Life-threatening hypotension in the immediate postoperative period of cataract surgery under topical anesthesia: a report of two cases.

BACKGROUND: Cataract surgery is one of the most frequent surgeries in the world. It is a very safe procedure mostly performed under topical anesthesia in outpatients centers. Due to the growing lack of anesthesiologists, cataract surgeries are more frequently performed without an anesthesiologist present in the operating room. Although extremely rare, life-threatening complications may occur. CASES PRESENTATION: We report two cases of cataract surgery complicated by severe hypotension that required emergency resuscitation in the immediate postoperative period and hospitalization in intensive care unit. Anaphylactic shock was confirmed in the first case and suspected in the second. CONCLUSIONS AND IMPORTANCE: Even though cataract surgery is a very safe procedure, it is essential to ensure the presence of an anesthesiologist to manage potential, though extremely rare, life-threatening complications such as anaphylactic reactions.

Philips Intellivue NMT module: precision and performance improvements to meet the clinical requirements of neuromuscular block management.

The variability or inaccuracy of acceleromyographic measurements could interfere with the interpretation of the train-of-four (TOF) ratio during neuromuscular block (NMB) recovery. This study evaluated the precision and performance of the Philips Intellivue NMT module (NMT) before (part 1) and after (part 2) several technical upgrades (i.e., firmware upgrade, new cable, and hand adapter) that were recently available. Two cohorts of 30 patients who were scheduled to undergo rhino/septoplasty under general anesthesia were included in the study. TOF ratios were recorded simultaneously every 15 s on both hands with the NMT and a TOF-Watch SX installed inside a SL TOF-Tube (TWX). Before rocuronium was administered and once final responses were stabilized, the average of the four successive measurements that determined the baselines and repeatability coefficients were compared using a z test. Simultaneous measurements were recorded at different NMB stages: onset, depth of NMB after intubation, when TWX recovered TOF count 2, TOF ratios 0.5 and 0.9, and when NMT recovered TOF ratio 0.9. The results were compared using a Student t test; p < 0.05 was considered significant. The NMT repeatability coefficients obtained in part 1 were significantly higher than with the TWX, they were significantly lower in part 2. Initially, the NMT significantly overestimated NMB recovery at every stage. Conversely, in the second part of the study, no difference reached statistical significance. With the recent upgrades and the new hand adapter, the NMT provided similar results compared with the TWX, Their implementation should be recommended in clinical practice.

Perioperative management of patients on direct oral anticoagulants.

Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10-15% of patients on oral anticoagulants will undergo an invasive procedure and expert groups have issued several guidelines on perioperative management in such situations. The perioperative guidelines have undergone numerous updates as clinical experience of emergency management has increased and perioperative studies including measurement of residual anticoagulant levels have been published. The high inter-patient variability of DOAC plasma levels has challenged the traditional recommendation that perioperative DOAC interruption should be based only on the elimination half-life of DOACs, especially before invasive procedures carrying a high risk of bleeding. Furthermore, recent publications have highlighted the potential danger of heparin bridging use when DOACs are stopped before an invasive procedure. As antidotes are progressively becoming available to manage severe bleeding or urgent procedures in patients on DOACs, accurate laboratory tests have become the standard to guide their administration and their actions need to be well understood by clinicians. This review aims to provide a systematic approach to managing patients on DOACs, based on recent updates of various perioperative guidance, and highlighting the advantages and limits of recommendations based on pharmacokinetic properties and laboratory tests.

Does the perioperative analgesic/anesthetic regimen influence the prevalence of long-term chronic pain after mastectomy?

STUDY OBJECTIVE: To investigate if the anesthetic/analgesic regimen is associated with the risk of reporting long-term chronic postmastectomy pain (CPMP). DESIGN: Cross-sectional survey SETTING: Academic hospital PATIENTS: A total of 267 women having undergone mastectomy with axillary lymph node dissection between 2003 and 2008 INTERVENTIONS: All patients were contacted between October and December 2012, with a questionnaire asking for persistent pain after surgery and its characteristics. MEASUREMENTS: Besides demographical data, tumor characteristics, and adjuvant treatment, we recorded type and doses of intraoperative anesthetics/analgesics (sufentanil, ketamine, clonidine, nonsteroidal anti-inflammatory drugs, MgSO4, propofol, or halogenated agents). RESULTS: Of the 128 patients returning analyzable questionnaires, 43.8% reported chronic pain (48.2% with neuropathic characteristics). Multivariate logistic/linear regression model showed 4 factors independently associated with persistent pain: recall of preoperative pain (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.09-1.48), chemotherapy (OR, 1.32; 95% CI, 1.13-1.55), need for strong opioids in postanesthesia care unit (OR, 1.30; 95% CI, 1.11-1.53), and halogenated agent anesthesia (OR, 0.81; 95% CI, 0.70-0.95). CONCLUSION: In conclusion, our study confirms the high prevalence of CPMP, 4 to 9 years after surgery. Recall of preoperative pain, chemotherapy, and need for strong opioids in the postanesthesia care unit were all associated with the presence of chronic pain. Of the intraoperative analgesics/anesthetics studied, only use of halogenated agents was associated with a lower prevalence of CPMP.

