Αρχειοθήκη ιστολογίου

Τρίτη 12 Σεπτεμβρίου 2017

Exercise Oscillatory Ventilation: Inter-reviewer Agreement and a Novel Determination.

Introduction: Determination of exercise oscillatory ventilation (EOV) is subjective and the inter-reviewer agreement has not been reported. The purpose of this study was, among patients with heart failure (HF): (1) determine the inter-reviewer agreement for EOV; and (2) describe a novel, objective, and quantifiable measure of EOV. Methods: This was a secondary analysis of the HEART Camp: Promoting Adherence to Exercise in Patients with Heart Failure study. EOV was determined through a blinded review by 6 individuals based on their interpretation of the EOV literature. Inter-reviewer agreement was assessed with Fleiss kappa ([kappa]). Final determination of EOV was based on agreement by 4 of the 6 reviewers. A new measure (ventilation dispersion index; VDI) was calculated for each test and its ability to predict EOV was assessed with the receiver operator characteristics curve (ROC). Results: Among 243 patients with HF (age=60+/-12 years; 45% women) the inter-reviewer agreement for EOV was fair ([kappa]=0.303) with 10-s discrete data averages and significantly better, but only moderate ([kappa]= 0.429) with 30-s rolling data averages. Prevalence of positive and indeterminate EOVs were 18% and 30% with the 10-s discrete averages and 14% and 13% with the 30-s rolling averages, respectively. VDI was strongly associated with EOV with area under the ROC= 0.852 to 0.890. Conclusions: Inter-reviewer agreement for EOV in patients with HF is fair to moderate which can negatively affect risk stratification. VDI has strong predictive validity with EOV; as such it might be a useful measure of prognosis in patients with HF. (C) 2017 American College of Sports Medicine

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The Influence of Foot-Strike Technique on the Neuromechanical Function of the Foot.

Purpose: The aim of this study was to investigate the influence of foot-strike technique on longitudinal arch mechanics and intrinsic foot muscle function during running. Methods: 13 healthy participants ran barefoot on a force-instrumented treadmill at 2.8ms-1 with a forefoot (FFS) and rear-foot (RFS, habitual) running technique, while kinetic, kinematic and electromyographic (EMG) data from the intrinsic foot muscles were collected simultaneously. The longitudinal arch was modeled as a single "mid-foot" joint representing motion of the rear-foot (calcaneus) relative to the forefoot (metatarsals). An inverse dynamic analysis was performed to estimate joint moments generated about the mid-foot, as well as mechanical work and power. Results: The mid-foot was more plantar flexed (higher arch) at foot contact when running with a forefoot running technique (RFS 0.2 +/- 1.8o v FFS 6.9 +/- 3.0o, ES = 2.7), however there was no difference in peak mid-foot dorsiflexion in stance (RFS -11.6 +/- 3.0o v FFS -11.4 +/- 3.4o, ES = 0.63). When running with a forefoot technique, participants generated greater moments about the mid-foot (27% increase, ES = 1.1) and performed more negative work (240% increase, ES = 2.2) and positive work (42% increase, ES = 1.1) about the mid-foot. Average stance phase muscle activation was greater for Flexor Digitorum Brevis (20% increase, ES = 0.56) and Abductor Hallucis (17% increase, ES = 0.63) when running with a forefoot technique. Conclusion: Forefoot running increases loading about the longitudinal arch and also increases the mechanical work performed by the intrinsic foot muscles. These findings have substantial implications in terms of injury prevention and management for runners who transition from a rear-foot to a forefoot running technique. (C) 2017 American College of Sports Medicine

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The role of the neural niche in brain metastasis

Abstract

Cancers with neurologic metastasis are a burdensome affliction. As primary cancer care improves, the incidence of metastatic cancer increases as a result of prolonged survival time. Because of this, advances in the understanding of the mechanisms of metastasis are important for the development of continuing management strategies. Knowing how metastatic tumor cells engage, survive, and proliferate in the central nervous system (CNS) is an important first step in developing treatment paradigms. The neural niche is the soil of the CNS that accommodates tumor cells, is a microenvironment of cell signaling that exists between the tumor cell and the native neural cellular network. Elements of the neural niche have been identified as acquaintances for metastatic tumor growth. As more is known about the neural niche, treatment strategies can be developed to target these networks of metastatic tumor progression.



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Blood Supply to the Integument of the Abdomen of the Rat: A Surgical Perspective.

Background: Many fundamental questions regarding the blood supply to the integument of the rat remain to be clarified, namely the degree of homology between rat and humans. The aim of this work was to characterize in detail the macro and microvascular blood supply to the integument covering the ventrolateral aspect of the abdominal wall of the rat. Methods: Two hundred five Wistar male rats weighing 250-350 g were used. They were submitted to gross anatomical dissection after intravascular colored latex injection (n = 30); conversion in modified Spalteholz cleared specimens (n=10); intravascular injection of a Perspex solution, and then corroded, in order to produce vascular corrosion casts of the vessels in the region (n = 5); histological studies (n = 20); scanning electron microscopy of vascular corrosion casts (n = 10); surgical dissection of the superficial caudal epigastric vessels (n = 100); and to thermographic evaluation (n = 30). Results: The ventrolateral abdominal wall presented a dominant superficial vascular system, which was composed mainly of branches from the superficial caudal epigastric artery and vein in the caudal half. The cranial half still received significant arterial contributions from the lateral thoracic artery in all cases and from large perforators coming from the intercostal arteries and from the deep cranial epigastric artery. Conclusions: These data show that rats and humans present a great deal of homology regarding the blood supply to the ventrolateral aspect of the abdominal integument. However, there are also significant differences that must be taken into consideration when performing and interpreting experimental procedures in rats. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Lymph node-positive prostate cancer after robotic prostatectomy and extended pelvic lymphadenectomy

Abstract

Optimal management of node-positive prostate cancer patients after prostatectomy remains a challenge. We evaluated clinically localized patients who demonstrated node positivity and identified predictors for secondary treatment. From 2010 to 2015, clinically localized prostate cancer patients who underwent robot prostatectomy with extended lymphadenectomy and node-positive disease on pathologic analysis were identified. Clinical N1, M1 or salvage cases were excluded. Patients were stratified based on secondary treatments. Kaplan–Meier method was used to determine the time to biochemical and metastatic recurrence. Multivariate logistic regression was used to identify predictors for additional treatment. 145 patients (45 no additional therapy, 47 adjuvant, 53 salvage) had a median follow-up of 31.2 months. Salvage patients had higher median pre-operative prostate-specific antigen (10.8 vs. 9.7 vs. 8.2, p = 0.1), higher percentage of pathologic Gleason ≥8 (50.9 vs. 38.3% and 22.2%, p < 0.01), and higher median-positive nodes (3 vs. 1 and 1, p < 0.0001) compared to adjuvant and no treatment groups, respectively. Pathologic Gleason ≥8 (OR = 3.5, p = 0.007) and positive nodes ≥2 (OR = 3.3, p = 0.006) were associated with additional therapy. In the no treatment group, two-year estimated BCRFS was 74.3%. Two-year metastatic recurrence-free rates for no treatment, adjuvant and salvage groups were 100, 87.5, and 80.9%, respectively (p = 0.01). Observation is a viable alternative for low metastatic burden patients. In the largest series of node-positive patients from robotic prostatectomy and extended lymphadenectomy, those with pathologic Gleason ≥8 and positive lymph nodes ≥2 were more likely to receive additional treatment.



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Risk factors for postoperative pneumonia after microsurgery for vestibular schwannoma

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Publication date: November 2017
Source:Clinical Neurology and Neurosurgery, Volume 162
Author(s): Chenghong Wang, Tengfei Li, Shaozhou Tang, Yuekang Zhang
ObjectivesPostoperative complications occurred in about 30% patients after vestibular schwannoma (VS) microsurgical excision. Although many specific complications have been extensively studied, postoperative pneumonia (POP) has received little attention. This study was designed to identify the risk factors for POP after microsurgery for VS.Patients and methodsPatients undergoing VS microsurgical resection (n=244) between December 2014 and November 2016 at West China Hospital of Sichuan University were retrospectively assessed for POP. Univariate and multivariate analyses were performed to identify the risk factors for POP.ResultsPOP (Clavien–Dindo grade II or higher) was diagnosed in 29 (11.9%) patients. Univariate analysis revealed that age (≥60years; p=0.013), diabetes mellitus (DM; p=0.040) and Koos grade IV (p=0.017) were significantly associated with POP. Multivariate analysis revealed that these factors were all independent risk factors for POP. Association between POP and prolonged postoperative hospitalization was also revealed. However, no risk factor associated with severity of POP was found in this study.ConclusionOlder age, DM and Koos grade IV were identified as independent risk factors for POP after microsurgery for VS Moreover, POP caused a prolonged hospital stay.



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DIP2C expression in breast cancer and its clinical significance

Publication date: Available online 12 September 2017
Source:Pathology - Research and Practice
Author(s): Jing Li, Jin Liang Ping, Bo Ma, Ying Rong Chen, Li Qin Li
IntroductionThe aim of this study was to investigate DIP2C expression in different subtypes of breast cancer tissues and cell lines and its correlation with clinicopathologic and histopathological features, in an effort to elucidate the DIP2C expression profile in breast cancer and its clinical significance.MethodsHereby, we investigated the DIP2C expression in breast cancer tissues using TMA-IHC method and the DIP2C expression in breast cell lines using quantitative RT-PCR.ResultsDIP2C displayed universal expression, being present in all the breast cancer subtypes. There were more cases that staining weakly in breast cancer tissues (n=79/150, 52.7%) than that in fibroadenomas tissues (n=2/18, 11.1%) and normal tissues (n=2/20, 10.0%) (χ2=21.84, P <0.001). Within different intrinsic subtypes of breast cancer assayed by IHC expression profiles, there were less cases of the strongly staining group in basal-like subtype (n=38/86, 44.2%) and HER-2 subtype (n=6/24, 25.0%) than that in luminal A (14/20, 70%) and luminal B (13/20, 65%) subtypes (χ2=11.77, p=0.008). Furthermore, DIP2C expression was positive correlated with ER (χ2=8.90, p=0.003) and PR expression (χ2=10.94, p=0.001), while negative correlated with EGFR expression (χ2=9.27, p=0.002), in accordance with the results of cell lines with different subtypes. Oncomine database also confirmed that, DIP2C was expressed lower in breast cancer tissues, and could indicate prognosis.Conclusionour data revealed DIP2C expression level decreased in breast cancer, especially in basal-like and HER-2 subtypes, and could be a valuable target for diagnosis on specific subtype of breast cancer.



