Prognostic significance of Daxx NCR (Nuclear/Cytoplasmic Ratio) in gastric cancer

Abstract

In addition to regulating apoptosis via its interaction with the death domain of Fas receptor, death domain associated protein 6 (Daxx) is also known to be involved in transcriptional regulation, suggesting that the function of Daxx depends on its subcellular localization. In this study, we aimed to explore Daxx subcellular localization in gastric cancer (GC) cells and correlate the findings with clinical data in GC patients. Seventy pairs of tissue samples (GC and adjacent normal tissue) were analyzed immunohistochemically for Daxx expression and localization (nuclear and cytoplasmic). The Daxx Nuclear/Cytoplasmic ratio (Daxx NCR) values in tissue microarray data with 522 tumor samples were further analyzed. The defined Prior cohort (n = 277, treatment between 2006 and 2009) and Recent cohort (n = 245, treatment between 2010 and 2011) were then used to examine the relationship between Daxx NCR and clinical data. The Daxx NCR was found to be clinically informative and significantly higher in GC tissue. Using Daxx NCR (risk ratio = 2.0), both the Prior and Recent cohorts were divided into high- and low-risk groups. Relative to the low-risk group, the high-risk patients had a shorter disease free survival (DFS) and overall survival (OS) in both cohorts. Importantly, postoperative chemotherapy was found having differential effect on high- and low-risk patients. Such chemotherapy brought no survival benefit, (and could potentially be detrimental,) to high-risk patients after surgery. Daxx NCR could be used as a prognosis factor in GC patients, and may help select the appropriate population to benefit from chemotherapy after surgery.

Daxx NCR can be used as a prognosis factor in GC patients, and may provide an alternative view on adjuvant chemotherapy in patients with gastric cancer.

http://ift.tt/2i4fkOh

AMBIGUITY IN A MASCULINE WORLD: Being a BRCA1/2 mutation carrier and a man with prostate cancer

Abstract

Background

Increased risk of prostate cancer(PCa) is observed in men with BRCA1/BRCA2 mutations. Sex and gender are key determinants of health and disease although unequal care exists between the sexes. Stereotypical male attitudes are shown to lead to poor health outcomes.

Methods

Men with BRCA1/2 mutations and diagnosed with PCa were identified and invited to participate in a qualitative interview study. Data were analysed using a Framework approach. 'Masculinity theory' was used to report the impact of having both a BRCA1/2 mutation and PCa.

Results

Eleven of 15 eligible men were interviewed. The umbrella concept of 'Ambiguity in a Masculine World' was evident. Men's responses often matched those of women in a genetic context. Men's BRCA experience was described, as 'on the back burner' but 'a bonus' enabling familial detection and early diagnosis of PCa. Embodiment of PCa took precedence as men revealed stereotypical 'ideal' masculine responses such as stoicism and control while creating new 'masculinities' when faced with the vicissitudes of having two gendered conditions.

Conclusion

Health workers are urged to take a reflexive approach, void of masculine ideals, a belief in which obfuscates men's experience. Research is required regarding men's support needs in the name of equality of care.

http://ift.tt/2vBMLg0

Epithelial-to-Mesenchymal and Mesenchymal-to-Epithelial Transition in Mesenchymal Tumors: A Paradox in Sarcomas?

The epithelial-to-mesenchymal transition (EMT) is a reversible process comprised of various subprograms via which epithelial cells reduce their intercellular adhesions and proliferative capacity while gaining a mesenchymal phenotype with increased migratory and invasive properties. This process has been well described in several carcinomas, which are cancers of epithelial origin, and is crucial to metastatic tumor cell dissemination and drug resistance. In contrast, the precise role of EMT-related processes in tumors originating from mesenchymal tissues, such as bone and soft-tissues sarcomas, is still largely unclear. In fact, although the existence of the EMT in sarcomas appears paradoxical because these cancers are, by definition, mesenchymal ab initio, accumulating evidence suggests that many sarcomas can undergo EMT-related processes, which may be associated with aggressive clinical behavior. These processes may be especially operative in certain sarcoma subtypes, such as carcinosarcomas displaying a biphenotypic morphology with characteristics of both mesenchymal and epithelial tumors. In this review, we discuss findings regarding the potential existence of EMT-related processes in sarcomas and propose that sarcomas can reside in a metastable state, enabling them to become either more mesenchymal or epithelial under specific conditions, which likely has important clinical implications. Cancer Res; 77(17); 1–6. ©2017 AACR.

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Transglutaminase 2 Is a Direct Target Gene of YAP-TAZ—Response

http://ift.tt/2i3iiTl

Transglutaminase 2 Is a Direct Target Gene of YAP/TAZ—Letter

http://ift.tt/2fJohvN

De Novo Lipid Synthesis facilitates Gemcitabine Resistance Through Endoplasmic Reticulum Stress In Pancreatic Cancer

Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients. Furthermore, we investigated the relationship between alterations in lipogenesis pathway and gemcitabine resistance by utilizing tissues from the genetically engineered mouse model and human pancreatic cancer patients. We observed a significant increase in fatty acid synthase (FASN) expression with increasing disease progression in a spontaneous pancreatic cancer mouse model, and a correlation of high FASN expression with poor survival in patients and poor gemcitabine responsiveness in cell lines. We observed a synergistic effect of FASN inhibitors with gemcitabine in pancreatic cancer cells in culture and orthotopic implantation models. Combination of gemcitabine and the FASN inhibitor orlistat significantly diminished stemness, in part due to induction of ER stress that resulted in apoptosis. Moreover, direct induction of ER stress with thapsigargin caused a similar decrease in stemness and showed synergistic activity with gemcitabine. Our in vivo studies with orthotopic implantation models demonstrated a robust increase in gemcitabine responsiveness upon inhibition of fatty acid biosynthesis with orlistat. Altogether, we demonstrate that fatty acid biosynthesis pathway manipulation can help overcome the gemcitabine resistance in pancreatic cancer by regulating ER stress and stemness.

http://ift.tt/2i4VBhN

Targeting a single alternative polyadenylation site coordinately blocks expression of androgen receptor mRNA splice variants in prostate cancer

Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3. Blocking this signal with morpholino technology or silencing of the polyadenylation factor CPSF1 caused a splice switch that inhibited expression of AR variants and blocked androgen-independent growth of CRPC cells. Our findings support the development of new therapies targeting the polyadenylation signal in AR intron 3 as a strategy to prevent expression of a broad array of AR variants in CRPC.

http://ift.tt/2fJnfzP

PPAR{gamma} Ligand-induced Annexin A1 Expression Determines Chemotherapy Response via Deubiquitination of Death Domain Kinase RIP in Triple Negative Breast Cancers

Metastatic breast cancer is still remain incurable so far, new specifically targeted and more effective therapies for triple negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data has established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines which model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and Peroxisome Proliferator-Activated Receptor gamma (PPAR). A similar correlation between these two markers was also established in our clinical breast cancer patients' specimens. To establish a link between these two markers in TNBC, we show de novo expression of ANXA1 is induced by activation of PPAR both in vitro and invivo and it has a predictive value in determining chemo-sensitivity to PPAR ligands. Mechanistically, we show for the first time PPAR-induced ANXA1 protein directly interacts with Receptor Interacting Protein-1 (RIP1), promoting its deubiquitination and thereby activating the caspase 8-dependent death pathway. We further identified this underlying mechanism also involved a PPAR-induced ANXA1-dependent autoubiquitination of cIAP1, the direct E3 ligase of RIP1, shifting cIAP1 towards proteosomal degradation. Collectively, our study provides first insight for the suitability of using drug-induced expression of ANXA1 as a new player in RIP1-induced death machinery in TNBCs. Hitherto, presenting itself both as an inclusion criterion for patient selection and surrogate marker for drug response in future PPAR chemotherapy trials.

http://ift.tt/2vHdiag

Outcome of hearing preservation related to tumor morphologic analysis in acoustic neuromas treated by gamma knife radiosurgery

Gamma Knife radiosurgery (GKRS) is an important part of the neurosurgical armamentarium in the treatment of acoustic neuromas. However, the treatment outcome related to the morphology of the tumor has not been...

http://ift.tt/2wNX92N

Classification of chronic radiation-induced ulcers in the chest wall after surgery in breast cancers

To explore the methods of clinical classification in chronic radiation-induced ulcers in the chest wall (CRUCWs).

http://ift.tt/2vBYcUU

Factors affecting survival after concurrent chemoradiation therapy for advanced hepatocellular carcinoma: a retrospective study

Concurrent chemoradiation therapy (CCRT) followed by hepatic arterial infusional chemotherapy (HAIC) was reported to be effective for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Howeve...

http://ift.tt/2wO8akw

Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity

Though the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity...

http://ift.tt/2vBUnio

STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4

Abstract

Background

Several of the thousands of human long noncoding RNAs (lncRNAs) have been functionally characterized, yet their potential involvement in hepatocellular carcinoma (HCC) remains poorly understood.

Methods

LncRNA-HOXD-AS1 was identified by microarray and validated by real-time PCR. The clinicopathological significance of HOXD-AS1 was analyzed by Kaplan-Meier method. Chromatin immunoprecipitation was conducted to examine the mechanism of HOXD-AS1 upregulation. The role of HOXD-AS1 in HCC cells was assessed both in vitro and in vivo. ceRNA function of HOXD-AS1 was evaluated by RNA immunoprecipitation and biotin-coupled miRNA pull down assays.

Results

In this study, we found that HOXD-AS1 was significantly upregulated in HCC tissues. Clinical investigation demonstrated high expression level of HOXD-AS1 was associated with poor prognosis and high tumor node metastasis stage of HCC patients, and was an independent risk factor for survival. Moreover, our results revealed that STAT3 could specifically interact with the promoter of HOXD-AS1 and activate HOXD-AS1 transcription. Knockdown of HOXD-AS1 significantly inhibited migration and invasion of HCC cells in vitro and distant lung metastasis in vivo. Additionally, HOXD-AS1 was enriched in the cytoplasm, and shared miRNA response elements with SOX4. Overexpression of HOXD-AS1 competitively bound to miR-130a-3p that prevented SOX4 from miRNA-mediated degradation, thus activated the expression of EZH2 and MMP2 and facilitated HCC metastasis.

Conclusions

In summary, HOXD-AS1 is a prognostic marker for HCC patients and it may play a pro-metastatic role in hepatocarcinogenesis.

http://ift.tt/2uZXai5

Patterns of locoregional failure following post-operative intensity-modulated radiotherapy to oral cavity cancer: quantitative spatial and dosimetric analysis using a deformable image registration workflow

We sought to identify spatial/dosimetric patterns of failure for oral cavity cancer patients receiving post-operative IMRT (PO-IMRT).

http://ift.tt/2vYZ1Ih

DVH- and NTCP-based dosimetric comparison of different longitudinal margins for VMAT-IMRT of esophageal cancer

To cover the microscopic tumor spread in squamous cell carcinoma of the esophagus (SCC), longitudinal margins of 3–4 cm are used for radiotherapy (RT) protocols. However, smaller margins of 2–3 cm might be rea...

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Study Uncovers Previously Unrecognized Effect of Chemotherapy

A new study conducted primarily in mice suggests that chemotherapy given before surgery for breast cancer can cause changes in cells in and around the tumor that are tied to an increased risk of the cancer spreading to other areas of the body.

http://ift.tt/2wNzboq

Neutrophils in cancer: prognostic role and therapeutic strategies

Abstract

Expression of high levels of immune cells including neutrophils has been associated with detrimental outcome in several solid tumors and new strategies to decrease their presence and activity are currently under clinical development. Here, we review some of the relevant literature of the role of neutrophils in different stages of the oncogenic process including tumor initiation, growth, proliferation or metastatic spreading and also focus on how neutrophil counts or the neutrophil-to-lymphocyte ratio may be used as a prognostic and predictive biomarker. Strategies to avoid the deleterious effects of neutrophils in cancer and to reduce their activity are discussed. Examples for such strategies include inhibition of CXCR1 and CXCR2 to decrease migration of neutrophils to tumoral areas or the inhibition of granulocyte colony stimulating factor to decrease the amount of neutrophils which has shown efficacy in preclinical models.

