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PubMed2004

Flexible cystoscopy assisted by hexaminolevulinate induced fluorescence: a new approach for bladder cancer detection and surveillance?

OBJECTIVE: The aim of this study was the assessment of flexible cystoscopy assisted by hexaminolevulinate (HAL) fluorescence. METHODS: This study was a prospective controlled, within-patient comparison of flexible HAL cystoscopy with standard flexible cystoscopy, HAL rigid and standard white light rigid cystoscopy. Eligible patients received an intravesical instillation of 50 ml hexylaminolevulinate 8 mM solution. First flexible than rigid cystoscopy was performed in each patient using a Combilight PDD system (Richard Wolf, Germany), which provided standard white light and blue light at 375 to 440 nm, with mapping of all lesions detected. All tumors and suspicious areas identified under white light and by red fluorescence with flexible or rigid cystoscopy were then resected by TUR or biopsied. The specimen was assessed by an independent blinded pathologist. RESULTS: In the 45 patients studied 41 (91%) patients had exophytic tumors, of which 39 (95.1%) were detected by HAL flexible cystoscopy and 40 (97.5%) by HAL rigid cystoscopy. 17 (37.8%) patients had concomitant or carcinoma in situ only, which was identified by HAL flexible cystoscopy in 14 (82.3%), by HAL rigid cystoscopy in 15 (88.2%), by flexible standard in 11 (64.7%) and by standard white light rigid cystoscopy in 13 (76.7%) patients. CONCLUSION: HAL fluorescence flexible cystoscopy compared to HAL rigid cystoscopy showed almost equivalent results in detecting papillary and flat lesions in bladder cancer patients. Both procedures were superior to standard white light flexible cystoscopy.

Adult↗
PubMed2001

Playing the waiting game ... the asymptomatic patient with recurrent ovarian cancer detected only by rising Ca125 levels.

The recurrence of ovarian cancer is usually heralded by an increase in the blood level of the tumour marker Ca125 but most oncologists are reluctant to initiate second-line chemotherapy before there is clinical or radiological evidence in addition to the increasing tumour marker. Thus patients have to spend an indefinite period of time, which can be as long as a year or more, knowing that their cancer has returned, but that treatment will be delayed until they have symptoms. For patients, this situation requires a change of outlook and an abandonment of the idea that early treatment is the best option. A dilemma exists for both oncologists and patients over the best time to begin aggressive treatment in this situation. This article explores some of the arguments for and against early treatment, in the hope that it might provide some insight into patients' concerns, and help patients to enjoy their symptom-free and treatment-free period of recurrence with some measure of tranquillity.

Antineoplastic Agents↗
PubMedDate not supplied

Immune complex-like materials in sera of patients with breast cancer: detection by complement-consumption assay.

Sera of patients with breast cancer were tested for the presence of immune complexes by a complement-consumption assay. To increase the concentration of immune complexes and thus improve the chances of their detection, sera were first ultracentrifuged and the sedimented material was assayed. Sera were considered to be positive if they consumed at least 75% of the hemolytic activity under the conditions of the test. Of the 60 patients tested, 45% were positive as compared with 13.5% positive sera among health blood bank donors. The presence of immune complexes could not be correlated with the extent of disease, the age of the patients, treatment or lack of treatment at the time of the test, or the time that had elapsed since diagnosis. In a few control tests, treatment of samples with DNase had no effect on their anticomplementary activity, whereas reduction with 2-mercaptoethanol abrogated the activity. These results strengthened the assumption that the substances binding complement were indeed immune complexes.

Adult↗
PubMed1988

Clinical characteristics of prostatic cancer detected by mass screening.

Since 1981 we have been studying prostate cancer (Pca) by mass screening in three cities, eight towns and seven villages in Gunma prefecture, Japan. From 1981 to 1985, 5,770 subjects were examined. The clinical character of Pca detected by mass screening is compared with control (i.e., Pca detected in the outpatient clinic in Gunma University). Of the 54 Pca patients detected by mass screening (Stage B: 28, C: 8, D: 18), approximately 50% had early-stage Pca. The ratio of early-stage Pca is significantly higher than in the control. An extended survival rate in high-stage Pca detected by mass screening also was observed through comparison with control. We determined two types of Pca in advanced stage: (1) asymptomatic or less symptomatic and better prognostic Pca found in mass screening and (2) symptomatic and worse prognostic Pca found in control.

Acid Phosphatase↗
PubMed2003

Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography.

