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1.
BMC Gastroenterol ; 21(1): 304, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332533

RESUMO

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the overall mortality is low, around 20% of patients have a complicated course of disease resulting in increased morbidity and mortality. There is an emerging body of evidence that the microbiome exerts a crucial impact on the pathophysiology and course of AP. For several decades multiple clinical and laboratory parameters have been evaluated, and complex scoring systems were developed to predict the clinical course of AP upon admission. However, the majority of scoring systems are determined after several days and achieve a sensitivity around 70% for early prediction of severe AP. Thus, continued efforts are required to investigate reliable biomarkers for the early prediction of severity in order to guide early clinical management of AP patients. METHODS: We designed a multi-center, prospective clinical-translational study to test whether the orointestinal microbiome may serve as novel early predictor of the course, severity and outcome of patients with AP. We will recruit 400 AP patients and obtain buccal and rectal swabs within 72 h of admission to the hospital. Following DNA extraction, microbiome analysis will be performed using 3rd generation sequencing Oxford Nanopore Technologies (ONT) for 16S rRNA and metagenomic sequencing. Alpha- and beta-diversity will be determined and correlated to the revised Atlanta classification and additional clinical outcome parameters such as the length of hospital stay, number and type of complications, number of interventions and 30-day mortality. DISCUSSION: If AP patients show a distinct orointestinal microbiome dependent on the severity and course of the disease, microbiome sequencing could rapidly be implemented in the early clinical management of AP patients in the future. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04777812.


Assuntos
Microbiota , Pancreatite , Doença Aguda , Humanos , Estudos Multicêntricos como Assunto , Prognóstico , Estudos Prospectivos , RNA Ribossômico 16S/genética , Índice de Gravidade de Doença
2.
Radiologe ; 61(6): 548-554, 2021 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-33931791

RESUMO

BACKGROUND: There is currently no S3 guideline that contains statements on the diagnosis and treatment of acute, chronic and autoimmune pancreatitis in a single guideline. OBJECTIVES: This article presents the most relevant recommendations relating to radiological imaging from the new "S3 guideline for pancreatitis". MATERIALS AND METHODS: The guideline was developed by the DGVS (German Society for Digestive and Metabolic Diseases). After an online-based Delphi survey, the statements were discussed by an interdisciplinary expert team at a 3-day consensus conference and then agreed upon. The level of evidence scheme (version 2) of the Oxford Centre for Evidence-based Medicine was used. RESULTS: The new German "S3 guideline pancreatitis" comprises for the first time all entities of pancreatitis, acute, chronic and autoimmune pancreatitis and contains a large number of innovations with regard to diagnostic imaging and therapy. In addition to the evidence-based recommendations for diagnosis and therapy, a German-language glossary of the revised Atlanta classification on acute pancreatitis was adopted by consensus of the interdisciplinary guideline expert team. Furthermore, protocol recommendations for the performance of computed tomography (CT) are provided for the first time. In this article we introduce the key recommendations and innovations in the field of diagnostic radiologic imaging for acute, chronic and autoimmune pancreatitis. CONCLUSIONS: In the future, every radiologist should have deep knowledge of the recommended time intervals for radiological imaging in acute pancreatitis and know the German terms for the description of acute pancreatitis; furthermore they should be able to classify the morphologies to the appropriate stages.


Assuntos
Pancreatite , Doença Aguda , Medicina Baseada em Evidências , Humanos , Pancreatite/diagnóstico por imagem , Pancreatite/terapia , Tomografia Computadorizada por Raios X
3.
Internist (Berl) ; 60(3): 235-246, 2019 03.
Artigo em Alemão | MEDLINE | ID: mdl-30635667

RESUMO

With an increasing number of hospital admissions, an average of 16-to 20 days in hospital per year, 34% of patients constantly taking pain medication, 57% in need of enzyme supplementation, and 29% with diabetes mellitus, chronic pancreatitis is a debilitating disease of high socio-economic relevance. In total, 33% of all patients suffering from chronic pancreatitis can no longer practice their original profession. The number of unemployed chronic pancreatitis patients due to prolonged stays in hospital or continued alcohol abuse is known to be as high as 40%. Continued alcohol abuse with a hazard ratio (HR) of 1.6, smoking with a HR of 1.4, and the presence of liver cirrhosis with a HR of 2.5 negatively affects the prognosis of chronic pancreatitis. In a patient cohort burdened with high co-morbidity, endoscopic therapy can provide short-term relief of symptoms. Endotherapy is the first line of management in chronic pancreatitis with symptomatic pancreatobiliary ductal obstruction. Further studies are required in certain key areas such as the use of fully covered self-expanding metallic stents for pancreatic ductal and biliary strictures. Long-term success rates can mainly be achieved by surgical procedures, which can be performed with acceptable morbidity in pancreatic centers. The current review focuses on the advantages and disadvantages of endoscopic and surgical treatment of chronic pancreatitis.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Endoscopia/métodos , Pancreatite Crônica/cirurgia , Colestase , Drenagem , Humanos , Ductos Pancreáticos , Pancreatite Crônica/diagnóstico , Esfinterotomia Endoscópica , Stents
4.
Br J Cancer ; 118(7): 947-954, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29515256

