Identification of the Collagen Types Essential for Mammalian Breast Acinar Structures.

Modeling human breast tissue architecture is essential to study the pathophysiological conditions of the breast. We report that normal mammary epithelial cells grown in human breast extracellular matrix (ECM) hydrogel formed acini structurally similar to those of human and pig mammary tissues. Type I, II, III and V collagens were commonly identified in human, pig, and mouse breast ECM. Mammary epithelial cells formed acini on certain types or combinations of the four collagens at normal levels of breast tissue elasticity. Comparison of the collagen species in mouse normal breast and breast tumor ECM revealed common and distinct sets of collagens within the two types of tissues. Elevated expression of collagen type I alpha 1 chain (Col1a1) was found in mouse and human breast cancers. Collagen type XXV alpha 1 chain (Col25a1) was identified in mouse breast tumors but not in normal breast tissues. Our data provide strategies for modeling human breast pathophysiological structures and functions using native tissue-derived hydrogels and offer insight into the potential contributions of different collagen types in breast cancer development.

Human Breast Extracellular Matrix Microstructures and Protein Hydrogel 3D Cultures of Mammary Epithelial Cells.

Tissue extracellular matrix (ECM) is a structurally and compositionally unique microenvironment within which native cells can perform their natural biological activities. Cells grown on artificial substrata differ biologically and phenotypically from those grown within their native tissue microenvironment. Studies examining human tissue ECM structures and the biology of human tissue cells in their corresponding tissue ECM are lacking. Such investigations will improve our understanding about human pathophysiological conditions for better clinical care. We report here human normal breast tissue and invasive ductal carcinoma tissue ECM structural features. For the first time, a hydrogel was successfully fabricated using whole protein extracts of human normal breast ECM. Using immunofluorescence staining of type I collagen (Col I) and machine learning of its fibrous patterns in the polymerized human breast ECM hydrogel, we have defined the microstructural characteristics of the hydrogel and compared the microstructures with those of other native ECM hydrogels. Importantly, the ECM hydrogel supported 3D growth and cell-ECM interaction of both normal and cancerous mammary epithelial cells. This work represents further advancement toward full reconstitution of the human breast tissue microenvironment, an accomplishment that will accelerate the use of human pathophysiological tissue-derived matrices for individualized biomedical research and therapeutic development.

Too Much of a Good Thing: Radioactive Iodine Ablation Use for Micropapillary Thyroid Carcinoma.

Radioactive iodine (RAI) is not routinely recommended for the adjuvant treatment of micropapillary thyroid carcinoma (MPTC). We aimed to report on clinical and pathologic factors associated with the use of RAI in these patients. We queried the Surveillance, Epidemiology, and End Results database for patients who underwent surgery for MPTC (tumor size ≤1 cm) from 1988 to 2009. We excluded patients without a biopsy-proven diagnosis, those diagnosed at autopsy, and patients with documented extra-thyroidal extension. Multivariate logistic regression models predicted the use of RAI based on patient, tumor, and treatment-related factors. We identified 24,076 patients with MPTC that were eligible for study inclusion. Of these, 6,172 (25.6%) received RAI. Lymph node metastases were present in 23.8 per cent of those for whom lymph node status was known. On multivariate analysis, an increasing number of positive nodes, increasing tumor size, Asian race, and male gender predicted the use of RAI. RAI use was less likely in those with advancing age, an increasing number of lymph nodes examined and patients that received less than a total thyroidectomy. Among node-negative patients, Asian race and increasing tumor size predicted the use of RAI. Factors predicting decreased use of RAI were an increasing number of lymph nodes examined, unknown race, less than a total thyroidectomy, and advancing age. A significant number of MPTC patients receive potentially unnecessary RAI.

Metastatic melanoma - a review of current and future treatment options.

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.

Relative value units poorly correlate with measures of surgical effort and complexity.

