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[Thrombophlebitis and cancer: evaluation of the diagnostic value of abdominal ultrasonography in the acute phase of a deep venous thrombosis. Report of 148 consecutive examinations].

If an association between venous thromboembolism and malignancy is now well established, there is no consensus about the investigations which should be performed to detect occult malignancy after deep vein thrombosis episode. We investigated the usefulness of systematic abdomino-pelvic ultrasonography in 148 consecutive patients older than 40 with deep vein thrombosis and or pulmonary embolism. Ultrasonography was abnormal in 8 patients (5.4%) and detected only 6 cancers. In 5 cases, clinical examination and laboratory tests were sufficient to suggest malignancy. Our results suggest that ultrasonography should not be systematically performed in patients with deep vein thrombosis. Decisions to performed additional diagnostic tests can be based on the finding of the initial clinical examination, that includes medical history, physical examination, routine laboratory tests and chest-x-ray.

Abdomen↗

Reimbursement of tumor marker tests.

The diffusion of new technology is significantly affected by coverage and reimbursement decisions. A variety of agencies (public and private) make decisions as to which technologies or treatments will be covered and what the levels of reimbursement will be. Recently, these agencies' coverage decisions have tended to be strongly affected by whether a technology is cost raising or cost reducing. Historically, a common effect of medical innovation has been improved quality of health care but with a corresponding increase in cost of delivery. The Medicare program has significant influence on the coverage policies of public and private third-party payers. This influence is especially visible in coverage and reimbursement decisions for cancer-related diagnostic procedures and systems. Coverage for these procedures and systems is not widespread because payers have not been convinced of the clinical usefulness of the assays. The industry must take the responsibility of working through the issues surrounding coverage and reimbursement of cancer-related diagnostic procedures with the payers. The ability to successfully negotiate payment for assays requires knowledge of Medicare coverage policies and a grasp of the reimbursement system.

Biomarkers, Tumor↗

Impact of low-dose CT on lung cancer screening.

Despite advances in therapy, the prognosis of lung cancer remains dismal due to the fact that most cases of lung cancer are diagnosed at advanced stages, when the chance of cure is poor. In cases detected at early stages prognosis is better. Unfortunately, early lung cancer usually causes no symptoms and is, consequently, rarely diagnosed. Therefore, screening for early asymptomatic lung cancer with diagnostic procedures appears promising particularly as risk factors for lung cancer are well known (cigarette smoking, occupational asbestos exposure and others) and screening could, therefore, focus on these risk groups. In the past, screening trials using analysis of sputum cytology and to some extent chest radiography have failed to demonstrate a reduction in lung-cancer mortality with screening, probably due to insufficient sensitivity of these tests for early lung cancer. During the last decade the introduction of spiral computed tomography (CT) has provided a technique with a much higher sensitivity for small lung cancers. Feasibility studies using low-radiation-dose CT demonstrated a high proportion of non-small-cell lung cancer at the initial examination (prevalence) with decreasing numbers of detected cancers at follow-up (incidence). The proportion of early-stage tumors was high both at prevalence and incidence examinations. The rate of invasive procedures for benign lesions was low; most indeterminate lesions could be classified with non-invasive diagnostic approaches. The proportion of interval cancers (cancers diagnosed by symptoms between two screening CT scans) was low. As, however, these one-arm feasibility trials are not appropriate to assess a potential mortality reduction through CT screening, prospective randomised multicenter trials were recently initiated in several countries to analyse the effect of CT screening on lung-cancer mortality.

Carcinoma, Non-Small-Cell Lung↗

[Diagnostic usefulness of Ca 19-9 antigen in cancer of the pancreas and neoplasms of the pancreato-biliary intersection].

Antigen CA 19-9 was measured in the serum of a group of 16 patients with pancreatic cancer, in 19 patients with non-pancreatic gastrointestinal malignancies, and in 19 others with benign pancreatobiliary disease. The test showed a high sensitivity with a low specificity and a positive predictive value for diagnosis of pancreatic cancer when confronted with a group of controls that included both benign and malignant gastrointestinal disease. The low specificity was due to high CA 19-9 values in other gastrointestinal cancers, especially in carcinoma of the ampulla and the biliary tract. When the latter were added to the group of patients with pancreatic cancer, and the diagnostic accuracy of the test was re-evaluated, sensitivity, specificity and both positive and negative predictive values increased. Values of CA 19-9 over 100 U/ml are highly predictive of malignancy in patients with pancreato-biliary disease.

