Value of fundamentals of laparoscopic surgery training in a fourth-year medical school advanced surgical skills elective.

BACKGROUND: Few data are available describing the benefits of initiating fundamentals of laparoscopic surgery (FLS) training during medical school. We hypothesized that an intense 1-month surgical skills elective that included FLS task training for fourth-year medical students (MS4s) would result in performance levels indistinguishable from graduating chief residents (PGY5) who had received clinical skill training and access to self-guided FLS curriculum. METHODS: From July 2007 through June 2011, 114 MS4s participated in a 1-month advanced surgical skills elective. The curriculum for the elective included cadaver dissections, patient management presentations, and surgical skill training (open surgical skills and basic laparoscopic skills modules performed on FLS trainers and virtual reality laparoscopic simulators). From June 2009 through June 2011, 21 PGY5s graduated who had never received formalized FLS skills training. These residents were tested on FLS by a certified proctor and the results recorded. The performance outcome measure was task completion time. Unpaired Student's t-test was used to compare the performance measures for each group. RESULTS: All PGY5s achieved FLS certification on their first attempt and completed enough cases for graduation. The MS4 group showed significantly better performance than the PGY5 group in the peg transfer and circle cut (P < 0.05). No difference was seen in the knot tying tasks between the two groups (P > 0.05) CONCLUSIONS: Incorporating FLS training into a 1 month-long medical school surgery elective enabled MS4s to achieve FLS performance similar to, or better than, the performance achieved by PGY5 surgery residents. We support the integration of FLS skills task training as a standard part of the skills training curriculum for medical students.

Impact of fundamentals of laparoscopic surgery training during medical school on performance by first year surgical residents.

BACKGROUND: Fundamentals of Laparoscopic Surgery (FLS) certification is a high stakes examination. The best training methods to enable successful certification are undetermined. We hypothesized that first year surgical residents (R01s) who had been pretrained as medical students would perform better during skills training than previously un-trained R01s. METHODS: This is an IRB-approved, retrospective review of FLS training data generated from a single surgical skills laboratory from July 2007 through June 2010. During the study period, there were 24 R01s with no previous FLS exposure (NOVICE group) and seven R01s who had undergone FLS task training while medical students (MS4 group). All R01s practiced the FLS skill tasks weekly for portions of the training sessions with informal feedback and teaching. Performance goals were proposed for each task based on local and national proficiency figures. The performance outcome measure was task completion time (TCT). Pretraining performance was designated iTCT and post-training fTCT. RESULTS: The MS4 group began with iTCTs for all four tasks that were significantly lower than the NOVICE iTCTs. At completion of the 16-wk training period, the MS4 group continued to demonstrate mean fTCTs that were lower for all four FLS skill tasks but only significantly for PEG, CIRCLE, and INTRA skill tasks. Both NOVICE and MS4 groups showed significant improvement for all four skill tasks (P < 0.05). CONCLUSIONS: In the current milieu of work-hour limitations, the integration of FLS skill training into medical school curriculum provided a durable advantage to the pretrained R01s, which was associated with higher levels of final performance.

MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf¹/cip¹).

PURPOSE: MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and proliferation in several solid epithelial cancers. Enhancer of zeste homolog 2 (EzH2) appears to be a functional target of miR-101. We explore the role of miR-101 and its interaction with EzH2 in epithelial ovarian carcinoma (EOC). METHODS: In situ hybridization (ISH) for miR-101 was performed on EOC patient tissues and normal controls. EOC cell lines were transfected with miR-101 and subjected to growth analysis and clonogenic assays. Cell motility was assessed by Boyden chamber and wound-healing assays. P21(waf1/cip1) and EzH2 interaction was assessed by Chromatin Immunoprecipitation (ChIP) assay in MDAH-2774 cells. SCID mice were assessed for tumor burden after injection with miR-101 or control vector-treated MDAH-2774 cells. RESULTS: ISH analysis revealed a decrease in miR-101 expression in EOC compared with normal tissue. MiR-101 re-expression in EOC cell lines resulted in increased apoptosis, decreased cellular proliferation, invasiveness, and reduced growth of tumor xenografts. CHIP assays revealed that re-expression of miR-101 inhibited the interaction of EzH2 with p21(waf1/cip1) promoter. CONCLUSIONS: MiR-101 re-expression appears to have antitumor effects, providing a better understanding of the role of miR-101 in EOC.

