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Diagnostic imaging of lung cancer after heart transplantation.

AIMS AND BACKGROUND: In heart transplant recipients pulmonary neoplasms are among the most frequent solid tumors; they have a rapid and aggressive course, and therefore require an early diagnosis. We describe the role that diagnostic imaging plays in different diagnostic moments of this disease. METHODS: We evaluated the incidence and diagnosis of lung cancer in patients who underwent heart transplants at our institution. Taking into account the few different diagnostic imaging techniques (chest X-ray, high-resolution computed tomography [CT], staging CT and CT-guided biopsy) used in standard surveillance protocols or indicated by clinical symptoms, we evaluated their diagnostic accuracy, their efficacy in tumor staging, and their impact on the therapeutic choices. RESULTS: Seventeen neoplasms in a total of 712 patients were diagnosed (2.4%). In 16 of these 17 cases chest X-ray (routinely performed as follow-up in 11 cases, indicated by symptoms in 5 cases) was diagnostic. In another 11 cases chest X-ray was false positive. The diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of chest X-ray was 98%, 91%, 98%, 50%, and 99%, respectively. Total-body CT correctly staged the tumors and provided information as to whether surgery was indicated or not (stage II or advanced). CONCLUSIONS: Chest X-ray is still the surveillance radiological technique in heart transplant recipients. Considering its low specificity and sensitivity, we propose high-resolution CT imaging during follow-up to identify pulmonary lesions as soon as possible and enable a differential diagnosis with parenchymal inflammation. The use of CT-guided fine-needle biopsy and culture examinations permits to differentiate neoplastic from inflammatory parenchymal opacities. Use of CT in cancer staging is effective for subsequent treatment choices.

Biopsy↗

[Cancer of the vulva. Diagnostic and therapeutic aspects apropos of a series of 90 cases].

The authors present a series of 90 cases of cancer of the vulva of which 10 were intra-epithelial and 80 were invasive. These were studied from the 1st January 1962 through to the 31st December 1980. The mean age was 70.04 years, the range being from 31 to 92 years of age. Most cases however were between the ages of 70 and 80. 37.7% of the patients were debilitated. The condition was brought to notice by the discovery of a tumour in 48.8% of the cases, the onset of pruritus in 20% of cases and pain in 14.4%. Most of the tumours were found on the labia majora and minora (in 52.2%). FIGO classification was of stage I in 12% of cases, stage II in 26.6%, stage III in 33.3% and stage IV in 28%. The methods for treating these conditions have been shown according to whether the tumour was intra-epithelial or invasive. Analysing the results confirms that this kind of cancer has a poor prognosis: 57.6% of survivors after 2 years but only 37.3% after 5 years (an actuariel calculation). 30 cases of relapses were analysed and also the complications that occurred. Among these were most frequently (25%) lymphocoeles, sutures falling out because of necrosis and infection (34.2%), urinary incontinence (35.2%). The circumstances in which the patients died were determined above all by the way the disease evolved locally, but in 13.3% of the cases there was metastatic disease. Finally, the difficulties of the diagnosis and of the definition of micro-invasive cancer of the vulva are commented on. The authors point out that the prognosis depends as much as anything on the amount the lymphatics are involved, the frequency and the problems of therapy that are posed by urinary incontinence which occurs after operation. They then give their ideas for treating the patients.

Adult↗

Knowledge of oral cancer risk factors and diagnostic concepts among North Carolina dentists. Implications for diagnosis and referral.

BACKGROUND: Dentists play a critical role in the early detection of oral and pharyngeal cancer (OPC). The authors administered a survey that assessed the level of knowledge among dentists regarding risk factors and diagnostic concepts. METHODS: In 2002, the authors mailed a 38-item, pretested survey to a random sample of 1,115 licensed dentists practicing in North Carolina. Three-level (low, medium, high) composite index scores for knowledge of risk factors and diagnostic concepts were created using previously developed scales. The authors formulated multivariable models for risk factor and diagnostic knowledge indexes. RESULTS: Of the 584 respondents, only 181 (31 percent) had consistent medium-to-high levels of knowledge on both highly correlated indexes. Dentists who had higher risk factor and diagnostic knowledge scores were significantly (P < .05) more likely to have heard of one or more diagnostic aids (odds ratio [OR], 2.7), to have graduated from dental school within the previous 20 years (OR, 1.8) and to have performed biopsies or referred five or more patients with suspicious lesions per year (OR, 1.7 and 1.5, respectively) than were less-knowledgeable respondents. CONCLUSIONS: More education is needed in dental schools, postgraduate programs and continuing education programs to enhance dental professionals' knowledge of OPC risk factors and diagnostic concepts. Such programs should include information about adjunctive diagnostic aids. PRACTICE IMPLICATIONS: Greater knowledge of risk factors and diagnostic concepts may result in more frequent patient referrals, biopsy procedures or both, thus aiding in the early diagnosis and treatment of patients with OPC.

