Search

Factors contributing to the use of preoperative MRI remain poorly understood.Data from a randomized controlled trial of stage 0-3 breast cancer patients undergoing breast conserving surgery between 2016 and 2018 were analyzed.Of the 396 patients in this trial, 32.6% had a preoperative MRI. Patient age, race, ethnicity, tumor histology, and use of neoadjuvant therapy were significant predictors of MRI use. On multivariate analysis, younger patients with invasive lobular tumors were more likely to have a preoperative MRI. Rates also varied significantly by individual surgeon (p 0.001); in particular, female surgeons (39.9% vs. 24.0% for male surgeons, p = 0.001) and those in community practice (58.9% vs. 14.2% for academic, p 0.001) were more likely to order preoperative MRI. Rates declined over the two years of the study, particularly among female surgeons.Preoperative MRI varies with patient age and tumor histology; however, there remains variability by individual surgeon.

BACKGROUND: It is known that breast cancer subtype (e.g., luminal vs. triple negative (TN)) can affect response to systemic therapy and prognosis; however, it is less well-understood whether these subtypes affect margin status and should therefore alter surgical management. METHODS: Data from two randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. The data were restricted to patients who had invasive carcinoma present in the PM specimen, and in whom data for all three receptors (ER, PR and HER-2) were known. Patients were classified as luminal if they were ER and/or PR+, HER-2 enriched if they were ER and PR negative but HER-2 positive, and TN if they were negative for all three receptors. We evaluated the impact of subtype on the margin status at the time the surgeon had completed their standard PM, prior to randomization to CSM vs. no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. RESULTS: 350 patients were included in this cohort for analysis. The median patient age was 64 (range; 32-94 years) and the median invasive tumor size was 1.2 cm (range; 0.6-8.0 cm). 326 (93.1%) were luminal type, 22 (6.3%) were triple negative, and 2 (0.6%) were HER-2 enriched. Subtype was significantly correlated with race (black patients were more likely to have TN disease than white patients, 22.2% vs. 3.8%, p=0.001), palpability (TN tumors were more likely to be palpable than luminal cancers 54.5% vs. 29.8%, p=0.007) and grade (78.9% of TN cancers were high grade vs. 13.5% of luminal cancers p0.05 for all). While patients with TN and HER-2 enriched tumors were more likely to receive neoadjuvant therapy, this did not reach statistical significance (p=0.117). Surgeons were no more likely to take selective margins on the basis of molecular subtype (p=0.413). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate: 33.7% for patients with luminal tumors vs. 36.4% for those with TN tumors, p=0.425). On multivariate regression controlling for molecular subtype, race, grade and palpability, the only factor which predicted positive margin status was grade (p=0.005), with high grade tumors being significantly more likely to have a positive margin than low grade tumors, independent of other factors (OR=3.503, 95% CI: 1.638-7.494, p=0.001). CONCLUSION: While molecular subtype correlates with race, tumor grade and palpability, it does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making. Citation Format: Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-McNatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric Brown, Amanda Mendiola, Mary Murray, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen McGowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura Walters, Tara McPartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar. Does breast cancer subtype impact margin status in patients undergoing partial mastectomy? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-15.

Background Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy. Methods Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. Patients were classified as luminal if they were ER and/or PR positive; HER2 enriched if they were ER and PR negative but HER2 positive; and TN if they were negative for all 3 receptors. The impact of subtype on the margin status was evaluated at completion of standard PM, prior to randomization to CSM versus no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. Results Molecular subtype was significantly correlated with race ( P = .011), palpability ( P = .007), and grade ( P < .001). Subtype did not correlate with Hispanic ethnicity ( P = .760) or lymphovascular invasion ( P = .756). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate 33.7% for patients with luminal tumors vs 36.4% for those with TN tumors, P = .425). Discussion Molecular subtype does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making.

De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation.Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use.Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1).Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients.

Background We sought to determine factors affecting time to surgery (TTS) to identify potential modifiable factors to improve timeliness of care. Methods Patients with clinical stage 0-3 breast cancer undergoing partial mastectomy in 2 clinical trials, conducted in ten centers across the US, were analyzed. No preoperative workup was mandated by the study; those receiving neoadjuvant therapy were excluded. Results The median TTS among the 583 patients in this cohort was 34 days (range: 1-289). Patient age, race, tumor palpability, and genomic subtype did not influence timeliness of care defined as TTS ≤30 days. Hispanic patients less likely to have a TTS ≤30 days ( P = .001). There was significant variation in TTS by surgeon ( P < .001); those practicing in an academic center more likely to have TTS ≤30 days than those in a community setting (55.1% vs 19.3%, P < .001). Patients who had a preoperative ultrasound had a similar TTS to those who did not (TTS ≤30 days 41.9% vs 51.9%, respectively, P = .109), but those who had a preoperative MRI had a significantly increased TTS (TTS ≤30 days 25.0% vs 50.9%, P < .001). On multivariate analysis, patient ethnicity was no longer significantly associated with TTS ≤30 ( P = .150). Rather, use of MRI (OR: .438; 95% CI: .287-.668, P < .001) and community practice type (OR: .324; 95% CI: .194-.541, P < .001) remained independent predictors of lower likelihood of TTS ≤30 days. Conclusions Preoperative MRI significantly increases time to surgery; surgeons should consider this in deciding on its use.

BackgroundRegistries and data sources contain information that can be used on an ongoing basis to improve quality of care and outcomes of people with diabetes. As a specific task of the EU Bridge Health project, we carried out a survey of diabetes-related data sources in Europe.ObjectivesWe aimed to report on the organization of different sources of diabetes information, including their governance, information infrastructure and dissemination strategies for quality control, service planning, public health, policy and research.MethodsSurvey using a structured questionnaire to collect targeted data from a network of collaborating institutions managing registries and data sources in 17 countries in the year 2017.ResultsThe 18 data sources participating in the study were most frequently academic centres (44.4%), national (72.2%), targeting all types of diabetes (61.1%) covering no more than 10% of the target population (44.4%). Although population-based in over a quarter of cases (27.8%), sources relied predominantly on provider-based datasets (38.5%), fewer using administrative data (16.6%). Data collection was continuous in the majority of cases (61.1%), but 50% could not perform data linkage. Public reports were more frequent (72.2%) as well as quality reports (77.8%), but one third did not provide feedback to policy and only half published ten or more peer reviewed papers during the last 5 years.ConclusionsThe heterogeneous implementation of diabetes registries and data sources hampers the comparability of quality and outcomes across Europe. Best practices exist but need to be shared more effectively to accelerate progress and deliver equitable results for people with diabetes.

Background There are several techniques for localization of non-palpable breast tumors, but comparisons of these techniques in terms of margin positivity and volume of tissue resected are lacking. Methods Between 2011-2013 and 2016-2018, 2 randomized controlled trials involving 10 centers across the United States accrued 631 patients with stage 0-3 breast cancer, all of whom underwent breast conserving surgery. Of these, 522 had residual non-palpable tumors for which localization was required. The localization technique was left to the discretion of the individual surgeon. We compared margin positivity and volume of tissue resected between various localization techniques. Results The majority of the patients (n = 465; 89.1%) had wire localization (WL), 50 (9.6%) had radioactive seed (RS) localization, and 7 (1.3%) had Savi Scout (SS) localization. On bivariate analysis, there was no difference in terms of margin positivity (37.8% vs. 28.0% vs. 28.6%, P = .339) nor re-excision rates (13.3% vs. 12.0% vs. 14.3%, P = .961) for the WL, RS, and SS groups, respectively. Further, the volume of tissue removed was not significantly different between the 3 groups (71.9 cm3 vs. 55.8 cm3 vs. 86.6 cm3 for the WL, RS, and SS groups, respectively, P = .340). On multivariate analysis, margin status was affected by tumor size (OR = 1.336; 95% CI: 1.148-1.554, PConclusions While there are a number of methods for tumor localization, choice of technique does not seem to influence volume of tissue resected nor margin status.

