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Truncated O-GalNAc glycosylation is an important feature of pancreatic ductal adenocarcinomas (PDAC) and expression of truncated O-GalNAc glycans is strongly associated with decreased survival and poor prognosis. It has been proven, that aberrant O-GalNAc glycosylation influence PDAC signaling to promote oncogenic properties, but elucidation of the influence of truncated O-GalNAc glycosylation on different signaling molecules has just been started. We herein elucidated the impact of aberrant O-GalNAc glycosylation on two important PDAC signaling pathways, namely AKT/mTOR and RAS/MAPK. In PDAC cells expressing truncated O-GalNAc glycans, we identified differentially expressed proteins associated with AKT/mTOR and RAS/MAPK pathways using quantitative proteomics. Since AKT, a key-signaling molecule in PDAC, was among the identified proteins, we analyzed AKT and found a strikingly enhanced S473 phosphorylation and identified a previously unknown O-GalNAc-modification. Consecutive analysis of COSMC knockdowns in PDAC revealed strong effects on AKT upstream and downstream effector molecules. Interestingly, truncated O-GalNAc glycans could facilitate an mTORC1 inhibitor resistance using AZD8055. In addition, as AKT/mTOR pathway has extensive cross talks with RAS/MAPK pathway we analyzed the pathways and found it negatively regulated. Finally, we found that the expression of epithelial-mesenchymal-transition markers, key features of aggressive PDACs cells, are enhanced and truncated O-GalNAc glycans enhance pancreatic cancer cell growth in a xenograft mouse model. Our study demonstrates that truncated O-GalNAc glycans have a strong impact on AKT/mTOR and RAS/MAPK signaling pathways, are modulated by EGF or IGF-1 signaling and should be considered for targeted therapy of these pathways in PDAC.
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OBJECTIVE: This study analyzes the clinicopathologic findings and their impact on outcome of patients so as to identify which patients benefit most from surgical treatment in chronic pancreatitis, especially in regard to pain relief. SUMMARY BACKGROUND DATA: The predominant symptom of chronic pancreatitis is chronic pain resulting in reduced quality of life. It is well known that the main reason for development of the disease is abuse of alcohol and nicotine, but only little data on factors influencing outcome are available. METHODS: One thousand one hundred forty-six consecutive patients who underwent surgery for chronic pancreatitis were included. Clinicopathologic data, including morphology of the pancreas in preoperative diagnostics and the histopathologic results, were evaluated. A long-term follow-up including Quality of Life and pain scores was performed. Additionally, we describe the novel Chronic Pancreatitis Pain Relief Score (CPPR-Score) as a tool for prediction of pain relief. RESULTS: Overall the rate of pain relief was 79.8% after surgery. The presence of an inflammatory mass in the pancreatic head larger than 4âcm (P < 0.001), presence of a dilated main pancreatic duct of over 4âmm (P < 0.001), histopathologically detected severe calcifications (P = 0.001) and severe fibrosis (P < 0.001) as well as ethanol induced disease (P < 0.001) found to be strong independent prognostic factors for pain relief. The CPPR-Score (0-5 points) proved to be a very good predictive score for pain-relief (P < 0.001). CONCLUSIONS: The rate of pain relief after surgical treatment in chronic pancreatitis is high and the commonly used procedures can be performed with acceptable morbidity and mortality. The Chronic Pancreatitis Pain Relief Score allows identifying patients who will benefit most from surgery.
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Dolor Postoperatorio/diagnóstico , Pancreatitis Crónica/cirugía , Calidad de Vida , Femenino , Humanos , Masculino , Persona de Mediana Edad , Manejo del Dolor/métodos , Dolor Postoperatorio/etiología , Pancreaticoduodenectomía , Pancreatitis Crónica/diagnóstico , Pronóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION/OBJECTIVE: Acute mesenteric ischemia (AMI) is difficult to diagnose. Since the established parameters have low sensitivity and specificity, the aim of this study is to analyze the diagnostic quality of the established parameters of AMI. METHODS: All patients that underwent emergency surgery due to suspected diagnosis of mesenteric ischemia at the University Medical Center Hamburg-Eppendorf between 2008 and 2014 were evaluated. Overall, 275 patients were enrolled and pre-, intra- and postoperative data were evaluated. RESULTS: In 200 patients, a mesenteric ischemia was confirmed intraoperatively, and 75 patients had no ischemia. Comparing these groups, the rate of patients with pH < 7.2 (25 vs. 12%; p = 0.021) and elevated mean CRP level (175 ± 117 mg/L vs. 139 ± 104 mg/L; p = 0.019) was significantly higher in ischemic patients. There was no significant difference in the level of preoperative lactate. Concerning abdominal CT scan, a sensitivity and specificity of 61 and 68%, respectively, was found. CONCLUSION: New diagnostic parameters are needed. So far, explorative laparotomy is the only reliable diagnostic method to detect mesenteric infarction.