Leptin induces a proliferative response in breast cancer cells but not in normal breast cells.

Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, a hormone excessively produced during obesity, is suggested to be involved in breast cancer. The aim of the study was to investigate procarcinogenic potential of leptin by evaluating influence of leptin on cell proliferation, cell cycle, apoptosis, and signaling on numerous breast cells lines, including 184B5 normal cells, MCF10A fibrocystic cells and MCF-7, MDA-MB-231, and T47D cancer cells. Expressions of leptin and Ob-R were analyzed using qRT-PCR and immunohistochemistry, proliferation using fluorimetric resazurin reduction test and xCELLigence system, apoptosis and cell cycle by flow cytometry, and effect of leptin on different signalling pathways using qRT-PCR and Western blot. Cells were exposed to increasing concentrations of leptin. All cell lines expressed mRNA and protein of leptin and Ob-R. Leptin stimulated proliferation of all cell lines except for 184B5 and MDA-MB-231 cells. Leptin inhibited apoptosis but didn't alter proportion of cells within cell cycle in MCF7 cells. Leptin induced overexpression of leptin, Ob-R, estrogen receptor, and aromatase mRNA in MCF-7 and T47D cells. Autoregulation induced by leptin, relationship with estrogen pathway, and proliferative and antiapoptic activity in breast cancer cells may explain that obesity-associated hyperleptinemia may be a breast cancer risk factor.

Assessing the dual activity of a chalcone-phthalocyanine conjugate: design, synthesis, and antivascular and photodynamic properties.

Photodynamic therapy (PDT) and vascular-disrupting agents (VDA) each have their advantages in the treatment of solid tumors, but also present drawbacks. In PDT, hypoxia at the center of the tumor limits conversion of molecular oxygen into singlet oxygen, while VDAs are deficient at affecting the rim of the tumor. A phthalocyanine-chalcone conjugate combining the VDA properties of chalcones with the PDT properties of phthalocyanines was designed to address these deficiencies. Its vascular targeting, photophysical, photochemical, photodynamic activities are reported herein.

Reciprocal interactions between breast tumor and its adipose microenvironment based on a 3D adipose equivalent model.

Breast cancer has become the most common cancer among women in industrialized countries. Obesity is well established as a risk factor, in particular owing to the attendant secretion of the entities called adipokines; there is growing evidence for a role of cells and factors present in the mammary tumor microenvironment such as fibroblasts, preadipocytes, adipocytes and their secretions. To study how the microenvironment influences breast cancer growth, we developed a novel tridimensional adipose model epithelialized with normal human keratinocytes or with breast cancer cell lines. These mimicked a breast tumor in contact with an adipose microenvironment and allowed monitoring of the interactions between the cells. Leptin and adiponectin, two major adipokines, and their respective receptors, ObRt and AdipoR1, were expressed in the model, but not the second adiponectin receptor, AdipoR2. The differentiation of preadipocytes into adipocytes was greater when they were in contact with the breast cancer cell lines. The contact of breast cancer cell lines with the microenvironment completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal pathways (ESR1, IL6). This tridimensional adipose model provides new insights into the interactions between breast cancer cells and their adipose microenvironment, and provides a tool to develop new drugs for the treatment of both cancer and obesity.

Breast cancer and obesity: in vitro interferences between adipokines and proangiogenic features and/or antitumor therapies?

