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1.
Pancreatology ; 24(2): 314-322, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38310036

RESUMO

BACKGROUND/OBJECTIVES: Pancreatic surgery may have a long-lasting effect on patients' health status and quality of life (QoL). We aim to evaluate patient-reported outcomes (PRO) 3 months after pancreatic surgery. METHODS: Patients scheduled for pancreatic surgery were enrolled in a prospective trial at five German centers. Patients completed PRO questionnaires (EQ-5D-5L, EORTC QLQ-PAN26, patient-reported happiness, and HADS-D), we report the first follow-up 3 months after surgery as an interim analysis. Statistical testing was performed using R software. RESULTS: From 2019 to 2022 203 patients were enrolled, a three-month follow-up questionnaire was available in 135 (65.5 %). 77 (57.9 %) underwent surgery for malignant disease. Patient-reported health status (EQ-5D-5L) was impaired in 4/5 dimensions (mobility, self-care, usual activities, pain, discomfort) for patients with malignant and 3/5 dimensions (mobility, self-care, usual activities) for patients with benign disease 3 months after surgery (p < 0.05). Patients with malignant disease reported an increase in depressive symptoms, patients with benign disease had a decrease in anxiety symptoms (HADS-D; depression: 5.00 vs 6.51, p = 0.002; anxiety: 8.04 vs. 6.34, p = 0.030). Regarding pancreatic-disease-specific symptoms (EORTC-QLQ-PAN26), patients with malignant disease reported increased problems with taste, weight loss, weakness in arms and legs, dry mouth, body image and troubling side effects at three months. Patients with benign disease indicated more weakness in arms and legs, troubling side effects but less future worries at three months. CONCLUSION: Patient-reported outcomes of patients undergoing pancreatic surgery for benign vs. malignant disease show important differences. Patients with malignant tumors report more severely decreased quality of life 3 months postoperatively than patients with benign tumors.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias , Humanos , Estudos Prospectivos , Qualidade de Vida , Medidas de Resultados Relatados pelo Paciente
2.
Langenbecks Arch Surg ; 409(1): 108, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570375

RESUMO

PURPOSE: Intraabdominal infections (IAI) are increasing worldwide and are a major contributor to morbidity and mortality. Among IAI, the number of multi-drug resistant organisms (MDRO) is increasing globally. We tested the Unyvero A50® for intraabdominal infections, compared the detected microorganisms and antibiotic resistance, and compared the results with those of routine microbiology. METHODS: We prospectively compared samples obtained from surgical patients using PCR-based Unyvero IAI cartridges against routine microbiology for the detection of microorganisms. Additionally, we identified clinical parameters that correlated with the microbiological findings. Data were analyzed using the t-test and Mann-Whitney U test. RESULTS: Sixty-two samples were analyzed. The PCR system identified more microorganisms, mostly Bacteroides species, Escherichia coli, and Enterococcus spp. For bacterial resistance, the PCR system results were fully concordant with those of routine microbiology, resulting in a sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of 100%. The sensitivity, specificity, PPV, and NPV for the detection of microorganisms were 74%, 58%, 60%, and 72%, respectively. CRP levels were significantly higher in patients with detectable microorganisms. We identified more microorganisms and bacterial resistance in hospital-acquired intra-abdominal infections by using the PCR system. DISCUSSION: IAI warrants early identification of the microorganisms involved and their resistance to allow for adequate antibiotic therapy. PCR systems enable physicians to rapidly adjust their antibiotic treatment. Conventional microbiological culture and testing remain essential for determining the minimal growth inhibition concentrations for antibiotic therapy.