Adult↗

Cancer of the endometrium: current aspects of diagnostics and treatment.

BACKGROUND: Endometrial cancer represents a tumor entity with a great variation in its incidence throughout the world (range 1 to 25). This suggests enormous possibilities of cancer prevention due to the fact that the incidence is very much endocrine-related, chiefly with obesity, and thus most frequent in the developed world. As far as treatment is concerned, it is generally accepted that surgery represents the first choice of treatment. However, several recommendations seem reasonable especially with lymphadenectomy, even though they are not based on evidence. All high-risk cases are generally recommended for radiotherapy. METHODS: A literature search of the Medline was carried out for all articles on endometrial carcinoma related to diagnosis and treatment. The articles were systematically reviewed and were categorized into incidence, etiology, precancerosis, early diagnosis, classification, staging, prevention, and treatment. The article is organized into several similar subheadings. CONCLUSIONS: In spite of the overall good prognosis during the early stages of the disease, the survival is poor in advanced stages or recurrences. Diagnostic measures are very well able to detect asymptomatic recurrences. These only seem justified if patients' chances are likely to improve, otherwise such measures increases costs as well as decrease the patients' quality of life. To date neither current nor improved concepts of endocrine treatment or chemotherapy have been able to substantially increase patients' chances of survival. Therefore, newer concepts into the use of antibodies e.g. trastuzumab in HER2-overexpressing tumors and the newer endocrine compounds will need to be investigated. Furthermore, it would seem highly desirable if future studies were to identify valid criteria for an individualized management, thereby maximizing the benefits and minimizing the risks.

Journal Article↗

Nuclear matrix protein expression in prostate cancer: possible prognostic and diagnostic applications.

Different lines of evidence suggest that the nuclear matrix (NM), the protein scaffold of the nucleus, represents a functional unit playing a pivotal role in the spatial and temporal coordination of the events of gene activation. Any change in the gene expression pattern, which occurs during carcinogenesis, may partially depend on an impairment of the regulatory functions of the NM. Therefore, increasing interest has been addressed to the study of NM modifications associated with malignant transformations and to potential clinical applications. Here, recent results on the NM changes in prostate cancer are discussed. Tumor cells are characterized by a more complex NM protein pattern compared to normal tissue: the development of poorly-differentiated tumors is characterized by the expression of proteins that are not present in hyperplastic tissues or in more differentiated tumors. In addition, a few newly-expressed proteins are significantly correlated with the risk of biochemical progression. The potential application of these proteins at the diagnostic and prognostic levels calls for further studies.

Animals↗

Diagnostic imaging of early gallbladder cancer: retrospective study of 53 cases.

To diagnose early gallbladder carcinoma is difficult but essential to improve the survival of the patients with this cancer. Fifty-three early gallbladder cancers were macroscopically divided into protruding and flat types. The diagnostic devises [ultrasonography (US), computed tomography (CT), and drip infusion cholangiography (DIC)] were compared for their ability of early detection. The specimens were examined cytologically for diagnosis during operation and the p53 protein was investigated. Thirty-three cases were of the protruding type, eighteen of the flat type, and two unclassified. Carcinoma tended to be missed when gallstones were present. Preoperative diagnosis of the flat type was difficult. Tumor location did not always correlate with the preoperative diagnosis. Of the misdiagnosed cases of the protruding type, half were missed with US and CT and were not visualized clearly by DIC. Among the flat type cancers, only three had no abnormal findings by diagnostic imaging. Cytologic examination was effective, and p53 was expressed only in early carcinoma, not in adenoma or dysplasia. Even in the presence of gallstones or cholecystitis, any abnormal findings should make one suspicious of gallbladder cancer. Cytology and p53 expression may be useful for the intraoperative diagnosis, and a combination of diagnostic methods is important.

Adenoma↗

Urinary organ specific neoantigen. A potentially diagnostic test for colorectal cancer.

Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A405: 0.717 +/- 0.500) vs 27 controls [0.121 +/- 0.273 (P < 0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N = 13), adenomas (N = 26), inflammatory bowel disease (N = 8), or having a normal colonoscopic examination (N = 24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P < 0.05). The presence of the M(r) 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC.