Effective Large Group Teaching for General Surgery.

Large group settings display no signs of disappearing. Most surgeons charged with this education have received no formal training. Lecturing remains the most common method of educating large groups. Even though factors required for an excellent lecture are known, their inconsistent application results in variation of effectiveness. Long-standing principles of rhetoric and recent advances in neuroscience, cognitive science, learning models, and teaching theory play a role in achieving effectiveness. This article makes recommendations for creating and delivering lectures, including active learning opportunities and modern innovations in information technology supporting teaching methods. Effective lecturing skills are acquired by persistent deliberate practice.

FLS skill retention (learning) in first year surgery residents.

BACKGROUND: Fundamentals of Laparoscopic Surgery (FLS) certification is reliable and valid; the American Board of Surgery requires FLS certification. Dynamics of skill retention after FLS training effect training schedules for residents. We hypothesized that the initial elevation of performance levels after FLS training would deteriorate predictably with time. METHODS: FLS performance data on 16 new surgical residents (R01s) was examined retrospectively. These R01s trained at 16 weekly sessions. Training included 4 FLS tasks, VR simulator tasks, and open surgical skills. FLS skills were practiced weekly with feedback but no instruction. Performance was tested PRE, POST, and DELAY. Outcome metrics were task completion times (TCTs). RESULTS: POST TCTs were below PRE TCTs in all R01s for all FLS tasks (P < 0.05). No difference was seen between the DELAY TCT and POST TCT for peg transfer (P = 0.726) and pattern cut (P = 0.114). The DELAY TCTs were longer than POST TCTs for extra- and intra corporeal knot-tying (P < 0.0001 and P = 0.029). Relative retention was 103% for peg transfer, 85% for pattern cut, 47% for extracorporeal knot tying, and 59% for intracorporeal knot tying. However, many individual's displayed DELAY TCT equal to or lower than POST TCT implying full retention. CONCLUSIONS: This study extends the data on FLS skill retention to an actual "production" training curriculum. This FLS training provided effective learning in R01s. Although performance levels fell across these tasks on average and for the majority of individual R01s, significant skill retention remained at 7-8 months. Early training will enable R01s to maintain or elevate skill levels with additional training sessions.

Cryotherapy for breast cancer: a feasibility study without excision.

PURPOSE: To assess the feasibility of percutaneous multiprobe breast cryoablation (BC) for diverse presentations of cancers that remained in situ after BC. MATERIALS AND METHODS: After breast magnetic resonance (MR) imaging and thorough consultation, patients underwent BC after giving informed consent. This study was approved by the institutional review board. In 12 BC sessions, 22 breast cancer foci (stages I-IV) were treated in 11 patients who refused surgery by using multiple 2.4-mm cryoprobes. Five patients had recurrent disease and six had new diagnoses. With use of only local anesthesia, six patients were treated with ultrasonographic (US) guidance and five were treated with both computed tomographic (CT) and US guidance. Saline injections and warming bags were used to protect the skin. Procedure success was defined as 1 cm visible ice beyond all tumor margins. MR imaging and/or clinical follow-up were available for up to 72 months after BC. RESULTS: US produced sufficient ice visualization for small tumors, whereas CT helped confirm overall ice extent. The mean pretreatment breast tumor diameter was 1.7 cm +/- 1.2 (range, 0.5-5.8 cm), and an average of 3.1 cryoprobes produced 100% procedural success with mean ice diameters of 5.1 cm +/- 2.2 (range, 2.0-10.0 cm). No significant complications, retraction, or scarring were noted. Biopsies at the margins of the cryoablation site immediately after BC and at follow-up were all negative. No local recurrences have been noted at an average imaging follow-up of 18 months. CONCLUSIONS: In conjunction with thorough pre- and postablation MR imaging, CT/US-guided multiprobe BC safely achieved 1 cm visible ice beyond tumor margins with minimal discomfort, good cosmesis, and no short-term local tumor recurrences.

Benefits of mock oral examinations in a multi-institutional consortium for board certification in general surgery training.

