Publication date: Available online 3 March 2018
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Ingmar L. Defize, Bernadette Schurink, Teus J. Weijs, Tom A.P. Roeling, Jelle P. Ruurda, Richard van Hillegersberg, Ronald L.A.W. Bleys
BackgroundInjury and subsequent leakage of unrecognized thoracic duct tributaries during transthoracic esophagectomy may lead to chylothorax. Therefore, we hypothesized that thoracic duct anatomy at the diaphragm is more complex than currently recognized and aimed to provide a detailed description of the anatomy of the thoracic duct at the diaphragm.Basic proceduresThe thoracic duct and its tributaries were dissected in 7 (2 male and 5 female) embalmed human cadavers. The level of origin of the thoracic duct and the points where tributaries entered the thoracic duct were measured using landmarks easily identified during surgery: the aortic and esophageal hiatus and the arch of the azygos vein.Main findingsThe thoracic duct was formed in the thoracic cavity by the union of multiple abdominal tributaries in 6 cadavers. In 3 cadavers partially duplicated systems were present that communicated with interductal branches. The thoracic duct was formed by a median of 3 (IQR: 3–5) abdominal tributaries merging 8.3 centimeters (IQR: 7.3–9.3cm) above the aortic hiatus, 1.8 centimeters (IQR: −0.4–2.4cm) above the esophageal hiatus, and 12.3 centimeters (IQR: 14.0–−11.0cm) below the arch of the azygos vein.ConclusionThis study challenges the paradigm that abdominal lymphatics join in the abdomen to pass the diaphragm as a single thoracic duct. In this study, this occurred in 1/7 cadavers. Although small, the results of this series suggest that the formation of the thoracic duct above the diaphragm is more common than previously thought. This knowledge may be vital to prevent and treat post-operative chyle leakage.
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- The anatomy of the thoracic duct at the level of t...
- Electrochemical testing of a novel alloy in natura...
- Brachytherapy in Head and Neck Cancers: “Are We Do...
- Aquatic Ecosystem Degradation of High Conservation...
- Quantitative Proteomics Identify the Possible Tumo...
- Adjuvant vinorelbine and cisplatin after complete ...
- Readiness of US General Surgery Residents for Inde...
- Questions Regarding Statistical Inferences, Qualit...
- Autologous Myoblasts for the Treatment of Fecal In...
- Prevent the Bleed: How Surgeons Can Lead the Natio...
- Dissecting Surgeon Behavior: Leveraging the Theore...
- A British Perspective on the American College of S...
- Randomized Controlled Trial of Liberal Versus Rest...
- Hospital Standards to Promote Optimal Surgical Car...
- Using Confidential Clinical Data Registries for Pu...
- Laparoscopic Versus Open Liver Resection for Color...
- Pushing the Envelope in Perihiler Cholangiocellula...
- Social Media as a Platform for Surgical Learning: ...
- Design Principles for Building a Leadership Develo...
- Magnetic Surgery: Results From First Prospective C...
- Minimally Invasive Thoracic Surgery 3.0: Lessons L...
- Volume Increases and Shared Decision-making in Joi...
- Prevalence of Musculoskeletal Disorders Among Surg...
- In the Next Issue
- The Global Incidence of Appendicitis: A Systematic...
- The Risk of Adverse Pregnancy Outcomes Following N...
- Phosphorus Loss Mitigation in Leachate and Surface...
- Review of “Who Makes It to the End? A Novel Predic...
- Factors Influencing Perception of Facial Attractiv...
- Re-Engineering the Cleft Craft Surgery: Function i...
- Mucosal Dehiscence After Alveolar Bone Graft in Cleft
- Critical Appraisal in Plastic Surgery: Nullius in ...
- Cell Polarity and PAR Complex Likely to Be Involve...
- Repair of the Nasal Floor by the Cleft Margin Flap...
- Surgical Management of Migraine Headache
- Alignment Strategy for Constricted Maxillary Denta...
- Nontraumatic Intradiploic Epidermoid Cyst and Olde...
- Nasopharyngoscopic Analyses through Anterior Maxil...
- Surgical Treatment of Synovial Chondromatosis in t...
- Complications From Surgically Assisted Rapid Maxil...
- Age-Related Volumetric Changes in Mandibular Condyles
- Evaluating Resident Perspectives on International ...
- Ecthyma Gangrenosum in the Eyelid
- Comparison of Postoperative Outcomes Between Monit...
- Maxillary Osteomyelitis Caused by Kocuria Species ...
- The Impact of Type-D Personality on Oral Health-Re...
- Mandibular Reconstruction by Osteogenic Distractio...
- Quadrupling Inhaled Glucocorticoid Dose to Abort A...
- Escalating Inhaled Glucocorticoids to Prevent Asth...
- Quintupling Inhaled Glucocorticoids to Prevent Chi...
- Innate immunity gene expression by epithelial cell...
- Treatment of pediatric esthesioneuroblastoma with ...
- Environmental factors associated with allergic rhi...
- Efficacy and safety of concurrent immunoradiothera...
- Phase I study of chemoradiotherapy using gemcitabi...
- Addition of bevacizumab to gemcitabine for platinu...
- S-1 (Teysuno) and gemcitabine in Caucasian patient...
- Phase 1 summary of plasma concentration–QTc analys...
- Role of TPMT and ITPA variants in mercaptopurine d...
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Σάββατο 3 Μαρτίου 2018
The anatomy of the thoracic duct at the level of the diaphragm: a cadaver study
Electrochemical testing of a novel alloy in natural and artificial body fluids
Publication date: Available online 3 March 2018
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Ioana Bunoiu, Mihaela Mindroiu, Claudiu Constantin Manole, Mihai Andrei, Adrian Nicoara, Ecaterina Vasilescu, Monica Popa, Andreea Cristiana Didilescu
There is a recent trend in tissue engineering and regenerative medicine to use nanotechnology and bionanomaterials to obtain materials that mimic the surface properties of a natural tissue. From this perspective, nanolevel tissue engineering can be viewed as a novel anatomy of the future. In this paper, a novel titanium-based alloy is studied following this strategy. The alloy nanostructuration is proposed as an improved alternative for restorative prosthodontics or an implantable biomaterial. Tests in i) standard solution of simulated body fluid (SBF) and ii) natural saliva were performed to investigate the alloy's electrochemical stability. The results show that nanochannel growth on the alloy surface confers a higher stability than that of the untreated one in both natural and simulated environments.