Assuntos
Infecção Hospitalar , Infecções Intra-Abdominais , Humanos , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/tratamento farmacológico , Antibacterianos/uso terapêutico , Valor Preditivo dos Testes , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Reação em Cadeia da Polimerase
3.
J Cell Mol Med ; 27(14): 2082-2092, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37390227

RESUMO

GP-2250, a novel anticancer agent, severely limits the energy metabolism, as demonstrated by the inhibition of hexokinase 2 and glyceraldehyde-3-phosphate dehydrogenase and a decrease of ATP. Rescue experiments with supplementary pyruvate or oxaloacetate demonstrated that a TCA cycle deficit largely contributed to cytotoxicity. Activation of the energy-deficit sensor, AMP-dependent protein kinase, was associated with increased phosphorylation of acetyl-CoA carboxylase and Raptor, pointing to a possible deficit in the synthesis of fatty acids and proteins as essential cell components. Binding of p65 to DNA was dose-dependently reduced in nuclear lysates. A transcriptional deficit of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) was substantiated by the downregulation of cyclin D1 and of the anti-apoptotic Bcl2, in line with reduction in tumour cell proliferation and induction of apoptosis, respectively. The upregulation of p53 concomitant with an excess of ROS supported apoptosis. Thus, the anticancer activity of GP-2250 is a result of disruption of energy metabolism and inhibition of tumour promotion by NF-κB.


Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Humanos , NF-kappa B/metabolismo , Adenilato Quinase/metabolismo , Quinase I-kappa B/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Apoptose , Fosforilação , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Metabolismo Energético , Neoplasias Pancreáticas
4.
Gastroenterology ; 163(5): 1407-1422, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35870514

RESUMO

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature. METHODS: We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance. RESULTS: The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-9 >2 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-9 <37 U/mL, 39.7%, 94.1%, and 76.3%, respectively. CONCLUSIONS: The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatite Crônica , Humanos , Antígeno CA-19-9 , Biomarcadores Tumorais , Curva ROC , Estudos de Casos e Controles , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/diagnóstico , Padrões de Referência , Carboidratos , Neoplasias Pancreáticas
5.
Pathobiology ; 90(2): 71-80, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35691289

RESUMO

INTRODUCTION: Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published. METHODS: We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2. RESULTS: Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis. DISCUSSION/CONCLUSION: Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismo , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Instabilidade de Microssatélites , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/análise , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo
6.
HPB (Oxford) ; 25(6): 667-673, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36842945

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) as well as postoperative biliary fistula (POBF) are considered the main source of postoperative morbidity and mortality after pancreatoduodenectomy (PD). However, little is known about the incidence and complications of combined POPF/POBF compared to isolated POPF or POBF. METHODS: This single-center study investigated retrospectively the incidence and postoperative outcome of combined POPF/POBF compared to isolated fistulas following PD in a tertiary German pancreatic center between 2009 and 2018. RESULTS: A total of 678 patients underwent PD for benign and malignant periampullary lesions. Combined fistulas occurred in 6%, isolated POPF in 16%, and isolated POBF in 2%. Pancreatic ductal adenocarcinoma and chronic pancreatitis had a protective effect on the occurrence of combined fistulas, whereas serous cystadenoma and pancreatic metastasis were risk factors. Morbidity (Grade C fistula, post-pancreatectomy hemorrhage, revisional surgery) and mortality was significantly higher in patients with combined fistulas than in those with isolated fistula. Moreover, the duration of ICU stay was longer. CONCLUSIONS: A combined POPF/POBF is associated with a significant increase of morbidity and mortality compared to isolated fistulas after PD. Early surgical revision in these patients may improve the postoperative survival rate.


Assuntos
Fístula Biliar , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomia/efeitos adversos , Estudos Retrospectivos , Fístula Biliar/complicações , Fístula Biliar/cirurgia , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Fístula Pancreática/epidemiologia , Neoplasias Pancreáticas/patologia , Fatores de Risco , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/epidemiologia
7.
Z Gastroenterol ; 60(10): 1517-1527, 2022 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-34820808