BACKGROUND We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM). METHODS One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as

OBJECTIVE Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. METHODS In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. RESULTS Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). CONCLUSION Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.

INTRODUCTION: Routine resection of cavity shave margins has been shown in single center studies to result in a significant reduction in positive margin and re-excision rates. In this prospective multicenter randomized controlled trial, we sought to validate these findings across practice settings. METHODS: Nine centers across the United States, varying in practice setting and patient population, participated in this clinical trial of 398 stage 0-III breast cancer patients undergoing partial mastectomy (with or without resection of selective cavity margins). Participants were stratified by clinical stage and randomized 1:1 to either have routine cavity shave margins resected (“shave”) or not (“no shave”). Randomization group was revealed to the surgeon intraoperatively, after they had completed their standard partial mastectomy and were ready to close. Positive margins were defined as “tumor at ink” for invasive cancer or within 2 mm for ductal carcinoma in situ (DCIS). Adverse events were defined as seromas requiring percutaneous drainage, and/or hematomas or abscesses requiring operative intervention. RESULTS: Median patient age was 65 (range; 29-94). 116 patients had invasive disease, 74 had DCIS, 179 had both, and 29 had no residual cancer at the time of partial mastectomy. The median invasive cancer size was 1.2 cm (range; 0.05-8.00 cm); the median extent of DCIS was 0.9 cm (range; 0.05-6.40 cm). The “shave” and “no shave” groups were well matched at baseline for clinicopathologic and demographic factors. FactorShave (n=197)No Shave (n=201)p-valueAge (years); median (range)67 (36-94)64 (29-89)0.585Race 0.062-- White173 (87.8%)164 (81.6%) -- Black20 (10.2%)33 (16.4%) -- Asian2 (1.0%)2 (1.0%) -- Native American0 (0%)2 (1.0%) -- Unknown/Declined2 (1.0%)0 (0%) Hispanic ethnicity28 (14.2%)32 (15.9%)0.806Invasive tumor size (cm); median (range)1.30 (0.09-8.00)1.20 (0.05-7.50)0.282DCIS extent (cm); median (range)0.80 (0.10-6.40)1.00 (0.05-5.50)0.906Invasive histology 0.556-- Ductal177 (89.8%)186 (92.5%) -- Lobular16 (8.1%)13 (6.5%) -- Mucinous3 (1.5%)2 (1.0%) -- Other1 (0.5%)0 (0%) Neoadjuvant therapy15 (7.6%)19 (9.5%)0.592Palpable tumor57 (28.9%)56 (27.9%)0.825Node positive*24 (16.3%)16 (10.6%)0.175*Of the 298 patients who had lymph nodes evaluated Prior to randomization, positive margin rates were similar in the “shave” and “no shave” groups (38.1% vs. 37.3%, respectively, p=0.918). After randomization, however, those in the “shave” group were significantly less likely than those in the “no shave” group to have positive margins (8.6% vs. 37.3%, respectively, p CONCLUSION: Resection of cavity shave margins significantly reduces positive margin and re-excision rates in patients with stage 0-III breast cancer undergoing partial mastectomy. Citation Format: Chagpar AB, Tsangaris T, Garcia-Cantu C, Howard-McNatt M, Chiba A, Berger AC, Levine E, Gass JS, Gallagher K, Lum SS, Martinez RD, Willis AI, Pandya SV, Brown EA, Fenton A, Mendiola A, Murray M, Haddad V, Solomon NL, Senthil M, Bansil H, Ollila D, Snyder SK, Edmonson D, Lazar M, Namm JP, Li F, Butler M, McGowan NE, Herrera ME, Avitan YP, Yoder B, Dupont E. Does resection of cavity shave margins result in lower positive margin and re-excision rates in patients with stage 0-III breast cancer? Results from a prospective multicenter randomized controlled trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD8-07.

n Abstract: As more women put off pregnancy until their 30s and beyond, the possibility of pregnancy-associated breast cancer (PABC) will rise. Treatment options for patients with PABC need to consider possible harm to the fetus. The goal of this study is to review our institution’s experience with sentinel lymph node (SLN) biopsies in patients with PABC. A prospectively accrued breast Institutional Review Board (IRB) approved data base was searched under separate IRB approval for cases of SLN biopsy in patients with PABC. Ten patients were identified between 1994 and 2006 out of 5,563 patients. A chart review was performed on all 10 patients. Ten patients with PABC and an average gestation age of 15.8 weeks underwent SLN biopsy. All patients successfully mapped. Positive SLN were identified in 5 ⁄ 10 patients (50%) while there was no evidence of metastases in 5 ⁄ 10 patients (50%). 9 ⁄ 10 (90%) of patients went on to deliver healthy children without any reported problems. One patient (10%) decided to terminate her pregnancy in the first trimester following surgery prior to the start of chemotherapy. SLN biopsy can safely be performed in patients with PABC with minimal risk to the fetus. By performing a SLN biopsy, a large proportion of patients with PABC may be spared the risk of a complete axillary lymph node dissection. n

Patients with neurofibromatosis type I and breast cancer represent a subset of people who may be considered at high risk for secondary cancers after conventional whole breast radiation therapy and breast conservation surgery. A case of a 49-year-old woman with neurofibromatosis type I is presented. She was diagnosed with a 1.1-cm right breast infiltrating ductal carcinoma. Clinical, diagnostic imaging, and pathologic features are discussed. Her initial treatment plan of breast conserving therapy was thwarted when her sentinel node biopsy was positive for micrometastatic disease in 1/14 lymph nodes. She elected to have a bilateral simple mastectomy. This case addresses the rare dilemma of offering breast conservation therapy as a viable option for patients with neurofibromatosis type I. Current data on radiation-induced secondary cancers such as sarcoma after treatment for breast and other cancers are reviewed.

The significance of micrometastatic disease in the sentinel lymph nodes (SLN) of patients with invasive breast cancer has been questioned. The objective of our study was to review the impact of micrometastatic carcinoma detected by SLN biopsy.Between January 1997 and May 2004, 2,408 patients with invasive breast cancer and an SLN with micrometastatic (N0[i+], N1mi) or no metastatic (N0[i-]) disease were identified through our breast database. Slide review was performed and reclassified by the 6(th) edition of the American Joint Committee on Cancer Staging Manual. Of these, 27 were excluded from analysis because of evidence of macrometastatic disease on slide review or enrollment in the American College of Surgeons Oncology Group Z10 study.Of 2,381 patients, 2,108 were N0(i-), 151 were N0(i+), and 122 were N1mi. Overall and disease-free survivals of patients with an N1mi SLN were substantially worse than those in patients with an N0(i-) SLN (p0.001 and p=0.006, respectively). Additional positive non-SLNs were identified in 15.5% (15 of 97) of N1mi patients and 9.3% (10 of 107) of N0(i+) patients undergoing completion axillary lymph node dissection. Overall survival of the N0(i+) SLN patients not undergoing axillary dissection was substantially less than those undergoing axillary dissection (p=0.02).Detection of micrometastatic carcinoma (N1mi) in the SLNs of invasive breast cancer patients is a major indicator of poorer survival compared with N0(i-) patients. Although survival of patients with an N0(i+) SLN does not statistically differ from that of N0(i-) patients, 9.3% of these patients had additional axillary nodal disease on axillary dissection, and N0(i+) patients had a decreased survival when axillary dissection was omitted.

