Assessing impact of organised breast screening across small residential areas-development and internal validation of a prediction model.

Monitoring screening mammography effects in small areas is often limited by small numbers of deaths and delayed effects. We developed a risk score for breast cancer death to circumvent these limitations. Screening, if effective, would increase post-diagnostic survivals through lead-time and related effects, as well as mortality reductions. Linked cancer and BreastScreen data at four hospitals (n = 2,039) were used to investigate whether screened cases had higher recorded survivals in 13 small areas, using breast cancer deaths as the outcome (M1), and a risk of death score derived from TNM stage, grade, histology type, hormone receptor status, and related variables (M2). M1 indicated lower risk of death in screened cases in 12 of the 13 areas, achieving statistical significance (p < .05) in 5. M2 indicated lower risk scores in screened cases in all 13 areas, achieving statistical significance in 12. For cases recently screened at diagnosis (<6 months), statistically significant reductions applied in 8 areas (M1) and all 13 areas (M2). Screening effects are more detectable in small areas using these risk scores than death itself as the outcome variable. An added advantage is the application of risk scores for providing a marker of screening effect soon after diagnosis.

A systematic review of surgical biopsy for LCIS found at core needle biopsy - do we have the answer yet?

BACKGROUND: The natural history of lobular carcinoma in-situ (LCIS) suggests that women are at increased risk of subsequent invasive breast cancer. Questions of effective management for women with this lesion have led to the need for evidence-based guidance and, in particular, guidance regarding management after LCIS is found at core needle biopsy (CNB). METHODS: A systematic review was conducted to determine the most appropriate management for women with LCIS found at CNB. A comprehensive search of the scientific literature was conducted to identify the literature pertaining to this population. Critical appraisal of the literature, data extraction and a narrative synthesis of the results were conducted. The outcome of interest was upgrade of diagnosis to invasive breast cancer or ductal carcinoma in-situ (DCIS). RESULTS: Sparse data, with limited generalisability and considerable uncertainty, are available for women with LCIS at CNB. Nine studies were identified that met pre-specified inclusion criteria. The reported estimates of upgrade of diagnosis from LCIS to invasive breast cancer or DCIS ranged from 2% to 25%. The body of evidence was limited by its retrospective nature, risk of selection bias and poor generalisability to all women with LCIS at CNB. Further, higher quality research is required to determine the best approach for women with LCIS at CNB with any certainty.

Independent predictors of breast malignancy in screen-detected microcalcifications: biopsy results in 2545 cases.

BACKGROUND: Mammographic microcalcifications are associated with many benign lesions, ductal carcinoma in situ (DCIS) and invasive cancer. Careful assessment criteria are required to minimise benign biopsies while optimising cancer diagnosis. We wished to evaluate the assessment outcomes of microcalcifications biopsied in the setting of population-based breast cancer screening. METHODS: Between January 1992 and December 2007, cases biopsied in which microcalcifications were the only imaging abnormality were included. Patient demographics, imaging features and final histology were subjected to statistical analysis to determine independent predictors of malignancy. RESULTS: In all, 2545 lesions, with a mean diameter of 21.8 mm (s.d. 23.8 mm) and observed in patients with a mean age of 57.7 years (s.d. 8.4 years), were included. Using the grading system adopted by the RANZCR, the grade was 3 in 47.7%; 4 in 28.3% and 5 in 24.0%. After assessment, 1220 lesions (47.9%) were malignant (809 DCIS only, 411 DCIS with invasive cancer) and 1325 (52.1%) were non-malignant, including 122 (4.8%) premalignant lesions (lobular carcinoma in situ, atypical lobular hyperplasia and atypical ductal hyperplasia). Only 30.9% of the DCIS was of low grade.Mammographic extent of microcalcifications >15 mm, imaging grade, their pattern of distribution, presence of a palpable mass and detection after the first screening episode showed significant univariate associations with malignancy. On multivariate modeling imaging grade, mammographic extent of microcalcifications >15 mm, palpable mass and screening episode were retained as independent predictors of malignancy. Radiological grade had the largest effect with lesions of grade 4 and 5 being 2.2 and 3.3 times more likely to be malignant, respectively, than grade 3 lesions. CONCLUSION: The radiological grading scheme used throughout Australia and parts of Europe is validated as a useful system of stratifying microcalcifications into groups with significantly different risks of malignancy. Biopsy assessment of appropriately selected microcalcifications is an effective method of detecting invasive breast cancer and DCIS, particularly of non-low-grade subtypes.

