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1.
Chirurgie (Heidelb) ; 94(6): 487-496, 2023 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-36894648

RESUMO

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic the standard inpatient care of patients was restricted to increase overall and intensive care capacity reserves for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected persons. OBJECTIVE: This article presents the impact of the COVID-19 pandemic on the surgical and postoperative care of bariatric patients in Germany. MATERIAL AND METHODS: A statistical analysis of the national StuDoQ/MBE register data for the period from 1 May 2018 until 31 May 2022 was performed. RESULTS: Throughout the entire study period there was a continuous increase in documented operations, which continued even during the COVID-19 pandemic. A significant intermittent decline in surgery performed was observed only during the imposition of first lockdown in the months of March to May 2020, with a minimum number of 194 cases performed monthly in April 2020. The pandemic had no measurable effect on the surgically treated patient population, the type of surgical procedure, the perioperative and postoperative outcomes and follow-up care. CONCLUSION: Based on the results of the StuDoQ data and the current literature, it can be deduced that bariatric surgery can be carried out with no increased risk during the COVID-19 pandemic and the quality of postoperative care is not impaired.


Assuntos
Cirurgia Bariátrica , COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/etiologia , Pandemias , SARS-CoV-2 , Controle de Doenças Transmissíveis , Alemanha/epidemiologia
2.
Langenbecks Arch Surg ; 406(7): 2343-2355, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34009458

RESUMO

PURPOSE: Postoperative pancreatic fistulae (POPF) present a serious and life-threatening complication after pancreatic head resections (PD). Therefore, reliable risk stratification to identify those at risk is urgently needed. The aim of this study was to identify postoperative laboratory parameters for the prediction of POPF in the early postoperative period. METHODS: One hundred eighty-two patients who underwent PD from 2012 until 2017 were retrospectively analyzed. Multivariate logistic regression was performed using the GLM (general linear model) method for model building. Two nomograms were created based on the GLM models of postoperative day one and postoperative day one to five. A cohort of 48 patients operated between 2018 and 2019 served as internal validation. RESULTS: Clinically relevant pancreatic fistulae (CR-POPF) were present in 16% (n = 29) of patients. Patients with CR-POPF experienced significantly more insufficiencies of gastroenterostomies, delayed gastric emptying, and more extraluminal bleeding than patients without CR-POPF. Multivariate analysis revealed multiple postoperative predictive models, the best one including ASA, main pancreatic duct diameter, operation time, and serum lipase as well as leucocytes on day one. This model was able to predict CR-POPF with an accuracy of 90% and an AUC of 0.903. Two nomograms were created for easier use. CONCLUSION: Clinically relevant fistula can be predicted using simple laboratory and clinical parameters. Not serum amylase, but serum lipase is an independent predictor of CR-POPF. Our simple nomograms may help in the identification of patients for early postoperative interventions.


Assuntos
Fístula Pancreática , Pancreaticoduodenectomia , Humanos , Nomogramas , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco
3.
Br J Surg ; 107(9): 1171-1182, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32259295

RESUMO

BACKGROUND: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.


ANTECEDENTES: Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox. RESULTADOS: En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.


Assuntos
Adenocarcinoma/tratamento farmacológico , Ampola Hepatopancreática , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante/métodos , Neoplasias do Ducto Colédoco/tratamento farmacológico , Desoxicitidina/análogos & derivados , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Quimioterapia Adjuvante/mortalidade , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Gencitabina
4.
Br J Surg ; 106(6): 747-755, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30706456