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Brachytherapy in Head and Neck Cancers: “Are We Doing It or Are We Done with It”
Abstract
We performed an e-Survey and reviewed the literature on the prevalence of use of brachytherapy in head and neck cancers in order to understand the patterns of care and probable application of this modality. A five-point questionnaire was prepared and sent to 300 oncologists through a web-based survey engine. This was done in preparation for my lecture on "Ongoing Research and Potential Research Avenues" in IBSCON held in Chennai in August 2016. SPSS software was used for the statistical analysis. Of a total of 300 emails that were sent out for the survey, 120 replies were received, which is 40%. Among the results of various questions, (i) 65% of the oncologists felt that there were > 300 ongoing studies in brachytherapy and out of them only 10–20 were on head and neck brachytherapy; (ii) 58% of the responders felt that external beam radiotherapy (EBRT) advances followed by lack of training and experience are the reasons for declining role of brachytherapy; (iii) among the responders, numbers of head and neck brachytherapy performed stand third after gynecological and breast brachytherapy. This survey shows that brachytherapy in head and neck cancers is an essential tool, but seldom practiced. If no path-breaking event happens, we may be dealing with it as a dying art.
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Aquatic Ecosystem Degradation of High Conservation Value Upland Swamps, Blue Mountains Australia
Abstract
Temperate highland peat swamps on sandstone (THPSS) are unique state and federally protected ecological communities. THPSS is a higher level classification which is comprised of multiple swamp communities which include Blue Mountains Swamps and Newnes Plateau Shrub Swamps. The Blue Mountains has a string of urban settlements surrounded by large expanses of undisturbed natural vegetation which have varied degrees of protection ranging from state forests to World Heritage national parks. This study investigated aquatic invertebrates from seven THPSS within the Greater Blue Mountains area. Four swamps drain catchments with varying degrees of urban development and associated impervious surfaces, and three swamps have non-urban, naturally vegetated catchments. Water chemistry of non-urban swamps was acidic (mean pH 4.70) and dilute (mean EC 26.7 uS/cm) and dominated by sodium and chloride ions with most other major ions at low concentrations often below detection limits (Belmer et al. 2015). In contrast, urban swamps had higher pH (mean 6.60) and salinity (mean 153.9 uS/cm) and were dominated by calcium and bicarbonate ions (Belmer et al. 2015). Aquatic macroinvertebrate abundance, family richness and % EPT taxa were all found to be lower within urban swamps when compared to non-urban swamps. These results support the hypothesis of Belmer et al. (2015) that urban runoff within THPSS catchments is affecting the condition of their aquatic ecosystems.
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Quantitative Proteomics Identify the Possible Tumor Suppressive Role of Protease-Activated Receptor-4 in Esophageal Squamous Cell Carcinoma Cells
Abstract
Exposure to carcinogens of tobacco smoke may result in methylation of protease-activated receptors-4 (PAR4) gene and further induces the loss of PAR4 expression, which is considered to be involved in carcinogenesis of esophageal squamous cell carcinoma (ESCC). Here we employed a TMT-based quantitative proteomic approach to identify PAR4-regulated changes of proteomic profiles in ESCC cells and to identify potentially therapeutic value. A total of 33 proteins were found significantly changed with 15 up-regulated and 18 down-regulated in PAR4-activating peptide (PAR4-AP) treated ESCC cells compared with controls. Bioinformatics analysis showed that key higher expressed proteins included those associated with apoptosis and tumor suppressor (e.g. CASP9), and lower expressed proteins included those associated with anti-apoptosis, autophagy and promoting cell proliferation (e.g. CHMP1B, PURA, PARG and HIST1H2AH). Western blot verified changes in five representative proteins including CASP9, CHMP1B, PURA, PARG and HIST1H2AH. Immunohistochemistry analysis showed that CHMP1B, PURA, PARG and HIST1H2AH expression in ESCC tissues were significantly higher than those in adjacent nontumorous tissues. Our findings will be helpful in further investigations into the functions and molecular mechanisms of PAR4 in ESCC.
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Adjuvant vinorelbine and cisplatin after complete resection of stage II and III non-small cell lung cancer: long-term follow-up of our study of Japanese patients
Abstract
Purpose
We reported previously a phase II study of adjuvant chemotherapy consisting of four cycles of vinorelbine (25 mg/m2) and cisplatin (40 mg/m2), given on days 1 and 8, every 4 weeks, to Japanese patients with completely resected stage II or III non-small cell lung cancer (NSCLC; UMIN 000005055). However, the follow-up was too short for us to evaluate a definitive 5-year overall survival rate and after-effects.
Methods
Between December 2006 and January 2011, 60 patients were enrolled in this study. We analyzed relapse-free and overall survival, long-lasting adverse effects, the influence of treatment on recurrent tumors, and the development of a second primary cancer, in relation with the regimen.
Results
After a median follow-up period of 95.8 months, the 5-year relapse-free and overall survival rates were 51.7 and 76.7%, respectively. Neuralgia developed in one patient and this was the only case of a long-lasting adverse effect. Recurrence developed in 31 patients, 29 of whom received intensive treatment. Although 16 s (or more) primary neoplasms developed among 13 patients, these were common carcinomas in Japan and did not include sarcoma or hematologic malignancies.
Conclusion
Adjuvant vinorelbine and cisplatin chemotherapy showed encouraging relapse-free and overall survival rates, and long-term safety in Japanese patients with resected NSCLC.
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Readiness of US General Surgery Residents for Independent Practice: Erratum
Questions Regarding Statistical Inferences, Quality of Life, and Conclusions From the COBRA Study
Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS)
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Prevent the Bleed: How Surgeons Can Lead the National Conversation About Firearm Safety Forward
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Dissecting Surgeon Behavior: Leveraging the Theoretical Domains Framework to Facilitate Evidence-based Surgical Practice
A British Perspective on the American College of Surgeons Conversation About Firearm Safety
Randomized Controlled Trial of Liberal Versus Restricted Fluid Management in Patients Undergoing Pancreatectomy: Erratum
Hospital Standards to Promote Optimal Surgical Care of the Older Adult: A Report From the Coalition for Quality in Geriatric Surgery
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Using Confidential Clinical Data Registries for Public Reporting and Pay for Performance
Laparoscopic Versus Open Liver Resection for Colorectal Liver Metastases—Which Is a More Suitable Standard Practice?