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Abdomen Agudo/diagnóstico , Abdomen Agudo/cirugía , Laparotomía , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/cirugía , Tomografía Computarizada por Rayos X/métodos , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Esophageal perforations are associated with high morbidity and mortality. Different nonoperative and operative treatment options have been proposed. This study focuses on the impact of different surgical treatments in nonmalignant esophageal perforations and tries to identify predictors of mortality in a single tertiary center over a 15-year period. METHODS: From 2002 to 2017, patients with surgically managed esophageal perforation were identified from our database. Patients with esophageal malignancies were excluded. Etiology, clinical data, treatment, and outcome were analyzed. A multivariate logistic regression analysis was performed to investigate the impact on mortality. RESULTS: A total of 72 patients were identified. The majority of perforations were iatrogenic (54.2%) followed by Boerhaave's syndrome (23.6%). Most ruptures were found in the distal third of the esophagus (59.7%) measuring <3 cm (61.1%). Patients were treated with exploration and drainage (8.3%), primary suture and patch reinforcement (36.1%), resection and restoration of continuity (25.0%), or resection without restoration of continuity (30.6%). Delayed therapy significantly correlated with sepsis (p < 0.0001) and mortality (p = 0.032). A correlation between an increasing perforation length with sepsis (p = 0.012) was observed. A higher Perforation Severity Score (PSS; OR 4.430; 95% CI 1.143-17.174; p = 0.031) and a higher American Society of Anesthesiologists (ASA) score (OR 2.923; 95% CI 1.011-8.448; p = 0.048) were associated with mortality in multivariate analysis. CONCLUSION: Esophageal perforations are associated with high mortality, and larger ruptures are associated with worse outcome. Rapid diagnosis and treatment are crucial for patient survival. Hence, PSS and ASA score help to identify high-risk patients. The advantage of surgical management lies in the rapid control of the septic focus in an already critically ill patient. Though, the kind of surgical technique needs to be adjusted to the individual situation.
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Perforación del Esófago/mortalidad , Perforación del Esófago/cirugía , Sepsis/etiología , Adulto , Anciano , Anciano de 80 o más Años , Ecocardiografía Transesofágica/efectos adversos , Perforación del Esófago/complicaciones , Perforación del Esófago/etiología , Perforación del Esófago/patología , Esófago/patología , Femenino , Gastroscopía/efectos adversos , Humanos , Masculino , Enfermedades del Mediastino/complicaciones , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tiempo de TratamientoRESUMEN
BACKGROUND: Thymic epithelial tumors are rare neoplasias. There are no internationally accepted standards to treat this complex oncological disease. The studies on which our knowledge is based frequently have methodological weaknesses. If the tumor is resectable, complete surgical excision is currently the first-line therapy. Thymic epithelial tumors respond to radiation. The therapeutic benefit of adjuvant radiotherapy depends on tumor stage. To validate and improve treatment, we share our current experiences with clinical management and surgical intervention. METHODS: This single-center retrospective study included 40 patients with primarily resectable thymic epithelial tumors who underwent resection with curative intent. The survival data was collected and presented according to Kaplan-Meier. Single- and multiple predictor survival analyses were carried out using the log-rank test and Cox proportional hazards model. RESULTS: Single-predictor survival analysis showed survival to be dependent on the Masaoka-Koga classification, WHO histological classification, resection status, surgical technique, and Clavien-Dindo grade for postoperative complications. Multiple predictor analysis confirms that the Masaoka-Koga stage (HR = 4.876, P = 0.032) and Clavien-Dindo grade (HR = 4.904, P = 0.011) are independent prognostic factors for survival. CONCLUSION: In addition to the Masaoka stage, the occurrence of severe postoperative complications represents an independent prognostic factor. Given the tumor's sensitivity to radiation, the use of neoadjuvant radiotherapy can be considered to downstage Masaoka-Koga stages III and higher, thus reducing surgical risks. Further prospective multicenter studies are urgently needed.