RESUMO

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Humanos , Imuno-Histoquímica , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Análise Serial de Tecidos , Gencitabina
5.
Br J Cancer ; 118(8): 1084-1088, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29523831

RESUMO

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.


Assuntos
Adenocarcinoma/tratamento farmacológico , Biomarcadores Tumorais/metabolismo , DCMP Desaminase/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Pancreatectomia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ribonucleosídeo Difosfato Redutase , Análise Serial de Tecidos
6.
Pancreatology ; 16(1): 110-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26602088

RESUMO

BACKGROUND: Semiquantitative EUS-elastography has been introduced to distinguish between malignant and benign pancreatic lesions. This study investigated whether semiquantitative EUS-guided transient real time elastography increases the diagnostic accuracy for solid pancreatic lesions compared to EUS-FNA. PATIENTS AND METHODS: This single centre prospective cohort study included all patients with solitary pancreatic lesions on EUS during one year. Patients underwent EUS-FNA and semiquantitative EUS-elastography during the same session. EUS and elastography results were compared with final diagnosis which was made on the basis of tissue samples and long-term outcome. RESULTS: 91 patients were recruited of which 68 had pancreatic malignancy, 17 showed benign disease and 6 had cystic lesions and were excluded from further analysis. Strain ratios from malignant lesions were significantly higher (24.00; 8.01-43.94 95% CI vs 44.00; 32.42-55.00 95% CI) and ROC analysis indicated optimal cut-off of 24.82 with resulting sensitivity, specificity and accuracy of 77%, 65% and 73% respectively. B-mode EUS and EUS-FNA had an accuracy for the correct diagnosis of malignant lesions of 87% and 85%. When lowering the cut-off strain ratio for elastography to 10 the sensitivity rose to 96% with specificity of 43% and accuracy of 84%, resulting in the least accurate EUS-based method. This was confirmed by pairwise comparison. CONCLUSION: Semiquantitative EUS-elastography does not add substantial value to the EUS-based assessment of solid pancreatic lesions when compared to B-mode imaging.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Endossonografia/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/métodos , Carcinoma , Estudos de Coortes , Cistos/diagnóstico , Cistos/patologia , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade
7.
Z Gastroenterol ; 54(4): 1, 2016 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-27168132

RESUMO

In the line "bismuth-containing quadruple therapy" of Table 7 (p 342), in the column "dosage" incorrectly at the three antibiotics respectively 1-1-1-1. The correct is: 3-3-3-3.

8.
Internist (Berl) ; 57(7): 717-23, 2016 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-27075316

RESUMO

A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G­CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.


Assuntos
Hipertireoidismo/induzido quimicamente , Hipertireoidismo/prevenção & controle , Metimazol/efeitos adversos , Plasmaferese/métodos , Tonsilite/induzido quimicamente , Tonsilite/prevenção & controle , Doença Aguda , Adulto , Antitireóideos/efeitos adversos , Terapia Combinada/métodos , Diagnóstico Diferencial , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Hipertireoidismo/diagnóstico , Tonsilite/diagnóstico , Resultado do Tratamento
10.
Z Gastroenterol ; 53(12): 1447-95, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26666283

RESUMO

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.


