Lactate Oxidase Disrupts Lactate-Activated RAS and PI3K Oncogenic Signaling.

LOX was recently shown to inhibit cancer cell proliferation and tumor growth. The mechanism of this inhibition, however, has been exclusively attributed to LOX depletion of TME lactate, a cancer cell energy source, and production of H2O2, an oxidative stressor. We report that TME lactate triggers the assembly of the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1)-associated protein complex, which includes GRB2, SOS1, KRAS, GAB1, and PI3K, for the activation of both the RAS and the PI3K oncogenic signaling pathways in breast cancer (BCa) cells. LOX treatment decreased the levels of the proteins in the protein complex via induction of their proteasomal degradation. In addition, LOX inhibited lactate-stimulated expression of the lactate transporters MCT1 and MCT4. Our data suggest that HCAR1 activation by lactate is crucial for the assembly and function of the RAS and PI3K signaling nexus. Shutting down lactate signaling by disrupting this nexus could be detrimental to cancer cells. HCAR1 is therefore a promising target for the control of the RAS and the PI3K signaling required for BCa progression. Thus, our study provides insights into lactate signaling regulation of cancer progression and extends our understanding of LOX's functional mechanisms that are fundamental for exploring its therapeutic potential.

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.

Tendon Volume Determination on Magnetic Resonance Imaging of Supraspinatus Tendinopathy.

OBJECTIVE: To determine the supraspinatus tendon volume using magnetic resonance imaging (MRI) in dogs with non-calcified supraspinatus tendinopathy (NCST), in dogs with orthopedic disease other than NCST, and in healthy dogs. STUDY DESIGN: Case series. ANIMALS: Twenty-two dogs (18 client-owned dogs; 4 purpose-bred dogs). METHODS: Dogs undergoing shoulder MRI were categorized as NCST if they were diagnosed with NCST only, had histologic confirmed diagnosis, underwent surgical treatment, and were available for follow-up longer than 4 months. Dogs with MRI performed for a forelimb lameness because of a diagnosis other than NCST were categorized as orthopedic control (OC). Healthy dogs from an unrelated study were categorized as healthy controls (HC). Tendon volume was determined from MRI using public domain software and compared across categories. RESULTS: The study included 9 NCST dogs, 9 OC dogs, and 4 HC dogs. The median tendon volume for NCST was 1,323 mm(3), OC was 630 mm(3), and HC was 512 mm(3). The volume was significantly higher in the NCST than OC (P = .0012) and HC (P = .003). There was no difference between OC and HC (P = .76). CONCLUSION: Dogs diagnosed with NCST had higher supraspinatus tendon volumes compared to dogs with other orthopedic disorders and healthy dogs.

100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series.

BACKGROUND: Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it. OBJECTIVE: We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma. METHODS: A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid. RESULTS: A 100% complete local response rate with long-term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors. LIMITATIONS: Small number of patients, retrospective review of charts, and lack of a comparison group were limitations. CONCLUSION: Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision.

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.

Detailed protocol for administration of intralesional IL-2 for the treatment of Stage IIIc and IV M1a metastatic melanoma based on current NCCN guidelines.

Melanoma claims approximately 9,000 lives in the United States annually. Patients who present with satellite, in-transit, or distant cutaneous metastases have limited treatment options and the prognosis for patients with metastatic disease remains poor. Surgical excision remains the most common treatment modality for cutaneous metastases, but may not address concurrent subclinical in-transit metastases. Other palliative treatment options include Bacillus Calmette-Guérin (BCG) and isolated limb perfusion (ILP). Although intravenous IL-2 has been used for treatment of metastatic melanoma since 1998, intralesional IL-2 has only now been included in the most recent National Comprehensive Cancer Network (NCCN) guidelines after case series and phase I/II clinical trials have shown promising results against Stage IIIc and IV M1a melanoma. Intralesional IL-2 protocols have varied markedly from study to study and there are no consensus guidelines available to help direct treatment. Herein, we present a detailed protocol for the administration of intralesional IL-2 that has been successfully used at two different institutions for treatment of cutaneous melanoma metastases.

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.

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.

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.

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.