We report an experimental study of the possibility of enhancing early bladder cancer diagnosis with fluorescence-image-guided endoscopic optical coherence tomography (OCT). After the intravesical instillation of a 10% solution of 5-aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm, emission of 620-700 nm) and OCT are performed on rat bladders to identify the photochemical and morphological changes associated with uroepithelial tumorigenesis. The preliminary results of our ex vivo study reveal that both fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT imaging has the potential to enhance the efficiency and sensitivity of early bladder cancer diagnosis.

Animals↗
PubMed1990

Evaluation of non-invasive diagnostic tests in detecting cancer of the pancreas.

Monoclonal antibody defined antigen (CA19-9), carcinoembryonic antigen (CEA), ultrasonography (US) and computerized tomography (CT) were carried out as the tests in 113 patients suspected to have pancreatic cancer. Of 98 patients who underwent operation, 55 were found to have pancreatic cancer, 25 benign pancreatic disease, and 18 cancer of the biliary tract. Follow-up study was carried out for more than 1 year in 15 other patients suffering from pancreatitis without surgical intervention. The accuracy of CA19-9, US, CEA and CT was 87%, 69%, 61% and 56% respectively. The sensitivity of each test was CA19-9, 98%; US, 89%; CT, 80%; and CEA, 38%. The sensitivity of parallel test combined with CA19-9 and CEA was 100%. It may be regarded as the first step to detect pancreatic cancer in suspected population. The specificity of each test was CEA, 82%; CA19-9, 76%; US, 50% and CT, 40%. And the specificity of serial tests combined with CA19-9 and US was 90%. When these two tests were both positive, pancreatic cancer was highly suspected.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

The histochemical G6PDH reaction but not the LDH reaction with neotetrazolium is suitable for the oxygen sensitivity test to detect cancer cells.

We used the oxygen sensitivity of the histochemical reaction to detect glucose-6-phosphate dehydrogenase (G6PDH) activity based on neotetrazolium (NT) reduction to discriminate cancer cells from normal cells. Formazan generation was strongly reduced in normal but not in malignant cells when the incubation was performed in oxygen instead of nitrogen. Competition for reductive equivalents between NT and oxygen via superoxide dismutase (SOD) has been suggested. Since SOD activity is usually decreased in cancer cells, NT reduction would not be hampered in these cells. We tested this hypothesis by demonstrating NAD-dependent lactate dehydrogenase (LDH) activity instead of NADP-dependent G6PDH activity in normal rat liver and colon, in human colon carcinoma, and in experimentally induced metastases of colon carcinoma in rat livers. Reactions for both enzymes were determined cytophotometrically in an atmosphere of pure oxygen or nitrogen. G6PDH acted as described previously, showing distinct activity in cancer cells but strongly reduced activity in normal cells after incubation in oxygen, but this was not the case with LDH because formazan was also generated in normal tissue in oxygen. It appeared that after 5 min of incubation at 37 degrees C the residual activity of G6PDH in an atmosphere of oxygen compared with nitrogen was 0% in normal liver tissue and 15% in normal colon epithelium, whereas in colon carcinoma and in colon carcinoma metastasis in liver it was 48% and 33%, respectively. The residual activity of LDH in oxygen was 30% in normal female rat liver, 75% in normal male rat liver, and 38% in normal colon epithelium, whereas the residual activity in colon carcinoma and metastases in liver was 54% and 24%, respectively. These experiments clearly indicate that the oxygen sensitivity phenomenon is not solely an effect of competition for reducing equivalents between NT and oxygen via SOD, because NADPH generated by G6PDH and NADH generated by LDH have a similar redox potential. Apparently the system is more complex. The role of specifically NADPH-converting cellular systems such as NADPH-cytochrome P450 reductase was excluded because incubations in the presence of exogenous NADPH as substrate for these systems revealed oxygen sensitivity. Involvement of NADPH-dependent lipid peroxidation in the oxygen sensitivity test is discussed.

Adenocarcinoma↗
PubMed1989

Breast cancer detected by screening: the importance of long-term follow-up.