Analysis of Variance↗

Diagnostic testing for prostate cancer detection: less is best.

The incidence of clinically organ-confined prostate cancer has markedly improved in programs designed to detect this disease by utilizing a combination of diagnostic modalities including digital rectal examination (DRE), transrectal ultrasonography (TRUS), and prostate-specific antigen (PSA). Biopsies were performed on 436 men who had abnormal findings on DRE, TRUS, or PSA. Overall, 39 percent of these men had histologic confirmation of prostate cancer. TRUS diagnosed more cancer (94%) than either DRE (80%) or PSA (89%), while the combination of TRUS and PSA diagnosed a similar number of cancers as the combination of DRE and PSA (100% vs 98%). The positive predictive value (PPV) of DRE and PSA combination was significantly better than that of TRUS and PSA (p = 0.01), but was not different from that of a combination of all three tests. DRE and PSA would have missed 4 cancers, but would have cost approximately 140 percent less than any program employing TRUS. Consequently, we recommend that the combination of DRE and PSA be used in primary early detection for prostate cancer and that TRUS be performed only when either or both DRE and PSA results are abnormal.

Costs and Cost Analysis↗

Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics.

The development of surface-enhanced Raman scattering (SERS)-active substrates for cancer gene detection is described. The detection method uses Raman active dye-labeled DNA gene probes, self-assembled monolayers, and nanostructured metallic substrates as SERS-active platforms. The mercaptohexane-labeled single-stranded DNA (SH-(CH(2))(6)-ssDNA)/6-mercapto-1-hexanol system formed on a silver surface is characterized by atomic force microscopy. The surface-enhanced Raman gene (SERGen) probes developed in this study can be used to detect DNA targets via hybridization to complementary DNA probes. The probes do not require the use of radioactive labels and have a great potential to provide both sensitivity and selectivity. The effectiveness of this approach and its application in cancer gene diagnostics (BRCA1 breast cancer gene) are investigated.

BRCA1 Protein↗

Molecular diagnostic markers for lung cancer in sputum and plasma.

Lung cancer is the leading cause of cancer deaths worldwide. This study was designed to select multiple DNA markers, which have high sensitivity and specificity to serve as biomarkers for diagnosis of lung cancer. We examined the promoter hypermethylation of three tumor suppressor genes by methylation-specific PCR (MSP), and the instability of eight microsatellite markers by loss of heterozygosity (LOH) and microsatellite instability (MSI) analyses in lung tumor tissues and matched sputum specimens from 79 lung cancer patients. On the basis of the results of sensitivity, specificity, and concordance from each marker analyzed, we selected seven biomarkers, which are LOH of D9S286, D9S942, GATA49D12, and D13S170, MSI of D9S942, and methylation of p16(INK4a) and RARbeta, from the sputum analyses. These selected etiologically associated biomarkers can potentially be used as supplemental diagnostic biomarkers for early lung cancer detection.

Biomarkers, Tumor↗

An overview of research in cancer diagnosis.

The diagnostic research program of the National Cancer Institute encompasses detection or screening, methods of diagnosis, and prognosis. The present objective of this program is diagnosis of 75% of all cancers at a time when 90% of these have not metastasized. The Institute's Divison of Cancer Biology and Diagnosis has directed its attention toward general diagnostic methods (immunologic, chemical, cytologic, imaging, and endoscopic) and organ site programs (breast, lung, cervix, bowel, bladder, and pancreas). The organ site programs usually involve multiple diagnostic techniques applied to a specific organ. Screening for asymptomatic cancer seems an important immediate objective. Optimum frequency of screening should be established for individual organ sites and for combinations of sites, to determine whether multi-site screening programs can significantly reduce mortality from cancer.

Breast Neoplasms↗

[Diagnostic radiation and the risk of cancer].