Adult↗

Regional cancer cytogenetics: a report on 1,143 diagnostic cases.

The results of studies from a regional cancer cytogenetics diagnostic service are reported. In a 10-year period, 1,143 marrow samples from patients with newly diagnosed leukemia and myelodysplastic syndrome were referred. Successful studies were completed on 992 cases (87%). Among all referred cases, the rates of detection of cytogenetically abnormal clones were 95% for chronic myelogenous leukemia (CML), 54% for acute lymphoblastic leukemia (ALL), 51% for acute myeloid leukemia (ANLL), and 43% for myelodysplastic syndrome (MDS). Of 169 cases of CML studied, 90.5% bore the standard Philadelphia chromosome (Ph), 3.55% had an unusual Ph, and 5.33% were Ph-negative. Among the 59 cases of cytogenetically abnormal MDS, common abnormalities observed were trisomy 8 and changes resulting in loss of material from the long arm of chromosomes 5 and 7, and 20q-. Of the 168 abnormal ANLL, there was a strikingly non-random pattern of aneuploidy, with monosomy 7 and trisomy 8 predominating. Common structural changes observed were changes resulting in loss of material from the long arm of chromosomes 5 and 7, trisomy 8, rearrangements of 11q23, t(15;17), t(8;21), rearrangements of 12q13 and 3q, inversion 16, trisomy 11, Ph, trisomy 21, t(6;9) and t(1;22). The differences between adult and pediatric findings were minor, with the exception of chromosome 5 abnormalities, which were common among adults with ANLL but rare in the pediatric cases. There were 273 ALLs with abnormal cytogenetic findings. There was preferential gain of chromosomes 21, X, 14, 6, 4, 18, 17, and 10 (in decreasing order of frequency) in leukemic clones. Of the 193 ALLs with structural changes, many fell into-well-defined categories with established correlations to FAB subtypes. Common changes in ALL were rearrangements of 9p, 12p, 6q, TCR loci, 11q23, Ig loci, and 8q24, and duplication of 1q, Ph, i(17q), t(1;19), i(9q) and dic(9;12). The detailed documentation of the cytogenetic findings in this relatively large, single-institution study will likely facilitate the further characterization of rare, primary cytogenetic changes associated with leukemias and MDS. From a managed health care perspective, regional cancer cytogenetic services may be cost-effective alternatives to single-institution laboratories.

Adult↗

Projecting the lifetime risk of cancer from exposure to diagnostic ionizing radiation for adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a disorder characterized by lateral curvature of the spine and is the most prevalent orthopedic disorder in this age group. The diagnosis and management of AIS requires multiple full-spinal radiographs, leading to potentially high doses of ionizing radiation. The purpose of this study was to estimate in a cohort of subjects with AIS the organ-specific doses of x-ray radiation from spinal radiographs and to calculate the lifetime number of cancers attributable to these exposures. The cohort consisted of AIS patients referred from 1960 to 1979 to a large pediatric hospital in Montreal, Quebec. Organ-specific x-ray doses were estimated using a Monte Carlo procedure that accounted for the radiant energy of the x-ray beam. Cumulative doses for each subject were obtained by summing the estimated doses over all radiographs. These estimates of dose and published estimates of risk from the U.S. National Academy of Sciences Fifth Committee on the Biological Effects of Ionizing Radiation were then incorporated into a life table procedure to project the excess lifetime risk of cancer. About 85% of the 2,181 subjects in the cohort were first referred for scoliosis between the ages of 11 and 17 y. The mean number of radiographs over an average 3-y follow-up period was 12. Organs receiving the highest mean cumulative doses (about 0.03 Gy) were the thyroid gland and the female breast. About 10 excess incident cancer cases (out of a total of 399 projected) and about four excess deaths (out of a total of 247 projected) were estimated to occur over the lifetime of the 1,847 women in the cohort. This is equivalent to an excess lifetime risk of about 1 to 2% (12-25/1,000) among women. Although doses today from spinal radiographs are considerably lower than two decades ago, doses and risks can be further reduced through the use of the posteroanterior view in place of the more traditional anteroposterior view.

Adolescent↗

Factors associated with adequacy of diagnostic workup after abnormal breast cancer screening results.

