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The use of molecular diagnostics in bladder cancer.

Bladder cancer is a common disease that causes significant morbidity and mortality in the United States. Early detection and routine surveillance are recommended in the management of this chronic and recurrent disease. Cystoscopic examination has been used for detection and follow-up; however, it is costly and is associated with patient discomfort. With advances in molecular biology and biochemistry, many diagnostic assays have been developed to supplement cystoscopy. The mechanisms and variable results of these assays are described. In addition, the economic and social implications of bladder cancer detection and surveillance are discussed.

Journal Article↗

Diagnostic evaluation of cancer patients with pelvic pain: comparison of scintigraphy, CT, and MR imaging.

Pelvic pain in cancer patients can result from several causes. The most appropriate choice of imaging techniques for evaluating such patients has not been established. We evaluated 27 cancer patients with pelvic pain by using radionuclide bone scintigraphy (24 patients), abdominal CT (27 patients), and pelvic MR imaging (27 patients) and used the correlation between symptoms and imaging findings to compare these imaging methods. The study population included 11 patients with Ewing sarcoma, six with other sarcomas, five with colorectal cancers, and five with other tumors. All patients had pelvic pain, and eight had pain radiating to a leg. Twenty-three patients had soft-tissue masses, and 19 had bone metastases; 16 had both. Findings on bone scans explained the symptoms in 17 (71%) of 24 patients, findings on CT in 23 (85%) of 27 patients, and findings on MR imaging in 25 (93%) of 27 patients. The difference between bone scanning and CT or MR was statistically significant (p less than .05); however, the difference between CT and MR imaging was not significant (p greater than .05). MR imaging detected 41 (98%) of 42 relevant lesions, whereas CT detected 31 (74%) of 42, and bone scanning 17 (44%) of 39. We conclude that MR is superior to either bone scanning or CT in the initial evaluation of pelvic pain in cancer patients. Such information can be important in directing the treatment of these patients.

Adolescent↗

[Immunoscintigraphy and intraoperative tumor search in ovarian cancer].

The diagnostic possibilities of immunoscintigraphy (IS) in ovarian cancer are discussed. Seventy-five patients were investigated by IS using the radioantibodies HMFG-2 (n = 63) or OC-125 (n = 12). The results showed a specificity of 75%, sensitivity of 87%, and accuracy of 84%. An intraoperatively usable gamma ray detection probe was developed in order to achieve better results than with conventional IS. Twelve patients were investigated using this probe. A future clinical value was indicated for intraoperative detection of lymphnode metastases and/or small tumor deposits.

Adult↗

Contrast-enhanced magnetic resonance mammography: does it affect surgical decision-making in patients with breast cancer?

BACKGROUND: Diagnostic imaging in women with suspected breast cancer should accurately detect and diagnose malignant tumors and facilitate the correct choice of therapy. Contrast-enhanced magnetic resonance mammography (CE-MRM) is potentially the imaging modality of choice for accurate patient management decisions. METHODS: A total of 164 women with suspected breast cancer based on clinical examination, conventional mammography and/or ultrasound each underwent preoperative bilateral CE-MRM using an axial 3D dynamic T1-weighted gradient-echo sequence and gadobenate dimeglumine as contrast agent. Images were evaluated by two readers in consensus. Histological evaluation of detected lesions was performed on samples from core biopsy or surgery. Determinations were made of the sensitivity, accuracy and positive predictive value of CE-MRM compared to mammography/ultrasound for the detection of malignant lesions and of the impact of CE-MRM for surgical decision-making. FINDINGS: Conventional mammography/ultrasound detected 175 lesions in the 164 evaluated patients. CE-MRM revealed 51 additional lesions in 34/164 patients; multifocal and multicentric cancer was detected in 7 and 4 additional patients, respectively, contralateral foci in 21 additional patients and pectoral muscle infiltration in 2 additional patients. CE-MRM also confirmed the absence or benignity of 3 and 1 lesions suspected of malignancy on mammography/ultrasound. The sensitivity and accuracy for malignant lesion detection and identification was 100% and 93.4%, respectively, for CE-MRM compared to 77.3% and 72.1% for mammography/ultrasound, respectively. Patient management was altered for 32/164 (19.5%) patients as a result of CE-MRM. INTERPRETATION: CE-MRM positively impacts patient management decisions and should be performed in all women with suspected breast cancer based on clinical examination, mammography and/or ultrasound.