Objective: The purpose of our study is to further clarify the incidence of ductal carcinoma in situ (DCIS) patients that are upstaged upon final pathology and/or have metastatic disease in the axilla. Methods: All patients were diagnosed with DCIS or DCIS with microinvasion (DCISm) on their diagnostic biopsy and received a sentinel lymph node (SLN) biopsy between 1994 and 2004. Six hundred seventy-five patients were divided into 613 patients with DCIS and 62 patients with DCISm. Results: Sixty-six of 675 (10%) were upstaged to invasive cancer. Fifty-five of 613 (9%) patients with DCIS were upstaged, whereas 11 of 62 (18%) patients with DCISm were upstaged. Forty-nine of 675 (7%) patients had SLN. Twenty-two of 49 (45%) patients with SLN had invasive carcinoma or DCISm on final histology. Conclusions: After review of histology, grade, type of biopsy, and mammographic findings, the combined findings of high grade, mass by mammography, and microinvasion predict patients at higher risk for invasive carcinoma. Selective utilization of SLN biopsy in DCIS is recommended. © 2005 Excerpta Medica Inc. All rights reserved.

BACKGROUND The current report provides results from a large retrospective analysis of intraoperative imprint cytology performed on axillary sentinel lymph nodes (IICN) removed over the course of 2137 breast surgeries (4905 lymph nodes). It is hoped that these results may serve as benchmarks for those interested in using this technique. METHODS The current study included 2078 patients with T1–2 invasive breast carcinoma who underwent sentinel lymph node biopsy (SLNB) and IICN. Lymph nodes were bivalved, imprinted, stained with Diff-Quik (Baxter Diagnostics, McGaw Park, IL), and reviewed by a cytopathologist. A positive intraoperative diagnosis led to immediate complete axillary lymph node dissection (CALND). On final pathology, lymph nodes found to be negative on hematoxylin and eosin staining were submitted for cytokeratin staining. RESULTS Of the 2137 cases for which SLNB was performed, 673 were found to have positive lymph node status on final pathology. Of these 673 cases, 359 were identified by IICN, resulting in a sensitivity rate of 53.3%. The specificity and overall accuracy rates for this technique were 99.5% and 85.0%, respectively. In IDC cases, IICN had a sensitivity rate of 55.5%, compared with 38.7% in ILC cases. Based on these results, the reoperative CALND rate was calculated to be approximately 14.7%, with 54.5% of these reoperative procedures being performed for cases in which lymph nodes positive only for micrometastases were found. Macrometastasis-positive lymph nodes that went undetected by IICN were present in only 154 of the 2137 cases examined (7.2%). CONCLUSIONS IICN accurately predicts final lymph node status in 85.0% of patients. Although the accuracy of this technique varies with tumor size and type, IICN remains a time-efficient and cost-effective adjunct to SLNB. Cancer (Cancer Cytopathol) 2005. © 2004 American Cancer Society.

The purpose of this study was to determine whether breast cancer patients who had prior breast augmentation presented at a more advanced stage than nonaugmented breast cancer patients, and to determine the mode of presentation and effectiveness of lymphatic mapping and sentinel lymph node biopsy in this same group of patients. A total of 4186 breast cancer patients from 1987 to 2002 were reviewed. Patients who had augmentation before their diagnosis of breast cancer were compared with a control group of nonaugmented breast cancer patients. The Wilcoxon rank sum test was used to compare tumor size, node positivity, and stage. The patient's age at presentation was also compared by the two-sided pooled t test. Seventy-six patients who previously underwent augmentation were identified with 78 breast cancers. Seventy percent (48 of 69) were initially detected by palpation, whereas 30 percent (21 of 69) were initially identified mammographically. Fifty-three percent (n = 41) underwent mastectomy and 47 percent (n = 37) underwent a lumpectomy. This compares with a 63.6 percent (2615 of 4110) breast conservation rate in the nonaugmented population during the same time period. The two groups did not differ regarding (tumor) size (p = 0.77), nodal positivity (p = 0.32), or stage (p = 0.34). The mean time between implant placement and a diagnosis of breast cancer was 14 years. The average age of the patients who had previously undergone augmentation at breast cancer diagnosis was 49.5 years (SD, 9.0 years) versus 57.1 years (SD, 13.5 years) for the nonaugmented patients (p < 0.0001). Forty-nine of the patients underwent lymphatic mapping, with a 100 percent success rate in identifying the sentinel lymph node. There have been no clinically detected axillary recurrences in the patients who had a negative sentinel lymph node biopsy. Breast cancer patients who have undergone previous augmentation are more likely to present with a palpable mass. This initial mode of detection does not appear to translate into a larger tumor size or worse prognosis. Breast conservation and lymphatic mapping can be performed successfully in previously augmented patients.

The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (< or =0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, < or =0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.

Peroxisome proliferator-activated receptors (PPARs) regulate storage and catabolism of fats and carbohydrates. PPARgamma activity increases insulin sensitivity and adipocyte differentiation at the expense of adipogenesis and weight gain. The goal of this study was to 1) clone the promoter of the human adipocyte fatty acid binding protein (aP2) gene, namely fatty acid-binding protein-4, 2) characterize its pharmacological regulation, and 3) determine its putative predictability for adipogenesis. Among the selected PPAR agonists, rosiglitazone and pioglitazone displayed the highest maximal efficacy (E(max)) on reporter-gene assays in COS-7 cells cotransfected by either a galactosidase 4-response element-based or a human aP2 promoter-based Luc reporter vector, along with either chimeric or full-length human PPAR expression plasmids. The non-subtype-selective 2-(4-[2-(3-[2,4-difluorophenyl]-1-heptylureido)ethyl]phenoxy)-2-methyl-butyric acid (GW-2331) and the compounds [4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propoxyl]phenoxy]-acetic acid (L-165041), (4-((2S,5S)-5-(2-(bis(phenylmethyl)amino)-2-oxoethyl)-2-heptyl-4-oxo-3-thiazolidinyl)butyl)-benzoic acid (GW-0072), and indomethacin behaved as partial agonists relative to pioglitazone in full-length human aP2-PPARgamma2. Beyond their partial PPARgamma agonist properties, these compounds elicited a lower maximal up-regulation of mouse aP2 mRNA in 3T3-L1 adipocytes as compared with pioglitazone; these properties paralleled a time-dependent increase in neutral lipids. By contrast, the selective PPARalpha agonist 2,2-dichloro-12-(4-chlorophenyl)dodecanoic acid (BM-17.0744) neither stimulated the human aP2-PPARalpha promoter reporter-gene assay, thus demonstrating a specific interaction between PPARgamma and the aP2 promoter, nor affected lipogenesis in 3T3-L1 cells. Altogether, these data characterized a functional promoter of the human aP2 gene; its in vitro pharmacological regulation in PPARgamma-mediated reporter-gene assay may represent an interesting complement or an alternative to time-consuming procedures aiming at discriminating PPAR ligands with low lipogenic properties.

