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Ulcerative colitis and colonic cancer. Problems in assessing the diagnostic usefulness of mucosal dysplasia.

To assess the association of mucosal dysplasia and colonic cancer in patients with ulcerative colitis and to avoid bias in biopsy interpretation that may have affected results of previous studies, the authors examined coded histology slides from colectomy specimens of 22 patients who had ulcerative colitis and colonic cancer and 22 patients who had ulcerative colitis but no colonic cancer. As expected, it was found that dysplasia occurred contiguous to each cancer. However, at a distance from the cancer (i.e., in histology blocks not containing cancer), some dysplasia was found (low or high grade) in 16/22 cases (73 percent), and high grade dysplasia in 11/22 cases (50 percent). These results suggest that there may be somewhat weaker association than previously reported between colonic cancer and dysplasia at a distance from the colonic cancer. Further, these results suggest that, in studies of dysplasia, it is important to avoid bias in biopsy interpretation and to describe sampling methods.

Adolescent↗

Gene expression profiling in human endometrial cancer tissue samples: utility and diagnostic value.

OBJECTIVE: Recently, gene expression profiling techniques have been used on several human cancers to classify tumor subgroups with a specific biological behavior, which were previously undetected by the conventional histopathologic staging systems. In the current study, the clinical usefulness and prognostic value of gene expression profiling in human endometrial carcinomas were studied. METHODS: A macro cDNA array, containing cDNAs of 588 genes selected from different areas of cancer research, was used to generate gene expression profiles of tumor tissue samples. The gene expression profiles of 12 endometrial cancers, 3 benign (e.g. noncancer) endometrial tissue samples and 3 myometrial tissue samples, taken from human surgical specimen, were compared. RESULTS: The efficacy to generate a gene expression profile of these tissue samples was 77%. The RNA samples could be randomly taken from the tissue samples and were highly reproducible. Cluster analysis of gene expression profiles of the different samples showed that the benign endometrial and the myometrial samples clustered separately from the tumor samples, indicating that the gene expression profiles were tissue specific and not patient specific. Cluster analysis of the tumor samples revealed two distinct tumor clusters. Ranking of the tumors in the two clusters showed high similarity with the histopathologic classification [International Federation of Gynecology and Obstetrics (FIGO) grading]. CONCLUSION: Classification of endometrial tumors on basis of their gene expression profiles showed similarity with the FIGO grading system.

Adult↗

Communication with close and distant relatives in the context of genetic testing for hereditary breast and ovarian cancer in cancer patients.

The psychological aspects of genetic testing for hereditary breast and ovarian cancer (HBOC) in cancer patients (diagnostic genetic testing) have so far received less attention than predictive genetic testing in unaffected persons. Our study is aimed at gaining insight into the psychological aspects of diagnostic genetic testing and at formulating practical recommendations for counseling. Cancer patients often play a key role in the communication of information to relatives because they were the first individuals to be tested in the family. The present article focuses on the communication to close and distant relatives about the hereditary cancer, the genetic test and its result. Participants previously diagnosed with breast and/or ovarian cancer, with a family history of these cancers and who requested DNA-testing, were eligible for the study. Of the 83 eligible patients who could be contacted, 63 participated (response rate = 76%). Twenty-six participants were members of a family where a BRCA1 or BRCA2 mutation was detected. The DNA-analysis in the family of 37 participants had not revealed any mutation. Data were collected by semi-structured interviews and psychological tests and questionnaires. The dissemination of information was largely focused on first-degree relatives. Communication to distant relatives about the genetic test and its result was problematic. Other than the genetic test result and age as "objective" predictors of informing distant relatives, little and/or superficial contact seemed to be the major subjective barrier to informing distant relatives. Furthermore, the knowledge about HBOC of these messengers reveals several shortcomings. Communication within the family should receive special attention during counseling.

Breast Neoplasms↗

Detection of BRAF mutation on fine needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer.