BACKGROUND: Women with certain characteristics, such as those residing in rural areas, are less likely screened for breast cancer. To enhance detection of early breast cancer, it is imperative that all women who have abnormal screening results receive appropriate diagnostic procedures. This study reports differences in receipt of diagnostic services following abnormal screening results. METHODS: Screening and diagnostic data were collected as part of a breast and cervical cancer early detection program aimed at reaching women of lower socioeconomic status. Women with completed diagnostic information after having abnormal screening results were included. We based adequacy of diagnostic services on guidelines from the Society for Surgical Oncology, The Commission on Cancer of the American College of Surgeons, and the Centers for Disease Control and Prevention. Several factors were assessed for their association with adequacy of diagnostic follow-up: income, age, race, education, health insurance status, rural-urban residence, reported breast lump, family history of breast cancer, and clinical beast examination or mammogram results. RESULTS: Overall, 14.1% of the 351 abnormal findings were considered inadequately followed up based on the algorithm used. Eighty percent involved an abnormal finding on a clinical breast examination regardless of the mammogram results. Rural women, those with abnormal clinical breast examination findings but normal or equivocal findings on mammograms, and those who self-discovered a mass were less likely to receive adequate follow-up than were their counterparts in multivariate analysis. Rural women were less likely to receive a biopsy or fine-needle aspiration, although it was indicated. One facility accounted for most of the inadequate follow-up screenings among urban women. CONCLUSIONS: Women who have specific demographic and clinical characteristics were less likely to have received adequate diagnostic services. Breast cancers could have been missed initially as a result of inappropriate follow-up. Further investigation of the clinical scenarios using chart reviews is warranted.

Algorithms↗

Barrett esophagus and cancer: pathogenesis, carcinogenesis, and diagnostic dilemmas.

A metaplastic process, in which native squamous epithelium of the distal esophagus is replaced by columnar epithelium, is known as Barrett esophagus (BE). Over the past years, intestinal metaplasia was recognized as a marker for BE. The risk for the development of esophageal adenocarcinoma in a patients with BE is much higher when compared to the normal population. Duodeno-gastro-esophageal reflux is supposed to play a role in the pathogenesis of BE and rising incidence of adenocarcinoma of the esophagus. With current therapeutic options, when clinical manifestation of this cancer occurs, it is too late for cure in the majority of patients. Therefore, attention should be focused on early diagnosis, for which molecular genetic techniques might become available. Current data on genetic alterations involved in carcinogenesis of BE are discussed. Grading of dysplasia in BE carries important clinical consequences for the individual patient: intensification of endoscopic surveillance or 'prophylactic esophagectomy'. Several morpho- and/or cytometric parameters may be used for discrimination between different grades of dysplasia in BE. Therefore, a new and original algorythm for the potential application of quantitative pathology in grading of dysplasia in patients with BE has been proposed. Molecular biology together with image analysis of histological spectrum of BE enable better understanding of the mechanisms of malignant degeneration and might ultimately lead to targeted cancer prevention and/or therapeutic interventions.

Adenocarcinoma↗

[18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography localizes residual thyroid cancer in patients with negative diagnostic (131)I whole body scans and elevated serum thyroglobulin levels.

Progressive dedifferentiation of thyroid cancer cells leads to a loss of iodine-concentrating ability, with resultant false negative, whole body radioactive iodine scans in approximately 20% of all differentiated metastatic thyroid cancer lesions. We tested the hypothesis that all metastatic thyroid cancer lesions that did not concentrate iodine, but did produce thyroglobulin (Tg), could be localized by [18F]2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET). We performed FDG-PET on 37 patients with differentiated thyroid cancer after surgery and radioiodine ablation who had negative diagnostic 131I whole body scans during routine follow-up. Serum Tg, Tg autoantibodies, neck ultrasounds, and other clinically indicated imaging procedures were performed to detect residual disease. In those with elevated Tg levels, FDG-PET localized occult disease in 71%, was false positive in one, and was false negative in five patients. The majority of false negative FDG-PET occurred in patients with minimal cervical adenopathy. Surgical resections, biopsies, 131 therapy, and differentiation therapy were performed based on the PET results. The FDG-PET result changed the clinical management in 19 of the 37 patients. In patients with elevated Tg levels, FDG-PET had a positive predictive value of 92%. In patients with low Tg levels, FDG-PET had a negative predictive value of 93%. No FDG-PET scans were positive in stage I patients; however, they were always positive in stage IV patients with elevated Tg levels. An elevated TSH level (i.e. hypothyroidism) did not increase the ability to detect lesions. FDG-PET is able to localize residual thyroid cancer lesions in patients who have negative diagnostic 131I whole body scans and elevated Tg levels, although it was not sensitive enough to detect minimal residual disease in cervical nodes.