RESUMO

Due to its rising incidence, pancreatic neoplasia, which mainly include adenocarcinomas, neuroendocrine and cystic neoplasia of the pancreas, is becoming increasingly relevant in everyday clinical practice.Based on a systematic literature search, a working group of pancreatic experts developed evidence-based recommendations for surgical indications in pancreatic neoplasia to improve the quality.There is a clear surgical indication for primary or secondary resectable pancreatic carcinomas without metastasis, for functionally active, symptomatic and functionally inactive neuroendocrine neoplasia of more than 2 cm in size and for cystic neoplasm with symptoms or signs of malignancy including all intraductal papillary-mucinous neoplasia (IPMN) of the main duct and mixed type, all mucinous-cystic neoplasia (MCN) > 4 cm and all solid pseudopapillary neoplasia (SPN). Surgery can be indicated for pancreatic carcinomas with isolated arterial vascular infiltration or for long periods of stable oligometastasis, regarding neuroendocrine neoplasias for metastasis or debulking surgery as well as for branch-duct IPMN with risk criteria and MCN <4 cm. There is no primary indication for surgery in locally advanced and metastatic pancreatic cancer or asymptomatic serous-cystic neoplasia (SCN).The indication for surgery should always be individualized taking into account age, comorbidities and patient wishes.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/cirurgia , Humanos , Pâncreas/patologia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas
8.
Int J Mol Sci ; 23(13)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35806313

RESUMO

Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.


Assuntos
Antineoplásicos , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Humanos , Mesotelioma/patologia , Mitomicina/farmacologia , Mitomicina/uso terapêutico , Necrose/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico
9.
Gut ; 70(11): 2150-2158, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33541865

RESUMO

OBJECTIVE: Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management. DESIGN: We conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines. A signature to distinguish CP from controls (n=160) was identified using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry on ethylenediaminetetraacetic acid (EDTA)-plasma and validated in independent cohorts. RESULTS: A Naive Bayes algorithm identified eight metabolites of six ontology classes. After algorithm training and computation of optimal cut-offs, classification according to the metabolic signature detected CP with an area under the curve (AUC) of 0.85 ((95% CI 0.79 to 0.91). External validation in two independent cohorts (total n=502) resulted in similar accuracy for detection of CP compared with non-pancreatic controls in EDTA-plasma (AUC 0.85 (95% CI 0.81 to 0.89)) and serum (AUC 0.87 (95% CI 0.81 to 0.95)). CONCLUSIONS: This is the first study that identifies and independently validates a metabolomic signature in plasma and serum for the diagnosis of CP in large, prospective cohorts. The results could provide the basis for the development of the first routine laboratory test for CP.


Assuntos
Metabolômica , Pancreatite Crônica/sangue , Plasma , Teorema de Bayes , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Gasosa , Cromatografia Líquida , Feminino , Humanos , Masculino , Espectrometria de Massas , Valor Preditivo dos Testes , Prognóstico , Estudo de Prova de Conceito
10.
Br J Surg ; 109(1): 37-45, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34746958

RESUMO

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. METHODS: In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. RESULTS: Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). CONCLUSION: A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. REGISTRATION NUMBER: NCT02588066 (http://www.clinicaltrials.gov).


Assuntos
Hemostasia Cirúrgica/métodos , Artéria Hepática/cirurgia , Ligamentos/cirurgia , Pancreaticoduodenectomia/métodos , Hemorragia Pós-Operatória/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia/efeitos adversos
11.
Pancreatology ; 21(5): 983-989, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33840637

RESUMO

BACKGROUND: Current guidelines discourage surgery for serous cystic neoplasms (SCN) of the pancreas, because of their benign character, slow growth, and excellent prognosis. Nevertheless, SCN continue to contribute up to 30% of resected cystic pancreatic lesions worldwide. METHODS: Spectrum of indications and outcomes of surgery were analysed in a retrospective series of 133 SCN at a single high-volume center in Germany between 2004 and 2019. RESULTS: Relevant symptoms justified surgery in 60% of patients with SCN, while 40% underwent surgery because of preoperative diagnostic uncertainty about suspected malignancy. There were 4 malignant SCN (3%). Ninety-day mortality was 0.75%, major morbidity - 15%, 10-year survival - 95%. Risks of malignant transformation and of postoperative mortality were similarly low. CONCLUSIONS: Surgery is reasonable and safe for symptomatic patients with SCN. Preoperative diagnostic uncertainty is the main reason for futile resections of benign asymptomatic SCN. Conservative management with close initial surveillance should be the first choice for this population. Surgery for supposed SCN without symptoms is justified only in carefully selected patients with suspected malignancy.