Numerous biomolecular markers have been studied to improve the accuracy of fine needle aspiration biopsy (FNAB) in the diagnostic and prognostic evaluation of thyroid tumors, but none of them has yet become clinically useful. The recently discovered BRAF mutation, which occurs specifically in papillary thyroid cancers (PTC) with a high prevalence and is associated with poor clinicopathological outcomes, has the potential to be a useful diagnostic and prognostic marker for PTC. In the present study, we investigated whether detection of BRAF mutation on FNAB specimens was technically possible and could be used as an adjunct diagnostic tool with routine FNAB. Evaluation of a new colorimetric mutation detection method demonstrated 100% sensitivity and 100% specificity in comparison with conventional DNA sequencing as the "gold standard" in a large pool of DNA samples from various primary thyroid tumor specimens and cell lines. We found this novel technique even more sensitive in detecting BRAF mutation on FNAB specimens than conventional sequencing. In a series of 48 patients undergoing thyroidectomy, mostly for thyroid cancer or for suspicion of cancer, we performed preoperative FNAB and, using the colorimetric mutation detection method, identified BRAF mutation on the cytological specimens. Prospective analysis showed that 50% of the nodules that proved to be PTC on surgical histopathology were correctly diagnosed by BRAF mutation analysis on FNAB specimens; there were no false positive findings. Thus, we have demonstrated the usefulness of BRAF mutation detection on FNAB specimens that can help diagnose and identify those PTC patients who may need more aggressive surgical treatment and vigilant clinical monitoring.

Biomarkers, Tumor↗

Prostate cancer relapse after therapy with curative intention: a diagnostic and therapeutic dilemma.

Prostate cancer is the most common malignant disease and second in causes of cancer death among men in Western Europe and North America. Despite improved surgical and irradiation techniques tumor relapse after curatively intended therapy is not uncommon. Due to the difficulty in discriminating local and systemic progression, it is often difficult to decide what this means for the patient and what kind of second-line treatment has to be given. Modern imaging techniques (MRI with endorectal coil, Choline-PET-CT, ProstaScint-Scan) are used for diagnosis of prostate cancer relapse. Nevertheless, early detection of local tumor relapse and likewise the detection of disseminated tumor cells often fails. To differentiate between local and systemic progression, prognostic factors of the primary tumor (grading, surgical margins, infiltration of the seminal vesicles, lymph node metastases) and PSA kinetics are used. The time from initial treatment to biochemical relapse and PSA doubling time are of highest prognostic relevance. Local progression allows second-line local treatment with potentially curative results (local irradiation after radical prostatectomy, salvage-surgery / cryotherapy / HIFU after irradiation), while in the case of systemic progress a palliative systemic therapy (hormonal treatment, chemotherapy, bisphosphonates) is indicated. Before deciding on the most appropriate therapy, prognostic factors and the patient's individual situation (co-morbidity, life expectancy, individual wishes) should be taken into account.

Biomarkers, Tumor↗

The clinical usefulness of 18-fluorodeoxyglucose positron emission tomography in the differential diagnosis, staging, and response evaluation after concurrent chemoradiotherapy for pancreatic cancer.

GOALS: The aims of this study were to determine the clinical use of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the differential diagnosis of patients with suspected pancreatic cancer and in the determination of tumor response after concurrent chemoradiotherapy for pancreatic cancer. BACKGROUND: Despite advances in diagnostic tools for pancreatic cancer, it is difficult to differentiate pancreatic cancer from mass-forming pancreatitis. Even with current imaging modalities, it is also difficult to assess tumor response to therapeutic intervention. STUDY: One hundred two patients with suspected pancreatic cancer were selected for this study. Dynamic computerized tomography (CT) scan and FDG-PET were used sequentially to diagnose pancreatic cancer. After diagnostic confirmation their diagnostic yields were compared. We also evaluated the treatment response in 15 patients who underwent chemoradiation therapy with dynamic CT scan and FDG-PET and compared their results. RESULTS: In 93 out of 102 patients, pancreatic cancer was confirmed. FDG-PET showed higher diagnostic accuracy than CT scan (95.1% vs. 76.5%). FDG-PET was also superior to CT in the detection of liver metastasis. FDG-PET detected treatment response in 5 out of 15 cases after chemoradiation therapy, whereas CT could not detect any treatment response. Comparing responder and nonresponder, FDG-PET was able to predict significantly different prognosis (399 vs. 233 d, P<0.05). CONCLUSIONS: FDG-PET is a very useful tool in diagnosing pancreatic cancer. FDG-PET may be also used as an adjunct for determining the treatment modality of pancreatic cancer and evaluating tumor response to chemoradiation therapy.

