Intraoperative Radiation for Breast Cancer with Intrabeam™: Factors Associated with Decreased Operative Times in Patients Having IORT for Breast Cancer.

INTRODUCTION: Intraoperative radiation with Intrabeam™ (IORT) for breast cancer is a newer technology recently implemented into the operating room (OR). This procedure requires time and coordination between the surgeon and radiation oncologist, who both perform their treatments in a single operative setting. We evaluated the surgeons at our center, who perform IORT and their OR times to examine changes in OR times following implementation of this new surgical procedure. We hypothesized that IORT is a technique for which timing could be improved with the increasing number of cases performed. METHODS: A prospectively maintained IRB approved database was queried for OR times (incision and close) in patients who underwent breast conserving surgery (BCS), sentinel lymph node biopsy with and without IORT using the Intrabeam™ system at our institution from 2011 to 2015. The total OR times were compared for each surgeon individually and over time. Next, the OR times of each surgeon were compared to each other. Continuous variables were summarized and then a prediction model was created using IORT time, OR time, surgeon, and number of cases performed. RESULTS: There were five surgeons performing IORT at our institution during this time period with a total of 96 cases performed. There was a significant difference observed in baseline surgeon-specific OR time for BSC (p = 0.03) as well as for BCS with IORT (p < 0.05), attributable to surgeon experience. The average BCS times were faster than the BCS plus IORT procedure times for all surgeons. The overall mean OR time for the entire combined surgical and radiation procedure was 135.5 min. The most common applicator sizes used were the 3.5 and 4 cm, yielding an average 21 min IORT time. Applicator choice did not differ over time (p = 0.189). After adjusting for IORT time and surgeon, the prediction model estimated that surgeons decreased the total BCS plus IORT OR time at a rate of -4.5 min per each additional 10 cases performed. CONCLUSION: Surgeon experience and applicator size are related to OR times for performing IORT for breast cancer. OR time for IORT in breast cancer treatment can be improved over time, even among experienced surgeons.

Predictive factors on outcomes in metaplastic breast cancer.

PURPOSE: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer, with limited data available regarding treatment and outcomes. This study aims to review patients with MBC treated at our tertiary care institution with an emphasis on the role of treatment modality and histologic classification. METHODS: With IRB-approval, we queried our pathology database for patients with MBC diagnosis. All cases were re-evaluated by dedicated breast pathologists and confirmed as MBC breast cancer. Patient demographics, clinical/pathologic histology, and treatment were analyzed with respect to outcomes including local-regional recurrence (LRR), distant metastasis (DM), and overall survival (OS). Univariate and multivariate Cox proportional hazards models were performed to evaluate the impact on outcomes. Kaplan-Meier methods estimated survival. RESULTS: We evaluated 113 patients with MBC diagnosed between 2002 and 2013. Median age was 61 years and median pathologic tumor size 2.5 cm; 76 (67%) were ER/PR/Her2 negative, 83 (74%) grade 3. Median follow-up was 38 months. 47 (42%) underwent breast conservation therapy (BCT), 66 (58%) had mastectomy, 61 (54%) underwent adjuvant radiation (RT), and 85 (75%) had chemotherapy. At 2 and 5 years, the LRR/DM/OS rates were 12%/15%/90% and 21%/35%/69%, respectively. On Cox regression analysis, only adjuvant RT correlated with reduced LRR [RR 3.1 (1.13-9.88), p = 0.027], while chemotherapy, type of surgery, and T-N stage did not. Only T-stage (p = 0.008) correlated with DM, however chemotherapy, RT, surgery type, and N-stage were not. Univariate analysis demonstrated histologic subtype did not significantly correlate with local (p = 0.54) or distant (p = 0.83) disease control. CONCLUSIONS: This study represents among the largest institutional experiences in the outcomes of MBC. At this time, there does not appear to be a clear histologic subset of MBC which has significantly different clinical outcomes from the other subtypes. Although limited in its sample size, this study shows RT remains important in local-regional control.

Retrospective study of the efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab/pertuzumab (TCH-P) in nonmetastatic HER2-positive breast cancer.