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Overexpression of KIFC1 and its association with spheroid formation in esophageal squamous cell carcinoma

Publication date: Available online 12 September 2017
Source:Pathology - Research and Practice
Author(s): Takeharu Imai, Naohide Oue, Yuji Yamamoto, Ryuichi Asai, Naohiro Uraoka, Kazuhiro Sentani, Kazuhiro Yoshida, Wataru Yasui
Esophageal squamous cell carcinoma (ESCC) is one of the most common human cancers. We previously reported that KIFC1 is involved in gastric cancer pathogenesis and that KIFC1 plays an important role in gastric cancer spheroid colony formation. However, the significance of KIFC1 in ESCC has not been examined. In the present study, we analyzed the expression and distribution of KIFC1 in 132 ESCC cases by immunohistochemistry. In contrast to weak or no staining of KIFC1 in non-neoplastic mucosa, ESCC tissue showed stronger, more extensive KIFC1 staining. In total, 95 (72%) of 132 ESCC cases were positive for KIFC1. Immunostaining of ALDH1 was also performed, and KIFC1-positive ESCC cases were significantly frequently found in ALDH1-positive ESCC cases compared with ALDH1-negative ESCC cases. Spheroid colony formation is an effective method to characterize CSCs, thus we analyzed sphere number and size at 15days in ESCC cells downregulated for KIFC1 by siRNA transfection. Both the number and size of sphere from TE-1 cells were significantly reduced in KIFC1 siRNA-transfected TE-1 cells than in negative control siRNA-transfected cells. These results suggest that KIFC1 plays an important role in ESCC pathogenesis.



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Epigallocatechin-3-gallate promotes apoptosis and reversal of multidrug resistance in esophageal cancer cells

Publication date: Available online 12 September 2017
Source:Pathology - Research and Practice
Author(s): Liang Liu, Yingchao Ju, Jing Wang, Rongmiao Zhou
Evidence for demonstrating the role of the green tea component epigallocatechin-3-gallate (EGCG) in esophageal squamous cell carcinoma cells is limited. In this study, we investigated apoptosis induced by EGCG and the underlying molecular mechanisms in human esophageal squamous cell carcinoma cells. The growth-inhibitory effects of EGCG on esophageal cancer cell (Eca109 and Ec9706) were detected by MTT. Using flow cytometry, we determined the cellular apoptosis, bcl-2, bax and caspase-3 protein expression in Eca109 and Ec9706 cells following treatment with EGCG for 24h. After treatment of Eca109/ABCG2 (an esophageal cancer multidrug resistance cell line) cells with adriamycin (ADM) combined with EGCG for 24h, the cellular apoptosis, mitochondrial membrane potential, ADM concentration in cells and ABCG2 protein expression were detected by flow cytometry. EGCG inhibited the growth of Eca109 and Ec9706 cells in a dose- and time- dependent manner. EGCG induced apoptosis, decreased the bcl-2 protein expression and increased the expression of bax and caspase-3 protein. The rate of apoptosis and ADM concentration in the Eca109/ABCG2 cells following treatment with ADM and EGCG were higher than that with ADM treatment alone, although the mitochondrial membrane potential was significantly lower (P <0.01). EGCG reduced the ABCG2 expression of Eca109/ABCG2 cells. Our data indicated that EGCG inhibited cell growth and induced esophageal cancer cell apoptosis. It reduced the bcl-2 protein expression and increased the bax and caspase-3 protein expression. EGCG reversed multi-drug resistance by reducing ABCG2 expression and increasing the anticancer drug concentration in cancer cells.



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The down-regulation of TAPP2 inhibits the migration of esophageal squamous cell carcinoma and predicts favorable outcome

Publication date: Available online 12 September 2017
Source:Pathology - Research and Practice
Author(s): Fang Liu, Fei Ye, Zongyu Guan, Yi Zhou, Fengjun Ji, Qing Zhang, Jianping Zhang, Tianyi Zhang, Songhua Lu
Tandem PH domain-containing proteins TAPP1 and TAPP2 are adaptor proteins that specifically bind to phosphatidylinositol-3,4-bisphosphate, or PI(3,4)P2, a product of phosphoinositide 3-kinases (PI3K). Although PI3K enzymes have multiple functions in cell biology, including cell migration, the functions of PI (3, 4) P2 and its binding proteins are not well understood. Previously studies found that TAPP2 is highly expressed in primary leukemic B cells that have strong migratory capacity. However, the function and underlying mechanisms of TAPP2 in ESCC remain largely unknown. In the present study, we investigated the level of TAPP2 in human esophageal squamous cell carcinoma (ESCC) tissues and in corresponding adjacent non-tumor tissues by immunohistochemistry (IHC) and western blot analyses. TAPP2 protein level was increased in ESCC tissues compared with corresponding adjacent non-tumor tissues. In vitro experiments showed that under-expression of TAPP2 reduced ESCC cell TE1 migration by wound-healing assays and transwell migration assays, and it was concurrent with the decreased expression of the phosphorylation of AKT. Taken together, these findings suggested that TAPP2 serves as oncogenic gene in ESCC and may serve as a new target for ESCC therapy.



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Mosasaurs and snakes have a periodontal ligament: timing and extent of calcification, not tissue complexity, determines tooth attachment mode in reptiles

Abstract

Squamates present a unique challenge to our understanding of dental evolution in amniotes because they are the only extant tooth-bearing group for which a ligamentous tooth attachment is considered to be absent. This has led to the assumption that mammals and crocodilians have convergently evolved a ligamentous tooth attachment, composed of root cementum, periodontal ligament, and alveolar bone, whereas squamates are thought to possess a single bone of attachment tissue that fuses teeth to the jaws. The identity and homology of tooth attachment tissues between squamates, crocodilians, and mammals have thus been a focal point of debate for decades. We provide a novel interpretation of the mineralized attachment tissues in two focal taxa in this debate, mosasaurids and snakes, and compare dental tissue histology with that of the extant crocodilian Caiman sclerops. We identify a periodontal ligament in these squamates that usually exists temporarily as a soft connective tissue anchoring each tooth to the alveolar bone. We also identify two instances where complete calcification of the periodontal ligament does not occur: in a durophagous mosasaur, and in the hinged teeth of fossil and modern snakes. We propose that the periodontal ligament rapidly calcifies in the majority of mosasaurids and snakes, ankylosing the tooth to the jaw. This gives the appearance of a single, bone-like tissue fusing the tooth to the jaw in ankylosed teeth, but is simply the end stage of dental tissue ontogeny in most snakes and mosasaurids.



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Issue Information - Contents



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Cover Image

Thumbnail image of graphical abstract

The cover image, by Miklos Perenyei et al., is based on the Operative Techniques Use of the self-retaining Alexis ring retractor in transoral robotic surgery, DOI: 10.1002/hed.24882.



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Pembrolizumab in the treatment of advanced urothelial cancer

Future Oncology, Ahead of Print.


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Cancer-Related Cognitive Changes

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Publication date: Available online 12 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Arash Asher, Kathleen Van Dyk, Sunita K. Patel, Robin Newman, Jessica Engle, Nancy Hutchinson, Lynne Padgett




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External Nasal Neuralgia: an Update

Abstract

Purpose of Review

External nasal neuralgia is a rare syndrome of atypical facial pain for which there is limited reports in the scientific literature. We aim to review diagnosis and provide an update on treatments for this rare condition.

Recent Findings

Etiology has been documented as post-traumatic due to direct trauma to the nose area and in few case reports, idiopathic. Sensory innervation of the nose arises from the ophthalmic and maxillary divisions of the trigeminal nerve. Direct injury to the nerve appears to be the etiology of post-traumatic external nasal neuralgia. Pathophysiology for idiopathic nasal neuralgia is poorly understood but it appears to be of a central etiology given lack of response to intranasal anesthetics. Pain can be episodic with episodes of tingling sensation lasting up to 30 min, two to three times per day, but for some patients it can be constant bruised sensation of mild to moderate pain. Diagnostic workup including magnetic resonance imaging of brain and computerized tomography of the sinuses are usually negative, but there have been few cases of a nasal contact point. Routine blood work including erythrocyte sedimentation rate is negative.

Summary

Treatment for this rare condition is varied with very few patients responding to tricyclic antidepressants, specifically amitriptyline. Another medication used as prevention is pregabalin with good results as well. Most patients respond to nerve blockade with local anesthetic to the external nasal nerve and sphenopalatine ganglion block and radiofrequency ablation. More reports of this condition need to be published in the scientific literature to assist with proper diagnosis and treatment of this condition.



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External Nasal Neuralgia: an Update

Abstract

Purpose of Review

External nasal neuralgia is a rare syndrome of atypical facial pain for which there is limited reports in the scientific literature. We aim to review diagnosis and provide an update on treatments for this rare condition.

Recent Findings

Etiology has been documented as post-traumatic due to direct trauma to the nose area and in few case reports, idiopathic. Sensory innervation of the nose arises from the ophthalmic and maxillary divisions of the trigeminal nerve. Direct injury to the nerve appears to be the etiology of post-traumatic external nasal neuralgia. Pathophysiology for idiopathic nasal neuralgia is poorly understood but it appears to be of a central etiology given lack of response to intranasal anesthetics. Pain can be episodic with episodes of tingling sensation lasting up to 30 min, two to three times per day, but for some patients it can be constant bruised sensation of mild to moderate pain. Diagnostic workup including magnetic resonance imaging of brain and computerized tomography of the sinuses are usually negative, but there have been few cases of a nasal contact point. Routine blood work including erythrocyte sedimentation rate is negative.

Summary

Treatment for this rare condition is varied with very few patients responding to tricyclic antidepressants, specifically amitriptyline. Another medication used as prevention is pregabalin with good results as well. Most patients respond to nerve blockade with local anesthetic to the external nasal nerve and sphenopalatine ganglion block and radiofrequency ablation. More reports of this condition need to be published in the scientific literature to assist with proper diagnosis and treatment of this condition.