Study objectives Tumor necrosis factor (TNF)-α has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-α, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and interferon (IFN)-γ cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. Design Prospective, observational study. Setting Thirty-one bed, university, medicosurgical department of intensive care. Patients Thirty-three adult patients with cardiogenic shock of recent ( Interventions None. Measurements and results TNF-α, IL-6, IL-10, TGF-β1, and IFN-γ plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-α within the promoter at position −308a→g, IL-6 within the promoter at position −174c→g, IL-10 within the promoter at position −1082a→g/-819t→c and −819t→c/-592a→c, TGF-β1 at codon 10t→c and codon 25c→g, and IFN-γ at intron 1 at position + 874t→a were studied. The 33 patients had a mean (± SD) age of 64 ± 17 years and a mean simplified acute physiology score II of 62.3 ± 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-α levels between the TNF-1 and the TNF-2 groups, but TGF-β1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-γ polymorphism was less common in the cardiogenic shock group (p = 0.034). Conclusions Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock.

Background The purpose of this study was to determine the difference in clinical outcomes for patients with histologically positive sentinel lymph nodes (SLN+) compared with patients with histologically positive nonsentinel second echelon lymph nodes (NSLN+). Methods Eight hundred thirteen node positive patients from a prospectively accrued database of 3,200 patients who underwent sentinel node mapping were evaluated. In all, 506 of the 813 patients (62%) were SLN+ only and 307 of the 813 patients (38%) were SLN+ plus at least one NSLN+. Patients' overall survival and disease-free survival were obtained and statistical analyses performed comparing the two groups. Results As the number of NSLN+ increased, there was a significant difference in disease-free survival ( P = 0.001) and overall survival ( P = 0.003) between those patients who had 0 to 4 NSLN+ and those who had 5 or more NSLN+. The SLN+ only patients did not show significant differences with respect to survival, based on the number of SLN+ (overall survival, disease-free survival; P = 0.742) Conclusions The survival (overall survival, disease-free survival) for patients with 3 or more SLN+ was not statistically different than for patients with 1 or 2 SLN+ ( P = 0.742). However, an alteration of biologic behavior was observed when multiple NSLN+ contain metastatic breast cancer. Involvement of 5 or more NSLN+ portends a significantly ( P = 0.001) worse prognosis, regardless of the number of SLN+.

Objective: To document the incidence of metastatic disease in complete axillary lymph node dissections (CALND) of patients with invasive carcinoma after a sentinel lymph node (SLN) biopsy, positive only by immunohistochemical staining for cytokeratin (CK-IHC). Methods: Sections of all SLNs, negative by routine histology, were immunostained and examined for cytokeratin positive cells. Sections of lymph nodes from CALND specimens were interpreted using routine hematoxylin and eosin (H&E) staining. Results: A total of 409 patients (29.6%) had metastatic disease in at least one sentinel lymph node on H&E examination. Of 971 H&E negative patients, 78 (8.0%) were positive only by CK-IHC. Sixty-two of the CK-IHC positive only patients underwent CALND. Nine of these 62 patients (14.5%) had metastases identified in the CALND specimen. Conclusions: Because 14.5% of patients with invasive breast cancer and SLNs positive only by CK-IHC were found to have H&E positive lymph nodes on CALND, we conclude first, that CK-IHC should be used to evaluate SLNs, and second, that CALND should be considered when SLNs are positive by CK-IHC only. This approach will result in an absolute reduction of the false negative rate (absolute false negative rate reduced by 2.6% in our series).

Age and body mass index (BMI) have been shown to correlate with an increased incidence of failure in identifying a sentinel lymph node (SLN). Mapping senior, overweight adults is common; therefore, the relationship of patient age and BMI on SLN biopsy success is essential. This study examines the mapping failures as they relate to age and BMI. From April 1994 to May 1999, patients underwent an injection of radiocolloid (450 mci) and blue dye (5 cc) prior to SLN biopsy. SLN biopsy failure was defined as lymph nodes being unidentifiable by blue dye or having an in vivo node radiocolloid count of less than 3:1 over background count. BMI was measured as (weight in pounds)(703)/(height in inches)(2); 1,356 patients were attempted for SLN mapping, and 54 failed (3.98%). The radioactive node count was inversely proportional to age ( p < 0.0001). The radioactive node count decreased by a mean of 34 counts per node with each additional year ( p < 0.001). The estimated odds ratios for success were 0.945 for age and 0.946 for BMI. Therefore, every increase of 1 year of age or one unit of BMI decreased the odds of success by approximately 5%. The mean BMI was 29.54 in failed patients and was 26.42 in successful mapping patients ( p = 0.042). Surgeons should be aware that node counts will decrease with increasing age and that increased age and BMI are potential risk factors for SLN mapping failure. However, increased age and/or BMI alone do not appear to be contraindications for SLN biopsy in older or overweight patients.

Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989 +/- 111 s in the vehicle group to 79 +/- 59 s with F 16915, P < 0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P < 0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6 +/- 7.4 %, n = 9 vs 17.6 +/- 3.4 %, n = 9 in the vehicle group, P < 0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.

Lymphatic mapping (LM) for breast cancer has made internal mammary node (IMN) detection practical and dependable. This study demonstrates the necessity of IMN removal when suggested by intraoperative radioguided surgery detection.From April 1998 to July 2000, 1273 patients underwent LM for breast cancer. LM was performed using the combined dye and radiocolloid technique. Patients were scanned operatively with a gamma probe over the IMN area, and most underwent preoperative lymphoscintigraphy. Nodes were removed from patients in whom radioactivity was detected in the internal mammary area.Thirty of the 1273 (2.4%) patients mapped had at least one IMN removed. Twenty-two of 30 (73.3%) had inner quadrant lesions. Five of 30 (16.7%) patients had IMNs that were positive for metastatic disease. Three of these five had no metastatic spread to the axillary sentinel lymph node (SLN). One of thirty (3.3%) patients with IMN localization had neither hot nor blue nodes detected in an SLN procedure.Radioguided SLN detection should be attempted in the IMN basin with all tumors. If an IMN is identified, it should be removed. IMN biopsy is a feasible, low-risk procedure when directed by radioguided LM and provides a guide for radiotherapy for patients with positive IMNs.

Background: Ductal carcinoma in situ (DCIS) is detected more often since the advent of mammography. A standardized pathologic staging and grading system does not exist, but nuclear grade is assuming greater importance. The history of DCIS is long, and its treatment is a controversial issue in breast cancer today. Methods: Data have been reviewed regarding the role of HER-2 expression as a prognostic variable, as a predictive factor for response to chemotherapy and hormonal therapies, and as a directed therapeutic target for breast cancer. Results: The NSABP protocol B06 revealed a recurrence rate of 43% in patients treated with local excision alone. Half of recurrences are still DCIS, but 50% are invasive. Local control is markedly improved by the addition of radiation. Recurrence is also minimized by careful cytologic review of margins. Sentinel lymph node biopsy has resulted in more accurate nodal staging. Conclusions: As a heterogeneous lesion, DCIS may not lend itself to a uniform treatment approach. Careful analysis of resection margins is required. As our understanding of the diagnosis and treatment of this disease develops, a coordinated team approach is optimal.

Serious limband life-threatening thromboembolic complications may result from immune-mediated, heparin-induced thrombocytopenia (HIT) type II. The authors describe three such cases associated with devastating outcomes. The clinical diagnosis of HIT II was based on (1) falling platelet count on heparin (< 150,000/mm3), (2) thromboembolic events on heparin, and (3) absence of new thrombotic events after heparin discontinuation. These distinct case presentations are discussed to broaden clinical awareness of HIT II. A high index of suspicion is warranted to prevent this catastrophic complication.