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Neoplasias Glandulares y Epiteliales , Neoplasias del Timo , Humanos , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/cirugía , Pronóstico , Estudios Retrospectivos , Timectomía , Neoplasias del Timo/patología , Neoplasias del Timo/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVES: Diverting esophagectomies in cases of benign esophageal perforations remain rare but potentially life saving procedures. Usually, an esophagostoma and a feeding jejunostomy or gastrostomy are created, and patients are given time to recover from the emergency situation. However, little is known about morbidity and mortality as well as the optimal timing for a staged reconstruction. METHODS: Patients with benign esophageal perforations were selected from our retrospective database. Perforations in esophageal malignancies were excluded to avoid bias on patients' general outcome. Clinical parameters and especially, the influence of the nutritional status indicated by the BMI (Body Mass Index) as well as serum albumin levels (g/l) were analyzed. RESULTS: A total of 24 patients with diverting esophagectomies were identified. Of these, 13 (54.2%) patients received a staged reconstruction after a median of 143.0 days. Patients presenting for their staged reconstruction demonstrated a significantly decreased level of their BMI (p = 0.026) as compared to their prior hospitalization. Interestingly, the relative decrease of BMI (8.5 kg/m2 vs. 4.3 kg/m2) and albumin levels (6.5 g/l vs. 0.0 g/l) was significantly different in patients with or without anastomotic leaks between both surgeries (p = 0.021; p = 0.034, respectively). In addition, higher rates of overall complications were associated with an increased rate of malnutrition. CONCLUSIONS: The relative amount of malnutrition indicated by BMI or serum albumin levels influences the rate of anastomotic leaks and general complications in patients with staged reconstruction after diverting esophagectomy for non-malignant esophageal perforations. Hence, reconstruction should be done as fast as possible to reduce the amount of malnutrition and a frequent assessment of the nutritional status must be done during recovery from the emergency surgery.
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Fuga Anastomótica/etiología , Perforación del Esófago/cirugía , Esofagectomía/efectos adversos , Albúmina Sérica/análisis , Adulto , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/epidemiología , Fuga Anastomótica/mortalidad , Índice de Masa Corporal , Estudios de Casos y Controles , Tratamiento de Urgencia/métodos , Perforación del Esófago/etiología , Femenino , Humanos , Masculino , Desnutrición/epidemiología , Desnutrición/prevención & control , Persona de Mediana Edad , Estado Nutricional/fisiología , Procedimientos de Cirugía Plástica/efectos adversos , Reoperación/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
Expression of the retinoic acid-induced protein 3 (RAI3) has been suggested to predict clinical outcome in a variety of malignancies. However, its role in esophageal cancers remains unclear. Immunohistochemical RAI3 staining was analyzed on tissue microarrays containing 359 esophageal adenocarcinomas (EAC) and 254 esophageal squamous cell carcinomas (ESCC). RAI3 immunostaining was typically absent or weakly detectable in the membranes in benign esophageal tissues. RAI3 staining was higher in malignant than in benign esophagus epithelium. High-levels of RAI3 staining were found in 79.2% of interpretable EACs and 55.9% of ESCCs. In EACs, strong RAI3 staining was associated with advanced pathological tumor stage (pâ¯<â¯.0001), high UICC stage (pâ¯<â¯.0001), high tumor grade (pâ¯=â¯.0133), and positive lymph nodal status (pâ¯=â¯.0002). Additionally, high RAI3 staining predicted shortened overall survival of EAC and ESCC patients (pâ¯=â¯.0298 and pâ¯=â¯.0227). RAI3 overexpression is associated with poor prognosis in esophageal cancers. We propose that RAI3 overexpression might play a biologically relevant role of RAI3 in esophageal cancers.
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Adenocarcinoma/patología , Biomarcadores de Tumor/análisis , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Receptores Acoplados a Proteínas G/biosíntesis , Adenocarcinoma/mortalidad , Adulto , Anciano , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
AIM: Information regarding the localization of the anatomic site of gastrointestinal (GI) tract perforation is essential for the following surgical procedure. The purpose of this study was to evaluate the significance of C-reactive protein (CRP) and other circulating markers for the prediction of the localization of intra-abdominal hollow organ perforation. METHODS: Measurements of serum markers were analyzed in 423 patients with GI tract perforations, who were divided according to the intraoperative diagnosis into colorectal and upper GI tract perforation groups. RESULTS: Levels of CRP were higher in patients with colorectal perforations than in upper GI tract perforations (p < 0.001). Moreover, high levels of CRP were associated with increased mortality of patients with hollow organ perforations (p = 0.009), which was largely driven by the subset of patients with perforations of the upper GI tract (p = 0.001). CONCLUSION: Increased CRP levels predict worse clinical outcome in patients with intra-abdominal hollow organ perforations and are associated with perforations in the colorectal tract. Thus, CRP might be a useful marker for preoperative risk stratification and prediction of the localization of the perforation site.