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THE USE OF HUNTING AND HERDING SPACES: STABLE ISOTOPE ANALYSIS OF LATE ARCHAIC AND EARLY FORMATIVE CAMELIDS IN THE TULAN TRANSECT (PUNA DE ATACAMA, CHILE)

ABSTRACT

We present the results of analyzing stable carbon and nitrogen isotopes in camelid remains found at the Late Archaic site TU-52 (ca. 5000-3800 BP), the Tarajne Phase site TU-94 and the Early Formative sites TU-54, TU-85 and TU-122 (ca. 3100-2400 BP). All of the sites are located in the Puna de Atacama (Northern Chile) along the 14 km Tulan transect, between the head of Tulan ravine (ca. 3000 m.a.s.l.) and the border of the Salar de Atacama (2317 m.a.s.l.). Our aim is to understand how the space was used by hunter-gatherers and early herders from the beginning of camelid domestication to the consolidation of herding practices. Isotopic analyses were complemented with osteometric data in order to correlate changes in animal size and isotopic values with the initiation of animal husbandry. Isotopic and ostemetric results show less variability of δ13C and δ15N values during the Late Archaic and Tarajne Phase, whereas variability is higher during the Early Formative. We postulate that during the latter period there was more widespread use of hunting and herding spaces along the Tulan ravine, including areas above 3000 m.a.s.l. as result of more consolidated herding practices, while the highlands were used as a complementary space to hold livestock near ritual sites and residential settlements.



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Antagonism of EG-VEGF receptors as targeted therapy for choriocarcinoma progression in vitro and in vivo

Purpose: Choriocarcinoma (CC) is the most malignant gestational trophoblastic disease that often develops from complete hydatidiform moles (CHM). Neither the mechanism of CC development nor its progression is yet characterized. We have recently identified EG-VEGF as a novel key placental growth factor that controls trophoblast proliferation and invasion. EG-VEGF acts via two receptors PROKR1 and PROKR2. Here, we demonstrate that EG-VEGF receptors can be targeted for CC therapy. Experimental design: Three approaches were used, i) a clinical investigation comparing circulating EG-VEGF in Control (n=20) and in distinctive CHM (n=38) and CC (n=9) cohorts, ii) an in vitro study investigating EG-VEGF effects on the CC cell line JEG3, and iii) an in vivo study including the development of a novel CC mouse model, through a direct injection of JEG3-luciferase into the placenta of gravid SCID-mice. Results: Both placental and circulating EG-VEGF levels were increased in CHM and CC (x5) patients. EG-VEGF increased JEG3 proliferation, migration and invasion, in 2D and 3D culture systems. JEG3 injection in the placenta caused CC development with large metastases compared to their injection into the uterine horn. Treatment of the animal model with EG-VEGF receptor's antagonists significantly reduced tumor development and progression and preserved pregnancy. Antibody-array and immunohistological analyses further deciphered the mechanism of the antagonist's actions. Conclusions: Our work describes a novel pre-clinical animal model of CC and brings evidences that EG-VEGF receptors can be targeted for CC therapy. This may provide safe and less toxic therapeutic options compared to the currently used multi-agent chemotherapies.



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Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping and Monitoring

Purpose: Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making. Patients and Methods: In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet (dd) PCR. Nine patients had received tumor-infiltrating lymphocyte (TIL) immunotherapy. ccfDNA data were aligned with the tumor HPV genotype, drug treatment, and clinical outcome. Results: In blinded tests, HPV ccfDNA was detected in 19/19 (100%) patients with HPV-positive metastatic cervical cancer but not in any of the 45 healthy blood donors. The HPV genotype harbored in the patients' tumors was correctly identified in 87/87 (100%) sequential patient serum samples from 9 patients who received TIL immunotherapy. In three patients who experienced objective cancer regression after TIL treatment, a transient HPV ccfDNA peak was detected 2-3 days after TIL infusion. Furthermore, persistent clearance of HPV ccfDNA was only observed in two patients who experienced complete response (CR) after TIL immunotherapy. Conclusions: HPV ccfDNA represents a promising tumor marker for non-invasive HPV genotyping and may be used in selecting patients for HPV type-specific T cell based immunotherapies. It may also have value in detecting anti-tumor activity of therapeutic agents and in the long-term follow-up of cervical cancer patients in remission.



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TMEM16A/ANO1 inhibits apoptosis via down-regulation of Bim expression

Purpose: TMEM16A is a calcium-activated chloride channel that is amplified in a variety of cancers, including 30% of head and neck squamous cell carcinomas (HNSCC), raising the possibility of an anti-apoptotic role in malignant cells. The present study investigated this using a multi-modal, translational investigation. Experimental Design: Combination of 1) in vitro HNSCC cell culture experiments assessing cell viability, apoptotic activation, and protein expression 2) in vivo studies assessing similar outcomes, and 3) molecular and staining analysis of human HNSCC samples. Results: TMEM16A expression was found to correlate with greater tumor size, increased Erk 1/2 activity, less Bim expression, and less apoptotic activity overall in human HNSCC. These findings were corroborated in subsequent in vitro and in vivo studies and expanded to include a cisplatin-resistant phenotype with TMEM16A overexpression. A cohort of 41 patients with laryngeal cancer demonstrated that cases that recurred after chemoradiation failure were associated with a greater TMEM16A overexpression rate than HNSCC that did not recur. Conclusions: Ultimately, this study implicates TMEM16A as a contributor to tumor progression by limiting apoptosis and as a potential biomarker of more aggressive disease.



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Facts and Hopes in Immunotherapy of Lymphoma and Myeloma

Immune checkpoint blockade has driven a revolution in modern oncology, and robust drug development of immune checkpoint inhibitors is underway in both solid tumors and hematologic malignancies. High response rates to programmed cell death 1 (PD-1) blockade using nivolumab or pembrolizumab in classical Hodgkin lymphoma (cHL) and several variants of non-Hodgkin lymphoma (NHL) revealed an intrinsic biologic sensitivity to this approach, and work is ongoing exploring combinations with immune checkpoint inhibitors in both cHL and NHL. There are also preliminary data suggesting antitumor efficacy of PD-1 inhibitors used in combination with immunomodulatory drugs in multiple myeloma (MM), and effects of novel monoclonal antibody therapies on the tumor microenvironment may lead to synergy with checkpoint blockade. Although immune checkpoint inhibitors are generally well-tolerated, clinicians must use caution and remain vigilant when treating patients with these agents in order to identify immune related toxicities and prevent treatment-related morbidity and mortality. Autologous stem cell transplant is a useful tool for treatment of hematologic malignancies and has potential as a platform for use of immune checkpoint inhibitors. An important safety signal has emerged surrounding the risk of graft-versus-host-disease (GVHD) associated with use of PD-1 inhibitors before and after allogeneic stem cell transplant. We aim to discuss the facts known to date in the use of immune checkpoint inhibitors for patients with lymphoid malignancies, and discuss our hopes for expanding the benefits of immunotherapy to patients in the future.



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Matrix screen identifies synergistic combination of PARP inhibitors and nicotinamide phosphoribosyltransferase (NAMPT) inhibitors in Ewing sarcoma

Purpose: While many cancers are showing remarkable responses to targeted therapies, pediatric sarcomas, including Ewing sarcoma, remain recalcitrant. To broaden the therapeutic landscape, we explored the in vitro response of Ewing sarcoma cell lines against a large collection of investigational and approved drugs to identify candidate combinations. Experimental Design: Drugs displaying activity as single agents were evaluated in combinatorial (matrix) format to identify highly active, synergistic drug combinations, and combinations were subsequently validated in multiple cell lines using various agents from each class. Comprehensive metabolomic and proteomic profiling was performed to better understand the mechanism underlying the synergy. Xenograft experiments were performed to determine efficacy and in vivo mechanism. Results: Several promising candidates emerged, including the combination of small molecule poly ADP-ribose polymerase (PARP) and nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, a rational combination as NAMPT inhibitors block the rate-limiting enzyme in the production of NAD+, a necessary substrate of PARP. Mechanistic drivers of the synergistic cell killing phenotype of these combined drugs included depletion of NMN and NAD+, diminished PAR activity, increased DNA damage, and apoptosis. Combination PARP and NAMPT inhibitors in vivo resulted in tumor regression, delayed disease progression and increased survival. Conclusions: These studies highlight the potential of these drugs as a possible therapeutic option in Ewing sarcoma.



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Targeting Prostate Cancer Subtype 1 by Forkhead box M1 Pathway Inhibition

Purpose: Prostate cancer was recently classified to three clinically relevant subtypes (PCS) demarcated by unique pathway activation and clinical aggressiveness. In this preclinical study, we investigated molecular targets and therapeutics for PCS1, the most aggressive and lethal subtype with no treatment options available in the clinic. Experimental Design: We utilized the PCS1 gene set and our model of enzalutamide (ENZR) castration-resistant prostate cancer (CRPC) to identify targetable pathways and inhibitors for PCS1. The findings were evaluated in vitro and ENZR CRPC xenograft model in vivo. Results: The results revealed that ENZR CRPC cells are enriched with PCS1 signature and that Forkhead box M1 (FOXM1) pathway is the central driver of this subtype. Notably, we identified Monensin as a novel FOXM1 binding agent that selectively targets FOXM1 to reverse the PCS1 signature and its associated stem-like features and reduces the growth of ENZR CRPC cells and xenograft tumors. Conclusions: Our preclinical data indicate FOXM1 pathway as a master regulator of PCS1 tumours, namely in ENZR CRPC, and targeting FOXM1 reduces cell growth and stemness in ENZR CRPC in vitro and in vivo. These preclinical results may guide clinical evaluation of targeting FOXM1 to eradicate highly aggressive and lethal PCS1 prostate cancer tumours.



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TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer (PCa). Aggressive PCa, defined by the progression from localized disease to metastasis, is responsible for the majority of PCa-associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of PCa patients, however they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary PCa cohorts (N = 1,900), two metastatic castration resistant PCa datasets (N = 293) and one prospective cohort (N = 1,385) to assess the impact of TOP2A and EZH2 expression on PCa cellular program and patient outcomes. We also performed immunohistochemical staining for TOP2A and EZH2 in a cohort of primary PCa patients (N = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel PCa-derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic PCa datasets that concurrent TOP2A and EZH2 mRNA and protein up-regulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in PCa cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data supports further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neo-adjuvant targeted therapy approaches.