The affinity of rifampin to bond to Dacron permits implantation of a vascular prosthesis with anti-staphylococcal bioactivity. The performance of rifampin-bonded Dacron grafts was evaluated in vitro and in vivo to develop a bonding technique with optimal graft bioactivity which was then used for in situ reconstruction of a biofilm graft infection. In vitro bioactivity was measured at 24-hr intervals for three types of Dacron prostheses (plain, gelatin, and collagen-impregnated) exposed to rifampin at varied concentrations and immersion times. Gelatin-impregnated grafts demonstrated superior bioactivity (P < 0.05). Rifampin concentration and graft type had a greater effect on bioactivity than immersion time (P < 0.01). Gelatin-impregnated grafts immersed in a 60 mg/ml rifampin solution for 15 min produced optimum bioactivity. Six grafts prepared in this fashion were used to replace the canine aorta. The level and duration of in vivo antistaphylococcal activity to Staphylococcus aureus and Staphylococcus epidermidis were less (P < 0.05) than those measured in vitro, but rifampin levels exceeded the study strain maximum inhibitory concentration for up to 48 hr. In a canine model, the rifampin-bonded gelatin-impregnated (N = 14) or nonbonded control (N = 10) grafts were used as in situ replacement for an established aortic graft infection caused by S. epidermidis. Replacement with a rifampin-bonded graft resulted in successful anatomic healing of perigraft and anastomotic tissue. Persistent biofilm colonization was confirmed in 8 of 10 controls versus 4 of 14 rifampin-bonded grafts (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

573 Background: Squamous cell carcinoma of the anal canal will be diagnosed in 28,000 individuals globally. Considered a rare cancer, the incidence of anal carcinoma continues to rise annually. Majority of patients present with locally advanced disease in which concurrent chemoradiation (CRT) will be provided with curative intent. The Anal Cancer IRCI Working Group was created to pursue novel approaches to the diagnosis, treatment, and surveillance of patients. Yet, surveillance following completion of CRT is not well established and varies as per NCCN (v2.2015) and ESMO guidelines. Methods: A 22-question survey provided to anonymous international GI subspecialists in various fields. Questions pertained to timing and type of diagnostic imaging, surveillance interval, approach to detection of complete response (CR), and prevention of sexual dysfunction. Results: Survey distribution was initiated in March 2015 and still ongoing. Thus far, 96 physicians responded. Conclusions: Carcinoma of the anal canal continues to rise in incidence annually. Surveillance following completion of CRT is warranted; however, global variability in practice patterns for surveillance exists. As such, the IRCI Anal Cancer Working Group intends to provide an international consensus surveillance statement. [Table: see text]

Atherosclerotic complications are related to the unstable character of the plaque rather than its volume. Vulnerable plaques often contain a large lipid core, a reduced content of smooth muscle cells (SMCs), and an accumulation of inflammatory cells. Regulation of this inflammatory response is an essential element in chronic inflammatory diseases such as atherosclerosis. Nuclear receptors and particularly peroxisome proliferator-activated receptors (PPARs) have emerged as therapeutic targets with a widespread impact on the treatment of metabolic disorders because they can modulate gene expression involved in lipid and glucose homeostasis and can exert anti-inflammatory properties. However, little is known about nuclear receptor effects on SMC inflammation, which produces large amounts of IL-6 and prostanoids. The aim of this study was to evaluate anti-inflammatory properties of nuclear receptor activators in a human physiological SMC model. We show that PPAR activators, as well as liver X receptor alpha, farnesoid X receptor and retinoid X receptor alpha activators, inhibit IL-1beta-induced SMC 6-keto PGF1alpha synthesis, an index of cyclooxygenase (COX)-2 activity, with IC(50) between 1 and 69 microM. In contrast, PPARgamma activators, as exemplified by rosiglitazone and pioglitazone, were unable to inhibit cytokine-induced 6-keto PGF1alpha synthesis. We also demonstrate for the first time that the COX-2 inhibitor rofecoxib can reduce 6-keto PGF1alpha production by both enzymatic inhibition and transcriptional repression. These results show that some nuclear receptor activators have SMC anti-inflammatory properties due to COX-2 inhibition which could participate in their anti-atherosclerotic properties beyond lipid impacts.

TPS792 Background: Metastatic squamous cell carcinoma of the anus (SCCA) is a rare condition with 5-year overall survival (OS) rate of 32%. CDDP/5-FU is commonly used in the first-line treatment of patients with ILR or metastatic disease. This practice is based on retrospective series and data from randomised trials are lacking. Recent retrospective studies showed promising activity of CBDCA/PTX in this setting. Methods: InterAACT is an international, multicentre, open label, randomised phase II trial comparing two chemotherapy regimens in patients with ILR or metastatic SCCA. Eligible patients are randomised in a 1:1 ratio to CDDP (60 mg/mq, D1q21) plus 5-FU (1000 mg/mq/24h, D1-4q21) or CBDCA (AUC 5, D1q28) plus PTX (80 mg/mq, D1,8,15q28). Stratification factors are: performance status, extent of disease, HIV status and country. The primary endpoint is response rate (RR). Secondary endpoints include progression-free survival, OS, toxicity and quality of life. Based on a RR estimate of 40% in the CDDP/5-FU arm 80 patients are to be recruited to detect 10% difference in RR between the two arms with 80% power (phase II selection trial design). Correlative biomarker analyses are planned in tumour tissue and blood samples. The trial is sponsored by The Royal Marsden NHS Foundation Trust and endorsed by the International Rare Cancer Initiative (IRCI) group. Approximately 50 centres in the UK, Europe (EORTC), Scandinavia, US (ECOG-ACRIN) and Australia (AGITG) are estimated to participate and recruitment is anticipated to be completed within 3 years. Recruitment started in December 2013. As of September 16, 2014, 6 sites in the UK are open to recruitment and 6 patients have been randomised (3 to CDDP/5-FU and 3 to CBDCA/PTX). InterAACT aims to provide the first randomised evidence for the treatment of ILR and metastatic SCCA, to identify the optimal chemotherapy backbone to combine with targeted agents in future studies and to confirm the feasibility of conducting an international multicentre trial for this rare tumour. Clinical trial information: NCT02051868.

Sentinel lymph node (SLN) biopsy combined with microstaging-associated immunohistochemical staining for cytokeratin more accurately assigns patients to their corresponding diagnostic stage. The purpose of this study was to compare the survival outcomes of node-negative patients who received an SLN biopsy with historical control data of node-negative patients who received routine complete axillary lymph node dissection (CALND) in the pre-SLN biopsy era.Under institutional review board approval, 2458 node-negative invasive breast cancer patients between the ages of 25 and 94 years (mean, 60 years) were treated at our institution from January 1986 to May 2004. Of these 2458 patients, 604 (25%) were evaluated with CALND, whereas 1854 (75%) were evaluated with SLN biopsy. All were treated according to the current stage-specific guidelines. Kaplan-Meier graphs of overall survival and disease-free survival were constructed for each group of patients, and the two groups were compared by using the log-rank test.Overall survival and disease-free survival for the CALND and SLN biopsy groups did not differ significantly (P = .98). The average number of lymph nodes extracted in the pre-SLN biopsy group was 18, whereas the average number of SLNs extracted in the post-SLN biopsy group was 3.The survival rate among node-negative breast cancer patients who received an SLN biopsy alone has proven to have no significant difference (P = .98) from the survival rate among node-negative patients who received a CALND. SLN biopsy alone should replace CALND as the primary tool for axillary staging of breast cancer in node-negative patients.