Adult↗

Soluble epidermal growth factor receptor (sEGFR) [corrected] and cancer antigen 125 (CA125) as screening and diagnostic tests for epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecologic cancers in the United States. Because women who are diagnosed with early stage disease have a better prognosis than women diagnosed with late stage disease, early detection represents a potentially practical approach to reduce the mortality associated with EOC. Unfortunately, no single screening test has proven to be effective for this purpose, and a valid and feasible screening program to detect early stage EOC in the general population has not yet been devised. Consequently, research has focused on coupling two or more screening modalities to improve program validity and feasibility. Serum cancer antigen 125 (CA125) and a soluble isoform of the epidermal growth factor receptor (p110 sEGFR) have been studied individually as biomarkers of ovarian cancer. In this study, we compare serum CA125 levels and sEGFR concentrations in women with EOC to women with benign gynecologic conditions of ovarian and non-ovarian origin. We show that serum sEGFR concentrations are lower in patients with EOC than in women with benign gynecologic conditions, whereas serum CA125 levels are higher in patients to EOC compared with women with benign gynecologic conditions. These data also reveal that age and serum sEGFR concentrations modify the association between CA125 levels and EOC versus benign gynecologic disease. Hence, age- and sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern EOC patients from women with benign ovarian tumors and non-ovarian gynecologic conditions. Our analyses show that parallel testing with fixed sEGFR and CA125 cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing with age- and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity, and overall accuracy to discern patients with EOC from women with benign ovarian and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and CA125, thus, has improved utility for screening and diagnosing EOC, which may increase the positive predictive value of a multimodal screening program that incorporates these biomarkers to detect and subsequently differentiate benign from malignant ovarian tumors.

Adult↗

Position of nuclear medicine modalities in the diagnostic workup of cancer patients: lung cancer.

This review summarizes the current literature and tries to define the status of nuclear medicine in the clinical workup of lung cancer patients. Nuclear medicine procedures and positron emission tomography (PET) with the EMEA-approved radiopharmaceutical fluorodeo-xyglucose (FDG) are indicated for the characterization of lung lesions; the nodal staging of non-small cell lung cancer (NSCLC); the detection of distant metastases; and for the diagnosis of recurrent disease. Recent studies have shown the clinical efficacy of nuclear medicine and especially of FDG-PET in the workup of lung cancer patients and its significant impact on patients' management. Conventional nuclear medicine procedures are established for the pre-therapeutic assessment of pulmonary perfusion and function (lung perfusion and ventilation scintigraphy) and for the detection of bone metastases (skeletal scintigraphy). In studies in thousands of patients, FDG-PET has been proved to be the most accurate non-invasive diagnostic test for the characterization of lung nodules and masses. It can be recommended at least for patients with increased risk at surgery. FDG-PET should be applied in candidates for surgery of lung cancer, as mediastinoscopy may be omitted if PET shows no metastases in the mediastinum, and because FDG-PET avoids futile surgery by a more accurate selection of patients, especially by the detection of unexpected distant metastases. In candidates for thoracic radiotherapy, FDG-PET can help to exclude extrathoracic disease which needs systemic treatment and to better define the target volume for radiation therapy. The time has come for FDG-PET to find its place in new guidelines for the workup of lung cancer patients.

Bone Neoplasms↗

Expression of bcl-2 by breast cancer: a possible diagnostic application.