http://ift.tt/2uG7Tml

Oncologic and Cosmetic Outcomes of Oncoplastic Breast Surgery in Locally Advanced Breast Cancer After Neoadjuvant Chemotherapy, Experience from a Developing Country

Abstract

Oncoplastic surgery (OPS) has emerged as a new approach for extending breast conserving surgery (BCS) possibilities, reducing both mastectomy and re-excision rates, while avoiding breast deformities. OPS is based upon the integration of plastic surgery techniques for immediate reshaping after wide excision for breast cancer. This is a prospective feasibility cohort study of oncoplastic breast surgery after neoadjuvant chemotherapy that was carried at the National Cancer Institute, Cairo University and included 70 patients. The primary outcome was the local recurrence rate. Secondary outcomes included survival and margins obtained as well as cosmetic outcomes. Survival analysis was performed. Oncoplastic breast surgery did not compromise oncologic safety in the patients included in the study. It even allowed wider margins of resection which could be associated with better oncologic outcomes. At the same time, it gave a better cosmetic outcome and therefore higher patient satisfaction. Oncoplastic breast surgery includes a wide spectrum of surgical techniques, ranging from the basic level I techniques in breast conserving surgery to the more complex procedures of level II which are broadly classified into volume replacement (therapeutic mammoplasty) and volume displacement procedures. We suggest that oncoplastic breast surgery techniques should be the standard of care in breast surgery. They are the basis for breast conserving surgery techniques in early breast cancer. In our experience, oncoplastic surgery is feasible in locally advanced tumours after downstaging with neoadjuvant chemotherapy without compromising the oncologic safety.

http://ift.tt/2vZ5R0E

Phase I dose-escalation study of pazopanib combined with bevacizumab in patients with metastatic renal cell carcinoma or other advanced tumors

Abstract

Background

Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors.

Methods

In this bicentric phase I trial with a 3 + 3 + 3 dose-escalation design, patients received oral pazopanib once daily plus intravenous infusion of bevacizumab every 2 weeks from D15, at one of the four dose levels (DL) planned according to the occurrence of dose limiting toxicities (DLT). 400 and 600 mg pazopanib were respectively combined with 7.5 mg/kg bevacizumab in DL1 and DL2, and 600 and 800 mg pazopanib with 10 mg/kg bevacizumab in DL3 and DL4. Tumor response was evaluated every 8 weeks. Blood samples were assayed to investigate pazopanib pharmacokinetics.

Results

Twenty five patients including seven mRCC were enrolled. Nine patients received the DL1, ten received the DL2. No DLT were observed at DL1, five DLT at DL2, and 3 DLT in the six additional patients who received the DL1. A grade 3 microangiopathic hemolytic anemia syndrome was observed in four (16%) patients. Five (22%) patients achieved a partial response. The mean (range) plasmatic concentrations of 400 and 600 pazopanib were respectively 283 (139–427) and 494 (227–761) μg.h/mL at Day 1, and 738 (487–989) and 1071 (678–1464) μg.h/mL at Day 15 i.e. higher than those previously reported with pazopanib, and were not directly influenced by bevacizumab infusion.

Conclusions

The combination of pazopanib and bevacizumab induces angiogenic toxicity in patients without any pre-existing renal or vascular damage. Even if a marginal efficacy was reported with five (22%) patients in partial response in different tumor types, the toxicity profile compromises the development of this combination.

Trial registration

The study was retrospectively registered on ClinicalTrials.gov (number NCT01202032) on 2010, Sept 14th.

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The association between patient attitudes and values and the strength of consideration for contralateral prophylactic mastectomy in a population-based sample of breast cancer patients

BACKGROUND

Little is known about how the individual decision styles and values of breast cancer patients at the time of treatment decision making are associated with the consideration of different treatment options and specifically with the consideration of contralateral prophylactic mastectomy (CPM).

METHODS

Newly diagnosed patients with early-stage breast cancer who were treated in 2013-2014 were identified through the Surveillance, Epidemiology, and End Results registries of Los Angeles and Georgia and were surveyed approximately 7 months after surgery (n = 2578; response rate, 71%). The primary outcome was the consideration of CPM (strong vs less strong). The association between patients' values and decision styles and strong consideration was assessed with multivariate logistic regression.

RESULTS

Approximately one-quarter of women (25%) reported strong/very strong consideration of CPM, and another 29% considered it moderately/weakly. Decision styles, including a rational-intuitive approach to decision making, varied. The factors most valued by women at the time of treatment decision making were as follows: avoiding worry about recurrence (82%) and reducing the need for more surgery (73%). In a multivariate analysis, patients who preferred to make their own decisions, those who valued avoiding worry about recurrence, and those who valued avoiding radiation significantly more often strongly considered CPM (P < .05), whereas those who reported being more logical and those who valued keeping their breast did so less often.

CONCLUSIONS

Many patients considered CPM, and the consideration was associated with both decision styles and values. The variability in decision styles and values observed in this study suggests that formally evaluating these characteristics at or before the initial treatment encounter could provide an opportunity for improving patient clinician discussions. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2i3rFSY

Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism

Abstract

Background

Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear.

Methods

A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular radiosensitivity. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the radiosensitivity of hepatoma in vivo.

Results

shRNA-induced Girdin silencing suppressed glycolysis and enhanced the radio-sensitivity of hepatic cell lines, HepG2 and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis.

Conclusion

Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.

http://ift.tt/2x0CdVy

Outcome of hearing preservation related to tumor morphologic analysis in acoustic neuromas treated by gamma knife radiosurgery

Abstract

Background

Gamma Knife radiosurgery (GKRS) is an important part of the neurosurgical armamentarium in the treatment of acoustic neuromas. However, the treatment outcome related to the morphology of the tumor has not been rigorously studied. In this cohort, we evaluated the morphological features of the tumor in the tumor response and neurological outcomes after GKRS.

