BACKGROUNDThe authors attempted to resolve the dilemma posed by the lack of unanimity concerning the optimal immunohistochemical (IHC) method for determining and scoring estrogen receptor (ER) and progesterone receptor (PR).METHODSSections for IHC were prepared from paraffin embedded tumor samples from 402 patients with lymph node positive breast carcinoma who had biochemical receptor values (obtained with the dextran‐coated charcoal [DCC] method) and who were enrolled in a prospective, randomized trial (National Surgical Adjuvant Breast and Bowel Project protocol B‐09). IHC receptors were scored independently by two observers according to percent, intensity, and any‐or‐none algorithms. Results from these evaluations and from two computer‐assisted evaluations, DCC, and common pathologic characteristics were analyzed for optimum splits for positive reactions in univariate and multivariate analyses using a tree‐structured model. Concordance, sensitivity, and specificity were determined between the DCC method and all other methods.RESULTSInterobserver agreement and concordance between the DCC method and the other methods and among the methods were high. Univariate analyses revealed that a positive ER score obtained with all methods was related significantly to overall survival (OS) at 5 years and at 10 years. Results related to PR scores and disease‐free survival and recurrence‐free survival were less consistent. In multivariate analysis, it also was found that all methods for scoring ER predicted a better prognosis for OS in patients with an unfavorable lymph node status at 5 years and 10 years. Patients in a favorable lymph node status group were discriminated further by nuclear grade.CONCLUSIONSAll IHC methods for scoring ER appeared valid as prognostic indicators of OS in patients with positive lymph nodes. The any‐or‐none IHC method, by virtue of its simplicity, represents an appropriate choice for practical use. Cancer 2005. © 2004 American Cancer Society.

Between 1971 and 1974, 1665 women with primary operable breast cancer were randomized into a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial (B‐04) conducted to evaluate the effectiveness of several different regimens of surgical and radiation therapy. No systemic therapy was given. Cells from archival paraffin‐embedded tumor tissue taken from 398 patients were analyzed for ploidy and S‐phase fraction (SPF) using flow cytometry. Characteristics and outcome of patients with satisfactory DNA histograms were comparable to those from whom no satisfactory cytometric studies were available. In patients with diploid tumors (43%), the mean SPF was 3.4% ± 2.3%; in the aneuploid population (57%), the SPF was 7.9% ± 6.3%. Only 29.9% ± 17.3% of cells in aneuploid tumors were aneuploid. Diploid tumors were more likely than aneuploid tumors to be of good nuclear grade (P less than 0.001) and smaller size (P equals 0.03). More tumors with high SPF were of poor nuclear grade than were tumors with low SPF (P equals 0.002). No significant difference in 10‐year disease‐free survival (P equals 0.3) or survival (P equals 0.1) was found between women with diploid or aneuploid tumors. Patients with low SPF tumors had a 13% better disease‐free survival (P equals 0.006) than those with a high SPF and a 14% better survival (P equals 0.007) at 10 years than patients with high SPF tumors. After adjustment for clinical tumor size, the difference in both disease‐free survival and survival between patients with high and low SPF tumors was only 10% (P equals 0.04 and 0.08, respectively). Although SPF was found to be of independent prognostic significance for disease‐free survival and marginal significance for survival, it did not detect patients with such a good prognosis as to preclude their receiving chemotherapy. The overall survival of patients with low SPF was only 53% at 10 years. These findings and those of others indicate that additional studies are necessary before tumor ploidy and SPF can be used to select patients who should or should not receive systemic therapy.

Common as well as unusual, heretofore unmentioned histopathologic features observed in 336 typical and 273 atypical medullary breast cancers from 6404 patients enrolled in various stage I and II protocols of the National Surgical Adjuvant Breast and Bowel Projects (NSABP) are presented. Both medullary types exhibited comparable pathologic findings, except for the infiltrative border and/or slight or absent tumor lymphoid infiltrate which by definition characterize the atypical form. Both also demonstrated a similar, high proclivity to be aneuploid, and to lack estrogen and progesterone receptors and nodal metastases. After appropriate statistical adjustments, survival (analyzed for 198 patients with typical and 149 with atypical medullary cancers) was found to be better for untreated, node-negative and node-positive patients treated with L-PAM + 5Fu who had typical medullary cancers than those with the NOS histologic type. The magnitude of this difference was 6% at 5 and 17% at 10 years post-operatively (cumulative odds = 1.81 with a 95% confidence interval of 1.08 - 3.3) for the former group, and 4% at 5 and 16% at 10 years (cumulative odds = 1.56 with a 95% confidence interval of 1.08 - 2.23) for the latter. Survival was comparable for patients with atypical medullary and NOS types in both situations. No clear difference in survival was found in untreated, positive node patients with the 3 histologic types examined, although the sample sizes in this subset were relatively small. This information as well as other pertinent considerations indicate that the prognosis of typical medullary cancer is not as 'good' as previously perceived. It is also concluded that there is insufficient evidence at present to exclude the atypical medullary variant as a histologic type of breast cancer.

We describe the design, modeling and production of a 3D printed manifold for attaching multiple respiration masks to a single ventilator machine. During a disaster surge this would allow up to four masks to be connected to a single ventilator source. In a disaster which involves high numbers of patients with lung damage, simultaneous respirator support may be required; however, the number of patients may quickly outnumber the available respirator machines. We explore the use of a rapid and low cost 3D printing method referred to as Fused Filament Deposition (FFD) for creation of a four-port ventilator manifold. This 3D printing method deposits layers of melted ABS plastic filament in a fine "stream" onto successive layers in order to form a three dimensional object. The standard file format for this object (manifold attachment) can be made globally available through the internet. It can be "printed" anywhere and anytime it is needed as a three dimensional object at extremely low cost (under two dollars per unit) and since the digital file that represents the object is modifiable, "derivative" versions can be redesigned to suit a broad range of potential applications, especially in areas with limited healthcare resources.

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