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Evaluation of an antibody to human milk fat globule antigen in the detection of metastatic carcinoma in pleural, pericardial and peritoneal fluids.

An antibody to human milk fat globule-2 (HMFG-2) antigen was investigated to assess its value in detecting tumors in pleural, pericardial and peritoneal fluids. One hundred forty consecutive fluids were evaluated using the avidin-biotin complex (ABC) technique. Conventional cytology and HMFG-2-stained smears were compared using the former as the standard for tumor detection. Discrepant results were found in 15 specimens (8 false negatives and 7 false positives). Causes for discrepancy between the methods included lack of HMFG-2 antigen on tumor cells, random sampling error and endometrial cells ectopically located in the pelvic cavity or introduced during uterine instrumentation. We conclude staining for HMFG-2 may be a useful adjuvant technique for the detection of rare tumor cells in body fluids provided there is a high index of suspicion of metastasis from an HMFG-2-positive primary neoplasm.

Antibodies, Monoclonal↗

Significance of mild cervical cytologic atypia in a sexually transmitted disease clinic population.

While the clinical management of patients with cytologic atypia consistent with cervical intraepithelial neoplasia (CIN) is well established, the management of so-called nondyskaryotic or benign atypias is controversial. The natural history of such atypias was prospectively studied in 124 patients attending a sexually transmitted disease clinic. The benign atypias were subdivided into different categories according to the cell type involved, and the patients were followed cytologically and colposcopically without cervical biopsy until they reached one of the study end points. Benign atypias often signified the presence of CIN: 17% of the patients had a smear consistent with CIN on the first study visit, and an additional 24% had such a smear by six months of follow-up. After 30 months of follow-up, the overall cumulative rate of biopsy-confirmed CIN 2 to CIN 3 was 13.5%; it was 12.5% among those with two consecutive smears showing benign atypias. Of the ten patients who reached biopsy-confirmed CIN 2 to CIN 3, a cytologic smear consistent with CIN was obtained in less than one year of follow-up in all but one case; however, colposcopic evidence of progression was seen in only half of the ten cases, suggesting a sampling error rather than true progression in many cases. Patients with metaplastic cell atypia had a higher progression rate to biopsy-confirmed CIN 2 to CIN 3 (21%) than did those with nonmetaplastic cell atypia (3%). This study provides direct evidence of the potential significance of metaplastic atypia as a marker of CIN. We conclude that patients with mild atypia are often found to have CIN and warrant further investigation by colposcopy and biopsy.

Adult↗

[Distribution and prevalence of Campylobacter pylori in the stomach].

We investigated the distribution and prevalence of Campylobacter pylori in the stomach and duodenum. In this study, 500 biopsy specimens were obtained from 245 patients. In each case, biopsy specimens were taken from more than 2 sites. C. pylori was detected by culture, urease test and acridine-orange stain. C. pylori was not detected on the intestinal metaplasia, gastric cancer tissue and duodenal mucosa without gastric metaplasia. In 21% of cases, C. pylori was detected in only one site. Because of the patchy distribution of C. pylori, more than 2 biopsy specimens from different sites were needed to avoid sampling error. Detection rate of C. pylori was almost equal in antrum, angle and body as well as in male and female. H2 receptor antagonists did not affect the detection rate of C. pylori. According to the endoscopic diagnosis of the biopsied site, C. pylori was detected in 87% of gastric ulcer, 60% of duodenal ulcer (duodenal mucosa with gastric metaplasia), 73% of chronic gastritis and 62% of endoscopically normal gastric mucosa.

Adolescent↗

Dermatoglyphic analysis of primary and secondary cleft palate patients.

No significant differences are found among the different groups. Some of the observed minor differences between the cleft and the control groups may be the result of sampling error. Our findings are not surprising because our cleft patients have no other congenital anomalies. Indeed aberrant dermatoglyphic patterns are found mainly in generalized dysmorphogenesis, such as in chromosomal syndromes, rather than in isolated congenital malformations, exception being made of course for congenital malformations of the hand itself.

Cleft Lip↗

Clinical assessment of melanoma thickness.

Melanoma tumour thickness is the best current predictor of prognosis. In 92 patients melanoma tumour thickness was estimated preoperatively on clinical assessment and compared to the histological thickness measured from fixed paraffin sections. Overall there was no significant difference between clinical and histological thickness. The two assessments were identical in 20 of 92 cases (22%). In 32 of the 92 cases (35%) there was a discrepancy greater than 25%, but 87 of the 92 patients had appropriate treatment where extent of surgery was tailored to clinical assessment of treatment. Clinical assessment has an important role in identifying occasional spurious histological thickness measurements, resulting from sampling errors. The ability to gauge melanoma thickness preoperatively also aids the planning of a rational treatment policy ranging from conservative treatment for thin lesions to radical surgery, which may include elective node dissection and adjuvant limb perfusion, for thicker tumours.