Material and methods

From July 2003 to December 2008, there were 93 cases of acoustic neuromas treated upfront with GKRS with 64 cases with serviceable hearing and 29 cases without serviceable hearing to fulfill the margin dose of 12Gy with at least follow up 5 years.

Results

The duration of symptom before GKRS in serviceable /no serviceable hearing was 7.9 ± 1.2 and 15.3 ± 3.1 months (p < 0.001) and associated no-hearing symptom was 70% and 35%, respectively (p < 0.001). There was 81.2% of hearing preservation after GKRS in serviceable hearing group including 27 cases of pear type (84%), 14 of linear type (70%), and 9 cases of sphere type (90%) (p < 0.01); however, there was no case of hearing improvement in the no-serviceable hearing group (0 of 29). There were 85% of patients with decreased tinnitus in serviceable hearing groups as compared to 61.5% of patients in no serviceable hearing group (p < 0.05). In multivariate analysis, the tumor morphology was highly correlated to hearing preservation rate (p < 0.01).

Conclusion

In the limited case of this cohort, we found that the tumor morphology and timing of treatment was highly correlated to the rate of hearing preservation. The sphere type of tumor morphology was associated with the best chance of hearing preservation.

http://ift.tt/2i28Qjb

Factors affecting survival after concurrent chemoradiation therapy for advanced hepatocellular carcinoma: a retrospective study

Abstract

Background

Concurrent chemoradiation therapy (CCRT) followed by hepatic arterial infusional chemotherapy (HAIC) was reported to be effective for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. However, transarterial chemoembolization (TACE) is not preferred in this setting. The aim of this study was to assess the factors affecting survival after CCRT, including additional TACE during repeated HAIC.

Methods

Thirty-eight patients who underwent CCRT as the initial treatment for Barcelona Clinic Liver Cancer stage C HCC with vascular invasion between 2009 and 2016 were reviewed retrospectively. During CCRT, 5-fluorouracil (5-FU) was infused via chemoport during the first and last five days of five weeks of external beam radiation therapy. After CCRT, repeated HAIC with cisplatin and 5-FU was performed monthly. Nineteen patients (50%) underwent additional TACE between repeated HAICs. Factors related to overall survival and progression free survival (PFS) were analyzed.

Results

The mean age of patients was 55 years (male:female, 33:5). Underlying liver diseases were hepatitis B, hepatitis C and non-B/C in 29, 1 and 8 patients, respectively. The median radiation dose was 4500 cGy. The objective response (OR) rate at one months after CCRT was 36.8%. The median PFS was 7.4 (range, 1.8 − 32.1) months. The median overall survival was 11.6 (range 2.8-65.7) months. Achieving an OR after CCRT (hazard ratio [HR], 0.028; P < 0.001), additional TACE (HR, 0.134, P < 0.001), and further rounds of HAIC (HR, 0.742, P = 0.001) were independent significant factors related to overall survival. The overall survival duration of patients with an OR after CCRT (median 44.2 vs. 6.6 months, P < 0.001) and additional TACE (median 19.8 vs. 9.1 months, P = 0.001) were significantly greater than those without an OR after CCRT or additional TACE.

Conclusion

Patients who achieved an OR after CCRT, underwent additional TACE, and were subjected to repeated rounds of HAIC following CCRT showed better survival after CCRT for advanced stage of HCC with vascular invasion. A further prospective study is needed to confirm the positive effect of additional TACE after CCRT.

http://ift.tt/2fI8ZY7

Classification of chronic radiation-induced ulcers in the chest wall after surgery in breast cancers

Abstract

Background and purpose

To explore the methods of clinical classification in chronic radiation-induced ulcers in the chest wall (CRUCWs).

Materials and methods

A total of 64 patients with CRUCWs were treated. We divided the cases into 3 types (mild, moderate, or severe) according to their clinical manifestations. Conservative treatments, axial-pattern myocutaneous or local flaps, or filleted flaps were applied correspondingly.

Results

The cases were divided as follows: mild (n = 11), moderate (n = 45), and severe (n = 8). Eight cases were cured by conservative surgical therapy. One case had a recurrence 6 months after conservative therapy and was cured by a latissimus dorsi myocutaneous flap. The transferred flaps all survived, including 26 transverse rectus abdominis myocutaneous flaps, 8 longitudinal rectus abdominis myocutaneous flaps, 6 latissimus dorsi myocutaneous flaps, 3 contralateral breast flaps, 5 lateral thoracic rotation flaps, and 7 filleted flaps. In 2 transverse rectus abdominis myocutaneous flaps and 2 latissimus dorsi myocutaneous flaps, distal necrosis appeared in small areas. The resulting wounds were salvaged with skin graft and full healing was achieved.

Conclusion

CRUCWs can be divided into three types. Surgical methods should vary with distinguished classifications. The effective classification of CRUCWs has definite instructive significance on the selection of surgical approaches.

http://ift.tt/2i28KrP

Comparison of photon volumetric modulated arc therapy, intensity-modulated proton therapy, and intensity-modulated carbon ion therapy for delivery of hypo-fractionated thoracic radiotherapy

Abstract

Purpose

The aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy.

Methods and materials

Ten selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i.e., GyE) in 15 fractions delivered with VMAT, IMPT, or IMCIT with the same optimization criteria. Treatment plans were then compared.

Results

There were no significant differences in target volume dose coverage or dose conformity, except improved D₉₅ was found with IMCIT compared with VMAT (p = 0.01), and IMCIT was significantly better than IMPT in all target volume dose parameters. Particle therapy led to more prominent lung sparing at low doses, and this result was most prominent with IMCIT (p < 0.05). Improved sparing of other thoracic organs at risk (OARs) was observed with particle therapy, and IMCIT further lowered the D_1cc and D_5cc for major blood vessels, as compared with IMPT (p = 0.01).

Conclusion

Although it was comparable to VMAT, IMCIT led to significantly better tumor target dose coverage and conformity than did IMPT. Particle therapy, compared with VMAT, improved thoracic OAR sparing. IMCIT, compared with IMPT, may further improve normal lung and major blood vessel sparing under limited respiratory motion.

http://ift.tt/2fHipmS

Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity

Abstract

Background

Though the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity-modulated radiotherapy (IMRT) can decrease doses to critical cardiopulmonary organs. To date, there have been no studies comparing both modalities as part of definitive chemoradiation (dCRT) for EC. Herein, we investigated local control and survival and evaluated clinical factors associated with these endpoints between cohorts.