Assessment of 1183 screen-detected, category 3B, circumscribed masses by cytology and core biopsy with long-term follow up data.

Discrete masses are commonly detected during mammographic screening and most such lesions are benign. For lesions without pathognomonically benign imaging features that are still regarded likely to be non-malignant (Tabar grade 3) reliable biopsy results would be a clinically useful alternative to mammographic surveillance. Appropriate institutional guidelines for ethical research were followed. Between Jan 1996--Dec 2005 grade 3B discrete masses detected in the setting of a large, population based, breast cancer screening programme are included. Patient demographics, fine needle aspiration biopsy (FNAB), core and surgical biopsy results are tabulated. The final pathology of excised lesions was obtained. Information regarding interval cancers was obtained from the State Cancer Registry records and also through long term follow-up of clients in subsequent rounds of screening. A total of 1183 lesions, mean diameter of 13.3 mm (+/-8.3 mm) and mean client age of 55.1 years (+/-8.8 years) are included. After diagnostic work up, 98 lesions (8.3%) were malignant, 1083 were non-malignant and a final histologic diagnosis was not established in two lesions. In the 27 months after assessment, no interval cancers were attributable to these lesions and during a mean follow up of 54.5 months, available in 84.9% of eligible women, only one cancer has developed in the same quadrant as the original lesion, although the two processes are believed to be unrelated. FNAB performed in 1149 cases was definitive in 80.5% cases (882 benign, 43 malignant) with a negative predictive value (NPV) of 99.8% (880 of 882) and a positive predictive value (PPV) of 95.2% (40 of 42, both intraductal papillomas). Core biopsy was performed in 178 lesions, mostly for indefinite cytology. Core biopsy was definitive in 79.8% cases (57% benign 22% malignant) with a PPV of 100% and NPV of 99.0%. In experienced hands FNAB is an accurate first line diagnostic modality for the assessment of 3B screen-detected discrete masses, providing definitive results in 80.5% of cases. When used as a second line modality, core biopsy had a similarly high rate of definitive diagnosis at 79.8%. The stepwise approach to the use of FNAB and core biopsy would reduce substantially the proportion of cases requiring surgical diagnostic biopsy. Given the low probability of malignancy and the imperative to limit the morbidity associated with cancer screening, the demonstration of the reliability of FNAB as a minimally invasive but highly accurate test for this particular subset of screen-detected lesions has significant clinical utility.

Population screening and intensity of screening are associated with reduced breast cancer mortality: evidence of efficacy of mammography screening in Australia.

BACKGROUND: Efficacy of breast screening may differ in practice from the results of randomized trials. We report one of the largest case-control evaluations of a screening service. METHODS: Subjects included 491 breast-cancer deaths affecting 45-80-year-old South Australian females during 2002-2005 (diagnosed after BreastScreen commencement) and 1,473 live controls (three per death) randomly selected from the State Electoral Roll after birth-date matching. Cancer Registry and BreastScreen records provided cancer and screening details. Risk estimates were calculated by BreastScreen participation, using conditional logistic regression. Interpretation was assisted by a population survey of risk factor prevalence by BreastScreen participation in 1,684 females aged > or =40 years. RESULTS: The relative odds (OR) (95% confidence limits) of breast-cancer death in BreastScreen participants compared with non-participants were 0.59 (0.47, 0.74). Compared with non-participants, the OR was 0.70 (0.47, 1.05) for women last screened through BreastScreen more than 3 years before diagnosis of the index case, and 0.57 (0.44, 0.72) for women screened more recently. The OR of 0.47 (0.34, 0.65) for women screened more frequently in the pre-diagnosis phase was lower than the 0.64 (0.50, 0.82) for other screened women. The overall OR of 0.59 approximated 0.70 when corrected for the screening self-selection bias observed in five randomized trials. However, multivariable analysis of survey data did not indicate a lower prevalence of breast-cancer risk factors among BreastScreen participants, suggesting that this correction may be inappropriate. CONCLUSIONS: Participation in screening was associated with a breast-cancer mortality reduction of between 30 and 41%, depending on assumptions about screening self-selection bias. A downward mortality risk by recency of last screen prior to cancer diagnosis, and frequency of recent screening, is consistent with a screening effect.

