[On certain diagnostic errors in pulmonary cancer clarified by tomography].
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The diagnostic value of intraoperative histologic examination of frozen sections of axillary lymph nodes was investigated in 243 patients with operable breast cancer. One to six hard or enlarged axillary nodes were sampled from the axillary pad which was derived from a partial axillary dissection (including level 1 and 2 nodes). Half of these nodes were histologically examined using frozen sections during surgery. After a total axillary dissection, both the axillary nodes in the partial axillary dissection and the nodes dissected at level 3 were histologically examined on permanent section. A mean of four nodes were sampled (range: 1 to 6). Axillary dissection yielded a mean of 22 nodes (range: 6 to 60). Axillary sampling detected the presence of metastases in 65 of 84 (77%) patients with positive axillary lymph nodes. In the patients in whom the axillary involvement was not identified by axillary sampling, however, the extent of axillary involvement was limited to levels 1 and 2. Therefore, a partial axillary dissection may be justified for patients in whom axillary involvement is not found on frozen section of nodes from axillary sampling, whereas a total axillary dissection should be performed for patients in whom axillary involvement is found by these procedures.
The diagnostic significance of measuring sialylated stage-specific embryonic antigen-1 (SLX) in pure pancreatic juice was evaluated in 20 patients with pancreatic cancer, 43 with chronic pancreatitis, 13 with cholecystolithiasis, and 15 control individuals. Four fractions of pure pancreatic juice were collected sequentially from the pancreatic duct by endoscopic cannulation. The SLX levels in all four fractions of pure pancreatic juice were significantly higher in patients with pancreatic cancer than in controls. On the other hand, patients with chronic pancreatitis or cholecystolithiasis did not have SLX levels that significantly differed from those of controls in any fraction. When the cut-off value was set as the mean concentration +2 times the standard deviation of the control values, the positive rates of SLX in the first fraction (washout phase) and the third fraction (secretory phase) of pure pancreatic juice from pancreatic cancer were 55% (11/20) and 40% (8/20), respectively. Although the false positive rates in the first fraction were high in chronic pancreatitis (30%) and cholecystolithiasis (31%), such high SLX levels in the third fraction were found only in one (2%) patient with chronic pancreatitis and in one (8%) with cholecystolithiasis. The specificities of the test for pancreatic cancer in the first fraction and the third fraction were 70% (39/56) and 96% (54/56), respectively. These results indicate that the measurement of SLX in the third fraction of pure pancreatic juice is useful as a specific marker for pancreatic cancer.
Diagnostic and therapeutic nerve blocks are potent tools that can be utilized as one component of the armamentarium in the overall management of cancer pain. With the advent of the multidisciplinary approach to cancer pain management, the appropriate role of nerve blocks should be examined in terms of timing and risk-benefit ratio for each individual patient. Improved patient selection, prior utilization of other lower risk techniques, improved understanding of patient goals, and changes in pain experience may result in higher success. The ultimate goal is to provide comfort without sacrificing other functions important to the patient and/or family.
OBJECTIVE: To examine the extent to which changes in diagnostic methods and classification are responsible for the striking increase in incidence of primary liver cancer in Denmark since 1943. DESIGN: Analysis of the time trends in sex specific, age standardised incidence of primary liver cancer and unspecified liver cancer (either secondary without known primary cancer or not specified as primary cancer) in the entire population from 1943 to 1985. By review of the 727 notifications from three periods of 5 years (1948-52, 1963-7, and 1978-82) the changes in histological diagnosis and classification were assessed. SETTING: Denmark. SUBJECTS: Notifications of liver cancer to the Danish cancer registry. RESULTS: Concomitant with the increase in primary liver cancer, the incidence of the unspecified liver cancer declined. The proportion of histologically diagnosed primary liver cancer rose from 85% to 98%, whereas the proportion for unspecified liver cancer rose from 12% to 51%. When the proportion of primary versus unspecified liver cancer obtained by histological diagnosis was extrapolated to all cases, the annual incidence of primary liver cancer was 4.4 rather than 1.6 per 100,000 population in 1948-52 and 6.0 rather than 5.5 per 100,000 in 1978-82. CONCLUSION: The increase in the incidence of primary liver cancer may be much smaller than the numbers of registered cases indicate. This example emphasises the need to consider diagnostic drift in time trend studies of disease incidence.
