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In July 2016, the American Society of Breast Surgeons published guidelines discouraging contralateral prophylactic mastectomy for average-risk women with unilateral breast cancer. We incorporated these into practice with structured patient counseling and aimed to assess the effect of this initiative on contralateral prophylactic mastectomy rates. We evaluated female patients with unilateral breast cancer undergoing mastectomy at our institution from January 2011 to November 2022. Variables associated with contralateral prophylactic mastectomy and trends over time were analyzed using the Wilcoxon rank sum test or χ2 analysis as appropriate. Among 3,208 patients, (median age 54 years) 1,366 (43%) had a unilateral mastectomy, and 1,842 (57%) also had a concomitant contralateral prophylactic mastectomy. Across all patients, contralateral prophylactic mastectomy rates significantly decreased post-implementation from 2017 to 2019 (55%) vs 2015 to 2016 (62%) (P =.01) but increased from 2020 to 2022 (61%). Immediate breast reconstruction rate was 70% overall (81% with contralateral prophylactic mastectomy and 56% without contralateral prophylactic mastectomy, P <.001). Younger age, White race, mutation status, and earlier stage were also associated with contralateral prophylactic mastectomy. Genetic testing increased from 27% pre-guideline to 74% 2020 to 2022, as did the proportion of patients with a pathogenic variant (4% pre-guideline vs 11% from 2020–2022, P <.001), of whom 91% had a contralateral prophylactic mastectomy. Among tested patients without a pathogenic variant and patients not tested, contralateral prophylactic mastectomy rates declined from 78% to 67% and 48% to 38% pre -and post-guidelines, respectively, P <.001. Implementation of specific patient counseling was effective in decreasing contralateral prophylactic mastectomy rates. While recognizing that patient choice plays a significant role in the decision for contralateral prophylactic mastectomy, further educational efforts are warranted to affect contralateral prophylactic mastectomy rates, particularly in the setting of negative genetic testing. [ABSTRACT FROM AUTHOR]

Adaptive management of protected coastal wetlands requires an understanding of barrier dynamics over long timescales as well as feedbacks with ecosystem processes. In this study, we examined diatom (siliceous algae) and Cladocera (crustacean zooplankton) subfossil remains preserved in sediments as (paleo)ecological indicators of barrier beach dynamics in coastal wetlands along the north-central shore of Lake Ontario. Sediments integrate information across seasons and habitats, accounting for spatiotemporal variability in ecological indicator taxa that is often missed in contemporary sampling efforts. Subfossil remains also allow for reconstruction of historical changes before contemporary monitoring began. We found that small benthic Fragilariaceae diatom taxa were most abundant in high-closure barrier beach wetlands, and were uncommon in drowned river mouth wetlands, while Cladocera assemblages did not reflect coastal wetland hydrogeomorphology. A high-resolution paleoecological study of McLaughlin Bay, a high-closure barrier beach wetland, showed that the abundance of small benthic Fragilariaceae decreased, and diatom diversity increased, when the barrier was breached in 2005 and 1954. Recent increases in small benthic Fragilariaceae were consistent with assessments by the local conservation authority that McLaughlin Bay has become less connected to Lake Ontario in recent years, lending support to artificial barrier beach manipulation as a strategy to improve water quality. Barrier beach dynamics create a natural disturbance regime that is important for maintaining biodiversity and water quality in protected coastal wetlands. Our study provides an approach to monitor and investigate coupled physical-ecological dynamics of barrier beach coastal wetlands over decadal to centennial timescales. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a multi-stage process initiated through the formation of a benign adenoma, progressing to an invasive carcinoma and finally metastatic spread. Tumour cells must adapt their metabolism to support the energetic and biosynthetic demands associated with disease progression. As such, targeting cancer cell metabolism is a promising therapeutic avenue in CRC. However, to identify tractable nodes of metabolic vulnerability specific to CRC stage, we must understand how metabolism changes during CRC development. Here, we use a unique model system – comprising human early adenoma to late adenocarcinoma. We show that adenoma cells transition to elevated glycolysis at the early stages of tumour progression but maintain oxidative metabolism. Progressed adenocarcinoma cells rely more on glutamine-derived carbon to fuel the TCA cycle, whereas glycolysis and TCA cycle activity remain tightly coupled in early adenoma cells. Adenocarcinoma cells are more flexible with respect to fuel source, enabling them to proliferate in nutrient-poor environments. Despite this plasticity, we identify asparagine (ASN) synthesis as a node of metabolic vulnerability in late-stage adenocarcinoma cells. We show that loss of asparagine synthetase (ASNS) blocks their proliferation, whereas early adenoma cells are largely resistant to ASN deprivation. Mechanistically, we show that late-stage adenocarcinoma cells are dependent on ASNS to support mTORC1 signalling and maximal glycolytic and oxidative capacity. Resistance to ASNS loss in early adenoma cells is likely due to a feedback loop, absent in late-stage cells, allowing them to sense and regulate ASN levels and supplement ASN by autophagy. Together, our study defines metabolic changes during CRC development and highlights ASN synthesis as a targetable metabolic vulnerability in later stage disease. • Adenoma cells elevate glycolysis early in tumour progression but maintain levels of oxidative metabolism. • Adenocarcinoma cells are more flexible with respect to fuel source, enabling proliferation in nutrient-poor environments. • Asparagine synthesis is a node of metabolic vulnerability in late-stage adenocarcinoma cells. • Adenocarcinoma cells are dependent on asparagine synthetase to support mTORC1 signalling and metabolism. • Adenoma cells are resistant to asparagine deprivation, this may be due their ability to supplement it through autophagy. [ABSTRACT FROM AUTHOR]

The standard of care for non-muscle-invasive bladder cancer (NMIBC) is transurethral resection followed by risk stratified use of intravesical immune- or chemotherapy and for multifocal, recurrent and high grade disease, radical cystectomy with high rates of cure. Bladder preservation analogous to the trimodality therapy approach in muscle-invasive bladder cancer (MIBC) has not been adequately explored but the available data suggests that NMIBC is a radioresponsive malignancy and that in a proportion of patients bladder preservation would be possible. Combination modality with chemotherapy, hypoxia sensitisation, hyperthermia and immunotherapy are all approaches which have been shown effective. Unfortunately the quality of the available data is poor. Although there are many putative prognostic biomarkers for progression in NMIBC none have emerged in clinical use and there are none predictive for response to non-surgical treatment. This would be an important component of future large scale studies to evaluate the precise role of radiotherapy within a multimodality schedule for bladder reservation in NMIBC. [ABSTRACT FROM AUTHOR]