The current report provides results from a large retrospective analysis of intraoperative imprint cytology performed on axillary sentinel lymph nodes (IIC(N)) removed over the course of 2137 breast surgeries (4905 lymph nodes). It is hoped that these results may serve as benchmarks for those interested in using this technique.The current study included 2078 patients with T1-2 invasive breast carcinoma who underwent sentinel lymph node biopsy (SLNB) and IIC(N). Lymph nodes were bivalved, imprinted, stained with Diff-Quik (Baxter Diagnostics, McGaw Park, IL), and reviewed by a cytopathologist. A positive intraoperative diagnosis led to immediate complete axillary lymph node dissection (CALND). On final pathology, lymph nodes found to be negative on hematoxylin and eosin staining were submitted for cytokeratin staining.Of the 2137 cases for which SLNB was performed, 673 were found to have positive lymph node status on final pathology. Of these 673 cases, 359 were identified by IIC(N), resulting in a sensitivity rate of 53.3%. The specificity and overall accuracy rates for this technique were 99.5% and 85.0%, respectively. In IDC cases, IIC(N) had a sensitivity rate of 55.5%, compared with 38.7% in ILC cases. Based on these results, the reoperative CALND rate was calculated to be approximately 14.7%, with 54.5% of these reoperative procedures being performed for cases in which lymph nodes positive only for micrometastases were found. Macrometastasis-positive lymph nodes that went undetected by IIC(N) were present in only 154 of the 2137 cases examined (7.2%).IIC(N) accurately predicts final lymph node status in 85.0% of patients. Although the accuracy of this technique varies with tumor size and type, IIC(N) remains a time-efficient and cost-effective adjunct to SLNB.

Lymphatic mapping redefined the clinical significance of axillary lymph nodes in the treatment of breast cancer. Current literature supports the concept that any patient diagnosed with invasive breast cancer should in fact have their sentinel lymph nodes evaluated. However, there are many cases of " special situations in lymphatic mapping " . These special situations mark an important point that should be considered: When and who should undergo lymphatic mapping? A summary of these considerations/cases will be the focus of this report.

Background Frozen section and intraoperative imprint cytology (IIC N ) are 2 methods used for intraoperative pathologic assessment of sentinel lymph nodes (SLNs). The SLN evaluation of patients with invasive lobular carcinoma (ILC) results in a relatively high number of false-negative results using either of these methods. The purpose of this study was to evaluate the added benefits that intraoperative immunohistochemical-cytokeratin staining (I CK-IHC ) can bring to IIC N in the evaluation of SLN in patients with ILC. Methods A total of 59 breast cancer patients with ILC underwent an SLN biopsy evaluated by our standard IIC N assessment in addition to I CK-IHC . The results of IIC N with I CK-IHC were compared with the final histopathologic assessment consisting of standard hematoxylin and eosin staining and additional cytokeratin staining of nodes. Results Intraoperative evaluation of SLN using IIC N and I CK-IHC correctly diagnosed the nodal status in 45 of 59 (76.3%) patients. On final histopathologic assessment, 31 of 59 (52.5%) patients were found to have positive nodes. Using I CK-IHC , 17 of these 31 positive cases (54.8%) were detected.Using IIC N alone, without the benefit of I CK-IHC , only 13 of 31 (41.9%) positive cases were detected intraoperatively. Conclusions For patients with ILC, I CK-IHC staining in addition to IIC N improves accuracy over using IIC N alone. In this study, I CK-IHC staining demonstrated a 12.9% improvement in the detection of SLN metastases in patients with ILC. Cytopathologists should consider employing I CK-IHC staining to evaluate the touch-imprint slides of SLN in ILC patients.

Background: This is a follow-up study to our previously reported data on local recurrence rates in patients whose lumpectomy margins were evaluated by intraoperative imprint cytology (IIC M ). The purpose of this study was to compare local recurrence rates for patients whose lumpectomy margins were evaluated with IIC M with local recurrence rates of those not evaluated by IIC M . Methods: A total of 1713 patients underwent lumpectomy treatment for breast cancer from 1988 to 2001 were prospectively entered into a computerized database and subsequently included in this study. Of the patients, 520 (group 1) had their surgery performed at an outside institution where conventional margin analysis was performed. Another 1193 (group 2) had their surgery performed at our institution where margins were evaluated by IIC M . For each histologic type and for the overall sample, probabilities of recurrence with time were estimated using the method of Kaplan and Meier. Results: IIC M overcomes sampling error inherent in the frozen section analysis and results in a diminished incidence of overall 5-year local recurrence from 8.8% to 2.8% (P 0.0001). The recurrence rates for each respective histologic subtype are reported for both absolute recurrences and probability of recurrence with time. Conclusions: IIC M provides an accurate evaluation of lumpectomy margins for patients undergoing breast-conservation treatment. IIC M was associated with an overall lower local recurrence rate. This series defined the utility of intraoperative imprint cytology for evaluation of margins in patients undergoing breast-conservation treatment. © 2004 Excerpta Medica, Inc. All rights reserved.

Objective To investigate the incidence of nodal metastasis in a consecutive series of patients treated at the authors' institution with highly selective criteria, and to determine the impact that lymphatic mapping and sentinel node biopsy have on the detection of nodal metastases in this carefully selected patient population. Methods Study patients were selected from the 7,750 breast cancer patients entered into the authors' database from April 1989 to August 2001, based on the following criteria: nonpalpable, T1 a and T1 b, non-high nuclear grade tumors, without lymphovascular invasion. Results Of the 7,750 patients in the database 1,327 (17%) were found to have T1 a and T1 b lesions. Three hundred eighty-nine patients were confirmed to meet all four selection criteria. This represents 5% (389/7,750) of the authors' breast cancer patients and 29.3% (389/1,327) of the authors' T1a/T1 b tumors. One hundred sixty patients were diagnosed before routine use of lymphatic mapping, and only one patient had a positive axillary lymph node. Two hundred twenty-nine patients underwent lymphatic mapping and sentinel lymph node biopsy, and 10 had a positive axillary lymph node. The difference in proportions of nodal positivity between the mapped and unmapped patients was significant. Conclusions This study clearly demonstrates the ability of lymphatic mapping and a more detailed examination of the sentinel node to increase the accuracy of axillary staging. It has been argued that this highly selected group of breast cancer patients possessing retrospectively identified favorable characteristics does not require axillary staging. This select population represents only 5% of breast cancer patients in this series, and the authors do not believe they can be accurately identified preoperatively. Therefore, the authors strongly argue for evaluation of the axillary nodal status by lymphatic mapping.

Endothelium injury is a primary event in atherogenesis, which is followed by monocyte infiltration, macrophage differentiation, and smooth muscle cell migration. Peroxisome proliferator-activated receptors (PPARs) are transcription factors now recognized as important mediators in the inflammatory response. The aim of this study was to develop a human endothelial model to evaluate anti-inflammatory properties of PPAR activators. PPAR proteins (alpha, delta and gamma) are expressed in EAhy926 endothelial cells (ECs). Pirinixic acid (Wy-14643), fenofibrate, fenofibric acid, the Merck ligand PPARdelta activator L-165041, 15-deoxy-Delta(12,14)-prostaglandin J2, but not rosiglitazone (BRL-49653) inhibited the induced expression of vascular cell adhesion molecule-1 (VCAM-1), as measured by enzyme linked immunosorbent assay (ELISA), and monocyte binding to activated-EAhy926 cells. The PPARdelta activator L-165041 had the greatest potency to reduce cytokine-induced monocyte chemotactic protein-1 (MCP-1) secretion. All PPAR activators tested which impaired VCAM-1 expression reduced significantly nuclear p65 amount. These results show that EAhy926 endothelial cells are an adequate tool to substantiate and characterize inflammatory impacts of PPAR activators.