The Southeast Michigan Center for Medical Education (SEMCME) is a consortium of teaching hospitals in the Greater Detroit metropolitan area. SEMCME pools its resources for several educational means, including mock oral board examinations. The educational and cost benefits to mock oral examinations on a multi-institutional basis in preparation for the American Board of Surgery (ABS) certifying examination were analyzed. Ten-year multi-institution data from the mock oral examinations were correlated with ABS certifying examination pass rates. Mock oral examination scores were available for 107 of 147 graduates, which included 12 candidates who failed their certifying examination on the first attempt (pass rate = 89%). Four of 31 examinees who had a low score (4.9 or less) in their mock oral exams failed their certifying examination in their first attempt. The cost of running the mock examination was low (approximately $35/resident for 50 residents). When graduates from the last 10 years were surveyed, the majority of respondents believed that the mock oral examination helped in their success and with their preparation for the certifying examination. Thus, the many benefits of administering the examination with the resources of a consortium of hospitals result in the accurate reproduction of real-life testing conditions with reasonable overall costs per resident.

Cytochrome p450 and glutathione transferase expression in human breast cancer.

PURPOSE: The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems may influence the biological effects of carcinogens, including estrogens. As such, these enzymes may predict the developmental risk of breast cancer, as well as be potential targets for chemoprevention. The purpose of this study was to compare the expression of GST-Pi and CYPs 1A1, 2B6, 2E1, and 3A4 in paired samples of normal and malignant breast tissue from patients with breast cancer and women undergoing reduction mammoplasty. EXPERIMENTAL DESIGN: Expression of CYPs 1A1, 2B6, 2E1, 3A4, and GST-Pi was quantified in breast tissue from 33 patients with breast cancer and in 17 women without history of cancer who underwent reduction mammoplasty. The expression of CYP 1A1, 2B6, 2E1, 3A4, and GST-Pi was quantified by immunoblotting. RESULTS: CYP 1A1, 2E1, and 3A4 expression was significantly lower (P < 0.05) in malignant tissue as compared with morphologically normal adjacent tissue. Conversely, GST-Pi expression was marginally lower in the normal tissue (P = 0.08). No significant difference in enzyme expression was seen between the tissue from reduction mammoplasty and normal tissue from breast cancer patients. There was a trend for higher expression of CYP 2B6 and GST-Pi in the estrogen receptor expressing tumors than those tumors without expression (P > 0.28). CONCLUSION: The expression of these enzymes was similar in morphologically normal breast tissue from patients with or without breast cancer. The expression of CYPs was down-regulated in the tumor tissue. The clinical significance of CYP alterations in breast cancer will need further characterization.

EZH2-shRNA-mediated upregulation of p21waf1/cip1 and its transcriptional enhancers with concomitant downmodulation of mutant p53 in pancreatic ductal adenocarcinoma.

PURPOSE: Enhancer of zeste homologue 2 (EZH2), a component of the chromatin modification protein complex, is upregulated in pancreatic ductal adenocarcinoma (PDAC), whereas loss of p53 and its downstream target, p21(waf1/cip1), is also observed frequently. We sought to investigate the role of the p53-p21(waf1/cip1) pathway in relation to EZH2-mediated inhibition of PDAC. METHODS: The PANC-1 cell line was utilized in chromatin immunoprecipitation, gene profiling, Western blot, cell invasion, cell proliferation, and tumor xenograft assays. RESULTS: Western blot analysis with antibodies that recognize both wild-type and mutant p53 did not show any alterations in band intensity; however, antibody that detects only mutant p53 showed a band of significantly lesser intensity with EZH2 knockdown. Western blot analysis further revealed a significant upregulation of p21(waf1/cip1). Gene expression profile analysis indicated significantly enhanced transcripts of transcriptional inducers of p21(waf1/cip1), with downregulation of mutant p53 transcript, corroborating the Western blot analysis. PANC-1 cells expressing EZH2-short hairpin RNA displayed markedly attenuated growth in SCID mice. CONCLUSION: Downregulation of mutant p53 with concomitant enhanced expression of p21(waf1/cip1) and its transcriptional trans-activators may contribute toward EZH2-mediated suppression of PDAC.

EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53.