Assuntos
Cistadenoma Seroso , Cisto Pancreático , Neoplasias Pancreáticas , Cistadenoma Seroso/cirurgia , Humanos , Pâncreas , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos
12.
Z Gastroenterol ; 59(3): 214-224, 2021 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-33506450

RESUMO

BACKGROUND: The support group "Arbeitskreis der Pankreatektomierten e. V. (AdP)" was founded in 1976 and is the largest group of individuals affected by pancreatic disease in Germany. Members of the AdP support patients with pancreatic disease. This patient-initiated, cross-sectional study intends to present the results of pancreatic surgery from the perspective of patients. METHODS: Since March the 3 rd, 2018, members of the AdP received a questionnaire with eleven categories of questions concerning their medical history. This data was gathered in a medical database and analysed. RESULTS: 625 members were operated upon, with 57.5 % receiving pancreaticoduodenectomy, 15.5 % distal pancreatectomy, 23.2 % total pancreatectomy, and 4.0 % another or unknown operation. 37.9 % were diagnosed with pancreatic cancer, 38.2 % with another type of pancreatic tumour, 25 % with pancreatitis, 4 % with autoimmune pancreatitis and 2.7 % with other rare entities.82 patients of 237 pancreatic cancer patients survived more than 5 years. 24.5 % of the 237 patients reported have a second primary malignancy and 13.9 % have close family members with pancreatic cancer.Weight loss after pancreatic surgery was dependant on the type of operation with the greatest after pancreatectomy (17.8 ±â€Š9.5 kg). The prevalence of diabetes was 54.1 %, the incidence of new onset perioperative diabetes 33.3 %. 91.5 % needed pancreatic enzyme replacement therapy, on average 189 417 IE/day. The reported quality of life was independent from type of surgery received. CONCLUSION: Following complex pancreatic surgery, patients are confronted with daily lifelong challenges. AdP members offering their shared experiences offer meaningful support to newly affected patients. Individuals affected by pancreatic disease could be an important but underutilised resource to studying these diseases.


Assuntos
Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/psicologia , Qualidade de Vida/psicologia , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia , Complicações Pós-Operatórias/mortalidade , Prevalência , Grupos de Autoajuda , Inquéritos e Questionários
13.
Hepatobiliary Pancreat Dis Int ; 20(3): 271-278, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33349608

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignant tumors due to unavailable screening methods, late diagnosis with a low proportion of resectable tumors and resistance to systemic treatment. Complete tumor resection remains the cornerstone of modern multimodal strategies aiming at long-term survival. This study was performed to investigate the overall rate of long-term survival (LTS) and its contributing factors. METHODS: This was a retrospective single-center analysis of consecutive patients undergoing pancreaticoduodenectomy (PD) for PDAC between 2007 and 2014 at the St. Josef Hospital, Ruhr University Bochum, Germany. Clinical and laboratory parameters were assessed and evaluated for prediction of LTS with Cox regression analysis. RESULTS: The overall rate of LTS after PD for PDAC was 20.4% (34/167). Median survival was 24 months regardless of adjuvant treatment. Carbohydrate antigen 19-9 levels, tumor grade, lymph vessel invasion, perineural invasion and reduced general condition were significantly associated with LTS in univariate analysis (P < 0.05). Serum levels of carbohydrate antigen 19-9, American Joint Committee on Cancer stage, tumor grade, abdominal pain, male, exocrine pancreatic insufficiency and duration of postoperative hospital stay were independent predictors of cancer survival in multivariable analysis. CONCLUSIONS: Cancer related characteristics are associated with LTS in multimodally treated patients after curative PDAC surgery.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Antígeno CA-19-9 , Carboidratos , Carcinoma Ductal Pancreático/cirurgia , Humanos , Masculino , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Pancreáticas
14.
Acta Chir Belg ; 121(1): 16-22, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31433745