The risk of radiation-related cancer following exposure to diagnostic radiation is of much concern. Diagnostic exposure is a repeated one to low dose radiation, while acute exposure occurred among atomic bomb survivors where the epidemiological survey contributes to the current cancer risk estimates of low doses. In several cohort studies on medical exposure at low doses, there is no statistical power of detection due to population size and no dose information. Even in cohort studies on occupational exposure there is no clear conclusion, however, a pooled analysis of nuclear workers in several countries is expected to produce a better basis for risk estimate at low doses. The risk estimate based on the linear non-threshold (LNT) dose response derived from the atomic bomb survivor data remains unresolved scientifically, and thus it has much uncertainty. Recent radiation biology suggests that a bystander effect and adaptive response might modify the estimated cancer risk based on the LNT model at low doses. However, there is no clear evidence in human data. The most effective way to clarify low-dose risk is to focus on the mechanism of radiation carcinogenesis. The risk from almost all diagnostic X-rays may be so small that no excess cancer incidence can be statistically detected.

Cohort Studies↗

Role of cell-free plasma DNA as a diagnostic marker for prostate cancer.

Recent evidence has shown elevated levels of cell-free plasma DNA in cancer patients. The aim of the present study was to quantify and compare the levels of cell-free plasma DNA in patients with prostate cancer, prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) to examine if it offered a useful diagnostic test. Blood samples were obtained from 37 patients attending a clinic for prostate biopsies. Samples were taken prior to biopsy, within 1 hour of the biopsy, and then 2 weeks later. DNA was extracted using a QIAamp blood kit (Qiagen) and plasma DNA measured, in genome equivalents/milliliter plasma (GE/mL), using real-time quantitative PCR for the beta-globin gene. Prior to biopsy, plasma DNA concentration in BPH patients was 936 GE/mL (median; range: 633-2074 GE/mL), while cancer and PIN patients had significantly higher levels of DNA at 1734 GE/mL (median; range: 351-3131 GE/mL; P = 0.01) and 1780 GE/mL (median; range: 1514-2732 GE/mL; P = 0.04), respectively. Comparison of plasma DNA concentration before and after biopsy showed that 60 minutes after biopsy values were significantly higher in both BPH (1494 GE/mL; range: 613-2522 GE/mL; P = 0.029) and cancer (2758; range: 1498-5226 GE/mL; P = 0.007) patients. ROC analysis of the data indicated a sensitivity of 85% and a specificity of 73% when DNA concentration of 1000 GE/mL was taken as an indicator of malignancy or PIN. The data suggest that quantification of cell-free plasma DNA may have an important diagnostic role in distinguishing benign and malignant prostate disease.

Adenocarcinoma↗

A comparison of invasive breast cancer detected in a screened population with invasive breast cancers detected at rapid access diagnostic facilities.

The objective of this study was to assess the impact of rapid access breast diagnostic facilities on the benefit of mammographic breast screening. Invasive cancers were compared for maximum diameter in two groups: group A--70 patients, with screen detected breast cancer aged 50-65, mean age 55.8; group B--46 patients, with symptomatic breast cancer aged 50-65, mean age 56.7. Group A patients had all been invited for screening and included interval cancers and cancers in lapsed attenders. Group B patients were detected at rapid access diagnostic facilities. In group A (screened) the invasive cancers had a mean diameter of 17.8 mm, with a median of 15 mm. Group B (unscreened) consisted of invasive cancers with a mean diameter of 25.2 mm, and a median of 25 mm. Thirty-two (46%) of the screened cancers were found to be less than 15 mm compared to 5 (11%) of the unscreened cancers, using the Wilcoxon Rank Sum Test, P<0.001. Although rapid access modern diagnostic facilities for breast cancers offer the ability to detect early cancers (11% in this survey), screen detected invasive cancers remain significantly smaller even when interval cancers and cancers in lapsed attenders are included.

Journal Article↗

BTA-TRAK--a useful diagnostic tool in urinary bladder cancer?

During recent years the BTA-TRAK-assay (Bard Diagnostics, Redmont, USA) has been described in several investigations to be of clinical utility for patients suffering from bladder cancer. In a prospective study we investigated over four months the voided urine samples of all consecutive patients undergoing cystoscopy independent of their clinical background (n = 244) with the BTA-TRAK-assay. With a specificity of 95% for benign urological diseases (cut off: 1300 U/mL) we found a sensitivity of 13% for active bladder tumours. Using healthy individuals as a reference group (cut off: 40 U/mL) we found a sensitivity of 56% (specificity 67%). Using the cut off value recommended by the manufacturer (14 U/mL) a specificity of 54% and a sensitivity of 62% was found. For patients without relapse (NED) versus patients with active bladder tumours we got a specificity of 55% and a sensitivity of 62%. Due to an insufficient specificity and sensitivity the BTA-TRAK-test is not able to replace cystoscopy nor to improve existing diagnostic strategies in bladder cancer.

Cystoscopy↗

[Detection of oncogenic mutations in sputum and its diagnostic value of lung cancer].

