Ted A. James

Variability in Reexcision Following Breast Conservation Surgery

CONTEXT Health care reform calls for increasing physician accountability and transparency of outcomes. Partial mastectomy is the most commonly performed procedure for invasive breast cancer and often requires reexcision. Variability in reexcision might be reflective of the quality of care. OBJECTIVE To assess hospital and surgeon-specific variation in reexcision rates following partial mastectomy. DESIGN, SETTING, AND PATIENTS An observational study of breast surgery performed between 2003 and 2008 intended to evaluate variability in breast cancer surgical care outcomes and evaluate potential quality measures of breast cancer surgery. Women with invasive breast cancer undergoing partial mastectomy from 4 institutions were studied (1 university hospital [University of Vermont] and 3 large health plans [Kaiser Permanente Colorado, Group Health, and Marshfield Clinic]). Data were obtained from electronic medical records and chart abstraction of surgical, pathology, radiology, and outpatient records, including detailed surgical margin status. Logistic regression including surgeon-level random effects was used to identify predictors of reexcision. MAIN OUTCOME MEASURE Incidence of reexcision. RESULTS A total of 2206 women with 2220 invasive breast cancers underwent partial mastectomy and 509 patients (22.9%; 95% CI, 21.2%-24.7%) underwent reexcision (454 patients [89.2%; 95% CI, 86.5%-91.9%] had 1 reexcision, 48 [9.4%; 95% CI, 6.9%-12.0%] had 2 reexcisions, and 7 [1.4%; 95% CI, 0.4%-2.4%] had 3 reexcisions). Among all patients undergoing initial partial mastectomy, total mastectomy was performed in 190 patients (8.5%; 95% CI, 7.2%-9.5%). Reexcision rates for margin status following initial surgery were 85.9% (95% CI, 82.0%-89.8%) for initial positive margins, 47.9% (95% CI, 42.0%-53.9%) for less than 1.0 mm margins, 20.2% (95% CI, 15.3%-25.0%) for 1.0 to 1.9 mm margins, and 6.3% (95% CI, 3.2%-9.3%) for 2.0 to 2.9 mm margins. For patients with negative margins, reexcision rates varied widely among surgeons (range, 0%-70%; P = .003) and institutions (range, 1.7%-20.9%; P < .001). Reexcision rates were not associated with surgeon procedure volume after adjusting for case mix (P = .92). CONCLUSION Substantial surgeon and institutional variation were observed in reexcision following partial mastectomy in women with invasive breast cancer.

Results of a national survey of surgical resident interest in international experience, electives, and volunteerism.

BACKGROUND Data are emerging about the essential nature of sustainable global surgical care and interest among North American surgeons. Currently, there is no formal mechanism for US surgical residents to participate in international training opportunities. A small, single-institution survey found that general surgery residents at New York University are highly motivated to pursue international training. But little research has addressed the attitudes of North American residents about international training. The goal of this study was to acquire a broader understanding of surgical resident interest in international training. STUDY DESIGN A structured questionnaire was administered anonymously and voluntarily to all American College of Surgeons resident members. RESULTS Seven hundred twenty-four residents completed surveys. Ninety-four percent of respondents planned careers in general surgery. Ninety-two percent of respondents were interested in an international elective, and 82% would prioritize the experience over all or some other electives. Fifty-four percent and 73% of respondents would be willing to use vacation and participate even if cases were not counted for graduation requirements, respectively. Educational indebtedness was high among respondents (50% of respondents carried >or=

Quality Measures for Breast Cancer Surgery: Initial Validation of Feasibility and Assessment of Variation Among Surgeons

100,000 debt). Despite debt, 85% of respondents plan to volunteer while in practice. The most frequent barriers identified by respondents were financial (61%) and logistic (66%). CONCLUSIONS American College of Surgeons resident members are highly motivated to acquire international training experience, with many planning to volunteer in the future. A consensus among stakeholders in North American surgical education is needed to further explore international training within surgical residency.