Obesity is now considered as a risk factor for breast cancer in postmenopausal women. Adipokine levels are modulated in obesity, and may play a role in carcinogenesis. Moreover, obesity increases risk of cancer mortality. Here, we hypothesized that this increase could be due to a modification in angiogenesis, capital event in the development of metastases, and/or in effectiveness of cancer treatments. To test these assumptions, following a same experimental design and simultaneously the effects of leptin and adiponectin on angiogenesis were investigated, and the impact of hyperleptinemia on anticancer drug effectiveness was measured in physiological and obesity situations. Focusing on angiogenesis, the proliferation of endothelial cells (HUVEC), which expressed leptin and adiponectin receptors, was stimulated by leptin and inhibited by adiponectin. Both adipokines globally reduced apoptosis and caspase activity. Leptin increased migration whereas adiponectin decreased migration, and leptin enhanced the area of the tubes formed by HUVEC cells while adiponectin inhibited their formation. MCF7 and MDA-MB-231 cells treated with leptin secreted more VEGF than untreated cells, whereas adiponectin treatment inhibited VEGF secretion. Finally, MCF7 cells pre-treated with leptin were more invasive than untreated cells. This effect was not reproduced in MDA-MB-231 cells. In the MCF7 breast cancer cell line, leptin could induce cell proliferation and reduced the efficacy of all breast cancer therapies (tamoxifen, 5-fluorouracil, taxol and vinblastin). These results suggest that, in obesity situation, leptin- in contrast to adiponectin - may promote tumor invasion and angiogenesis, leading to metastases 'apparition, and reduce treatment efficacy, which could explain the increased risk of cancer mortality in cases of overweight. The evidence suggests adipokines influence breast cancer issue and could play a significant role, especially in obese patients for which hyperleptinemia, hypoadiponectinemia and increased metastatic potential are described.

[Leptin: Involvement in the pathophysiology of breast cancer]. / Leptine : implication dans la physiopathologie du cancer du sein.

More than one million new cases of breast cancer are diagnosed each year worldwide and more than 400,000 deaths occur due to this pathology. Obesity is a risk factor for postmenopausal breast cancer and the place held by the adipose tissue and secretions (i.e. adipokines) begins to be recognized. Indeed, firstly, plasma adipokine levels, modulated in obesity situation, could have effects "remotely" on mammary carcinogenesis and, secondly, breast cancer cells are surrounded by adipocyte microenvironment, which is probably more important in the case of obesity, and may be locally influenced by it. In this context, leptin appears to be strongly involved in mammary carcinogenesis and may contribute to the angiogenesis process and local pro-inflammatory mechanisms, especially in obese patients for whom increased metastatic potential and risk of mortality are described.

Zinc-α2-glycoprotein: a proliferative factor for breast cancer? In vitro study and molecular mechanisms.

Zinc-α2-glycoprotein (ZAG) is a new adipokine whose gene expression is downregulated in obese patients. We recently reported ZAG expression in breast tumor or healthy breast tissue and detected this expression at high levels in ductal carcinoma and in normal epithelial adjacent tissue but not in normal tissue of healthy women. In the present study, we used two human breast tumor cell lines (MCF-7 and MDA-MB­231) and one fibrocystic breast cell line (MCF­10a) to examine whether recombinant ZAG has an effect on proliferative/apoptotic response in breast cancer cell lines. ZAG seemed to exert a proliferative effect on breast cancer cell proliferation [+11 to 27% in MCF-7 with (ZAG) = 5-20 µg/ml; +13% in MDA-MB-231 with (ZAG) = 5 µg/ml] and, on the contrary, an anti-proliferative effect in the fibrocystic breast cell line [-5 to -8% in MCF-10a with (ZAG) = 5-10 µg/ml]. ZAG was able to modulate gene and protein expression involved in the apoptotic response. However, further studies are required to fully elucidate the effects of ZAG on the proliferation of mammary cells.

New insights into anticarcinogenic properties of adiponectin: a potential therapeutic approach in breast cancer?

Obesity is a recognized breast cancer risk factor in postmenopausal women. A recent hypothesis suggests a major role for adipose tissue in carcinogenesis. During many years, the adipose tissue was only considered as a fat storage of energy. This tissue is now described as an endocrine organ secreting a large range of molecules called adipokines. Among these adipokines, adiponectin may play a major role in breast cancer. Plasma adiponectin levels were found to be decreased in cases of breast cancer and in obese patients. Adiponectin may act directly on breast cancer cells by inhibiting proliferation and angiogenesis or by stimulating apoptosis. Increasing adiponectin levels may be of major importance in the prevention and/or the treatment of breast cancer. This therapeutic approach may be of particular significance for obese patients. The beneficial effects of adiponectin and its possible therapeutic applications will be discussed in this review.