The enhancer of zeste homolog 2 (EZH2) methyltransferase is a transcriptional repressor. EZH2 is abnormally elevated in epithelial ovarian cancer (EOC). We demonstrated that EZH2 knockdown inhibited cell growth, activated apoptosis, and enhanced chemosensitivity. Further, silencing of EZH2 resulted in re-expression of p21(waf1/cip1) and down-regulation of mutant p53. Finally, EZH2 knockdown contributed to attenuated EOC growth in SCID mice.

Restoration of E-cadherin expression in pancreatic ductal adenocarcinoma treated with microRNA-101.

PURPOSE: To investigate the possibility of inhibiting the progression of pancreatic ductal adenocarcinoma (PDAC) by facilitating the expression of E-cadherin through the enforced expression of microRNA-101 (miR-101). METHODS: In situ hybridization was conducted with archival tissue using a double digoxigenin-labeled probe. Chromatin immunoprecipitation (ChIP) assay was conducted with EZ-Magna ChIPTM A. Gene profile analysis, Western blot, and immunoprecipitation assays were performed using standard protocols. RESULTS: We found that decreased miR-101 expression observed in archival patient tissues was significantly associated with poor prognosis indicated by low-intensity staining in high-grade tumors. ChIP assays using anti-enhancer of zeste homolog 2 (EZH2) antibodies indicated not only the interaction of EZH2 to the CDH1 (E-cadherin) promoter, but also that this interaction was significantly diminished in cells transfected with pre-miR-101. We observed a global downregulation of trimethylated lysine 27 of H3 histone (H3K27me3) along with upregulation of the enzymes histone deacetylase -1 and -2 with the re-expression of miR-101. Further, we observed lesser levels of transcriptional factors that inhibit the CDH1 promoter with pre-miR-101 treatment. Western blot analysis confirmed the enhanced E-cadherin expression. PANC-1 cells transduced with pre-miR-101 displayed markedly attenuated growth in SCID mice. CONCLUSION: These results suggest the potential therapeutic use of miR-101-enforced expression for inhibition of PDAC.

Laser capture microdissection of pancreatic ductal adeno-carcinoma cells to analyze EzH2 by Western Blot analysis.

Pure populations of tumor cells are essential for the identification of tumor-associated proteins for the development of targeted therapy. In recent years, laser capture microdissection (LCM) has been used successfully to obtain distinct populations of cells for subsequent molecular analysis. The polycomb group (PcG) protein, enhancer of zeste homolog 2 (EzH2), a methyl-transferase that plays a key role in -transcriptional gene repression, is frequently overexpressed in several malignant tumors. High levels of EzH2 are often associated with advanced disease stage in many solid tumors; however, its role in the pathogenesis of pancreatic ductal adeno-carcinoma (PDAC) is poorly understood. Because of the limited sample availability and the absence of in vitro amplification steps for proteins, the use of LCM for proteomics studies largely depends on highly sensitive protein detection methods. Here, we developed a faster and sensitive Western blot protocol and validated it for the detection of EzH2 in ∼2,000 cells. Initially, cultured PANC-1 cells were used to optimize protein electrophoresis and western blotting conditions. Gradient gel electrophoresis in combination with optimized antibody concentrations, and a sensitive chemiluminescent assay provided a strong signal. In order to further confirm the role of EzH2 in PDAC, employing siRNA-mediated gene silencing via long lasting plasmid vectors containing shRNA, we investigated the potential role of EzH2 gene silencing in pancreatic cancer regression. Positive correlation of EzH2 expression was observed with advanced stage, serous histology, and increasing grade in pancreatic cancer patient tissues. Further EzH2 knockdown resulted in decreased cell growth and invasiveness. The findings of this study emphasize that western blotting of a LCM-generated pure population of cancer cells may be a valuable technique for the study of tumor-specific proteins.

Qualitative and quantitative outcomes of audience response systems as an educational tool in a plastic surgery residency program.