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Proteína C-Reactiva/análisis , Perforación Intestinal/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Femenino , Enfermedades Gastrointestinales/sangre , Enfermedades Gastrointestinales/diagnóstico , Humanos , Perforación Intestinal/sangre , Masculino , Persona de Mediana EdadRESUMEN
In this paper, prediction models are proposed which allow the mineralogical characterization of particle systems observed by X-ray micro tomography (XMT). The models are calibrated using 2D image data obtained by a combination of scanning electron microscopy and energy dispersive X-ray spectroscopy in a planar cross-section of the XMT data. To reliably distinguish between different minerals the models are based on multidimensional distributions of certain particle characteristics describing, for example, their size, shape, and texture. These multidimensional distributions are modeled using parametric Archimedean copulas which are able to describe the correlation structure of complex multidimensional distributions with only a few parameters. Furthermore, dimension reduction of the multidimensional vectors of particle characteristics is utilized to make non-parametric approaches such as the computation of distributions via kernel density estimation viable. With the help of such distributions the proposed prediction models are able to distinguish between different types of particles among the entire XMT image.
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BACKGROUND: RBM3 expression has been suggested as prognostic marker in several cancer types. The purpose of this study was to assess the prevalence and clinical significance of altered RBM3 expression in esophageal cancer. METHODS: RBM3 protein expression was measured by immunohistochemistry using tissue microarrays containing samples from 359 esophageal adenocarcinoma (EAC) and 254 esophageal squamous cell cancer (ESCC) patients with oncological follow-up data. RESULTS: While nuclear RBM3 expression was always high in benign esophageal epithelium, high RBM3 expression was only detectable in 66.4% of interpretable EACs and 59.3% of ESCCs. Decreased RBM3 expression was linked to a subset of EACs with advanced UICC stage and presence of distant metastasis (P = 0.0031 and P = 0.0024). In ESCC, decreased RBM3 expression was associated with advanced UICC stage, high tumor stage, and positive lymph node status (P = 0.0213, P = 0.0061, and P = 0.0192). However, RBM3 expression was largely unrelated to survival of patients with esophageal cancer (EAC: P = 0.212 and ESCC: P = 0.5992). CONCLUSIONS: In summary, the present study shows that decreased RBM3 expression is associated with unfavourable esophageal cancer phenotype, but not significantly linked to patient prognosis.
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Biomarcadores de Tumor , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al ARN/genética , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Neoplasias Esofágicas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Evaluación del Resultado de la Atención al Paciente , Fenotipo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
In this paper, three-dimensional (3D) image data of ore particle systems is investigated. By combining X-ray microtomography with scanning electron microscope (SEM)-based image analysis, additional information about the mineralogical composition from certain planar sections can be gained. For the analysis of tomographic images of particle systems the extraction of single particles is essential. This is performed with a marker-based watershed algorithm and a post-processing step utilizing a neural network to reduce oversegmentation. The results are validated by comparing the 3D particle-wise segmentation empirically with 2D SEM images, which have been obtained with a different imaging process and segmentation algorithm. Finally, a stereological application is shown, in which planar SEM images are embedded into the tomographic 3D image. This allows the estimation of local X-ray attenuation coefficients, which are material-specific quantities, in the entire tomographic image.
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Chronic pancreatitis is a common disease accompanied with considerable morbidity and mortality. Complications associated with chronic pancreatitis, such as pseudocysts, stenosis of adjacent anatomic structures or pain that cannot be managed conservatively, may be treatable surgically or interventionally by endoscopy. Surgery is superior to endoscopy in regard to long-term pain management. Duodenum preserving pancreatic resection is the surgical procedure of choice in patients with inflamed changes of the head of the pancreas. The best timing of surgery, the ideal standardized perioperative management are the focus of current research.