Variation in detection of ductal carcinoma in situ during screening mammography: a survey within the International Cancer Screening Network

OBJECTIVES To identify and quantify surgical outcomes as possible quality measures of initial breast cancer surgery and to assess variation among surgeons. DESIGN Descriptive analysis of concurrently collected outcome measures. SETTING University hospital with a designated breast cancer center. PATIENTS Patients with a preoperative diagnosis of invasive breast cancer or ductal carcinoma in situ undergoing their initial cancer surgery from April 1, 2003, to March 30, 2008. MAIN OUTCOME MEASURES Eight measures were identified: (1) total mastectomy rate; (2) close (<1 mm) and positive margin rate following initial partial mastectomy; (3) number of operations required in breast conservation; (4) number of nodes obtained from sentinel lymph node biopsy; (5) number of nodes from axillary dissection; (6) proportion of patients with positive sentinel lymph node biopsy undergoing axillary dissection; (7) use of intraoperative lymph node assessment; and (8) time from diagnosis to surgery. RESULTS Nine hundred ten operations (218 for ductal carcinoma in situ, 692 for invasive breast cancer) were performed by 6 surgeons. Variation existed among surgeons in the combined close and positive margin rate, number of nodes obtained from sentinel lymph node biopsy, and use of intraoperative lymph node assessment. No significant variation was seen for the overall mastectomy rate, mean number of operations, positive margin rate alone, and number of lymph nodes from axillary dissection. CONCLUSIONS Quality indicators for breast cancer surgery can be identified and readily monitored. Outcome variation exists at a high-volume breast center. Further study into the causes and effects of this variation on short- and long-term patient outcomes as well as health care costs is needed.

Registry-based study of trends in breast cancer screening mammography before and after the 2009 U.S. Preventive Services Task Force recommendations.

BACKGROUND There is concern about detection of ductal carcinoma in situ (DCIS) in screening mammography. DCIS accounts for a substantial proportion of screen-detected lesions but its effect on breast cancer mortality is debated. The International Cancer Screening Network conducted a comparative analysis to determine variation in DCIS detection. PATIENTS AND METHODS Data were collected during 2004-2008 on number of screening examinations, detected breast cancers, DCIS cases and Globocan 2008 breast cancer incidence rates derived from national or regional cancer registers. We calculated screen-detection rates for breast cancers and DCIS. RESULTS Data were obtained from 15 screening settings in 12 countries; 7,176,050 screening examinations; 29,605 breast cancers and 5324 DCIS cases. The ratio between highest and lowest breast cancer incidence was 2.88 (95% confidence interval (CI) 2.76-3.00); 2.97 (95% CI 2.51-3.51) for detection of breast cancer; and 3.49 (95% CI 2.70-4.51) for detection of DCIS. CONCLUSIONS Considerable international variation was found in DCIS detection. This variation could not be fully explained by variation in incidence nor in breast cancer detection rates. It suggests the potential for wide discrepancies in management of DCIS resulting in overtreatment of indolent DCIS or undertreatment of potentially curable disease. Comprehensive cancer registration is needed to monitor DCIS detection. Efforts to understand discrepancies and standardise management may improve care.

Increased efficacy of doxorubicin delivered in multifunctional microparticles for mesothelioma therapy

PURPOSE To determine whether the 2009 U.S. Preventive Services Task Force (USPSTF) guidelines for breast cancer mammography screening were followed by changes in screening utilization in the state of Vermont. MATERIALS AND METHODS This retrospective study was HIPAA compliant and approved by the institutional review board, with waiver of informed consent. Trends in screening mammography utilization during 1997-2011 were examined among approximately 150,000 women aged 40 years and older in the state of Vermont using statewide mammography registry data. RESULTS The percentage of Vermont women aged 40 years and older screened in the past year declined from 45.3% in 2009% to 41.6% in 2011 (an absolute decrease of -3.7 percentage points; 95% confidence interval [CI]: -3.3, -4.1). The largest decline in utilization was among women aged 40-49 years (-4.8 percentage points; 95% CI: -4.1, -5.4), although substantial declines were also observed among women aged 50-74 years (-3.0 percentage points; 95% CI: -2.6, -3.5) and women aged 75 years and older (-3.1 percentage points; 95% CI: -2.3, -4.0). The percentage of women aged 50-74 years screened within the past 2 years declined by -3.4 percentage points (95% CI: -3.0, -3.9) from 65.4% in 2009 to 61.9% in 2011. CONCLUSION After years of increasing screening mammography utilization in Vermont, there was a decline in screening, which coincided with the release of the 2009 USPSTF recommendations. The age-specific patterns in utilization were generally consistent with the USPSTF recommendations, although there was also evidence that the percentage of women aged 50-74 years screened in the past 2 years declined since 2009.

