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Hypermethylation of the CpG islands in the promoter region of the GSTP1 gene in prostate cancer: a useful diagnostic and prognostic marker?

BACKGROUND: Recently, many studies have focused on the potential diagnostic value of the promoter hypermethylation of the GSTP1 gene in prostate cancer. METHOD: A total of 144 patients, undergoing eight-core prostatic biopsies for a clinically suspected prostate cancer, was analyzed. Two different tissue samples were collected from the same area of the prostate and then divided for both genomic DNA extraction and pathological examination. In order to perform molecular analysis, prostatic tissue samples were digested with the methylation-sensitive restriction enzyme HpaII and then amplified by conventional polymerase chain reaction (PCR). RESULTS: Prostate cancer was diagnosed in 42/144 patients, and promoter hypermethylation of GSTP1 gene was detected in 31/42 of prostate cancer (sensitivity=74%) and in 2/102 of negative specimens (specificity=98%). A significant association between GSTP1 promoter hypermethylation both with a Gleason score >or=7 (Fisher's exact P=0.01) and the presence of Gleason grade 4 and/or grade 5 (Fisher's exact P=0.03) was found. CONCLUSION: Promoter hypermethylation of the GSTP1 gene is a highly specific--but not a very sensitive--marker of prostate cancer. Our data showed a significant association between the methylation status of the GSTP1 gene and Gleason score and grade, suggesting a potential prognostic value of this epigenetic DNA alteration.

Aged↗

[Cervical cancer and pregnancy--diagnostic and therapeutic problems. Report of four cases and review of the literature].

In this publication are presented four cases of pregnant women with a cervical cancer (with preoperative staging) as follow: the first pregnant 6-7 g.w., stage T1a1, No, Mo, the second 19-20 g.w., staged as T2a, Nx, Mo; the third--in 20-21 g.w., stage T1b2, Nx, Mo and the fourth in 29-30 g.w., with premature rupture of membranes and stage T1b2, Nx, Mo. To all patients was performed radical hysterectomy with pelvic lymphnode dissection, and to three of them followed by radiotherapy. To the first operation was performed after induced abortion, to the second hysterectomy was with a fetus in uterus, the third and fourth were with Sectio parva and Sectio caesarea, followed at the same time by radical hysterectomy. The different diagnostic and therapeutic approaches to pregnant women with a cervical cancer, depending of the stage of the disease, the term of pregnancy and the patient and physician's desire are discussed.

Adult↗

Radioiodine uptake in thyroid cancer patients after diagnostic application of low-dose 131I.

The aim of this study was to investigate the influence of the diagnostic administration of 74 MBq 131I on subsequent uptake of therapeutic radioiodine in thyroid cancer patients. Retention measurements were performed using a whole-body counter in 24 patients 6 weeks after total thyroidectomy. Profile scans were performed 2, 24, 48 and 72 h after the administration of the diagnostic dose and 72 h after the administration of the ablation-therapeutic dose (4.4 GBq). The mean ( +/- S.D.) effective half-life of the diagnostic dose in thyroid remnants was 40.3 +/- 23.0 h. The uptake in the thyroid remnants of the subsequent ablation dose 72 h after administration was 30.4 +/- 19.8% of that predicted from the diagnostic study. The greater reduction in uptake was associated with the longer half-life of iodine and higher uptake in the thyroid remnants at 24 h, with a longer interval between surgery and administration of the diagnostic dose and a shorter period between administration of the diagnostic and ablation doses. Our results show that a diagnostic dose of 74 MBq 131I markedly reduces thyroid uptake of an ablation dose of 131I. This should be taken into account during radiation dose planning whenever a quantitative dosimetric study is to be performed.

Female↗

Salivary diagnostics for oral cancer.

Oral cancers annually strike 38,000 individuals in the United States and hundreds of thousands of others around the globe. Despite treatment advances, the disease's overall five-year survival rate has not improved in the past three decades and remains among the worst of all cancers. One factor behind oral cancer's high mortality is the challenge detecting it at its early stages. The use of saliva for the detection of oral cancer has been a historical goal that has yet to come to fruition. This review highlights translational research efforts in alignment with initiatives sparked by the National Institute of Dental and Craniofacial Research toward bringing saliva diagnostics to fruition and, in particular, for saliva-based oral cancer detection.

Biopsy↗

Mammary gland anatomy and the role of mammography and ultrasonography in the early diagnostics of breast cancer. A case report.

Progress in imaging techniques has brought a solution to the problem of the early diagnosis of breast cancer. An interesting case of breast cancer is presented here, pictures of the malignant tumour are demonstrated and the usefulness of new diagnostic methods analysed. The presentation of this case may contribute to greater effectiveness in early breast cancer detection.

Aged↗

State of the science: molecular classifications of breast cancer for clinical diagnostics.

Over the past few years, the study of genomics has embarked on developing gene expression-based classifications for tumors-an initiative that promises to revolutionize cancer medicine. High-throughput genomic platforms, such as microarray and SAGE, have found gene expression signatures that correlate to important clinical parameters used in current staging and are providing additional information that will improve standard of care. Although implementing a molecular taxonomy for prognosis and treatment would likely benefit cancer patients, there remain significant obstacles to using these assays within the current diagnostic framework. Since most genomic assays are being performed from fresh tissue, there is a need to either change the practice of formalin-fixing and paraffin-embedding tissue or adapting the assays for use on degraded RNA specimens. To date, even the most mature data sets, such as molecular classifications for breast cancer, still fall short of the number of patients needed to generalize the results to treating large populations. To implement these assays in large scale, there will need to be standardization of sample procurement, preparation, and analysis. Certainly, the greatest improvements in patient care will come through tailored therapies as genomics is coupled with clinical trials that randomize cohorts to different treatments. This manuscript reviews the current standards of care, presents progress that is being made in the development of genomic assays for breast cancer and discusses options for implementing these new tests into the clinical setting.