Pushing the Envelope in Perihiler Cholangiocellularcarcinoma Surgery: TIPE-ALPPS
Social Media as a Platform for Surgical Learning: Use and Engagement Patterns Among Robotic Surgeons
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Design Principles for Building a Leadership Development Program in a Department of Surgery
Magnetic Surgery: Results From First Prospective Clinical Trial in 50 Patients
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Minimally Invasive Thoracic Surgery 3.0: Lessons Learned From the History of Lung Cancer Surgery
Volume Increases and Shared Decision-making in Joint Replacement Bundles
Prevalence of Musculoskeletal Disorders Among Surgeons Performing Minimally Invasive Surgery: A Systematic Review
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In the Next Issue
The Global Incidence of Appendicitis: A Systematic Review of Population-based Studies
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The Risk of Adverse Pregnancy Outcomes Following Nonobstetric Surgery During Pregnancy: Estimates From a Retrospective Cohort Study of 6.5 Million Pregnancies
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Phosphorus Loss Mitigation in Leachate and Surface Runoff from Clay Loam Soil Using Four Lime-Based Materials
Abstract
The increased eutrophication phenomenon in Quebec lakes calls for an urgent phosphorus-reducing strategy to meet the Quebec water quality standard of 0.03 mg L−1 for phosphorus (P). The objective of this research was to evaluate the application of four lime-based products in reducing P losses through subsurface leachate and surface runoff and to determine their optimum application. Two sets of experiments were conducted: laboratory leaching study and runoff study with a rainfall simulator, using a clay loam soil collected from the Pike river watershed. The former followed a flow method with a full factorial design in three replicates. Soil columns were amended with different application dosages of lime ranging from 0 to 2% by soil weight. The results showed that all four lime-based products could be promising amendments in reducing P losses in the leachate. According to statistical analysis of ANOVA, high calcium hydrated lime and lime kiln dust #2 were found to be the most effective with an optimum application dosage of 1% while reducing total dissolved phosphorus concentrations in leachate from 0.057 to 0.009 and 0.023 mg L−1, respectively. For the runoff study, a rainfall simulator with a maximum rainfall intensity of 2 cm h−1 was built. High calcium hydrated lime and lime kiln dust #2 were able to reduce total dissolved phosphorus to 0.034 and 0.037 mg L−1, respectively. However, particulate phosphorus was significantly increased at the studied application rate. The results from this study can offer a promising measure in reducing total dissolved phosphorus in groundwater while providing a solution to the existing environment issue of eutrophication.
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Review of “Who Makes It to the End? A Novel Predictive Model for Identifying Surgical Residents at Risk for Attrition” by Yeo HL, Abelson JS, Mao J, Lewis F, Michelassi F, Bell R, Sedrakyan A, Sosa JA in Ann Surg 266: 499–507, 2017
Factors Influencing Perception of Facial Attractiveness: Gender and Dental Education
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Re-Engineering the Cleft Craft Surgery: Function is an Essential Element of the Repair
Mucosal Dehiscence After Alveolar Bone Graft in Cleft
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Critical Appraisal in Plastic Surgery: Nullius in Verba
Cell Polarity and PAR Complex Likely to Be Involved in Dexamethasone-Induced Cleft Palate
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Repair of the Nasal Floor by the Cleft Margin Flap in Bilateral Complete Cleft Lip
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Surgical Management of Migraine Headache
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Alignment Strategy for Constricted Maxillary Dental Arch in Patients With Unilateral Cleft Lip and Palate Using Fixed Orthodontic Appliance
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Nontraumatic Intradiploic Epidermoid Cyst and Older Age: Association or Causality?
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Nasopharyngoscopic Analyses through Anterior Maxillary Distraction Osteogenesis for Adolescent Patients With Cleft Palate
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Surgical Treatment of Synovial Chondromatosis in the Inferior Compartment of the Temporomandibular Joint With Articular Disc Involvement
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Complications From Surgically Assisted Rapid Maxillary Expansion With HAAS and HYRAX Expanders
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Age-Related Volumetric Changes in Mandibular Condyles
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Evaluating Resident Perspectives on International Humanitarian Missions
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Ecthyma Gangrenosum in the Eyelid
Comparison of Postoperative Outcomes Between Monitored Anesthesia Care and General Anesthesia in Closed Reduction of Nasal Fracture
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Maxillary Osteomyelitis Caused by Kocuria Species in a Patient Who Is on Long-Term Uncontrolled Use of Methylprednisolone
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The Impact of Type-D Personality on Oral Health-Related Quality of Life in Cleft Lip and Palate Adolescents
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Mandibular Reconstruction by Osteogenic Distraction Due to Two Different Injuries
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Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations
Asthma is one of the most common chronic diseases, with an estimated 300 million people affected worldwide. Acute exacerbations of asthma are frightening for patients, cause considerable illness and death, and account for a large proportion of the overall costs related to asthma. Although plans for…
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Escalating Inhaled Glucocorticoids to Prevent Asthma Exacerbations
Inhaled glucocorticoids are pivotal to achieve asthma control and disease stability in both children and adults; despite their use, with or without other treatments, many patients with asthma have ongoing episodic disease exacerbations. Often, these are linked to provocative factors such as viral…
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Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations
Asthma exacerbations are common events, particularly in school-age children. Exacerbations are costly and are associated with considerable complications. In addition, asthma exacerbations may lead to progressive loss of lung function and greater asthma severity over time. Although conventional…
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Innate immunity gene expression by epithelial cells of upper respiratory tract in children with adenoid hypertrophy
A major role of the innate immunity in the defence of mucosal tissue is well established. However, a balance between the main components of the immunity such as toll-like receptors (TLRs) and defensins in the pathology of upper respiratory tract in children has not been addressed yet. Our aim was to investigate the gene expression of some TLRs as well as alpha and beta-defensins in children suffered from adenoid hyperthrophy in comparison with healthy children.
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Treatment of pediatric esthesioneuroblastoma with smell preservation
Olfactory neuroblastoma is a rare malignant tumor of neuroectodermal origin and represents the most common cancer of the nasal cavity in pediatric age. The gold standard of treatment consists of en bloc resection, numerous studies have shown as the endoscopic approaches permit good control of the disease improving the quality of life after the treatment. Herein we describe the case of a 13-year-old patient referred to our outpatient clinic with a polypoid multi-lobed lesion occupying the left nasal cavity and imaging that confirmed a left-sided nasal mass without cribriform plate involvement (Kadish B).
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Environmental factors associated with allergic rhinitis symptoms in Japanese university students: A cross-sectional study
Numerous studies have reported that various environmental factors during early life are key determinants for developing allergic disease. Herein, we aimed to investigate the impact of environmental factors on allergic rhinitis.
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Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab
Abstract
Background
The objective of this study was to evaluate the efficacy and safety of concurrent immune checkpoint inhibitor therapy and radiotherapy (immunoradiotherapy) in patients with metastatic melanoma after progression on nivolumab.
Patients and methods
A retrospective review was performed on 16 consecutive patients with metastatic melanoma treated with concurrent immunoradiotherapy after progression on nivolumab. Best responses to immunoradiotherapy were assessed either inside or outside of the radiation fields. The target lesions ratio (the sum of the diameters of the target lesions inside the irradiated fields/all target lesions) was also assessed.