This study updates a 10- to 15-year follow-up of 136 patients with breast cancer among 10,187 symptom-free participants in a screening program. Mammography was the sole detection modality in 76 (56%) patients. The combination of mammography and physical examination revealed 41 (30%) cancers, whereas 19 (14%) were detected on physical examination alone. There were 26 (19%) noninvasive and 110 (81%) invasive neoplastic lesions. Positive axillary nodes were found in 34 (25%) patients, and 102 (75%) patients had negative nodes. For the entire group 5- and 10-year survival rates were 84.5% and 75%, respectively. After a minimum follow-up of 10 years and a median of 13.5 years, 102 patients are alive; one of these has a recurrence of cancer. Among the 34 patients who are no longer living, 14 died of causes unrelated to breast cancer. Two patients in the group in which diagnosis was based on mammography alone died of breast cancer, for a breast cancer-related fatality rate of 2.6% (2/76). By contrast, the breast cancer-related mortality of patients whose tumors were palpable at the time of detection was 30% (18/60) (p = 0.00001). This study suggests that long-term survival of patients whose breast cancer is detected by screening is, in large measure, dependent on the ability to detect malignant lesions before they become palpable.

Adult↗
PubMed1996

Disseminated epithelial tumor cells in bone marrow of patients with esophageal cancer: detection and prognostic significance.

Minimal residual disease in patients with operable esophageal cancer is frequently missed by current noninvasive tumor staging. Here we applied an immunocytochemical cytokeratin assay that allows identification of individual esophageal carcinoma cells disseminated to bone marrow. Prior to therapy, bone marrow was aspirated from the upper iliac crest of 71 patients with esophageal cancer at various disease stages as well as an age-matched control group of 20 noncarcinoma patients. Tumor cells in cytologic bone marrow preparations were detected with monoclonal antibodies (mAbs) CK2, KL1, and A45-B/B3 to epithelial cytokeratins (CKs) using the alkaline phosphatase antialkaline phosphatase method. CK-positive cells were found in 14 (36.8%) of 38 cancer patients treated with curative intent and 16 (48.5%) of 33 patients with extended disease. The overall frequency of these cells was 1 per 4 x 10(5) to 82 per 4 x 10(5) mononuclear cells with no significant differences between patients at different tumor stages. After a short median follow-up of 9.5 months (3-24 months), 7 of 11 patients who underwent complete surgical resection but had tumor cells in bone marrow presented with tumor relapse compared to 2 of 19 corresponding patients without such cells (p < 0.01). It was concluded that although bone marrow is not a preferential site of overt metastasis of esophageal cancer, the frequent occurrence of isolated tumor cells at this distant site indicates that hematogenous dissemination of viable malignant cells occurs early in tumor progression.

Bone Marrow↗
PubMed2004

The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation study.

BACKGROUND: Malignant cells characteristically possess high levels of plasminogen activator, which induce local fibrinolysis. The DR-70 immunoassay is a newly developed test, which quantifies fibrin degradation products in serum by a proprietary antibody. AIM: To evaluate the DR-70 immunoassay as a detection assay for the presence of gastrointestinal cancers. METHODS: We prospectively collected blood sera of 85 patients with histologically proven tumour and 100 healthy blood donors. Ten microlitres of the sera was used for the DR-70 immunoassay. Nineteen patients had a hepatocellular and 10 cholangiocellular carcinoma, 13 cancer of the pancreas, 30 colorectal cancer, 10 stomach cancer and three cancer of the oesophagus. RESULTS: Receiver-operator curve analysis revealed <0.7 microg/mL as the best cut-off value to distinguish between patients with cancer and healthy controls. Using this cut-off value, the DR-70 immunoassay showed a good clinical performance with a sensitivity of 91% and a specificity of 93%. Patients with advanced tumour spread showed significantly higher DR-70 values than those with early-stage tumours (P < 0.0003). CONCLUSION: The DR-70 immunoassay reliably differs between cancer patients and healthy controls. Therefore, it promises to become a useful test for the detection of cancer in clinical practice.

Adult↗
PubMed1997

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

Detection of molecular alterations is of potential significance for diagnosis and prognosis in bladder cancer. Fluorescence in situ hybridization (FISH) allows visualization and quantitation of genes and chromosomes on a cell by cell level and can easily be applied to urinary cells. To evaluate the sensitivity of FISH for detection of DNA aberrations in bladder cancer, formalin-fixed tissues of 293 tumors were examined by FISH and flow cytometry (FCM). Centromere probes for the chromosomes X, Y, 1, 7, 9, and 17 were used for FISH analysis. FISH was more sensitive for detection of quantitative DNA aberrations than FCM. An aberration of at least one chromosome was found in 107 of 108 tumors (99%), which were tetraploid, aneuploid, or multiploid, and in 29 of 49 tumors (59%), which were diploid, by FCM. The frequency of FISH aberrations showed greater differences between pTa (47%) and pT1 tumors (85%; P < 0.0001) than between stages pT1 and pT2-4 (98%). The marked genetic difference between pTa and pT1 tumors argues against the concept of grouping pTa and pT1 tumors together as "superficial bladder cancer." The frequency of tumors with chromosomal aberrations detected by FISH increased with the number of chromosomes examined. Aneusomy was seen in 68% of grade 1 tumors examined for > or = 4 chromosomes, suggesting that the cytological diagnosis of bladder cancer recurrences could be substantially improved by FISH.