Feasibility study on the MammoSite in early-stage breast cancer: initial experience.

The aims of this study were to evaluate the feasibility, practicality, efficacy and safety of the delivery of accelerated partial breast irradiation using the MammoSite for the boost phase. Six patients aged 53-69 years with stage T1N0, T2N0, Grade I-II invasive ductal carcinoma received 9-10 Gy prescribed at 1 cm from the MammoSite balloon surface in two fractions of 4.5-5 Gy 6 h apart. The MammoSite was inserted 20-37 days postoperatively. External beam radiation therapy to the whole breast commenced 1-5 days after accelerated partial breast irradiation. The maximum skin dose ranged from 3 to 9 Gy. The skin-cavity distance ranged from 7 to 19 mm. Local discomfort resolved as the scar healed spontaneously within 3-5 days. No Grade III or higher acute toxicity or local infection was recorded. The ease of insertion and accuracy of dosimetry makes the MammoSite suitable for use in properly selected women with early-stage breast cancer in a trial setting.

Histopathological features of breast cancer in carriers of ATM gene variants.

AIMS: Germline variants in the ataxia telangiectasia mutated (ATM) gene have been implicated in increased breast cancer risk. The aim of this study was to determine whether the histopathology of breast cancers occurring in ATM variant carriers is distinctive or resembles the described BRCA1 mutation-associated phenotype. METHODS: The histopathological features of breast cancers occurring in ATM variant carriers from multiple-case breast cancer families were compared with matched controls. The test group included 21 cases of in situ and/or invasive cancer from carriers of either the IVS10-6T-->G, 2424V-->G or 1420L-->F ATM variants in the absence of BRCA1 or BRCA2 mutations. An additional four invasive cancers from carriers of a pathogenic BRCA1 mutation in the context of a familial ATM variant were also examined. RESULTS: The histopathology of breast cancers in ATM variant-only carriers was not significantly different from controls and known features of BRCA1 mutation-associated cancer were rarely seen. In contrast, these features were prominent in the small group of cases with a pathogenic BRCA1 mutation. CONCLUSIONS: Breast cancer occurring in carriers of ATM variants is not associated with distinctive histopathological features and does not resemble the tumour phenotype commonly observed in BRCA1 mutation carriers.

Detection by screening mammography is a powerful independent predictor of survival in women diagnosed with breast cancer.

Four hundred and sixteen invasive breast cancers, detected initially by mammography, were compared with 929 presenting symptomatically, all treated at a South Australian teaching hospital. Predictable differences included lower stages and grades, less vascular invasion and proliferative activity, and more hormone-receptor expression among the mammographically detected. Unpredicted differences included significantly higher survivals for mammographically detected cases throughout the 9 year follow-up period after adjusting for stage and the Nottingham Prognostic Index. In a multivariable analysis, differences in stage, grade, and hormone receptor expression accounted for only about half the survival advantage of mammographically detected tumours. Accounting for additional person and tumour characteristics had only a marginal effect on this result. This suggests that detection by mammography has independent favourable prognostic significance beyond that explained by conventional indicators. If confirmed, this finding would have important implications for the prognostic advice given to women and may merit further investigation into its underlying biological mechanisms.

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study.

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC ) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC.

Removal of two sentinel nodes accurately stages the axilla in breast cancer.

BACKGROUND: Assessment of lymph node status in breast cancer is still necessary for staging. Sentinel lymph node biopsy (SNB) may provide accurate staging with less morbidity than axillary clearance. The aim of this study was to assess the effect of the number of sentinel nodes removed on the false-negative rate. METHODS: Data were collected prospectively from 395 women undergoing SNB for breast cancer, between June 1995 and December 2001. All nodes that were hot and/or blue were removed and analysed. RESULTS: During this interval 136 patients who had SNB were lymph node positive. The median number of sentinel nodes removed was two (range one to five). The overall false-negative rate of SNB in these women was 7.1 per cent. If only one sentinel node had been removed, the false-negative rate would have been 16.5 per cent. The removal of more than two nodes had no effect on axillary staging in all but two women. CONCLUSION: In early breast cancer, when there were multiple sentinel nodes, removal of two sentinel nodes significantly reduced the false-negative rate compared with removal of one node. Removing more than two sentinel nodes did not significantly reduce the false-negative rate further.