RESUMO

BACKGROUND: Nationwide audits facilitate quality and outcome assessment of pancreatoduodenectomy. Differences may exist between countries but studies comparing nationwide outcomes of pancreatoduodenectomy based on audits are lacking. This study aimed to compare the German and Dutch audits for external data validation. METHODS: Anonymized data from patients undergoing pancreatoduodenectomy between 2014 and 2016 were extracted from the German Society for General and Visceral Surgery StuDoQ|Pancreas and Dutch Pancreatic Cancer Audit, and compared using descriptive statistics. Univariable and multivariable risk analyses were undertaken. RESULTS: Overall, 4495 patients were included, 2489 in Germany and 2006 in the Netherlands. Adenocarcinoma was a more frequent indication for pancreatoduodenectomy in the Netherlands. German patients had worse ASA fitness grades, but Dutch patients had more pulmonary co-morbidity. Dutch patients underwent more minimally invasive surgery and venous resections, but fewer multivisceral resections. No difference was found in rates of grade B/C postoperative pancreatic fistula, grade C postpancreatectomy haemorrhage and in-hospital mortality. There was more centralization in the Netherlands (1·3 versus 13·3 per cent of pancreatoduodenectomies in very low-volume centres; P < 0·001). In multivariable analysis, both hospital stay (difference 2·49 (95 per cent c.i. 1·18 to 3·80) days) and risk of reoperation (odds ratio (OR) 1·55, 95 per cent c.i. 1·22 to 1·97) were higher in the German audit, whereas risk of postoperative pneumonia (OR 0·57, 0·37 to 0·88) and readmission (OR 0·38, 0·30 to 0·49) were lower. Several baseline and surgical characteristics, including hospital volume, but not country, predicted mortality. CONCLUSION: This comparison of the German and Dutch audits showed variation in case mix, surgical technique and centralization for pancreatoduodenectomy, but no difference in mortality and pancreas-specific complications.


Assuntos
Auditoria Médica , Pancreaticoduodenectomia/normas , Padrões de Prática Médica/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos , Avaliação de Resultados em Cuidados de Saúde , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/mortalidade , Pancreaticoduodenectomia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros
5.
Pathologe ; 39(Suppl 2): 231-235, 2018 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-30361775

RESUMO

BACKGROUND: In histopathological routine diagnostics, three-dimensional tissue samples are analyzed histologically and/or immunohistochemically in two-dimensional sectional planes due to the high expenditure of time and the lack of digitization possibilities. AIM: Here, we demonstrate the application of three-dimensional reconstruction to solid tumors and analyze inter-/intratumoral heterogeneity with respect to epithelial-mesenchymal transition (EMT). METHODS: Tissue samples from pancreatic, lung, colorectal, and breast cancers as well as colorectal liver metastases were serially processed in 4µm sections. For individual analyses, alternating stains (cytokeratin AE1/3, zinc finger E­box-binding homeobox 1 (ZEB1), eCadherin) were performed. Subsequently, the tumor cells were analyzed for their morphology (epitheloid amoeboid, mesenchymal) and the expression of ZEB1 and eCadherin. For statistical analysis, all tumor cell aggregates were hierarchically annotated and analyzed. RESULTS: Tumor buds are predominantly associated with the main tumor mass. Furthermore, a shutteling of eCadherin could be observed within tumor cell aggregates smaller than nine cells. ZEB1 is only increasingly expressed in tumor cell groups smaller than five cells. CONCLUSIONS: The initial tumor budding and the subsequent decoupling of the tumor bud from the main tumor mass is most likely a two-part process. However, the EMT is not statistically significantly increased within the tumor bud detached from the main tumor mass. It could be shown that the currently valid and known definition of a tumor bud as a cell cluster of less than or equal to five cells cannot be completely classified in the concept of EMT represented by eCadherin and ZEB1.


Assuntos
Neoplasias da Mama , Neoplasias Hepáticas , Caderinas , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Humanos , Imageamento Tridimensional , Homeobox 1 de Ligação a E-box em Dedo de Zinco
6.
Transl Oncol ; 11(6): 1307-1322, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30172883

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with frequent post-surgical local recurrence. The combination of adjuvant chemotherapy with radiotherapy is under consideration to achieve a prolonged progression-free survival (PFS). To date, few studies have determined the proteome profiles associated with response to adjuvant chemoradiation. We herein analyzed the proteomes of primary PDAC tumors subjected to additive chemoradiation after surgical resection and achieving short PFS (median 6 months) versus prolonged PFS (median 28 months). Proteomic analysis revealed the overexpression of Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) and Monoamine Oxidase A (MAOA) in the short PFS cohort, which were corroborated by immunohistochemistry. In vitro, specific inhibition of ALDH1A1 by A37 in combination with gemcitabine, radiation, and chemoradiation lowered cell viability and augmented cell death in MiaPaCa-2 and Panc 05.04 cells. ALDH1A1 silencing in both cell lines dampened cell proliferation, cell metabolism, and colony formation. In MiaPaCa-2 cells, ALDH1A1 silencing sensitized cells towards treatment with gemcitabine, radiation or chemoradiation. In Panc 05.04, increased cell death was observed upon gemcitabine treatment only. These findings are in line with previous studies that have suggested a role of ALDH1A1 chemoradiation resistance, e.g., in esophageal cancer. In summary, we present one of the first proteome studies to investigate the responsiveness of PDAC to chemoradiation and provide further evidence for a role of ALDH1A1 in therapy resistance.