Aged↗

Radiation exposure from diagnostic and therapeutic treatments and risk of breast cancer.

An association between low-dose diagnostic X-ray exposure or therapeutic radiation treatment and breast cancer risk has not been established. To further investigate the issue, we analysed data from a case-control study of breast cancer in Connecticut in 1994-1997. A total of 1217 subjects (608 breast cancer cases and 609 controls), 30-80 years old, participated in the study. A standardized, structured questionnaire was used to collect information through in-person interviews on diagnostic or therapeutic radiation and other breast cancer risk factors. An odds ratio (OR) of 1.7 (95% confidence interval (CI) 0.8-3.6) was observed for postmenopausal women with therapeutic radiation treatment for skin problems such as ringworm and acne, and an OR of 2.5 (95% CI 1.0-6.8) for those who reported having been treated six or more times. Radiation treatment received at younger ages seems to carry a higher risk. In earlier studies therapeutic radiation for skin problems has been associated with an increased risk of breast cancer. Therefore, it is possible that scattered radiation from these treatments could increase the risk of breast cancer. Radiation exposure from diagnostic X-rays was not associated with a significantly increased risk of breast cancer in this study.

Adult↗

Cytologic diagnosis of oral, esophageal, and peripheral lung cancer.

Oral cavity. Most carcinomas in situ of the oral cavity present as red or pink lesions that do not have a keratinized surface. Scrapings of such lesions readily disclose abnormal squamous cells diagnostic of cancer. Scrapings of the keratinized white lesions (so-called leukoplakia) are of no diagnostic value. Dentists, who are most likely to uncover precancerous lesions, are apparently not aware of the diagnostic options based on simple scrape smears. The method is also applicable to follow-up of patients with treated cancer of the oral cavity. Esophagus. Cytologic evaluation of esophageal cancer, initially by washings and subsequently by brushings under endoscopic control, is an established method of diagnosis. The diagnostic results are very good in symptomatic cancer patients and have an accuracy reaching 85-90%. Unfortunately the results of treatment of advanced lesions are very poor, with 5-year survival of only about 5%. Serious efforts at detection of early esophageal cancer started in China in the 1960s, using an abrasive balloon technique which was applied to asymptomatic populations in high risk areas such as Linxian in the Henan province of Central China. The Chinese investigators reported the finding of numerous precancerous lesions of the esophagus classified as carcinoma in situ and as dysplasia. Surgical resection of some of the precursor lesions apparently resulted in a significant drop in the rate of invasive carcinoma, although the statistical results were not convincingly presented. The balloon technique has been tested by us and by others in South Africa and in Transkei, confirming its efficacy in the diagnosis of early esophageal cancer. Peripheral lung. Sputum and bronchial brush cytology may uncover bronchogenic carcinoma in situ and early invasive cancers located in the primary or secondary bronchi. Small, peripheral lung lesions usually do not shed cells in sputum or brushings, and their discovery is usually based on roentgenologic finding. The identity of such lesions can be confirmed in most cases by a transcutaneous aspiration. Most of the peripheral malignant lesions are small adenocarcinomas or epidermoid carcinomas, both resectable by routine surgical procedures. Less commonly, oat cell carcinomas may be observed and these lesions should not be treated by surgery. Benign lesions such as granulomatous inflammation and fungal infections may also be identified by aspiration techniques. The prognosis of the resectable carcinomas varies with their size and the presence or absence of regional lymph node metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytodiagnosis↗

Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications.

