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Compression or expansion of morbidity? Trends in healthy-life expectancy in the elderly Austrian population between 1978 and 1998.

The aim of our study is to test the theories of compression or expansion of morbidity on the basis of data on the elderly population of Austria. Our data come from four microcensus surveys for the years 1978, 1983, 1991, and 1998. We use self-perceived health ratings to calculate healthy-life expectancy for the elderly population aged 60-89. Because our data are based on four cross-sectional surveys, we devote the first part of the paper to the consequences of possible sampling and non-sampling errors in our analysis of time trends. We come to the conclusion that, although the absolute number of years lived in good health may be overestimated, the time trend in healthy-life expectancy over the 20 years most probably is unbiased. The second part of the paper describes trends in healthy-life expectancy for the Austrian population. Our results suggest that both healthy-life expectancy and the ratio of healthy years to life expectancy increased between 1978 and 1998. Thus, in Austria ill health seems to be more and more compressed into the later years of life. Contrary to Fries's hypothesis, however, life expectancy does not seem to be approaching a maximum average life span in Austria, as mortality rates at older ages have been continuously decreasing over the last 20 years.

Aged↗

Accuracy of fine needle aspiration biopsy in head and neck tumors.

PURPOSE: Fine-needle aspiration biopsy (FNAB) is frequently used in the diagnosis of lesions occurring in the head and neck region. This study evaluated the correlation between the findings on FNAB and the histological findings observed after surgery. MATERIALS AND METHODS: A review of 218 patients who underwent FNAB of a head or neck tumor was performed. Cytological reports were classified into the following diagnostic categories: negative or positive for malignant cells and unsatisfactory. False-positive, false-negative, true-positive (sensitivity), and true-negative (specificity) rates were calculated. RESULTS: Twelve specimens did not allow an adequate diagnosis (5.5%). Among benign tumors, 96.2% of the cases were correctly diagnosed, and 3.8% were nondiagnostic specimens. Among malignant tumors, 86.4% of cases were correctly identified. There were two (3.4%) false-negatives and six (10.2%) nondiagnostic specimens, with a total false-negative rate of 13.6%. CONCLUSIONS: Sampling errors present a minor problem with FNAB. Most nondiagnostic or incorrect specimens were caused by nonhomogenous lesions, with poor placement of the needle and an insufficient amount of aspirated material. FNAB is a useful modality for the diagnosis of head and neck masses.

Adenolymphoma↗

Comprehensive Cancer Centre Amsterdam Barrett Advisory Committee: first results.

BACKGROUND: Treatment and follow-up policy for Barrett's oesophagus are dependent on the grade of dysplasia. However, sampling error of random biopsy protocols and subjectivity of pathological grading may hamper endoscopic surveillance. METHODS: The Amsterdam Comprehensive Cancer Center Barrett Advisory Committee (BAC) is a regional multidisciplinary consultative working-group, offering revision of pathology, revision of pathology plus additional endoscopic diagnostics, or referral for treatment. RESULTS: Between July 1998 and July 1999 30 patients were referred to the B.A.C for advice; eighteen patients were referred because of suspicion of high grade dysplasia. Reassessment of biopsies, including additional quantitative pathology, with or without additional endoscopic diagnostics, led to adjustment of the grading of dysplasia in 15 patients (50%). A suspicion of low grade dysplasia was rejected in nine out of ten cases. Adjustment of the original diagnosis often influenced further therapy or follow-up. CONCLUSIONS: reassessment of conventional pathology, quantitative pathology, and additional diagnostic procedures might improve the accuracy of diagnosis and staging of malignant degeneration of Barrett's oesophagus, although experience is still limited. The complexity of the management of these patients demands a specialised multidisciplinary approach. A Barrett Advisory Committee can offer valuable contributions to the treatment of patients with Barrett's oesophagus.

Academic Medical Centers↗

Noise reduction in elastograms using temporal stretching with multicompression averaging.