8.
Chirurg ; 89(1): 32-39, 2018 01.
Artigo em Alemão | MEDLINE | ID: mdl-29197019

RESUMO

Quality indicators are by definition indirect measures of quality. The selection for the field of pancreatic surgery was based on the clinical relevance and controllability, scientific evidence and the practicability of data acquisition. In terms of outcome quality, hospital mortality, the composite endpoint MTL30 (mortality-transfer-length of stay), and major complications (Clavien-Dindo classification grades 3b and 4) were chosen as being essential. With respect to structural quality, the presence of interventional radiology with constant availability was considered essential. To evaluate target values two strategies were used: a systematic literature search and evaluation of the current numbers from the German Society for General and Visceral Surgery (DGAV) StuDoQ|Pancreas registry for the years 2014-2016. The results are presented in the following consensus statement.


Assuntos
Pâncreas , Neoplasias Pancreáticas , Indicadores de Qualidade em Assistência à Saúde , Consenso , Mortalidade Hospitalar , Humanos , Pâncreas/cirurgia , Neoplasias Pancreáticas/cirurgia , Sistema de Registros
9.
Chirurg ; 88(11): 977-982, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-28761965

RESUMO

From a sociopolitical aspect there is increasing interest in the quality of healthcare. In this context valid, reproducible, comparable and risk-adjustable markers that are easily identified have become crucial for consistent documentation of quality. We recommend MTL30 (mortality, transfer, length of stay) as one of these markers to consistently measure the quality of large visceral surgical interventions. The MTL30 subsumes a number of known markers that may help to predict postoperative complications. The MTL30 is considered to be fulfilled when a patient on the 30th day following surgery, a) has died b) is still in the hospital or c) has been transferred to another acute care hospital. The evaluation of the StuDoQ register of the German Society for General and Visceral Surgery (DGAV) shows that MTL30 occurs significantly more often than any of the individual parameters. The correlation between MTL30 and other patient-specific risk factors, e.g. American Society of Anesthesiologists classification (ASA), age, etc. enables a risk adjustment.


Assuntos
Biomarcadores , Cirurgia Geral/normas , Garantia da Qualidade dos Cuidados de Saúde/normas , Sistema de Registros , Sociedades Médicas , Procedimentos Cirúrgicos Operatórios/normas , Vísceras/cirurgia , Alemanha , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/mortalidade
11.
Surg Today ; 47(3): 271-279, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27236779

RESUMO

PURPOSE: To assess the available evidence on the prognostic factors for the 5-year survival for patients with distal cholangiocarcinoma (DCC) following surgical resection. METHODS: We performed a comprehensive search of abstracts included in databases where relevant studies were published between January 2000 and August 2015. Risk ratios (RRs), 95 % confidence intervals (95 % CIs), and random-effects model were calculated using RevMan 5.3 software. RESULTS: A total of 23 observational studies involving 2063 patients with DCC were analyzed. The meta-analysis showed that postoperative adjuvant chemotherapy was not confirmed as a prognostic factor, with similar 5-year survival rates between those receiving and not receiving chemotherapy (RR 0.71; 95 % CI 0.21-2.36; P = 0.57). Perineural invasion (RR 0.51; 95 % CI 0.40-0.64; P < 0.00001), lymph node metastasis (RR 0.51; 95 % CI 0.38-0.70; P < 0.0001), positive resection margin status (RR 2.11; 95 % CI 1.36-3.30; P = 0.001), and not-well-differentiated adenocarcinoma (RR 1.77; 95 % CI 1.39-2.25; P < 0.00001) were associated with shorter survival. CONCLUSIONS: Perineural invasion, lymph node metastasis, resection margin status, and tumor differentiation were the significant prognostic factors for the 5-year survival.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/cirurgia , Idoso , Neoplasias dos Ductos Biliares/patologia , Quimioterapia Adjuvante , Colangiocarcinoma/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias de Tecido Nervoso/patologia , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
Chirurg ; 88(1): 11-17, 2017 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-27844112