Methods

We retrospectively analyzed 93 patients (3DCRT n = 49, IMRT n = 44) who received dCRT at our institution between 2000 and 2012 with the histologic diagnosis of nonmetastatic EC, a Karnofsky performance status of ≥70, curative treatment intent, and receipt of concomitant CRT. Patients were excluded if receiving <50 Gy. Kaplan-Meier analysis was used to evaluate the endpoints of local relapse rate (LR), progression-free survival (PFS), and overall survival (OS). Cox proportional hazards modeling addressed factors associated with outcomes with univariate and multivariate approaches. Rates of acute toxicities and basic dosimetric parameters were compared between 3DCRT and IMRT patients.

Results

Mean follow-up was 34.7 months. The 3-year LR was 28.6% in the 3DCRT group and 22.7% in the IMRT group (p = 0.620). Median PFS were 13.8 and 16.6 months, respectively (p = 0.448). Median OS were 18.4 and 42.0 months, respectively (p = 0.198). On univariate analysis, only cumulative radiation dose was associated with superior LR (hazard ratio (HR) 0.736; 95% confidence interval (CI) 0.635 – 0.916, p = 0.004). Factors clearly affecting survival were not observed.

Conclusions

When comparing 3DCRT- versus IMRT-based dCRT, no survival benefits were observed. However, we found a lower local recurrence rate in the IMRT group potentially owing to dose-escalation. Prospective data are needed to verify the presented results herein.

http://ift.tt/2i1W1Fp

A meta-analysis: microRNAs’ prognostic function in patients with nonsmall cell lung cancer

Abstract

Accumulating papers have demonstrated that microRNAs play an important role in the progression of lung cancer, mainly as oncogenic and tumor suppressive. Therefore, microRNAs may influence the survival of lung cancer patients. In this meta-analysis, we evaluated the role of microRNAs in affecting the overall survival in nonsmall cell lung cancer (NSCLC) patients, which may provide valuable information for the treatment of nonsmall cell lung cancer. We used keywords to retrieve literatures from online databases PUBMED, EMBASE and Web of Science and included 12 studies into our investigation according to pre-set criteria. Then, we analyzed the data with stata13.1 to evaluate the microRNAs role on the prognosis of NSCLC patients. NSCLC patients with higher microRNAs expression levels tend to show lower overall survival. HR (hazard ratio): 2.49, 95% CI (confidence interval): 1.84–3.37. Besides, both oncogenic and tumor suppressive microRNAs have an evident influence on prognosis with HR values of 2.60 (95% CI: 2.12–3.19) and 0.41 (95% CI: 0.05–0.34), respectively. microRNAs, especially from tissue, have an influence on overall survival of NSCLC patients, which indicates that microRNAs could serve as potential prognostic markers for NSCLC and may provide a treatment strategy for advanced NSCLC patients.

The article is different from other researches about miRNAs' function in cancer patients, which considered much miRNAs to evaluate its comprehensive influence as there were kinds of miRNAs existed in human body instead of only one or several kinds of them. So there was a new idea in it.

http://ift.tt/2uEStPw

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer

Abstract

Purpose

To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients.

Methods

From 2012 to 2016, 106 patients (median age 74 years, range 50–94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent ¹⁸F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1–3 cm) in 86 patients (81%) and IIA (T2a/b, 3–5 cm) in 20 patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5 Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%.

Results

Median follow-up was 15 months (range 0.5–46 months). Acute side effects were mild (fatigue grade 1–2 in 20% and dyspnea grade 1–2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80–96%) at 2 years and 77% (95%CI 56–98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23–31 months). Overall survival was 77% (95%CI 65–85%) at 2 years and 56% (95%CI 39–73%) at 3 years.

Conclusion

CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

http://ift.tt/2vzSeUE

Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region

Abstract

Purpose

Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region.

Materials and methods

DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively.

Results

DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels.

Conclusion

Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

http://ift.tt/2wLwbIZ

Predictive and prognostic impact of tumour-infiltrating lymphocytes in triple-negative breast cancer treated with neoadjuvant chemotherapy

Carmen Herrero-Vicent, Angel Guerrero, Joaquin Gavilá, Francisco Gozalbo, Abraham Hernandez, Sergio Sandiego, Maria Asunción Algarra, Ana Calatrava, Vicente Guillem-Porta and Amparo Ruiz-Simón

http://ift.tt/2uF0EeA

Metastasizing pleomorphic adenoma of the parotid gland

Javier Soteldo and Nathasha Aranaga

http://ift.tt/2uY4KJW

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer

Abstract

Purpose

To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients.

Methods

From 2012 to 2016, 106 patients (median age 74 years, range 50–94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent ¹⁸F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1–3 cm) in 86 patients (81%) and IIA (T2a/b, 3–5 cm) in 20 patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5 Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%.

Results

Median follow-up was 15 months (range 0.5–46 months). Acute side effects were mild (fatigue grade 1–2 in 20% and dyspnea grade 1–2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80–96%) at 2 years and 77% (95%CI 56–98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23–31 months). Overall survival was 77% (95%CI 65–85%) at 2 years and 56% (95%CI 39–73%) at 3 years.

Conclusion

CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

http://ift.tt/2vzSeUE

Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region

Abstract

Purpose

Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region.

Materials and methods

DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively.

Results

DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels.