OBJECTIVE: To find a new method to molecular biological detection of lung cancer. METHOD: The sputum specimens from 96 cases of lung cancer and other lung patients were detected for K-ras and p53 mutations by using polymerase chain reaction(PCR) and restriction fragment length polymorphism and and immunohistochemistry (IHC) techniques. RESULT: 38 out of 62 sputum specimens of lung cancer patients were positive for cytology: Sensitivity was 61%. NPV (negative predictive value) was 59%; p53 was overexpressed in 48 cases: Sensitivity was 77%. NPV was 66%; k-ras was positive in 21 cases: Sensitivity was 34%, NPV 42%; The combination of conventional cytology and molecular screening(k-ras + p53) produced a sensitivity value of 92%(P < 0.05) with an NPV of 84%(P < 0.05); In 24 cases of patients whose cytology of sputum was false negative, 17 were found either p53 or k-ras positive of which 7 patients were identified to be lung cancer in the follow-up study. CONCLUSION: These results suggest that detection of oncogene mutation in sputum enhanced and added to the diagnostic value of conventional cytology. It is a promising approach to early lung cancer detection and massive screening in terms of its rapidity, economy and simplicity.

Adenocarcinoma↗

Hospital costs, cancer patients, and surgical diagnostic related groups.

This study of 4,359 Medicare patients in 107 noncancer stratified surgical Diagnostic Related Groups (DRGs) tested the hypothesis that patients with a diagnosis of a malignancy (i.e., cancer) in these DRGs would have higher resource utilization than patients without a diagnosis of a malignancy (i.e., noncancer) in these same surgical DRGs. The 1,008 cancer patients had 3.2 times the financial loss ($1,617 per patient vs. $510 per patient) compared to the 3,351 noncancer patients (P less than .05). Patients with cancer had a greater percentage of outliers, more diagnosis (P less than .0001) and procedures (P less than .0001) per patient, and a higher mortality (P less than .01) than patients without cancer. These findings raise the question of the equity of DRG payment for patients with cancer in many surgical DRGs. Financial disincentives to treat certain groups of Medicare cancer patients at our hospital may affect both their access and quality of care in the future.

Aged↗

[Diagnostic value of aspiration cytology with ERCP].

ERCP is of great value in diagnosing malignant pathology of the biliopancreatic duct system. However, the ERCP endoscopic characteristics in malignant stenosis often lack specificity and are difficult to differentiate from those of chronic pancreatitis. In these cases histological confirmation is essential to diagnosis. With the aim of increasing the diagnostic possibilities of ERCP in pancreatic cancer--particularly when associated with chronic pancreatitis--we performed aspiration cytology of pancreatic juice obtained via endoscopic cannulation of the main pancreatic duct using ERCP in 102 patients with suspected periampullar pathology, chronic pancreatitis and/or pancreatic cancer. The diagnostic sensitivity of cytology for pancreatic malignancy was 33.3%, versus 60% for cancer of Vater's papilla. Specificity was 100% in both cancers. We observed no false positive results or complications. On combining both techniques, i.e., ERCP and cytology of the pancreatic juice, sensitivity increased to 100% for pancreatic malignancy, 77.7% for chronic pancreatitis (characteristic ERCP radiographic images and absence of neoplastic cells) and 100% in the case of ampullomas. Difficulties in the differential diagnosis between advanced chronic pancreatitis and pancreatic cancer persist with ERCP alone. In such cases aspiration cytology may secure a definitive diagnosis--particularly when neoplastic cells are demonstrated (Class IV).

Adult↗

Omission of mediastinal lymph node dissection in lung cancer: its techniques and diagnostic procedures.

To reduce or omit a mediastinal lymph node dissection in the patients with clinical stage I non-small cell lung cancer (NSCLC), several authors examined the prevalence of metastatic sites of lymph nodes. Because lymphatic drainage usually heads for the upper mediastinum in upper lobe cancer and for the lower mediastinum in lower lobe cancer, upper and lower mediastinal lymph node dissection could be reduced in lung cancers of lower lobe and upper lobe. By using sentinel node (SN) navigation surgery, it is possible to omit mediastinal lymph node dissection. Radiological findings are also useful to determine reduction of mediastinal lymph node dissection. In clinical stage Ia adenocarcinomas that show ground glass opacity (GGO) findings on computed tomography (CT) or negative for fluorodeoxyglucose accumulation on positron emission tomography (PET), mediastinal lymph node dissection can be omitted, because these types of adenocarcinomas rarely metastasize to the lymph nodes. By using these procedures, mediastinal lymph node dissection can be reduced or omitted with little risk of local recurrence.

Carcinoma, Non-Small-Cell Lung↗