Results
Among the patients, seven received ipilimumab and radiotherapy (Ipi-RT), six received nivolumab and radiotherapy (Nivo-RT), and three sequentially received Ipi-RT and Nivo-RT. The overall response rate (all patients regardless of inside or outside radiation fields) was 30%. The response rate inside the radiation fields was 68.8% for all patients combined. The response rates of Ipi-RT and Nivo-RT inside the radiation fields were 37.5 and 100% (P = 0.03), respectively. Grade 3 adverse events were observed in three patients treated with Ipi-RT. The target lesions ratio was a predictive marker of disease control rate among patients treated with Nivo-RT.
Conclusions
This study showed that concurrent immunoradiotherapy is an option for patients with metastatic melanoma after progression on nivolumab.
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Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer
Abstract
Purpose
For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen.
Methods
Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined. Patients were classified according to the designated dose levels of chemoradiotherapy using the GnP regimen. After additional 6 cycles of the GnP regimen were administered, surgery was considered if the patients had stable disease and tumor marker levels had normalized.
Results
DLT (grade 4 thrombocytopenia) was observed only in 1 of 12 patients, and the RD was set at level 3. Grade 3–4 leukopenia was observed in 9 (75.0%) patients, and neutropenia in 7 (58.3%). The response rate was 41.7%, and the disease control rate was 100%. Conversion surgery was performed in 6 (50%) patients, and curative resection (R0) was performed in all 6 patients (100%). Stratification according to the Evans classification system demonstrated one patient with grade 1b, one with grade 2, two with grade 3, and two with grade 4 disease.
Conclusion
The RD for weekly administration was 800 mg/m2 for gemcitabine and 100 mg/m2 for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.
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Addition of bevacizumab to gemcitabine for platinum-resistant recurrent ovarian cancer: a retrospective analysis
Abstract
Purpose
To compare a cohort of patients with platinum-resistant recurrent ovarian cancer (PROC) treated with bevacizumab and gemcitabine (Bev–Gem) to that of patients treated only with gemcitabine (Gem).
Methods
Between 2011 and 2017, we identified the Bev–Gem and Gem PROC groups. The regimen included 1000 mg/m2 of Gem on days 1, 8, and 15, and 15 mg/m2 of Bev on day 1, every 4 weeks. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of the administration of Bev–Gem or Gem until disease progression or death.
Results
The Bev–Gem and Gem groups included 18 and 29 patients, respectively. More patients had advanced stage disease in the Bev–Gem group (p = 0.048); no other characteristics differed between the groups. The response rates [ratio of complete remission (CR) to partial remission (PR)] of Bev–Gem and Gem were 38.9 and 3.4%, respectively (p < 0.01). The clinical benefit rates [combined percentages of CR, PR, and stable disease] of the Bev–Gem and Gem groups were 88.9 and 41.4%, respectively (p = 0.04). PFS and OS of the Bev–Gem group were superior (p < 0.01, p = 0.03, respectively). Bev–Gem was the better prognostic factor of both PFS [hazard ratio (HR) 0.17, p < 0.01] and OS (HR 0.31, p = 0.01). The frequency of hematologic and non-hematologic adverse effects was similar in each group.
Conclusion
Bev–Gem regimens improved PFS and OS for PROC. Furthermore, the adverse effects of Bev–Gem were tolerable. Thus, Bev–Gem could be a candidate treatment strategy for PROC.
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S-1 (Teysuno) and gemcitabine in Caucasian patients with unresectable pancreatic adenocarcinoma
Abstract
Purpose
Gemcitabine has been standard of care in advanced pancreatic adenocarcinomas (PC) for almost two decades. Randomized, primarily Japanese, studies have shown promising efficacy when combined with S-1 (GemS-1); however, no data are published in Caucasian patients. We report the first study with a combination of GemS-1 in an unselected cohort of Caucasian PC patients.
Methods
In this observational cohort study, we analyzed efficacy and toxicity prospectively.
Results
From July 2012 to July 2014, 64 patients received at least one cycle of GemS-1. 16 patients started therapy with gemcitabine and capecitabine (GemCap) but switched to GemS-1 after median 3 cycles of GemCap due to toxicity (hand-foot syndrome). 48 patients received GemS-1 as initial therapy. For the complete cohort, median age was 68 years (range 44–80); 22 patients (34%) had locally advanced PC; 42 patients (66%) had metastatic disease. Five patients had received prior adjuvant therapy with gemcitabine and 9 pts had received prior first-line therapy. The most common adverse event was fatigue (86%), however, only grade 3 in 3%. Five patients (8%) developed febrile neutropenia. Median PFS was 8.1 (95% CI 6.9–9.0) months and median OS was 11.7 (95% CI 10.7–13.1) months in the whole GemS-1 population. In the 48 patients starting with GemS-1, median PFS was 7.7 (95% CI 6.7–8.9) months and median OS was 11.5 (95% CI 9.7–12.3) months.
Conclusions
The combination of gemcitabine and S-1 is safe and associated with promising efficacy in a Caucasian population; however, this needs to be confirmed in prospective clinical trials.
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Phase 1 summary of plasma concentration–QTc analysis for idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors and AML
Abstract
Purpose
Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. The aim of this analysis is to examine the potential of idasanutlin to prolong the corrected QT (QTc) interval by evaluating the relationship between plasma idasanutlin concentration and QTc interval.
Method
Intensive plasma concentration QTc interval data were collected at the same timepoints, from three idasanutlin (RO5503781) phase 1 studies in patients with solid tumors and AML. QTc data in absolute values and changes from baseline (Δ) were analyzed for a potential association with plasma idasanutlin concentrations with a linear mixed effect model. Categorical analysis was also performed.
Results
A total of 282 patients were exposed to idasanutlin and had at least one observation of QTc and idasanutlin plasma concentration. There was no apparent increase of QTcF or ΔQTcF in a wide idasanutlin plasma concentration range, even at concentrations exceeding the exposure matching the dose adopted in the ongoing phase 3 study (300-mg BID). Categorical analysis did not detect a potential signal of QT prolongation.
Conclusion
The concentration–QTc analysis indicates that idasanutlin does not prolong the QT interval within the targeted concentration range currently in consideration for clinical development.
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Role of TPMT and ITPA variants in mercaptopurine disposition
Abstract
Purpose
To explore the levels of thioguanine incorporated into DNA (DNA-TG), and erythrocyte levels of 6-thioguanine nucleotides (Ery-TGN) and methylated metabolites (Ery-MeMP) during 6-mercaptopurine (6MP)/Methotrexate (MTX) therapy of childhood acute lymphoblastic leukemia (ALL) and the relation to inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT) gene variants.