BACKGROUND: The relationship between procedural relative value units (RVUs) for surgical procedures and other measures of surgeon effort are poorly characterized. We hypothesized that RVUs would poorly correlate with quantifiable metrics of surgeon effort. METHODS: Using the 2010 American College of Surgeons - National Surgical Quality Improvement Program (NSQIP) database, we selected 11 primary current procedural terminology codes associated with high volume surgical procedures. We then identified all patients with a single reported procedural RVU who underwent nonemergent, inpatient general surgical operations. We used linear regression to correlate length of stay (LOS), operative time, overall morbidity, frequency of serious adverse events (SAEs), and mortality with RVUs. We used multivariable logistic regression using all preoperative NSQIP variables to determine other significant predictors of our outcome measures. RESULTS: Among 14,481 patients, RVUs poorly correlated with individual LOS (R(2) = 0.05), operative time (R(2) = 0.10), and mortality (R(2) = 0.35). There was a moderate correlation between RVUs and SAEs (R(2) = 0.79) and RVUs and overall morbidity (R(2) = 0.75). However, among low- to mid-level RVU procedures (11-35) there was a poor correlation between SAEs (R(2) = 0.15), overall morbidity (R(2) = 0.05), and RVUs. On multivariable analysis, RVUs were significant predictors of operative time, LOS, and SAEs (odds ratio 1.06, 95% confidence interval: 1.05-1.07), but RVUs were not a significant predictor of mortality (odds ratio 1.02, 95% confidence interval: 0.99-1.05). CONCLUSIONS: For common, index general surgery procedures, the current RVU assignments poorly correlate with certain metrics of surgeon work, while moderately correlating with others. Given the increasing emphasis on measuring and tracking surgeon productivity, more objective measures of surgeon work and productivity should be developed.

Text messaging among residents and faculty in a university general surgery residency program: prevalence, purpose, and patient care.

BACKGROUND: There is little information about the use of text messaging (texting) devices among resident and faculty physicians for patient-related care (PRC). OBJECTIVE: To determine the prevalence, frequency, purpose, and concerns regarding texting among resident and attending surgeons and to identify factors associated with PRC texting. DESIGN: E-mail survey. SETTING: University medical center and its affiliated hospitals. PARTICIPANTS: Surgery resident and attending staff. OUTCOME MEASURES: Prevalence, frequency, purpose, and concerns regarding patient-related care text messaging. RESULTS: Overall, 73 (65%) surveyed physicians responded, including 45 resident (66%) and 28 attending surgeons (62%). All respondents owned a texting device. Majority of surgery residents (88%) and attendings (71%) texted residents, whereas only 59% of residents and 65% of attendings texted other faculty. Most resident to resident text occurred at a frequency of 3-5 times/d (43%) compared with most attending to resident texts, which occurred 1-2 times/d (33%). Most resident to attending (25%) and attending to attending (30%) texts occurred 1-2 times/d. Among those that texted, PRC was the most frequently reported purpose for resident to resident (46%), resident to attending (64%), attending to resident (82%), and attending to other attending staff (60%) texting. Texting was the most preferred method to communicate about routine PRC (47% of residents vs 44% of attendings). Age (OR: 0.86, 95% CI: 0.79-0.95; p = 0.003), but not sex, specialty/clinical rotation, academic rank, or postgraduate year (PGY) level predicted PRC texting. CONCLUSIONS: Most resident and attending staff surveyed utilize texting, mostly for PRC. Texting was preferred for communicating routine PRC information. Our data may facilitate the development of guidelines for the appropriate use of PRC texting.

Comparative morbidity and mortality from cervical or thoracic esophageal anastomoses.

BACKGROUND: In the modern era of esophagectomy, we hypothesized that perioperative morbidity and mortality from cervical or thoracic sites of anastomoses would not be different. METHODS: We used the American College of Surgeons National Surgical Quality Improvement Program database to identify patients who underwent esophagectomy for lower esophageal or gastroesophageal (GE) junction malignancies from 2005 to 2010. Patients were categorized as having either a cervical or thoracic anastomosis based on CPT codes. RESULTS: There were 601 (66%) cervical and 308 (34%) thoracic anastomoses. Cervical anastomoses were associated with greater than 2 units of blood transfusion in a higher proportion of patients (10% vs. 3%, P = 0.001), and higher superficial surgical site infections (13% vs. 7%, P = 0.003). There were no difference in rates of organ/space infections (6% vs. 7%, P = 0.70), overall morbidity (38% vs. 39%, P = 0.84), or mortality (3% vs. 4%, P = 0.34). Median length of stay was similar (11.5 days cervical vs. 11 days thoracic, P = 0.89), even among patients with organ/space infections (18 days cervical vs. 21 days thoracic, P = 0.49). On multivariate analysis thoracic anastomosis was not a significant predictor of increased overall morbidity (OR 1.13: 95%CI 0.83-1.54). CONCLUSION: After esophagectomy, the site of anastomosis does not predict an increased risk of perioperative morbidity or mortality.

Age-related disparities in use of completion lymphadenectomy for melanoma sentinel lymph node metastasis.