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most common complication following distal pancreatectomy. This retrospective study investigated the effects of autologous fibrin sealant (Vivostat©) in reducing the incidence of POPF after distal pancreatectomy. METHODS: A matched pairs analysis was performed to compare the incidence of clinically relevant POPF of 41 patients who underwent a distal pancreatectomy with application of autologous fibrin sealant (Vivostat©) with a historical control group. RESULTS: Clinically relevant POPF were present in 11 patients in the study group (27%) and in 13 patients in the control group (32%, p = .639). No patient of the study group required emergency angiographic treatment for postoperative hemorrhage due to POPF, whereas three patients were identified in the control group (7%, p = .079). CONCLUSIONS: POPF cannot be prevented under treatment with autologous fibrin sealant (Vivostat©). We observed the tendency of a lower rate of postoperative pancreatic hemorrhage due to POPF. However, prospective randomized controlled studies are required.


Assuntos
Adesivo Tecidual de Fibrina , Fístula Pancreática , Adesivo Tecidual de Fibrina/uso terapêutico , Humanos , Incidência , Pancreatectomia/efeitos adversos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos
15.
BMC Gastroenterol ; 20(1): 403, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256637

RESUMO

BACKGROUND: Pancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI). This allows the study of digestive processes and pancreatic enzyme replacement therapies. However, detailed descriptions of the surgical procedure, perioperative management, a determination of exocrine pancreatic insufficiency are scarce in the literature. Data of the long-term health status of minipigs upon EPI induction are still not available. Therefore, the present study describes in detail an experimental approach to the induction of exocrine pancreatic insufficiency via pancreatic duct ligation in minipigs and the long term follow up of the animal's health state. METHODS: 14 Goettingen minipigs underwent pancreatic duct ligation via midline laparotomy for the induction of exocrine pancreatic insufficiency. Fecal fat content, fat absorption, chymotrypsin levels, body weight and blood vitamin and glucose levels were determined. RESULTS: Exocrine pancreatic insufficiency was successfully induced in 12 Goettingen minipigs. Two minipigs failed to develop exocrine insufficiency most likely due to undetected accessory pancreatic ducts. All animals tolerated the procedure very well and gained weight within 8 weeks after surgery without requiring pancreatic enzyme replacement therapy. The follow up for approx. 180 weeks showed a stable body weight and health state of the animals with normal blood glucose levels (Table 1). From approx. 130 weeks post pancreatic duct ligation, all animals were supplemented with pancreatic enzymes and vitamins resulting in blood concentrations almost within the reference range. CONCLUSIONS: Pancreatic duct ligation in minipigs is an excellent method of inducing exocrine pancreatic insufficiency. It is important to identify and ligate accessory pancreatic ducts since persistence of accessory ducts will lead to maintenance of exocrine pancreatic function. The EPI model caused no persistent side effects in the animals and has the potential to be used in long-term EPI studies with up to 100 weeks post-OP without supplementation with enzymes and vitamins.


Assuntos
Insuficiência Pancreática Exócrina , Animais , Insuficiência Pancreática Exócrina/etiologia , Seguimentos , Pâncreas/cirurgia , Ductos Pancreáticos/cirurgia , Suínos , Porco Miniatura
16.
Anesth Analg ; 131(2): 537-543, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31295179

