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V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a negative immune-checkpoint protein that suppresses T-cell responses. To determine whether VISTA synergizes with another immune-checkpoint, programmed death 1 (PD-1), this study characterizes the immune responses in VISTA-deficient, PD-1-deficient (KO) mice and VISTA/PD-1 double KO mice. Chronic inflammation and spontaneous activation of T cells were observed in both single KO mice, demonstrating their nonredundancy. However, the VISTA/PD-1 double KO mice exhibited significantly higher levels of these phenotypes than the single KO mice. When bred onto the 2D2 T-cell receptor transgenic mice, which are predisposed to development of inflammatory autoimmune disease in the CNS, the level of disease penetrance was significantly enhanced in the double KO mice compared with in the single KO mice. Consistently, the magnitude of T-cell response toward foreign antigens was synergistically higher in the VISTA/PD-1 double KO mice. A combinatorial blockade using monoclonal antibodies specific for VISTA and PD-L1 achieved optimal tumor-clearing therapeutic efficacy. In conclusion, our study demonstrates the nonredundant role of VISTA that is distinct from the PD-1/PD-L1 pathway in controlling T-cell activation. These findings provide the rationale to concurrently target VISTA and PD-1 pathways for treating T-cell-regulated diseases such as cancer. [ABSTRACT FROM AUTHOR]

The metabolic syndrome is a clinically important but often misunderstood topic. A concept in evolution, controversy surrounds the metabolic syndrome. The medical literature documents disagreement in the criteria for diagnosis, a shift in emphasis as to the roles of obesity and insulin resistance as underlying causes, and questions about the fundamental clinical utility of the syndrome. The practical strengths and limitations of the metabolic syndrome in clinical practice are reviewed. [ABSTRACT FROM AUTHOR]

The metabolic syndrome is a clinically important but often misunderstood topic. A concept in evolution, controversy surrounds the metabolic syndrome. The medical literature documents disagreement in the criteria for diagnosis, a shift in emphasis as to the roles of obesity and insulin resistance as underlying causes, and questions about the fundamental clinical utility of the syndrome. The practical strengths and limitations of the metabolic syndrome in clinical practice are reviewed. [ABSTRACT FROM AUTHOR]

Purpose: A NIR tomography system that combines frequency domain (FD) and continuous wave (CW) measurements was used to image normal and malignant breast tissues. Methods: FD acquisitions were confined to wavelengths less than 850 nm because of detector limitations, whereas light from longer wavelengths (up to 948 nm) was measured in CW mode with CCD-coupled spectrometer detection. The two data sets were combined and processed in a single spectrally constrained reconstruction to map concentrations of hemoglobin, water, and lipid, as well as scattering parameters in the breast. Results: Chromophore concentrations were imaged in the breasts of nine asymptomatic volunteers to evaluate their intrasubject and intersubject variability. Normal subject data showed physiologically expected trends. Images from three cancer patients indicate that the added CW data is critical to recovering the expected increases in water and decreases in lipid content within malignancies. Contrasts of 1.5 to twofold in hemoglobin and water values were found in cancers. Conclusions: In vivo breast imaging with instrumentation that combines FD and CW NIR data acquisition in a single spectral reconstruction produces more accurate hemoglobin, water, and lipid results relative to FD data alone. [ABSTRACT FROM AUTHOR]