BACKGROUND: Guidelines recommend that patients with melanoma metastatic to the sentinel lymph node (SLN) undergo a completion lymphadenectomy (CLND) of the affected lymph node basin. We have previously reported on decreased use of SLN biopsy among elderly patients. We hypothesized that elderly patients with SLN metastases would have lower rates of CLND relative to their younger counterparts. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent SLN biopsy for intermediate thickness cutaneous melanoma (Breslow thickness 1.01 mm-4.00 mm) from 2004 to 2008 and were found to have SLN metastasis. Patients were categorized according to age by decade. We then used multivariate logistic regression models to predict receipt of CLND. Additional covariates included sex, race/ethnicity, T stage, tumor histology, tumor location, and ulceration. The likelihood of receiving a CLND was reported as OR with 95% CI; significance was set at P ≤ 0.05. RESULTS: Entry criteria were met by 765 patients. Of these, 548 (71.6%) patients underwent CLND. On multivariate analysis, patients in the age groups 70-79 y old (OR 0.39, CI 0.20-0.78; P = 0.007) and ≥ 80 y old (OR 0.27, CI 0.12-0.61; P = 0.001) were less likely to undergo CLND than the youngest age group (1-39 y old). CONCLUSIONS: Elderly patients with SLN metastasis are less likely to receive CLND than their younger counterparts. A multi-center randomized clinical trial evaluating the potential survival benefit of CLND is ongoing. Further research to assess reasons why the elderly are less likely to receive CLND are needed.

Extremity soft tissue tumor surgery by surgical specialty: a comparison of case volume among oncology and non-oncology-designated surgeons.

INTRODUCTION: We sought to characterize the extent of extremity soft tissue tumor (ESTT) resections among surgical specialties, hypothesizing that substantial variation exists in the number of ESTT resections performed by specialty. METHODS: We queried the UHC-AAMC database for data from 85 institutions for years 2007-2009. We abstracted data on total number of musculoskeletal (MSK) procedures, number of subcutaneous (SQ), deep, and malignant ESTT resections, and anatomic site of resection. Data were available for 4,682 practitioners including the following specialties: general surgery (GS, N = 2,195), plastic surgery (PS, N = 792), surgical oncology (SO, N = 533), general orthopedics (GO, N = 1,079), and orthopedic oncology (OO, N = 83). RESULTS: The mean number of all MSK procedures performed per year was 19.0 ± 2.3 GS, 179.6 ± 3.0 PS, 32.4 ± 6.2 SO, 798.6 ± 115.4 GO, and 482.9 ± 6.5 OO (P = 0.001). SQ ESTT resections per year were similar among specialties (1.7 ± 0.3 GS, 2.7 ± 0.3 PS, 2.4 ± 0.4 SO, 1.7 ± 0.5 GO, 4.7 ± 0.2 OO), while deep and malignant resections were more likely performed by OO (combined deep and malignant: 0.9 ± 0.1 GS, 2.0 ± 0.4 PS, 9.9 ± 0.6 SO, 5.8 ± 0.3 GO, and 63.6 ± 8.1 OO, P = 0.001). Adjusting for number of physicians in the database, of the total deep and malignant ESTT resections, 9.4% were performed by GS, 7.7% by PS, 26.0% by SO, 30.8% by GO, and 26.0% by OO. CONCLUSION: Nearly 50% of deep and malignant ESTT resections are performed by non-oncology-designated surgeons. Approximately 17% are performed by practitioners who complete an average of one to two of these procedures per year. These findings may have significant implications for quality of care in soft tissue tumor surgery.

Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

The intact parathyroid hormone (iPTH) assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa). We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I) and 1997 to 2006 (era II, when the iPTH assay was in standard use). We estimated overall survival (OS) and disease-specific survival (DSS) using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with distant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa.

Assessing rural-urban disparities in the use of sentinel lymph node biopsy for melanoma.

BACKGROUND: We hypothesized that patients in urban areas with intermediate thickness cutaneous melanoma would have higher rates of sentinel lymph node biopsy (SLNB) relative to their rural-dwelling counterparts. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for intermediate thickness cutaneous melanoma from 2004-2008. Patients were categorized as coming from urban or rural counties based on a nine-point scale. We used multivariate logistic regression models to predict use of SLNB. Covariates examined included sex, race/ethnicity, age, T stage, tumor histology, tumor location, and ulceration. The likelihood of undergoing SLNB was reported as OR with 95% CI. RESULTS: Of 8441 patients, 8382 (99.3%) had complete information regarding use of SLNB. On multivariate analysis, patients from rural counties had a decreased likelihood of receiving a SLNB (OR 0.87, CI 0.78-0.97; P = 0.014). Additional factors associated with a decreased likelihood of receiving a SLNB included increasing age, Asian/Hispanic/Unknown race, and head and neck or overlapping primary tumor site. CONCLUSIONS: Patients in rural areas are less likely to receive a SLNB for intermediate thickness cutaneous melanoma than their urban-dwelling counterparts.