Background: The surgical management of breast cancer has changed markedly with the development of lymphatic mapping and sentinel lymph node (SLN) biopsy. Lymphatic mapping technique varies with respect to injection method, mapping agent, and surgical technique. The decision to pursue the internal mammary nodes (IMN) is another source of controversy. Methods: From April 1998 to November 2000, 1,470 patients underwent lymphatic mapping for breast cancer and were prospectively entered into the breast database. The combined technique method was used, consisting of both isosulfan blue dye and technetium-99 labeled sulfur colloid. Patients with inner quadrant lesions and suspicion for internal mammary metastasis had preoperative lymphoscintigraphy. Those with internal mammary radioactivity noted by either lymphoscintigraphy or gamma probe underwent removal of the internal mammary sentinel nodes. Results: Thirty-six of the 1,470 (2.4%) patients mapped had at least 1 internal mammary lymph node removed. Inner quadrant lesions were present in 24 of the 36 (67%) IMN mapped patients. Of the 36 patients mapping to the IM area, 5 (14%) had at least 1 IM node positive. Two of the 5 (40%) had only IM metastasis, with 1 of these patients having 5 of 5 IMN positive and no disease detected in her axilla. A total of 2 of the 5 (40%) IM positive patients had more than 1 IMN positive. Twenty-eight of the 36 (78%) IM node harvested patients had preoperative lymphoscintigraphy, with 18 (64%) IMN appearing on imaging. Complications occurred in 3 of the 36 (8%) IMN mapped patients, without clinical significance. Conclusions: Mapping to the IMN basin with the finding of metastasis results in N3 disease by the current staging system. The consequence for these patients is radiation therapy to the IMN basin. It is significant to note that 14% (5 of 36) were upstaged as result of IMN detection and 40% (2 of 5) had multiple positive IMNs. Substantial disease was detected in these 5 patients necessitating additional radiation therapy while avoiding IM radiation and its attendant complications in 86% of patients mapping to the IM basin.

Regional nodal status is the most powerful predictor of recurrence and survival in women with breast cancer. Lymphatic mapping and sentinel lymph node (SLN) biopsy have been found to accurately predict the regional nodal status. Preoperative lymphoscintigraphy has been used in melanoma patients to identify the basins at risk for metastases when primary sites are located in watershed areas of the body. This study was performed to define the role of lymphoscintigraphy for axillary nodal staging in women with breast cancer. Specifically, can preoperative lymphoscintigraphy define a population of women with breast cancer who have multidirectional drainage or who do not drain to the axilla and need no axillary dissection?516 patients with invasive breast cancer were accrued in a national breast lymphatic mapping trial sponsored by the U.S. Department of Defense. Preoperative lymphoscintigraphy images were produced using filtered technetium-99 sulfur colloid. Lymphatic drainage to axillary and internal mammary sites was noted.Drainage to an axillary SLN was found in 335 (65%) patients, and internal mammary or extra-axillary drainage was noted in 52 (10%) patients. By using sensitive hand-held probes and vital blue dye intraoperatively, the overall success rate of finding an axillary SLN was 85%. Of the 335 patients who had an axillary SLN identified with imaging, all had successful SLN biopsy procedures. Although no SLNs could be imaged in 181 patients, 153 (85%) of these patients had an axillary SLN identified with intraoperative mapping. For 28 patients in which lymphoscintigraphy was negative and intraoperative mapping was unsuccessful, complete axillary node dissection was performed, and 13 (46%) of these patients were found to have metastatic disease in the basin.Preoperative lymphoscintigraphy can identify those women with primary breast cancers who have extra-axillary regional basin drainage such as internal mammary. The ability to image an axillary SLN was associated with a high success rate of being able to find the node intraoperatively with a combination mapping technique. In a high percentage of patients with negative lymphoscintigraphy, the SLN was identified with more sensitive hand-held probes. Therefore, patients who have a negative preoperative lymphoscintigraphy and intraoperatively are found to have no "hot" spot in the axilla with the hand-held probe still need an axillary node dissection, because 46% of these patients contain metastatic disease in the axilla.

Introduction. To date, studies of breast cancer lymphatic mapping (LM) have analyzed success with respect to individual surgeons. However, LM and sentinel lymph node biopsy (SLNBx) are procedures that require institutional multidisciplinary cooperation between the departments of radiology, pathology, and surgery. Thus, it is important to evaluate these procedures with respect to the institution. This study examines 30 institutions to clarify the value of the institutional volume index (IVI) (cases/month) to the outcome of LM and SLNBx in breast cancer. Methods. From July 1997 to July 1999, 30 institutions participated in the Department of Defense national breast LM trial. All participants underwent a 2-day training course for surgeons, nuclear medicine physicians, and pathologists. The records for each institution were prospectively accrued and submitted to a database. The false negatives, failure rates, and IVI were calculated for each institution. A logistic regression model plots the relationship between IVI and institutional failure rate. Using a multivariate analysis, mapping failure was analyzed as a function of case number with respect to the individual surgeon and the institution as a whole. Results. False negative results were demonstrated in only 5 (4%) cases among all institutions and were excluded from further analysis due to small numbers. Mapping failures were found in all but 7 of the 30 institutions whose data were complete. There were 71 mapping failures among 74 surgeons over 555 cases, which yielded an overall failure rate of 12.79% (71 555). The logistic regression model revealed an inverse relationship between IVI and institutional failure rate. However, the multivariate analysis revealed that the individual surgeon performance was the most significant factor in determining institutional mapping success. Conclusion. Failure to map can be a function of multiple factors including surgical skill, surgical volume index, and injection method of the SLN patient, all under the quality control of an institution. The surgical failure rate on the other hand is a function of surgical skill, surgical volume, and injection methods. While differences in mapping success exist across institutions, this disparity is not due to factors associated with the institution as a whole, but lie with the individual surgeon.

Indications for prophylactic mastectomy (PM) range from LCIS to BRCA 1-2 positive, cosmesis, and cancer phobia. Occult cancers have been found in up to 5% of PM cases. Consequently, consideration must be given to the role of sentinel lymph node (SLN) biopsy as a diagnostic procedure in these patients as PM excludes the subsequent option of SLN biopsy.From April 1994 to November 1999, all patients undergoing PM had SLN biopsy after four quadrant periareolar injections of radiocolloid (450 mci) and blue dye (5 cc). All patients were prospectively accrued to the computerized database of breast patients. The SLN were all evaluated with hematoxylin and eosin (HE) as well as CAM5.2 cytokeratin immunohistochemical (CK-IHC) stains.Over a 67-month period, 1,356 patients were mapped; 57 patients underwent PM in which 148 nodes (2.6 nodes per patient) were evaluated. Nodes were examined by routine HE and CK-IHC staining. Two patients, neither of whom was found to have a cancer in the prophylactic mastectomy breast, were found to have a positive SLN by CK-IHC staining. Infiltrating carcinoma was discovered within the PM breasts of 2 additional patients. Sentinel lymph node biopsy was negative for malignancy by HE as well as CK-IHC stains. No lymphedema has been detected in PM patients.Sentinel node biopsy has been shown to be an accurate and minimally invasive method of evaluating the lymphatic basin. This study shows that the absence of known disease within the breast does not preclude the presence of occult cancer or metastatic nodal disease. Four patients (7%) had a significant change in their surgical management as a direct result of sentinel lymph node biopsy. Two patients were spared the complications of a complete axillary node dissection. This minimally invasive procedure accurately evaluated the known disease status and provided new diagnostic information. Most important, once a mastectomy is performed, the opportunity for SLN biopsy is lost should a cancer be found within the breast specimen.