RESUMO

BACKGROUND: Studies demonstrated that operating room personnel are exposed to anesthetic gases such as sevoflurane (SEVO). Measuring the gas burden is essential to assess the exposure objectively. Air pollution measurements and the biological monitoring of urinary SEVO and its metabolite hexafluoroisopropanol (HFIP) are possible approaches. Calculating the mass of inhaled SEVO is an alternative, but its predictive power has not been evaluated. We investigated the SEVO burdens of abdominal surgeons and hypothesized that inhaled mass calculations would be better suited than pollution measurements in their breathing zones (25 cm around nose and mouth) to estimate urinary SEVO and HFIP concentrations. The effects of potentially influencing factors were considered. METHODS: SEVO pollution was continuously measured by photoacoustic gas monitoring. Urinary SEVO and HFIP samples, which were collected before and after surgery, were analyzed by a blinded environmental toxicologist using the headspace gas chromatography-mass spectrometry method. The mass of inhaled SEVO was calculated according to the formula mVA = cVA·(Equation is included in full-text article.)·t·ρ VA aer. (mVA: inhaled mass; cVA: volume concentration; (Equation is included in full-text article.): respiratory minute volume; t: exposure time; and ρ VA aer.: gaseous density of SEVO). A linear multilevel mixed model was used for data analysis and comparisons of the different approaches. RESULTS: Eight surgeons performed 22 pancreatic resections. Mean (standard deviation [SD]) SEVO pollution was 0.32 ppm (0.09 ppm). Urinary SEVO concentrations were below the detection limit in all samples, whereas HFIP was detectable in 82% of the preoperative samples in a mean (SD) concentration of 8.53 µg·L (15.53 µg·L; median: 2.11 µg·L, interquartile range [IQR]: 4.58 µg·L) and in all postoperative samples (25.42 µg·L [21.39 µg·L]). The mean (SD) inhaled SEVO mass was 5.67 mg (2.55 mg). The postoperative HFIP concentrations correlated linearly to the SEVO concentrations in the surgeons' breathing zones (ß = 216.89; P < .001) and to the calculated masses of inhaled SEVO (ß = 4.17; P = .018). The surgeon's body mass index (BMI), age, and the frequency of surgeries within the last 24 hours before study entry did not influence the relation between HFIP concentration and air pollution or inhaled mass, respectively. CONCLUSIONS: The biological SEVO burden, expressed as urinary HFIP concentration, can be estimated by monitoring SEVO pollution in the personnel's individual breathing zone. Urinary SEVO was not an appropriate biomarker in this setting.


Assuntos
Poluentes Ocupacionais do Ar/urina , Anestésicos Inalatórios/urina , Monitoramento Ambiental/métodos , Exposição Ocupacional/prevenção & controle , Sevoflurano/urina , Cirurgiões , Adulto , Poluentes Ocupacionais do Ar/análise , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/análise , Procedimentos Cirúrgicos do Sistema Digestório/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/normas , Projetos Piloto , Estudos Prospectivos , Sevoflurano/administração & dosagem , Sevoflurano/análise , Cirurgiões/normas
17.
Z Gastroenterol ; 58(6): 533-541, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32544965

RESUMO

Colorectal cancer is one of the leading malignancies and still accounts for almost 25 000 deaths in Germany each year. Although there is accumulating data on the molecular basis, treatment and clinical outcome of patients within clinical trials evidence from the real-world setting is mostly lacking. We started the molecular registry trial Colopredict Plus in 2013 to collect clinical and molecular data from a real-world cohort of patients with early colon cancer stage II and III in 70 German colon cancer centers focusing on the prognostic impact of high microsatellite instability. In this interim report, we characterize a clinical cohort of 2615 patients, of whom 1787 tissue probes were analyzed. Microsatellite status was assessed using immunhistochemistry and fragment length analysis, with a concordance of 91.4 %. These established histopathological methods are sensitive and cost-effective. The median age was 72 years, significantly higher compared to clinical trial populations, with a median Charlson Comorbidity Index of 3. The stage-dependent incidence of microsatellite instability was 23.7 % and was associated with female gender, BRAF-mutation, UICC stage II and localization in the right colon. Survival calculated in disease free, relapse free and overall survival significantly differed between MSI-H and MSS, in favor of MSI-H patients. Multivariate age-adjusted analyses of relapse-free survival, disease-free survival, and overall survival highlighted microsatellite instability as a robust and positive prognostic marker for early colon cancer independent of age.