The diagnostic sensitivity of USI for localization of a tumor of the pancreatic head was 89.3%, specificity--69.7%, exactness--84.4%. When the tumor was localized in the body-tail these indices were 85.7%, 73.4% and 78.7% respectively. The sensitivity of CT in cases when the localization of the tumor was in the head of the pancreas was 84.9%, specificity--72.2%, exactness--76.5%. When the tumors were localized in the body-tail these indices were 89.5%, 75.4% and 80.9% respectively. An associated analysis of information of the ultrasound and CT concerning the structure of the pancreas made the exactness of the diagnosis of malignization as high as 87.6%, specificity as high as 81.3%, sensitivity as high as 93.7%. The informative value of USI and CT depended on the tumor size, the presence of an inflammatory reaction of the pancreas, the character of a complication, if any, or of their combinations, localization and size of the pathological focus. In the investigation no alterations in the pancreas characteristic only of cancer were found. Thus, a comparison of diagnostic potentials of USI and CT has shown that one method does not exclude, but only supplements the other. CT gives more reliable results in the assessment of the process spread to the surrounding tissues and regional lymph nodes, especially when the tumor is localized in the area of the pancreas tail. USI helps to make more exact assessment of the involvement in the process of the common bile duct, pancreatic duct, and of the visceral vessels by the Doppler examination.
Primary care physicians (PCPs) often do not recommend complete diagnostic evaluation (CDE; i.e., diagnostic colonoscopy or the combination of flexible sigmoidoscopy and barium enema X-ray procedures) for patients with an abnormal screening fecal occult blood test (FOBT+) result. Information is needed to understand why PCPs do not recommend CDE. In the spring of 1994, a telephone survey was carried out using a random sample of 520 PCPs in Pennsylvania or New Jersey who had patients that were targeted for an FOBT screening program. Survey data were obtained from 363 (70%) PCPs on physician practice characteristics; personal background; perceptions concerning FOBT screening, CDE performance, and patient behavior; social influence related to CDE; and intention to recommend CDE for FOBT+ patients. Physician CDE intention scores were distributed as follows: low (22%), moderate (51%), and high (27%). Multivariate analyses demonstrate that physician board certification status, time in practice, belief in CDE efficacy, and belief that CDE is standard practice were positively associated with CDE intention, whereas concern about CDE-related costs was negatively associated with CDE intention. Among physicians in larger practices, perceived FOBT screening efficacy was negatively associated with CDE intention, and belief in the benefit of CDE was positively associated with outcome. There is substantial variability in CDE intention among PCPs. Physician perceptions about FOBT screening and follow-up are associated with CDE intention, are likely to influence CDE performance, and may be amenable to educational intervention. Additional research is needed to evaluate the impact of educational interventions on CDE intention and performance.
The diagnostic significance of three polyamines (putrescine, spermidine and spermine), of carcinoembryonic antigen and of phosphoglucose isomerase have been compared in sera of patients with breast cancer or benign breast disease and normal age matched controls. The results of the study indicate that the performance of spermine was more striking than that of any of the other markers. The estimation of spermine may prove to be a valuable parameter not only in detection but also in prediction of recurrence of the disease.
We conducted a meta-analysis using results from the Korean literature to determine whether prostate-specific antigen (PSA) or digital rectal examination (DRE) or transrectal ultrasonography (TRUS) provides a better diagnostic outcome for possible prostate cancer patients. An extensive literature search of MedRIC database et al. (1980 to 2003) was performed using the medical subject headings "PSA", "DRE", "TRUS" and "prostate cancer". Of the 108 articles that we retrieved, 13 studies (2,029 subjects) were selected for this meta-analysis. The criteria for quality evaluation were as follows: the study subjects must have been compared clinically for suspected prostate cancer, and the articles must have included individual data about sensitivity and specificity for this diagnostic triad based on the biopsy results as a reference standard. For the quantitative meta-analysis process the Hasselblad method was utilized. The pooled sensitivity and specificity for a PSA level greater than 4ng/mL were 91.3 % and 35.9 %, respectively; and those for a PSA level greater than 10ng/mL were 77.3 % and 67.5 %, respectively; and those for DRE were 68.4 % and 71.5 %, respectively; and those for TRUS were 73.6 % and 61.3 %, respectively. According to the results in a fixed effect model for PSA criteria, the estimates of d for PSA4 and PSA10 were 0.8517 [95 % confidence interval (CI): 0.6694, 1.0340] and 1.0996 (95 % CI: 0.9459, 1.2534), respectively. Also, according to the results using a random effect model for both DRE and TRUS criteria, the estimates of d for DRE and TRUS were 0.8398 (95 % CI: 0.7169, 0.9627) and 0.8002 (95 % CI: 0.6714, 0.9289), respectively. The detection rate for combination testing of PSA, DRE and TRUS for the diagnosis of prostate cancer jumped further to 68.3 % or to 76.8 %. In conclusion, this study suggests that this diagnostic triad for prostate cancer was noneffective when they were used separately. Therefore, we recommend that the urologists should use PSA together with DRE and TRUS for the primary diagnosis of prostate cancer in men with lower urological symptoms.