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Drenaje , Pancreatectomía , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/cirugía , Calidad de Vida , Drenaje/métodos , Humanos , Pancreatectomía/métodos , Pancreatitis Crónica/diagnóstico por imagen , Resultado del TratamientoRESUMEN
The identification and accurate characterization of discrete grains of rare minerals in sulfide base-metal ores is usually a cumbersome procedure due to the small grain sizes (typically <10 µm) and complex mineral assemblages in the material. In this article, a new strategy for finding and identifying indium minerals, and quantifying their composition and abundance is presented, making use of mineral liberation analysis (MLA) and electron probe microanalysis (EPMA). The method was successfully applied to polymetallic massive sulfide ores from the Neves-Corvo deposit in Portugal. The presence of roquesite and sakuraiite could be systematically detected, their concentration quantified by MLA measurements, and their identity later confirmed by EPMA analyses. Based on these results, an almost complete indium deportment could be obtained for the studied samples. This validates the approach taken, combining automated mineralogy data with electron microprobe analysis. A similar approach could be used to find minerals of other common minor and trace elements in complex base-metal sulfide ores, for example Se, Ge, Sb, or Ag, thus permitting the targeted development of resource technologies suitable for by-product recovery.
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BACKGROUND AND OBJECTIVE: Cyclin D1 is an important regulator protein for the G1-S cell cycle phase transition. The aim of this trial was to evaluate the impact of the CCND1 polymorphism G870A and corresponding protein expression and CCND1 amplification on the survival of the patients. METHODS: 425 patients with ductal pancreatic adenocarcinoma who underwent resection were included after histopathological confirmation. DNA was analyzed for Cyclin D1 polymorphisms, immunhistochemical examination and fluorescence in situ hybridization analysis of the tumor were performed. RESULTS: Overall, the mean survival was 22.9 months (20.5-25.3). The survival in patients with Cyclin D1 G870A polymorphism Adenine/Adenine was 15.1 months (95% CI 11.3-18.9), 21.5 months (17.4-25.6) for Adenine/Guanine, and 29.4 months (95% CI 23.8-35.0) for Guanine/Guanine (P = 0.003). A shorter survival was associated with strong/moderate protein expression in immunohistochemistry (IHC) compared to weak/no expression (P = 0.028). Additionally, a significant coherency between unfavourable polymorphism (AA/AG) and increased protein expression was detected (P = 0.005). CONCLUSIONS: A strong impact on survival of Cyclin D1 G870A polymorphism and the detected corresponding protein expression was found. The biological mechanism of CCND1 in carcinogenesis has not been fully examined; but at present Cyclin D1 seems to be an interesting biomarker for the prognosis of ductal adenocarcinoma.
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Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/mortalidad , Ciclina D1/genética , Hibridación Fluorescente in Situ/métodos , Neoplasias Pancreáticas/mortalidad , Polimorfismo Genético/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/secundario , Ciclina D1/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Post-pancreatic surgical morbidity is frequent but often manageable by less invasive means than re-operation. Yet, some complications can become hazardous and life threatening. Herein, the results of a completion pancreatectomy (CP) to cope with severe post-operative pancreatic fistulas (POPF) and bleeding complications after major pancreatic resections for suspected pancreatic malignancy are presented. METHODS: CPs to treat severe post-pancreatic index-surgery complications between January 2002 and January 2012 were selected out of a prospective database. Indications for CP as well as perioperative data were prospectively collected and retrospectively assessed. RESULTS: In 20 of 521 Kausch-Whipple Resections (3.8%), a CP was necessary to treat post-index surgery morbidity. Indications included insufficiency of the pancreaticojejunal anastomosis with resulting POPF in 14 (70.0%) patients, severe bleeding complications in 6 (30.0%) patients, and a severe portal vein thrombosis in 1 (5.0%) patient. In 7 (35.0%) of the 20 patients, the course was complicated by remnant pancreatitis. Eleven (55.0%) of the 20 patients died during the hospital stay. Median time to re-operation did not significantly differ between survivors and in-hospital deaths (10.0 vs. 8.0 days; p = 0.732). Median hospital stay of the surviving patients was 31.0 (range 10-113) days. Re-operations following CPs were necessary in 5 (55.6%) of the 9 patients who survived and in 9 (81.8%) out of 11 patients who died. CONCLUSIONS: Post-pancreatic resection complications can become hazardous and result in severely ill patients requiring maximum therapy. CP in these cases has a high mortality but serves as an ultima ratio to cope with deleterious complications.