Elastography uses estimates of the time delay (obtained by cross-correlation) to compute strain estimates in tissue due to quasistatic compression. Because the time delay estimates do not generally occur at the sampling intervals, the location of the cross-correlation peak does not give an accurate estimate of the time delay. Sampling errors in the time-delay estimate are reduced using signal interpolation techniques to obtain subsample time-delay estimates. Distortions of the echo signals due to tissue compression introduce correlation artifacts in the elastogram. These artifacts are reduced by a combination of small compressions and temporal stretching of the postcompression signal. Random noise effects in the resulting elastograms are reduced by averaging several elastograms, obtained from successive small compressions (assuming that the errors are uncorrelated). Multicompression averaging with temporal stretching is shown to increase the signal-to-noise ratio in the elastogram by an order of magnitude, without sacrificing sensitivity, resolution or dynamic range. The strain filter concept is extended in this article to theoretically characterize the performance of multicompression averaging with temporal stretching.

Algorithms↗

Electron microscopy as a tool in the diagnosis of endocrine tumors.

Electron microscopy (EM) has provided a large amount of information toward the discovery of endocrine cell systems and the analysis of endocrine tumors. In the diagnosis of endocrine tumors EM is most often not decisive. This is due to sampling errors, tumor cell diversity, pleomorphism of cellular organelles, particularly of secretory granules, and to the lack of reliable structural markers of biologic behaviour of tumor cells. For diagnostic purposes EM has been superseded by immunocytochemical techniques, and in the near future recombinant DNA technology will probably lead to further progress in the precision of analysis of hormone production by tissues, cells and tumors. On the other hand, EM combined with other techniques is a powerful tool in research.

Adenoma↗

Postradiotherapy prostate biopsies: what do they really mean? Results for 498 patients.

PURPOSE: Postradiotherapy (RT) prostate biopsies are prone to problems in interpretation. False negatives due to sampling error, false positives due to delayed tumor regression, and indeterminate biopsies showing radiation effect in residual tumor of uncertain viability are common occurrences. METHODS AND MATERIALS: A cohort of 498 men treated with conventional RT from 06/87-10/96 were followed prospectively with systematic transrectal ultrasound (TRUS)-guided post-RT prostate biopsies, starting 12-18 months after RT. If there was residual tumor but further decline in serum prostate-specific antigen (PSA), biopsies were repeated every 6-12 months. Patients with negative biopsies were rebiopsied at 36 months. Residual tumor was evaluated for RT effect and proliferation markers. The 498 men had 978 biopsies. Median time of the first biopsy (n = 498) was 13 months, biopsy #2 (n = 342) 28 months, biopsy #3 (n = 110) 36 months, biopsy #4 (n = 28) 44 months, and biopsy #5 (n = 4) 55 months. Median follow-up is 54 months (range 13-131). One hundred seventy-five patients (34%) had prior hormonal therapy for a median of 5 months (range 1-60). RESULTS: Clinical stage distribution was T1b: 46; T1c: 50; T2a: 115; T2b/c: 170; T3: 108; T4: 11; Tx: 1. Distribution by Gleason score was: 28% Gleason score 2-4; 42%: 5-6; 18%: 7; and 12%: 8-10. Seventy-one men have died, 26 of prostate cancer and 45 of other causes. Actuarial failure-free survival by T stage at 5 years is T1b: 78%; T1c: 76%; T2a: 60%; T2b/c: 55%; T3: 30%; and T4: 0%. Actuarial freedom from local failure at 5 years is T1b: 83%; T1c: 88%; T2a: 72%; T2b/c: 66%; T3: 58%; and T4: 0%. The proportion of indeterminate biopsies decreases with time, being 33% for biopsy 1, 24% for biopsy 2, 18% for biopsy 3, and 7% for biopsy 4. Thirty percent of indeterminate biopsies resolved to NED status, regardless of the degree of RT effect, 18% progressed to local failure, and 34% remained as biopsy failures with indeterminate status within the time frame of this report. Positive staining for proliferation markers was associated with both subsequent local failure and also any type of failure. In multivariate analysis, only PSA nadir (p = 0.0002) and biopsy status at 24-36 months (p = 0. 0005) were independent predictors of outcome. CONCLUSIONS: Post-RT prostate biopsies are not a gold standard of treatment efficacy, but are an independent predictor of outcome. Positive immunohistochemical staining for markers of cellular proliferation is associated with subsequent local failure. Indeterminate biopsies, even when showing marked RT effect, cannot be considered negative.