Background: Autologous transfusion (AT) has long been considered unsafe in major oncologic operations due to a theoretic risk of spreading metastatic disease, however, few data support this assumption.Study Design: We conducted a retrospective analysis of 147 patients who underwent partial hepatectomy for colorectal cancer metastases at a single institution. Seventy-four patients received AT only and 73 received no transfusion (NT). We compared the overall survival and recurrence-free survival of these groups using Kaplan-Meier survival curves and adjusted hazard ratios.Results: Patients who received AT had greater blood loss, more extensive resections, and longer procedure times. There were no differences in age, sex, proportion colon vs rectal cancer, or Fong Clinical Risk Score. Mean follow-up was 54 months. Median overall survival in the AT group was 59 months compared with 54 months in the NT group (p = 0.69) on log-rank test. No difference in overall survival was noted after adjusting for age, sex, Fong score, type of cancer (colon vs rectal), receipt of neoadjuvant therapy, receipt of adjuvant therapy, extent of resection and blood loss (hazard ratio AT vs NT 0.58; 95% CI 0.31 to 1.11; p = 0.10). Recurrence-free survival was also similar in the AT and NT groups (27% vs 37%; p = 0.22). The adjusted hazard ratio for recurrence-free survival was 0.95 (95% CI 0.54 to 1.65; p = 0.85).Conclusions: Autologous blood transfusion is not associated with an increased recurrence risk or a higher mortality rate. Surgeons performing liver resections for patients with colorectal cancer metastases can safely transfuse filtered autologous blood. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data to inform appropriate opioid prescribing for patients who are discharged after a hospital admission for a surgical procedure.Study Design: We studied 333 inpatients discharged to home after bariatric, benign foregut, liver, pancreas, ventral hernia, and colon surgery. Chronic opioid users or patients who had complications were excluded. Home opioid usage was quantified in 90% of the remaining patients by questionnaires and phone surveys.Results: Eighty-five percent of patients were prescribed an opioid and 38% of prescribed opioid pills were taken. Fifteen opioid pills satisfied the opioid needs of 88% of patients discharged on postoperative day (POD) 1. For patients discharged after POD 1, in multivariate analysis, the number of opioid pills used at home was associated with the number taken the day before discharge (p < 0.0001) and patient age (p = 0.006), but not the type of surgery. Forty-one percent of patients took no opioids the day before discharge, 33% took 1 to 3, and 26% took more than 4 pills. Eighty-five percent of patients' home opioid requirements would be satisfied using the following guideline: if no opioid pills are taken the day before discharge, no prescription is needed; if 1 to 3 opioid pills are taken the day before discharge, then a prescription for 15 opioid pills is given at discharge; and if 4 or more pills are taken the day before discharge, then a prescription for 30 opioid pills is given at discharge. If these guidelines were used, the number of opioid pills prescribed would decrease by 40%.Conclusions: For patients admitted after surgical procedures, post-discharge opioid use is best predicted by usage the day before discharge. Use of this guideline could decrease opioid prescriptions substantially and effectively treat patients' pain. [ABSTRACT FROM AUTHOR]

Introduction: Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing.Methods: Spatial frequency domain imaging (SFDI) was used to quantify near-infrared (NIR) optical parameters at the surface of 47 lumpectomy tissue specimens. Spatial frequency and wavelength-dependent reflectance spectra were parameterized with matched simulations of light transport. Spectral images were co-registered to histopathology in adjacent, stained sections of the tissue, cut in the geometry imaged in situ. A supervised classifier and feature-selection algorithm were implemented to automate discrimination of breast pathologies and to rank the contribution of each parameter to a diagnosis.Results: Spectral parameters distinguished all pathology subtypes with 82% accuracy and benign (fibrocystic disease, fibroadenoma) from malignant (DCIS, invasive cancer, and partially treated invasive cancer after neoadjuvant chemotherapy) pathologies with 88% accuracy, high specificity (93%), and reasonable sensitivity (79%). Although spectral absorption and scattering features were essential components of the discriminant classifier, scattering exhibited lower variance and contributed most to tissue-type separation. The scattering slope was sensitive to stromal and epithelial distributions measured with quantitative immunohistochemistry.Conclusions: SFDI is a new quantitative imaging technique that renders a specific tissue-type diagnosis. Its combination of planar sampling and frequency-dependent depth sensing is clinically pragmatic and appropriate for breast surgical-margin assessment. This study is the first to apply SFDI to pathology discrimination in surgical breast tissues. It represents an important step toward imaging surgical specimens immediately ex vivo to reduce the high rate of secondary excisions associated with breast lumpectomy procedures. [ABSTRACT FROM AUTHOR]