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Genomic characterisation of vulvar (pre)cancers identifies distinct molecular subtypes with prognostic significance

Background Vulvar cancer (VC) can be sub-classified by human papilloma virus (HPV) status. HPV negative VCs frequently harbour TP53 mutations, however in-depth analysis of other potential molecular genetic alterations is lacking. We comprehensively assessed somatic mutations in a large series of vulvar (pre)cancers. Methods We performed targeted next generation sequencing (17 genes), p53 immunohistochemistry and HPV-testing on 36 VC and 82 precursors (sequencing cohort). Subsequently, the prognostic significance of the three subtypes identified in the sequencing cohort was assessed in a series of 236 VC-patients (follow-up cohort). Results Frequent recurrent mutations were identified in HPV negative vulvar (pre)cancers in TP53 (42% and 68%), NOTCH1 (28% and 41%) and HRAS (20% and 31%). Mutation frequency in HPV positive vulvar (pre)cancers was significantly lower (p-value = 0.001). Furthermore, a substantial subset of the HPV negative precursors (35/60, 58.3%) and VC (10/29, 34.5%) were TP53 wild type (wt), suggesting a third, not-previously described, molecular subtype. Clinical outcomes in the three different subtypes (HPV+, HPV-/p53wt, HPV-/p53abn) were evaluated in a follow-up cohort consisting of 236 VC patients. Local recurrence rate was 5.3% for HPV+, 16.3% for HPV-/p53wt and 22.6% for HPV-/p53abn tumors (p=0.044). HPV positivity remained an independent prognostic factor for favourable outcome in the multivariable analysis (p=0.020). Conclusion HPV- and HPV+ vulvar (pre)cancers display striking differences in somatic mutation patterns. HPV-/p53wt VC appear to be a distinct clinicopathologic subgroup with frequent NOTCH1 mutations. HPV+ VC have a significant lower local recurrence rate, independent of clinicopathological variables, opening opportunities for reducing overtreatment in VC.



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Multi-Spectral Optoacoustic Tomography (MSOT) of human breast cancer.

Purpose: In a pilot study, we introduce fast handheld Multi-Spectral Optoacoustic Tomography (MSOT) of the breast at 28 wavelengths, aiming to identify high-resolution optoacoustic (photoacoustic) patterns of breast cancer and non-cancerous breast tissue. Experimental Design: We imaged 10 female patients aged 48-81 years with malignant non-specific breast cancer or invasive lobular carcinoma. Three healthy volunteers aged 31-36 years were also imaged. Fast-MSOT was based on unique single-frame-per-pulse (SFPP) image acquisition employed to improve the accuracy of spectral differentiation over using a small number of wavelengths. Breast tissue was illuminated at the 700 - 970 nm spectral range over 0.56 seconds total scan time. MSOT data were guided by ultrasonography and X-ray mammography or MRI. Results: The extended spectral range allowed the computation of oxygenated hemoglobin (HBO2), deoxygenated hemoglobin (HB), total blood volume (TBV), lipid and water contributions, allowing first insights into in-vivo high-resolution breast tissue MSOT cancer patterns. TBV and Hb/HBO2 images resolved marked differences between cancer and control tissue, manifested as a vessel rich tumor periphery with highly heterogeneous spatial appearance compared to healthy tissue. We observe significant TBV variations between different tumors and between tumors over healthy tissues. Water and fat lipid layers appear disrupted in cancer vs. healthy tissue; however offer weaker contrast compared to TBV images. Conclusion: In contrast to optical methods, MSOT resolves physiological cancer features with high resolution and revealed patterns not offered by other radiological modalities. The new features relate to personalized and precision medicine potential.



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The American Academy of Oral Medicine Clinical Practice Statement: Somatic symptom and related disorders

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Publication date: Available online 12 September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology





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Predictors of epinephrine dispensing and allergy follow-up after emergency department visit for anaphylaxis

National guidelines recommend that patients with anaphylaxis be prescribed an epinephrine auto-injector (EAI) and referred to an allergy/immunology (A/I) specialist.

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Apport de la volumétrie au rajeunissement facial. Partie 2 : produits de comblement

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Publication date: Available online 12 September 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): P. Bui, A. Pons Guiraud, C. Lepage
Les produits injectables dits produits de comblement ou fillers sont utilisés pour gommer l'atrophie et la ptôse liées à l'âge et pour leurs effets tenseurs dits « pseudo-liftants ». Ils ne remplacent pas le lifting cervicofacial mais le retardent ou, lorsqu'ils sont injectés après l'acte chirurgical, en pérennisent le résultat. Parmi les produits de comblement utilisés, l'acide hyaluronique occupe une place prépondérante et incontestée, dépassant largement celle de l'acide L-polylactique ou de l'hydroxylapatite de calcium. Les voies d'abord et les méthodes d'injections sont communes à tous les produits de comblement et calquées sur celles de la graisse autologue, volumateur de référence, avec cependant quelques particularités. Le produit utilisé, le niveau de réticulation de l'acide hyaluronique, et la profondeur d'injection dépendent du site d'injection et de l'effet escompté. Cet effet s'étend du comblement des rides superficielles au remodelage de certaines parties du visage. Les complications liées à l'utilisation de ces produits de comblement sont bien connues, en particulier pour l'acide hyaluronique pour lequel la surcorrection est la plus fréquente des complications. Pour limiter les risques de complications mais aussi pour proposer à chaque patient les corrections qui lui sont le mieux adaptées, le chirurgien plasticien doit, avant toute intervention, interroger le patient et pratiquer un examen médical précis.Injectable substances known as fillers are used to palliate age-related atrophy and ptosis, and for their so-called "pseudo-lifting" action. They do not replace face and neck lift, but allow it to be postponed or, when injected after surgical lifting, make the result durable. Hyaluronic acid has a predominant and unchallenged place among fillers, well ahead of poly-L-lactic acid or calcium hydroxyapatite. Approaches and injection methods are the same for all fillers, corresponding to those for autologous fat injection, the reference substance, with a few particularities. The substance used, the level of hyaluronic acid reticulation, and the depth of the injection depend on the injection site and intended effect. Effects range from smoothing superficial wrinkles to remodeling whole parts of the face. Complications related to such fillers are well known, especially in the case of hyaluronic acid, where overcorrection is the most frequent. To limit the risk of complications and also to offer each patient the most individually adapted corrections, before any procedure, the plastic surgeon needs to question the patient and perform precise medical examination.



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Three-dimensional imaging, an important factor of decision in breast augmentation

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Publication date: Available online 12 September 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): A. de Runz, D. Boccara, N. Bertheuil, F. Claudot, M. Brix, E. Simon
IntroductionSince the beginning of the 21st century, three-dimensional imaging systems have been used more often in plastic surgery, especially during preoperative planning for breast surgery and to simulate the postoperative appearance of the implant in the patient's body. The main objective of this study is to assess the patients' attitudes regarding 3D simulation for breast augmentation.MethodA study was conducted, which included women who were operated on for primary breast augmentation. During the consultation, a three-dimensional simulation with Crisalix was done and different sized implants were fitted in the bra.ResultsThirty-eight women were included. The median age was 29.4, and the median prosthesis volume was 310mL. The median rank given regarding the final result was 9 (IQR: 8–9). Ninety percent of patients agreed (66% absolutely agreed, and 24% partially agreed) that the final product after breast augmentations was similar to the Crisalix simulation. Ninety-three percent of the patients believed that the three-dimensional simulation helped them choose their prosthesis (61% a lot and 32% a little). After envisaging a breast enlargement, patients estimated that the Crisalix system was absolutely necessary (21%), very useful (32%), useful (45%), or unnecessary (3%). Regarding prosthesis choice, an equal number of women preferred the 3D simulation (19 patients) as preferred using different sizes of implants in the bra (19 patients).ConclusionThe present study demonstrated that 3D simulation is actually useful for patients in order to envisage a breast augmentation. But it should be used as a complement to the classic method of trying different sized breast implants in the bra.



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Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

Related Articles

Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

Otol Neurotol. 2017 Sep 07;:

Authors: Takahashi K, Morita Y, Ohshima S, Izumi S, Kubota Y, Horii A

Abstract
HYPOTHESIS: The temporal bone shows regional differences in bone development.
BACKGROUND: The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis.
METHODS: Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions.
RESULTS: The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively.
CONCLUSION: To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.

PMID: 28891871 [PubMed - as supplied by publisher]



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Postoperative Delirium in Indian Patients Following Major Abdominal Surgery for Cancer: Risk Factors and Associations

Abstract

Postoperative delirium (POD) is not uncommon following major abdominal surgery with its incidence ranging between five and 51%. As cancer affects disproportionately, the population older than 65 years and as delirium is more common in the elderly, surgical oncology patients are at a higher risk of developing POD. The present study was undertaken to explore the impact and associations of POD in Indian patients undergoing oncological major abdominal surgery. A retrospective review of the electronic medical records in a tertiary cancer care institution of all postoperative patients who had undergone major gastrointestinal gynaecological and urological abdominal surgery for cancer and required psycho-oncology referral was performed. Patient, surgery and postoperative outcome-related data were collected. Statistical analysis was performed using univariate and multivariate logistic regression analysis. Out of 824 patients who underwent major abdominal surgery, 33 patients (4.0%) were diagnosed with POD. In univariate analysis, older age and history of addiction were found to be statistically significantly associated with POD (p < 0.001). Among the postoperative factors, respiratory complications (p < 0.001), sepsis (p < 0.05), ICU stay > 24 h (p < 0.05) and electrolyte impairment (p < 0.05) were the significant associations with the POD. Thirty-day mortality was higher in the POD group (p < 0.05). In multivariate logistic regression analysis, advanced age, addictions, respiratory complications and sepsis were found to be significant associations with POD, p < 0.001. Postoperative delirium is associated with higher mortality. Older age, postoperative respiratory complications and sepsis are common contributory factors of postoperative delirium.



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Estimating Vocal Effort from the Aerodynamics of Labial Fricatives: A Feasibility Study

Vocal effort in loud voice is produced with increased subglottal pressure during vowels and increased supraglottal pressure during consonants. In the paper, our main objective is to check whether it was supported by a parallel increase in the airflow resistance of the laryngeal articulator and of the supralaryngeal articulator, here the lips.