Adult↗

Estimating the need for radiotherapy for lung cancer: an evidence-based, epidemiologic approach.

BACKGROUND AND OBJECTIVES: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of lung cancer that will require RT at any point in the evolution of the illness. METHODS: A systematic review of the literature was undertaken to identify indications for RT for lung cancer, and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of lung cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error, was estimated by sensitivity analysis. RESULTS: It was shown that 53.6% +/- 3.3% of small-cell lung cancer (SCLC) cases develop one or more indications for RT at some point in the course of the illness, 45.4% +/- 4.3% in their initial treatment, and 8.2% +/- 1.5% later for recurrence of progression. Overall, 64.3% +/- 4.7% of non-small-cell lung cancer (NSCLC) cases require RT, 45.9% +/- 4.3% in their initial treatment, and 18.3% +/- 1.8% later in the course of the illness. The proportion of NSCLC cases that ever require RT is stage dependent; 41.0% +/- 5.5% in Stage I; 54.5% +/- 6.5% in Stage II; 83.5% +/- 10.6% in Stage III; and 65.7% +/- 7.6% in Stage IV. In total, 61.0% +/- 3.9% of all patients with lung cancer will develop one or more indications for RT at some point in the illness, 44.6% +/- 3.6% in their initial treatment, and 16.5% +/- 1.5% later for recurrence or progression. CONCLUSION: This method provides a rational starting point for the long-term planning of radiation services, and for the audit of access to RT at the population level. We now plan to extend this study to the other major cancer sites to enable us to estimate the appropriate RT treatment rate for the cancer population as a whole.

Algorithms↗

An evidence-based estimate of appropriate radiotherapy utilization rate for breast cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. We sought to use an evidence-based approach to estimate the proportion of incident cases of breast cancer that will require RT at any point in the evolution of the illness. METHODS AND MATERIALS: We undertook a systematic review of the literature to identify indications for RT for breast cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error was estimated by sensitivity analysis. RESULTS: It was estimated that 66.4% +/- 4.8% of breast cancer patients develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 56.3%-72.4% on sensitivity analysis. Of all breast cancer patients, 57.3% +/- 4.7% require RT in their initial treatment and 9.1% +/- 1.0% do so later for recurrence or progression. The proportion of patients who ever require RT is stage dependent: 39.8% +/- 1.1% in ductal carcinoma in situ; 68.6% +/- 4.1% in Stage I invasive carcinoma; 81.5% +/- 2.3% in Stage II; 95.3% +/- 0.3% in Stage III; and 63.7% +/- 0.3% in Stage IV. CONCLUSION: This method provides a rational starting point for the long-term planning of RT services and for the audit of access to RT at the population level. By completing such evaluations in the major cancer sites, it will be possible to estimate the appropriate RT treatment rate for the cancer population as a whole.

Algorithms↗

Evidence-based estimate of appropriate radiotherapy utilization rate for prostate cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of prostate cancer that should receive RT at any point in the evolution of the illness. METHODS AND MATERIALS: A systematic review of the literature was undertaken to identify indications for RT for prostate cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of prostate cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error using alternative sources of information was estimated by sensitivity analysis. RESULTS: It was estimated that 61.2% +/- 5.6% of prostate cancer cases develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 57.3%-69.8% on sensitivity analysis. Of all prostate cancer patients, 32.2% +/- 3.8% should receive RT in their initial treatment and 29.0% +/- 4.1% later for recurrence or progression. The proportion of cases that ever require RT is risk grouping dependent; 43.9% +/- 2.2% in low-risk disease, 68.7% +/- 3.5% in intermediate-risk disease; and 79.0% +/- 3.8% in high-risk locoregional disease. For metastatic disease, the predicted rate was 66.4% +/- 0.3%. CONCLUSION: This method provides a rational starting point for the long-term planning of radiation services and for the audit of access to RT at the population level. By completing such evaluations in major cancer sites, it will be possible to estimate the appropriate RT rate for the cancer population as a whole.