Lymph node biopsy is employed in many cancer surgeries to identify metastatic disease and to determine cancer stage, yet morbidity and diagnostic delays associated with lymph node biopsy could be avoided if noninvasive imaging of nodal involvement were reliable. Molecular imaging has potential in this regard; however, variable delivery and nonspecific uptake of imaging tracers have made conventional approaches ineffective clinically. Here we present a method of correcting for nonspecific uptake with injection of a second untargeted tracer that allows for quantification of tumor burden in lymph nodes. We confirmed the approach in an athymic mouse model of metastatic human breast cancer by targeting epidermal growth factor receptor, a cell surface receptor overexpressed by many cancers. We observed a significant correlation between in vivo (dual-tracer) and ex vivo measures of tumor burden (r = 0.97, P < 0.01), with an ultimate sensitivity of approximately 200 cells (potentially more sensitive than conventional lymph node biopsy). [ABSTRACT FROM AUTHOR]

To justify a practice change, it is critical to determine if opioids prescribed after surgery, surgery prescription (Rx) opioids, are in fact associated with opioid misuse and diversion. Currently, there is only limited data to support this assumption. We administered a 40-question survey to US adults (18+) who had received a surgery Rx opioid within the last 5 y on Amazon Mechanical Turk, an online crowdsourcing worksite. Incidence and risk factors for surgery Rx opioid misuse, self-reported taking of surgery Rx opioids in a way other than instructed by a provider, and diversion, self-reported having one's surgery Rx opioids shared, sold, or stolen, were analyzed. The government validated Opioid Risk Tool (ORT) was used. A total of 966 participants from all 50 states met inclusion: 52% were male, 43% were aged 30-39 y, and 79% self-identified as white. Overall, 34% (n = 333) of respondents reported misusing their surgery Rx opioids and risk factors included working in healthcare, scoring high on the ORT, experiencing an elevated mood with opioids, refilling a Rx, and keeping leftover pills. A total of 22% (n = 212) reported diverting their surgery Rx opioids, and risk factors included working in healthcare, scoring high on the ORT, undergoing plastic surgery, refilling a Rx, and keeping leftover pills. Rates of surgery Rx opioid misuse and diversion in the US may be as high as one in three and one in five adults, respectively. Efforts to improve leftover pill disposal and risk stratification for prescribing patterns may help to mitigate risk. [ABSTRACT FROM AUTHOR]

Background: To optimize responsible opioid prescribing after inpatient operation, we implemented a clinical trial with the following objectives: prospectively validate patient-centered opioid prescription guidelines and increase the FDA-compliant disposal rate of leftover opioid pills to higher than currently reported rates of 20% to 30%.Study Design: We prospectively enrolled 229 patients admitted for 48 hours or longer after elective general, colorectal, urologic, gynecologic, or thoracic operation. At discharge, patients received a prescription for both nonopioid analgesics and opioids based on their opioid usage the day before discharge: if 0 oral morphine milligram equivalents (MME) were used, then five 5-mg oxycodone pill-equivalents were prescribed; if 1 to 29 MME were used, then fifteen 5-mg oxycodone pill-equivalents were prescribed; if 30 or more MME were used, then thirty 5-mg oxycodone pill-equivalents were prescribed. We considered patients' opioid pain medication needs to be satisfied if no opioid refills were obtained. To improve FDA-compliant disposal of leftover pills, we implemented patient education, convenient drop-box, reminder phone call, and questionnaire.Results: Our opioid guideline satisfied 93% (213 of 229) of patients. Satisfaction was significantly higher in lower opioid usage groups (p = 0.001): 99% (99 of 100) in the 0 MME group, 90% (91 of 101) in the 1 to 29 MME group, and 82% (23 of 28) in the 30 or more MME group. Overall, 95% (217 of 229) of patients used nonopioid analgesics. Sixty percent (138 of 229) had leftover pills; 83% (114 of 138) disposed of them using an FDA-compliant method and 51% (58 of 114) used the convenient drop-box. Of 2,604 prescribed pills, only 187 (7%) were kept by patients.Conclusions: This clinical trial prospectively validated a patient-centered opioid discharge prescription guideline that satisfied 93% of patients. FDA-compliant disposal of excess pills was achieved in 83% of patients with easily actionable interventions. [ABSTRACT FROM AUTHOR]