BACKGROUND: In-training evaluations in graduate medical education have typically been challenging. Although the majority of standardized examination delivery methods have become computer-based, in-training examinations generally remain pencil-paper-based, if they are performed at all. Audience response systems present a novel way to stimulate and evaluate the resident-learner. The purpose of this study was to assess the outcomes of audience response systems testing as compared with traditional testing in a plastic surgery residency program. METHODS: A prospective 1-year pilot study of 10 plastic surgery residents was performed using audience response systems-delivered testing for the first half of the academic year and traditional pencil-paper testing for the second half. Examination content was based on monthly "Core Quest" curriculum conferences. Quantitative outcome measures included comparison of pretest and posttest and cumulative test scores of both formats. Qualitative outcomes from the individual participants were obtained by questionnaire. RESULTS: When using the audience response systems format, pretest and posttest mean scores were 67.5 and 82.5 percent, respectively; using traditional pencil-paper format, scores were 56.5 percent and 79.5 percent. A comparison of the cumulative mean audience response systems score (85.0 percent) and traditional pencil-paper score (75.0 percent) revealed statistically significantly higher scores with audience response systems (p = 0.01). Qualitative outcomes revealed increased conference enthusiasm, greater enjoyment of testing, and no user difficulties with the audience response systems technology. CONCLUSIONS: The audience response systems modality of in-training evaluation captures participant interest and reinforces material more effectively than traditional pencil-paper testing does. The advantages include a more interactive learning environment, stimulation of class participation, immediate feedback to residents, and immediate tabulation of results for the educator. Disadvantages include start-up costs and lead-time preparation.

Lobular carcinoma in situ.

The diagnosis of lobular carcinoma in situ (LCIS) provokes considerable anxiety in patients owing to misconceptions about this diagnosis. Initially LCIS was considered a premalignant lesion, but it is now a marker of increased risk. The number of women diagnosed with LCIS has increased in recent years most likely owing to more rigorous breast cancer screening. Implications of this diagnosis and management options are discussed in this review.

A phase II study of docetaxel, doxorubicin, and infusional 5-fluorouracil in the treatment of patients with locally advanced breast cancer.

OBJECTIVE: The primary aim of this study was to estimate the rate of clinical and pathologic response to preoperative docetaxel, doxorubicin, and infusional 5-fluorouracil in patients with locally advanced breast cancer. Secondary objective included the determination of toxicity profile. PATIENTS AND METHODS: Thirty-nine patients (median age 49 years) with histologically confirmed locally advanced breast cancer (stage IIIA or IIIB) were studied. Patients received 4 courses of chemotherapy with docetaxel (75 mg/m2 iv over 1 hour), doxorubicin (50 mg/m2 iv bolus), and 5-fluorouracil (300 mg/m2/d as continuous iv infusion on days 1-5). Treatment cycles were repeated every 21 days. Prophylactic filgastrim 5 microg/kg s/c QD was administered to all patients. Definitive surgery was performed after the completion of 4 cycles of therapy. Pathologic complete response was defined as the absence of invasive cancer in both the breast and ipsilateral axillary lymph nodes. RESULTS: The clinical objective response rate (partial plus complete) was 87% (95% confidence interval [CI]: 76-98%). Three patients (8%) had complete pathologic response. Two patients progressed preoperatively. Thirteen patients (33%) developed neutropenic fever. Fifty-three percent of the patients were hospitalized for treatment related complications. No cardiotoxicity or treatment related deaths were observed. CONCLUSIONS: Triple cytotoxic therapy based on concurrent doxorubicin and docetaxel with infusional 5-flourouracil (5-FU) does not appear to significantly improve the pathologic response in patients with locally advanced breast cancer.

Cryotherapy for breast fibroadenomas.

PURPOSE: To assess freezing protocols, imaging, and clinical outcomes of percutaneous ultrasonographically (US)-guided cryotherapy for breast fibroadenomas. MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained. Forty-two biopsy-confirmed fibroadenomas were treated in 29 patients (mean age, 27 years) by using a 2.4-mm cryoprobe inserted into the fibroadenoma with US guidance. The first seven patients underwent conscious sedation, but the other 22 patients required only local anesthesia. US and thermocouple monitoring of the procedure were performed to evaluate freeze protocols based on tumor size. Saline injections protected the skin and/or chest wall. US follow-up was performed at 1 week and at 1, 3, 6, and 12 months. Pre- and 12-month postcryotherapy mammograms were available for seven patients who were over 30 years old. chi(2) and Student t tests were used to assess frequency and mean differences, respectively. RESULTS: The 22 patients who underwent local anesthesia reported minimal discomfort. No significant complications were noted, and patients were very pleased with the resolution of palpable mass effect and cosmetic results. The average pretreatment fibroadenoma volume of 4.2 cm(3)+/- 4.7 (standard deviation) was reduced to 0.7 cm(3)+/- 0.8 at 12-month follow-up (73% reduction, P < .001). US produced excellent ice visualization beyond tumor margins, while thermocouples confirmed cytotoxic temperatures approximately 5 mm behind the visible leading edge. Two patients elected to undergo either removal or biopsy of a residual mass, which revealed a shrunken hyaline matrix with preserved collagenous architecture. Mammograms showed comparable resolution of mass effects with mild surrounding parenchymal reaction. CONCLUSION: Cryotherapy of fibroadenomas is a safe, effective, and virtually painless clinic-based (ie, outpatient) treatment option with good cosmesis.