Assuntos
Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Instabilidade de Microssatélites , Repetições de Microssatélites/genética , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Sistema de Registros , Taxa de Sobrevida
18.
Acta Chir Belg ; 120(1): 30-34, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30614389

RESUMO

Background: Pancreatic cancer is a fatal disease most often diagnosed at an advanced stage. Most patients already suffer from irresectable tumor or distant metastases being most commonly found in the liver or the lung. However, cerebral metastases occur extremely rare.Methods: We performed a retrospective analysis of our database to identify all patients diagnosed with pancreatic cancer and cerebral metastases who underwent surgical treatment in our department from January 2004 to November 2016.Results: Only 0.2% (4 of 2492) were diagnosed with cerebral metastases. Two patients had surgical resection of the cerebral metastases. One patient underwent palliative radiation therapy and the fourth patient received only palliative therapy. Mean interval between initial diagnosis and development of brain metastases was 8.5 months (range 1-20). Mean survival period after diagnosis of brain metastases was 4.75 months (range 1-10).Conclusions: Cerebral metastases of pancreatic cancer occur extremely rare. They are associated with an advanced tumor stage, commonly liver and lung metastases. All patients presenting with neurological symptoms, multifocal metastases, and significantly elevated CA 19-9 levels are suspicious of sustaining cerebral metastases and should undergo brain imaging.


Assuntos
Adenocarcinoma/secundário , Neoplasias Encefálicas/secundário , Neoplasias Pancreáticas/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Zentralbl Chir ; 145(4): 365-373, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32599635

RESUMO

Neuroendocrine neoplasms of the pancreas (pNEN) have an increasing incidence and prevalence. Thus, this entity is of increasing clinical significance. Patients with pNEN become clinically apparent due to different and unspecific symptoms. Some tumours secrete hormones and peptides and become clinically symptomatic. In general, these tumours can metastasise early and even small tumours lead to distant metastases. Nonetheless, primary tumour size and grading are important prognostic factors. On the basis of a systematic literature research and the formulation of key issues according to the PICO system, therapeutic concepts were established. These concepts were evaluated with a Delphi process among the members of the pancreas research group and the indications for surgery group of the German Society of General and Visceral Surgery. Thus this article gives an overview of the surgical treatment modalities and indications for the treatment of pNEN. Surgery is still the gold standard in treatment and the only potential chance of cure. Surgery is indicated for sporadic as well as hereditary pNEN > 2 cm independent of the functional activity. A so called "wait and see" strategy might be indicated in smaller pNEN; however, there is little evidence for this approach. In this respect, pNEN of 1 - 2 cm represent a surgical indication. The treatment of hereditary pNEN is challenging and should be interdisciplinary. Even in the case of distant metastases, a curative approach might be feasible and multimodal treatment is indicated.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos
20.
Zentralbl Chir ; 145(4): 383-389, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32726816

RESUMO

Chronic pancreatitis is a recurrent disease with repeating exacerbations of inflammation of the pancreatic gland - associated with belt-like back pain. Without treatment, recurrent chronic pancreatitis leads to development of opioid-dependent pain. The chronic pancreatitis leads to recurrent hospital stays for the affected patient and socioeconomic challenges. In progress it can lead to local complications of chronic pancreatitis, such as formation of pseudocysts, biliary duct obstruction, duodenal obstruction or portal hypertension. The aim of this article is a detailed description of the indication for surgical therapy in chronic pancreatitis. The underlying analysis was a systematic literature research and evaluation, the formulation of key questions according to the PICO system and the evaluation of indications and key statements and questions, as implemented in a three level Delphi process among the members of the pancreas research group and the indications for the surgery group of the German Society of General and Visceral Surgery (DGAV). Surgical resection of the inflammatory pancreatic head pseudotumour, after initial conservative therapy, is a highly efficient therapy for the control of pain and the avoidance of complications in chronic pancreatitis. For this purpose, well evaluated surgical strategies are available. Delay in surgical therapy can lead to chronic pain, kachexia and malnutrition and increase complications of surgical therapy.


Assuntos
Pancreatite Crônica/cirurgia , Doença Crônica , Drenagem , Humanos , Pâncreas , Pancreatectomia
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