Expression of bcl-2 is most commonly associated with the t(14;18) translocation present in most folicular lymphomas (1). More recently, bcl-2 oncoprotein has been identified in normal tissues and in nonhematologic malignancies. In this study, we investigate the use of bcl-2 as a marker to distinguish metastatic breast carcinoma from primary lung and gastric cancers, and we evaluate the role of bcl-2 as an independent prognostic factor in breast carcinoma and its relationship to other breast cancer markers. bcl-2 immunostains were done on 371 adenocarcinomas of the breast, lung, and stomach. Additionally, 231 samples of metastases from patients with breast or gastric cancer were evaluated for bcl-2 expression. All breast cancer tissue samples had immunohistochemical data on expression of estrogen and progesterone receptors, p53, neu/cerb2, and MIB-1. A large proportion (79.3%) of invasive breast carcinomas expressed bcl-2, whereas only 5.6% and 8.3% of pulmonary and gastric carcinomas did. Moreover, staining was moderate to intense in 70.2% of the breast cancers, compared with only one specimen of lung carcinoma (1.9%) and gastric carcinoma (0.9%) that showed moderate staining. There was agreement of bcl-2 expression between primary and metastatic sites in all specimens except one. Expression of bcl-2 in breast adenocarcinomas was significantly associated with hormone receptor positivity and low histologic grade. Nonetheless, 20.6% of bcl-2-positive specimens were estrogen receptor negative and 24.2% of bcl-2-positive specimens were progesterone receptor negative. Neither the presence nor the absence of bcl-2 expression significantly predicted disease-free survival or overall survival in patients with breast cancer. We conclude that adenocarcinomas with intense bcl-2 staining are more likely to be of breast than of pulmonary or gastric origin. We recommend the addition of bcl-2 to a panel of antibodies (estrogen receptor, GCDFP-15, and S100) that might contribute to the identification of a larger proportion of metastatic breast carcinomas, because almost one-half of the estrogen-receptor negative cancers were bcl-2 positive.

Adenocarcinoma↗

[A diagnostic protocol for gastric cancer in old age].

After examining the various diagnostic methods used for gastric cancer, the paper analyses all geriatric patients affected by this disease and hospitalised in the Institute of Pathological Surgery at the University of Pavia between 1/1/1974 and 31/12/1986. The results obtained confirmed that: the subjective symptoms of the elderly patient affected by gastric cancer differ in a large number of cases from those in adults; in some cases, in fact, the disease is silent for long periods of time, whereas it is only slight in others; tests performed revealed neoplasia and possible metastases. In conclusion, although the symptomatology in elderly patients is not clear, some symptoms (weight loss, anemia, etc.) may give the doctor cause for concern. Diagnosis may be made using a variety of tests, ranging from the more commonplace (X-ray of the digestive tract, echography, gastroscopy with biopsy, etc.) to the most recent techniques (immunoscintigraphy).

Aged↗

A prototype for unsupervised analysis of tissue microarrays for cancer research and diagnostics.

The tissue microarray (TMA) technique enables researchers to extract small cylinders of tissue from histological sections and arrange them in a matrix configuration on a recipient paraffin block such that hundreds can be analyzed simultaneously. TMA offers several advantages over traditional specimen preparation by maximizing limited tissue resources and providing a highly efficient means for visualizing molecular targets. By enabling researchers to reliably determine the protein expression profile for specific types of cancer, it may be possible to elucidate the mechanism by which healthy tissues are transformed into malignancies. Currently, the primary methods used to evaluate arrays involve the interactive review of TMA samples while they are viewed under a microscope, subjectively evaluated, and scored by a technician. This process is extremely slow, tedious, and prone to error. In order to facilitate large-scale, multi-institutional studies, a more automated and reliable means for analyzing TMAs is needed. We report here a web-based prototype which features automated imaging, registration, and distributed archiving of TMAs in multiuser network environments. The system utilizes a principal color decomposition approach to identify and characterize the predominant staining signatures of specimens in color space. This strategy was shown to be reliable for detecting and quantifying the immunohistochemical expression levels for TMAs.

Adolescent↗

Features of early gastric cancer detected by modern diagnostic technique.

To ascertain how the clinicopathologic features of early gastric cancer detected by current diagnostic tools had changed clinical features, we compared 711 early gastric cancer patients with 933 advanced gastric cancer patients regarding age, sex, and tumor location. We found that the proportion of early gastric cancer cases did not change according to age. However, the proportion of early gastric cancer cases in the proximal part was significantly lower than that observed in the distal part (p < 0.01). We conclude that recent diagnostic improvements have rendered age no longer a major deterrent for early detection of gastric cancer. However, a careful examination of the proximal stomach is called for because it is so hard to detect small lesions in that area.

Adult↗

The value of cytology in the diagnostics of lung cancer.