• Bone marker data paired with pain scores from a large prospective randomised trial. • No correlation seen between NTx or Cystatin C and pain response. • Reduction in NTx concentrations seen 4 weeks after ibandronate. • No change NTx after radiotherapy suggesting a different mechanism of action to ibandronate. The Radiotherapy IBandronate (RIB) trial compared single dose radiotherapy and a single infusion of ibandronate in 470 bisphosphonate naïve patients with metastatic bone pain from prostate cancer randomised into a non-inferiority two arm study. Results for the primary endpoint of pain score response at 4 weeks showed that the ibandronate arm was non-inferior to single dose radiotherapy. In addition to pain assessments including analgesic use made at baseline, 4, 8, 12, 26 and 52 weeks, urine was collected at baseline, 4 and 12 weeks. It was subsequently analysed for urinary N-telopeptide (NTx) and cystatin C. Linear regression models were used to compare the continuous outcome measures for urinary markers within treatment arms and baseline measurements were included as covariates. Interaction terms were fitted to allow for cross-treatment group comparisons. The primary endpoint of the RIB trial was worst pain response at 4 weeks and there was no treatment difference seen. Urine samples and paired pain scores at 4 weeks were available for 273 patients (radiotherapy 168; ibandronate 159) The baseline samples measured for the RIB trial had an average concentration of 193 nM BCE/mM creatinine (range of 7.3–1871) compared to the quoted normal range of 33 nM BCE/mM creatinine (3 to 63). In contrast the average value of Cystatin C was 66 ng/ml (ranges ND – 1120 ng/ml) compared to the quoted normal range of 62.9 ng/ml (ranges 12.6–188 ng/ml). A statistically significant reduction in NTx concentrations between baseline and 4 weeks was seen in the ibandronate arm but not in the radiotherapy arm. No correlation between pain response and urinary marker concentration was seen in either the ibandronate or radiotherapy cohort at any time point. NTx was significantly raised compared to the normal range consistent with a role as a biomarker for bone metastases from prostate cancer. A significant reduction in NTx 4 weeks after ibandronate is consistent with its action in osteoclast inhibition which was not seen after radiotherapy implying a different mode of action for radiation. There was no correlation between bone biomarker levels and pain response. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: There are limited data on pretreatment imaging features that can predict response to neoadjuvant chemotherapy (NAC). To extract volumetric pretreatment MRI radiomics features and assess corresponding associations with breast cancer molecular subtypes, pathological complete response (pCR), and residual cancer burden (RCB) in patients treated with NAC.Materials and Methods: In this IRB-approved study, clinical and pretreatment MRI data from patients with biopsy-proven breast cancer who received NAC between September 2009 and July 2016 were retrospectively analyzed. Tumors were manually identified and semi-automatically segmented on first postcontrast images. Morphological and three-dimensional textural features were computed, including unfiltered and filtered image data, with spatial scaling factors (SSF) of 2, 4, and 6 mm. Wilcoxon rank-sum tests and area under the receiver operating characteristic curve were used for statistical analysis.Results: Two hundred and fifty nine patients with unilateral breast cancer, including 73 (28.2%) HER2+, 112 (43.2%) luminal, and 74 (28.6%) triple negative breast cancers (TNBC), were included. There was a significant difference in the median volume (p = 0.008), median longest axial tumor diameter (p = 0.009), and median longest volumetric diameter (p = 0.01) among tumor subtypes. There was also a significant difference in minimum signal intensity and entropy among the tumor subtypes with SSF = 4 mm (p = 0.009 and p = 0.02 respectively) and SSF = 6 mm (p = 0.007 and p < 0.001 respectively). Additionally, sphericity (p = 0.04) in HER2+ tumors and entropy with SSF = 2, 4, 6 mm (p = 0.004, 0.02, 0.047 respectively) in luminal tumors were significantly associated with pCR. Multiple features demonstrated significant association (p < 0.05) with pCR in TNBC and with RCB in luminal tumors and TNBC, with standard deviation of intensity with SSF = 6 mm achieving the highest AUC (AUC = 0.734) for pCR in TNBC.Conclusion: MRI radiomics features are associated with different molecular subtypes of breast cancer, pCR, and RCB. These features may be noninvasive imaging biomarkers to identify cancer subtype and predict response to NAC. [ABSTRACT FROM AUTHOR]

This investigation used portable air cleaners (PACs) and quantitative filter forensics (QFF) to assess week-long average airborne concentrations of SARS-CoV-2 RNA in homes occupied with COVID-symptomatic individuals, classrooms, and dining locations throughout Toronto, Canada. PACs were deployed for one week each, and dust from filters was collected via vacuuming. SARS-CoV-2 RNA from filter dust was quantified using reverse transcription-polymerase chain reaction (RT-PCR). RNA quantities and PAC metadata were used to estimate airborne concentrations of SARS-CoV-2 RNA. The highest concentrations of RNA were found in isolation rooms (median concentration = 8.68 RNA copies/m3). Classrooms had lower concentrations during summer than in fall and winter (median concentration of sampling weeks when RNA was present = 0.02 RNA copies/m3 and 0.11 RNA copies/m3, respectively), which may be attributed to differences in classroom occupancy among other factors. Limitations include unknown recovery efficiency of RNA from filters and the dynamics of concentrations due to the temporal averaging of QFF. Our results are consistent with previous research highlighting the effectiveness of isolation in preventing distribution of high concentrations of SARS-CoV-2 RNA throughout a home. Overall, QFF is a beneficial tool for environmental sampling of respiratory airborne viral RNA such as SARS-CoV-2 RNA, that can be implemented for long-term sampling in mixed-occupancy environments. [Display omitted] • Quantitative filter forensics provides week-long estimates of airborne SARS-CoV-2 RNA. • Isolation rooms have the highest SARS-CoV-2 RNA concentrations in homes. • Classrooms have seasonal differences in concentrations of SARS-CoV-2 RNA. • No significant difference in RNA quantification between RT-dPCR and RT-dPCR. [ABSTRACT FROM AUTHOR]

Management of patients with classic lobular carcinoma in situ diagnosed on core needle biopsy remains controversial, in part because of clinicopathologic overlap with atypical lobular hyperplasia. Although atypical lobular hyperplasia on core needle biopsy is observed because of its low upgrade rate (~1%), consensus is lacking for lobular carcinoma in situ. Therefore, we evaluated lobular carcinoma in situ upgrade rates. With institutional review board approval, we identified 90 patients (from October 2008 to December 2019) with lobular carcinoma in situ on core needle biopsy as their highest-risk lesion. We excluded patients with concurrent ipsilateral cancer. Variables associated with upgrade were assessed with logistic regression. Of the 90 patients, 81 (90%), median age 55 y, underwent surgical excision. Indications for diagnostic core needle biopsy included mammographic calcifications (48, 53.3%), mass/distortion (28, 31.1%), and non-mass enhancement (12, 13.3%). Final surgical pathology upgraded 11 of 81 patients (13.6%, 95% CI: 7.8%–22.7%) to cancer: invasive lobular (n = 7), invasive ductal (n = 1), and ductal carcinoma in situ/pleomorphic lobular carcinoma in situ (n = 3). Only 1 patient with invasive cancer was node-positive. Concurrent contralateral cancer (OR 4.41, 95% CI: 1.06–17.38, P =.04) and larger lesion size (OR 1.78 per 1 cm, 95% CI: 1.19–2.95, P =.005) predicted upgrade. Our data suggest that, unlike atypical lobular hyperplasia, lobular carcinoma in situ identified on core needle biopsy should be surgically excised. The high proportion of upgrades to early stage invasive lobular carcinoma underscores the value of this approach. [ABSTRACT FROM AUTHOR]

A web-based survey of pediatric care providers revealed differences in their preference for clinical charts that monitor growth in children with obesity. These findings are attributed to pediatric specialty training. Very few providers believe the currently available Centers for Disease Control and Prevention 2000 body mass index-for-age charts adequately track growth in children with obesity. [ABSTRACT FROM AUTHOR]

Immediate breast reconstruction after mastectomy may confer more complication rates in the elderly. Therefore, granular analysis of postmastectomy complications in women aged ≥65 years may help formulate clinical guidelines to improve patient selection and outcomes. We identified patients undergoing mastectomy with or without immediate reconstruction from our breast surgery database (2014–2018). Complications requiring treatment were compared between patients aged ≥65 and <65 years. A total of 1,721 mastectomies were performed in 1,698 patients; 85.8% had a 30-day follow-up. Of these patients, 968 (65.6%) had immediate breast reconstruction, of whom 95 (9.8%) were aged ≥65 years. Among patients aged ≥65 years, 27.6% underwent mastectomy with immediate breast reconstruction compared with 77.1% of women aged <65 years (P <.001). Overall complication rates were not greater for older compared with younger mastectomy patients but were for older versus younger patients who had mastectomy with immediate breast reconstruction (12.6% vs 6.8%; P =.04). Hematoma requiring reoperation was more frequent in patients aged ≥65 years (5.3% vs 0.9%; P =.006). Necrosis (5.3% vs 2.6%; P =.18) and 30-day unplanned readmissions (7.4% vs 4.0%; P =.18) were not greater. Despite low overall postoperative complication rates, we found some clinically relevant differences between older and younger patients after mastectomy with immediate breast reconstruction. Additional investigation of contributing factors may help further refine patient selection. In the interim, elderly patients should be counseled on their somewhat greater risk of postoperative complications to facilitate shared decision making. [ABSTRACT FROM AUTHOR]