RESUMO

BACKGROUND: Pancreaticojejunostomy and pancreaticogastrostomy are the two techniques for pancreatic anastomosis that are widely established for the reconstruction after pancreaticoduodenectomy. Pancreaticogastrostomy is the most recent and to date less frequently performed method, the history, techniques and indications of which are presented. METHOD: Review of the literature and current evidence. RESULTS: Current evidence from randomized controlled trials and meta-analyses does not demonstrate significant differences in complication rates or pancreatic function after pancreaticogastrostomy versus pancreaticojejunostomy. CONCLUSION: Pancreaticogastrostomy is the technically less demanding procedure, offering at least the same level of safety as pancreaticojejunostomy. Minimally invasive and parenchyma-sparing procedures provide new areas of application for this anastomotic technique.


Assuntos
Anastomose Cirúrgica/métodos , Gastrostomia/métodos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Seguimentos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pancreatectomia/métodos , Testes de Função Pancreática , Neoplasias Pancreáticas/mortalidade , Pancreaticojejunostomia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Taxa de Sobrevida
13.
Clin Genet ; 90(4): 343-50, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26916598

RESUMO

The basal transcription of heme oxygenase-1 (HO-1) regulation is dependent upon a GT repeat germ line polymorphism (GTn) in the promoter of the HO-1 gene. We determined the prognostic value of HO-1 promoter polymorphism on the natural postoperative course of complete resected oesophageal cancer. Genomic DNA from 297 patients was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters, disseminated tumour cells in bone marrow (DTC) and clinical outcome. Depending on short allele with <25 and long allele with ≥25, GTn repeats three genotypes (SS, SL and LL) were defined. A diverse role of GTn was evident in squamous cell carcinoma (SCC) and adenocarcinoma (AC). In SCC, the SS genotype presented less advanced tumours with lower rate DTC in bone marrow and relapse compared with L-allele carriers. In contrast, AC patients with the SS genotype displayed a complete opposing tumour characteristic. The disease-free (DFS) and overall survival (OS) in SCC patients was markedly reduced in LL genotypes (p < 0.001). In AC contrarily the SS genotype patients displayed the worst DFS and OS (p < 0.001). GTn is a strong prognostic factor with diverse prognostic value for recurrence and survival in AC and SCC.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Heme Oxigenase-1/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Análise Mutacional de DNA , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Heme Oxigenase-1/química , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Sequências Repetitivas de Ácido Nucleico , Resultado do Tratamento
14.
Ann Surg ; 263(3): 440-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26135690

RESUMO

OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.


Assuntos
Pancreatopatias/cirurgia , Pancreaticoduodenectomia , Pancreaticojejunostomia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Hemorragia/epidemiologia , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/mortalidade , Fístula Pancreática/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco
15.
Mol Oncol ; 10(1): 40-58, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26304112

RESUMO

Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome ("secretome"), including reduced levels of anti-angiogenic factors, elevated levels of transforming growth factor (TGF) ß, and an impact on matrix processing enzymes. Functionally, FAPα mildly induces sprout formation by human umbilical vein endothelial cells. Moreover, loss of FAPα leads to a more epithelial cellular phenotype and this effect was rescued by exogenous application of TGFß. In collagen contraction assays, FAPα induced a more contractile cellular phenotype. To characterize the proteolytic profile of FAPα, we investigated its specificity with proteome-derived peptide libraries and corroborated its preference for cleavage carboxy-terminal to proline residues. By "terminal amine labeling of substrates" (TAILS) we explored FAPα-dependent cleavage events. Although FAPα acts predominantly as an amino-dipeptidase, putative FAPα cleavage sites in collagens are present throughout the entire protein length. In contrast, putative FAPα cleavage sites in non-collagenous proteins cluster at the amino-terminus. The degradomic study highlights cell-contextual proteolysis by FAPα with distinct positional profiles. Generally, our findings link FAPα to key aspects of CAF biology and attribute an important role in tumor-stroma interaction to FAPα.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Gelatinases/fisiologia , Proteínas de Membrana/fisiologia , Proteínas de Neoplasias/metabolismo , Proteoma , Serina Endopeptidases/fisiologia , Células Estromais/metabolismo , Linhagem Celular Tumoral , Endopeptidases , Fibroblastos/metabolismo , Humanos , Proteólise , Fator de Crescimento Transformador beta/metabolismo
16.
Chirurg ; 86(9): 855-60, 2015 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-26319178

