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1.
Int J Oral Sci ; 12(1): 7, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32080164

RESUMO

Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded (n = 7) and non-infraoccluded (n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432 (2.3%) genes were differentially expressed between the two groups (false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez; tissues that are central to the ankylotic process. We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.

2.
Ann Surg ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31972650

RESUMO

BACKGROUND: Esophagectomy is a technically challenging procedure, associated with significant morbidity. The introduction of minimally invasive esophagectomy (MIE) has reduced postoperative morbidity. OBJECTIVE: Although the short-term effect on complications is increasingly being recognized, the impact on long-term survival remains unclear. This study aims to investigate the association between postoperative complications following MIE and long-term survival. METHODS: Data were collected from the EsoBenchmark Collaborative composed by 13 high-volume, expert centers routinely performing MIE. Patients operated between June 1, 2011 and May 31, 2016 were included. Complications were graded using the Clavien-Dindo (CD) classification. To correct for short-term effects of postoperative complications on mortality, patients who died within 90 days postoperative were excluded. Primary endpoint was 5-year overall survival. RESULTS: A total of 915 patients were included with a mean follow-up time of 30.8 months (standard deviation 17.9). Complications occurred in 542 patients (59.2%) of which 50.2% had a CD grade ≥III complication [ie, (re)intervention, organ dysfunction, or death]. The incidence of anastomotic leakage (AL) was 135 of 915 patients (14.8%) of which 84 patients were classified as a CD grade ≥III. Multivariable analysis showed a significantly deteriorated long-term survival in all patients with AL [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.25-2.24]. This inverse relation was most distinct when AL was scored as a CD grade ≥III (HR 1.83, 95% CI 1.30-2.58). For all other complications, no significant association with long-term survival was found. CONCLUSION: The occurrence and severity of AL, but not overall complications, after MIE negatively affect long-term survival of esophageal cancer patients.

3.
Nucleic Acids Res ; 48(1): 472-485, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31745551

RESUMO

Site-specific recombinases (SSRs) such as the Cre/loxP system are useful genome engineering tools that can be repurposed by altering their DNA-binding specificity. However, SSRs that delete a natural sequence from the human genome have not been reported thus far. Here, we describe the generation of an SSR system that precisely excises a 1.4 kb fragment from the human genome. Through a streamlined process of substrate-linked directed evolution we generated two separate recombinases that, when expressed together, act as a heterodimer to delete a human genomic sequence from chromosome 7. Our data indicates that designer-recombinases can be generated in a manageable timeframe for precision genome editing. A large-scale bioinformatics analysis suggests that around 13% of all human protein-coding genes could be targetable by dual designer-recombinase induced genomic deletion (dDRiGD). We propose that heterospecific designer-recombinases, which work independently of the host DNA repair machinery, represent an efficient and safe alternative to nuclease-based genome editing technologies.

4.
Diabetes Metab Syndr Obes ; 12: 2479-2487, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819573

RESUMO

Introduction: The proportion of hospitalized patients with diabetes as a secondary diagnosis increases continuously. Therefore, we have developed a team-based interprofessional and telemedicine-based diabetes management system named TeDia ("Telemedical Diabetology") and implemented it in an inpatient setting. The aim of the retrospective real-world study was to show the clinical impact of TeDia following its implementation. Material and methods: TeDia is characterized by an interpersonal and telemedicine-based exchange of hospital routine data between specially trained nurses ("diabetes managers") and external diabetologists. It was implemented in three acute hospitals of the Düsseldorf Catholic Hospital Group in Düsseldorf, Germany. Clinical awareness of diabetes, diabetes-related complications and diagnosis-related group (DRG)-based revenues were analyzed using ICD routine coding. Furthermore, the frequency of HbA1c determinations as well as hospitalization days were investigated. Results: Before (2010), during (2012) and after the implementation of TeDia (2014), the number of patients with ICD coding for diabetes, decompensated diabetes, diabetic neuropathy, diabetic nephropathy as well as complicated diabetes increased by +18%, +93%, +101%, +113% and +89%, respectively. Using the same DRG grouper, revenues increased by +53% (from 27 (2013) to 42 (2014) DRG points). Frequency of HbA1c determinations rose by +85%, whereas the time for an average length of stay decreased by -12% (-0, 91 days) in comparison to patients without diabetes. Conclusion: TeDia improved clinical awareness for diabetes and its complications. This new treatment model increased revenues and reduced hospital days indicating enhanced treatment quality. Our findings emphasize the necessity of novel technologies in inpatient settings for the improvement of efficacy, safety and efficiency of diabetes care.

