A rat model to investigate quality of recovery after abdominal surgery.

INTRODUCTION: Major advances in therapies to optimize recovery after surgery have been limited by the lack of an animal model that can mimic major domains of postoperative sickness behavior in humans. We hypothesized that the integration of commonly impaired domains of quality of recovery in humans could be reproduced in a rat model. OBJECTIVES: To create a rat model that can mimic surgical recovery in humans. METHODS: Adult male Sprague-Dawley rats were used in the development of a quality of recovery score after surgery. Six physiological parameters or behaviors were tested in naive, sham, and laparotomized animals. A quality of recovery score was constructed and ranged from 18 (no impairment) to 0 (gross impairment). We treated animals with a nutraceutical intervention consisting of aspirin and eicosapentaenoic acid. Inflammatory markers and specialized proresolving mediators were measured in serum and the intestinal mucosa of rats, respectively. RESULTS: We observed a significant reduction in quality of recovery scores on postoperative days 1 (median, interquartile: 6 [4.75-8.25] vs naive rats: 17.5 [15.5-18]), 2 (median, interquartile: 13 [11.25-13.25], P < 0.001 vs naive rats: 17 [17-18], P = 0.001), and 3 (median, interquartile: 14.5 [13.5-16] vs naive rats: 17 [15.75-18], P < 0.02). Surgery promoted a significant increase in the concentrations of inflammatory cytokines, but it reduced levels of interleukin-12p70 and macrophage colony-stimulating factor. Lipoxin B4 and 13-HODE were significantly higher in laparotomized rats. Aspirin + eicosapentaenoic acid substantially improved recovery scores and modulated the postsurgical inflammatory response. CONCLUSION: Our novel rat model can be used to study mechanisms governing surgical recovery in rats.

Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu-opioid receptor.

The Mu-opioid receptor (MOR) has been implicated in tumorigenesis and metastasis. Methylnaltrexone (MNTX), an antagonist of MOR, has shown to inhibit tumor growth and metastasis in lung cancer cell lines. The effect of MNTX on other cell lines such as head and neck squamous cell carcinoma (HNSCC) has not been investigated. We measured the expression and activity of the receptor in different HNSCC cell lines. Then, we evaluated the impact of modulating the expression MOR and the effect of MNTX on the proliferation, clonogenic activity, invasion, and migration of two HNSCC (FaDu and MDA686Tu) cell lines expressing MOR and one cell line (UMSCC47) not expressing the receptor. We also evaluated the impact of MNTX on tumor growth and metastasis formation in vivo. Activation of the receptor with [d-Ala2,N-Me-Phe4, Gly5-ol] (DAMGO) caused a significant reduction in cyclic adenosine monophosphate levels in FaDu cells. Knockdown of MOR inhibited in vitro aggressive cell behaviors on FaDu and MDA686Tu cells and correlated with a reduction in markers of epithelial-mesenchymal transition. In vitro studies showed that MNTX strongly inhibited the proliferation, clonogenic activity, invasion, and migration of FaDu and MDA686Tu cells but has no effect on UMSCC47 cells. In vivo experiments demonstrated that MNTX suppresses tumor growth in HNSCC cell tumor-bearing mice. Our studies indicate that MOR could be considered as a therapeutic target to treat HNSCC.

Mu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma.

AIMS: In vitro and in vivo studies suggest that the mu-opioid receptor (MOR) is involved in tumorigenesis, and metastasis in cancer. In humans, the use of MOR agonists (opioids) is associated with head and neck squamous cell carcinoma (HNSCC) progression. In the present study, we aimed to examine the role of MOR activation in MOR (+) HNSCC. MAIN METHODS: FaDu, MDA686Tu and UMSCC47 cell lines were used in in vitro and in vivo experiments. Cells and animals were treated with a highly selective MOR agonist DAMGO, [D-Ala (2), Me Phe (4), Glycol (5)]-enkephalin] or saline 0.9%. KEY FINDINGS: MOR activation significantly increased the proliferation, colony formation, invasion, and migration of FaDu and MDA6868Tu cells and promoted tumor growth in vivo. SIGNIFICANCE: These findings suggest that MOR is implicated in tumorigenesis of HNSCC. Overall, our findings identify that MOR could be used as a potential therapeutic target in patients with MOR (+) HNSCC.

Persistent and Chronic Postoperative Opioid Use in a Cohort of Patients with Oral Tongue Squamous Cell Carcinoma.