Assuntos
Endoscopia Gastrointestinal/normas , Pancreatectomia/normas , Testes de Função Pancreática/normas , Pancreatite/diagnóstico , Pancreatite/terapia , Guias de Prática Clínica como Assunto , Doença Crônica , Alemanha , Humanos , Estados Unidos
11.
ESMO Open ; 9(4): 102944, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503144

RESUMO

BACKGROUND: Over the past two decades, our group has conducted five multicenter trials focusing on first-line systemic therapy for patients with advanced pancreatic cancer. The current pooled analysis was designed to evaluate prognosis over time and the impact of clinical characteristics on survival. PATIENTS AND METHODS: Individual patient data were derived from five prospective, controlled, multicenter trials conducted by the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO): 'Gem/Cis', 'Ro96', 'RC57', 'ACCEPT' and 'RASH', which recruited patients between December 1997 and January 2017. RESULTS: Overall, 912 patients were included. The median overall survival (OS) for all assessable patients was 7.1 months. OS significantly improved over time, with a median OS of 8.6 months for patients treated from 2012 to 2017 compared with 7.0 months from 1997 to 2006 [hazard ratio (HR) 1.06; P < 0.004]. Eastern Cooperative Oncology Group performance status (HR 1.48; P < 0.001), use of second-line treatment (HR 1.51; P < 0.001), and Union for International Cancer Control (UICC) stage (III versus IV) (HR 1.34, P = 0.002) had a significant impact on OS. By contrast, no influence of age and gender on OS was detectable. Comparing combination therapy with single-agent chemotherapy did not demonstrate a survival benefit, nor did regimens containing epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as afatinib or erlotinib, compared with chemotherapy-only arms. Patients with early-onset pancreatic cancer (age at study entry of ≤50 years, n = 102) had a similar OS compared with those >50 years (7.1 versus 7.0 months; HR 1.13; P = 0.273). The use of a platinum-containing regimen was not associated with better outcomes in patients with early-onset pancreatic cancer. CONCLUSIONS: Within this selected group of patients treated within prospective clinical trials, survival has shown improvement over two decades. This effect is likely attributable to the availability of more effective combination therapies and treatment lines, rather than to any specific regimen, such as those containing EGFR-TKIs. In addition, concerning age and sex subgroups, the dataset did not provide evidence for distinct clinical behavior.


Assuntos
Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Alemanha , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Adulto , Estudos Prospectivos , Idoso de 80 Anos ou mais , Prognóstico
12.
Z Gastroenterol ; 51(4): 358-62, 2013 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-23585264

RESUMO

The German Journal of Gastroenterology celebrates its fifties anniversary in 2013. Over half a century original studies, reviews and guidelines covering the topics of acute and chronic pancreatitis as well as pancreatic cancer have assumed a prominent role on its pages. Already in the first edition of the Journal Haemmerli and Hefti have summarized the Zurich experience with chronic pancreatitis and provided a detailed state-of-the-art review for the year 1963. 50 years later the current guidelines of the German Society of Digestive and Metabolic Diseases (DGVS) have been published in the same Journal and allow to summarize the scientific progress over this period. Back then chronic pancreatitis was regarded as a rare disorder (tenfold less common than e. g. acute pancreatitis or pancreatic cancer). This misconception had little to do with actual prevalence but with highly insensitive diagnostic tests, particularly in the area of diagnostic imaging. While pathogenetic factors for chronic pancreatitis, including a possible genetic disposition, were largely known in 1963, our understanding of their cellular mechanisms has very much improved. The greatest progress in diagnostic options was achieved by the introduction of novel imaging techniques such as ultrasound and endoscopic ultrasound, ERCP, CT and MRCP. In terms of therapy the notion that a blockage of pancreatitic secretion is an effective pharmacological option has been abandoned and endoscopic intervention and surgical treatment have been newly developed as alternatives.


Assuntos
Diagnóstico por Imagem/história , Endoscopia Gastrointestinal/história , Gastroenterologia/história , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/terapia , História do Século XX , História do Século XXI , Humanos
13.
Z Gastroenterol ; 51(3): 278-86, 2013 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-23299901

RESUMO

The introduction of the G-DRG reimbursement system has greatly increased the pressure to provide cost effective treatment in German hospitals. Reimbursement based on diagnosis-related groups, which requires stratification of costs incurred is still not sufficiently discriminating the disease severity and severity in relation to the intensive costs in gastroenterology. In a combined retrospective and prospective study at a tertial referral centre we investigated whether this also applies for decompensated liver cirrhosis. In 2006, 64 retrospective cases (age 57 ± 12.9; ♂ 69.2 %, ♀ 29.8 %) with decompensated liver cirrhosis (ICD code K76.4) were evaluated for their length of hospitalisation, reimbursement as well as Child and MELD scores. In 2008, 74 cases with decompensated liver cirrhosis were treated in a prospective study according to a standardised and evidence-based clinical pathway (age 57 ± 12.2; 73 % ♂, ♀ 27 %). Besides a trend in the reduction of length of hospital stay (retrospective: 13.6 ± 8.6, prospective 13.0 ± 7.2, p = 0.85) overall revenues from patients treated according to a evidence-based clinical pathway were lower than the calculated costs from the InEK matrix. Costs of medication as a percentage of reimbursement amount increased with increasing severity. In both years we could demonstrate an inverse correlation between daily reimbursement and disease severity which precluded cost coverage. For the cost-covering hospital treatment of patients with decompensated liver cirrhosis an adjustment of the DRG based on clinical severity scores such as Child-Pugh or MELD is warranted, if evidence-based treatment standards are to be kept.