Methods
Blood samples were drawn during 6MP/MTX maintenance therapy from 132 children treated for ALL at Rigshospitalet, Copenhagen. The samples were analysed for thiopurine metabolites and compared to TPMT (rs1800460 and rs1142345) and ITPA (rs1127354) genotypes.
Results
Median DNA-TG (mDNA-TG) levels were higher in TPMT and ITPA low-activity patients as compared to wildtype patients (TPMTLA 549 vs. 364 fmol/µg DNA, p = 0.007, ITPALA 465 vs. 387 fmol/µg DNA, p = 0.04). mDNA-TG levels were positively correlated to median Ery-TGN (mEry-TGN)(rs = 0.37, p = 0.001), but plateaued at higher mEry-TGN levels. DNA-TG indices (mDNA-TG/mEry-TGN) were 42% higher in TPMTWT patients as compared to TPMTLA patients but no difference in DNA-TG indices was observed between ITPAWT and ITPALA patients (median 1.7 vs. 1.6 fmol/µg DNA/ nmol/mmol Hb, p = 0.81). DNA-TG indices increased with median Ery-MeMP (mEry-MeMP) levels (rs = 0.25, p = 0.001).
Conclusions
TPMT and ITPA genotypes significantly influence the metabolism of 6MP. DNA-TG may prove to be a more relevant pharmacokinetic parameter for monitoring 6MP treatment intensity than cytosolic metabolites. Prospective trials are needed to evaluate the usefulness of DNA-TGN for individual dose adjustments in childhood ALL maintenance therapy.
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Long-term results of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer
Abstract
Purpose
The purpose of this phase I/II study was to evaluate the feasibility and efficacy of S-1 plus cisplatin at the recommended schedule with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).
Methods
Eligible patients with LA-NSCLC were treated with cisplatin intravenously at a dose of 60 mg/m2 on day 8 plus oral S-1 at a dosage of 40 mg/m2 twice per day for two different treatment schedules for up to 4 cycles. Patients also concurrently received 60 Gy of thoracic radiation in 30 fractions. The primary endpoint of the phase II study was the proportion of patients who survived for more than 2 years.
Results
Between August 2005 and October 2010, a total of 45 patients were enrolled in this phase I/II study; their long-term survival was then followed for a median period of 5.8 years. Nineteen of the 39 patients in the phase II study survived for more than 2 years and met the primary endpoint of the study. The median overall survival period was 24.9 months [95% confidence interval (CI) 17.4–74.5 months], and the 2- and 5-year overall survival rates were 51.0 and 43.0%, respectively. The response rate was 85%, and the median progression-free survival period was 13.8 months (95% CI 9.5–27.1 months). Hematological toxicity was mild. Grade 3 febrile neutropenia and pneumonitis was observed in 5 and 5%, respectively.
Conclusion
Our study indicated that S-1 plus cisplatin with concurrent thoracic radiotherapy yielded encouraging survival outcomes and an acceptable safety profile for LA-NSCLC.
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A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer
Abstract
Purpose
Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of approximately 16 months. Novel methods to improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in pancreatic cancer and is FDA-approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced pancreatic carcinoma.
Methods
We performed a phase 1 study using a 3 + 3 dose escalation strategy to determine the safety and tolerability of dose-escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with two cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy.
Results
Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n = 3) or 125 mg/m2 (n = 6). There were no observed grade 3 gastrointestinal toxicities. One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%) and neutropenia (11%). No grade 4 toxicities were observed. Following chemoradiotherapy, four patients (borderline resectable, n = 2 and unresectable, n = 2) underwent surgical resection, all with negative margins and with significant treatment effect with limited tumor viability.
Conclusions
The combination of fractionated radiation and weekly full dose nab-paclitaxel was safe and well-tolerated.
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2-Deoxy- d -glucose enhances TRAIL-induced apoptosis in human gastric cancer cells through downregulating JNK-mediated cytoprotective autophagy
Abstract
Purpose
TNF-related apoptosis-inducing ligand (TRAIL) resistance significantly limits its use in clinical practice. It has been reported that 2-deoxy-d-glucose (2-DG) can enhance TRAIL's cytotoxicity. Our studies were designed to investigate the mechanisms of 2-DG reversing TRAIL resistance therapy in gastric cancer cells.
Methods
Gastric cancer cells (MGC803, SGC7901) were treated with 2-DG and TRAIL. Cell viability was determined by CCK-8 assay and detection of apoptosis by flow cytometry. Autophagic and apoptosis protein expression and c-Jun NH2-terminal kinase (JNK) phosphorylation were determined by Western blotting. Autophagy response and JNK activities were inhibited by specific inhibitor, 3MA or SP600125, respectively. LDH release assay was used to detect cytotoxicity.
Results
We confirmed that TRAIL triggered an autophagic response in TRAIL-resistant gastric cancer cells, MGC803 and SGC7901, and depended on JNK activation. Blocking autophagy or JNK activation with specific inhibitor, 3MA or SP600125, potentiated cell death and caspase-3 activation. Furthermore, we confirmed that 2-DG inhibited the viability of gastric cancer cells, phosphorylation of JNK induced by TRAIL and increased gastric cancer cells to TRAIL-induced apoptosis.
Conclusions
Taken together, we show that 2-DG can sensitize TRAIL-induced apoptosis, at least in part, through suppressing JNK-mediated cytoprotective autophagic signaling in MGC803 and SGC7901cells. These results may have significant implications for the development of new strategies to reverse TRAIL resistance in gastric tumor.
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Effects of posaconazole (a strong CYP3A4 inhibitor), two new tablet formulations, and food on the pharmacokinetics of idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors
Abstract
Purpose
Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. To optimize its dosing conditions, a number of clinical pharmacology characteristics were examined in this multi-center trial in patients with advanced solid tumors.
Method
This was an open-label, single-dose, crossover clinical pharmacology study investigating the effects of strong CYP3A4 inhibition with posaconazole (Part 1), two new oral formulations (Part 2), as well as high-energy/high-fat and low-energy/low-fat meals (Part 3) on the relative bioavailability of idasanutlin. After completing Part 1, 2, or 3, patients could have participated in an optional treatment with idasanutlin. Clinical endpoints were pharmacokinetics (PK), pharmacodynamics (PD) of MIC-1 elevation (Part 1 only), and safety/tolerability.
Results
The administration of posaconazole 400 mg BID × 7 days with idasanutlin 800 mg resulted in a slight decrease (7%) in Cmax and a modest increase (31%) in AUC for idasanutlin, a marked reduction in Cmax (~ 60%) and AUC0 (~ 50%) for M4 metabolite, and a minimal increase (~ 24%) in serum MIC-1 levels. Cmax and AUC were both 45% higher for the SDP formulation. While the low-fat meal caused a less than 20% increase in all PK exposure parameters with the 90% CI values just outside the upper end of the equivalence criteria (80–125%), the high-fat meal reached bioequivalence with dosing under fasting.