Conclusion

Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

http://ift.tt/2wLwbIZ

Successful intravenous thrombolysis for ischemic stroke after reversal of dabigatran anticoagulation with idarucizumab: a case report

Non-vitamin K antagonist oral anticoagulants, including dabigatran, are currently widely used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Recently, ida...

http://ift.tt/2vXUGp7

Oral manifestations, dental management, and a rare homozygous mutation of the PRDM12 gene in a boy with hereditary sensory and autonomic neuropathy type VIII: a case report and review of the literature

Hereditary sensory and autonomic neuropathy type VIII is a rare autosomal recessive inherited disorder. Chen et al. recently identified the causative gene and characterized biallelic mutations in the PR domain-co...

http://ift.tt/2vF0wJ6

A Case of Immediate Hypersensitivity Reaction to Maltitol

Background. Maltitol is a sugar alcohol that is frequently used as a noncaloric sweetener, although it is also used as an excipient, a plasticizer in gelatin capsules, and an emollient. It has not been previously described as an agent involved in immediate hypersensitivity reactions. Methods. We report on an anaphylactoid reaction with pharyngeal occlusion suffered by a 60-year-old man after ingestion of a candy containing maltitol syrup. A prick-to-prick test was performed with the candy and maltitol powder. Other allergens were excluded as causative agents of the adverse reaction, although the patient refused to undergo an oral challenge test with the candy. A basophil activation test (BAT) was performed with maltitol powder, and a dose-response curve was generated. The test was also performed in 3 healthy controls. Results. Both prick-to-prick tests were negative. The result of the BAT was positive at all the concentrations tested in the patient's blood and negative in all the controls. Conclusions. The BAT can help to clarify the agents implicated in an adverse reaction and can reduce the risk involved in diagnosis. The BAT can also prove useful in the study of reactions caused by low-molecular-weight antigens, for which routine diagnostic tests are not feasible.

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Die beste multimodale Therapie beim lokal fortgeschrittenen Nasopharynxkarzinom

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Dose-escalated radiation therapy is associated with better overall survival in patients with bone metastases from solid tumors: a propensity score-matched study

Abstract

We aimed to compare the overall survival (OS) of patients with bone metastases (BM) from solid tumors after standard-dose radiotherapy ([RT]; 30 Gy administered in 10 fractions; EQD_2Gy = 32.5 Gy) and dose-escalated RT (EQD_2Gy > 32.5 Gy). We retrospectively reviewed the clinical charts of 1795 patients (median age, 62.3 years; age range, 18–96 years) with BM from solid tumors who were referred for RT to our institute between 2000 and 2013. These patients were assigned to the standard-dose (n = 1125; 63%) and dose-escalated (n = 670; 37%) RT groups. OS, estimated as the duration between the first RT session and death, served as the main outcome measure. The dose-escalated RT group had a significantly better OS than the standard-dose RT group (P = 0.000). After allowing potential confounders in multivariate analysis, the RT dose retained its independent association with OS (hazard ratio [HR], 0.837; 95% confidence interval [CI], 0.753–0.929, P = 0.001). After propensity score matching of the baseline characteristics of both groups, RT dose retained its independent association with OS (HR, 0.887; 95% CI, 0.737–0.951; P = 0.011) on multivariate analysis. Dose-escalated RT exerted more favorable effects on OS in patients with non-lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis. Dose-escalated RT was significantly associated with better OS in patients with BM from solid malignancies, particularly among those with non-lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis.

Dose-escalated radiotherapy (with >30 Gy doses administered in 10 fractions) was significantly associated with better overall survival in patients with bone metastases from solid malignancies, particularly among those with non-lung cancer, without multiple metastases, without symptoms, and with favorable prognosis.

http://ift.tt/2fI96mC

Die beste multimodale Therapie beim lokal fortgeschrittenen Nasopharynxkarzinom

http://ift.tt/2vEtdpS

Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience

Abstract

Background

Osteosarcoma is the most frequent primary malignant bone tumour, and its incidence is higher in children and adolescents, for whom it represents more than 10% of solid cancers. Despite the introduction of adjuvant and neo-adjuvant chemotherapy that markedly increased the success rate in the treatment, aggressive surgery is still needed and a considerable percentage of patients do not survive due to recurrences or early metastases. Boron Neutron Capture Therapy (BNCT), an experimental radiotherapy, was investigated as a treatment that could allow a less aggressive surgery by killing infiltrated tumour cells in the surrounding healthy tissues. BNCT requires an intense neutron beam to ensure irradiation times of the order of 1 h. In Italy, a Radio Frequency Quadrupole (RFQ) proton accelerator has been designed and constructed for BNCT, and a suitable neutron spectrum was tailored by means of Monte Carlo calculations. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator.

Methods

The therapeutic efficacy of BNCT was analysed evaluating the dose distribution obtained in a clinical case of femur osteosarcoma. Mixed field dosimetry was assessed with two different formalisms whose parameters were specifically derived from radiobiological experiments involving in vitro UMR-106 osteosarcoma cell survival assays and boron concentration assessments in an animal model of osteosarcoma. A clinical case of skull osteosarcoma treated with BNCT in Japan was re-evaluated from the point of view of dose calculation and used as a reference for comparison.

Results

The results in the case of femur osteosarcoma show that the RFQ beam would ensure a suitable tumour dose painting in a total irradiation time of less than an hour. Comparing the dosimetry between the analysed case and the treated patient in Japan it turns out that doses obtained in the femur tumour are at least as good as the ones delivered in the skull osteosarcoma. The same is concluded when the comparison is carried out taking into account osteosarcoma irradiations with photon radiation therapy.

Conclusions

The possibility to apply BNCT to osteosarcoma would allow a multimodal treatment consisting in neo-adjuvant chemotherapy, high-LET selective radiation treatment and a more conservative surgery.

http://ift.tt/2wZXEG9

The role of human papillomavirus on the prognosis and treatment of oropharyngeal carcinoma

Abstract

Human papillomavirus positive oropharyngeal cancer (HPV-positive OPC) is a distinct subtype of head and neck carcinoma (HNC) distinguished from HPV-negative HNC by its risk factor profile, clinical behavior, and molecular biology. Compared to HPV-negative HNC, HPV-positive OPC exhibits significantly better prognosis and an enhanced response to treatment. Recognition of the survival benefit of HPV-positive tumors has led to therapeutic de-intensification strategies aiming to mitigate treatment-related toxicities while maintaining high response rates. In this review, we summarize key aspects of oral HPV infection and the molecular mechanisms of HPV-related carcinogenesis. We review the clinical and molecular characteristics of HPV-positive OPC that contribute to its improved prognosis compared to HPV-negative HNC. We also discuss current and emerging treatment strategies, emphasizing potential mechanisms of treatment sensitivity and the role of therapeutic de-intensification in HPV-positive OPC. Lastly, we examine literature on the management and prognosis of recurrent/metastatic HPV-positive OPC with a focus on the role of salvage surgery in its management.

http://ift.tt/2vEtY1S

Biography—David Menter

http://ift.tt/2vXOc9C

Preoxygenation Before Extubation: A Road to Patient Safety Less Traveled!