5.
Ann Surg ; 270(5): 820-826, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31634181

RESUMO

OBJECTIVE: The aim of this study was to describe anastomotic techniques used for total minimally invasive transthoracic esophagectomy (ttMIE) and to analyze the associated morbidity. BACKGROUND: ttMIE faces increasing application in surgical treatment of esophageal cancer. For esophagogastric reconstruction, different anastomotic techniques are currently used, but their effect on postoperative anastomotic leakage and morbidity has not been investigated. PATIENTS AND METHODS: Patients were selected from a basic dataset, collected during a 5-year period from 13 international surgical high-volume centers. Endpoints were anastomotic leakage rate and postoperative morbidity in correlation to anastomotic techniques, measured by the Clavien-Dindo classification and the Comprehensive Complication Index (CCI). RESULTS: Five anastomotic techniques were identified in 966 patients after ttMIE: intrathoracic end-to-side circular-stapled technique in 427 patients (double-stapling n = 90, purse-string n = 337), intrathoracic (n = 109) or cervical (n = 255) side-to-side linear-stapled, and cervical end-to-side hand-sewn (n = 175). Leakage rates were similar in intrathoracic and cervical anastomoses (15.9% vs 17.2%, P = 0.601), but overall complications (56.7%% vs 63.7%, P = 0.029) and median 90-day CCI {21 [interquartile range (IQR) 0-36] vs 29 [IQR 0-40], P = 0.019} favored intrathoracic reconstructions. Leakage rates after intrathoracic end-to-side double-stapling (23.3%) and cervical end-to-side hand-sewn (25.1%) techniques were significantly higher compared with intrathoracic side-to-side linear (15.6%), end-to-side purse-string (13.9%), and cervical side-to-side linear-stapled esophagogastrostomies (11.8%) (P < 0.001). Multivariable analysis confirmed anastomotic technique as independent predictor of leakage after ttMIE. CONCLUSION: Results of this analysis present the current status of the technical evolution of ttMIE with anastomotic leakage as predominant surgical complication. However, technique-related morbidity requires cautious interpretation considering the long learning curve of this complex surgical procedure.

6.
Zentralbl Chir ; 2019 Oct 24.
Artigo em Alemão | MEDLINE | ID: mdl-31648358

RESUMO

BACKGROUND: The aim of the consensus approach was to improve the quality of care by agreement on definitions and standards, in order to harmonise lymphadenectomy during lung metastasectomy. METHODS: The Delphi process consisted of two rounds of anonymous voting before discussion at a consensus meeting to reach final consensus within a group of experts. Consensus was assumed when > 75% of the panel agreed. RESULTS: Of 76 invited experts (board certified thoracic surgeons leading high-volume thoracic departments), 49 and 47 participated in the first and second round questionnaire, respectively. 43 experts attended the consensus meeting and reached consensus on the following: surgical approach for solitary subpleurally located lung metastasis is videothoracoscopy compared to anterolateral thoracotomy for multiple lung metastases. Lymphadenectomy is performed irrespective of the surgical approach. Systematic lymphadenectomy or sampling are core elements of pulmonary metastasectomy for colorectal, renal and non-seminomatous testicular cancer. The size of pulmonary metastasis does not influence lymphadenectomy per se. Pulmonary metastasectomy is not abolished in case of intraoperatively detected lymph node metastases. CONCLUSIONS: An expert group agreed on recommendations for lymphadenectomy during pulmonary metastasectomy using the Delphi process.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31496202