The study looked for an optimal set of genes differentiating between papillary thyroid cancer (PTC) and normal thyroid tissue and assessed the sources of variability in gene expression profiles. The analysis was done by oligonucleotide microarrays (GeneChip HG-U133A) in 50 tissue samples taken intraoperatively from 33 patients (23 PTC patients and 10 patients with other thyroid disease). In the initial group of 16 PTC and 16 normal samples, we assessed the sources of variability in the gene expression profile by singular value decomposition which specified three major patterns of variability. The first and the most distinct mode grouped transcripts differentiating between tumor and normal tissues. Two consecutive modes contained a large proportion of immunity-related genes. To generate a multigene classifier for tumor-normal difference, we used support vector machines-based technique (recursive feature replacement). It included the following 19 genes: DPP4, GJB3, ST14, SERPINA1, LRP4, MET, EVA1, SPUVE, LGALS3, HBB, MKRN2, MRC2, IGSF1, KIAA0830, RXRG, P4HA2, CDH3, IL13RA1, and MTMR4, and correctly discriminated 17 of 18 additional PTC/normal thyroid samples and all 16 samples published in a previous microarray study. Selected novel genes (LRP4, EVA1, TMPRSS4, QPCT, and SLC34A2) were confirmed by Q-PCR. Our results prove that the gene expression signal of PTC is easily detectable even when cancer cells do not prevail over tumor stroma. We indicate and separate the confounding variability related to the immune response. Finally, we propose a potent molecular classifier able to discriminate between PTC and nonmalignant thyroid in more than 90% of investigated samples.

Adolescent↗

[Cancer of the esophagus and cardia: diagnostic problems].

For many decades, the problem of cancer of the esophagus has been dominated by constant failure in diagnosis and therapy. Today the widespread use of upper digestive endoscopy could seem to constitute, for the moment, the only hope of changing this situation. Leaving aside the clinical, radiological, and enoscopic symptomatology of invasive esophageal cancer, this study is limited to practical considerations on the technology of endoscopic diagnosis in esophageal cancerology; the endoscopic expression of carcinoma "in situ" and chronic irritative esophageal condition; the precancerous and early-stage symptomatology of cancer of the esophagus; and the problem of "pseudo-cancer" of the esophagus.

Biopsy↗

[Complex diagnostic method of early forms of cancer of the uterine cervix].

A complex of diagnostic procedures including extended colposcopy, aiming biopsy, cytological examination and endocervical curettage was carried out in 110 patients for differential diagnosis between precancerous diseases and early forms of carcinoma of the uterine cervix. Application of the complex diagnostic method may be recommended for identification of early stages of malignancy in cervix uteri. Due to the findings obtained, it becomes possible to give a more accurate definition of pathologic process necessary for determination of therapy to be carried out in patients with cervical carcinoma in situ which has been detected without colposcopy. Cytological method appeared to provide much information on tissue specimens.

Adult↗

Rapid and quantitative detection of human septin family Bradeion as a practical diagnostic method of colorectal and urologic cancers.

BACKGROUND: Malignant tumor progression is a complex and multi-gene event which can not be easily detected or predicted. The detection of malignant cells using marker genes is hampered by the fact that these markers are only expressed by certain malignancies or lack sensitivity and/or specificity. We have reported a human septin family gene Bradeion, which shows strong cancer-specific expression in colorectal and urologic cancers as a result of carcinogenesis. MATERIAL/METHODS: Diagnostic efficacy and validity of Bradeion gene expression were tested by two independent systems, one is a protein detection method using monoclonal antibody based immuno-chromatographic membrane strip tests (a nitrocellulose test strip assay), and another is a gene expression detection method, quantitative RT-PCR. The technology has been established using Bradeion fusion proteins, in vitro cultivated human cancer cell lines, and also patients' test samples with controls. RESULTS: Bradeion test strip by combination with two monoclonal antibodies are valid for the detection of 1 ng/ml Bradeion, and successfully applied for patient urine samples with no false-positive results. Positive detection rates were over 70% of the patient urine samples so far tested (prostate cancer, renal cell carcinoma, and bladder cancer) in 15 to 30 minutes. Quantitative RT-PCR resulted in significantly high copy numbers of 0.4-3.0-3.0 x 10(5) per microg total RNA in patients' tissue samples, whereas those from normal tissue or other cancers found negative. CONCLUSIONS: The present study introduces the practical diagnostic methods using a disease-specific molecular marker, which provides safe, economical, and rapid clinical screening of cancer.