BACKGROUND: Recently, the concept of persistent postsurgical opioid use has been described for patients undergoing cancer surgery. Our hypothesis was based on the premise that patients with oral tongue cancer require high dosages of opioids before, during, and after surgery, and thus a large percentage of patients might develop persistent postsurgical opioid use. METHODS: After institutional review board approval, we conducted a retrospective study that included a cohort of patients with oral tongue cancers who underwent curative-intent surgery in our institution. Multivariable logistic regression models were fit to study the association of the characteristics of several patients with persistent (six months after surgery) and chronic (12 months after surgery) postoperative opioid use. RESULTS: A total of 362 patients with oral tongue malignancies were included in the study. The rate of persistent use of opioids after surgery was 31%. Multivariate analysis showed that patients taking opioids before surgery and those receiving adjuvant therapy were 2.9 and 1.78 times more likely to use opioids six months after surgery. Fifteen percent of the patients were taking opioids 12 months after surgery. After adjusting for clinically relevant covariates, patients complaining of moderate tongue pain before surgery and those taking opioids preoperatively had at least three times higher risk of still using these analgesics one year after surgery. CONCLUSIONS: Patients with oral tongue cancers have a high risk of developing persistent and chronic postsurgical opioid use.

Correction: Impact of epidural analgesia on the systemic biomarker response after hepatic resection.

[This corrects the article DOI: 10.18632/oncotarget.26549.].

Impact of epidural analgesia on the systemic biomarker response after hepatic resection.

BACKGROUND: Perioperative inflammation is associated with poor oncologic outcomes. Regional analgesia has been shown mitigate some of these inflammatory changes and be associated with better oncologic outcomes in patients with hepatic malignancies. The mechanism for this effect, however, remains unclear. The authors sought to compare systemic biomarker concentrations in a comprehensive and oncologically relevant panel in the perioperative setting between patients undergoing thoracic epidural analgesia (TEA) and intra-venous patient- controlled analgesia (IV-PCA) for resection of hepatic metastatic disease. RESULTS: Clinicopathologic variables and baseline biomarkers were similar between TEA (n = 46) and IV-PCA (n = 16) groups. Of the biomarkers which were significantly changed from baseline, there was a lower fold change from baseline in the TEA patients compared to IV-PCA including IL-6 (13.5vs19.1), MCP-1 (1.9vs3.0), IL-8 (2.4vs3.0), and Pentraxin-3 (10.8vs15.6). Overall decreased systemic concentrations of TGFb signaling were noted in TEA patients on POD1 TGFb3 (243.2 vs. 86.0, p = 0.005), POD3 TGFb1 (6558.0 vs. 2063.3, p = 0.004), POD3 TGFb2 (468.3 vs. 368.9, p = 0.036), POD3 TGFb3 (132.2 vs. 77.8, p = 0.028), and POD5 TGFb3 (306.5 vs. 92.2, p = 0.032). POD1 IL-12p70 concentrations were significantly higher in TEA patients (8.3 vs. 1.6, p = 0.024). CONCLUSION: Epidural analgesia damped the postoperative inflammatory response and systemic immunosuppressive signaling, as well as promoted Th1 systemic signaling early in the post-operative period after hepatic resection for metastatic disease. These differences elaborate on known mechanisms for improved oncologic outcomes with regional anesthesia, and may be considered for biomarker monitoring of effective regional anesthesia in oncologic surgery. MATERIALS AND METHODS: Patient data, including clinicopathologic variables were collected for this study from the database of a randomized controlled trial comparing perioperative outcomes in patients undergoing hepatic resection with TEA vs. IV-PCA. Patients undergoing resection for metastatic disease were selected for this study. Plasma concentrations (pg/mL) of well-studied biomarkers (IL-1b/2/4/5/6/7/8/10/12p70/13/17, MCP-1 IFNγ, TNFα, MIP-1b, GM-CSF, G-CSF, VEGF, Resistin, TGFb1, TGFb2, and TGFb3), as well as novel perioperative markers (CXCL12, CXCL10, Omentin-1, sLeptin R, Vaspin, Pentraxin-3, Galactin-3, FGF-23, PON-1, FGF-21) were measured preoperatively, and on postoperative day (POD)1, POD3, and POD5 using multiplex bead assays. Clinicopathologic variables and perioperative variations in these biomarkers were compared between TEA vs IV-PCA groups.