RESUMO

Hernias are among the most common long-term complications after bariatric surgery. Besides incisional hernias, which occur very often after conventional open bariatric surgery, internal hernias after bariatric surgery constitute a special challenge. The incidence of internal hernias after bariatric surgery is more common than for other upper gastrointestinal tract operations. Internal hernias are not limited to laparoscopic procedures but are also observed after conventional open gastric bypass surgery. As the incidence is significantly increased after laparoscopic interventions, there seems to be a close association with minimally invasive procedures. The clinical symptoms of internal hernias without complete obstruction are non-specific and the correct diagnosis is often not straightforward. In addition to the aspects of prevention of internal hernias in laparoscopic surgery, this article discusses the diagnosis and treatment, taking into account the various forms of internal hernia after bariatric operations.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Hérnia Ventral/cirurgia , Complicações Pós-Operatórias/cirurgia , Seguimentos , Derivação Gástrica/efeitos adversos , Hérnia Ventral/diagnóstico , Hérnia Ventral/etiologia , Humanos , Laparoscopia/efeitos adversos , Mesentério/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Reoperação
17.
BMC Genomics ; 16: 559, 2015 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-26220445

RESUMO

BACKGROUND: Formalin-fixed, paraffin-embedded (FFPE) tissues represent the most abundant resource of archived human specimens in pathology. Such tissue specimens are emerging as a highly valuable resource for translational proteomic studies. In quantitative proteomic analysis, reductive di-methylation of primary amines using stable isotopic formaldehyde variants is increasingly used due to its robustness and cost-effectiveness. RESULTS: In the present study we show for the first time that isotopic amine dimethylation can be used in a straightforward manner for the quantitative proteomic analysis of FFPE specimens without interference from formalin employed in the FFPE process. Isotopic amine dimethylation of FFPE specimens showed equal labeling efficiency as for cryopreserved specimens. For both FFPE and cryopreserved specimens, differential labeling of identical samples yielded highly similar ratio distributions within the expected range for dimethyl labeling. In an initial application, we profiled proteome changes in clear cell renal cell carcinoma (ccRCC) FFPE tissue specimens compared to adjacent non-malignant renal tissue. Our findings highlight increased levels of glyocolytic enzymes, annexins as well as ribosomal and proteasomal proteins. CONCLUSION: Our study establishes isotopic amine dimethylation as a versatile tool for quantitative proteomic analysis of FFPE specimens and underlines proteome alterations in ccRCC.


Assuntos
Aminas/química , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Proteoma/análise , Proteômica , Isótopos de Carbono/química , Carcinoma de Células Renais/metabolismo , Cromatografia Líquida de Alta Pressão , Formaldeído/química , Humanos , Marcação por Isótopo , Neoplasias Renais/metabolismo , Inclusão em Parafina , Espectrometria de Massas em Tandem
18.
J Pathol ; 234(3): 410-22, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25081610

RESUMO

Cancer cell invasion takes place at the cancer-host interface and is a prerequisite for distant metastasis. The relationships between current biological and clinical concepts such as cell migration modes, tumour budding and epithelial-mesenchymal transition (EMT) remains unclear in several aspects, especially for the 'real' situation in human cancer. We developed a novel method that provides exact three-dimensional (3D) information on both microscopic morphology and gene expression, over a virtually unlimited spatial range, by reconstruction from serial immunostained tissue slices. Quantitative 3D assessment of tumour budding at the cancer-host interface in human pancreatic, colorectal, lung and breast adenocarcinoma suggests collective cell migration as the mechanism of cancer cell invasion, while single cancer cell migration seems to be virtually absent. Budding tumour cells display a shift towards spindle-like as well as a rounded morphology. This is associated with decreased E-cadherin staining intensity and a shift from membranous to cytoplasmic staining, as well as increased nuclear ZEB1 expression.