Conclusion
In patients with solid tumors, multiple doses of posaconazole, a strong CYP3A4 inhibitor, minimally affected idasanutlin PK and PD without clinical significance. The SDP formulation improved rBA/exposures by ~ 50% without major food effect.
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A note on improved statistical approaches to account for pseudoprogression
Abstract
Responses to immuno-oncology agents are often subject to misinterpretation as apparent tumor growth due to immune infiltration leads to the appearance of progressive disease and can result in the discontinuation of effective therapeutic agents. Better statistical strategies to determine experimental outcomes are needed to distinguish between true and pseudoprogression. We applied time-to-event statistical analyses methods that account for study design features and capture the longitudinal and panoramic aspects of pseudoprogression to test superiority of a combination of RRx-001, a novel tumor-associated macrophage polarizing agent in Phase 2, and an anti-PD-L1 antibody in a myeloma preclinical model, comparing to traditional, mean-based mixed effects modeling approaches that did not show statistical significance. Nonparametric p values for the difference of cumulative incidence rates of time to ≥ 50% tumor growth reduction and its associated restricted mean survival times are computed and found to be statistically significant. Kaplan–Meier description of time-to-volume reduction (≥ 50%) coupled with Cox's proportional hazards model follows the data longitudinally and therefore permits an analysis of immune infiltration resolution, making it an improved method for analysis of preclinical experiments with immuno-oncology agents.
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Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma
Abstract
Purpose
The purpose of this study was to assess the efficacy and safety of cetuximab plus platinum-based chemotherapy for patients specifically diagnosed with recurrent or metastatic oral squamous cell carcinoma (OSCC).
Methods
We conducted a multicenter retrospective observational study of patients who underwent first-line cetuximab plus platinum-based chemotherapy between December 2012 and June 2015. 65 patients received weekly cetuximab (week 1, 400 mg/m2; subsequent weeks, 250 mg/m2) plus a maximum of six 3-weekly cycles of cisplatin (80 or 100 mg/m2, day 1) or carboplatin (at an area under the curve of 5 mg/mL/min as a 1-h intravenous infusion on day 1) and 5-fluorouracil (800 or 1000 mg/m2/day, days 1–4). Patients with stable disease who received cetuximab plus platinum-based chemotherapy continued to receive cetuximab until disease progression or unacceptable toxicities, whichever occurred first.
Results
The median follow-up was 10.5 (range 1.2–34.2) months. The best overall response and the disease control rates were 46.2 and 67.7%, respectively. The median overall survival and progression-free survival rates were 12.1 and 7.8 months, respectively. The most common grades 3–4 adverse events were skin rash (9.2%) followed by leukopenia (6.2%). None of the adverse events were fatal.
Conclusion
The results of our multicenter retrospective study, which was the largest of its kind to date, suggest that first-line cetuximab plus platinum-based chemotherapy is suitable and well-tolerated for the systemic therapy of recurrent or metastatic OSCC.
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A novel way to manage trastuzumab cardiotoxicity
Abstract
Purpose
Trastuzumab is the most widely prescribed anti-HER2 humanized monoclonal antibody. Cardiac toxicity is the only limiting toxicity of trastuzumab and it is of particular concern in patients with complete response, since the drug needs to be stopped, with a risk of disease relapse. To date, no pharmacological data on trastuzumab cardiotoxicity in patients have been made available. Here, we provide proof of concept, demonstrating that it was possible to prevent trastuzumab-induced cardiotoxicity by modifying the drug administration schedule.
Methods
In this paper, we report the case of a patient with metastatic breast cancer responding to trastuzumab, who developed severe cardiac toxicity twice using a 3-weekly regimen. Considering preclinical pharmacological data on trastuzumab cardiotoxicity, we hypothesized that a weekly schedule of trastuzumab with lower peaks of serum concentration could be safe while remaining efficient. With the patient's consent, we started a weekly combination of carboplatin (AUC2) and trastuzumab (2 mg/kg) with close monitoring of trastuzumab concentrations.
Results
We successfully controlled the disease for an additional 6 months with relevant trough concentrations of trastuzumab of around 50 mg/L. Another important aspect is that, with this weekly schedule, we observed no cardiac toxicity, and the left ventricular ejection fraction remained stabilized, at over 50%.
Conclusions
Trastuzumab is the most widely prescribed anti-HER2 monoclonal antibody for the treatment of HER2 metastatic breast cancer, and it is the only drug that has been approved for the treatment of localized HER2 breast cancer, 1-year treatment being required after surgery. In case of cardiac toxicity, particularly in women over 60 years of age, a weekly regimen with lower peaks of concentration could be an alternative to the standard 3-weekly regimen.
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A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies
Abstract
Purpose
The artemisinin class of anti-malarial drugs has shown significant anti-cancer activity in pre-clinical models. Proposed anti-cancer mechanisms include DNA damage, inhibition of angiogenesis, TRAIL-mediated apoptosis, and inhibition of signaling pathways. We performed a phase I study to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of intravenous artesunate (IV AS).
Methods
Patients were enrolled in an accelerated titration dose escalation study with planned dose levels of 8, 12, 18, 25, 34 and 45 mg/kg given on days 1 and 8 of a 21-day cycle. Toxicities were assessed using the NCI CTCAE (ver. 4.0), and response was assessed using RECIST criteria (version 1.1). Pharmacokinetic (PK) studies were performed during cycle 1.
Results
A total of 19 pts were enrolled, 18 of whom were evaluable for toxicity and 15 were evaluable for efficacy. DLTs were seen at dosages of 12 (1 of 6 patients), 18 (1 of 6) and 25 mg/kg (2 of 2), and were neutropenic fever (Gr 4), hypersensitivity reaction (Gr 3), liver function test abnormalities (Gr 3/4) along with neutropenic fever, and nausea/vomiting (Gr 3) despite supportive care. The MTD was determined to be 18 mg/kg. No responses were observed, while four patients had stable disease, including three with prolonged stable disease for 8, 10, and 11 cycles, for a disease control rate of 27%. PK parameters of AS and its active metabolite, dihydroartemisinin (DHA), correlated with dose.
Conclusion
The MTD of intravenous artesunate is 18 mg/kg on this schedule. Treatment was well tolerated. Modest clinical activity was seen in this pre-treated population.
ClinicalTrials.gov Identifier
NCT02353026.