Correlation of tumor volume and surface area with lymph node status in patients with multifocal/multicentric breast carcinoma.

BACKGROUND: Multicentric breast carcinomas have a higher frequency of axillary lymph node metastasis than unifocal tumors of similar stage. It remains unclear whether this merely reflects larger tumor volumes or a different biologic behavior. The authors have shown previously that when aggregate tumor diameter are used for staging, unifocal and multifocal tumors have a similar frequency of axillary lymph node metastasis. However, summing diameter overestimates actual tumor volume because volume is proportional to the third power of the diameter. Therefore, the aim of the current study was to reanalyze the relation between size and axillary lymph node status by correcting for tumor volumes and surface areas. METHODS: Volumes and surface areas of 122 breast tumor specimens with multiple macroscopic nodules (two foci: n = 95; three foci: n = 22; three foci: n = 5) were calculated by approximating the shape of each tumor nodule to an ellipsoid (for volume) or to a prolate spheroid (for area). For comparison, the authors used an internal control series, comprised of 469 macroscopic unifocal tumors. For all patients, multiple assessments of largest tumor size and combined size of all foci were correlated with the status of axillary lymph nodes. The associations between lymph node status, tumor volume or area, and multifocality were modeled using univariate and multivariate logistic regression. RESULTS: When either the largest or the aggregate tumor volume was used as a size estimate, tumor specimens with multiple nodules had a higher frequency of lymph node involvement compared with unifocal tumors of a similar volume or area. The odds ratio (OR) for having positive lymph nodes was 2.34 for aggregate volume measurement (P < 0.001). Surface area estimates yielded similar results (OR = 2.2, P < 0.001). CONCLUSIONS: Breast tumors with multiple macroscopic nodules had a different biology, with a propensity to dissemination at smaller tumor volumes (i.e., there was another factor besides volume alone that accounted for the differences in behavior).

Histopathologic analysis of atypical lesions in image-guided core breast biopsies.

Appropriate follow-up of patients with needle core breast biopsies (NCBB) showing atypical hyperplasia remains unclear because previous studies show that subsequent open biopsies in variable proportions of these patients reveal ductal carcinoma in situ (DCIS) or even invasive carcinoma, indicating significant sampling artifact. NCBB with diagnoses of atypia were morphologically classified into groups as follows: I, ALH (n = 24); II, ADH with minimal cytologic atypism (n = 90); III, atypia, other (9 columnar, 2 apocrine, 11 atypical papillary); IV, severe ADH/borderline DCIS (n = 31). Mammographic and histologic features, including the number of foci of atypia in the NCBB and the calcification span, were then correlated with presence of DCIS or invasive tumor in subsequent open excisions. Open excisional biopsies showed more severe lesions in 12% of Group I-III cases (8% in Group I, 9% in Group II, and 27% in Group III), of which 15 were DCIS and one was an invasive tubular carcinoma (0.3 cm). Of the DCIS, 60% (n = 9) were < or =5 mm, and 13 of 15 (87%) were low grade. The NCBB cavity was immediately adjacent to the more severe lesions in 88% (n = 14) of cases, in keeping with sampling error. The subset showing severe ADH with borderline nuclear features in contrast was associated with a high likelihood (63%) of DCIS in follow-up excisions. NCBB with atypical papillary features also showed a high frequency of DCIS (4/11, 36%) in subsequent open excisions. Other factors associated with more severe lesions on open biopsy included the number of atypical foci in the NCBB (>4, P <.05) and the mammographic calcification span (>2.0 cm, P <.0001). Atypical lesions diagnosed in NCBB samples are radiographically and morphologically heterogeneous, accounting for the variable frequency of DCIS or invasive neoplasm identified in subsequent open excisions, which are usually focal, low grade, and a consequence of sampling artifact (i.e., adjacent to the NCBB cavity). DCIS is more likely if microcalcifications are mammographically extensive or if atypia is multifocal or is associated with borderline cytologic features.