Normal tissue complication probability (NTCP) models can be useful to estimate the risk of fibrosis after breast-conserving surgery (BCS) and radiotherapy (RT) to the breast. However, they are subject to uncertainties. We present the impact of contouring variation on the prediction of fibrosis. 280 breast cancer patients treated BCS-RT were included. Nine Clinical Target Volume (CTV) contours were created for each patient: i) CTV_crop (reference), cropped 5 mm from the skin and ii) CTV_skin, uncropped and including the skin, iii) segmenting the 95% isodose (Iso 95%) and iv) 3 different auto-contouring atlases generating uncropped and cropped contours (Atlas_skin/Atlas_crop). To illustrate the impact of contour variation on NTCP estimates, we applied two equations predicting fibrosis grade ≥ 2 at 5 years, based on Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) models, respectively, to each contour. Differences were evaluated using repeated-measures ANOVA. For completeness, the association between observed fibrosis events and NTCP estimates was also evaluated using logistic regression. There were minimal differences between contours when the same contouring approach was followed (cropped and uncropped). CTV_skin and Atlas_skin contours had lower NTCP estimates (−3.92%, IQR 4.00, p < 0.05) compared to CTV_crop. No significant difference was observed for Atlas_crop and Iso 95% contours compared to CTV_crop. For the whole cohort, NTCP estimates varied between 5.3% and 49.5% (LKB) or 2.2% and 49.6% (RS) depending on the choice of contours. NTCP estimates for individual patients varied by up to a factor of 4. Estimates from "skin" contours showed higher agreement with observed events. Contour variations can lead to significantly different NTCP estimates for breast fibrosis, highlighting the importance of standardising breast contours before developing and/or applying NTCP models. • Differences in breast radiotherapy contouring after breast-conserving surgery influence the estimated probability of normal tissue complications. • For individual patients, the estimated risk of grade ≥ 1 breast fibrosis at five years after radiotherapy varies by up to factor of 4. • It is essential to define and standardise contours when developing/applying NTCP models. [ABSTRACT FROM AUTHOR]

The cultivation and commercialization of American elderberries (Sambucus nigra subsp. canadensis), rich in acylated anthocyanins, is nascent. In this study, American elderberry juice and pomace extract were spray dried using soy protein isolate (SPI) or tapioca starch (TS) as carriers to develop functional food ingredients. Physicochemical, morphological, and bioactive properties were analyzed, and an in vitro gastrointestinal digestion model was used to study polyphenol bioaccessibility. An efficient spray drying process (solids recovery >60%) was established. Elderberry particles produced with SPI had higher solubility (60%–64%), lower porosity (69%–70%), and better flowability (22% Carr index, 1.29 Hausner ratio). Spray dried particles produced with tapioca starch showed significantly higher total polyphenol content (42–49 mg gallic acid equivalent/g sample), proanthocyanidin content (0.76–2.86 mg proanthocyanidin-B2/g sample), and anthocyanins (7.86–33.80 mg/g sample) for both elderberry juice and pomace extract, compared to SPI-derived ones. Particles of encapsulated elderberry juice or pomace extract with SPI had higher bioaccessibility compared to non-encapsulated elderberry juice or TS-derived particles. Overall, spray drying American elderberry juice and pomace extract is an effective and sustainable strategy to create novel ingredients for multiple food applications. These findings offer an industry-friendly technological solution to develop value-added ingredients for the emerging American elderberry market. [Display omitted] • More than 75% acylated anthocyanins were detected in American elderberries. • Higher bioaccessibility was observed for SPI-derived elderberry particles. • Higher amounts of TPC, PAC, ACY were observed for tapioca-starch derived particles. • SPI-derived particles showed better flowability, solubility, and morphology. • Overall, the spray drying solids recovery was (>60%) for all treatments. [ABSTRACT FROM AUTHOR]

In April 2021, the Japanese government decided to release tonnes of radioactive wastewater from the wrecked Fukushima nuclear power plant into the ocean, a decision that will likely to pose a direct threat to the marine environment of not only Japan, but also the jurisdictional waters of neighboring countries. Legal measures such as litigation against Japan has been an option for the neighboring countries, although they require more time than available, unless interim measure are ordered. Based on a multidisciplinary research approach that integrates open-source research data, authoritative data and conclusions, this paper shows that since the ocean is a complex and changeable system and radionuclides could be redistributed by the ocean currents and eddies, the radioactive wastewater discharge will cause or likely to cause contamination in fish products and fishing grounds and have negative impact on marine life and humans. In response to the widely known skepticism regarding the application and efficiency of international law concerning the 2011 Fukushima Daichii accident, this paper argues that the nuclear law, ocean law and general principles of international law do provide sufficient constraints on the forthcoming radioactive wastewater discharge. Among the IAEA's legal documents, the Convention on Nuclear Safety (CNS) and the Convention on Early Notification are the most applicable conventions to the Fukushima radioactive wastewater discharge. Treaty interpretation of the "at sea" element in the London Dumping Convention and its Protocol is crucial to determine the legitimacy of the planned oceanic discharge activity of Japan. In addition, legal characterization of sources of pollution, the place in which the oceanic discharge activity occurred and Japan's substantive and procedural obligation under the United Nations Convention on the Law of the Sea (UNCLOS) will also affect the treaty application in the forthcoming oceanic discharge. This paper proposes that for the international community as a whole, long term (regional and global cooperation) and short-term measures (inter-State cooperation) need to be taken into consideration in order to tackle Japan's decision as well as laying the framework for any similar discharges that could follow Japan's example. [ABSTRACT FROM AUTHOR]

Background: Many plant-derived chemicals have been studied for their potential benefits in ailments including inflammation, cancer, neurodegeneration, and cardiovascular disease. The health benefits of phytochemicals are often attributed to the targeting of reactive oxygen species (ROS). However, it is not always clear whether these agents act directly as antioxidants to remove ROS, or whether they act indirectly by blocking ROS production by enzymes such as NADPH oxidase (NOX) enzymes, or by influencing the expression of cellular pro- and anti- oxidants.Hypothesis/purpose: Here we evaluate the pro- and anti-oxidant and NOX-inhibiting qualities of four phytochemicals: celastrol, resveratrol, apigenin, and piperine.Study Design: This work was done using the H661 cell line expressing little or no NOX, modified H661 cells expressing NOX1 and its subunits, and an EBV-transformed B-lymphoblastoid cell line expressing endogenous NOX2. ROS were measured using Amplex Red and nitroblue tetrazolium assays. In addition, direct ROS scavenging of hydrogen peroxide or superoxide generated were measured using Amplex Red and methyl cypridina luciferin analog (MCLA).Results: Of the four plant-derived compounds evaluated, only celastrol displayed NOX inhibitory activities, while celastrol and resveratrol both displayed ROS scavenging activity. Very little impact on ROS was observed with apigenin, or piperine.Conclusion: The results of this study reveal the differences that exist between cell-free and intracellular pro-oxidant and antioxidant activities of several plant-derived compounds. [ABSTRACT FROM AUTHOR]