RESUMO

BACKGROUND: Identification of pre-therapeutic predictive markers in gastro-esophageal cancer is essential for individual-oriented treatment. This study evaluated the relationship of multimodality parameters derived from intravoxel incoherent motion method (IVIM), 18F- FDG-PET, CT perfusion and dynamic contrast enhanced MRI in patients with gastro- esophageal cancer and investigated their histopathological correlation. METHODS: Thirty-one consecutive patients (28 male; median age 63.9 years; range 37-84 years) with gastro-esophageal adenocarcinoma (n=22) and esophageal squamous cell carcinoma (n=9) were analyzed. IVIM parameters: pseudodiffusion (D*), perfusion fraction (fp), true diffusion (D) and the threshold b-value (bval); PET-parameters: SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT perfusion parameters: blood flow (BF), blood volume (BV) and mean transit time (MTT); and MR perfusion parameters: time to enhance, positive enhancement integral, time-to-peak (TTP), maximum- slope-of-increase, and maximum-slope-of-decrease were determined, and correlated to each other and to histopathology. RESULTS: IVIM and PET parameters showed significant negative correlations: MTV & bval (rs = -0.643, p = 0.002), TLG & bval (rs = -0.699, p < 0.01) and TLG & fp (rs = -0.577, p = 0.006). Positive correlation was found for TLG & D (rs = 0.705, p = 0.000). Negative correlation was found for bval & staging (rs = 0.590, p = 0.005). Positive correlation was found for positive enhancement interval & BV (rs = 0.547, p = 0.007), BF & regression index (rs = 0.753, p = 0.005) and for time-to-peak & staging (rs = 0.557, p = 0.005). CONCLUSIONS: IVIM parameters (bval, fp, D) provide quantitative information and correlate with PET parameters (MTV, TLG) and staging. IVIM might be a useful tool for additional characterization of gastro-esophageal cancer.

8.
BMC Cancer ; 19(1): 662, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272485

RESUMO

BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Linfonodos/patologia , Metástase Linfática/diagnóstico , Intervalo Livre de Doença , Esofagectomia , Seguimentos , Humanos , Excisão de Linfonodo , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico
9.
J Anat ; 234(5): 709-717, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30834524

RESUMO

The present study investigates how sexual dimorphism in the human mandible develops in three-dimensionally during adolescence. A cross-sectional sample of mandibular meshes of 268 males and 386 females, aged between 8.5 and 19.5 years of age, were derived from cone beam computed tomography and were analysed using geometric morphometric methods. Growth trajectories of the mandible in males and females were modelled separately using a recently developed non-linear kernel regression framework. Growth rate and direction at a dense array of points all over the mandibular surface were visualized within each group and compared between groups. We found that mandibular sexual dimorphism already exists at 9 years of age, but this is mostly in size not in shape. The differential growth rate and duration between the sexes during pubertal growth largely explained by adult sexual dimorphism: the growth direction in both males and females is similar but the male mandible changed more quickly and over a longer period than the female mandible, where the growth rate peaked and declined earlier. This results in increasing dimorphism in form, which is evident in both size and shape. The development of dimorphic features, concentrated in the chin and ramus, were further visualized. The dense morphometric approach provides detailed three-dimensional quantitative assessment of the development of sexual dimorphism of the mandible.

10.
Eur J Cancer ; 112: 1-8, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30878666

RESUMO

Multimodal primary treatment of localised adenocarcinoma of the stomach, the oesophagus and the oesophagogastric junction (AEG) was reviewed by a multidisciplinary expert panel in a moderated consensus session. Here, we report the key points of the discussion and the resulting recommendations. The exact definition of the tumour location and extent by white light endoscopy in conjunction with computed tomography scans is the backbone for any treatment decision. Their value is limited with respect to the infiltration depth, lymph node involvement and peritoneal involvement. Additional endoscopic ultrasound was recommended mainly for tumours of the lower oesophagogastric junction (i.e. AEG type II and III according to Siewert) and in early cancers before endoscopic resection. Laparoscopy to diagnose peritoneal involvement was thought to be necessary before the start of neoadjuvant treatment in all gastric cancers and in AEG type II and III. In general, perioperative multimodal treatment was suggested for all locally advanced oesophageal tumours and for gastric cancers with a clinical stage above T1N0. There was consensus that the combination of fluorouracil, folinic acid, oxaliplatin and docetaxel is now a new standard chemotherapy (CTx) regimen for fit patients. In contrast, the optimal choice of perioperative CTx versus neoadjuvant radiochemotherapy (neoRCTx), especially for AEG, was identified as an open question. Expert treatment recommendations depend on the tumour location, biology, the risk of incomplete (R1) resection, response to treatment, local or systemic recurrence risks, the predicted perioperative morbidity and patients' comorbidities. In summary, any treatment decision requires an interdisciplinary discussion in a comprehensive multidisciplinary setting.

11.
Gastric Cancer ; 22(1): 172-189, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846827

RESUMO

BACKGROUND: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. METHODS: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. RESULTS: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. CONCLUSION: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.