Biomarkers, Tumor↗

The role of laparoscopy in preoperative staging of esophageal cancer.

BACKGROUND: Diagnostic laparoscopy has been used to determine resectability and to prevent unnecessary laparotomy in patients with advanced esophageal cancer. The objective of this prospective study was to evaluate the role of laparoscopy in conjunction with computed tomography (CT) scan in staging patients with esophageal cancer. METHODS: From March 1995 to October 1998, 59 patients with biopsy-proven esophageal cancer underwent diagnostic laparoscopy with concurrent vascular access device and feeding jejunostomy tube placement. RESULTS: Laparoscopy changed the treatment plan in 10 of 59 patients (17%). Of the patients with normal-appearing regional or celiac nodes, 78% were confirmed by biopsy to be tumor free, whereas 76% of patients with abnormal-appearing nodes were confirmed by biopsy to have node-positive disease. CONCLUSIONS: Diagnostic laparoscopy is useful for detecting and confirming nodal involvement and distant metastatic disease that potentially would alter treatment and prognosis in patients with esophageal cancer.

Adult↗

Diagnostic delay in cancer of the breast.

The occurence of delay in the diagnosis of breast cancer was investigated in 115 women with breast cancer. Earlier breast disease and earlier consultations for breast symptoms were thoroughly inquired about and analysed. The part of "diagnostic delay" referred to "doctor's delay" occurred in one fifth of the breast cancer patients but in one third of the patients under 50 years of age compared to one seventh of the patients over 50 years. The reasons for delay were: incomplete investigation of palpable or suspected breast tumour, non-representativeness of surgical biopsy or of slides taken for histopathological examination, underestimation of atypia at histopathological examination, unsatisfactory follow-up after biopsy of suspected tumour.

Adult↗

Prognostic significance of residual cancer tissue after diagnostic biopsy in breast carcinoma. Three-year short-term results.

Among 3264 cases of breast carcinoma undergoing diagnostic biopsy and frozen section followed by one-stage mastectomy, the occurrence of residual cancer tissue (RCT) was evaluated as part of a prospective, nationwide trial in Denmark. RCT was defined by the presence of cancer left in relation to the biopsy cavity in the mastectomy specimen. A significantly higher cumulative recurrence rate within 3 yr was found in cases with residual cancer compared to cases without this finding. The difference was most pronounced in the premenopausal high-risk group. Therefore, RCT in the wall of the biopsy cavity is considered a prognostic hazard by itself.

Biopsy↗

Diagnostic delay in breast cancer: correlation with disease stage and prognosis.

Diagnostic delay in a group of 189 women with breast cancer was studied and correlated with first symptom, stage of disease, histologic grade and prognosis. Diagnostic delay was divided into patient delay (time from the patient's discovery of a symptom to the first medical consultation) and system delay (time from medical diagnosis to treatment). Patients were divided into five groups by patient-delay time: 0 to 30 days; 31 to 90 days; 91 to 180 days; 181 to 365 days; and greater than 365 days. The median diagnostic delay was 60 days (range, 4-980) and was not influenced by patient age, marital status or nature of first symptom. A consistent and direct relationship was found between delay and tumor size, nodal involvement, presence of metastases, and histologic grade of disease at diagnosis. No correlation was found between diagnostic delay and histologic type distribution. The three-year survival rate after treatment was significantly lower for patients with a longer delay. Our data indicate that diagnostic delay appears to be an important determinant of stage at diagnosis in women with breast cancer and that it has an important influence on survival. In most cases, delay was mainly patient dependent (60 days); the median system-dependent delay was 15 days (range, 4-47). Since early treatment is generally accepted to be one of the most important determinants of prognosis in breast cancer patients, a reduction in diagnostic delay may lengthen survival time.

Adult↗

Plasma chromogranin A in patients with prostate cancer improves the diagnostic efficacy of free/total prostate-specific antigen determination.

INTRODUCTION: We ascertained whether plasma chromogranin A enhances the power of serology assessing prostate cancer (PC). MATERIALS AND METHODS: We studied 56 PC and 83 benign prostatic hyperplasia (BPH) patients. In the sera we measured total prostate-specific antigen (tPSA) and free PSA (fPSA) and calculated the ratio between fPSA and tPSA (f/tPSA). In plasma samples the levels of chromogranin A (CgA) were also assayed. RESULTS: PC patients had higher CgA (p < 0.005) and tPSA (p < 0.05) levels, and a lower f/tPSA ratio (p < 0.001), than BPH patients. When f/tPSA and CgA were combined, the diagnostic sensitivity was enhanced (57-73%), while the specificity had only an 8% reduction (from 89 to 80%). CgA was only correlated to the Gleason PC score (p < 0.05). CONCLUSIONS: CgA determination in PC may enhance the diagnostic accuracy of the f/tPSA assay and provides useful information on the tumor grade.

Aged↗