Carcinoma, Transitional Cell↗
PubMed2006

Joint National Cancer Institute-Food and Drug Administration workshop on research strategies, study designs, and statistical approaches to biomarker validation for cancer diagnosis and detection.

Cancer remains the second leading cause of death in the United States, in spite of tremendous advances made in therapeutic and diagnostic strategies. Successful cancer treatment depends on improved methods to detect cancers at early stages when they can be treated more effectively. Biomarkers for early detection of cancer enable screening of asymptomatic populations and thus play a critical role in cancer diagnosis. However, the approaches for validating biomarkers have yet to be addressed clearly. In an effort to delineate the ambiguities related to biomarker validation and related statistical considerations, the National Cancer Institute, in collaboration with the Food and Drug Administration, conducted a workshop in July 2004 entitled "Research Strategies, Study Designs, and Statistical Approaches to Biomarker Validation for Cancer Diagnosis and Detection." The main objective of this workshop was to review basic considerations underpinning the study designs, statistical methodologies, and novel approaches necessary to rapidly advance the clinical application of cancer biomarkers. The current commentary describes various aspects of statistical considerations and study designs for cancer biomarker validation discussed in this workshop.

Biomarkers, Tumor↗
PubMed1999

Breast cancer detection with 99m-Tc-sestamibi scintigraphy, mammography, and fine-needle aspiration cytology: comparative study in 64 surgically treated patients.

BACKGROUND: In breast cancer, mammography (MG) fails to reveal malignancy in 10% to 15% of patients, and its sensitivity is limited by dense breast tissue. The aim of this study was to evaluate the usefulness of 99m-Tc-sestamibi scintimammography (SMM) in conjunction with MG and fine needle aspiration (FNA) cytology in the detection of low-stage breast cancer. METHODS: A total of 64 women (median age 58 years, range 32-86 years), 53 (82.8%) with palpable and 11 (17.2%) with nonpalpable breast mass, underwent SMM; 61 patients had MG and 62 underwent FNA cytology. At histological examination, breast cancer was found in 59 (92.2%) of the women (pTis = 2, pT1a = 2, pT1b = 13, pT1c = 20, pT2 = 22). RESULTS: Of the 61 patients who had MG, 45 (73.8%) showed signs of cancer or abnormalities. Of the 62 patients who had FNA cytology, 55 (88.7%) showed malignancy. In 5 (8.1%) patients, atypical ductal hyperplasia or complex sclerosing lesions were found. MG, SMM, and FNA cytology were 80.4%, 78.0%, and 96.5% sensitive, respectively, and their positive predictive value was 97.8%, 100%, and 100%, respectively. In all patients, cancer was at least detected by one of these three techniques. CONCLUSIONS: In women with suspicious MG or abnormal FNA cytology that required further investigations, SMM may be helpful in surgical planning and should be considered in most patients before biopsy as an additional noninvasive procedure.

Adult↗
PubMed2006

Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection.

BACKGROUND: The noninvasive identification of bladder tumors may improve disease control and prevent disease progression. Aberrant promoter methylation (i.e., hypermethylation) is a major mechanism for silencing tumor suppressor genes and other cancer-associated genes in many human cancers, including bladder cancer. METHODS: A quantitative fluorogenic real-time polymerase chain reaction (PCR) assay was used to examine primary tumor DNA and urine sediment DNA from 15 patients with bladder cancer and 25 control subjects for promoter hypermethylation of nine genes (APC, ARF, CDH1, GSTP1, MGMT, CDKN2A, RARbeta2, RASSF1A, and TIMP3) to identify potential biomarkers for bladder cancer. We then used these markers to examine urine sediment DNA samples from an additional 160 patients with bladder cancers of various stages and grades and from an additional 69 age-matched control subjects. Data were analyzed on the basis of a prediction model and were internally validated using a jacknife procedure. All statistical tests were two-sided. RESULTS: For all 15 patients with paired DNA samples, the promoter methylation pattern in urine matched that in the primary tumors. Four genes displayed 100% specificity. Of the 175 bladder cancer patients, 121 (69%, 95% confidence interval [CI] = 62% to 76%) displayed promoter methylation in at least one of these genes (CDKN2A, ARF, MGMT, and GSTP1), whereas all control subjects were negative for such methylation (100% specificity, 95% CI = 96% to 100%). A logistic prediction model using the methylation levels of all remaining five genes was developed and internally validated for subjects who were negative on the four-gene panel. This combined, two-stage predictor produced an internally validated ROC curve with an overall sensitivity of 82% (95% CI = 75 % to 87%) and specificity of 96% (95% CI = 90% to 99%). CONCLUSION: Testing a small panel of genes with the quantitative methylation-specific PCR assay in urine sediment DNA is a powerful noninvasive approach for the detection of bladder cancer. Larger independent confirmatory cohorts with longitudinal follow-up will be required in future studies to define the impact of this technology on early detection, prognosis, and disease monitoring before clinical application.