Primary liver cancer (PLC) rates have risen dramatically during the past few decades in some regions, particularly in Japan, where PLC is now the third major cause of cancer death. PLC is one of the most difficult tumors to diagnose correctly, because (i) the liver is a frequent site of cancer metastasis and (ii) death from PLC is often attributed to cirrhosis or chronic hepatitis. Also, because the disease is often rapidly fatal, a large proportion of liver cancer cases are identified based on death certificates alone without confirmation by clinical records. Thus, worldwide differences in published incidence rates for this disease reflect regional or national differences in both the accuracy of death certificates and the sensitivity of diagnostic methods. By comparing death certificate causes of death with those based on pathology review, we were able to adjust 1958--1994 incidence rates for a large Japanese cohort for these errors. Although the death certificate false-positive error rate declined, the false-negative error rate remained high throughout the study. The introduction of improved liver cancer diagnostic methods in Japan in the early 1980s was associated with a sharp increase in PLC incidence. We conclude that errors in death certificate causes of death and changes in liver cancer diagnostic techniques have had an important impact on the reported incidence of this disease. Taking these factors into account, rates of hepatocellular carcinoma rose between 2.4- and 4.3-fold in our Japanese cohort from 1960 to 1985, peaked about 1993 and declined thereafter. Incidence rates of cholangiocarcinoma remained stable through 1987.
In 42 patients with suspected recurrent colorectal cancer, results of conventional diagnostic methods were compared with those of immunoscintigraphy. In 69% of all cases, the intraoperative findings of a second-look operation served for validation, whereas in 31% close follow-up was used. Recurrent tumors were successfully localized in 83% of patients by conventional methods, whereas immunoscintigraphy was expressive in 57% of cases. Immunoscintigraphy was disappointing especially because of its low sensitivity (23%) and low predictive value (positive, 33%; negative, 37%) with regard to successful diagnosis of extrahepatic tumors compared with the results of conventional methods (77% sensitivity; positive, 94%; negative, 79%). The rate of false-positive results was relatively high with immunoscintigraphy (n = 12), 83% of which were related to extrahepatic recurrent tumors. The value of immunoscintigraphy using an immunococktail of 131-J-labeled F(ab')2 fragments of monoclonal antibodies against CEA, with Ca 19-9 as an additional diagnostic tool for early detection of recurrent colorectal cancer, must therefore be viewed critically.
PURPOSE: Endorectal coil MRI is widely used in the diagnostic workup of prostate cancer, but diagnostic accuracy rates reported in the literature are quite variable. We report our personal experience with endorectal coil MRI in the local staging of prostate carcinoma. MATERIAL AND METHODS: Forty consecutive patients with histologically proved prostate carcinoma were examined with endorectal coil MRI at high field strength (1.5 T). All patients underwent a sagittal T1-weighted SE location sequence (TR 400, TE 20), an axial T1-weighted SE (TR 400, TE 20), two axial T2-weighted FSE sequences (TR 3000, TE 102, ETL 8) with and without fat suppression, and a coronal T2-weighted FSE sequence (TR 3000, TE 102, ETL 8); an axial Fast Multiplanar Spoiled Gradient Recalled (FMSPGR) dynamic sequence after Gd-DTPA injection was also performed in 18 patients. MR staging of local tumor spread was done according to the current literature criteria. All patients were submitted to radical prostatectomy, and histologic macrosections on the same plane as MR images were obtained from surgical specimens. MR and histologic staging were compared to assess MR accuracy in detecting capsular infiltration, seminal vesicles and apex involvement. The diagnostic yield of Gd-DTPA was also investigated. RESULTS: MRI correctly staged 31 of 40 cases (77.5%). MR accuracy was 80% in detecting capsular infiltration (85.7% sensitivity and 73.6% specificity), 90% in seminal vesicle involvement (91.6% sensitivity, 89.2% specificity) and 72.5% in apex involvement (79.1% sensitivity, 62.5% specificity). Dynamic studies with Gd-DTPA did not improve staging accuracy in any case. DISCUSSION AND CONCLUSIONS: In agreement with most of the current literature, MRI showed moderate overall accuracy in the local staging of prostate carcinoma. Particularly, MRI had good accuracy in detecting seminal vesicle involvement but moderate sensitivity and specificity in demonstrating capsular infiltration and apex involvement. Due to its high cost, MRI should not be routinely used in prostate cancer staging but should be reserved to the patients whose clinical and serological data suggest extraprostatic tumor spread, whose preoperative demonstration could avoid noncurative surgery.