Influence of physician specialty on treatment recommendations in the multidisciplinary management of soft tissue sarcoma of the extremities.

IMPORTANCE: Although prospective randomized data are available to guide the multidisciplinary management of soft tissue sarcoma (STS) of the extremities, controversy exists regarding adjuvant chemotherapy and radiation therapy. OBJECTIVE: To determine if clinical specialty introduces bias in recommendations for multimodality treatment of STS. DESIGN: Electronic survey. SETTING: Database of active members of the American Society of Clinical Oncology, the Society of Surgical Oncology, and the Connective Tissue Oncology Society. PARTICIPANTS: Members of specialty oncology societies with an active interest in STS. EXPOSURE: Physician specialty. MAIN OUTCOMES AND MEASURES: Survey responses regarding the multidisciplinary management of STS were scored on a 5-point Likert scale and analyzed using analysis of variance. RESULTS: The questionnaire was completed by 320 of 490 potential respondents (65%), including medical (18%), radiation (8%), orthopedic (22%), and surgical oncologists (45%). Respondents concurred on the use of radiation therapy for margins positive for tumor, for high-grade tumors, for improvement in local control, for tumors larger than 10 cm, and for tumors in close proximity to a neurovascular bundle. Respondents diverged on the use of radiation therapy for tumors 5 to 10 cm in size, for low-grade tumors, for radiation-associated STS, and for survival benefit. Only radiation oncologists felt that radiation therapy was underutilized as a treatment modality (mean [SEM] Likert scale score, 2.44 [0.12]; P < .001). There was agreement on the use of chemotherapy for synovial sarcoma, for high-grade tumors, for tumors larger than 10 cm, for patients younger than 50 years of age, and for survival benefit. Medical oncologists were more likely to recommend chemotherapy for margins positive for tumor (mean [SEM] score, 3.12 [0.12]; P = .03) and for improvement in local control (mean [SEM] score, 2.91 [0.12] P = .08). Surgical oncologists placed the least emphasis on chemotherapy in the overall treatment plan (mean [SEM] score, 2.60 [0.07]; P = .001). CONCLUSIONS AND RELEVANCE: Specialty bias exists in adjuvant treatment recommendations for STS. This highlights the importance of multidisciplinary STS tumor boards and interdisciplinary care to facilitate consensus decision making for individual patients.

Sentinel lymph node biopsy in patients with thick primary cutaneous melanoma: patterns of use and underuse utilizing a population-based model.

Background. Sentinel lymph node biopsy (SLNB) for thick cutaneous melanoma is supported by national guidelines. We report on factors associated with the use and underuse of SLNB for thick primary cutaneous melanoma. Methods. The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for thick primary cutaneous melanoma from 2004 to 2008. We used multivariate logistic regression models to predict use of SLNB. Results. Among 1,981 patients, 833 (41.8%) did not undergo SLNB. Patients with primary melanomas of the arm (OR 2.07, CI 1.56-2.75; P < 0.001), leg (OR 2.40, CI 1.70-3.40; P < 0.001), and trunk (OR 1.82, CI 1.38-2.40; P < 0.001) had an increased likelihood of receiving a SLNB, as did those with desmoplastic histology (OR 1.47, CI 1.11-1.96; P = 0.008). A decreased likelihood of receiving SLNB was noted for advancing age ≥ 60 years (age 60 to 69: OR 0.58, CI 0.33-0.99, P = 0.047; age 70 to 79: OR 0.32, CI 0.19-0.54, P < 0.001; age 80 or more: OR 0.10, CI 0.06-0.16, P < 0.001) and unknown race/ethnicity (OR 0.21, CI 0.07-0.62; P = 0.005). Conclusions. In particular, elderly patients are less likely to receive SLNB. Further research is needed to assess whether use of SLNB in this population is detrimental or beneficial.

Nomograms to predict risk of in-hospital and post-discharge venous thromboembolism after abdominal and thoracic surgery: an American College of Surgeons National Surgical Quality Improvement Program analysis.