BACKGROUND: Pertuzumab is FDA approved in the preoperative setting in combination with trastuzumab and chemotherapy, in women with nonmetastatic HER2 + breast cancer. The TRYPHAENA trial (n = 77) reported a pathologic complete response rate (pCR), i.e., ypT0ypN0, of 52 % in patients treated with neoadjuvant (docetaxel, carboplatin, trastuzumab, & pertuzumab) TCH-P. Aside from this study, there is limited information regarding the safety and efficacy of TCH-P in the neoadjuvant setting. Our goal was to evaluate the safety and efficacy of neoadjuvant TCH-P in a non-clinical trial setting. MATERIALS AND METHODS: Cancer data registry was utilized to identify patients with HER2 + nonmetastatic breast cancer that received neoadjuvant TCH-P. pCR was defined as the absence of invasive or noninvasive cancer in breast and lymph nodes, i.e., ypT0ypN0. RESULTS: 70 patients with a median age of 52 years met our inclusion criteria. Clinical staging was I-8.5 %; II-68.5 %; and III-22.8 %. 60 % of patients had hormone receptor (HR)-positive tumors. 23 % (16/71) of patients required dose reduction for rash, diarrhea, neuropathy, or thrombocytopenia. Overall, no patients developed grade 3-4 left ventricular systolic dysfunction(LVSD); an asymptomatic reduction in LVEF of >10 % was observed in three patients. The overall observed pCR rate was 53 %. As expected, the pCR rate was higher in patients with HR-negative breast cancer than for patients with HR+ disease: 69 % (20/29) vs. 42 % (17/41), respectively. The axillary downstaging rate was approximately 53 % (19/36). CONCLUSION: Neoadjuvant TCH-P, in a nonclinical trial setting, was associated with a pCR rate of 53 % similar the reported rate in TRYPHAENA. Toxicity was manageable, with no patients experiencing symptomatic heart failure.

Medical student documentation in electronic health records: a collaborative statement from the Alliance for Clinical Education.

PURPOSE: The electronic health record (EHR) is an important advancement in health care. It facilitates improvement of health care delivery and coordination of care, but it creates special challenges for student education. This article represents a collaborative effort of the Alliance for Clinical Education (ACE), a multidisciplinary group formed in 1992. ACE recognizes the importance of medical student participation in patient care including the ability of documentation. This article proposes guidelines that can be used by educators to establish expectations on medical student documentation in EHRs. SUMMARY: To provide the best education for medical students in the electronic era, ACE proposes to use the following as practice guidelines for medical student documentation in the EHR: (a) Students must document in the patient's chart and their notes should be reviewed for content and format, (b) students must have the opportunity to practice order entry in an EHR--in actual or simulated patient cases--prior to graduation, (c) students should be exposed to the utilization of the decision aids that typically accompany EHRs, and (d) schools must develop a set of medical student competencies related to charting in the EHR and state how they would evaluate it. This should include specific competencies to be documented at each stage, and by time of graduation. In addition, ACE recommends that accreditation bodies such as the Liaison Committee for Medical Education utilize stronger language in their educational directives standards to ensure compliance with educational principles. This will guarantee that the necessary training and resources are available to ensure that medical students have the fundamental skills for lifelong clinical practice. CONCLUSIONS: ACE recommends that medical schools develop a clear set of competencies related to student in the EHR which medical students must achieve prior to graduation in order to ensure they are ready for clinical practice.

Teaching technical skills to medical students during a surgery clerkship: results of a small group curriculum.

BACKGROUND: Opportunities for medical students to learn and perform technical skills during their clinical years have decreased. Alternative means to provide instruction are increasingly important. METHODS: Third-year students were assigned to three weekly small group tutorial sessions during their surgery clerkship. One hour sessions covered the following: suturing/knot tying, tubes (Foley catheter/NG tube), and lines (i.v. placement/arterial puncture). Students used a self-reported checklist to report their experience performing these procedures in the hospital after being exposed to them in the skills sessions. These data were compared with results prior to the implementation of the skills curriculum. Results were compared by Fisher's exact test. RESULTS: Seventy-seven students had evaluable checklists during the control period, and 69 were evaluable during the study period. Participations in four specific skills were compared: Foley catheter placement, nasogastric tube insertion/removal, i.v. placement, and arterial stick. In all four skills, students were more likely to have performed the task after having been introduced to it in the skills sessions. For both Foley catheter placement (96% versus 90%; P = 0.05) and NG tube insertion/removal (70% versus 53%; P = 0.06) there was a trend toward a higher incidence of participation, although statistical significance was not met. However, for both IV placement (64% versus 18%; P = 0.0001) and arterial puncture (48% versus 18%; P = 0.0002) there were significant increases in participation between the study periods. CONCLUSIONS: These results suggest that a small group technical skills curriculum facilitates learning of specific technical skills and appears to increase participation in all of the skills taught and assessed. This may be one strategy to introduce students to technical skills during the surgery clerkship and improve participation of these skills in the hospital setting.