Assuntos
Adenocarcinoma/patologia , Transição Epitelial-Mesenquimal , Invasividade Neoplásica/patologia , Biomarcadores Tumorais/análise , Humanos , Imageamento Tridimensional , Imuno-Histoquímica
19.
J Gastrointest Surg ; 18(3): 464-75, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24448997

RESUMO

BACKGROUND: Postpancreatectomy hemorrhage is a rare but often severe complication after pancreatic resection. The aim of this retrospective study was to define incidence and risk factors of postpancreatectomy hemorrhage and to evaluate treatment options and outcome. PATIENTS AND METHODS: Clinical data was extracted from a prospectively maintained database. Descriptive statistics, univariate and multivariate risk factor analysis by binary logistic regression were performed with SPSS software at a significance level of p = 0.05. RESULTS: N = 1,082 patients with pancreatic resections between 1994 and 2012 were included. Interventional angiography was successful in about half of extraluminal bleeding. A total of 78 patients (7.2 %) had postpancreatectomy hemorrhage (PPH), and 29 (2.7 %) were grade C PPH. Multivariate modeling disclosed a learning effect, age, BMI, male sex, intraoperative transfusion, portal venous and multivisceral resection, pancreatic fistula and preoperative biliary drainage as independent predictors of severe postpancreatectomy hemorrhage. High-risk histopathology, age, transfusion, pancreatic fistula, postpancreatectomy hemorrhage and pancreatojejunostomy in pancreatoduodenectomies were independent predictors of mortality. CONCLUSIONS: Our study identifies clinically relevant risk factors for postpancreatectomy hemorrhage and mortality. Interventional treatment of extraluminal hemorrhage is successful in about half of the cases and if unsuccessful constitutes a valuable adjunct to operative hemostasis. Based on our observations, we propose a treatment scheme for PPH. Risk factor analysis suggests appropriate patient selection especially for extended resections and pancreatogastrostomy for reconstruction in pancreatoduodenectomy.


Assuntos
Hemostase Endoscópica , Pancreatectomia/mortalidade , Fístula Pancreática/mortalidade , Hemorragia Pós-Operatória , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Angiografia , Transfusão de Sangue , Índice de Massa Corporal , Criança , Competência Clínica , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Pancreatopatias/patologia , Pancreatopatias/cirurgia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/mortalidade , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/mortalidade , Hemorragia Pós-Operatória/terapia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Adulto Jovem
20.
Chirurg ; 82(8): 691-7, 2011 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-21340587

RESUMO

BACKGROUND: Whereas pancreatic tail resection is routinely and safely performed in several institutions, laparoscopic resection of the pancreatic head is only performed by a handful of surgeons worldwide, none of them in Germany. PATIENTS AND METHODS: We review our experience with 9 laparoscopic pancreatic head resections (lap-PPPD) performed between March and September 2010. The operations were performed using a hybrid approach with complete laparoscopic pylorus-preserving pancreatic head resection and successive reconstruction via a small retrieval incision. Perioperative outcome was compared to 605 open pancreatic head resections (1997-2010). RESULTS: In the group lap-PPPD 3 out of 9 conversions had to be performed due to oncologic reasons. There were no significant differences in perioperative outcome when comparing open-PPPD to lap-PPPD. CONCLUSION: Laparoscopic pancreatic head resection with hybrid open reconstruction combines the potential advantages of laparoscopic resection with the safety of an open pancreatic anastomosis. Even at the beginning of the learning curve the procedure can be performed with no concessions to safety or duration of the operation.


Assuntos
Ampola Hepatopancreática/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Laparoscopia/métodos , Tumores Neuroendócrinos/cirurgia , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreatite Crônica/cirurgia , Complicações Pós-Operatórias/etiologia , Lesões Pré-Cancerosas/cirurgia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Complicações Intraoperatórias/cirurgia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia/métodos , Reoperação , Estudos Retrospectivos
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