Background Guidelines advise modified radical mastectomy following neoadjuvant systemic therapy for T4 breast cancer. We studied the influence of current systemic therapy and tumor subtype on pathologic stage and practice patterns to identify patients for whom less aggressive operative treatment might be considered. Methods We identified 98 clinical T4 M0 cases operated on at our institution from October 2008–July 2015. Patient, tumor, and treatment variables were analyzed. Results Clinical T4 substage was 7% T4a, 32% T4b, 3% T4c, and 58% T4d. Tumor biologic subtype was 41% ER+/HER2−, 36% HER2+, and 23% ER−/HER2−. A total of 86 patients (88%) had neoadjuvant systemic therapy; 87% of patients underwent total mastectomy, 9% skin-sparing mastectomy, and 4% breast conservation. Axillary dissection was performed in 74% of patients and sentinel node surgery with (14%) or without (11%) axillary dissection in the remainder; 41/98 (42%) were lymph node negative at operation. The pathologic complete response rate in the breast (31%) and axilla (39%, cN+ cases) correlated with biologic subtype ( P < .0001). Overall 5-year, disease-free, and breast cancer–specific survival were 68% and 86%. Conclusion Alignment with guidelines was substantial for both breast and axillary operation. Favorable breast cancer–specific survival suggests current multidisciplinary treatment has improved outcomes. Careful assessment of pathology and treatment response may identify clinical T4 patients appropriate for breast or axillary conservation. [ABSTRACT FROM AUTHOR]

Anti-cancer host defense mechanisms are traditionally considered to consist of tumor suppressor genes and immune surveillance by cells of the innate and adaptive immune systems. However, there is mounting evidence that components of the acute phase protein response (APPR), and, in particular, certain cationic host defense peptides (HDPs), also contribute to anti-cancer host defense. In a number of in vitro studies, certain HDPs have been shown to be cytotoxic to tumor cells either directly through cancer cell membrane destabilization and lysis or through the initiation of apoptosis in the cancer cell. In addition, many cancer cells elaborate the pro-inflammatory cytokine interleukin-6, which in turn produces an APPR that involves the release of HDPs. It is therefore possible that the release of pro-inflammatory cytokines by cancer cells initiates a poorly understood anti-tumor response by the host that involves HDP induction. We hypothesize that the APPR may form an important anti-cancer host defense response. This may be an important consideration in light of cancer treatments designed to decrease systemic inflammation. Blunting of the anti-cancer effect of the APPR may also contribute to the increased cancer rates seen in chronic immunosuppressive states. [ABSTRACT FROM AUTHOR]

Background Rates of contralateral prophylactic mastectomy (CPM) have been increasing nationally. The goal of this study was to evaluate recent trends in rates of CPM and immediate breast reconstruction (IBR). Methods After institutional review board approval, we evaluated all surgical procedures for women with newly diagnosed unilateral stages 0–III breast cancer from January 2009 to December 2014. Patients opting for therapeutic mastectomy were classified as either unilateral mastectomy or bilateral mastectomy, if CPM was performed, and according to whether or not they underwent IBR. Analysis was performed using trend tests for univariate associations and both binary and multinomial logistic regression for multivariate analysis. Results There were 3,195 women who underwent surgery for breast cancer—51% lumpectomy, 49% therapeutic mastectomy. Of the 1,571 patients undergoing therapeutic mastectomy, 829 (53%) underwent bilateral mastectomy. The rates of therapeutic mastectomy did not change over the study period ( P = .92), but the use of IBR among patients undergoing therapeutic mastectomy increased from 37% in 2009 to 68% in 2014 ( P < .0001). The use of bilateral mastectomy with IBR increased from 26% in 2009 to 46% in 2014 ( P < .0001), whereas conversely the use of bilateral mastectomy without IBR decreased from 22% to 12% ( P < .0001). IBR was associated with bilateral mastectomy; 69% of patients opting for IBR also underwent bilateral mastectomy compared with 38% choosing bilateral mastectomy in the group without IBR (adjusted odds ratio, 2.7; 95% CI, 2.1–3.5; P < .0001). Conclusion Over recent years, rates of bilateral mastectomy have remained high. The use of IBR increased substantially for women undergoing therapeutic mastectomy and women undergoing IBR were significantly more likely to opt for bilateral mastectomy. The availability of IBR may influence patients’ decisions to pursue bilateral mastectomy. [ABSTRACT FROM AUTHOR]

Background Pathologic nipple discharge is managed customarily with diagnostic subareolar duct excision. We evaluated for features predictive of malignancy to identify cases where operation might be avoided. Methods We studied 311 consecutive subareolar duct excisions for pathologic nipple discharge from January 2008 to July 2014. χ 2 tests were used to test for associations with final pathology. Results In 27 cases, cancer was diagnosed preoperatively. Among the remaining 284, 26 (9%) were diagnosed with cancer and 8 (3%) with atypia at operation. At greatest risk of upstage to cancer were patients with prior ipsilateral breast cancer (3/8; 38%), BRCA mutation (2/3; 67%) or atypia on core needle biopsy (CNB; 3/8 [38%]). Excluding these patients lowered cancer and atypia upstages (7% [18/265] and 3% [7/265]), with bloody (versus serous) discharge ( P = .001), and focal imaging abnormality ( P = .02), the strongest risk factors. Serous discharge and either normal imaging or a benign CNB had a 1.3% cancer upstage rate. Conclusion Despite contemporary imaging, pathologic nipple discharge upstage rates to malignancy and atypia remain high, especially with prior ipsilateral breast cancer, BRCA mutation, or atypia on CNB. Absent these risk factors, patients with serous discharge and a benign CNB or normal imaging (cancer risk <2%) may be considered for nonoperative management. [ABSTRACT FROM AUTHOR]

Abstract: Abrupt dietary transitions and feeding of rapidly fermentable diets are common practices in the horse industry and have been associated with digestive and metabolic disorders that can impair the performance of horses. The present study investigated the effect of dietary transition from pasture grazing to confinement with concentrate feeding, and back, on fecal pH and bacterial populations of Streptococcus spp and Lactobacillus spp. Six Thoroughbred fillies, previously grazing perennial ryegrass and white clover-based pasture, were housed in individual stalls and fed an increasing ratio of concentrate to conserved forages for 13 days (days 1-13), followed by an abrupt transition back to only pasture-grazing for 3 days (days 14-16). The concentrate was initially offered at 0.83 kg dry matter (DM)/d and increased to 5 kg DM/d, whereas ensiled alfalfa was initially offered at 0.61 kg DM/d, increasing to 1.22 kg DM/d. Meadow hay was initially offered at 6.73 kg DM/d, decreasing to 1.6 kg DM/d. Fecal specimens were collected daily for determination of pH, and every 2 days for quantitative analysis of Streptococcus spp and Lactobacillus spp. Mean fecal pH increased significantly from pasture baseline values (pH 6.18) during the initial confinement and supplementation on day 1 (6.37), day 2 (6.52), day 3 (6.58), and day 4 (6.43) (standard error of mean [SEM]: 0.056; P < .001). By day 5, mean fecal pH values had decreased to, and remained at, baseline values until the horses returned to pasture, when another increase occurred at day 15 (6.45). Fecal colony forming units (cfu) of Streptococcus spp and Lactobacillus spp increased linearly (r = 0.94; P < .001) from 6.0 and 6.1 log10 cfu/g on day -4, to 7.8 log10 cfu/g on day 14 (SEM: 0.2 P < .001), respectively. Fecal cfu decreased on return to a pasture-only diet (P < .001). In this study, the increment of bacterial populations was associated with a relatively stable fecal pH and highlights the difficulty in identifying the effects of dietary transition on the equine hindgut health, without microbial culture. [Copyright &y& Elsevier]

Abstract: In this review, we will focus on one particular class of stromal targeted therapy, i.e. the bone seeking radiopharmaceuticals (BSRs), but will also highlight selected issues related to the bone stroma as these concepts are new, rapidly evolving, and clearly linked to the underlying BSR mechanisms of targeting and action. Herein we review clinical BSR-trials of significance with randomized trials at center stage. Furthermore, we cover a new class of BSR in late clinical development based on bone-stromal targeted alpha-particle irradiation. Lastly, we discuss potential advances in combining BSR with bisphosphonates and/or chemotherapy and emphasize the feasibility of repeated dosing. [Copyright &y& Elsevier]