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Epidemiology of Cervical Spine Injuries in High School Athletes Over a Ten-Year Period

Over 7 million athletes participate in high school (HS) sports annually, with both the benefits of physical activity and risks of injury. While catastrophic cervical spine injuries have been studied, limited data are available characterizing less severe cervical spine injuries in HS athletes.

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Non-surgical treatment of delayed onset brachial plexopathy due to hypertrophic clavicular callus- a case report

Clavicular fractures are common injuries which are traditionally managed non-surgically without clinically significant sequelae. However, they may develop hypertrophic callus formation that compresses the brachial plexus. These cases may present months to years after initial injury with varying degrees of pain, paresthesia and weakness on the affected side, and are usually treated by surgical resection of the hypertrophic callus. We present a case of brachial plexopathy due to hypertrophic clavicular callus causing weakness and paresthesia.

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CT Characterization and Comparison with Polysomnography for Obstructive Sleep Apnea Evaluation

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Publication date: Available online 12 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Khaisang Chousangsuntorn, Thongchai Bhongmakapat, Navarat Apirakkittikul, Witaya Sungkarat, Nucharin Supakul, Jiraporn Laothamatas
PurposeWe hypothesized that computed tomography (CT) combined with portable polysomnography (PSG) may visualize anatomical data related to obstructive sleep apnea (OSA). This study aims to evaluate computed tomographic findings during sleep apnea and assess their associations with PSG data and patient characteristics.Patients and MethodsWe designed a prospective cross-sectional study in patients with OSA. The patients were scanned during awake states and apneic episodes. Associations of predictor variables, i.e. PSG data [respiratory disturbance index (RDI)] and patient characteristics [body-mass index (BMI), neck circumference (NC) and waist circumference (WC)], and outcome variables, i.e. CT findings during apneic episodes, were assessed by logistic regression analysis. CT findings during apneic episodes were categorized as to: level of obstruction, single-level [retropalatal (RP) or retroglossal (RG)] or multi-level (mixed RP and RG); degree of obstruction (partial or complete); and pattern of collapse [complete concentric collapse (CCC) or other patterns].ResultsFifty-eight adult patients with OSA were scanned. The mean ± standard deviation (SD) RDI, BMI, NC, and WC were 41.6 ± 28.55, 27.80 ± 5.43 kg/m2, 38.3 ± 4.3 cm, and 93.8 ± 13.6 cm, respectively. There were no variables observed which distinguished between the presence of single- and multi-level airway obstruction in this study. A high RDI (≥30) was associated with the presence of complete obstruction and CCC [odds ratios (95% confident interval) were 6.33 (1.55–25.90) and 3.77 (1.02–13.91) compared to those with lesser RDIs, respectively].ConclusionIncreased RDI appears to be an important variable for predicting the presence of complete obstruction and CCC during sleep apnea. Scanning during apneic episodes, using low-dose volumetric CT combined with portable PSG, provided better anatomic and pathologic findings in OSA than detected with scans during awake state.



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Re-introducing the delto-acromial perforator flap: clinical experience and cadaver dissection

Although perforator flaps from the pectoral branch of the thoraco-acromial (TA) axis have been well-described, there are few reports of perforator flaps based on the delto-acromial (DA) branches. We have found a reliable perforator coming off the DA branch of the TA axis, and have named a flap based on this vessel the delto-acromial perforator (DAP) flap. We describe our experience with the DAP flap together with a fresh cadaver anatomical study.

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Development and testing of a decision aid for women considering delayed breast reconstruction

The decision to have post-mastectomy breast reconstruction (PMBR) is highly complex and many women feel ill equipped to make this decision. Decision aids have been advocated to promote patient involvement in decision-making by streamlining and standardizing communication between the patient and the health care professional. In this study, we report on the development and testing of a decision aid (DA) for breast cancer survivors considering delayed PMBR.

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Cognitive reactions of nurses exposed to cancer patients' traumatic experiences: A qualitative study to identify triggers of the onset of compassion fatigue

Abstract

Objective

Nurses in cancer care are considered to be at risk for compassion fatigue because they are frequently exposed to patients' traumatic experiences. However, only a few effective empirical studies have been conducted in this field, and cognitive factors in particular have not been sufficiently studied. This study aims to describe the components of nurses' cognitive reactions from their exposure to cancer patients' traumatic experience to the onset of compassion fatigue.

Methods

In this qualitative study, 30 nurses in cancer care were purposively selected. Data were collected through semi-structured interviews and analyzed using content analysis and the constant comparative method.

Results

Forty attributes were identified from 613 statements and classified into 11 categories: sense of professional inadequacy, compassion for patients and their families, desire to support patients and their families, rumination on oneself or one's family, sense of professional mission, dissatisfaction with medical staff, desire to integrate with colleagues, desire to avoid one's duties, conflict between one's belief and reality, reconsideration of the meaning of life, and sense of powerlessness over cancer.

Conclusions

This study identified important components of cognitive reactions of nurses who encounter the traumatic experiences of cancer patients in Japan. This information can contribute to the understanding of the onset of compassion fatigue and provide the foundation for nurses in cancer care to avoid and recover from compassion fatigue.



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BRAF mutation as a novel driver of eosinophilic cystitis

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A study on different therapies and prognosis-related factors for 101 patients with SCLC and brain metastases

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Clinicopathological characteristics and experience in the treatment of giant retroperitoneal liposarcoma: A case report and review of the literature

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Primary facial reanimation in head and neck cancer

Facial paralysis (FP) carries profound implications for those afflicted. Apart from the devastating functional impairments, facial nerve paralysis disrupts the innate connection between mimetic muscles and emotions. This can create a barrier to social interactions leading to a decline in quality of life [1].

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Primary facial reanimation in head and neck cancer

Facial paralysis (FP) carries profound implications for those afflicted. Apart from the devastating functional impairments, facial nerve paralysis disrupts the innate connection between mimetic muscles and emotions. This can create a barrier to social interactions leading to a decline in quality of life [1].

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A rare tumour of the masseter muscle

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Publication date: Available online 12 September 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): C.A. Righini, H. Gil, I. Atallah




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Data sharing to serve ethics, transparency and reproducibility of medical science

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Publication date: Available online 12 September 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Laccourreye, P. Bonfils, R. Garrel, R. Jankowski, A. Karkas, N. Leboulanger, M. Makeieff, C. Righini, C. Vincent, C. Martin




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Surgical Treatment of Extraesophageal Manifestations of Gastroesophageal Reflux Disease

Abstract

Objective

To review the current literature on the role of antireflux surgery (ARS) for the treatment of extraesophageal manifestations of GERD.

Summary background data

The extraesophageal manifestations of gastroesophageal reflux disease (GERD) include chronic cough, laryngopharyngeal reflux, and asthma. They are responsible for significant morbidity in affected patients and a high economic burden on healthcare resources. We recently published a larger review on the symptoms, diagnosis, medical, and surgical treatment of the extraesophageal manifestations of GERD. Through our investigation, we found that the role of ARS for respiratory symptoms was unclear. Hence, we resorted through the data of our previous meta-analysis to compile a comprehensive and focused review on the role of ARS for respiratory symptoms.

Methods

Using the archive of our previous meta-analysis, we selected studies extracted from the MEDLINE, Cochran, PubMed, Google Scholar, and Embase databases pertaining to the surgical treatment of extraesophageal manifestations of reflux (cough laryngopharyngeal reflux, and asthma). We applied a similar reporting methodology as was used in our previous manuscript and then hand searched the bibliographies of included studies yielding a total of 27 articles for review. We graded the level of evidence and classified recommendations by size of treatment effect per the American Heart Association Task Force on Practice Guidelines.

Results

Observational data indicated that syndromes of chronic cough, laryngopharyngeal reflux and asthma might improve after antireflux surgery only in highly selected patients—likely those with non-acid reflux—while those patients with objective markers of asthma severity do not. Because of the varied methods of diagnosis and surgical technique, non-comparative observational data may be unreliable. Additionally, our search found no randomized controlled trials (RCTs) comparing antireflux surgery to medical therapy in the treatment of cough or laryngopharyngeal reflux. One RCT compared medical treatment to antireflux surgery in patients with asthma, but medical treatment included high-dose H2 blockers instead of PPIs.

Conclusions

Extraesophageal manifestations of GERD are common, costly, and difficult to treat. ARS might be effective in highly selected patients, especially in those whose extraesophageal manifestations are caused by non-acid reflux. The available data to date are generally of poor quality or outdated. Well-designed randomized controlled trials or large-scale observational cohort studies are urgently needed.



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Contemporary Approaches to Perioperative IV Fluid Therapy

Abstract

Background

Intravenous fluid therapy is required for most surgical patients, but inappropriate regimens are commonly prescribed. The aim of this narrative review was to provide evidence-based guidance on appropriate perioperative fluid management.

Method

We did a systematic literature search of the literature to identify relevant studies and meta-analyses to develop recommendations.

Results

Of 275 retrieved articles, we identified 25 articles to inform this review. "Normal" saline (0.9% sodium chloride) is not physiological and can result in sodium overload and hyperchloremic acidosis. Starch colloid solutions are not recommended in surgical patients at-risk of sepsis or renal failure. Most surgical patients can have clear fluids and/or administration of carbohydrate-rich drinks up to 2 h before surgery. An intraoperative goal-directed fluid strategy may reduce postoperative complications and reduce hospital length of stay. Regular postoperative assessment of the patient's fluid status and requirements should include looking for physical signs of dehydration or hypovolemia, or fluid overload. Both hypovolemia and salt and water overload lead to adverse events, complications and prolonged hospital stay. Urine output can be an unreliable indicator of hydration status in the postoperative surgical patient. Excess fluid administration has been linked to acute kidney injury, gastrointestinal dysfunction, and cardiac and pulmonary complications.

Conclusion

There is good evidence supporting the avoidance of unnecessary fasting and the value of an individualized perioperative IV fluid regimen, with transition to oral fluids as soon as possible, to help patients recover from major surgery.



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Erratum to: Paraesophageal Hernia and Reflux Prevention: Is One Fundoplication Better than the Other?