Assuntos
Técnica Delfos , Gastrectomia/efeitos adversos , Complicações Intraoperatórias , Complicações Pós-Operatórias , Neoplasias Gástricas/cirurgia , Consenso , Humanos
12.
Mult Scler ; 25(8): 1170-1177, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-29932341

RESUMO

BACKGROUND: While studying the etiology of multiple sclerosis (MS) in children has several methodological advantages over studying etiology in adults, studies are limited by small sample sizes. OBJECTIVE: Using a rigorous methodological process, we developed the Pediatric MS Tool-Kit, a measurement framework that includes a minimal set of core variables to assess etiological risk factors. METHODS: We solicited input from the International Pediatric MS Study Group to select three risk factors: environmental tobacco smoke (ETS) exposure, sun exposure, and vitamin D intake. To develop the Tool-Kit, we used a Delphi study involving a working group of epidemiologists, neurologists, and content experts from North America and Europe. RESULTS: The Tool-Kit includes six core variables to measure ETS, six to measure sun exposure, and six to measure vitamin D intake. The Tool-Kit can be accessed online ( www.maelstrom-research.org/mica/network/tool-kit ). CONCLUSION: The goals of the Tool-Kit are to enhance exposure measurement in newly designed pediatric MS studies and comparability of results across studies, and in the longer term to facilitate harmonization of studies, a methodological approach that can be used to circumvent issues of small sample sizes. We believe the Tool-Kit will prove to be a valuable resource to guide pediatric MS researchers in developing study-specific questionnaire.

13.
Psychosomatics ; 60(1): 37-46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30064729

RESUMO

BACKGROUND: The use of involuntary psychiatric holds (IPH) to detain patients who lack the capacity to make health care decisions due to nonpsychiatric conditions is common. While this practice prevents patient harm, it also deprives civil liberties, risks liability for false imprisonment, and may hinder disposition. Medical incapacity hold (MIH) policies, which establish institutional criteria and processes for detaining patients who lack capacity but do not meet criteria for an IPH, provide a potential solution. METHODS: A retrospective chart review was conducted on adult medical/surgical inpatients placed on an IPH or MIH over the 1-year periods before and after implementation of a MIH policy at an academic medical center. The primary outcome was frequency of IPH utilization in patients who did not qualify for an IPH as determined by 2 independent physician reviewers. A Cohen's kappa was calculated to determine inter-rater reliability. Differences in patient demographics and outcomes were compared using a Student's t-test, Wilcoxon rank-sum test, and Pearson chi-square test (α = 0.05). RESULTS: The Cohen's kappa was 0.72 indicating substantial agreement. Seventy MIHs were placed after implementation (mean duration 4.3 days). Before MIH implementation, 17.6% of IPHs were placed on non-qualifying patients, which decreased to 3.9% following MIH implementation (p < 0.01). The average length of stay for patients on an IPH or MIH did not change following MIH implementation. No instances of patient elopement, grievances, or litigation were found. CONCLUSION: MIH policies benefit both patients lacking capacity and the health care systems seeking to protect them while avoiding inappropriate use of IPHs.


Assuntos
Tratamento Psiquiátrico Involuntário/estatística & dados numéricos , Tratamento Involuntário/métodos , Competência Mental , Centros Médicos Acadêmicos , Traumatismos Craniocerebrais , Feminino , Encefalopatia Hepática , Humanos , Hemorragias Intracranianas , Masculino , Pessoa de Meia-Idade , Política Organizacional , Insuficiência Renal , Estudos Retrospectivos , Sepse , Recusa do Paciente ao Tratamento
14.
Dentomaxillofac Radiol ; 48(2): 20180261, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30379569