Aged↗
PubMed2000

Prognostic significance of occult bone marrow micrometastases of breast cancer detected by quantitative polymerase chain reaction for cytokeratin 19 mRNA.

Amplification of cytokeratin 19 (CK19) transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a highly sensitive assay for the detection of bone marrow micrometastases (BMM) of breast cancer, but recent studies have demonstrated the occurrence of false-positive results due to low-level, illegitimately transcribed CK19 in normal bone marrow tissue. One approach to solve this problem is to develop a quantitative CK19 RT-PCR assay and to introduce a cut-off value which can distinguish between illegitimate expression and cancer-specific expression levels. In the present paper, we describe a quantitative CK19 RT-PCR assay using a real-time automated PCR system. The number of CK19 transcripts was normalized to that of GAPDH transcripts as an internal control for quality and quantity of cDNA. The cut-off value for the ratio of CK19 to GAPDH transcripts was set at 10(-4) since the ratio never exceeded this value in the control bone marrow samples (n = 12). In total, 117 bone marrow aspirates from stage I - III patients with invasive breast cancers were subjected to CK19 RT-PCR assay and immunocytological examination. Forty (34.2%) were found to be BMM-positive by CK19 RT-PCR assay whereas only three (2.6%) were found to be BMM-positive by immunocytology. Multivariate analysis has shown that occult BMM detected by CK19 RT-PCR is a significant risk factor for relapse, being independent of axillary lymph node metastases.

Bone Marrow Neoplasms↗
PubMed2001

[Disseminated bone marrow metastases from gastric cancer: detection and monitoring the effectiveness of chemotherapy by bone marrow scintigraphy].

Disseminated bone marrow metastasis of cancer is a critical condition, frequently complicated by disseminated intravascular coagulation (DIC). A 32-year-old man with gastric cancer was diagnosed as having disseminated bone marrow metastases. Bone scintigraphy demonstrated many abnormal radionuclide accumulations in the whole body. Bone marrow aspiration revealed cancer cells. Bone marrow scintigraphy with 111In-Cl3 demonstrated central marrow failure and peripheral expansion. The remission of DIC was observed after sequential methotrexate and 5-FU therapy, then uptake of radionuclide in the central bone marrow was remarkably improved by bone marrow scan. After thirteen anti-cancer chemotherapies, recurrence of DIC was suspected because of the reduction of blood platelet count. Nevertheless, repeated bone marrow scan still demonstrated the central bone marrow clearly. The patient discharged from our hospital without the recurrence of DIC. We considered bone marrow scintigraphy is useful in the detection of disseminated bone marrow metastases of cancer and monitoring the effectiveness of chemotherapy.

Adult↗
PubMedDate not supplied

Report on the American Cancer Society Workshop on Community Cancer Detection, Education, and Prevention Demonstration Projects for Underserved Populations.

The American Cancer Society has been funding six pilot projects organized with the stated purpose of demonstrating how to implement cancer prevention and control projects for socioeconomically disadvantaged and underserved populations. This article reports on the results of a workshop held to evaluate project experiences and develop recommendations for the future.

Adult↗
PubMed2003

[Breast cancer detection and medicalization of public health].

The aim of reducing breast cancer mortality announced in the report on health in France published in 1994 strongly implicated the promotion of screening and early surgical treatment. However, this mortality has not evolved significantly in France, although more and more cancers have been found and operated upon. The increased prevalence rates of histological diagnoses of breast cancer obtained from the studies of autopsies published has shown that the screening has discovered non-terminal, benign cancers. It has been estimated that 120 of the surgical operations conducted per day in France in 1999 have been carried out to remove non-terminal, benign cancers. Public health has an ethical responsibility to face in terms of the allocation of resources and must remain vigilant in order to avoid excessive screening and unnecessary interventions.

Breast Neoplasms↗