Objective: Data from multicenter studies support observation of small abdominal aortic aneurysms (AAAs) over open repair (OR), but the role of endovascular repair (EVAR) is unclear pending outcome of the Positive Impact of EndoVascular Options for Treating Aneurysm earLy (PIVOTAL) trial. Our goal was to predict the outcome of the trial by comparing results of small AAA repair using EVAR vs OR at a tertiary institution. Methods: Using selection criteria of PIVOTAL trial, we reviewed clinical data of 194 consecutive patients, who underwent EVAR or OR for 4.0-5.0 cm AAAs between 1997 and 2004. All-cause and aneurysm-related deaths, complications, reinterventions, ruptures, and conversions were documented; factors affecting outcome were analyzed using χ 2 tests, Wilcoxon rank-sum tests, logistic regression Kaplan-Meier method with log-rank tests, and Cox proportional hazards regression. Median follow-up was 3.9 years (range, 1 month to 9 years). Results: A total of 194 patients, 162 males, 32 females (mean age: 71 years, range, 46-86) underwent 162 OR and 32 EVAR. EVAR patients were older (mean 74 ± 6 vs 71 ± 7, P = .002), had lower ejection fraction (mean 54 ± 11 vs 61 ± 13, P = .0002), and less likely to have ever smoked (69% vs 85%, P = .03) than OR patients. Thirty-day mortality was 1.3% (2/162) for OR and 0% for EVAR (0/33) (P = not significant [NS]). There were 49 systemic complications (7 EVAR, 42 OR, P = NS) and 10 local complications (3 EVAR, 7 OR, P = NS). During follow-up, there were no conversions and no ruptures. Freedom from reinterventions at 5 years was 83.1% ± 6.9% for EVAR and 95.3% ± 1.8% for OR (P = 0.02). There were 26 deaths (3 EVAR, 23 OR); but no procedure or aneurysm-related death was confirmed after 30 days (cause unknown in 16 deaths, 62%). Survival rates at 1-year were 96.6% ± 3.4% for EVAR and 97.4% ± 1.3% for OR; 5-year rates were 86.9% ± 7.2% ± EVAR and 86.9% ± 3.3% for OR (P = 0.69). Multivariate analysis revealed age (hazard ratio = 1.1 per year, P = .0496) and AAA size (hazard ratio = 13.8 per 1 cm, P = .03) were associated with death but EVAR vs OR was not (P = .23). Conclusion: For repair of small AAAs, results of EVAR vs OR are not different at 5 years at a tertiary institution. Multicenter studies confirmed OR were not superior to observation in these patients. We predict the PIVOTAL study will conclude EVAR is not superior to observation. [Copyright &y& Elsevier]

Objective: Two-thirds of the US population is overweight or obese. Sedentary lifestyles and occupations are one factor in the development of obesity. Methods to help reduce sedentary work environments may help reduce obesity. The purpose of this study was to determine the feasibility of using a walking workstation during computed tomographic image interpretation. Methods: Two radiologists reinterpreted 100 clinical computed tomographic examinations they had previously interpreted, each while walking at 1 mph on a treadmill using an electronic workstation. Ten cases were reviewed per session. The time period between the initial conventional interpretations and the reinterpretations was greater than one year, to reduce recall bias. Discrepant findings were ranked according to a classification system based on clinical importance on a scale ranging from 1 to 6. Discrepant findings classified as greater than or equal to 3 were considered significant. Detection rates for the initial interpretations and reinterpretations were determined for each reviewer and compared using a paired t-test. Results: A total of 1,582 findings were reported (825 by reviewer 1 and 757 by reviewer 2). There were 459 findings with clinical importance of 3 or higher. For reviewer 1 (91 cases of at least one important finding), the mean detection rates were 99.0% for the walking technique and 88.9% for the conventional interpretations (P = .0003). For reviewer 2 (89 cases with at least one important finding) the mean detection rates were 99.1% for the walking technique and 81.3% for the conventional interpretations (P < .0001). Conclusion: The use of a walking workstation for the interpretation of cross-sectional images is feasible. Further studies are needed to assess the potential impact on diagnostic accuracy. [Copyright &y& Elsevier]

Objectives: To assess expansion rate of common iliac artery aneurysms (CIAAs) and define outcomes after open repair (OR) and endovascular repair (EVAR). Methods: Clinical data of 438 patients with 715 CIAAs treated between 1986 and 2005 were retrospectively reviewed. Size, presentations, treatments, and outcomes were recorded. Kaplan-Meier method with log-rank tests and χ2 test were used for analysis. Results: Interventions for 715 CIAAs (median, 4 cm; range, 2-13 cm) were done in 512 men (94%) and 26 women (6%); 152 (35%) had unilateral and 286 (65%) had bilateral CIAAs. Group 1 comprised 377 patients (633 CIAAs) with current or previously repaired abdominal aortic aneurysm (AAA). Group 2 comprised 15 patients (24 CIAAs) with associated internal iliac artery aneurysm (IIAA). Group 3 comprised 46 patients (58 isolated CIAAs). Median expansion rate of 104 CIAAs with at least two imaging studies was 0.29 cm/y; hypertension predicted faster expansion (0.32 vs 0.14 cm/y, P = .01). A total of 175 patients (29%) were symptomatic. The CIAA ruptured in 22 patients (5%, median, 6 cm; range, 3.8-8.5 cm), and the associated AAA ruptured in 20 (4%). Six (27%) ilioiliac or iliocaval fistulas developed. Repairs were elective in 396 patients (90%) and emergencies in 42 (10%). OR was performed in 394 patients (90%) and EVAR in 44 (10%). The groups had similar 30-day mortality: 1% for elective, 27% for emergency repairs (P < .001); 4% after OR (elective, 1%; emergency, 26%), and 0% after EVAR. No deaths occurred after OR of arteriovenous fistula. Complications were more frequent and hospitalization was longer after OR than EVAR (P < .05). Mean follow-up was 3.7 years (range, 1 month-17.5 years). The groups had similar 5-year primary (95%) and secondary patency rates (99.6%). At 3 years, secondary patency was 99.6% for OR and 100% for EVAR (P = .66); freedom from reintervention was similar after OR and EVAR (83% vs 69%, P = .17), as were survival rates (76% vs 77%, P = .70). Conclusions: The expansion rate of CIAAs is 0.29 cm/y, and hypertension predicts faster expansion. Because no rupture of a CIAA <3.8 cm was observed, elective repair of asymptomatic patients with CIAA ≥3.5 cm seems justified. Although buttock claudication after EVAR remains a concern, results at 3 years support EVAR as a first-line treatment for most anatomically suitable patients who require CIAA repair. Patients with compressive symptoms or those with AVF should preferentially be treated with OR. [Copyright &y& Elsevier]

Background: Little data address outcome in patients with sentinel lymph node (SN) metastases without completion axillary lymph node dissection (CALND). This study was designed to assess locoregional recurrence in patients with positive SNs who did not undergo CALND. Methods: An IRB-approved, retrospective chart review was conducted on breast cancer patients with a positive SN. Follow-up information on outcomes was obtained via mailed questionnaires and chart review. Comparative analyses were performed between patients who did and did not undergo CALND after a positive sentinel lymph node biopsy. Results: From November 1998 to June 2004, 625 breast cancer patients had a positive sentinel lymph node biopsy. One-hundred and eighteen patients with ≤0.2 mm nodal metastases (N0i+) were excluded from the study. Of the remaining 507 patients, 421 underwent CALND and 86 did not. In comparison to patients who had CALND, patients who did not undergo CALND had smaller primary tumors (2 vs 2.6 cm, P = .0007) and were more likely to have a single positive sentinel node (92% vs 77%, P = .002). The metastasis size of the sentinel node was smaller compared to patients who underwent axillary dissection (1.7 vs 6.4 mm, P < .0001). Mean predicted probability of nonsentinel node metastasis in patients who did not undergo CALND was 20% compared to 47% in patients who did (P < .0001). During a median follow-up of 30 months, there were no axillary recurrences. Conclusions: These data confirm that patients who have a positive sentinel node biopsy and do not undergo CALND have a lower risk profile for axillary disease. In this lower risk subset, axillary treatment may not be necessary. [Copyright &y& Elsevier]