Humans↗

An evidence-based estimate of the appropriate radiotherapy utilization rate for colorectal cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require RT are based almost entirely on expert opinion. The objective of this study was to estimate the proportion of incident cases of colorectal cancer that should receive RT using an evidence-based approach. METHODS AND MATERIALS: A systematic review of the literature was undertaken to identify indications for RT for colorectal cancer, and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of colorectal cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error was estimated by sensitivity analysis. RESULTS: It was estimated that 23.7% +/- 1.0% of colorectal cancer cases develop one or more indications for RT at some point in the course of the illness: 20.9% +/- 1.1% as part of their initial treatment, and 2.8% +/- 0.5% later for recurrence or progression. We estimated that 7.1% +/- 0.8% of colon carcinoma patients will require RT at some point in the course of the illness: 4.0% +/- 0.7% as part of their initial treatment, and 3.1% +/- 0.4% later for recurrence or progression. We estimated that 72.3% +/- 1.0% of rectal carcinoma patients will require RT at some point in the course of the illness: 69.6% +/- 0.9% as part of their initial treatment and 2.7% +/- 0.2% later for recurrence or progression. CONCLUSIONS: This method provides a rational starting point for the long-term planning of radiation services, and for the audit of access to RT at the population level. By completing such evaluations in the major cancer sites, it will be possible to estimate the appropriate RT treatment rate for the cancer population as a whole.

Colonic Neoplasms↗

Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer.

PURPOSE: To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). METHODS AND MATERIALS: The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. RESULTS: Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0. 033). CONCLUSION: A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients.

Analysis of Variance↗

Hypoxia and necrosis in rat 9L glioma and Morris 7777 hepatoma tumors: comparative measurements using EF5 binding and the Eppendorf needle electrode.

PURPOSE: The purpose of this study was to assess the presence of tumor hypoxia using two independent techniques: binding of the 2-nitroimidazole EF5 and Eppendorf needle electrode measurements. The distribution of tumor hypoxia was assessed with respect to tumor necrosis in corresponding histological studies. METHODS AND MATERIALS: Each of several rats bearing a subcutaneous 9L glioma or Morris 7777 hepatoma tumor was given EF5 i.v. to a final, whole-body concentration of 100 microM. About 2.5 h later, each rat was anesthetized, and needle electrode measurements were made in the tumor along 1-5 tracks (30-200 individual measurements). At 3 h post-EF5 injection, the tumor was excised and frozen. Frozen sections were analyzed for the presence and distribution of binding of EF5 and necrosis using immunohistochemical techniques followed by staining with hematoxylin and eosin (H&E). The histochemical analysis and electrode readings in similar regions of the tumor were compared. RESULTS: Electrode measurements were taken at 0.4-mm intervals along one-dimensional tracks, whereas EF5 binding measurements from tissue sections contained two-dimensional information at high spatial resolution ( approximately 2.5 micro). The EF5 measurements showed greater spatial heterogeneity than did the electrode measurements. In tumor regions with minimal necrosis, needle tracks with relatively high pO(2) readings were usually found to contain relatively low EF5 binding, and vice versa. Because EF5 binding is inversely related to tissue pO(2), this result was expected. The expected inverse correlation of the two techniques was most disparate in necrotic tumor regions (confirmed by H&E staining), where needle electrode measurements showed low to zero pO(2) values, but little or no EF5 binding was found. CONCLUSION: The two methods compared in this study operate in fundamentally different ways and provide substantially different information. EF5 binding provided detailed spatial information on the distribution of hypoxia in viable tumor tissue. There was no EF5 binding in necrotic tumor tissue because cells in such tissue were unable to metabolize the drug. In contrast, output from the needle electrode method appeared to represent a "track-average" tissue pO(2) and did not distinguish between extreme hypoxia and either macroscopic or microscopic necrosis. At the present time, the importance of tumor necrosis in determining treatment response is unknown. However, our data suggest that the Eppendorf needle electrode technique will overestimate the presence of hypoxia. Both techniques are potentially limited by sampling errors in tumors with heterogeneous distributions of hypoxia.