RESUMO

OBJECTIVES:: To propose a reliable and practical method for automatically segmenting the mandible from CBCT images. METHODS:: The marker-based watershed transform is a region-growing approach that dilates or "floods" predefined markers onto a height map whose ridges denote object boundaries. We applied this method to segment the mandible from the rest of the CBCT image. The height map was generated to enhance the sharp decreases of intensity at the mandible/tissue border and suppress noise by computing the intensity gradient image of the CBCT itself. Two sets of markers, "mandible" and "background" were automatically placed inside and outside the mandible, respectively in a novel image using image registration. The watershed transform flooded the gradient image by dilating the markers simultaneously until colliding at watershed lines, estimating the mandible boundary. CBCT images of 20 adolescent subjects were chosen as test cases. Segmentation accuracy of the proposed method was evaluated by measuring overlap (Dice similarity coefficient) and boundary agreement against a well-accepted interactive segmentation method described in the literature. RESULTS:: The Dice similarity coefficient was 0.97 ± 0.01 (mean ± SD), indicating almost complete overlap between the automatically and the interactively segmented mandibles. Boundary deviations were predominantly under 1 mm for most of the mandibular surfaces. The errors were mostly from bones around partially erupted wisdom teeth, the condyles and the dental enamels, which had minimal impact on the overall morphology of the mandible. CONCLUSIONS:: The marker-based watershed transform method produces segmentation accuracy comparable to the well-accepted interactive segmentation approach.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Mandíbula , Tomografia Computadorizada de Feixe Cônico Espiral , Adolescente , Algoritmos , Animais , Biomarcadores , Gatos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Mandíbula/diagnóstico por imagem , Dente Serotino
15.
BMC Biotechnol ; 18(1): 75, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30477471

RESUMO

BACKGROUND: The creation of functional skeletal muscle via tissue engineering holds great promise without sacrificing healthy donor tissue. Different cell types have been investigated regarding their myogenic differentiation potential under the influence of various media supplemented with growth factors. Yet, most cell cultures include the use of animal sera, which raises safety concerns and might lead to variances in results. Electrospun nanoscaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability. We therefore aimed to develop a serum-free myogenic differentiation medium for the co-culture of primary myoblasts (Mb) and mesenchymal stromal cells derived from the bone marrow (BMSC) and adipose tissue (ADSC) on electrospun poly-ε-caprolacton (PCL)-collagen I-nanofibers. RESULTS: Rat Mb were co-cultured with rat BMSC (BMSC/Mb) or ADSC (ADSC/Mb) two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-nanofibers. Differentiation media contained either AIM V, AIM V and Ultroser® G, DMEM/Ham's F12 and Ultroser® G, or donor horse serum (DHS) as a conventional differentiation medium. In 2D co-culture groups, highest upregulation of myogenic markers could be induced by serum-free medium containing DMEM/Ham's F12 and Ultroser® G (group 3) after 7 days. Alpha actinin skeletal muscle 2 (ACTN2) was upregulated 3.3-fold for ADSC/Mb and 1.7-fold for BMSC/Mb after myogenic induction by group 3 serum-free medium when compared to stimulation with DHS. Myogenin (MYOG) was upregulated 5.2-fold in ADSC/Mb and 2.1-fold in BMSC/Mb. On PCL-collagen I-nanoscaffolds, ADSC showed a higher cell viability compared to BMSC in co-culture with Mb. Myosin heavy chain 2, ACTN2, and MYOG as late myogenic markers, showed higher gene expression after long term stimulation with DHS compared to serum-free stimulation, especially in BMSC/Mb co-cultures. Immunocytochemical staining with myosin heavy chain verified the presence of a contractile apparatus under both serum free and standard differentiation conditions. CONCLUSIONS: In this study, we were able to myogenically differentiate mesenchymal stromal cells with myoblasts on PCL-collagen I-nanoscaffolds in a serum-free medium. Our results show that this setting can be used for skeletal muscle tissue engineering, applicable to future clinical applications since no xenogenous substances were used.


Assuntos
Diferenciação Celular , Técnicas de Cocultura/métodos , Colágeno/metabolismo , Células-Tronco Mesenquimais/citologia , Mioblastos/citologia , Actinina , Animais , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Técnicas de Cocultura/instrumentação , Meios de Cultura Livres de Soro/química , Meios de Cultura Livres de Soro/metabolismo , Células-Tronco Mesenquimais/metabolismo , Desenvolvimento Muscular , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Poliésteres , Ratos , Engenharia Tecidual , Tecidos Suporte/química
16.
Ann N Y Acad Sci ; 1434(1): 149-155, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30191569

RESUMO

Esophageal surgery for esophageal cancer has been performed for over a century now. Minimally invasive esophagectomy (MIE) was first described in 1992, and it is now a standard approach in many countries. However, MIE is technically difficult and requires a long learning curve. It takes >100 cases to train for MIE with gastric tube reconstruction with an intrathoracic anastomosis. A possible option to overcome several challenges of MIE might be the use of a robotic system. A robot-assisted MIE was first described in 2005, and long-term results have shown its feasibility and safety. Over the years, different approaches for esophagectomy have been established. Our review discusses these developments and recent literature on open, minimally invasive and robotic esophageal surgery.


