are needed to assess further the diagnostic value of this approach.
Adolescent↗
Angiotensin converting enzyme-independent, local angiotensin II-generation in human pancreatic ductal cancer tissues.
Hypovascularity is an outstanding characteristic of pancreatic ductal cancer by diagnostic imaging: most pancreatic ductal cancers are hypovascular or avascular, and tumor vessels are seldom seen on angiography. However, we found that the vasculature was not always poor on angiography of surgically resected specimens of locally advanced pancreatic ductal cancers. To elucidate these controversial findings, we focused on angiotensin II, a vasoconstrictor which is directly produced from angiotensinogen at acidic pH by active trypsin. We examined whether a local angiotensin II-generating system exists in pancreatic ductal cancer tissue. We measured angiotensin II concentration and angiotensin converting enzyme (ACE) activity in tissues from normal pancreas, pancreatic ductal cancers, colon cancers, and hepatocellular carcinomas. After surgically resected specimens were homogenized, angiotensin II concentration and ACE activity in tissues were measured using the florisil method and the Kasahara method, respectively. Tissue angiotensin II levels in pancreatic ductal cancer (n=13) were significantly higher than those of normal pancreas (n=7), colon cancers (n=7), or hepatocellular carcinomas (n=7). However, there was no significant difference in the ACE activity in tissue between them. This study provides in vivo evidence of an ACE-independent, angiotensin II-generating system in pancreatic ductal cancer tissues and suggests that locally formed angiotensin II may act on the pre-existing pancreatic arteries around the tumor, leading to formation of hypovascular or avascular regions.
Angiotensin II↗
The value of warning signals of cancer in general practice.
Seven warning signals of cancer are poor diagnostic indicators of cancer, but for some patients awareness of warning signals may help reducing diagnostic delay. The usefulness of warning signals recorded by general practitioners at consultation is evaluated for a group of 80 patients who developed cancer 0-18 months after the consultation. Warning signals of cancer were recorded at the consultations in 20 cancer patients and in 13 matched control patients. For three cancer patients the warning signal was considered not related to the cancer. Recognition of warning signals related to the cancer disease was considered useful for nine out of 17 patients, somewhat useful for five and hardly useful at all for three patients.
Adult↗
Diagnostic approach to pancreatic cancer.
Adenocarcinoma of the pancreas ranks fourth as a cause of cancer death in adults in the United States and is the second most common cause of cancer deaths of all gastrointestinal-related carcinomas. It usually presents late in its course. In this article, the authors discuss the clinical features of pancreatic cancer, with emphasis on those that allow early detection of the disease. They also review diagnostic methods and preoperative and perioperative staging that allows the appropriate application of surgical and palliative therapeutic modalities. Despite the significant progress that has been made, further research studies are needed to advance the therapeutic approach to this aggressive cancer.
Adenocarcinoma↗
Three-dimensional contrast-enhanced power Doppler ultrasonography and conventional examination methods: the value of diagnostic predictors of prostate cancer.
OBJECTIVE: To investigate the value of three-dimensional contrast-enhanced power Doppler ultrasonography (3D-CE-PDU) in the diagnosis of prostate cancer and to compare 3D-CE-PDU with digital rectal examination (DRE), prostate-specific antigen (PSA) levels, grey-scale ultrasonography (GSU) and PDU. PATIENTS AND METHODS: The study comprised 30 patients with localized prostate cancer scheduled to undergo radical prostatectomy and 29 with clinical BPH scheduled to undergo transurethral microwave thermotherapy. The 3D-CE-PDU examinations were carried out using 2.5 g of microbubble ultrasound contrast medium; the images were stored digitally to allow off-line analysis. All the reconstructed 3D images of the prostate were evaluated blindly in random order by two investigators (one expert and one novice). The images were scored according to asymmetry (0-2) and vessel distribution (0-3). Marked asymmetry (2) and/or a focal increase in vascularity (> 2) were considered as suspicious for prostate malignancy. Diagnostic predictions using the DRE, PSA level, GSU, PDU, 3D-CE-PDU and their combinations were investigated using receiver operating characteristic (ROC) curves. RESULTS: True-positive and true-negative rates of the 3D-CE-PDU were 87% (26/30) and 79% (23/29), respectively, for the expert observer. The sensitivity of 3D-CE-PDU was higher than that of DRE, GSU and PDU, but not PSA level, and the specificity was lower, again except for PSA level. However, when compared with those of the other modalities in single-test evaluations, 3D-CE-PDU, and a combination of 3D-CE-PDU and PSA level, had the largest area under the ROC curve (0. 830 and 0.933, respectively). The diagnostic agreement between the examiners was 76% (Cohen kappa statistic, 0.5). CONCLUSION: In this selected group of patients, 3D-CE-PDU alone was a better diagnostic tool than the DRE, PSA level, GSU or PDU alone. The most suitable diagnostic predictor for prostate cancer was a combination of 3D-CE-PDU and PSA level.
Aged↗