Humans↗

Use and prognostic value of staging mediastinoscopy in non-small-cell lung cancer.

One hundred sixty patients had preoperative mediastinoscopy, resection of the primary tumor, and complete mediastinal lymphadenectomy for non-small-cell carcinoma of the lung. Minimum follow-up was 24 months (mean 40 months). Postoperative staging based on histologic examination of the specimen of the lung and mediastinal lymphadenectomy categorized 59 patients in stage I, 28 in stage II, and 73 in stage III (20 T3N0, 12 T3N1, 29 T1 or T2N2, and 12 T3N2). The sensitivity rate of cervical mediastinoscopy for detection of mediastinal node metastasis was 48.7%. False-negative results of mediastinoscopy occurred in 21 of 41 patients with normal mediastinoscopy: unreachable nodes in eight patients, sampling error of reachable nodes in 11 patients, and error on frozen section in two patients. Eleven of 65 patients with clinical stage I disease and normal mediastinum on chest roentgenogram had mediastinal node involvement; only three were detected by mediastinoscopy, which resulted in a low sensitivity rate (27.3%) and a high rate of unnecessary mediastinoscopy (62/65 patients). The sensitivity of mediastinoscopy increased as the amount of disease present, as measured by the clinical stage of disease or positive gallium 67 scan of mediastinum, increased. Eleven of 29 patients with T1 to T2N2 disease discovered at mediastinoscopy had similar survival rates compared with 18 of 29 patients who had a normal mediastinoscopy examination and mediastinal node involvement discovered at thoracotomy.

Carcinoma, Non-Small-Cell Lung↗

Fine needle aspiration biopsy cytology of major salivary glands.

Fine needle aspiration biopsy of the major salivary glands was performed on 160 patients. In 146 patients with satisfactory samples, the cytologic diagnosis was correlated with clinical follow-up and histologic findings. There were 122 benign lesions, including 47 tumors. There were 24 malignant lesions, 10 of which were primary and 14 metastatic. The overall accuracy was 98%. The sensitivity of the technique was 87.5%. There was no false-positive diagnosis. There were three false-negative diagnoses due to sampling errors and inexperience during the initial period of the study. This study documents that needle aspiration biopsy cytology of the salivary glands is accurate, simple, rapid, inexpensive, well tolerated and harmless to the patient.

Adenocarcinoma↗

Imaging techniques for myocardial inflammation.

Dilated cardiomyopathy (DC) represents a heterogeneous group of disorders which results in morbidity and mortality in young individuals. Recent evidence suggests that a subset of these patients have histologic evidence of myocarditis which is potentially treatable with immunosuppression. The identification of myocardial inflammation may therefore lead to development of therapeutic regimens designed to treat the cause rather than the effect of the myocardial disease. Ultimately, this may result in improvement in the abysmal prognosis of DC. The currently accepted technique for identification of active myocardial inflammation is endomyocardial biopsy. This technique is not perfect, however, since pathologic standards for the diagnosis of myocarditis have not been established. Furthermore, focal inflammation may give rise to sampling error. The inflammation-avid radioisotope gallium-67 citrate has been used as an adjunct to biopsy improving the yield of myocarditis from 7 percent to 36 percent. Serial imaging correlates well to biopsy results. Future studies are designed to study the applicability of lymphocyte labelling techniques to myocardial inflammatory disease.

Animals↗

A new approach to the quality control of steroid receptor assays.

Lyophilized cytosols prepared from calf uterus and human breast tumor tissue are commonly used to assess the reliability of routine steroid receptor assays. However, preanalytical error (sample preparation, storage, homogenization) cannot be detected in this way. Participating laboratories were asked to mail us all their receptor results obtained over a four-month interval, and to include some information about the patients involved (age, menopausal status, nodal status). After verifying the homogeneity of the populations investigated, we computed consensus means for the percentages of positive samples and for their absolute value. Despite the homogeneity of the characteristics of the populations studied, results from some laboratories systematically differed from the consensus mean. This approach to the quality control of steroid receptors allows evaluation of the whole procedure, from sample preparation to analysis, and thus may be helpful as an addition to the usual practice of distribution of cytosols and tissue powders for assay.

Age Factors↗

Endomyocardial biopsy in 30 patients with primary amyloidosis and suspected cardiac involvement.