International variation in management of screen-detected ductal carcinoma in situ of the breast

New and effective treatment strategies are desperately needed for malignant mesothelioma (MM), an aggressive cancer with a poor prognosis. We have shown previously that acid‐prepared mesoporous microspheres (APMS) are nontoxic after intrapleural or intraperitoneal (IP) administration to rodents. The purpose here was to evaluate the utility of APMS in delivering chemotherapeutic drugs to human MM cells in vitro and in two mouse xenograft models of MM. Uptake and release of doxorubicin (DOX) alone or loaded in APMS (APMS‐DOX) were evaluated in MM cells. MM cell death and gene expression linked to DNA damage/repair were also measured in vitro. In two severe combined immunodeficient mouse xenograft models, mice received saline, APMS, DOX or APMS‐DOX injected directly into subcutaneous (SC) MM tumors or injected IP after development of human MMs peritoneally. Other mice received DOX intravenously (IV) via tail vein injections. In comparison to DOX alone, APMS‐DOX enhanced intracellular uptake of DOX, MM death and expression of GADD34 and TP73. In the SC MM model, 3× weekly SC injections of APMS‐DOX or DOX alone significantly inhibited tumor volumes, and systemic DOX administration was lethal. In mice developing IP MMs, significant (p < 0.05) inhibition of mesenteric tumor numbers, weight and volume was achieved using IP administration of APMS‐DOX at one‐third the DOX concentration required after IP injections of DOX alone. These results suggest APMS are efficacious for the localized delivery of lower effective DOX concentrations in MM and represent a novel means of treating intracavitary tumors.

Are mastectomy rates a reasonable quality measure of breast cancer surgery

BACKGROUND Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. METHODS We sought screen-detected DCIS data from the ICSN countries identified during 2004-2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. RESULTS Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50-69 years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67-90% of DCIS received breast conservation surgery (BCS), and in 41-100% of the cases this was followed by radiotherapy; 6.4-59% received sentinel lymph node biopsy (SLNB) only and 0.8-49% axillary dissection (ALND) with 0.6% (range by programmes 0-8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. CONCLUSIONS Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction.

Acute inflammation induced by the biopsy of mouse mammary tumors promotes the development of metastasis

BACKGROUND Quality measures of breast cancer clinical management adopted by the National Quality Forum do not address the quality of surgical performance. We evaluated mastectomy rate as one potential quality indicator. METHODS We reviewed the surgical management of small (stage T1; < or =2 cm) invasive breast tumors in patients treated from April 2003 through April 2007 at our institution. For patients undergoing mastectomy, factors leading to the selection of mastectomy were analyzed. RESULTS We identified 496 patients with invasive breast cancer: 433 did not undergo neoadjuvant chemotherapy, and 319 of these had pathologic tumors < or =2 cm in size. Of these, 55 (17.2%) underwent initial mastectomy. Medical contraindications to breast conservation were identified in 42 of 319 (13.2%) patients, whereas the selection of mastectomy was attributed to patient choice in 13 of 319 (4.1%) patients. CONCLUSIONS Medical contraindications to breast-conserving therapy were much more common than patient choice as the indication for mastectomy. Institution- or surgeon-specific mastectomy rates are unlikely to reflect the complexity of decision making in the surgical management of patients with breast cancer.

Sentinel lymph node in breast cancer.

Development of metastasis in peripheral tissues is a major problem in the fight to cure breast cancer. Although it is becoming evident that chronic inflammation can contribute to tumor progression and metastasis, the effect of acute inflammation in primary tumor is less known. Using mouse models for breast cancer here we show that biopsy of mammary tumors increases the frequency of lung metastases. This effect is associated with the recruitment of inflammatory cells to the lung and elevated levels of certain cytokines such as IL-6 in the lung airways. Antiinflammatory treatment prior to and after the biopsy reduces the development of metastases triggered by the biopsy. In addition, while lack of IL-6 does not affect primary tumor development, it protects from increasing number of metastases upon biopsy. Thus, our studies show that in addition to chronic inflammation, acute immune response caused by invasive procedures in the primary tumor may cause an increased risk on peripheral metastases, but the risk could be decreased by anti-inflammatory treatments.