Clinical impact of false-negative sentinel node biopsy in primary breast cancer.

BACKGROUND: The aim was to assess the false-negative sentinel node biopsy rate in women with early breast cancer and its implications in patient treatment. METHODS: Between January 1995 and March 2001, 328 consecutive patients with clinically lymph node-negative primary operable breast cancer underwent lymphatic mapping and sentinel node biopsy using a combination of preoperative lymphoscintigraphy and/or blue dye. All underwent immediate axillary dissection. The intraoperative success rate in sentinel node identification, false-negative rate, predictive value of negative sentinel node status and overall accuracy were assessed. The clinical features and primary tumour characteristics for each false-negative case were reviewed. RESULTS: The sentinel node was identified in 285 (86.9 per cent) of 328 women. The false-negative rate was 7.9 per cent (eight of 101). Most members of the breast multidisciplinary team would have instituted adjuvant systemic therapy for six false-negative cases based on clinical features and primary tumour histology. In all, only two (0.7 per cent) of 285 women who had sentinel node biopsy may have had their management and survival prospects potentially jeopardized owing to a false-negative sentinel node. CONCLUSION: The results of this study suggest that the clinical impact of a false-negative sentinel node is low.

Spindle cell ductal carcinoma in situ. An unusual variant of ductal intra-epithelial neoplasia that simulates ductal hyperplasia or a myoepithelial proliferation.

Seventeen examples of a variant of ductal carcinoma in situ (DCIS) composed exclusively or predominantly of spindle cells arranged in fascicles, whorls, and solid sheets are described. The fascicular arrangement of the spindle cells simulates the "streaming" phenomenon associated with ordinary intraductal epithelial hyperplasia (IDH). This process also resembles the myoid, solid form of intraductal myoepithelial proliferation. The women ranged in age from 38 years to 79 years with a mean age of 59.3 years. Five patients presented with a palpable mass. The remaining tumors were discovered using mammography. The radiological appearances of the lesions raised concern for carcinoma, but there were no distinctive mammographic findings to suggest an unusual variant of DCIS. Cytological preparations were suspicious for malignancy in two patients and were reported as malignant in another case. Sixteen patients were treated with wide local excision, and one woman had a partial mastectomy. The tumors measured from 3 mm to 15 mm (mean 8.65 mm). In three cases, minute foci of stromal invasion were associated with the spindle cell DCIS. In another specimen, a 2.7-cm invasive ductal carcinoma of no special type was identified in an area away from the foci of the spindle cell DCIS. None of the patients has experienced recurrence or metastasis during the relatively short mean follow-up period of 16.2 months (range 4-77 months). Spindle cell DCIS is distinguished from the streaming pattern of ordinary IDH by its solid growth pattern, lack of secondary spaces or peripheral fenestrations, uniformity of appearance and distribution of nuclei, cytological atypia in the range of low to intermediate-grade DCIS, and negative immunoreaction with CK-34betaE12 (HMW-CK903). When fenestrations are present, they are evident in areas of cribriform DCIS that merge with the solid, spindle cell areas in hybrid ducts harboring both patterns. This admixture, with conventional cribriform DCIS, and the association with foci of invasive ductal carcinoma in some cases further help recognition and confirmation of this lesion as in situ carcinoma. When there is no transition from the spindle cells to recognizable cribriform DCIS, distinction from intraductal myoepithelial hyperplasia (myoepitheliosis) requires immunostains for actin and S-100 protein. Recognition of this pattern of DCIS is important in order to avoid its frequent misclassification as a benign lesion.

False-positive reports in fine needle biopsy of breast lesions.

A review of the literature reveals considerable variations in the diagnostic accuracy of fine needle biopsy (FNB) of breast lesions between series, partly due to different methods of calculation, different definitions, and insufficient numbers of cases with adequate follow-up to provide reliable statistics. The best larger series have a false-positive rate between 0.2 and 0.3%, slightly higher for non-palpable than for palpable lesions. The cytological patterns of a range of benign lesions which may cause diagnostic difficulties and may be misdiagnosed as malignant by FNB are described, and guidelines to reduce the risk of false-positive diagnoses are proposed.