Background: Opioid prescribing guidelines for partial mastectomy (PM) and PM with sentinel lymph node biopsy (PM-SLNB) recommend prescribing anywhere from 0 to 15 oxycodone pills for postoperative pain. We sought to eliminate opioids after breast-conserving surgery.Study Design: In January 2017, we implemented a perioperative pathway in which patients received (1) preoperative acetaminophen, (2) pre-incisional bupivacaine skin infiltration, (3) post-excision bupivacaine wound deposition, (4) intraoperative ketorolac, (5) instructions to use both acetaminophen and ibuprofen for postoperative analgesia, and (6) counseling to set the expectation that opioids would not be required. We measured the percentage of patients who received, filled, and used opioid prescriptions. We compared this to historical institutional data from 2016.Results: There were 226 patients (mean age: 62 ± 13 years) who underwent surgery: 50% (114 of 226) underwent PM alone and 50% (112 of 226) PM-SLNB. Twenty-four patients (11%) required opioids in the recovery unit, and 14 (6%) were discharged home with a prescription. Five of the 14 patients (36%) did not fill their prescription. Among the patients who did fill their prescription, only 1 patient used opioids. In addition, 2 (1%) patients had difficulty managing their postoperative pain and were prescribed opioids within 7 days of surgery. Ultimately, 99% (223 of 226) of patients managed their postoperative pain after discharge without opioids. This represents a significant decrease in opioid use after breast conserving surgery, from 40% in 2016 to 1% after pathway implementation, p < 0.001.Conclusions: When a multimodal nonopioid pain pathway was implemented, 99% of patients undergoing breast-conserving surgery did not require opioids after discharge. [ABSTRACT FROM AUTHOR]

Background: Due to its short duration of therapy and low rates of local recurrence, women undergoing breast conservation are increasingly opting for partial breast irradiation with the MammoSite (Cytyc/Hologic) catheter. In early follow-up studies, few complications were reported. Few data, however, exist regarding longer-term complications. We compared the long-term local toxicities of MammoSite partial breast irradiation with those resulting from whole breast radiation. Study Design: This was a retrospective study performed in a single academic medical center. All patients who underwent breast-conserving surgery between 2003 and 2008, who met institutional criteria for brachytherapy, were included. We compared women treated with MammoSite with patients treated with whole breast radiation therapy (WBRT). Endpoints included incidence of palpable masses at the lumpectomy site, telangiectasias, and local recurrence. Results: Seventy-one MammoSite patients and 245 WBRT patients were well matched with regard to clinical characteristics. Median follow-up was 4 years. A palpable mass developed at the site of lumpectomy in 27% of the MammoSite patients compared with 7% of the WBRT patients (p < 0.0001). Telangiectasias developed more frequently in the MammoSite group than in the WBRT group (24% vs 4%, p < 0.001). Forty-two percent of patients treated with MammoSite developed a palpable mass, telangectasia, or both. Conclusions: Palpable masses and telangiectasias are frequent long-term complications after MammoSite brachytherapy and occur at a significantly higher rate after MammoSite brachytherapy than after WBRT. This increased rate of long-term local toxicity should be considered when counseling women on options for adjuvant radiation therapy after breast-conserving surgery. [Copyright &y& Elsevier]