Animals↗

Utility of staging laparoscopy in subsets of biliary cancers : laparoscopy is a powerful diagnostic tool in patients with intrahepatic and gallbladder carcinoma.

BACKGROUND: The aim of this study was to evaluate the utility of staging laparoscopy in patients with biliary cancers in the era of modern diagnostic imaging. METHODS: From September 2002 through August 2004, 39 consecutive patients with potentially resectable cholangiocarcinoma underwent preoperative staging laparoscopy before laparotomy. Preoperative imaging included ultrasonography and triphasic computed tomography for all patients and magnetic resonance cholangiography in 35 patients (90%). Final pathological diagnosis included 20 hilar cholangiocarcinomas (HC), 11 intrahepatic cholangiocarcinomas (IHC), and eight gallbladder carcinomas (GBC). RESULTS: During laparoscopy, unresectable disease was found in 14/39 patients (36%). The main causes of unresectability were peritoneal carcinomatosis (11/14) and liver metastases (5/14). At laparotomy, nine patients (37%) were found to have advanced disease precluding resection. Vascular invasion and nodal metastases were the main causes of unresectability during laparotomy (eight out of nine). In detecting peritoneal metastases and liver metastases, laparoscopy had an accuracy of 92 and 71%, respectively. All patients with vascular or nodal involvement were missed by laparoscopy. For prediction of unresectability disease, the yield and accuracy of laparoscopy were highest for GBC (62% yield and 83% accuracy), followed by IHC (36% yield and 67% accuracy) and HC (25% yield and 45% accuracy) CONCLUSION: Staging laparoscopy ensured that unnecessary laparotomy was not performed in 36% of patients with potentially resectable biliary carcinoma after extensive preoperative imaging. In patients with biliary carcinoma that appears resectable, staging laparoscopy allows detection of peritoneal and liver metastasis in one third of patients. Both vascular and lymph nodes invasions were not diagnosed by this procedure. Due to these limitations, laparoscopy is more useful in ruling out dissemination in GBC and IHC than in HC.

Adult↗

Poor prognosis of gallbladder cancer persists regardless of improved diagnostic methods. Incidence and results of surgery during 20 years in Helsinki.

BACKGROUND AND AIMS: The ominous prognosis of primary gallbladder cancer is well-known. This study assesses whether the prognosis has improved, and whether the substantial development in the radiologic imaging techniques is reflected in the survival of these patients. MATERIAL AND METHODS: The series consisted of 122 patients operated on for primary cancer in the gallbladder in the Helsinki City area between 1970 and 1990. RESULTS: The mean age of the patients was 68.6 years and did not change during the period, but there was a significant proportional increase in male patients. Only 2% of patients had a localized disease at the time of diagnosis, and there was no improvement in the diagnostic sensitivity during the observation period. Yet, the number of unexpected postoperative cancer diagnoses increased from 4% to 15% during the two decades. The primary mortality decreased from 21% to 13%, the one-year survival increased from 7% to 13%, whereas the five-year survival remained unchanged. CONCLUSIONS: During the past two decades the frequency of surgery for primary gallbladder cancer has increased significantly among males in the Helsinki City area. Regardless of the improved immediate survival the long-term survival has remained poor. The marked development in radiologic techniques is not reflected in the prognosis of these patients. Even under conditions in which the potential for the diagnosis of a malignant gallbladder disease is available, the opportunities for radical surgery are not utilized maximally, which is a cause for concern.

Adult↗

CEA and CA 15-3 in pleural effusion of advanced breast cancer patients: clinical relevance and diagnostic value.