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Fuga Anastomótica/cirugía , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Fístula Pancreática/cirugía , Neoplasias Pancreáticas/cirugía , Hemorragia Posoperatoria/cirugía , Terapia Recuperativa/métodos , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/etiología , Femenino , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Páncreas/cirugía , Fístula Pancreática/etiología , Pancreatoyeyunostomía/efectos adversos , Pancreatitis/etiología , Complicaciones Posoperatorias/mortalidad , Hemorragia Posoperatoria/etiología , Reoperación , Estudios RetrospectivosRESUMEN
Identification and accurate characterization of platinum-group minerals (PGMs) is usually a very cumbersome procedure due to their small grain size (typically below 10 µm) and inconspicuous appearance under reflected light. A novel strategy for finding PGMs and quantifying their composition was developed. It combines a mineral liberation analyzer (MLA), a point logging system, and electron probe microanalysis (EPMA). As a first step, the PGMs are identified using the MLA. Grains identified as PGMs are then marked and coordinates recorded and transferred to the EPMA. Case studies illustrate that the combination of MLA, point logging, and EPMA results in the identification of a significantly higher number of PGM grains than reflected light microscopy. Analysis of PGMs by EPMA requires considerable effort due to the often significant overlaps between the X-ray spectra of almost all platinum-group and associated elements. X-ray lines suitable for quantitative analysis need to be carefully selected. As peak overlaps cannot be avoided completely, an offline overlap correction based on weight proportions has been developed. Results obtained with the procedure proposed in this study attain acceptable totals and atomic proportions, indicating that the applied corrections are appropriate.
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OBJECTIVES: In severe acute pancreatitis, the administration of fluids in the presence of positive fluid responsiveness is associated with better outcome when compared to guiding therapy on central venous pressure. We compared the effects of such consequent maximization of stroke volume index with a regime using individual values of stroke volume index assessed prior to severe acute pancreatitis induction as therapeutic hemodynamic goals. DESIGN: Prospective, randomized animal study. SETTING: University animal research laboratory. SUBJECTS: Thirty domestic pigs. INTERVENTIONS: After randomization, fluid resuscitation was started 2 hours after severe acute pancreatitis induction and continued for 6 hours according to the respective treatment algorithms. In the control group, fluid therapy was directed by maximizing stroke volume index, and in the study group, stroke volume index assessed prior to severe acute pancreatitis served as primary hemodynamic goal. MEASUREMENTS AND MAIN RESULTS: Within the first 6 hours of severe acute pancreatitis, the study group received a total of 1,935.8 ± 540.7 mL of fluids compared with 3,462.8 ± 828.2 mL in the control group (p < 0.001). Pancreatic tissue oxygenation did not differ significantly between both groups. Vascular endothelial function, measured by flow-mediated vasodilation before and 6 hours after severe acute pancreatitis induction, revealed less impairment in the study group after treatment interval (-90.76% [study group] vs -130.89% [control group]; p = 0.046). Further, lower levels of heparan sulfate (3.41 ± 5.6 pg/mL [study group] vs 43.67 ± 46.61 pg/mL [control group]; p = 0.032) and interleukin 6 (32.18 ± 8.81 pg/mL [study group] vs 77.76 ± 56.86 pg/mL [control group]; p = 0.021) were found in the study group compared with control group. Histopathological examination of the pancreatic head and corpus at day 7 revealed less edema for the study group compared with the control group (1.82 ± 0.87 [study group] vs 2.89 ± 0.33 [control group, pancreatic head]; p = 0.03; 2.2 ± 0.92 [study group] vs 2.91 ± 0.3 [control group, pancreatic corpus]; p = 0.025). CONCLUSIONS: Individualized optimization of intravascular fluid status during the early course of severe acute pancreatitis, compared with a treatment strategy of maximizing stroke volume by fluid loading, leads to less vascular endothelial damage, pancreatic edema, and inflammatory response.