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Grinspan’s Syndrome: A Rare Case with Malignant Transformation
Aim. Oral lichen planus (OLP) is one of the common chronic inflammatory, noninfectious, and precancerous oral mucosal diseases that affect the stratified squamous epithelium in adults. Grinspan et al. reported an association of OLP with diabetes mellitus and vascular hypertension and called that Grinspan's syndrome in 1966. We aim to present a case of Grinspan's syndrome with malignant transformation. Case Presentation. A 60-year-old man who presented with a ten-year history of OLP diagnosed clinically and histologically was referred to our otolaryngology department with a painless swallowing in the left buccal mucosa for 3 months. Clinical examination revealed several plaques, striated white lesions in the buccal mucosa bilaterally, and an exophytic tumor in the left buccal mucosa. Histopathological examination showed lichen planus bilaterally and oral squamous cell carcinoma in the left buccal mucosa. The tumor had been developed on the preexisting areas of lichen planus which had been histologically proven before. The tumor was removed completely, and the tissue defect on the buccal mucosa was repaired with a split-thickness skin graft. Conclusion. Patients with OLP should be followed up periodically in a long term at close intervals for early diagnosis of malignant transformation.
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Low Frequency repetitive Transcranial Magnetic Stimulation: Potential role in treatment of patients with hemispheric cerebellar strokes
Source:Brain Stimulation
Author(s): Isabelle Buard, Jean M. Berliner, Benzi M. Kluger
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Has the question “Number of pulses or number of sessions for rTMS in major depression” been answered adequately?
Source:Brain Stimulation
Author(s): Christos Theleritis, Constantin R. Soldatos
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Detection of GSK-3β activation index in pediatric chronic tonsillitis is an indicator for chronic recurrent inflammation
Chronic tonsillitis (TC) is among the most common bacterial diseases in pediatric otolaryngology. We aimed to evaluate the expression of glycogen synthase kinase 3β (GSK-3β) in a cohort of children with chronic tonsillitis (TC), and the correlation between GSK-3β activity index and inflammatory profiles of TC.
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Dynamic imaging with sialography combined with sialendoscopy to manage a foreign body in Stensen's duct
We describe sialography as a dynamic imaging modality useful in establishing the diagnosis and planning for treatment of a parotid gland ductal foreign body.
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Transoral robotic excision of laryngeal papillomas with Flex® Robotic System — A novel surgical approach
Recurrent respiratory papillomatosis results in hoarseness, stridor and airway obstruction. Management is surgical, with most surgeons using microdebrider or laser. Transoral robotic surgery (TORS) has been successfully utilised for the excision of oropharyngeal malignancies and paediatric airway surgery. This is the first case report of TORS being used for the excision of laryngeal papillomas.
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Does blindness affect ocular vestibular evoked myogenic potentials?
The aim of the present study was to investigate the influence of blindness on ocular vestibular evoked myogenic potentials (oVEMP) responses.
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Individualized colorectal cancer screening based on the clinical risk factors: beyond family history of colorectal cancer
Individuals without a family history of colorectal cancer (CRC) are screened uniformly despite interpersonal risk. To assess individual risk, we examined the age-specific prevalence of advanced colorectal neoplasia (ACRN) according to clinical risk factors and fecal immunochemical test (FIT) results.
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Visceral obesity as a risk factor for colorectal adenoma occurrence in surveillance colonoscopy
The aim of this study was to examine the prospective association between visceral obesity and the incidence and recurrence of colorectal adenoma.
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Feasibility and safety of micro-forceps biopsy in the diagnosis of pancreatic cysts
The tissue acquisition and diagnostic yield of cyst fluid cytology is low-to-moderate and rarely provides a specific diagnosis. The aim of this study was to compare the tissue acquisition and diagnostic tissue yield of micro-forceps biopsy (MFB) with cyst fluid cytology.
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The effects of botulinum toxin injections on plantar flexor spasticity in different phases after stroke. A secondary analysis from a double-blind, randomized trial
There are no guidelines on the ideal time to inject botulinum toxin (BT-A) for lower leg spasticity in stroke patients. An early injection may produce unwanted weakness, interfering with gait recovery.
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Support device for percutaneous endoscopic gastrostomy tube
During the treatment for head and neck cancer patients often require a percutaneous endoscopic gastrostomy (PEG) to maintain adequate nutritional intake.1 Complications associated with a PEG include leakage,2 widening of the stoma, and dislodgement of the tube.3 These complications may in turn result in the need for placement of a new tube.
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Placement of an arch bar for intermaxillary fixation using two wires for each dental arch
If a single long wire is used for each dental arch it may loosen as the wire stretches,1 and several wires take more time to fix to the arch bars.2 We describe a alternative method of placement using a wire 20–25cm long for each side of each dental arch. This prevents loosening of the arch bar and reduces the time taken to do it.
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Meta-Analysis of Renal Function Following Suprarenal or Infrarenal Endovascular Aneurysm Repair
Publication date: Available online 3 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Philip W. Stather, James Ferguson, Ayoola Awopetu, Jonathan R. Boyle
Objective/BackgroundThe effect of suprarenal (SR) as opposed to infrarenal (IR) fixation on renal outcomes post-endovascular aneurysm repair (EVAR) remains controversial. This meta-analysis aims to update current understanding of this issue.MethodsA prior meta-analysis was updated through a Preferred Reporting Items for Systematic reviews and Meta-Analyses search for additional studies published in the last 3 years reporting on renal dysfunction or related outcomes post-EVAR. Random effects meta-analysis was undertaken using SPSS.ResultsA total of 25 non-randomised studies comparing SR with IR fixation were included, totalling 54,832 patients. In total, 16,634 underwent SR and 38,198 IR. Baseline characteristics, including age, baseline estimated glomerular filtration rate, diabetes, cardiac disease, and smoking, were similar between the groups. There was a small but significant difference in outcomes for renal dysfunction at the study end point (SR 5.98% vs. IR 4.83%; odds ratio [OR] 1.29, 95% confidence interval [CI] 1.28–1.40 [p < .001]); however, at 30 days and 12 months there was no significant difference, and this did not hold up to sensitivity analysis. Incidence of renal infarcts (SR 6.6% vs. IR 2.3%; OR 2.78, 95% CI 1.46–5.29 [p = .002]), renal stenosis (SR 2.4% vs. IR 0.8%; OR 2.89, 95% CI 1.00–8.38 [p = .05]), and renal artery occlusion (SR 2.4% vs. IR 1.2%; OR 2.21, 95% CI 1.15–4.25 [p = 0.02]) favoured IR fixation; however, there was no difference in haemodialysis rates.ConclusionThis meta-analysis has identified small but significantly worse renal outcomes in patients having SR fixation devices compared with IR; however, there was no difference in dialysis rates and a small effect on renal dysfunction, which did not stand up to rigorous sensitivity analysis. This should be taken into consideration during graft selection, and further studies must assess renal outcomes in the longer term, and in those with pre-existing renal dysfunction.