Clinical and histological factors associated with sentinel node identification in breast cancer.

BACKGROUND: Although sentinel lymph node biopsy is likely to be offered as a method of assessing nodal status in primary breast cancer, the inability to identify the sentinel node at the time of surgery will limit the number of patients who may benefit from the procedure. The purpose of the present study was to identify factors that are associated with intraoperative identification of the sentinel node(s). METHODS: Between September 1995 and May 1999, lymphatic mapping using a combination of preoperative lymphoscintigraphy and/or blue dye was performed on 169 consecutive patients with clinically lymph node-negative primary operable breast cancer. Clinical and histological factors were assessed using univariate and multivariate analysis to determine those that were associated with intraoperative identification of the sentinel node. RESULTS: The sentinel node was identified at the time of surgery in 142 cases (84%). Of the clinical factors assessed, preoperative identification of the sentinel node on lymphoscintigraphy (P < 0.0001), use of blue dye in combination with isotope (P = 0.001), symptomatic palpable tumours (P < 0.05) and the experience of the surgeon (P = 0.03) were significant in identifying the sentinel node at operation. No histological factor was associated with intraoperative identification of the sentinel node. Using multivariate analysis, positive identification of the sentinel node on lymphoscintigram, the experience of the surgeon and the use of both blue dye and isotope for sentinel node mapping were independent factors associated with intraoperative sentinel node identification. The lymphoscintigram result was the strongest independent factor according to its beta value, a measure of the weight of significance. CONCLUSION: Patients undergoing sentinel lymph node mapping and biopsy should be warned of the possibility of failure of sentinel node identification at operation. Our results suggest that the best predictor of intraoperative sentinel node identification is the visualization of the sentinel node on preoperative lymphoscintigraphy. The result of the lymhoscintigram may allow for additional preoperative counselling of the patient regarding the success or failure of sentinel node biopsy. Technical factors such as the experience and diligence of the surgeon, as well as the sentinel node mapping technique, are also important in determining the success of the procedure.

Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma.

BACKGROUND: Many empiric protocols are used to detect metastases in sentinel lymph nodes (SLNs), but comparison of the efficacy of these methods is impractical because tissue is lost in processing, making reassessment with another policy difficult. Consequently, performance indicators of this test are largely unknown. DESIGN: The authors retrospectively examined 112 SLNs removed from 89 patients with breast carcinoma treated at the authors' institution and used the histologic data to devise a mathematic model of a SLN with Matlab modeling software. The authors simulated examination of this computer-generated (virtual) lymph node according to several macroscopic and histologic sampling protocols and for each protocol assessed the probability of detecting micrometastases of specified sizes. The authors used published costing figures to estimate the cost of the policies. RESULTS: Direct comparison of 6 sectioning strategies currently in use by pathology laboratories showed the chances of detecting a 500-microm metastasis ranged from 20% to 75%. Four of the 6 protocols had a less than 30% chance of detecting metastases of this size. The detection rate of smaller metastases was poorer. Cost was not a good discriminator because some policies were more efficient than others. CONCLUSIONS: The detection of metastases is highly dependent on the methods used to look for them. The authors' simulations suggest that commonly used methods of examining lymph nodes have high false-negative rates, particularly for small metastases. There is an urgent need for pathologists and clinicians to agree on the minimum size of SLN metastases that will be sought by histology and set standard methods for examining these lymph nodes.

Reliability of sentinel node status in predicting axillary lymph node involvement in breast cancer.

OBJECTIVES: To assess the reliability of determining sentinel node status in staging regional lymph nodes in breast cancer. DESIGN AND SETTING: Prospective validation study in a major public teaching hospital, comparing histological sentinel node status with that of remaining axillary nodes. PATIENTS: 117 women who underwent sentinel node biopsy and axillary dissection for primary breast cancer between 1995 and 1998. MAIN OUTCOME MEASURES: Intraoperative success rate in sentinel node identification; false negative rate; predictive value of negative sentinel node status; overall accuracy of sentinel node status. RESULTS: The sentinel node was identified at operation in 95 patients (81.2%). Tumour involvement of the sentinel node was demonstrated in 29 of 31 women (93.5%; 95% CI, 79%-99%). Sixty-four of the 66 women in whom the sentinel node was negative for tumour showed no further involvement of remaining axillary nodes (standard haematoxylin-eosin histological assessment), giving a predictive value of negative sentinel node status of 97% (95% CI, 89%-100%). The overall accuracy in 95 women in whom sentinel node status was compared with axillary node status was 97.9%. CONCLUSIONS: Histopathological examination of the sentinel node is an accurate method of assessing axillary lymph node status in primary breast cancer and is likely to be incorporated into future surgical management of women with primary breast cancer.