Thirty patients with primary amyloidosis in whom cardiac involvement was suspected underwent endomyocardial biopsies. Medical records and biopsies were reviewed and echocardiograms were interpreted by observers who were unaware of the recorded findings. Cardiac amyloidosis was documented by endomyocardial biopsy in 30 (100%) of the patients. In two patients, amyloid was present in only one of four specimens, suggesting that a minimum of four biopsy samples is necessary to eliminate the possibility of sampling error. Only 36 (55%) of 65 biopsy specimens of extracardiac tissues contained amyloid. Findings were positive for amyloidosis in 11 (58%) of 19 rectal biopsies and in 16 (52%) of 31 bone marrow biopsies. Of interest, only the endomyocardial biopsy tissues were positive for amyloid in eight (27%) of the 30 patients, among whom 12 extracardiac biopsies had been performed. Two-dimensional echocardiography was consistent with the diagnosis of amyloidosis in 19 (68%) of 28 patients and was abnormal but nonspecific in the remainder. Endomyocardial biopsy frequently provides information about cardiac involvement with amyloid when biopsy of other organs is negative or echocardiography is nonspecific.

Adult↗

Quantitative methods in the tuberculosis epidemiology and in the evaluation of BCG vaccination programs.

Controversies concerning the protective efficacy of the BCG vaccination result mostly from the fact that quantitative methods have not been used in the evaluation of the BCG programs. Therefore, to eliminate the current controversy an unconditional requirement is to apply valid biostatistical models to analyse the results of the BCG programs. In order to achieve objective statistical inferences and epidemiological interpretations the following conditions should be fulfilled: data for evaluation have to be taken from epidemiological trials exempt from sampling error, since the morbidity rates are not normally distributed an appropriate normalizing transformation is needed for point and confidence interval estimations, only unbiased point estimates (dependent variables) could be used in valid models for hypothesis tests, in cases of rejected null hypothesis the ranked estimates of the compared groups must be evaluated in a multiple comparison model in order to diminish the Type I error in the decision. The following quantitative methods are presented to evaluate the effectiveness of BCG vaccination in Hungary: linear regression analysis, stepwise regression analysis and log-linear analysis.

Adolescent↗

Histologic prognosticators in stage I squamous cell carcinoma of the vulva.

Sixty-four cases of stage I vulvar squamous cell carcinoma were analyzed histologically to define a patient subset at minimum risk for recurrence or nodal metastases. Three patterns of invasion were predefined: carcinoma in situ with early stromal invasion (33%), pushing (8%), and infiltrative (59%). Infiltrative pattern and invasion deeper than 1.5 mm equally predicted nodal metastases (P = .045), although depth measurement in biopsy specimens was subject to sampling error. Confluence and absence of carcinoma in situ each predicted extranodal recurrence (P = .011). Local recurrence appeared more related to inadequate surgical margins than failure to perform radical vulvectomy. Carcinoma in situ with early stromal invasion represents a group at zero risk for nodal metastases. We recommend wide local excision for all stage I lesions. In general, omission of lymphadenectomy should be reserved for cases of carcinoma in situ with early stromal invasion.

Adult↗

Assessment of tumor control following definitive radiotherapy in carcinoma of the prostate--a continuing dilemma.

Following completion of radiotherapy, clinically detectable (palpable) and histologically identifiable prostate carcinoma may persist for an extended period before it undergoes complete resolution. Although in most patients treated with adequate radiotherapy tumor resolution by both clinical and histological criteria occurs in the first 2 years, in a proportion of patients complete resolution may occur during the third year or even later. Since the proportion of patients with late resolution appears to be quite small, it seems reasonable to use the histologically identifiable tumor in the biopsy specimen beyond the second postirradiation year as a criterion for the diagnosis of treatment failure. The available data are insufficient to establish, by histological evaluation, the true pattern of tumor resolution. To achieve such a goal one would need to assess a substantial population of patients, adequately irradiated in a standardized manner, by systemic periodic biopsies over several years. To avoid selection biases, all patients, regardless of the clinical findings, would need to undergo biopsies. To avoid sampling errors, particularly in patients without palpable abnormalities, multiple specimens would need to be obtained from several quadrants of the prostate. The studied population should not receive hormonal management in conjunction with radiotherapy. Only completion of this ideal, hypothetical study and correlation of the biopsy results with long-term follow-up data on local failure, the incidence of distant metastases, and survival would make possible meaningful interpretation of the biopsy results in the future. Only then would it become possible to assign a statistical probability of local and/or distal failure as a function of the biopsy status at a certain point in time.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Genetic aspects of Perthes' disease. A critical review.