Assuntos
Procedimentos Clínicos/economia , Medicina Baseada em Evidências/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Cirrose Hepática/economia , Cirrose Hepática/terapia , Medicina Baseada em Evidências/métodos , Feminino , Alemanha/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Pacientes Internados/estatística & dados numéricos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
15.
Chirurg ; 93(4): 369-372, 2022 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-35254456

RESUMO

Acute pancreatitis is a primary sterile inflammation of the pancreas, which is characterized by an unphysiological enzyme activation. This leads to an inflammatory reaction with edema, vascular damage and cell decay. The first German interdisciplinary S3 guidelines on chronic pancreatitis were published in 2012. Under the auspices of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and with the participation of various societies and patient representatives, the guidelines were recently revised and extended, Comprehensive S3 guidelines on acute and chronic pancreatitis were compiled and agreed by consensus. This article presents the important clinical aspects on acute pancreatitis from these guidelines in a compact form and the recommendations are justified.


Assuntos
Pancreatite Crônica , Doença Aguda , Consenso , Humanos , Pâncreas , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/terapia
16.
Chirurg ; 93(5): 429-440, 2022 May.
Artigo em Alemão | MEDLINE | ID: mdl-35307787

RESUMO

The new German S3 guidelines on ductal pancreatic adenocarcinoma were published for the first time on the homepage of the Association of the Scientific Medical Societies in Germany (AWMF) in December 2021 as a new update and thus the second update (first update 2013) and contain a large number of innovations in terms of diagnostics and treatment. The guidelines were organized and led by the German Society for Digestive and Metabolic Diseases (DGVS). In this article we would like to present the central content and innovations related to the radiological diagnostics of ductal pancreatic adenocarcinoma. The most important innovations are the highest recommendation strength in favor of computed tomography (CT) when assessing tumor spread as well as the adaptation of the European guidelines for cystic tumors by magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) as the method of first choice. A further innovation is the implementation of a structured reporting of CT findings for describing the anatomical tumor resectability on the basis of the publication presented by the Abdominal Imaging Working Group and the Oncological Imaging Working Group of the German Radiological Society. There is no evidence for the implementation of radiological imaging in the field of aftercare or in the field of screening.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias Pancreáticas
17.
Radiat Oncol ; 17(1): 18, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078490

RESUMO

BACKGROUND: Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. METHODS: This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the "mean cumulative pain index" rated every 4 weeks until death or end of study using numeric rating scale. DISCUSSION: An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life. TRIAL REGISTRATION: German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213.


Assuntos
Adenocarcinoma/radioterapia , Dor do Câncer/radioterapia , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/radioterapia , Radiocirurgia/métodos , Radioterapia Guiada por Imagem , Adenocarcinoma/secundário , Humanos , Neoplasias Pancreáticas/patologia , Estudos Prospectivos
18.
Sci Rep ; 12(1): 8538, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35595856

RESUMO

Physical stress is common in GI endoscopists, leading to musculoskeletal disorders. Considering the increasing complexity of interventional GI endoscopy with prolonged examination time, work-related musculoskeletal disorders have come into focus. However, data on work-related health stress in German endoscopists are elusive. The aim of this study was therefore to investigate the prevalence and consequences of work-related musculoskeletal disorders in German endoscopists. A 24-item questionnaire on endoscopy-associated musculoskeletal disorders and standardized pain assessment was developed by an interdisciplinary team of endoscopists and sports medics. The survey was distributed online by the leading German societies for gastroenterology and endoscopy. Overall, 151 German practicing endoscopists took part in the study. Regarding the average number of endoscopic procedures per week, the study collective consisted mainly of high-volume endoscopists. The survey showed that most participants suffered from general musculoskeletal disorders (82.8%) and from work-related musculoskeletal disorders (76.8%). The most affected body parts were the neck, low back, thumb, and shoulder. Temporary absence from work due to symptoms was reported by 9.9% of the respondents. Over 30% of participating endoscopists stated the need for analgesics or physiotherapy due to musculoskeletal disorders. Age, professional experience and work time were identified as relevant risk factors for musculoskeletal health issues. A high number of German endoscopists are affected by musculoskeletal disorders due to specific working postures and repetitive movements with a large impact on personal health. Further interventional studies are mandatory to improve the risk prevention of endoscopic activity.