BACKGROUND: Postoperative venous thromboembolism (VTE) is increasingly viewed as a quality of care metric, although risk-adjusted incident rates of postoperative VTE and VTE after hospital discharge (VTEDC) are not available. We sought to characterize the predictors of VTE and VTEDC to develop nomograms to estimate individual risk of VTE and VTEDC. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified 471,867 patients who underwent inpatient abdominal or thoracic operations between 2005 and 2010. We excluded primary vascular and spine operations. We built logistic regression models using stepwise model selection and constructed nomograms for VTE and VTEDC with statistically significant covariates. RESULTS: The overall, unadjusted, 30-d incidence of VTE and VTEDC was 1.5% and 0.5%, respectively. Annual incidence rates remained unchanged over the study period. On multivariate analysis, age, body mass index, presence of preoperative infection, operation for cancer, procedure type (spleen highest), multivisceral resection, and non-bariatric laparoscopic surgery were significant predictors for VTE and VTEDC. Other significant predictors for VTE, but not VTEDC, included a history of chronic obstructive pulmonary disease, disseminated cancer, and emergent operation. We constructed and validated nomograms by bootstrapping. The concordance indices for VTE and VTEDC were 0.77 and 0.67, respectively. CONCLUSIONS: Substantial variation exists in the incidence of VTE and VTEDC, depending on patient and procedural factors. We constructed nomograms to predict individual risk of 30-d VTE and VTEDC. These may allow more targeted quality improvement interventions to reduce VTE and VTEDC in high-risk general and thoracic surgery patients.

Negligible effect of perioperative epidural analgesia among patients undergoing elective gastric and pancreatic resections.

BACKGROUND: There are conflicting data regarding improvements in postoperative outcomes with perioperative epidural analgesia. We sought to examine the effect of perioperative epidural analgesia vs. intravenous narcotic analgesia on perioperative outcomes including pain control, morbidity, and mortality in patients undergoing gastric and pancreatic resections. METHODS: We evaluated 169 patients from 2007 to 2011 who underwent open gastric and pancreatic resections for malignancy at a university medical center. Emergency, traumatic, pediatric, enucleations, and disseminated cancer cases were excluded. Clinicopathologic data were reviewed among epidural (E) and non-epidural (NE) patients for their association with perioperative endpoints. RESULTS: One hundred twenty patients (71 %) received an epidural and 49 (29 %) did not. There were no significant differences (P > 0.05) in mean pain scores at each of the four days (days 0-3) among the E (3.2 ± 2.7, 3.2 ± 2.3, 2.3 ± 1.9, and 2.1 ± 1.9, respectively) and NE patients (3.7 ± 2.7, 3.4 ± 1.9, 2.9 ± 2.1, and 2.4 ± 1.9, respectively). Within each of the E and NE patient groups, there were significant differences (P < 0.0001) in mean pain scores from day 0 to day 3 (P < 0.0001). Of the E patients, 69 % also received intravenous patient-controlled analgesia (PCA). Ileus (13 % E vs. 8 % NE), pneumonia (12 % E vs. 8 % NE), venous thromboembolism (6 % E vs. 4 % NE), length of stay [11.0 ± 12.1 (8, 4-107) E vs. 12.2 ± 10.7 (7, 3-54) NE], overall morbidity (36 % E vs. 39 % NE), and mortality (4 % E vs. 2 % NE) were not significantly different. CONCLUSIONS: Routine use of epidurals in this group of patients does not appear to be superior to PCA.

Utilization of sentinel lymph node biopsy in patients with ductal carcinoma in situ undergoing mastectomy.

BACKGROUND: Current guidelines suggest consideration of sentinel lymph node biopsy (SLNB) for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy. Our objective was to identify factors influencing the utilization of SLNB in this population. METHODS: We used the Surveillance Epidemiology and End Results database to identify all women with breast DCIS treated with mastectomy from 2000 to 2008. We excluded patients without histologic confirmation, those diagnosed at autopsy, those who had axillary lymph node dissections performed without a preceding SLNB, and those for whom the status of SLNB was unknown. We used multivariate logistic regression reporting odds ratios (OR) and 95% confidence intervals (CI) to evaluate the relationship of patient- and tumor-related factors to the likelihood of undergoing SLNB. RESULTS: Of 20,177 patients, 51% did not receive SLNB. Factors associated with a decreased likelihood of receiving a SLNB included advancing age (OR 0.66; 95% CI 0.62-0.71), Asian (OR 0.75; CI 0.68-0.83) or Hispanic (OR 0.84; 95% CI 0.74-0.96) race/ethnicity, and history of prior non-breast (OR 0.57; 95% CI 0.53-0.61). Factors associated with an increased likelihood of receiving a SLNB included treatment in the east (OR 1.28; 95% CI 1.17-1.4), intermediate (OR 1.25; 95% CI 1.11-1.41), high (OR 1.84; 95% CI 1.62-2.08) grade tumors, treatment after the year 2000, and DCIS size 2-5 cm (OR 1.54; 95% CI 1.42-1.68) and >5 cm (OR 2.43; 95% CI 2.16-2.75). CONCLUSIONS: SLNB is increasingly utilized in patients undergoing mastectomy for DCIS, but disparities in usage remain. Efforts at improving rates of SLNB in this population are warranted.