Histologic and radiographic analysis of ductal carcinoma in situ diagnosed using stereotactic incisional core breast biopsy.

BACKGROUND: Stereotactic incisional core breast biopsy (SCBB) is a highly specific technique for diagnosing ductal carcinoma in situ (DCIS) in patients with suspicious mammographic microcalcifications. However, its sensitivity for excluding the presence of coexisting occult invasive disease in this setting is not fully established. DESIGN: We correlated SCBB findings to subsequent lumpectomy/mastectomy (lx/mx) results in 122 cases of DCIS. In 29 of these cases, the SCBB showed microscopic invasion (n = 15) or foci that were suspicious for invasion (n = 14). Likelihood for invasive disease in subsequent lx/mx samples from each case then was compared with various parameters, including DCIS grade, extent and mammographic findings. RESULTS: Overall, 13% of cases in which the SCBB showed DCIS only (i.e., without any evidence of invasion), had invasive disease in the subsequent excision. This finding was significantly correlated with DCIS grade (low: 0/26 [0%], intermediate: 2/31 [6%], high: 10/36 [28%], P <.001). Invasive lesions were usually small (nine T1a, one T1b, and two T1c) and typically present within more extensive fields of DCIS (no invasion: 1.5 cm DCIS size; invasion: 2.8 cm mean DCIS size, P =.01). This was reflected by greater extent of involvement in the SCBB (5/8 cases with invasion had >15 ducts involved, versus 4/23 with <15 ducts involved, P =.03). SCBB that were suspicious or positive for microinvasion demonstrated invasion in most subsequent excision (susp: 7/14 [50%], microinv: 11/15 [73%]), generally of significant extent (11/18 T(1b-c)). CONCLUSIONS: 1. Patients with SCBB showing high grade DCIS and DCIS suspicious or positive for microinvasion have a significant and high likelihood, respectively, of harboring occult invasive neoplasm. They should accordingly be carefully evaluated radiographically, and possibly with sentinel node biopsy to facilitate axillary staging. 2. Likelihood of occult invasion is correlated with overall DCIS size/extent.

Ethnicity related differences in the survival of young breast carcinoma patients.

BACKGROUND: African-American women face an increased risk of early-onset breast carcinoma compared to white American women, and breast carcinoma has been reported to be particularly aggressive in premenopausal women. METHODS: Surveillance, Epidemiology, and End Results Program data were analyzed for 507 African-American and 1378 white patients from Detroit diagnosed with breast carcinoma under the age of 40 between 1990 and 1999. RESULTS: The proportion of in situ disease detected in African-American patients between 1995 and 1999 nearly doubled compared to the 1990-1994 interval (11.3% compared to 6.4%) but was consistently lower than the proportion of in situ disease seen in white patients for the same intervals (15.7% and 16.4% respectively). Evaluation of patients with invasive disease revealed that African-American patients had larger mean tumor size (3.4 cm versus 2.6 cm; P < 0.001), lower rates of localized disease (42.4% versus 52.1%; P < 0.001), higher rates of estrogen receptor negativity (61.9% versus 44.4%; P < 0.001), and higher proportions of medullary tumors (5.8% versus 3.3%; P = 0.021). Cox proportional hazards survival analysis adjusted for age, tumor size, nodal status, hormone receptor status, and histology showed higher mortality rates for African-American patients at all disease stages. Relative risk of death for African-American patients was 1.94 in patients with localized disease (95% confidence interval [CI], 1.23-3.05), 1.58 for regional disease (95% CI = 1.18-2.11), and 2.32 for distant disease (95% CI = 1.15-4.69). CONCLUSIONS: These findings show that young African-American breast carcinoma patients face an increased mortality risk. Additional studies evaluating risk and treatment response in this subset of patients are warranted.