Serum and pleural effusion fluid were tested for CEA concentration in 83 advanced breast cancer patients, in 43 of whom CA 15-3 was also determined. All pleural effusions were clinically malignant. The sensitivity of the CEA test for the presence of pleural metastases was closer to that of the CA 15-3 test in effusion (0.59 and 0.79, respectively) than the sensitivity of CEA compared to CA 15-3 in serum (0.43 vs. 0.79). The use of two markers combined with cytology increased the diagnostic rate from 48% (cytologically positive) to 88% (cytologically positive and/or with one or both markers increased in effusion). A high diagnostic rate in cytologically negative effusions (65%), and in effusions presented as the sole metastatic involvement (100%), points to the clinical value of these two markers. Our results show that markers produced by pleural metastases may be secreted either into the effusion fluid or into serum, or both. This finding, as well as some other observations, are discussed in the present paper.

Antigens, Tumor-Associated, Carbohydrate↗

[Diagnostic modalities and treatment of cancer of the pancreas. Evolution in the population in the department of Côte d'Or from 1976 to 1988].

There is no study establishing time trends for the diagnostic and therapeutic approaches to pancreatic cancer based on population data. The data of the Registry of Digestive Tumors of Côte-d'Or (France) were used to this end in 544 cancers diagnosed between 1976 and 1988. The proportion of the histologically confirmed cases increased annually by 13.4% (P < 0.001). This was mainly due to progress in percutaneous biopsy (+25.7% per year between 1983 and 1988, P < 0.001). As regards the diagnosis, ultrasonography was used more frequently (+21.9% per year, P < 0.001) as well as CT scan since its introduction in 1983 (+19.6% per year, P < 0.001). Pancreatic cancer was diagnosed by sonography in 16.7% of the cases in 1976 and 70.6% in 1988 (mean annual variation: +5.7%, P < 0.001). The proportions for CT scan were 12.8% in 1983 and 23.5% in 1988 (mean annual variation: +3.5%, NS). There was no significant change in the use of retrograde cholangiopancreatography over time. Other diagnosis criteria were less frequently used: laparoscopy was no longer used after 1983 and intraoperative diagnosis was made less frequently (-2.5% per year, P < 0.001). Endoscopy or radiographic data were rarely used as a diagnosis criterion. These changes in approaches to the diagnosis of pancreatic cancer were not accompanied by any progress in diagnosis stage, therapeutic approach or survival suggesting that when clinical symptoms become evident, pancreatic cancer is already advanced. Therapeutic advances, early diagnosis in patient at risk or identification or reasons for pancreatic cancer are the only means of progress in this problem.

Antineoplastic Combined Chemotherapy Protocols↗

Removal of more lymph nodes may provide better outcome, as well as more accurate pathologic findings, in patients with bladder cancer--analysis of role of pelvic lymph node dissection.

OBJECTIVES: To examine the role of pelvic lymph node dissection (PLND) in patients who underwent radical cystectomy for bladder cancer. The diagnostic and therapeutic role of PLND is still controversial in bladder cancer. The extent of PLND and the necessary number of lymph nodes to remove have not been defined. METHODS: This retrospective review included 146 patients with refractory superficial and muscle-invasive disease treated with radical cystectomy, regional PLND (internal iliac, external iliac, and obturator nodes) and urinary diversion from January 1990 to December 2002. RESULTS: Lymph node metastases were detected in 25 patients (17.1%). The average number of nodes removed in the node-positive and node-negative patients was 13.9 and 14.2, respectively. Although no difference was found in disease-specific survival in the node-negative patients when stratified by the number of nodes removed (13 or more versus less than 13), a significant survival advantage was found in the node-positive patients with 13 or more nodes removed versus less than 13 nodes removed. The patients with four or more positive nodes had a worse outcome than those with less than four positive nodes. However, even if the patients had less than four positive nodes, the survival of patients with less than 13 nodes removed was as poor as that of the patients with four or more positive nodes. CONCLUSIONS: In this series, the removal of 13 or more pelvic lymph nodes was essential for more accurate pathologic examination to predict patient outcome and contributed to an increased chance of survival.

Adult↗