Contradictory theories of the mode of inheritance of Perthes' disease have been largely due to sampling error, which is revealed by comparison of four series. Confusion also has been caused by the unequal sex incidence of the disease. Family data from a series of 87 boys and 58 girls with Perthes' disease were combined with those of Gray et al. (223 boys and 44 girls) to provide the largest possible group for analysis. Proportions of first-, second-, and third-degree relatives affected were recorded separately for each sex of index cases and each sex of relatives. Comparison of the incidence of Perthes' disease in relatives with that in the general population of the same sex revealed features of multifactorial inheritance, and a gradient of 35:4:4:1 from first:second:third-degree relatives to the general population. Equal estimates of heritability (h2) from first cousin and sib data suggest that environmental factors are of relatively little importance in etiology. Heritability from sib data was 84 +/- 4%, giving a recurrence risk of 2.6% for sibs and offspring, which agrees with the empirical figure of 2.4%. It is argued that the concentration of cases in certain families is not inconsistent with multifactorial inheritance.

Female↗

The use of endoscopic biopsy in evaluation of polypoid lesions of the colon.

Use of flexible endoscopes affords biopsy sampling of polypoid lesions of the colon, especially within the rectum and sigmoid colon by flexible fiberoptic sigmoidoscopes. Histologic examination of colonic biopsies usually allows division of polyps into neoplastic and non-neoplastic categories. There are significant limitations to such biopsies, however, due to sampling error and inability to reach deep submucosal cores of polyps where malignant invasion may occur. When properly aware of its limitations, the endoscopist will find the endoscopic biopsy a valuable aid in planning the therapeutic approach to a polypoid lesion of the colon.

Adenoma↗

Morphological evaluation of opossum lower esophageal sphincter.

Studies were performed in the opossum to evaluate the morphological characteristics of the lower esophageal sphincter. The sphincter and the esophageal body were identified manometrically and fixed in situ by perfusion with aldehyde fixative. Light microscopy revealed that: (1) longitudinal muscle layers of the sphincter and the esophageal body were similar in thickness and compactness, and (2) circular muscle of the sphincter was thicker and was composed of muscle fasciculi with abundant intervening connective tissue as compared to the compact muscle fasciculi of the circular muscle of the esophageal body. Electron microscopy showed the circular muscle fibers of the sphincter to have irregular protuberances from their surfaces, whereas the circular muscle fibers of the esophageal body possessed smooth surfaces. Several types of junctional complexes between adjacent muscle fibers were observed; however, there was no difference in their distribution in the sphincter or esophageal body. The majority of the nerve varicosities contained a mixture of agranular (350 to 450 A) and large dense core vesicles (800 to 1600 A); varicosities containing small granular vesicles were not found in any area of the esophagus. When varicosities were cut along the longitudinal axis of the axon, they often showed grouping of similar vesicle types in different areas along the axon varicosities. There was no difference in the type of varicosities found in the sphincter or the esophageal body. These studies show that: (1) circular muscle of the sphincter can be morphologically distinguished from that of the esophageal body; (2) there is no difference in the morphology of the nerve terminals or the vesicle types in the two areas; and (3) classification of the varicosities based upon the predominance of the vesicle types may be artifactual because of sampling error.

Animals↗

Fine-needle aspiration cytology in gynecologic oncology. I. Diagnostic accuracy.

A prospective study was undertaken to determine the diagnostic accuracy of fine-needle aspiration (FNA) cytology in gynecology. A total of 77 aspirations were performed on 74 patients. In 34 instances the purpose was to rule out or confirm a diagnosis of primary disease, and in 43 cases the procedure was used for suspected metastatic disease or disease recurrent after surgery, radiation therapy, and/or chemotherapy. Excellent correlation was noted between the cytologic and subsequent histopathologic diagnoses of 58 aspirations from patients who also underwent surgical biopsy. Two specimens were false negatives as the result of sampling errors. The applicability of FNA cytology in the field of gynecolotic oncology is discussed.

Adult↗

Detection of surface and core antigens of hepatitis B virus in the liver of 164 human subjects. A study by immunoperoxidase and orcein staining.

The surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV) have been searched by optic microscopy in the liver specimens from patients hospitalized for various conditions and from 38 HGsAg chronic carriers. The study was done blindly using Shikata et al.'s orcein staining on fixed and frozen material and direct immunoperoxidase on frozen material with antisera specific for surface (anti-HBs) and core (anti-HBc) antigens of HBV. No liver staining could be found in the 98 HBsAg seronegative patients. Among the 28 HBsAg seropositive patients, only 3 showed positive staining: 1 patient with acute viral hepatitis showed nuclear staining with anti-HBc; 2 patients with postnecrotic cirrhosis showed cytoplasmic staining with anti-HBs and/or orcein, and one of them also showed nuclear staining with anti-HBc. In contrast, among the 38 chronic carriers, 25 showed positive cytoplasmic staining with anti-HBs and/or orcein, while one of them (with chronic aggressive hepatitis) also showed nuclear staining with anti-HBc. Anti-HBs and orcein staining are equally sensitive and specific for the detection of HBsAg in hepatocytes; discrepant results can be attributed to sampling error of distribution of HBsAg in small liver fragments.

Hepatitis B Antigens↗