Combined analysis of phase III trials evaluating [99mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma.

BACKGROUND: [(99m)Tc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [(99m)Tc]tilmanocept to vital blue dye. METHODS: Patients received [(99m)Tc]tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [(99m)Tc]tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials. RESULTS: Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [(99m)Tc]tilmanocept, for 98.7 % concordance (p < 0.001). [(99m)Tc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [(99m)Tc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [(99m)Tc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [(99m)Tc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [(99m)Tc]tilmanocept. No serious adverse events were attributed to [(99m)Tc]tilmanocept. CONCLUSIONS: [(99m)Tc]Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.

Complete pathologic response to neoadjuvant radiotherapy is predictive of oncological outcome in patients with soft tissue sarcoma.

UNLABELLED: We sought to determine if complete pathological necrosis (pathCR) predicts favorable oncological outcome in soft tissue sarcoma (STS) patients receiving pre-operative radiation monotherapy (RT). PATIENTS AND METHODS: We evaluated 30 patients with primary STS treated with neoadjuvant RT followed by definitive resection, from 2000 to 2010 at our institution. We defined ≥ 95% tumor necrosis as pathCR. RESULTS: There were 22 STS of the extremities (73%), 7 of the retroperitoneum (23%), and 1 (4%) of the trunk. The median pathological percentage of tumor necrosis was 35% (range 5-100%) with three tumors (10%) demonstrating pathCR. With a median follow-up of 40 months, the 5-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and overall survival (OS) for the entire cohort were 100%, 61% ± 11%, and 69% ± 11%, respectively. Among patients with pathCR, 3-year DRFS was 100% compared to 63±11% in patients without pathCR (p=0.28). CONCLUSION: Following neoadjuvant RT for STS, pathCR is associated with a clinically but not statistically significant 37% improvement in 3-year DRFS.

Treatment options for metaplastic breast cancer.

Metaplastic breast cancer (MBC) is a malignancy characterized by the histologic presence of two or more cellular types, commonly a mixture of epithelial and mesenchymal components. MBC is rare relative to invasive ductal carcinoma (IDC), representing less than 1% of all breast cancers. Other than a lower rate of lymph node metastases, MBC tumors display poorer prognostic features relative to IDC. Due to its low incidence and pathological variability, the ideal treatment paradigm for MBC is unknown. Because of its rarity, MBC has been treated as a variant of IDC. Despite similar treatment regimens, however, patients with MBC have worse outcomes. Recent research is focused on biological differences between MBC and IDC and potential novel targets for chemotherapeutic agents. This paper serves as a summation of current literature on approaches to the multidisciplinary treatment of patients with MBC.

Geographic variation in utilization of sentinel lymph node biopsy for intermediate thickness cutaneous melanoma.

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is the standard for evaluation of the draining lymphatic basin for intermediate thickness melanoma. Despite this, SLNB has not been uniformly adopted. We hypothesized that there are geographic areas of the United States where patients are less likely to receive SLNB. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for intermediate thickness cutaneous melanoma (Breslow thickness 1.00-4.00 mm) from 2004 to 2008. Patients were categorized according to geographic area based on the reporting registry. Multivariate logistic regression models predicted use of SLNB. RESULTS: Entry criteria were met by 8957 patients. On multivariate analysis, patients from the South were less likely (OR 0.54, CI 0.48-0.62; P < 0.001) to receive a SLNB. Additional factors associated with a decreased likelihood of receiving a SLNB included head and neck primary tumor site, high or unknown serum LDH, Asian, Hispanic, Native American or unknown race, and increasing age. CONCLUSIONS: Patients from the South were less likely to receive a SLNB for an intermediate thickness cutaneous melanoma. This report of geographic disparities on a national level should be confirmed locally to better guide interventions aimed at eliminating these disparities.