Assuntos
Doenças Musculoesqueléticas , Doenças Profissionais , Endoscopia Gastrointestinal/efeitos adversos , Alemanha/epidemiologia , Humanos , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/etiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Prevalência , Fatores de Risco , Inquéritos e Questionários
19.
Pancreatology ; 11(1): 57-67, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21474970

RESUMO

BACKGROUND/AIMS: Acute pancreatitis (AP) is characterized by premature zymogen activation, systemic inflammatory response resulting in inflammatory infiltrates, sustained intracellular calcium, neurogenic inflammation and pain. The inhibitory neurotransmitter and cytoprotective amino acid glycine exerts a direct inhibitory effect on inflammatory cells, inhibits calcium influx and neuronal activation and therefore represents a putative therapeutic agent in AP. METHODS: To explore the impact of glycine, mild AP was induced in rats by supramaximal cerulein stimulation (10 µg/kg BW/h) and severe AP by retrograde injection of sodium taurocholate solution (3%) into the common biliopancreatic duct. 100/300 mmol glycine was administered intravenously before induction of AP. To elucidate the effect of glycine on AP, we determined pathomorphology, pancreatic cytokines as well as proteases, serum lipase and amylase, pancreatic and lung MPO activity and pain sensation. RESULTS: Glycine administration resulted in a noticeable improvement of pathomorphological alterations in AP, such as a reduction of necrosis, inflammatory infiltrates and cytoplasmic vacuoles in cerulein pancreatitis. In taurocholate pancreatitis, glycine additionally diminished pancreatic cytokines and MPO activity, as well as serum lipase and amylase levels. CONCLUSIONS: Glycine reduced the severity of mild and much more of severe AP by attenuating the intrapancreatic and systemic inflammatory response. Therefore, glycine seems to be a promising tool for prophylactic treatment of AP. and IAP.


Assuntos
Glicinérgicos/uso terapêutico , Glicina/uso terapêutico , Pancreatite/prevenção & controle , Animais , Ceruletídeo/toxicidade , Quimioprevenção , Citocinas/metabolismo , Modelos Animais de Doenças , Enzimas/metabolismo , Injeções Intravenosas , Masculino , Necrose/induzido quimicamente , Necrose/prevenção & controle , Medição da Dor , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Pancreatite/patologia , Ratos , Ratos Sprague-Dawley , Ácido Taurocólico/toxicidade
20.
Eur Surg Res ; 47(2): 98-107, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21720167

RESUMO

BACKGROUND/AIMS: To develop a clinically relevant immunocompetent murine model to study pancreatic cancer using two different syngeneic pancreatic cancer cell lines and to assess MRI for its applicability in this model. METHODS: Two cell lines, 6606PDA and Panc02, were employed for the experiments. Cell proliferation and migration were monitored in vitro. Matrigel™ was tested for its role in tumor induction. Tumor cell growth was assessed after orthotopic injection of tumor cells into the pancreatic head of C57/BL6 mice by MRI and histology. RESULTS: Proliferation and migration of Panc02 were significantly faster than those of 6606PDA. Matrigel did not affect tumor growth/migration but prevented tumor cell spread after injection thus avoiding undesired peritoneal tumor growth. MRI could reliably monitor longitudinal tumor growth in both cell lines: Panc02 had a more irregular finger-like growth, and 6606PDA grew more spherically. Both tumors showed local invasiveness. Histologically, Panc02 showed a sarcoma-like undifferentiated growth pattern, whereas 6606PDA displayed a moderately differentiated glandular tumor growth. Panc02 mice had a significantly shorter (28 days) survival than 6606PDA mice (50 days). CONCLUSION: This model closely mimics human pancreatic cancer. MRI was invaluable for longitudinal monitoring of tumor growth thus reducing the number of mice required. Employing two different cell lines, this model can be used for various treatment and imaging studies.


Assuntos
Carcinoma Ductal Pancreático/patologia , Transplante de Neoplasias/métodos , Neoplasias Pancreáticas/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Colágeno , Combinação de Medicamentos , Humanos , Laminina , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica/patologia , Neoplasias Experimentais/patologia , Proteoglicanas , Fatores de Tempo , Transplante Isogênico
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