Low correlation between subjective and objective measures of knowledge on surgery clerkships.

BACKGROUND: Medical student knowledge is assessed during surgical clerkships subjectively and objectively. Subjective evaluation depends on faculty assessment during clinical and didactic interactions. Objective measurement derives from standardized tools, such as the National Board of Medical Examiners Surgery Subject test (shelf). Few efforts have been made to characterize the correlation between subjective and objective measures of medical knowledge. STUDY DESIGN: All 308 third-year medical students who completed the 8-week surgery clerkship at the University of North Carolina at Chapel Hill between July 2005 and June 2007 received subjective assessment of knowledge on 3 clinical rotations (one 4-week core and two 2-week elective rotations) and a longitudinal small-group tutorial. Faculty evaluators assigned percentile scores to rate students' knowledge base relative to their peers. In addition, students took the shelf test the last day of clerkship, and percentile scores were assigned based on National Board of Medical Examiners-supplied normative data from first-time test-takers within the same academic quarter. Subjective versus objective knowledge scores were plotted overall, and Pearson product-moment correlation coefficients were generated for core, elective, and tutorial assessments. RESULTS: There were only weak linear relationships noted between subjective faculty-assigned knowledge scores and objective shelf scores. Pearson correlations were 0.24 for core rotations (4 weeks exposure), 0.14 for elective rotations (2 weeks exposure), and 0.22 for tutorials (1-hour exposure/week during 8 weeks), with p values <0.0001. CONCLUSIONS: Faculty assessment of knowledge is only weakly correlated with shelf performance. Faculty evaluations after 4-week rotations or longitudinal small-group interactions are better correlated with shelf scores than after 2-week electives.

Focus group study of hand hygiene practice among healthcare workers in a teaching hospital in Toronto, Canada.

OBJECTIVE: To understand the behavioral determinants of hand hygiene in our hospital. DESIGN: Qualitative study based on 17 focus groups. SETTING: Mount Sinai Hospital, an acute care tertiary hospital affiliated with the University of Toronto. PARTICIPANTS: We recruited 153 healthcare workers (HCWs) representing all major patient care job categories. METHODS: Focus group discussions were transcribed verbatim. Thematic analysis was independently conducted by 3 investigators. RESULTS: Participants reported that the realities of their workload (eg, urgent care and interruptions) make complete adherence to hand hygiene impossible. The guidelines were described as overly conservative, and participants expressed that their judgement is adequate to determine when to perform hand hygiene. Discussions revealed gaps in knowledge among participants; most participants expressed interest in more information and education. Participants reported self-protection as the primary reason for the performance of hand hygiene, and many admitted to prolonged glove use because it gave them a sense of protection. Limited access to hand hygiene products was a source of frustration, as was confusion related to hospital equipment as potential vehicles for transmission of infection. Participants said that they noticed other HCWs' adherence and reported that others HCWs' hygiene practices influenced their own attitudes and practices. In particular, HCWs perceive physicians as role models; physicians, however, do not see themselves as such. CONCLUSIONS: Our results confirm previous findings that hand hygiene is practiced for personal protection, that limited access to supplies is a barrier, and that role models and a sense of team effort encourage hand hygiene. Educating HCWs on how to manage workload with guideline adherence and addressing contaminated hospital equipment may improve compliance.

A CRASH course in procedural skills improves medical students' self-assessment of proficiency, confidence, and anxiety.