Animals↗

Central core disease and congenital neuromuscular disease with uniform type 1 fibers in one family.

We report a family in which the father had central core disease and his son had congenital neuromuscular disease with uniform type 1 fibers. This is the first report of such a combination. Although they had no recognized mutation in the ryanodine receptor gene, it is highly likely that the son also had central core disease but without core structures. The absence of cores may be due to the muscle sample or the young age of the patient since core structures have been reported to increase with age. Although the prevalence of core structures in individual muscles is unknown, there is a possibility of sampling error. In some patients, congenital neuromuscular disease with uniform type 1 fibers is closely related to or identical with central core disease.

Adult↗

Biopsy techniques. Diagnosis of melanoma.

The biopsy of a suspicious pigmented lesion is critical to establishing a correct and complete diagnosis. It allows the dermatopathologist accurately to diagnose melanoma and to gauge maximum depth of invasion (and other histologic criterion). This, in turn, influences the extent of further necessary surgery or other adjuvant therapy. Furthermore, choosing the appropriate biopsy technique provides adequate cosmetic results, bearing in mind that the excisional technique is ideal because it removes the suspicious lesion en toto. Excisional biopsies should extend to the subcutaneous fat by means of a punch biopsy, a fusiform ellipse, or a saucerization. Incisional biopsies can be performed in certain circumstances, but should be done so with caution because sampling error may lead to missed diagnosis or inaccurate histologic criterion, such as depth.

Biopsy, Needle↗

Cardiac iron deposition in idiopathic hemochromatosis: histologic and analytic assessment of 14 hearts from autopsy.

In each heart taken from autopsies of 14 men with idiopathic hemochromatosis, the conduction system, atria and 10 sites in the ventricles were histologically graded for stainable iron. Stainable iron was exclusively sarcoplasmic; none was observed in the interstitium. The histologic grade for the same anatomic site varied among hearts and among different anatomic sites in the same heart. Ten hearts had stainable iron in all ventricular sites; one of the three hearts from patients who had undergone therapeutic phlebotomy had no iron at any site. Seven hearts had iron in the atria but at a lesser grade than that found in the ventricles; six hearts had mild focal iron deposition in the atrioventricular conduction system. None of the 14 hearts had stainable iron in the sinus node. Elemental iron was quantitated by atomic absorption spectroscopy in ventricular specimens contiguous to those studied histologically and also in age-matched control hearts. Elemental iron content was markedly increased in hearts with idiopathic hemochromatosis compared with control hearts (p less than 0.01). The quantity of elemental iron varied greatly, similar to stainable iron, but was highest subepicardially. Among the hearts from the 11 patients without prior phlebotomy, three had no stainable iron in the right ventricular septal subendocardium, suggesting that sampling error may be a problem in the evaluation of hemochromatosis by endomyocardial biopsy. The sarcoplasmic location of the iron indicates that cardiac involvement in idiopathic hemochromatosis represents a storage disease and not an infiltrative process; this finding is consistent with the normal ventricular wall thicknesses observed.

Adult↗

Evaluation of biopsy classification for rejection: relation to detection of myocardial damage by monoclonal antimyosin antibody imaging.