Objectives: Widespread application of infrarenal endovascular aneurysm repair (EVAR) has resulted in a proportionate increase in open juxtarenal aortic aneurysm (JAA) repairs. Fenestrated endograft technology for JAA is developing rapidly, but only limited outcomes are known. The aim of this study was to review our open JAA experience in an era of fenestrated endograft technology, identify factors associated with increased surgical risk, determine early and midterm outcome, and provide a basis for comparison for future endovascular procedures. Methods: Data from 126 consecutive patients who underwent elective JAA repair requiring suprarenal aortic clamping from 2001 to 2006 were analyzed retrospectively. Electronic medical chart reviews were used to record 30-day complication rates. Multivariate analyses were performed to identify risk factors associated with surgical morbidity. Mail-out questionnaires and telephone surveys were conducted to determine long-term follow-up. Results: Ninety-eight males and 28 females (median age 74 years; range 55 to 93) were included in the study. Preoperative risk factors included: coronary artery disease (CAD) 58%, pulmonary disease 41%, renal insufficiency (serum creatinine [Cr] > 1.5mg/dL) 17%, and diabetes 9%. Fifteen patients underwent concomitant renal artery revascularization. Mean operative time was 319 minutes (range 91 to 648). Thirty-day mortality was 1/126 (0.8%). Median hospital length of stay was 7 days (range 3 to 85); median intensive care unit length of stay was 2 days (1 to 64). Complications included renal insufficiency (Cr increase > 0.5 mg/dL) in 22 (18%), cardiac in 17 (13%), and pulmonary in 14 (11%). Five patients required temporary hemodialysis; only one after hospital dismissal. Mean follow-up was 48 months (range 9-80). On multivariate analysis, age ≥ 78 years (P = .001), male gender (P = .04), hypertension (P =.01), previous myocardial infarction (P = .047), and diabetes (P =.009) were predictive of cardiac complications. Renal artery revascularization (P = .01) and prior MI (P = .04) were multivariate predictors of pulmonary complications. Both prolonged operative (≥351 minutes, P = .02) and renal ischemia (≥23 minutes, P =.004) times predicted postoperative renal insufficiency. One, 3, and 5-year cumulative survival rates were 93.9%, 78.3%, and 63.8%, respectively and were not significantly different than an age- and gender-matched sample of the US population (P = .16). Mortality was not predicted by any specific risk factors. Conclusions: Open surgical repair of JAA is associated with low mortality and remains the gold standard. Although 18% had renal complications, only one patient had permanent renal failure. Patients with a combination of physiologic and anatomic risk factors identified on multivariate analysis may benefit from fenestrated endograft repair. [Copyright &y& Elsevier]

Purpose: Studies have suggested good long-term success rates with bone–patellar tendon–bone (BPTB) autograft and BPTB allograft in anterior cruciate ligament (ACL) reconstruction, but the numbers reported in available prospective studies may be underpowered to elucidate significant differences between the two groups. Here, we present a meta-analysis to compare the results of BPTB autograft and BPTB allograft in primary ACL reconstruction. Methods: A systematic review of prospective trials using BPTB autograft and BPTB allograft tissue for ACL reconstruction with a minimum 2-year follow-up was performed. Summary odds ratios (ORs), confidence intervals, and P values were calculated. Results: Of 548 studies, 6 fulfilled our inclusion criteria, with 256 patients in the autograft and 278 patients in the allograft group. Allograft patients were more likely to rupture their graft than autograft patients (OR, 5.03; P = .01) and more likely to have a hop test less than 90% of the nonoperative side (OR, 5.66; P < .01). When irradiated and chemically processed grafts were excluded from analysis, no significant differences were found between allograft and autograft patients with respect to graft rupture, rate of reoperation, normal/near normal IKDC scores, Lachman exam, pivot shift exam, patellar crepitus, hop test, or return to sport. Conclusions: In this meta-analysis, ACL reconstruction with BPTB autograft was favored over BPTB allograft for graft rupture and hop test parameters. However, when irradiated and chemically processed grafts were excluded, results were not significantly different between the two graft types. Level of Evidence: Level III, systematic review of prospective nonrandomized cohort studies. [Copyright &y& Elsevier]

Background: Popliteal artery aneurysms (PAAs) are rare, but thromboembolic complications may result in limb loss. To define complications and outcomes after open surgical repairs, we reviewed our experience. Methods: Clinical data of patients with PAA seen between 1985 and 2004 at Mayo Clinic, Rochester, Minnesota, were reviewed and outcomes in 289 patients with open revascularization were analyzed. Kaplan-Meier method with log-rank tests, χ2, and Wilcoxon rank sum tests were used for analysis. Results: A total of 358 PAAs were treated in 289 patients, consisting of 281 (97%) men and eight (3%) women. There were 133 (46%) unilateral and 156 (54%) bilateral PAAs with a mean diameter of 2.9 cm (range, 1.5 to 9 cm). Abdominal aortic aneurysm (AAA) was more frequent with bilateral than unilateral PAAs (65% [101/156] vs 42% [56/133] P = .001). There were 144 (40%) asymptomatic limbs (group 1), 140 (39%) had chronic symptoms (group 2), and 74 (21%) had acute ischemia (group 3). Great saphenous vein (GSV) was used in 242 limbs (68%), polytetrafluoroethylene (PTFE) in 94 (26%), and other types of graft in 22 (6%). Early mortality was 1% (3/358), all in group 3 (4% [3/74]). Six of seven patients with perioperative myocardial infarctions belonged to group 3 (8%). The 30-day graft thrombosis rate was 4%, with 1% in group 1 (1/144), 4% in group 2 (5/140), and 9% in group 3 (7/74). All six early amputations (8%) were in group 3, five with failed bypass (4 PTFE, 1 GSV). Mean follow-up was 4.2 years (range, 1 month to 20.7 years). The 5-year primary and secondary patency rates were 76% and 87%, respectively, higher with GSVs (85% and 94%) than PTFE (50% and 63%, P < .05). Seven recurrent PAAs (2%) required reintervention. The 5-year freedom from reintervention was 100% after endoaneurysmorrhaphy vs 97% after ligations (P = .03). Five-year limb salvage rate was 97% (85% in group 3). There was no limb loss in group 1 and none in group 2 with GSV. In group 3, preoperative thrombolysis reduced the amputation rate in class II patients with marginally threatened limbs (96% vs 69%, P = .02). Conclusion: Acute presentation of PAA continues to carry high mortality and cardiac morbidity; although preoperative thrombolysis appears to improve results, the 8% early and 15% late amputation rates remain ominous. Early elective repair is recommended because these patients had no surgical mortality, a low rate of complications, and asymptomatic patients had no limb loss at 5 years. GSV and endoaneurysmorrhaphy continues to be the gold standard for open repair of PAA. [Copyright &y& Elsevier]

Brachytherapy has changed dramatically in the last decade, with the widespread introduction of high-dose rate afterloading systems having greater flexibility of source loading patterns and smaller sources enabling new anatomic sites to be considered. This has been harnessed to the major developments in cross-sectional imaging and dosimetry planning systems to enable highly conformal radiotherapy to be delivered accurately and reliably by brachytherapy. There has been a major change in the distribution of sites treated, the majority being prostate, gynecologic, and breast treatments, whereas an emerging role as a simple but effective palliative treatment in bronchus, esophagus, and rectal cancers has also been recognized. [Copyright &y& Elsevier]