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Fluidoterapia/métodos , Inflamación/terapia , Pancreatitis/terapia , Volumen Sistólico/fisiología , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Endotelio Vascular/fisiopatología , Ensayo de Inmunoadsorción Enzimática , Glicocálix/metabolismo , Hemodinámica , Heparitina Sulfato/sangre , Inflamación/fisiopatología , Estudios Prospectivos , Distribución Aleatoria , Índice de Severidad de la Enfermedad , Porcinos , Sindecano-1/sangreRESUMEN
OBJECTIVE: The aim of this study was to report on 15-year long-term results of a randomized controlled trial comparing extended drainage procedure (Frey) and classical resectional procedure [pylorus-preserving pancreatoduodenectomy (PD)] in patients with chronic pancreatitis. BACKGROUND: Chronic pancreatitis is a common inflammatory disease with a prevalence of 10 to 30 cases per 100,000 inhabitants. It is characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. Different surgical procedures are used in treatment of persistent pain. METHODS: Sixty-four patients suffering from chronic pancreatitis with inflammatory mass in the pancreatic head were randomly assigned in 2 treatment groups (PD, n = 32) and (Frey, n = 32). The perioperative course of the randomized controlled trial and the 7 years follow-up have been previously published. All participating patients were contacted with a standardized, validated questionnaire (EORTC QLQ C30) to evaluate the long-term survival, quality-of-life pain, and exocrine and endocrine function. RESULTS: In the 15-year long-term follow-up, the pain control was good and comparable between both groups, but the quality of life was better after Frey procedure in regard of the physical status [PD: 100 (0-100) vs PD: 60 (0-100) (P = 0.011)]. No significant differences in terms of the Pain Score were detected between both groups [PD: 7 (0-100) vs Frey 4 (0-100) P = 0.258]. Seven patients after Frey OP and 6 patients after PD were free of pain. Analyzing the postoperative overall survival, a higher long-term mortality was found after PD (53%) than that found after Frey procedure (30%) resulting in a longer mean survival (14.5 ± 0.8 vs 11.3 ± 0.8 years; P = 0.037). No correlation between endocrine or exocrine pancreatic function and pain was found, whereas continuous alcohol consumption was associated with poorer outcome regarding quality of life (P < 0.001) and pain score (P < 0.001). CONCLUSIONS: PD and Frey procedure provide good and permanent pain relief and improvement of the quality of life in long-term follow-up. In addition, a longer survival was found after the organ sparing resection. Together with better short-term results, the organ-sparing procedure seems to be favorable in treatment of chronic pancreatitis.
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Pancreatectomía/métodos , Pancreaticoduodenectomía , Pancreatitis/cirugía , Adulto , Consumo de Bebidas Alcohólicas , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dimensión del Dolor , Dolor Postoperatorio , Pruebas de Función Pancreática , Píloro/cirugía , Calidad de Vida , Encuestas y Cuestionarios , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study. METHODS: In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO2) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination. RESULTS: Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05). CONCLUSIONS: TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis.
Asunto(s)
Anestesia Epidural , Microcirculación/efectos de los fármacos , Pancreatitis/terapia , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Hemodinámica , Consumo de Oxígeno , Pancreatitis/patología , Pancreatitis/fisiopatología , Estudios Prospectivos , Análisis de Supervivencia , Porcinos , Tórax , Equilibrio HidroelectrolíticoRESUMEN
In this study, synthetic pure cassiterite and cassiterite doped with two different Fe contents were successfully recrystallized by means of sintering. Their crystal structure and chemical compositions were characterized by X-ray powder diffraction (XRD) as well as scanning electron microscopy (SEM) combined with energy-dispersive X-ray (EDX) analysis. Their floatability was studied by microflotation with a diphosphonic acid surfactant named Lauraphos301 as a collector. Unlike the addition of ferric ions in solution, which strongly depressed the floatability of all of the cassiterite samples, a much higher flotation efficiency of the Fe-doped cassiterite samples was found especially at lower collector concentrations. The cassiterite floatability is proportional to the Fe content in cassiterite at a broad range of pH, and the recovery has the following order: cassiterite with 1417 ppm Fe > cassiterite with 1165 ppm Fe > pure cassiterite. The electrokinetic behavior of the cassiterite samples with and without the collector was studied by electrophoretic measurements and revealed that the chemical interaction dominated the adsorption. With the help of the particle shape analysis, a more angular shape was found for the Fe-doped cassiterite samples. Moreover, without the influence of particle shape, much abundant adsorption of Lauraphos301 was found on the Fe-doped cassiterite samples by AFM topography imaging. The minor amount of Fe in the cassiterite lattice and a more angular shape of the Fe-doped cassiterite samples were believed to enhance floatability collectively. The study reveals that the influence of the chemical composition of the minerals on flotation was almost inextricably bound up with particle morphology and emphasizes the importance of considering both factors and investigating them individually for the flotation study.