BACKGROUND: Medical students enter the clinical education years with minimal exposure to procedural skills. This study aims to determine the effect of a pre-clinical skills course on students' ratings of proficiency, confidence, and anxiety levels. METHODS: An elective pre-clinical course in procedural skills was given to medical students prior to clinical rotations. Self-assessment of proficiency, confidence, and anxiety in performing these skills was made prior to and on completion of the course. RESULTS: Course participants reported low proficiency and confidence, and high anxiety regarding performing procedural skills. Following the course, there was significant improvement in self-assessed proficiency, confidence, and anxiety. There were no gender differences in responses. CONCLUSIONS: Medical students entering clinical rotations have poor self-assessment of proficiency, low confidence, and high anxiety regarding procedural skills. A concentrated course in procedural skills significantly improved students' assessment of their proficiency, confidence, and anxiety levels.

Ductal carcinoma in situ of the breast and heparanase-1 expression: a molecular explanation for more aggressive subtypes.

BACKGROUND: Ductal carcinoma in situ of the breast (DCIS) forms a heterogeneous group of lesions with varying invasive potential. This study tested whether heparanase-1 (HPR1), an endoglycosidase that specifically degrades the heparan sulfate (HS) proteoglycans in the breast extracellular matrix, was associated with the most aggressive DCIS subtypes. STUDY DESIGN: Fifty-seven DCIS specimens and 10 normal breast specimens were examined for HPR1 expression using immunohistochemical staining. Twenty-seven arbitrarily selected specimens were also examined for HS deposition by immunofluorescence staining, confirming HPR1 activity. Patient medical records were obtained to explore a possible association between biologic potential using Van Nuys Prognostic Index (VNPI) and HPR1 expression. RESULTS: Twenty-one (75%) of 28 comedo and microinvasive DCIS specimens stained HPR1 positive; 4 (14%) of 29 other subtypes (papillary, cribriform, and solid subtypes) stained HPR1 positive on immunohistochemistry (p = 0.003). Among 27 DCIS stained for HS, we found that 8 (67%) of 12 HPR1-negative DCIS had intact HS deposition in the extracellular basement membrane; none of the 15 HPR1-positive DCIS stained HS positive. Six (86%) of seven DCIS with VNPI scores 8 to 9 and 14 (50%) of 28 DCIS with VNPI scores 5 to 7 were HPR1 positive; only 3 (17%) of 18 DCIS with VNPI scores 3 to 4 were HPR1 positive. Median VNPI score in patients with HPR1-positive DCIS was 7 (range 3 to 9), compared with 4.5 (range 3 to 7) in patients with HPR1-negative DCIS (p < 0.001). CONCLUSIONS: HPR1 was expressed at a significantly higher frequency in the invasive comedo and DCIS with microinvasion subtypes than in the noninvasive subtypes. HPR1 expression was inversely associated with HS deposition in the extracellular basement membrane of the DCIS. HPR1 expression was associated with a higher VNPI score. These observations suggest that HPR1 expression in DCIS can play an important role in development of DCIS into an invasive breast cancer.

Heparanase-1 expression is associated with the metastatic potential of breast cancer.

BACKGROUND: Metastasis of malignant breast cells is in part mediated through degradation of the extra-cellular matrix by proteolysis, enabling malignant cells to migrate through the surrounding stroma. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate (HS) moiety of proteoglycans, a component of the extracellular matrix and basement membrane. METHODS: Fifty-one primary breast tumors, 13 lymph node metastases, 4 ductal carcinoma in situ, 7 benign, and 5 normal specimens were examined for HPR1 expression using immunohistochemical staining. The functional role of HPR1 expression was determined by examining HS deposition using immunofluorescence staining. RESULTS: Sixteen of 30 breast carcinomas (53%) with sentinel node metastasis expressed HPR1. In contrast, only 5 of 21 nonmetastatic primary breast carcinomas (23%) were HPR1 positive. Eighteen of 30 breast carcinomas between 1 and 5 cm expressed HPR1, compared with 3 of 21 HPR1-positive specimens in tumors < or =1 cm. Statistical analysis revealed that HPR1 expression was associated with breast tumor metastases (P =.04) and primary tumors between 1 and 5 cm (P =.002). Ninety percent of HPR1-positive tumors lacked HS deposition, suggesting an inverse correlation between HPR1 expression and HS deposition. CONCLUSIONS: HPR1 expression correlates with the lack of HS deposition and with the metastatic potential of breast cancers. The frequency of HPR1 is significantly higher in breast tumors between 1 and 5 cm than in tumors < or =1 cm.