The impact of intraoperative opioid use on survival after oral cancer surgery.

OBJECTIVES: To investigate the impact of opioid use on cancer recurrence after oral cancer surgery. We hypothesized that the amount of opioids administered during oral cancer surgery is an independent predictor of recurrence free survival (RFS) and overall survival (OS). METHODS: After Institutional Review Board approval, we collected demographic, tumor related, intraoperative and survival data of patients who had oral cancer surgery. Multivariable Cox proportional hazards models were used to determine the impact of important covariates on RFS and OS. RESULTS: 268 patients were included. After adjusting for significant covariates, the amount of opioids administered during surgery was not an independent predictor of RFS (HR: 1.27 [CI 95%, 0.838-1.924], p=0.26). However, we observed an association between opioid consumption and shorter OS (HR=1.77, [CI 95%=0.995-3.149]. p=0.05). CONCLUSIONS: High requirements of opioids during surgery increase the risk of recurrence and mortality by 27% and 77%, although the association is not statically significant.

Severe perioperative bleeding in renal cell carcinoma after elective pericardiocentesis associated left ventricular puncture: case report. / Hemorragia perioperatoria grave asociada a punción del ventrículo izquierdo post pericardiocentesis en un paciente con carcinoma de células renales: reporte de caso.

In the United States during the year 2015, approximately 61,560 patients are expected to be diagnosed with kidney cancer and 14,080 to die from the disease. We present the case of a patient with renal cell carcinoma who suffered severe perioperative bleeding and coagulopathy after emergency sternotomy. We also engage in relevant aspects of perioperative anesthesia care including the considerations and management of coagulopathy, liver failure and renal failure in the oncologic patient. The case is a 49-year-old man with vena cava tumor thrombus who underwent radiologic tumor embolization, left radical nephrectomy, and inferior vena cava (IVC) thrombectomy. Postoperatively, he developed sepsis, multiple organ failure, and a pericardial effusion requiring pericardiocentesis. During pericardiocentesis, he suffered an iatrogenic left entricular perforation, requiring an emergency sternotomy and left ventricular repair. Cancer patients are often challenging for surgical and anesthesia teams, emergency care requires an organized and comprehensive approach. The use of recombinant factor VIIa NovoSeven can help in managing severe postoperative bleeding after cardiothoracic surgery in oncologic patients, but further studies should be done to confirm this.

En los Estados Unidos se estimó que, durante el 2015, unos 61 560 pacientes serían diagnosticados con cáncer renal y que 14 080 morirían por esta enfermedad. Presentamos el caso de un paciente con carcinoma de células renales y trombo tumoral de vena cava inferior que sufrió una hemorragia perioperatoria grave y coagulopatía después de una esternotomía de emergencia. También abordamos aspectos relevantes del cuidado anestésico perioperatorio incluyendo consideraciones y manejo de coagulopatía, falla renal y hepática en un paciente oncológico. El caso es un hombre de 49 años que fue llevado a embolización tumoral guiada por radiología, nefrectomía radical izquierda y trombectomía de vena cava inferior. En el período postoperatorio desarrolló sepsis, falla orgánica múltiple y efusión pericárdica que requirió pericardiocentesis. Durante la pericardiocentesis sufrió perforación iatrogénica de ventrículo izquierdo que necesitó esternotomía de emergencia y reparación del ventrículo izquierdo. Los pacientes con cáncer son a menudo un reto para el equipo de cirugía y anestesia, y el cuidado de emergencia requiere un abordaje integral y organizado. El uso de factor recombinante VIIa NovoSeven puede ayudar en el manejo de la hemorragia severa perioperatoria después de cirugía cardiotorácica en pacientes oncológicos, pero se deben hacer estudios posteriores para confirmarlo.

Do Not Burn Your Airway Bridge: A Technique to Safely Exchange a Tracheostomy Tube for a Tracheal Tube.

Tracheostomy is one of the most ancient and commonly performed surgical procedures. When tracheostomized patients require a subsequent intervention, it is usually necessary to exchange the tracheostomy tube for a tracheal tube, which can be dangerous. These potential complications may be overlooked or underestimated by the anesthesia providers. An inability to ventilate the patient and replace the tube after removal of a fresh tracheostomy tube can escalate rapidly to a life-threatening crisis. We present a case in which an airway exchange catheter was used to safely replace a tracheostomy tube with a tracheal tube in a patient with a fresh tracheostomy.