OBJECTIVES: This study sought to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global estimate of myocardial transplant-related cardiac damage detected by myocardial uptake of monoclonal antimyosin antibodies. BACKGROUND: The diagnosis and treatment of acute cardiac allograft rejection is based on the interpretation of endomyocardial biopsies. Because allograft rejection is a multifocal process and biopsy is obtained from a small area of the right ventricle, sampling error may occur. Global assessment of myocardial damage associated with graft rejection is now possible with the use of antimyosin scintigraphy. The present study was undertaken to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global assessment of transplant-related myocardial damage detected by antimyosin scintigraphy. METHODS: Biopsies (n=395) from 112 patients were independently interpreted by three pathologists in a blinded manner according to the original Stanford four-grade (normal, mild, moderate and severe) and the current International Society of Heart and Lung Transplantation (ISHLT) seven-grade (0, 1A, 1B, 2, 3A, 3B and 4) classifications. The results were correlated with 395 antimyosin studies performed at the time of the biopsies. The heart/lung ratio of antimyosin antibody uptake was used to assess the severity of myocardial damage. RESULTS: In the Stanford biopsy grade classification, significantly higher antimyosin uptake, indicating increasing degrees of myocardial damage, were associated with normal (1.78+/-0.26), mild (1.88+/-0.31) and moderate (1.95+/-0.38) biopsy classifications for rejection (p < 0.01). In the ISHLT classification, significant differences were detected only for antimyosin uptake associated with grades 0 (1.77+/-0.26) and 3A (1.98+/-0.39) but not for intermediate scores (1A, 1B and 2). In view of the similar intensity of antibody uptake among the various grades, ISHLT biopsy scores were regrouped: normal biopsies in grade A; 1A and 1B as grade B; and 2 and 3A as grade C. Antimyosin uptake in grades A, B and C was 1.78+/-0.26, 1.88+/-0.31, 1.95+/-0.38, respectively (p < 0.01). CONCLUSIONS: The current ISHLT seven-grade scoring system does not reflect the progressive severity of myocardial damage associated with heart transplant rejection. Because myocardial damage constitutes the basis of treatment for allograft rejection, there is a need to reevaluate the ISHLT grading system, given its importance for multicenter trials.

Antibodies, Monoclonal↗

New directions in breast biopsy: review of current minimally invasive methods and presentation of a new coaxial technique.

Minimally invasive core breast biopsy methods are replacing hook-wire-guided surgery wherever ultrasound and stereotactic equipment are available. Cost efficiency is improved, but sampling errors inherent in these techniques cause underestimations of malignancy and the degree of invasiveness in a small but significant number of patients. Diagnostic accuracy improves with increasing specimen weight. The trend is to take many cores. How much tissue is enough to enable a confident diagnosis? Recent research suggests that 1 g of tissue is sufficient. A new coaxial biopsy method presented here can retrieve a contiguous 1-g block of tissue from the center of a mammographic lesion, without stereotactic guidance. This specimen may be superior to multiple small cores obtained by biopsy guns and vacuum devices.

Biopsy↗

Does eradication of Helicobacter pylori reverse atrophic gastritis or intestinal metaplasia? Data from Japan.

In Japan, more reports showing improvement of atrophy or IM after eradication have appeared than reports showing no change. Many authors take biopsy specimens from the lesser and greater curvatures of the antrum and body and incisura angularis and make a histologic assessment using the standardized Updated Sydney System. Sampling errors should be taken into account, however. Interobserver agreement is poor in grading of atrophy. Apart from these problems, it seems almost certain that some patients show improvement or regression of atrophy or IM after eradication. Takizawa et al, evaluating many gastritis specimens, observed that antral IM might regress after eradication in the antral mucosa, where some pyloric glands remained under IM because pyloric glands and IM shared the proliferative zone, and that body IM replacing total fundic glands might hardly regress (T. Takizawa, MD, personal communication). Suto et al showed in an animal model that pseudopyloric glands differentiated into chief and parietal cells. Watanabe et al examined the influence of gastric pH on IM in x-irradiated rats and showed that increased acid secretion was associated with partial disappearance of IM without Paneth cells. Because gastric acid secretion of hypochlorhydric patients with body-predominant gastritis increased into normal range 1 to 6 months after eradication, it is possible that IM may regress in human subjects whose acid-secreting capacity recovers after eradication. The point of no return at which eradication leads to regression of atrophy and IM is not known. It is unknown how long IM takes to regress after eradication. There may be some differences in the characteristics between patients with and without improvement. Factors other than H. pylori (e.g., environmental factors) also should be investigated.

Gastritis, Atrophic↗