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Caveolin-1 is Markedly Downregulated in Patients with Early-Stage Colorectal Cancer

Abstract

Background

Caveolin-1 (CAV-1), the main scaffold protein in caveolae, is frequently deregulated in human cancer. Of importance, this protein has been described to show tumor suppressor or oncogenic properties depending on the cell type and the stage of the disease. In fact, its role in colorectal cancer (CRC) remains to be fully clarified due to discrepancies in the literature.

Methods

We analyzed CAV-1 by western blot in a set of early-stage CRC patients with paired tumor tissue and normal colonic mucosa available. CAV-1 mRNA and expression levels of miR-124, 133 and 802 were quantified by real-time PCR.

Results

We found CAV-1 strongly downregulated in 76.2% of tumor samples and associated with the subgroup of elderly patients (p = 0.027). We observed by real-time PCR a lack of correlation between CAV-1 mRNA and protein levels in some cases with CAV-1 downregulated by western blot, and miR-124 deregulation was identified as a potential contributing alteration to decrease CAV-1 protein expression.

Conclusion

CAV-1 is commonly downregulated in patients with primary CRC, which suggests its tumor suppressor role in early stages of this disease. Moreover, based on our findings, the previous discrepancies observed in different studies to date could be due to a complex posttranscriptional CAV-1 regulation.



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Letter to the Editor: Reply



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Clinicopathological Significance and Prognosis of Medullary Thyroid Microcarcinoma: A Meta-analysis

Abstract

Background

The objective of the present meta-analysis was to evaluate the clinicopathological significance and prognosis of micro-MTC compared to macro-MTC.

Methods

Relevant articles were obtained by searching the PubMed and MEDLINE databases. A meta-analysis was performed using 15 eligible studies. In addition, subgroup analysis based on heredity was performed in patients diagnosed with micro-MTC.

Results

The rate of extrathyroidal extension of micro-MTC [0.118 (95% CI 0.073–0.185)] was significantly lower than that of macro-MTC [0.303 (95% CI 0.224–0.395)]. Micro-MTC [0.229 (95% CI 0.161–0.314)] had a significantly lower rate of cervical lymph node (LN) metastasis compared to macro-MTC [0.595 (95% CI 0.486–0.694)]. The rate of multifocality was not significantly different between micro-MTC and macro-MTC [0.394 (95% CI 0.244–0.566) vs. 0.320 (95% CI 0.234–0.421), respectively]. The rate of distant metastasis did not differ significantly between micro-MTC [0.082 (95% CI 0.017–0.314)] and macro-MTC [0.068 (95% CI 0.009–0.376)]. Patients with micro-MTC showed significantly higher disease-free survival rates [hazard ratio [HR] 0.406 (95% CI 0.288–0.575), I 2 = 40.563%] compared to patients with macro-MTC.

Conclusion

Micro-MTC has aggressive features, such as multifocality and distant metastasis, similar to macro-MTC and a non-negligible rate of extrathyroidal extension and cervical LN metastasis. We suggest that treatment of micro-MTC should be approached with a similar focus as that of macro-MTC. Considering that less extrathyroidal extension and cervical LN metastasis occur in patients with micro-MTC compared to macro-MTC, we propose that treatment of micro-MTC, which has a relatively low disease burden status, should be viewed as an opportunity for improving prognosis.



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Is Routine Prophylactic Cholecystectomy Necessary During Gastrectomy for Gastric Cancer? Reply



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Paraesophageal Hernia and Reflux Prevention: Is One Fundoplication Better than the Other?

Abstract

Background

The management of paraesophageal hernia (PEH) is one of the most debated in surgery. Trends regarding indications, approach (open, laparoscopic, thoracoscopic), sac excision, mesh placement, and routine performance of fundoplication have changed over time. Today, most surgeons tend to perform a laparoscopic PEH repair that entails the excision of the sac, liberal use of a mesh to buttress the hiatus, and the addition of an anti-reflux procedure. Nevertheless, very little has been written on which type of fundoplication should be performed in these patients. Therefore, the goal of our study was to provide an evidence-based overview of which type of fundoplication should be performed during a PEH repair and the role of preoperative function tests in the decision-making

Methods

We searched the MEDLINE, Cochran, PubMed, Google Scholar, and Embase databases for papers published between 1996 and 2016 pertaining to the surgical treatment of PEH. We hand-searched the bibliographies of included studies and we excluded all reviews and case reports. We selected clinical studies and technical reports. We only considered papers stating rationales for the type of fundoplication performed.

Results

Our search yielded 24 articles: 17 clinical studies and 7 technical reports. In five of the clinical studies, a fundoplication was added only to patients with reflux symptoms. In all clinical studies, the most performed procedure was a total fundoplication (Nissen or Nissen-Rossetti), whereas a partial fundoplication (Toupet more frequently than Dor) or no fundoplication was reserved to those with impaired esophageal motility. All seven technical reports recommended a tailored approach and suggested adding a partial fundoplication (mainly Toupet) when the manometric findings showed esophageal dismotility.

Conclusion

The argument of whether or not a fundoplication should be added to a PEH repair in patients without evidence of reflux still persists. However, this review highlights that, when a fundoplication is performed, a tailored approach based on preoperative function tests is almost always preferred.



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Enhanced Recovery After Surgery: Can We Rely on the Key Factors or Do We Need the Bel Ensemble ?

Abstract

Background

The success of enhanced recovery (ERAS) pathways depends on the actual application of the intended protocol (adherence), but its full implementation remains challenging. In order to potentially streamline the pathway, it is indispensable to know the impact of individual items and the entire protocol on clinical outcomes.

Methods

Retrospective analysis including all consecutive colorectal ERAS patients since implementation (May 2011) until February 2014; demographics, adherence and outcomes were retrieved from a prospectively maintained database. Primary outcome was the impact of individual item and of the entire protocol on complications (overall and major) and length of hospital stay. Statistical analysis included logistic multivariate regression and adjustment for confounding factors.

Results

There were 328 patients with complete data sets analyzed. A minimally invasive approach [odd ratio (OR) 0.62; confidence interval (CI) 0.4–0.9] was significantly associated with less overall complications. In contrast, the use of prophylactic nasogastric tubes (OR 3.18; CI 1.4–7.4), prophylactic abdominal and pelvic drains (OR 1.96; 1.2–3.2) and intraoperative thoracic epidural analgesia (OR 1.76; CI 1.3–2.4) were associated with more overall complications. Minimal invasive approach was further associated with reduced hospital stay (OR 0.5; CI 0.4–0.7) and less major complications (OR 0.58; CI 0.4–0.8). Higher adherence to the entire ERAS protocol was associated with significantly less complications (P < 0.001) and shorter hospital stay (P < 0.001).

Conclusions

Minimally invasive surgery was the single most important component of the ERAS pathway while nasogastric tubes, drains and epidurals should be avoided. Overall, increasing adherence with the protocol was associated with better outcomes and should be the goal.



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Glycemic Status and Prognosis of Patients with Squamous Cell Carcinoma of the Esophagus

Abstract

Background

The impact of glycemic status on esophageal squamous cell carcinoma (ESCC) prognosis is unclear.

Methods

A total of 623 patients who underwent curative subtotal esophagectomy for ESCC were evaluated. Diabetes was defined as a prior diagnosis of diabetes under treatment or newly diagnosed diabetes based on preoperative glycosylated hemoglobin (HbA1c) levels. Poor glycemic control was defined as HbA1c ≥ 7.0%, whereas good glycemic control was defined as HbA1c < 7.0%. The impact of glycemic status on long-term survival after esophagectomy was evaluated.

Results

Among the 623 patients, 64 (10.3%) had diabetes including 30 (4.8%) with poor glycemic control. Although diabetes did not influence patient survival, patients with poor glycemic control had worse overall and disease-specific survival compared with those with good glycemic control (P = 0.011 and 0.039, respectively). Comparing poor glycemic control with good glycemic control, the hazard ratios (HRs) for overall and disease-specific mortality were 1.91 (1.15–3.18) and 1.89 (1.02–3.49) in univariate analysis. After multivariate adjustment, poor glycemic control also had increased risk of overall and disease-specific mortality [HR 1.72 (95% CI 1.02–2.88) and 1.65 (95% CI 0.89–3.08), respectively]. Poor glycemic control did not increase the risk of overall or disease-specific mortality in patients with stages 0–II disease but significantly increased this risk in those with stages III–IV disease [HR 2.05 (1.14–3.69) and 1.95 (1.01–3.80), respectively].

Conclusions

Poor glycemic control is an independent risk factor for overall and disease-specific mortality after esophagectomy for advanced-stage ESCC.



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Esophagojejunostomy Using the Purse-String Suturing Device After Laparoscopic Total or Proximal Gastrectomy for Gastric Cancer

Abstract

Background

Performing a safe esophagojejunostomy is important for the standardization of laparoscopic total gastrectomy. We have performed intracorporeal esophagojejunostomy by a circular stapler using the purse-string suturing device that we co-developed. The advantage of this device is that it makes use of the same surgical procedure as open surgery, but it does not depend on the surgeon's technical skills since this device does not require the laparoscopic hand-sewn technique. Furthermore, we have also adapted this device for double-tract reconstruction after laparoscopic proximal gastrectomy. In this study, we present the surgical procedures and postoperative short-term outcomes that were obtained using this novel technique.

Methods

We enrolled 94 patients that underwent intracorporeal esophagojejunostomy by circular stapler using our device after laparoscopic total or proximal gastrectomy for gastric cancer between November 2009 and October 2016.

Results

Postoperative complications related to esophagojejunostomy were due to anastomotic stenosis in two cases (2.1%) and leakage of the jejunum stump in one case (1.1%).

Conclusions

Intracorporeal esophagojejunostomy by circular stapler using the purse-string suturing device is safe and feasible. This method can be one of the standard procedures for performing intracorporeal esophagojejunostomy.



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Choledochal Malformation in Children: Lessons Learned from a Dutch National Study

Abstract

Introduction

A choledochal malformation (CM) is a rare entity, especially in the Western world. We aimed to determine the incidence of CM in the Netherlands and the outcome of surgery for CM in childhood.

Methods

All pediatric patients who underwent a surgical procedure for type I–IV CM between 1989 and 2014 were entered into the Netherlands Study group on choledochal cyst/malformation. Patients with type V CM were excluded from the present analysis. Symptoms, surgical details, short-term (<30 days) and long-term (>30 days) complications were studied retrospectively.