In order to elucidate the relative contributions made by cytology and histology in the diagnosis of lung cancer, we studied the cytology and histology reports of all patients who received a microscopic diagnosis of lung cancer in our hospital during the 7 years 1996-2002. This gave a total of 407 patients. The most frequent diagnoses were squamous cell carcinoma (34.9%), adenocarcinoma (24.8%), and small cell carcinoma (17.8%). One hundred and fifteen patients (28.3%) received their microscopic diagnosis based only on cytology, which therefore proved to be of great diagnostic value. The most useful type of cytology specimen was taken by bronchial lavage or bronchial brushing. These types of specimens provided the diagnosis in 71 patients (17.4%). Cytology was especially capable of finding squamous cell carcinomas. Small cell carcinomas were underrepresented (9.6% versus 17.8%) and unspecified carcinomas greatly overrepresented (9.6% versus 2.9%) among the diagnoses obtained by cytology alone. We conclude that cytology is of considerable diagnostic value, although not as specific as histology for the subtyping of carcinomas. Clinicians should be more aware of the usefulness of cytology, especially in cases where it is difficult to obtain bronchoscopic biopsy samples for histological examination.

Cytodiagnosis↗

Diagnostic criteria and cancer risk of proliferative breast lesions.

Breast cancer risk assessment in women following a benign breast biopsy is a promising area with regard to intermediate endpoint determination, and has been particularly fostered by the consensus agreement concerning the risk attributed to specific diagnoses [1]. Several recent studies have largely verified this approach [2-4], and a recent report demonstrates general agreement among most expert pathologists regarding diagnostic criteria for these lesions [5]. However, in a limited number of cases, determining exact levels of risk for individual patients has been problematic as a result of a failure by pathologists to achieve consensus on diagnostic criteria for these same lesions. This situation has arisen primarily because it is much more tenable to disagree over subjective diagnostic criteria, than it is to argue with robustly supported epidemiological data. Without agreement on reproducible diagnostic criteria, widely promulgated consensus risk estimates for these specific histologic entities are no longer applicable. In addition, those individuals who choose different diagnostic criteria for proliferative breast lesions fail to realize that the terminology, epidemiological risk estimates, and diagnostic criteria used by Dupont and Page are inexorably linked. Since the publication of the consensus statement [1], those using the terms of "atypical ductal hyperplasia" and "atypical lobular hyperplasia" have by default accepted the diagnostic criteria of Dupont and Page. Therefore, surgical pathologists who desire to make use of the consensus risk estimates must familiarize themselves with diagnostic criteria for the various histologic entities that comprise proliferative disease of the breast as defined by Dupont and Page [6].(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Maryland dental hygienists' knowledge and opinions of oral cancer risk factors and diagnostic procedures.

OBJECTIVES: To examine Maryland dental hygienists' (DHs) knowledge of oral cancer risk factors and diagnostic procedures, as well as opinions about the currency and adequacy of their oral cancer knowledge, educational preparation, interest in, and preferred types of, continuing education courses. METHODS: Seven hundred DHs were randomly selected from a registry of 2677 Maryland licensed dental hygienists. A mailed survey instrument provided baseline data on 331 (RR = 60%) DHs. Stratified tabular and logistic analytical techniques were employed (alpha level < or =0.05). RESULTS: Most correctly identified tobacco use (99.7%) and alcohol use (89%) as risk factors; however, 31% incorrectly identified poor oral hygiene as a risk factor. 64% of DHs correctly identified older age as a risk factor, yet only 16% identified that the majority of oral cancers are diagnosed in the 60+ year old age group. Nearly 91% correctly identified the examination procedures of the tongue for oral cancer detection; while only 16% of DHs correctly identified erythroplakia and leukoplakia as the conditions most likely associated with oral cancer. CONCLUSIONS: Gaps in knowledge exist and strongly suggest the need for continuing education courses to clarify risk factors and diagnostic procedures associated with earlier oral cancer detection and prevention.

Adult↗

[Clinical and diagnostic characteristics of the early forms of stomach cancer].