No abstract available

http://ift.tt/2wZUFxK

Response to Dr O'Reilly-Shah et al.

No abstract available

http://ift.tt/2w5BhCX

Chronic Pain and Associated Factors in India and Nepal: A Pilot Study of the Vanderbilt Global Pain Survey.

BACKGROUND: Evaluation and treatment of chronic pain worldwide are limited by the lack of standardized assessment tools incorporating consistent definitions of pain chronicity and specific queries of known social and psychological risk factors for chronic pain. The Vanderbilt Global Pain Survey (VGPS) was developed as a tool to address these concerns, specifically in the low- and middle-income countries where global burden is highest. METHODS: The VGPS was developed using standardized and cross-culturally validated metrics, including the Brief Pain Inventory and World Health Organization Disability Assessment Scale, as well as the Pain Catastrophizing Scale, the Fibromyalgia Survey Questionnaire along with queries about pain attitudes to assess the prevalence of chronic pain and disability along with its psychosocial and emotional associations. The VGPS was piloted in both Nepal and India over a 1-month period in 2014, allowing for evaluation of this tool in 2 distinctly diverse cultures. RESULTS: Prevalence of chronic pain in Nepal and India was consistent with published data. The Nepali cohort displayed a pain point prevalence of 48% to 50% along with some form of disability present in approximately one third of the past 30 days. Additionally, 11% of Nepalis recorded pain in 2 somatic sites and 39% of those surveyed documented a history of a traumatic event. In the Indian cohort, pain point prevalence was approximately 24% to 41% based on the question phrasing, and any form of disability was present in 6 of the last 30 days. Of the Indians surveyed, 11% reported pain in 2 somatic sites, with only 4% reporting a previous traumatic event. Overall, Nepal had significantly higher chronic pain prevalence, symptom severity, widespread pain, and self-reported previous traumatic events, yet lower reported pain severity. CONCLUSIONS: Our findings confirm prevalent chronic pain, while revealing pertinent cultural differences and survey limitations that will inform future assessment strategies. Specific areas for improvement identified in this VGPS pilot study included survey translation methodology, redundancy of embedded metrics and cultural limitations in representative sampling and in detecting the prevalence of mental health illness, catastrophizing behavior, and previous traumatic events. International expert consensus is needed. (C) 2017 International Anesthesia Research Society

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Opportunities and Limitations in Mobile Technology.

No abstract available

http://ift.tt/2w5JCqa

Systemic Hypotension Following Intravenous Administration of Nonionic Contrast Medium During Computed Tomography: Iopromide Versus Iodixanol.

BACKGROUND: In light of the increasing number of radiologic interventions performed under general anesthesia, the effects of contrast media (CM) on circulation and organ perfusion are of paramount importance. The objectives of this study were to systematically quantify effects on blood pressure, heart rate, and kidney function following intravenous administration of nonionic CM with normal and low osmolality. METHODS: In this controlled, double-blinded phase IV clinical trial, 40 consecutive patients were randomly assigned to receive repeated measures of either low-osmolar iopromide or iso-osmolar iodixanol. Normal saline solution (NSS) served as control. Blood pressure and heart rate were measured continuously from 1 minute before until 3 minutes after administration of CM and NSS. Urine output was recorded hourly. RESULTS: Administration of iopromide resulted in systemic hypotension lasting up to 300 seconds (105 +/- 61 seconds) with the lowest mean arterial pressure of 39 mm Hg (56.7 +/- 12.2 mm Hg). Iopromide caused a systolic/diastolic decrease of 31/26 mm Hg (P .640). CONCLUSIONS: Administration of low-osmolar iopromide was followed by a significant transient decrease in blood pressure and a rise in heart rate. Anesthetists and radiologists should be aware of these effects in patients in whom short episodes of disturbed tissue microcirculation may pose a clinical risk. (C) 2017 International Anesthesia Research Society

http://ift.tt/2x023cu

Refractory Intracranial Hypertension: The Role of Decompressive Craniectomy.

Raised intracranial pressure (ICP) is associated with worse outcomes after acute brain injury, and clinical guidelines advocate early treatment of intracranial hypertension. ICP-lowering therapies are usually administered in a stepwise manner, starting with safer first-line interventions, while reserving higher-risk options for patients with intractable intracranial hypertension. Decompressive craniectomy is a surgical procedure in which part of the skull is removed and the underlying dura opened to reduce brain swelling-related raised ICP; it can be performed as a primary or secondary procedure. After traumatic brain injury, secondary decompressive craniectomy is most commonly undertaken as a last-tier intervention in a patient with severe intracranial hypertension refractory to tiered escalation of ICP-lowering therapies. Although decompressive craniectomy has been used in a number of conditions, it has only been evaluated in randomized controlled trials after traumatic brain injury and acute ischemic stroke. After traumatic brain injury, decompressive craniectomy is associated with lower mortality compared to medical management but with higher rates of vegetative state or severe disability. In patients with stroke-related malignant hemispheric infarction, hemicraniectomy significantly decreases mortality and improves functional outcome in adults 60 years, but results in a higher proportion of severely disabled survivors compared to medical therapy in this age group. Decisions to recommend decompressive craniectomy must always be made not only in the context of its clinical indications but also after consideration of an individual patient's preferences and quality of life expectations. This narrative review discusses the management of intractable intracranial hypertension in adults, focusing on the role of decompressive craniectomy in patients with traumatic brain injury and acute ischemic stroke. (C) 2017 International Anesthesia Research Society

http://ift.tt/2w65OjU

Risk Stratification for Major Postoperative Complications in Patients Undergoing Intra-abdominal General Surgery Using Latent Class Analysis.