Massive localized lymphedema in the morbidly obese: a histologically distinct reactive lesion simulating liposarcoma.

We report 14 cases of a soft tissue lesion in the limbs of morbidly obese adults that presents as a large mass and histologically simulates well-differentiated liposarcoma (WDL). Based on its distinctive clinical setting and morphologic identity to diffuse lymphedema we have termed this process massive localized lymphedema (MLL). All cases occurred in morbidly obese adults (mean weight 372 lbs; mean age 47 years). Women predominated (9 women; 5 men). The lesions affected the proximal medial aspect of the extremities (12 thigh; 2 arm) and were unilateral in all but two patients. Etiologically significant antecedent events include ipsilateral axillary lymphadenectomy in both patients with arm lesions, chronic lymphedema resulting from vein-stripping 10 years prior in one patient. inguinal lymphadenectomy for anal carcinoma in another patient, and significant blunt trauma to the inner thigh during a motor vehicle accident in a third patient. The tumors were long standing ( I-IO years) and extremely large (mean size 33.4 cm, 7408 g). Clinically, they were diffuse, ill-defined masses that histologically consisted of lobules of mature fat interrupted by expanded connective tissue septa. The constituents of the septa were fine, fibrillary collagen, edema fluid, and uniformly distributed fibroblasts. Clusters of capillaries were frequently found at the interface between fat and connective tissue. The widened septa simulated the fibrous bands of sclerosing WDL, but MLL lacks the degree of nuclear atypia seen in the former. The consistent clustering of reactive vessels at the interface between the fat and fibrous tissue also contrasted with WDL. Six patients experienced persistent or recurrent lesions within 10 months to 10 years. No aggressive growth or histologic progression was observed during this time, however. Awareness of the features of MLL is important to avoid misclassification of this reactive lesion with WDL.

RANTES chemokine expression in cell-mediated transplant rejection of the kidney.

RANTES (regulated upon activation, normal T cell expressed and secreted) is a chemotactic cytokine (a chemokine) for memory T lymphocytes, monocytes, and eosinophils. RANTES expression was studied in renal allograft biopsy specimens. Although RANTES was not expressed in samples taken one hour after transplantation, or in native renal biopsy specimens from patients with cyclosporin nephrotoxicity, it was expressed during cell-mediated transplant rejection. RANTES mRNA was detected in infiltrating mononuclear cells and renal tubular epithelium, and RANTES protein was localised to mononuclear cells, tubular epithelium, and vascular endothelium. This suggests RANTES has a role in allograft rejection.

Bactericidal activity of tigemonam, alone and in combination with gentamicin.

The in vitro bactericidal activity of tigemonam, alone and in combination with gentamicin, was evaluated against various strains of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella enteritidis, Enterobacter cloacae, Proteus mirabilis, and Proteus vulgaris. Minimum inhibitory and bactericidal concentrations were determined on three consecutive days with an inoculum of 10(5) colony-forming units (CFU)/mL or a culture in the logarithmic growth phase. The results found tigemonam to be rapidly bactericidal against most Enterobacteriaceae isolated. In addition, the killing curves indicated a synergism between tigemonam and subinhibitory concentrations of gentamicin.

Bactericidal Activity of Tigemonam, Alone and in Combination with Gentamicin.

The in vitro bactericidal activity of tigemonam, alone and in combination with gentamicin, was evaluated against various strains of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella enteritidis, Enterobacter cloacae, Proteus mirabilis, and Proteus vulgaris. Minimum inhibitory and bactericidal concentrations were determined on three consecutive days with an inoculum of 105 colony-forming units (CFU)/mL or a culture in the logarithmic growth phase. The results found tigemonam to be rapidly bactericidal against most Enterobacteriaceae isolated. In addition, the killing curves indicated a synergism between tigemonam and subinhibitory concentrations of gentamicin.