Purpose: Few large series document surgical outcomes for patients with pararenal abdominal aortic aneurysms (PAAAs), defined as aneurysms including the juxtarenal aorta or renal artery origins that require suprarenal aortic clamping. No standard endovascular alternatives presently exist; however, future endovascular branch graft repairs ultimately must be compared with the gold standard of open repair. To this end, we present a 10-year experience. Methods: Between 1993 and 2003, 3058 AAAs were repaired. Perioperative variables, morbidity, and mortality were retrospectively assessed. Renal insufficiency was defined as a rise in the concentration of serum creatinine by ≥0.5 mg/dL. Factors predicting complications were identified by multivariate analyses. Morbidity and 30-day mortality were evaluated with multiple logistic regression analysis. Results: Of a total of 3058 AAA repairs performed, 247 were PAAAs (8%). Mean renal ischemia time was 23 minutes (range, 5 to 60 minutes). Cardiac complications occurred in 32 patients (13%), pulmonary complications in 38 (16%), and renal insufficiency in 54 (22%). Multivariate analysis associated myocardial infarction with advanced age (P = .01) and abnormal preoperative serum creatinine (>1.5 mg/dL) (P = .08). Pulmonary complications were associated with advanced age (P = .03), renal artery bypass (P = .02), increased mesenteric ischemic time (P = .01), suprarenal aneurysm repair (P < .0008), and left renal vein division (P = .01). Renal insufficiency was associated with increased mesenteric ischemic time (P = .001), supravisceral clamping (P = .04), left renal vein division (P = .04), and renal artery bypass (P = .0002), but not renal artery reimplantation or endarterectomy. New dialysis was required in 3.7% (9/242). Abnormal preoperative serum creatinine (>1.5 mg/dL) was predictive of the need for postoperative dialysis (10% vs 2%; P = .04). Patients with normal preoperative renal function had improved recovery (93% vs 36%; P = .0002). The 30-day surgical mortality was 2.5% (6/247) but was not predicted by any factors, and in-hospital mortality was 2.8% (7/247). Median intensive care and hospital stays were 3 and 9 days, respectively, and longer stays were associated with age at surgery (P = .007 and P = .0002, respectively) and any postoperative complication. Conclusions: PAAA repair can be performed with low mortality. Renal insufficiency is the most frequent complication, but avoiding renal artery bypass, prolonged mesenteric ischemia time, or left renal vein transection may improve results. [Copyright &y& Elsevier]

Because little information is currently available on the epidemiology of shoulder arthroplasty, this study was designed to evaluate the characteristics of patients undergoing this procedure and changes in practice patterns. Residents of Olmsted County, Minnesota, who underwent shoulder arthroplasty between 1976 and 2000 were identified (98 residents, 112 procedures). A relatively lower initial rate of shoulder arthroplasty was followed by a statistically significant steady increase (P < .0001), with an age- and sex-adjusted annual operative incidence rate of 1.4 per 100,000 person-years (1976-1980) to 10.1 per 100,000 person-years (1996-2000). Increased utilization of shoulder arthroplasty during the last decade was mainly a result of its application in osteoarthritis. A significant need exists for examination of utilization patterns for shoulder arthroplasty. An aging population and an increased demand and awareness by the public regarding interventions to improve quality of life will shape the future of arthroplasty, reinforcing the need for future studies of this nature. [Copyright &y& Elsevier]

Objectives: To determine the short- and long-term outcomes of patients treated operatively for Takayasu’s arteritis and the effect of disease activity on results. Methods: Forty-two (17%) of the 251 patients enrolled in our Takayasu’s arteritis registry between 1975 and 2002 required operation for symptomatic disease. Data were obtained from the registry, patient records, phone correspondence, and written surveys. Results: There were 38 females and 4 males with a median age of 29 years (range, 12 to 56 years), and 32 (76%) were white. Sixty operations were performed for symptomatic disease. The mean duration of symptoms before operation was 5.6 months (range, 0 to 25 months). Thirteen (31%) patients had active disease and underwent operation for acute presentation or failure of medical management. Thirty-nine patients (93%) had operation for occlusive disease. Twenty-two (52%) patients had involvement of both the great and abdominal aortic branch vessels; 10 (24%) had great vessel disease alone; 9 (21%) had involvement of abdominal arteries; and 1 (2%) had coronary artery disease. There was no operative death, myocardial infarction, major stroke, or renal failure. Three patients had early graft thrombosis, two had a minor stroke, and two developed hyperperfusion syndrome. The median follow-up was 6.7 years (range, 1 month to 19.3 years). Eleven (26%) patients required 15 graft revisions; five of the patients had active disease at the time of initial operation. All early revisions (<1 year) were in patients with active disease. By Kaplan-Meier analysis, freedom from revision at 5 and 10 years was 100% in patients with quiescent disease not requiring steroids (group I, n = 5, 12%), 95% and 81% in patients whose disease was quiescent on steroids (group II, n = 24, 57%), 57% in patients with active disease on steroids (group III, n = 7, 17%), and 33% in patients with active disease and no long-term steroids (group IV, n = 6, 14%) (P < .006). The rate of revision or progression of disease at another site in 5 years was 0% in group 1, 10% in group 2, 57% in group 3, and 67% in group 4 (P < .001) The differences were even more pronounced when an analysis was done on the basis of disease activity alone, irrespective of steroid use. During the follow-up period, 3 of 39 great vessel, 2 of 18 mesenteric/renal, and 1 of 9 aortofemoropopliteal reconstructions occluded. The predicted mortality for patients was 4% at both 5 and 10 years (95% CI) respectively (confidence interval [CI], 0% to 11%) and 10 (CI, 0% to 14%) years, respectively. Conclusions: The minority of patients with Takayasu’s arteritis require operation. In our predominantly white female patient population, occlusive symptoms were the most common indication for operation. Operation for these selected patients was safe, with no operative mortality, myocardial infarction, major stroke, or renal failure. Patients with active disease requiring operation are more likely to require revision or develop progressive symptomatic disease at another site. Long-term survival is excellent, regardless of disease activity at the time of operation. [Copyright &y& Elsevier]

Objective: Currently, the risk of aneurysm sac rupture after endovascular abdominal aortic aneurysm repair (EVAR) is estimated by using a group of anatomic variables. Available techniques for pressure monitoring include either direct measurement using catheter-based techniques or indirect measurement requiring implantation of a pressure sensor during aneurysm repair. None of these methods is without limitations. Radiation pressure, such as that generated by a modulated ultrasound (US) beam, can induce surface vibration at a distance. The velocity of the resulting surface waves depends on the tensile stress of the vibrated surface. By measuring the change in wave velocity, it is possible to detect the change in tensile stress and calculate the pressure through the vibrated surface. We tested this concept in an in vitro aneurysm model. Methods: Rubber tubes and explanted porcine abdominal aortas were used to model an aneurysm sac. The surface of the model was vibrated with an amplitude-modulated US beam. The resulting motion was detected either by reflected laser light or by Doppler US. The phase of the propagating wave was measured to assess changes in velocity with different pressures. Results: Increasing hydrostatic pressure in the rubber model correlated well with the cumulative phase shift (R 2 = 0.96-0.99; P < .0001). By using a pump to generate dynamic pressure (between 110 and 200 mm Hg), the cumulative phase shift correlated well with the square of the mean pressure (R 2 = 0.92; P < .0001); however, the correlation with pulse pressure was poor (24-36 mm Hg; r = 0.38; P < .02). In the porcine in vitro aortic sac model, the cumulative phase shift detected with both laser (r = 0.94-0.99; P < .0001) and Doppler (r = 0.96-0.99; P < .0001) correlated well with the aneurysm pressure. Conclusions: Application of vibrometry for noninvasive measurement of aortic aneurysm sac tension is feasible in an in vitro setting. The concept of vibrometry may be used to detect endotension noninvasively after EVAR. Vibrometry may also be used to estimate wall stress in native aneurysms, and it may predict the risk of aneurysm rupture. Clinical Relevance: Vibrometry may offer a technique for completely noninvasive monitoring of aneurysm sac pressure after EVAR. Vibrometry is based on the following principles: radiation pressure, such as that generated by modulated US, can induce surface vibration at a distance; by measuring the change in wave velocity of vibration, it is possible to detect changes in tensile stress and calculate the pressure through the vibrated surface. We tested this concept in an in vitro model and found that application of vibrometry for noninvasive measurement of aortic aneurysm sac tension is feasible. Vibrometry may also be used to estimate wall stress in native aneurysms. [Copyright &y& Elsevier]