The small number of nodes harvested with lymphatic mapping and sentinel lymph node (SLN) biopsy has allowed a more detailed pathologic examination of those nodes. Immunohistochemical stains for cytokeratin (CK-IHC) have been used in an attempt to minimize the false negative rate for SLN mapping. This study examines the value of CK-IHC positivity in predicting further lymph node involvement in the axillary basin. From April 1998 through May 1999, 519 lymphatic mappings and SLN biopsies were performed for invasive breast cancer. SLNs were examined by imprint cytology, hematoxylin and eosin (H&E), and CK-IHC. Patients with evidence of metastatic disease by any of the above techniques were eligible for complete axillary node dissection (CAND). The frequency with which these modalities predicted further lymph node involvement in the axillary basin was compared. Of the 519 lymphatic mappings, 39 patients (7.5%) had a CK-IHC-positive-only SLN. Five (12.8%) of these 39 patients had at least 2 SLNs positive by CK-IHC. Twenty-six of the CK-IHC-positive-only patients underwent CAND. Three of these 26 patients (11.5%) had additional metastases identified after CAND. The sensitivity levels with which each modality detected further axillary lymph node involvement were as follows: CK-IHC, 98 per cent; H&E, 94 per cent; and imprint cytology, 87 per cent. A logistic regression to compare the prognostic value of the three modalities was performed. All were significant, with odds ratios of 19.1 for CK-IHC ( P = 0.015), 5.3 for H&E ( P = 0.033), and 3.86 for imprint cytology ( P = 0.0059). These data validate the enhanced detection of CK-IHC for the evaluation of SLNs. Detection of CK-IHC-positive SLNs appears to warrant CAND in patients with invasive breast cancer. However, the therapeutic value of CAND or adjuvant therapies based on CK-IHC-positive SLNs would be best answered by prospective randomized trials.

Breast cancer presenting as axillary adenopathy without radiographic or clinical breast abnormality is a rare entity accounting for less than 1% of all breast cancers.[1,2] In the past, extended searches for an extramammary site were conducted, but this extensive workup was unproductive and therefore not recommended.[3] Most authors currently advise that carcinoma found in an axillary node in a woman should be treated as breast cancer even in the absence of clinical or mammographic findings.[3] The recommended treatment is mastectomy. Tumors that are not recognized by mammography or clinical observation have been treated recently with breast preservation consisting of total breast irradiation with 50 Gy to 55 Gy. A 12% local recurrence rate was found compared with 56% in the nonirradiated breast. [4] A specific and sensitive diagnostic modality to locate an occult tumor is needed for breast conservation.

Rheumatoid arthritis is a multi-system disease. Pulmonary manifestations and complications include pleural disease, pulmonary infections, pneumonitis and interstitial pulmonary fibrosis, bronchogenic carcinoma, arteritis with pulmonary hypertension, obliterative bronchiolitis, bronchiectasis, and amyloidosis. Pulmonary rheumatoid nodules, including rheumatoid pneumoconiosis (Caplan's Syndrome), can result in spontaneous pneumothorax. In this article, the authors present a patient with rheumatoid arthritis and recurrent spontaneous pneumothorax. Through investigation, a bronchopleural fistula caused by a rheumatoid nodule was revealed. The authors also discuss the potential pitfalls caused by a lung nodule in a patient with rheumatoid arthritis, including the overlap with bronchogenic carcinoma and confusion with tuberculosis.

An assay for antibody-dependent cell-mediated cytotoxicity which uses whole blood as effector and autologous lymphocytes sensitized with rabbit anti-human lymphocyte serum as targets is assessed. Comparison with performances of purified lymphocytes shows that whole blood yields approximately the same cytotoxicity levels as the lymphocytes which can be separated from the corresponding volume of blood. This equivalence is not seen at the early stage of cytolysis, whole blood reaching its plateau stage 1 h later. A contribution of phagocytic cells to lysis of the target cells is ruled out. The presence of plasma does not modify the cytolytic capacity of the blood of healthy subjects. The test may be performed with less than 1 ml of blood and is suitable for repeated evaluation of the immunologic status of patients, for evaluation of plasma factors in diseases and of the effects of agents inducing lymphocyte redistribution.

The Feel4Diabetes-study adhered to the Declaration of Helsinki and the conventions of the Council of Europe on human rights and biomedicine and was approved by each local ethical committee. More specifically, in Belgium, by the Medical Ethics Committee of the Ghent University Hospital (ethical approval code: B670201524237; date approval: 21/04/15); in Bulgaria, by the Ethics Committee of the Medical University of Varna (ethical approval code: 52/10–3-201r; date approval: 10/03/16) and the Municipalities of Sofia and Varna, as well as the Ministry of Education and Science local representatives; in Finland, by the hospital district of Southwest Finland ethical committee (ethical approval code: 174/1801/2015; date approval: 13/03/15); in Greece, by the Bioethics Committee of Harokopio University (ethical approval code: 46/3–4-2015; date approval: 03/04/15) and the Greek Ministry of Education; in Hungary, by the National Committee for Scientific Research in Medicine (ethical approval code: 20095/2016/EKU; date approval: 29/03/16); and in Spain, by the Clinical Research Ethics Committee and the Department of Consumers’ Health of the Government of Aragón (ethical approval code: CP03/2016; date approval: 08/04/15)., The authors would like to thank all families who participated and the members of the Feel4Diabetes-study Group (). We gratefully acknowledge the financial support of the European Community., Parental health is associated with children’s health and lifestyles. Thus, the aim of the present study was to assess lifestyle behaviours of children of parents with insulin resistance (IR) and at risk of type 2 diabetes. 2117 European families from the Feel4Diabetes-study were identifed as being at risk for diabetes with the FINDRISC questionnaire and included in the present study. One parent and one child per family were included. Parental IR was considered when homeostasis model assessment (HOMA) was equal or higher than 2.5. Children’s screen-time, physical activity and diet were assessed and clustered by K-means. Weight and height were measured and children’s body mass index (BMI) was calculated. For children, a Healthy Diet Score (HDS) was calculated. Linear regression and multilevel logistic regression analyses were performed to assess the associations between parental IR and children’s lifestyle behaviours in 2021. Children of parents with IR had higher BMI (p, Bioethics Committee of Harokopio University 03/04/15, Department of Consumers’ Health of the Government of Aragón 08/04/15, CP03/2016, Ministerio de Ciencia and innovación FJCI-2017–34967, National Committee for Scientific Research in Medicine 29/03/16, Horizon 2020 Framework Programme 643708, European Commission, Ministry of Education, Youth and Science 13/03/15, 174/1801/2015, Universitair Ziekenhuis Gent 21/04/15, B670201524237, Medical University - Varna 10/03/16, Ministry of National Education and Religious Affairs