Results

Between January 1989 and December 2014, 91 pediatric patients underwent surgery for CM at a median age of 2.1 years (0.0–17.7 years). All patients underwent resection of the extrahepatic biliary tree with restoration of the continuity via Roux-en-Y hepaticojejunostomy. Twelve patients (12%) were operated laparoscopically. Short-term complications, mainly biliary leakage and cholangitis, occurred in 20 patients (22%), without significant correlations with weight or age at surgery or surgical approach. Long-term postoperative complications were mainly cholangitis (13%) and anastomotic stricture (4%). Eight patients (9%) required radiological intervention or additional surgery. Surgery before 1 year of age (OR 9.3) and laparoscopic surgery (OR 4.4) were associated with more postoperative long-term complications. We did not observe biliary malignancies during treatment or follow-up.

Conclusion

Surgery for CM carries a significant short- and long-term morbidity. Given the low incidence, we would suggest that (laparoscopic) hepatobiliary surgery for CM should be performed in specialized pediatric surgical centers with a wide experience in laparoscopy and hepatobiliary surgery.



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Prognostic Scoring System for Patients Who Present with a Gastric Outlet Obstruction Caused by Advanced Pancreatic Adenocarcinoma

Abstract

Background

Gastroenterostomy and stent placement are the most common palliative procedures for patients with a gastric outlet obstruction caused by advanced pancreatic adenocarcinoma. Gastroenterostomy is regarded as the optimum treatment for patients in whom a longer survival is expected, while stent placement is preferred for patients whose survival is likely to be relatively short. However, prognosis of such patients has not been fully evaluated.

Methods

This study included patients undergoing gastroenterostomy or duodenal stent placement for gastric outlet obstruction caused by advanced pancreatic adenocarcinoma between 2002 and 2015. Prognostic factors found to be significant based on a multivariate analysis were given a prognostic score according to their hazard ratios (HR). The overall survivals stratified according to the total prognostic score were compared.

Results

The median survival time of all cohorts was 4.2 months. The multivariate analyses demonstrated a neutrophil-to-lymphocyte ratio (NLR) ≥ 4 (HR = 4.01, p < 0.001), presence of liver metastases (HR = 1.90, p = 0.002), and presence of cancer pain (HR = 2.08, p < 0.001) to be significant prognostic factors. Regarding the HR, NLR ≥ 4, liver metastases and cancer pain were subsequently scored as 2, 1, and 1, respectively. The median survival time was 9.4 months in patients with a score of 0 or 1 and 3.3 months in patients with a score of 2–4, respectively.

Conclusion

The scoring system clearly demonstrates the patient survival. Patients with scores of 0 or 1 are favorable candidates for gastroenterostomy, while patients with scores of 2–4 are candidates for stent placement.



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Rives Technique for the Primary Larger Inguinal Hernia Repair: A Prospective Study of 1000 Repairs

Abstract

Objective

We report a prospective study of repairs using the Rives technique of the more difficult primary inguinal hernias, focusing on the immediate post-operative period, clinical recurrence, testicular atrophy, and chronic pain. A mesh placed in the preperitoneal space can reduce recurrences and chronic pain.

Methods

For the larger primary inguinal hernias (Types 3, 4, 6, and some 7), we favour preperitoneal placement of a mesh, covering the myopectineal orifice by means of a transinguinal (Rives technique) approach. The Rives technique was performed on 943 patients (1000 repairs), preferably under local anaesthesia plus sedation in ambulatory surgery.

Results

The mean operative time was 31.8 min. Pain assessment after 24 h with an Andersen scale and a categorical scale gave two patients with intense pain on the Andersen scale, and four patients who thought their state was bad. Surgical wound complications were below 1%, and urinary retention was 1.2% mostly associated with spinal anaesthesia and, in one case, bladder perforation. There was spermatic cord and testicular oedema with some degree of orchitis in 17 patients. The clinical follow-up of 849 repairs (86.4%), mean (range) 30.0 (12–192) months, gave five recurrences (0.6%), three cases (0.4%) of testicular atrophy, and 37 (4.3%) of post-operative chronic pain (8 patients with visual analogue scale of 3–10).

Conclusions

The Rives technique requires a sound knowledge of inguinal preperitoneal space anatomy, but it is an excellent technique for the larger and difficult primary inguinal hernias, giving a low rate of recurrences and chronic pain.



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Targeted Therapy and Local Control: The Dynamic Duo



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Usefulness of Mapping Biopsy in the Treatment of Penoscrotal Extramammary Paget’s Disease

Abstract

Background

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy; however, the standard treatment of EMPD has not been established. In this study, we applied mapping biopsy to penoscrotal EMPD and evaluated its effects.

Methods

A retrospective chart review was performed to determine the outcomes of patients with primary penoscrotal EMPD who underwent surgery at our institution between 2007 and 2014. Patients were divided into two groups (one group underwent mapping biopsy, while the other group did not), and the difference between the two groups was analyzed. The 5-year tumor-free rate was estimated using the Kaplan–Meier method, and the risk factors for local recurrence were also estimated.

Results

A total of 44 patients were analyzed, and the mean follow-up of patients was 50.27 months. Patients who underwent mapping biopsy showed significantly lower tumor involvement at permanent and frozen biopsies and a lower local recurrence rate than those who did not undergo mapping biopsy. The 5-year tumor-free rate was significantly higher in the mapping biopsy group than in the non-mapping biopsy group. Multivariable analysis demonstrated that age at operation, mapping biopsy, and false-negative results at frozen biopsy were associated with local recurrence.

Conclusions

Mapping biopsy is beneficial to reduce local recurrence in penoscrotal EMPD.



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Impact of Sustained Virological Response to Interferon Therapy on Recurrence of Hepatitis C Virus-Related Hepatocellular Carcinoma

Abstract

Background

Although achieving a sustained virological response (SVR) in hepatitis C virus (HCV) infection is recognized as improving liver function and reducing hepatocellular carcinoma (HCC) development, its impact on HCC recurrence is unclear. This study investigated how preoperative SVR achievement by interferon treatment affects HCC recurrence in patients undergoing hepatic resection.

Methods

The study subjects were 521 patients with HCV infection who underwent initial and curative hepatic resection for HCC. To adjust for confounding factors between the SVR and non-SVR groups, propensity score-matching analysis was performed.

Results

After propensity score matching, 45 of the 49 patients in the SVR group, and an equal number of the 472 patients in the non-SVR group, were matched. The two groups had similar distributions of clinicopathological characteristics. In the matched cohort, the 3-, 5-, and 7-year recurrence-free survival rates after surgery were 56, 45, and 37%, respectively, in the SVR group, and 34, 23, and 7.2%, respectively, in the non-SVR group (p = 0.033). Additionally, the 3-, 5-, and 7-year overall survival rates after surgery were 82, 80, and 75%, respectively, in the SVR group, and 78, 64, and 44%, respectively, in the non-SVR group (p = 0.065). The 1- and 2-year cumulative recurrence rates in the early phase showed no significant difference between the SVR and non-SVR groups (p = 0.27). however, the 3-, 5-, and 7-year cumulative recurrence rates in the late phase were 14, 32, and 43%, respectively, in the SVR group, and 33, 55, and 86%, respectively, in the non-SVR group (p = 0.037).

Conclusion

Achievement of SVR may reduce postoperative recurrence after hepatic resection.



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Impact of Patient Age on the Postoperative Survival in Pancreatic Head Cancer

Abstract

Background

Some reports have stated that pancreatoduodenectomy for elderly patients have comparable morbidity and mortality to that of young patients. However, the long-term outcomes of these patients have not been fully evaluated, especially for pancreatic head cancer.

Methods

A total of 227 patients who underwent pancreatoduodenectomy for pancreatic head cancer between 2007 and 2014 were included. They were stratified according to age: young (<70 years), elderly (70 to <80 years), and very elderly (≥80 years). The short- and long-term outcomes were evaluated.

Results

There were no significant differences in terms of morbidity among the three groups. The median disease-free survival times were 15 months in the young, 11 months in the elderly, and 7 months in the very elderly. The disease-free survival of the young patients was significantly better than that in both the elderly and the very elderly (p = 0.012 and p = 0.016). The median overall survival times were 30 months in the young, 20 months in the elderly, and 14 months in the very elderly. The overall survival of the young patients was significantly better than that in both the elderly and the very elderly (p = 0.007 and p < 0.001). The difference was marginal between the elderly and the very elderly (p = 0.053). Multivariate analysis revealed that lymph node metastasis (p < 0.001), age ≥80 years (p = 0.013), lack of adjuvant chemotherapy (p = 0.003), blood transfusion (p = 0.015), and CA 19-9 ≥300 U/ml (p = 0.040) were significant prognostic factors.

Conclusions

Patient age influenced the survival after pancreatoduodenectomy for pancreatic cancer.



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2017 Update on the Querleu–Morrow Classification of Radical Hysterectomy

Abstract

Background

One of the most important principles in modern cervical cancer surgery is the concept of tailoring surgical radicality. In practice, this means abandoning the "one-fits-all" concept in favor of tailored operations. The term "radical hysterectomy" is used to describe many different procedures, each with a different degree of radicality. Anatomic structures are subjected to artificial dissection artifacts, as well as different interpretations and nomenclatures. This study aimed to refine and standardize the principles and descriptions of the different classes of radical hysterectomy as defined in the Querleu–Morrow classification and to propose its universal applicability.

Methods

All three authors independently examined the current literature and undertook a critical assessment of the original classification. Images and pathologic slides demonstrating different types of radical hysterectomy were examined to document a consensual vision of the anatomy. The Cibula 3-D concept also was included in this update.

Results

The Querleu–Morrow classification is based on the lateral extent of resection. Four types of radical hysterectomy are described, including a limited number of subtypes when necessary. Two major objectives remain constant: excision of central tumor with clear margins and removal of any potential sites of nodal metastasis.

Conclusion

Studies evaluating radicality in the surgical management of cervical cancer should be based on precise, universally accepted descriptions. The authors' updated classification presents standardized, universally applicable descriptions of different types of hysterectomies performed worldwide, categorized according to degree of radicality, independently of theoretical considerations.