Percutaneous transluminal renal angioplasty (PTRA) is the primary treatment for renal fibromuscular dysplasia (RFMD). Surgical revascularization is limited to patients who fail or are unsuitable for PTRA. All patients who were operated on with RFMD since the indications for renal PTRA were expanded in our institution were retrospectively reviewed. Outcome included patency, hypertension, and renal function. Twenty-six patients had reconstruction of 32 renal arteries between 1998 and 2004. The mean age was 47.1?±?14 years; the majority (81%) were female. Six patients had bilateral disease and three had a solitary kidney. Operations were done for hypertension in 25 patients, renal artery aneurysm in 8, and chronic dissection in 1, alone or in combination. Six patients had a failed PTRA and 20 were unsuitable for it. Aortorenal bypass was done most often (n?=?28) and saphenous vein was the preferred conduit (n?=?25). The distal anastomosis was to the main renal artery in 13 patients and to the branch arteries in 19. Ex vivo repair was needed in five patients. Five intraoperative revisions were done because of abnormalities on duplex scan. One patient died unexpectedly 42 days after operation from myocardial infarction. Extrarenal complications occurred in five patients. Median follow-up was 2.4 (range, 42 days to 6.3) years and was available in all but one patient (96%). Two bypasses occluded at 3 and 376 days, which resulted in loss of the kidneys. One graft stenosis was treated successfully with PTRA at 239 days. All failures occurred in men. One-year cumulative primary patency was 89?±?8% and was not adversely affected by prior PTRA or complex repair. Hypertension at 1 year was cured in 27% of the patients and improved in 60%. No patient developed acute or chronic renal failure. Surgical reconstruction for RFMD has excellent short-term patency. Failed PTRA or complex reconstructions did not adversely affect outcome. [ABSTRACT FROM AUTHOR]

Background Neither chemotherapy with a single-alkylating agent nor aggressive combination chemotherapy cures advanced stage low-grade non-Hodgkin lymphomas, even when combined with radiotherapy. Our aim was to compare administration of immediate chlorambucil treatment with a policy of delaying chlorambucil until clinical progression necessitated its use, in asymptomatic patients with advanced-stage, low-grade non-Hodgkin lymphoma.Methods 309 patients with asymptomatic, advanced-stage, low-grade non-Hodgkin lymphomas were recruited from 44 UK centres between Feb 1, 1981, and July 31, 1990. 158 patients were randomised to receive immediate systemic therapy with oral chlorambucil 10 mg per day continuously. The remaining 151 were randomised to an initial policy of observation, with systemic therapy delayed until disease progression. In both groups, local radiotherapy to symptomatic nodes was allowed.Findings Median length of follow-up was 16 years. Overall survival or cause-specific survival did not differ between the two groups (median overall survival for oral chlorambucil 5·9 [range 0–17·8] years and for observation 6·7 [0·5–18·9] years, p=0·84; median cause-specific survival 9 [0–17·8] years and 9·1 [0·67–18·9] years, respectively p=0·44). In a multivariate analysis, age younger than 60 years, erythrocyte sedimentation rate (ESR) 20 mm/h or less, and stage III disease, conferred significant advantages in both overall survival (p<0·0001, 0·03, and 0·03, respectively) and cause-specific survival (p=0·002, 0·008, and 0·001, respectively). In the observation group, at 10 years’ follow-up, 19 patients were alive and had not received chemotherapy. The actuarial chance of not needing chemotherapy (non-lymphoma deaths censored) at 10 years was 19% (40% if older than 70 years).Interpretation An initial policy of watchful waiting in patients with asymptomatic, advanced stage low-grade non-Hodgkin lymphoma is appropriate, especially in patients older than age 70 years. [Copyright &y& Elsevier]

Background and Purpose: Between 30% and 47% of patients treated with definitive radiotherapy (RT) for prostate cancer are at risk of intraprostatic recurrence during follow-up. Re-irradiation with stereotactic body RT (SBRT) is emerging as a feasible and safe therapeutic option. However, no consensus or guidelines exist on this topic. The purpose of this ESTRO ACROP project is to investigate expert opinion on salvage SBRT for intraprostatic relapse after RT.Materials and Methods: A 40-item questionnaire on salvage SBRT was prepared by an internal committee and reviewed by a panel of leading radiation oncologists plus a urologist expert in prostate cancer. Following the procedure of a Delphi consensus, 3 rounds of questionnaires were sent to selected experts on prostate re-irradiation.Results: Among the 33 contacted experts, 18 (54.5%) agreed to participate. At the end of the final round, participants were able to find consensus on 14 out of 40 questions (35% overall) and major agreement on 13 questions (32.5% overall). Specifically, the consensus was reached regarding some selection criteria (no age limit, ECOG 0-1, satisfactory urinary flow), diagnostic procedures (exclusion of metastatic disease, SBRT target defined on the MRI) and therapeutic approach (no need for concomitant ADT, consideration of the first RT dose, validity of Phoenix criteria for salvage SBRT failure).Conclusion: While awaiting the results of ongoing studies, our ESTRO ACROP Delphi consensus may serve as a practical guidance for salvage SBRT. Future research should address the existing disagreements on this promising approach. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is an independent risk for hypertension, cerebral artery stenosis, stroke and hypercoagulability.1 Our research objective was to assess whether sleep disordered breathing affects the peripheral circulation, decreases perfusion as measured by TcPO2 and decreases the odds that a partial-foot amputation site will heal. We hypothesized that OSA would be an independent risk factor causing delayed healing of partial-foot amputations. We conducted a retrospective, observational study on a total of 307 patients who had TcPO2 measurements and underwent partial-foot amputation. Twenty-five of these patients had OSA. In our study, patients with OSA had a 3.7-fold increase in odds of healing within 3 months in comparison with patients without OSA. Of note, 16 patients (64%) with OSA were not treated with continuous positive airway pressure (CPAP) and healed within 3 months. Our results do not support our hypothesis that the presence of sleep apnea may impair healing of partial foot amputations. Further studies are needed to fully determine the effect of OSA and its treatment on TcPO2s and healing. [Copyright &y& Elsevier]

• Visitor number scales with parking capacity. • Charging parking locations receive more visitors than non-charging ones. • Location-specific attractions (e.g. seals) may greatly affect visitor numbers. • Relating visitor number to parking features provides baseline of recreation use. • Parking interventions potentially effective in managing recreation. With an increasing global population, there is growing demand for access to natural greenspaces for recreation. The importance of such access is now widely recognised, for example in terms of improvements to physical and psychological health. Because recreation can also result in damage to ecological interest, there is a need to balance access and nature conservation. As the primary mode by which visitors arrive to many sites is by car, parking characteristics may influence on-site visitor levels. However, few studies have related visitor use to parking features. Using data from 55 unpublished studies, we consider how parking type (e.g. formal car parks, laybys), parking capacity, presence/absence of facilities and charging relate to the visitor volume at sites designated for their nature conservation interest. A negative binomial regression model to control for the effect of habitat type and season is then developed. The number of visitors was significantly different between parking locations with different capacities. Compared to the smallest locations (2.7 visitors per hour), this difference was strongest for the largest locations (12.5 visitors per hour). Visitor numbers varied less between parking types and with the presence/absence of facilities. Locations where parking was charged, across all capacities, had significantly more visitors than free-of-charge locations. These results provide estimates of typical levels of use at different parking locations. However, visitor numbers might also be influenced by a site's attractiveness. Further studies on visitor numbers before and after introducing measures are needed, to provide empirical evidence for the effect of parking interventions. [ABSTRACT FROM AUTHOR]