BACKGROUND: Preoperative risk stratification is a critical element in assessing the risks and benefits of surgery. Prior work has demonstrated that intra-abdominal general surgery patients can be classified based on their comorbidities and risk factors using latent class analysis (LCA), a model-based clustering technique designed to find groups of patients that are similar with respect to characteristics entered into the model. Moreover, the latent risk classes were predictive of 30-day mortality. We evaluated the use of latent risk classes to predict the risk of major postoperative complications. METHODS: An observational, retrospective cohort of patients undergoing intra-abdominal general surgery in the 2005 to 2010 American College of Surgeons National Surgical Quality Improvement Program was obtained. Known preoperative comorbidity and risk factor data were entered into LCA models to identify the latent risk classes. Complications were defined as: acute kidney injury, acute respiratory failure, cardiac arrest, deep vein thrombosis, myocardial infarction, organ space infection, pneumonia, postoperative bleeding, pulmonary embolism, sepsis/septic shock, stroke, unplanned reintubation, and/or wound dehiscence. Relative risk regression determined the associations between the latent classes and the 30-day complication risks, with adjustments for the surgical procedure. The area under the curve (AUC) of the receiver operator characteristic curve assessed model performance. RESULTS: LCA fit a 9-class model on 466,177 observations. The composite complication risk was 18.4% but varied from 7.7% in the lowest risk class to 56.7% in the highest risk class. After adjusting for procedure, the latent risk classes were significantly associated with complications, with risk ratios (95% confidence intervals) (compared to the class with the average risk) varying from 0.56 (0.54-0.58) in the lowest risk class to 2.15 (2.11-2.20) in the highest risk class, a 4-fold difference. In models incorporating surgical procedure, latent risk class, and the American Society of Anesthesiologists Physical Status, the AUC for composite complications was 0.76 (0.76-0.76). However, for individual complications, there was heterogeneity in model performance using these variables, with AUCs ranging from 0.70 (0.69-0.71) for pulmonary embolus to 0.90 (0.90-0.90) for acute respiratory failure. CONCLUSIONS: LCA can be used to classify patients undergoing intra-abdominal general surgery based on preoperative risk factors, and the classes are independently associated with postoperative complications. However, model performance is not uniform across individual complications, resulting in variations in the utility of preoperative risk stratification tools depending on the complication evaluated. (C) 2017 International Anesthesia Research Society

http://ift.tt/2wZVPt4

The Opiorphin Analog STR-324 Decreases Sensory Hypersensitivity in a Rat Model of Neuropathic Pain.

BACKGROUND: Neuropathic pain represents a therapeutic challenge, and treatments with increased efficacy and tolerability still need to be developed. Opiorphin protects endogenous enkephalins from degradation, potentiating enkephalin-dependent analgesia via the activation of opioid pathways. Enkephalins are natural ligands of opioid receptors, with strong affinity for [delta]-opioid receptors. Expression of functional [delta]-opioid receptors increases in sensory neurons after peripheral nerve injury in neuropathic pain models. In a postoperative pain model, opiorphin and its stable analog STR-324 have an analgesic potency comparable to that of morphine, but without adverse opioid-related side effects. Consequently, administration of endogenous opiorphin peptides or STR-324 might be effective in managing peripheral neuropathic pain. METHODS: In this study, STR-324 was administered intravenously over the course of 7 days to rats with mononeuropathy induced by L5-L6 spinal nerve root ligation. The rats exhibited mechanical allodynia, thermal hyperalgesia, and spontaneous pain-related behavior throughout the testing period. RESULTS: Here, we report that the continuous administration of STR-324 significantly reduced mechanical allodynia and spontaneous pain-related behavior from day 2 to day 7 in animals that received 10 or 50 [micro]g/h of STR-324 as compared to placebo-treated animals (P

http://ift.tt/2w5LwY6

Ultrasound Guided Regional Anesthesia, 2nd ed.

No abstract available

http://ift.tt/2x01eQG

The Effect of Adductor Canal Block on Knee Extensor Muscle Strength 6 Weeks After Total Knee Arthroplasty: A Randomized, Controlled Trial.

BACKGROUND: Total knee arthroplasty (TKA) reduces knee extensor muscle strength (KES) in the operated limb for several months after the surgery. Immediately after TKA, compared to either inguinal femoral nerve block or placebo, adductor canal block (ACB) better preserves KES. Whether this short-term increase in KES is maintained several weeks after surgery remains unknown. We hypothesized that 48 hours of continuous ACB immediately after TKA would improve KES 6 weeks after TKA, compared to placebo. METHODS: Patients scheduled for primary unilateral TKA were randomized to receive either a continuous ACB (group ACB) or a sham block (group SHAM) for 48 hours after surgery. Primary outcome was the difference in maximal KES 6 weeks postoperatively, measured with a dynamometer during maximum voluntary isometric contraction. Secondary outcomes included postoperative day 1 (POD1) and day 2 (POD2) KES, pain scores at rest and peak effort, and opioid consumption; variation at 6 weeks of Knee Osteoarthritis Outcome Score, patient satisfaction, and length of hospital stay. RESULTS: Sixty-three subjects were randomized and 58 completed the study. Patients in group ACB had less pain at rest during POD1 and during peak effort on POD1 and POD2, consumed less opioids on POD1 and POD2, and had higher median KES on POD1. There was no significant difference between groups for median KES on POD2, variation of Knee Osteoarthritis Outcome Score, patient satisfaction, and length of stay. There was no difference between groups in median KES 6 weeks after surgery (52 Nm [31-89 Nm] for group ACB vs 47 Nm [30-78 Nm] for group SHAM, P= .147). CONCLUSIONS: Continuous ACB provides better analgesia and KES for 24-48 hours after surgery, but does not affect KES 6 weeks after TKA. Further research could evaluate whether standardized and optimized rehabilitation over the long term would allow early KES improvements with ACB to be maintained over a period of weeks or months. (C) 2017 International Anesthesia Research Society

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Letters to the Editor.

No abstract available

http://ift.tt/2wZLu00