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Sustained Growth of a University-Based Endocrine Surgery Program Over 10 Years

Abstract

Background

Endocrine surgery continues to mature as a subspecialty field. We describe the clinical performance of an academic endocrine surgery program (ESP) over its first 10 years.

Methods

We examined all endocrine procedures performed during the 10-year period (2006–2015) following the inception of the ESP. Institutional and state-level data on case volume, patient geographic origin, and hospital-side costs were obtained.

Results

Endocrine case volume increased by approximately ninefold over the study period (from 102 cases in 2006 to 919 cases in 2015). The rate of growth remained approximately linear, and was driven by geographic expansion of referral regions coupled with transitioning low- to moderate-acuity operations to venues outside of the main tertiary care hospital. Market share across the eight-county Southern California region grew by more than twofold over the study period. Increased utilization of outpatient surgery led to cost reductions, averaging 11.1% per case by 2015.

Conclusions

Establishment of an academic ESP can lead to sustained clinical growth and a fundamental shift in regional referral patterns. The nation's continued need for skilled high-volume endocrine surgeons represents opportunities for medical centers to institute their own dedicated endocrine surgery programs.



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Prognostic value of systemic immune-inflammation index in patients with gastric cancer

Inflammation-based indexes have been used to predict survival and recurrence in cancer patients. Systemic immune-inflammation index (SII) was reported to be associated with prognosis in some malignant tumors. ...

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DRα1-MOG-35-55 treatment reduces lesion volumes and improves neurological deficits after traumatic brain injury

Abstract

Traumatic brain injury (TBI) results in severe neurological impairments without effective treatments. Inflammation appears to be an important contributor to key pathogenic events such as secondary brain injury following TBI and therefore serves as a promising target for novel therapies. We have recently demonstrated the ability of a molecular construct comprised of the human leukocyte antigen (HLA)-DRα1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRα1-MOG-35-55 construct) to reduce CNS inflammation and tissue injury in animal models of multiple sclerosis and ischemic stroke. The aim of the current study was to determine if DRα1-MOG-35-55 treatment of a fluid percussion injury (FPI) mouse model of TBI could reduce the lesion size and improve disease outcome measures. Neurodeficits, lesion size, and immune responses were determined to evaluate the therapeutic potential and mechanisms of neuroprotection induced by DRα1-MOG-35-55 treatment. The results demonstrated that daily injections of DRα1-MOG-35-55 given after FPI significantly reduced numbers of infiltrating CD74+ and CD86+ macrophages and increased numbers of CD206+ microglia in the brain concomitant with smaller lesion sizes and improvement in neurodeficits. Conversely, DRα1-MOG-35-55 treatment of TBI increased numbers of circulating CD11b+ monocytes and their expression of CD74 but had no detectable effect on cell numbers or marker expression in the spleen. These results demonstrate that DRα1-MOG-35-55 therapy can reduce CNS inflammation and significantly improve histological and clinical outcomes after TBI. Future studies will further examine the potential of DRα1-MOG-35-55 for treatment of TBI.



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A patient with mitochondrial disorder due to a novel mutation in MRPS22

Abstract

MRPS22 gene defect is a very rare newly discovered mitochondrial disorder. We report a 4-month-old severely affected male infant with MRPS22 mutation. Whole exome sequencing revealed a novel homozygous splicing mutation c.339 + 5 G > A in MRPS22 gene. He has mild dysmorphism, hypotonia, developmental delay but not hypertrophic cardiomyopathy and tubulopathy which differ from other majority of reported patients. Therefore, hypertrophic cardiomyopathy and tubulopathy may not be considered as constant features of MRPS22. With this case report, we also present first symmetrical bilateral brainstem and medial thalamic lesions, and cerebellar and cerebral atrophy on a brain MR imaging follow-up of ten months.



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Coenzyme Q10 and niacin mitigate streptozotocin- induced diabetic encephalopathy in a rat model

Abstract

Diabetic encephalopathy is an important complication of diabetes characterized by cognitive impairment, neurochemical and structural abnormalities. This study aimed to investigate the effect of coenzyme Q10 (CoQ10) and niacin as well as their combination in the treatment of encephalopathy associated with streptozotocin (STZ)- induced diabetes in rats. Glibenclamide (reference diabetic drug) and donepezil hydrochloride (acetylcholinesterase inhibitor) were also evaluated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). One month after STZ injection, diabetic rats were treated with the aforementioned drugs for two weeks. The evaluation was done through measuring glucose level, total antioxidant capacity (TAC), interleukin 6 (IL6), DNA degradation as well as serotonin and noradrenaline as neurotransmitters. The present data illustrated that combining CoQ10 and niacin exhibiting the most potent effect in improving the measured parameters and ameliorating some of diabetes complications.



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Neuropilin-2 rs849563 gene variations and susceptibility to autism in Iranian population: A case-control study

Abstract

Autism spectrum disorders (ASD) are neurodevelopmental disruptions usually diagnosed in the first three years of child's life that characterized by some impairments in verbal and nonverbal communication, problems in social interactions and repetitive behaviors. The neuropilin-2 (NRP2) gene has been shown to both guide axons and control neuronal migration in the central nervous system (CNS). In this study the association between the NRP2 gene and autism using a cohort of 120 Iranian children (50 cases with autism and 70 control cases) was analyzed. Single nucleotide polymorphism (SNP) was genotyped by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analyses. There was significant difference between the genotype and allele frequency between control and patient groups (P = 0.003 and P = 0.01, respectively). The prevalence of genotype frequencies of TT and TG in autistic children were 40% and 60%, respectively, while in controls were 68.5% and 31.5%, respectively. The heterozyote TG was associated with an increased risk of autism compared with TT genotype (OR = 3.72, 95%CI = 1.53–6.95, P = 0.02). The allele frequencies of T and G in autistic children were 78.5% and 21.4%, respectively and in controls were 84.2% and 15.7%, respectively. The NRP2 G allele conferred a 2.29-fold increased risk to autism relative to the T allele (OR = 2.29, 95%CI = 1.23–4.29, P = 0.009). The results of this study showed that there is a significant association between rs849563 polymorphism and autism in the studied population. However in order to obtain a definitive conclusion larger studies with more samples are required to confirm the results of this study.



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Unresolved and critical issues in autoimmune rheumatic diseases

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Publication date: Available online 12 September 2017
Source:Autoimmunity Reviews
Author(s): Andrea Doria, Mariele Gatto, Luca Iaccarino, Piercarlo Sarzi-Puttini




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Spatial discrimination of glioblastoma and treatment effect with histologically-validated perfusion and diffusion magnetic resonance imaging metrics

Abstract

The goal of this study is to spatially discriminate tumor from treatment effect (TE), within the contrast-enhancing lesion, for brain tumor patients at all stages of treatment. To this end, the diagnostic accuracy of MRI-derived diffusion and perfusion parameters to distinguish pure TE from pure glioblastoma (GBM) was determined utilizing spatially-correlated biopsy samples. From July 2010 through June 2015, brain tumor patients who underwent pre-operative DWI and DSC-MRI and stereotactic image-guided biopsy were considered for inclusion in this IRB-approved study. MRI-derived parameter maps included apparent diffusion coefficient (ADC), normalized cerebral blood flow (nCBF), normalized and standardized relative cerebral blood volume (nRCBV, sRCBV), peak signal-height (PSR) and percent signal-recovery (PSR). These were co-registered to the Stealth MRI and median values extracted from the spatially-matched biopsy regions. A ROC analysis accounting for multiple subject samples was performed, and the optimal threshold for distinguishing TE from GBM determined for each parameter. Histopathologic diagnosis of pure TE (n = 10) or pure GBM (n = 34) was confirmed in tissue samples from 15 consecutive subjects with analyzable data. Perfusion thresholds of sRCBV (3575; SN/SP% = 79.4/90.0), nRCBV (1.13; SN/SP% = 82.1/90.0), and nCBF (1.05; SN/SP% = 79.4/80.0) distinguished TE from GBM (P < 0.05), whereas ADC, PSR, and PH could not (P > 0.05). The thresholds for CBF and CBV can be applied to lesions with any admixture of tumor or treatment effect, enabling the identification of true tumor burden within enhancing lesions. This approach overcomes current limitations of averaging values from both tumor and TE for quantitative assessments.



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Her2 positive subtype and breast cancer brain metastasis: any effect of anti-Her2 targeted therapy?



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Nucleolar and spindle associated protein 1 promotes the aggressiveness of astrocytoma by activating the Hedgehog signaling pathway

Abstract

Background

The prognosis of human astrocytoma is poor, and the molecular alterations underlying its pathogenesis still needed to be elucidated. Nucleolar and spindle associated protein 1 (NUSAP1) was observed in several types of cancers, but its role in astrocytoma remained unknown.

Methods

The expression of NUSAP1 in astrocytoma cell lines and tissues were measured with western blotting and Real-Time PCR. Two hundred and twenty-one astrocytoma tissue samples were analyzed by immunochemistry to demonstrate the correlation between the NUSAP1 expression and clinicopathological characteristics. 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay, colony formation, transwell matrix penetration assay, wound healing assay and anchorage-independent growth assay were used to investigate the biological effect of NUSAP1 in astrocytoma. An intracranial brain xenograft tumor model was used to confirm the oncogenic role of NUSAP1 in human astrocytoma. Luciferase reporter assay was used to investigate the effect of NUSAP1 on Hedgehog signaling pathway.

Results

NUSAP1 was markedly overexpressed in astrocytoma cell lines and tissues compared with normal astrocytes and brain tissues. NUSAP1 was found to be overexpressed in 152 of 221 (68.78%) astrocytoma tissues, and was significantly correlated to poor survival. Further, ectopic expression or knockdown of NUSAP1 significantly promoted or inhibited, respectively, the invasive ability of astrocytoma cells. Moreover, intracranial xenografts of astrocytoma cells engineered to express NUSAP1 were highly invasive compared with the parental cells. With regard to its molecular mechanism, upregulation of NUSAP1 in astrocytoma cells promoted the nuclear translocation of GLI family zinc finger 1 (GLI1) and upregulated the downstream genes of the Hedgehog pathway.

Conclusion

These findings indicate that NUSAP1 contributes to the progression of astrocytoma by enhancing tumor cell invasiveness via activation of the Hedgehog signaling pathway, and that NUSAP1 might be a potential prognostic biomarker as well as a target in astrocytoma.



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