Assuntos
Neoplasias Esofágicas , Esofagectomia/métodos , Esôfago , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esôfago/patologia , Esôfago/cirurgia , Humanos
17.
Dis Esophagus ; 31(13): 1, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30219910

RESUMO

Background: Esophagectomy has a high incidence of postoperative morbidity. Complications lead to a decreased short-term survival, however the influence of those complications on long-term survival is still unclear. Most of the performed studies are small, single center cohort series with inconclusive or conflicting results. Minimally invasive esophagectomy (MIE) has been shown to be associated with a reduced postoperative morbidity. In this study, the influence of complications on long-term survival for patients with esophageal cancer undergoing a MIE were investigated. Methods: Data was collected from the EsoBenchmark database, a collaboration of 13 high-volume centers routinely performing MIE. Patients were included in this database from June 1, 2011 until May 31, 2016. Complications were scored according to the Clavien-Dindo (CD) classification for surgical complications. Major complications were defined as a CD grade ≥ 3. The data were corrected for 90-day mortality to correct for the short-term effect of postoperative complications on mortality. Overall survival was analyzed using the Kaplan Meier, log rank- and (uni- and multivariable) Cox-regression analyses. Results: A total of 926 patients were eligible for analysis. Mean follow-up time was 30.8 months (SD 17.9). Complications occurred in 543 patients (59.2%) of which 39.3% had a major complication. Anastomotic leakage (AL) occurred in 135 patients (14.5%) of which 9.2% needed an intervention (CD grade ≥ 3). A significant worse long-term survival was observed in patients with any AL (HR 1.73, 95% CI 1.29-2.32, P < 0.001) and for patients with AL CD grade ≥3 (HR 1.86, 95% CI 1.32-2.63, P < 0.001). Major cardiac complications occurred in 18 patients (1.9%) and were related to a decreased long-term survival (HR 2.72, 95% CI 1.38-5.35, p 0.004). For all other complications, no significant influence on long-term survival was found. Conclusion: The occurrence and severity of anastomotic leakage and cardiac complications after MIE negatively affect long-term survival of esophageal cancer patients. Disclosure: All authors have declared no conflicts of interest.


Assuntos
Fístula Anastomótica/mortalidade , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Procedimentos Cirúrgicos Minimamente Invasivos/mortalidade , Complicações Pós-Operatórias/mortalidade , Adulto , Idoso , Fístula Anastomótica/etiologia , Bases de Dados Factuais , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
18.
Am J Orthod Dentofacial Orthop ; 154(2): 238-248.e1, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075926

RESUMO

INTRODUCTION: The aims of this study were to evaluate, using 3-dimensional superimposition techniques, the skeletal changes in Class II subjects with different vertical facial patterns treated with the Herbst appliance and to compare these skeletal changes to those of Class II controls treated with elastics. METHODS: Sixteen Herbst patients who met the inclusion criteria were divided into 2 equal groups based on vertical facial pattern as determined by the Frankfort mandibular plane angle (brachyfacial, ≤22°; mesofacial, 23°-29°) and had cone-beam computed tomographs taken before treatment, 8 weeks after Herbst appliance removal, and after subsequent fixed appliance treatment. Eleven Class II control patients treated with fixed appliances and elastics had cone-beam computed tomographs taken before and after treatment. Three-dimensional models were generated from the cone-beam computed tomography images, registered on the anterior cranial bases, and analyzed using color maps and point-to-point measurements. RESULTS: There were minimal differences in treatment response between the 2 Herbst groups across all skeletal parameters measured. The Herbst subjects showed a greater inferior displacement of anterior nasal spine compared with the Class II controls (Herbst brachyfacial, -1.44 mm; Herbst mesofacial, -1.95 mm) with other maxillary changes being clinically insignificant. The Herbst subjects showed greater inferior displacement of B-point compared with the Class II controls (Herbst brachyfacial, -2.59 mm; Herbst mesofacial, -2.75 mm). There were no statistically significant differences in mean linear mandibular measurements. All groups showed a trend toward posterior displacement of the condyles and glenoid fossae from the start to the end of treatment, with no significant differences across the 3 groups. There were minimal differences in the changes in gonial angle and Frankfort mandibular plane angle across all groups. CONCLUSION: Approximately 2 years after Herbst treatment, the Herbst subjects with different vertical facial patterns showed similar patterns of skeletal change compared with the Class II controls treated with elastics.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Face/anatomia & histologia , Imagem Tridimensional , Má Oclusão de Angle Classe II/diagnóstico por imagem , Má Oclusão de Angle Classe II/terapia , Aparelhos Ortodônticos Funcionais , Dimensão Vertical , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
19.
BMC Cancer ; 18(1): 548, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29743108