In spite of advances in diagnostics and therapeutics, cancer remains the second leading cause of death in the U.S. Successful cancer treatment depends not only on better therapies but also on improved methods to assess an individual's risk of developing cancer and to detect cancers at early stages when they can be more effectively treated. Current cancer diagnostic imaging methods are labor-intensive and expensive, especially for screening large asymptomatic populations. Effective screening strategies depend on methods that are noninvasive and detect cancers in their early stages of development. There is increasing interest and enthusiasm in molecular markers as tools for cancer detection and prognosis. It is hoped that newly discovered cancer biomarkers and advances in high-throughput technologies would revolutionize cancer therapies by improving cancer risk assessment, early detection, diagnosis, prognosis, and monitoring therapeutic response. These biomarkers will be used either as stand-alone tests or to complement existing imaging methods.
The diagnostic value of pyruvate-kinase type tumor M2 (Tumor M2-PK) has been investigated in different tumors, and showed interesting results in cases of renal cancer, pancreatic cancer, lung cancer and some cases of gastric cancer. In this study we investigated EDTA-plasma of 68 patients with gastrointestinal cancer, 22 patients with inflammatory bowel disease (IBD) and 60 healthy controls. Sensitivity of Tumor M2-PK was 70.6% for all GI-tumors, that of CA19-9 was 55.4% and that of CEA was 53.3%. In pancreatic cancer CA19-9 showed the best sensitivity. In oesophageal/gastric cancer Tumor M2-PK was most sensitive and in colorectal cancer CEA and Tumor M2-PK showed the best results. The specificity of Tumor M2-PK was 90-96, 7%. In IBD some individuals showed elevated Tumor M2-PK levels but there was no correlation to CRP or to the clinical activity score. The results indicated that Tumor M2-PK might be a valuable marker in gastrointestinal cancer.
Present diagnostic techniques do not allow the detection of early metastatic spread of tumor cells, although this spread largely determines the clinical course of patients with small primary cancers. By use of monoclonal antibody CK2 to the epithelial cytokeratin component number 18 (CK18), individual disseminated carcinoma cells present in bone marrow of cancer patients can now be identified (G. Schlimok, I. Funke, B. Holzmann, G. Göttlinger, G. Schmidt, H. Häuser, S. Swierkot, H. H. Warnecke, B. Schneider, H. Koprowski, and G. Riethmüller, Proc. Natl. Acad. Sci. USA, 84: 8672-8676, 1987; F. Lindemann, G. Schlimok, P. Dirschedl, J. Witte, and G. Riethmüller, Lancet, 340: 685-689, 1992). In the present study, we applied this approach to patients with operable non-small cell lung cancer. CK18 was expressed on 84 of 88 (95.5%) primary adenocarcinomas and squamous cell carcinomas. Irrespective of primary tumor histology, single aspirates of iliac bone marrow from 18 of 82 (21.9%) lung cancer patients exhibited between 1 and 531 CK18+ cells/4 x 10(5) nucleated marrow cells. The specificity of our assay is underlined by the small rate of "false-positive" cells being observed in only 2 of 117 (1.7%) marrow samples from control patients with no evidence for an epithelial malignancy at the time of aspiration. Comparison with established risk factors demonstrated positive correlations (P < 0.05) between the size and histological grade of the primary carcinoma and cytokeratin positivity in iliac bone marrow. In contrast, the association with the metastatic involvement of regional lymph nodes was only weak (P = 0.09). Following a median observation period of 13 months, patients who displayed cytokeratin-positive cells in iliac bone marrow at the time of primary surgery relapsed more frequently as compared to patients with a negative marrow finding (66.7 versus 36.6%; P < 0.05). This difference was even more pronounced by comparing the rates of manifest skeleton metastasis observed in both groups (26.7 versus 2.4%; P < 0.005). Finally, colabeling of CK18+ cells in marrow with monoclonal antibodies to proliferation-associated markers, such as the nucleolar antigen p120 or the tyrosine kinase receptor erbB2, exemplified the oncogenic capacity of CK18+ micrometastatic cells. In conclusion, CK18+ cells present in the bone marrow of patients with apparently operable non-small cell lung cancer exhibit the potential to form solid metastases. Therefore, the approach presented here may be used to determine the risk of early relapse in operable non-small cell lung cancer with potential consequences for adjuvant therapy.
We reviewed the medical records and images of 39 women with palpable breast masses, including 18 cases with breast cancer and 21 cases with benign breast mass, to compare diagnostic accuracy and clinical agreement between ultrasonography and mammography in breast cancer detection. We showed that the operating characteristics of ultrasonography, including sensitivity, specificity and positive likelihood ratio, were superior to that of mammography. We also confirmed that the established malignant criteria for malignancy, including lobulated shape, irregular contour and non-uniform internal echo in ultrasonography, and stellate mass in mammography, were statistically significant in distinguishing breast cancer from benign breast lesion. Moreover, the interobserver agreement kappa of ultrasonography and mammography were 0.64 and 0.59, respectively. Ultrasonography was also superior to mammography in attaining clinical agreement between the different observers in breast cancer detection.