Clinical and diagnostic problems of early stomach cancer were considered for 157 patients with diagnosis confirmed after operation. Gastroenterological diseases were not mentioned in the past medical history of 22.9% of the patients only. 48.4% of the patients had the so-called stomach precancerous diseases, 28.7% other diseases of the alimentary tract. At diagnosis of carcinoma, 51.6% of the patients had clinical signs of previous diseases. The importance of prophylactic medical examination in the diagnosis of early stomach cancer was emphasized (cancer was detected actively in 84.7%). Since the gross appearance of early stomach cancer looks like benign lesions, the x-ray and endoscopic methods might not be quite informative. Morphological examination of the spot biopsy material raised preoperative diagnostic accuracy up to 92.3%.

Adult↗

Generation and characterization of monoclonal antibodies against choline kinase alpha and their potential use as diagnostic tools in cancer.

Choline kinase alpha (ChoKalpha) is a metabolic enzyme involved in the synthesis of phosphatidylcholine, recently implicated in cancer onset since it is overexpressed in a variety of human cancers such as mammary, lung, colorectal and prostate adenocarcinomas. Furthermore, overexpression of ChoKalpha in human HEK293T cells confers them oncogenic properties with the induction of tumors after subcutaneous injection in nude mice. ChoKalpha levels in tumor samples have been analyzed using polyclonal antibodies and Western blotting. These techniques have considerable limitations and do not allow for a precise and efficient evaluation of the real significance of ChoK overexpression in human carcinogenesis. We developed a set of monoclonal antibodies with high specificity and sensitivity against ChoKalpha, and characterized their properties. We provide evidence that the newly generated MoAbs against ChoKalpha have potential use in cancer diagnosis by conventional immunohistochemistry techniques.

Animals↗

Role of "saturation biopsy" in the detection of prostate cancer among difficult diagnostic cases.

OBJECTIVES: To determine the role of extensive prostate biopsy ("saturation biopsy") among selected men with unexplained worrisome prostate-specific antigen (PSA) parameters. Clinicians are commonly faced with the dilemma of elevating PSA levels despite negative prostate biopsy results in patients without symptoms of prostatitis. METHODS: Thirty-seven patients underwent saturation biopsy. This consisted of 24 peripheral zone cores, 6 to 12 transition zone cores, and 2 lateral lobe transurethral samples. All procedures were done under anesthesia. Patients were discharged home with catheters in situ. All patients had undergone at least three prior sets of transrectal ultrasound-guided prostate biopsies, including transition zone assessment. Twelve, eight, and five patients had had four, five, and six prior prostate biopsies, respectively. Specimens were sent for pathologic examination in groups of six to determine the marginal benefit of the additional sampling. RESULTS: The mean age of the cohort was 62.4 years (range 39 to 75). The median PSA and percent free PSA was 22.4 ng/mL (range 7.8 to 73.8) and 0.11 (range 0.04 to 0.17), respectively. Five patients (13.5%) had detectable carcinoma at saturation biopsy. The grade distribution was Gleason score 8 for 1 patient, Gleason score 7 for 2 patients, and Gleason score 6 for 2 patients. In all cases, carcinoma was detected in the first 18 peripheral zone cores. Acute prostatitis was noted in 19% of specimens. The procedure was well tolerated, although 4 patients required prolonged (greater than 1 week) catheter drainage for urinary retention. All patients were spontaneously voiding by week 3. CONCLUSIONS: Most men with multiple previous biopsies and increasingly worrisome PSA parameters do not have cancer. The marginal utility of the saturation biopsy is low. Although rare additional cases will be detected using this technique, 18-core peripheral sampling is recommended for these difficult diagnostic cases.

Acute Disease↗

[Histogenesis and diagnostic of kidney cancer in the light of electron microscopic data].

Electron microscopic examinations of human renal carcinoma showed that both light and dark (granular) differentiated tumour cells may have ultrastructural features of the cells of any nephron segment. In the light of these results and concepts of the capacity of undifferentiated tumour cells for specific differentiation, the decisive importance in histogenesis (cytogenesis) of the renal carcinoma belongs not to the site of its origin in one or another nephron segment but to the level of differentiation of stem cells (polypotent or monopotent) undergoing malignization and to the direction of their further differentiation. The paper presents concrete ultrastructural differential diagnostic features of renal carcinoma cells.

Cell Transformation, Neoplastic↗