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Prevalence of Abdominal Aortic Aneurysms in the General Population and in Subgroups at High Cardiovascular Risk in Italy. Results of the RoCAV Population Based Study
Publication date: Available online 3 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Francesco Gianfagna, Giovanni Veronesi, Matteo Tozzi, Antonino Tarallo, Rossana Borchini, Marco M. Ferrario, Lorenza Bertù, Andrea Montonati, Patrizio Castelli
ObjectivesPrevalence data on abdominal aortic aneurysm (AAA) in women, subjects younger than 65 years and in subgroups carrying specific risk factors are scarce. AAA prevalence was evaluated in an Italian population including women and younger subjects, stratifying for the presence of cardiovascular disease (CVD) risk factors and CVD risk score.Materials and methodsA population based cross-sectional study was conducted between 2013 and 2016. Men aged 50–75 and women aged 60–75 years, resident in the city of Varese (northern Italy), were randomly selected from the civil registry. A vascular surgeon performed an abdominal aortic ultrasound scan at four sites using the leading edge to leading edge method. CVD risk score was computed using the ESC-SCORE algorithm. The age and gender specific prevalence was estimated, stratifying by the presence of CVD and cardiovascular risk factors.ResultsAmong the 3755 subjects with a valid ultrasound measurement, 63 subjects with an AAA were identified (5 referred for surgical intervention), among whom 34 were not previously known (30 men 1.3%, 95% CI 0.9–1.8; 4 women 0.3%, 95% CI 0.1–0.8). Considering age classes in men only, the highest prevalence of screen detected AAA was found in subjects aged 65–70 (1.2%; 95% CI 0.4–2.5) and 70–75 (2.5%; 95% CI 1.4–4.0) years. Among 65–75 year old men, the highest AAA prevalence was found in subjects with a previous myocardial infarction (MI 4.9%, 95% CI 2.0–9.9) and in ever-smokers reporting more than 15 pack years of smoking (4.1%, 95% CI 2.5–6.3). Among the younger subjects, those having an ESC-SCORE higher than 5% or a previous CVD (MI or stroke) showed a prevalence of 1.4% (95% CI 0.3–4.2; prevalence including subaneurysms 6.7%, 95% CI 3.7–11.0%).ConclusionsIn the study population, both a general screening program in 65–75 year old men and an approach targeted to subgroups at higher risk merit evaluation in a cost-effectiveness study. In 50–64 year old men, strategies for population selection should consider CVD risk stratification tools.
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Local mechanisms regulating selective cargo entry and long-range trafficking in axons
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Laura F Gumy, Casper C Hoogenraad
The polarized long-distance transport of neuronal cargoes depends on the presence of functional and structural axonal subcompartments. Given the heterogeneity of neuronal cargoes, selective sorting and entry occurs in the proximal axon where multiple subcellular specializations such as the axon initial segment, the pre-axonal exclusion zone, the MAP2 pre-axonal filtering zone and the Tau diffusion barrier provide different levels of regulation. Cargoes allowed to pass through the proximal axon spread into the more distal parts. Recent findings show that diverse cargo distributions along the axon depend on the compartmentalized organization of the cytoskeleton and the local regulation of multiple motor proteins by microtubule associated proteins. In this review, we focus on the local mechanisms that control cargo motility and discuss how they play a role in the overall circulation of axonal cargoes.
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The biological and behavioral computations that influence dopamine responses
Source:Current Opinion in Neurobiology, Volume 49
Author(s): WR Stauffer
Phasic dopamine responses demonstrate remarkable simplicity; they code for the differences between received and predicted reward values. Yet this simplicity belies the subtle complexity of the psychological, computational, and contextual factors that influence this signal. Advances in behavioral paradigms and models, in monkeys and rodents, have demonstrated that phasic dopamine responses reflect numerous behavioral computations and factors including choice, subjective value, confidence, and context. The application of optogenetics has provided evidence that dopamine reward prediction error responses cause value learning. Furthermore, studies using advanced circuit tracing techniques have begun to uncover the biological network implementation of the reward learning algorithm. The purpose of this review is to summarize the recent advances in dopamine neurophysiology and synthesize an updated account of the behavioral function of dopamine signals.
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Prefabricated fibula free flap with dental implants for mandibular reconstruction
Publication date: Available online 2 March 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): D. Pauchet, J.-L. Pigot, F. Chabolle, C.-A. Bach
Free fibula transplant is routinely used for mandibular reconstruction in head and neck cancer. Dental rehabilitation, the objective of mandibular reconstruction, requires the use of dental implants as supports for fixed or removable dentures. Positioning of fibular bone grafts and implants determines implant osseointegration and the possibilities of dental rehabilitation.Prefabrication of a fibula free flap with dental implants prior to harvesting as a free flap can promote implant osseointegration. The position of the implants must then be precisely planned.Virtual surgery and computer-assisted design and prefabrication techniques are used to plan the reconstruction and then reproduce this planning by means of tailored fibula and mandible cutting guides, thereby ensuring correct positioning of fibular bone fragments and implants.The prefabricated fibula free flap technique requires two surgical procedures (prefabrication and flap transfer) and precise preoperative planning.Prefabricated fibula free flap with dental implants, by improving the quality of osseointegration of the implants before flap transfer, extends the possibilities of prosthetic rehabilitation in complex secondary mandibular reconstructions.
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Germline control of somatic Kras mutations in mouse lung tumors
Abstract
Somatic KRAS mutations are common in human lung adenocarcinomas and are associated with worse prognosis. In mice, Kras is frequently mutated in both spontaneous and experimentally induced lung tumors, although the pattern of mutation varies among strains, suggesting that such mutations are not random events. We tested if the occurrence of Kras mutations is under genetic control in two mouse intercrosses. Codon 61 mutations were prevalent, but the patterns of nucleotide changes differed between the intercrosses. Whole genome analysis with SNPs in (A/J x C57BL/6)F4 mice revealed a significant linkage between a locus on chromosome 19 and two particular codon 61 variants (CTA and CGA). In (AIRmax x AIRmin)F2 mice, there was a significant linkage between SNPs located on distal chromosome 6 (around 135 Mbp) and the frequency of codon 61 mutation. These results reveal the presence of two loci, on chromosomes 6 and 19, that modulate Kras mutation frequency in different mouse intercrosses. These findings indicate that somatic mutation frequency and type are not simple random events, but are under genetic control. This article is protected by copyright. All rights reserved
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