RESUMO

BACKGROUND: Pathologic response to neoadjuvant chemotherapy (neoCTX) is a prognostic factor in many cancer types, and early prediction would help to modify treatment. In patients with gastric and esophagogastric junction (AEG) cancer, the accuracy of FDG PET-CT to predict early pathologic response after neoadjuvant chemotherapy (neoCTX) is currently not known. METHODS: From a consecutive cohort of 72 patients, 44 patients with resectable, locally-advanced gastric cancer or AEG Siewert type II and III received neoCTX after primary staging with endoscopic ultrasound, PET-CT and laparoscopy. Overall, 14 patients did not show FDG uptake, and the remaining 30 were restaged by PET-CT 14 days after the first cycle of neoCTX. Metabolic response was defined as decrease of tumor standardized uptake value (SUV) by ≥35%. Major pathologic regression was defined as less than 10% residual tumor cells. RESULTS: Metabolic response after neoCTX was detected in 20/30 (66.7%), and non-response in 10/30 (33.3%) patients. Among metabolic responders, n = 10 (50%) showed major and n = 10 (50%) minor pathologic regression. In non-responders, n = 9 (90%) had minor and 1 (10%) a major pathologic regression. This resulted in a sensitivity of 90.9%, specificity 47.3%, positive predictive value 50%, negative predictive value 90% and accuracy of 63.3%. CONCLUSION: Response PET-CT after the first cycle of neoCTX does not accurately predict overall pathologic response. However, PET-CT reliably detects non-responders, and identifies patients who should either immediately proceed to resection or receive a modified multimodality therapy. TRIAL REGISTRATION: The trial was registered and approved by local ethics committee PB_2016-00769.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias Gástricas/diagnóstico por imagem , Adulto , Idoso , Cárdia/diagnóstico por imagem , Cárdia/patologia , Cárdia/cirurgia , Endossonografia , Junção Esofagogástrica/diagnóstico por imagem , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18/administração & dosagem , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Resultado do Tratamento
20.
Artigo em Inglês | MEDLINE | ID: mdl-29745630

RESUMO

BACKGROUND: Positron emission tomography (PET) / computed tomography (CT) is among the most frequently used imaging modalities for initial staging of gastro-oesophageal (GE) cancer, whereas CT-perfusion (CTP) provides different multiparametric information. This proof of concept study compares CTP- and PET-parameters in patients with GE cancer to evaluate correlations and a possible prognostic value of a combined PET/CTP imaging procedure. METHODS: A total of 31 patients with F-18-FDG-PET/CT and CTP studies were prospectively analysed. Patients had adenocarcinoma (n = 22) and oesophageal squamous cell carcinoma (SCC, n = 9). Imaging was performed before start of treatment. CTP parameters [blood flow (BF), blood volume (BV), mean transit time (MTT)] and metabolic parameters [(maximum and mean standardised uptake values and standard deviation (SUVmax, SUVmean, SUVsd), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG)], as well as flow metabolic product [FMP (BF × SUVmax)] were determined and their relationship was compared. Additionally their association to clinical parameters (differentiation grading, staging, HER2-status, follow-up status) and to histopathological regression (post-neoadjuvant regression grading) was evaluated. RESULTS: Correlation between parameters of both modalities was significant between MTT and MTV (r = 0.375, p = 0.038); no other significant correlation was found. Patients with complete histopathological regression showed significantly lower BF and BV than patients with nearly complete or partial response. TLG and regression grading showed significant correlation with staging. All other quantitative parameters for CTP and PET data did not correlate significantly with histopathological regression grading, differentiation or staging. CONCLUSIONS: The combination of PET and CTP parameters (FMP) showed no significant prognostic value. Significant correlations were only found between MTT and MTV, which indicates a possible perfusional/metabolic coupling. Therefore, pre-therapeutic CTP and PET- parameters provide complementary information about the pre-therapeutic tumour status and are not interchangeable. Only CTP parameters might be able to predict complete histopathological regression. On the other hand, only PET parameters are correlated with staging.

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