Adenocarcinoma, Follicular↗

[Diagnostic imaging in lung cancer].

Lung cancer is one of the major causes of death as one of the most frequent malignant diseases in Hungary. Imaging examinations, especially computed tomography (CT), magnetic resonance imaging (MRI) and positron emission computed tomography (PET-CT) play eminent role in the detection, differential diagnosis, staging and follow-up of the disease. The purpose of this article is to review the role and efficacy of the available modalities and to define the diagnostic algorithm appropriate in different periods of the disease.

Humans↗

[Endoscopic diagnostic errors in colon cancer].

The results of colonoscopy in 567 patients with malignant tumors of the colon have shown that in 10,0% of cases there were errors in primary endoscopic diagnosis due to inferior examination of the colon, missing of malignant tumors, misinterpretation of the alterations revealed. The authors believe that a single endoscopic examination can not be considered decisive, especially when tumor had been clinically or roentgenologically suspected. Only repeated dynamic observations during 12-14 months with 1-3 month intervals can give final conclusions. The authors believe the thorough early analysis, knowledge of endoscopic symptoms, correct estimation of the data of colonoscopy and biopsy to allow avoiding serious diagnostic errors in future.

Biopsy↗

[The significance of bilateral diagnostic lymphadenectomy in thyroid cancer. Tactical operative procedure in the 1st intervention].

In 101 patients with differentiated (papillary n = 74, follicular n = 20, or medullary n = 7) thyroid cancer and lymph node metastases a modified radical neck dissection (unilateral or bilateral) had been performed. After the examination of the lymph nodes in several stations the retrospective analysis showed positive nodes within the internal jugular vein (= central reservoir) in 96% of all cases independent of the tumor site. Only tumors in dorsal parts of the thyroid or in the isthmus (4%) showed other modes of lymphatic spread. Therefore during the first exploration the bilateral excision of the lymph nodes of the internal jugular vein (= diagnostic lymphadenectomy) by Kocher' incision is representative whether an extensive lymphatic spread has occurred.

Adenocarcinoma↗

Defining the diagnostic algorithm in pancreatic cancer.

Most patients with pancreatic cancer present with a mass on radiologic studies, however, not every pancreatic mass is cancer. Since radiological studies alone are insufficient to establish the diagnosis of a pancreatic mass and patient management depends on a definitive diagnosis; confirmatory cytology or histology is usually required. As a minimally invasive procedure, EUS and EUS FNA avoid the risk of cutaneous or peritoneal contamination that may occur with CT or US-guided investigations and is less invasive than surgical interventions. As a result, EUS FNA of pancreatic masses is becoming the standard for obtaining cytological diagnosis. This chapter presents an EUS-based diagnostic algorithm for the evaluation of pancreatic lesions and is based upon a review of the pertinent literature in the field of pancreatic endosonography that has been the most influential in helping to guide this evolving field. Realizing there is much overlap among the EUS characteristics of various pancreatic lesions, for the sake of simplicity we have structured our discussion in broad terms of solid versus cystic lesions and discuss various pancreatic lesions within this framework. The additional contributors to this round table discussion have been asked to provide a more dedicated, focused discussion of the various subcategories of pancreatic lesions in greater detail than we could hope to achieve here. We provide this final contribution to the round table as a means of bringing the discussion back to the big picture of pancreatic lesions, rather than trying to hone in on the fine details of any one subclass.

Decision Trees↗

Bronchoscopic invasive diagnostic techniques in the cancer patient.

The cancer patient often presents with fever and pulmonary infiltrates, in particular during the course of chemotherapy or after bone marrow transplantation. In these conditions, specific diagnoses are mainly related to an infective cause, but noninfectious processes, malignant or not, are also found alone or in combination with infection. Identification of the pulmonary process can be achieved by bronchoscopic techniques, including bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB). BAL may help identify opportunistic organisms but also bacterial pneumonia, provided quantitative cultures are performed, and TBB has been shown to increase the diagnostic yield of BAL. These two procedures should then be combined, provided there is no contraindication.

Biopsy↗