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1.
Ann Oncol ; 34(1): 91-100, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36209981

RESUMO

BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).


Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Desoxicitidina , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Albuminas , Paclitaxel , Terapia Neoadjuvante , Adjuvantes Imunológicos/uso terapêutico , Neoplasias Pancreáticas
2.
Strahlenther Onkol ; 197(1): 8-18, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32914237

RESUMO

PURPOSE: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. METHODS: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. RESULTS: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001). CONCLUSION: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Terapia Neoadjuvante , Oxaliplatina/administração & dosagem , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Complicações Pós-Operatórias , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Análise de Sobrevida , Gencitabina
3.
Acta Chir Belg ; 121(5): 314-319, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32374654

RESUMO

BACKGROUND: Late metastasizing into pancreatic tissue is a special hallmark of renal cell carcinomas (RCC). A very low prevalence leads to scarce data about therapy, prognosis and spreading pathways. The aim of the study was to analyze whether a high fat content in the pancreas facilitates RCC metastases formation. A model for density measurement of pancreatic tissue has been developed and evaluated. Pancreatic fat content was measured comparing Hounsfield units (HU) of CT scans. METHODS: In a consecutive single centre retrospective database of 3600 patients with pancreatic resections, only 12 patients (0.3%) cases of RCC metastases in the pancreas were found. HU were measured in 3 pancreatic regions: head, body and tail in patients' CT scans. HU values were compared to a control population and results aligned with recent literature. RESULTS: We revealed a prevalence of pancreatic metastases of RCC in 0.3% of cases. The formation of RCC in the pancreas occurred within 14 ± 5.6 years after initial diagnosis of RCC. 83.3% of the patients were alive after a follow-up period of up to 48 months. Clinical data analysis revealed an affinity for metastatic formation to lipomatous pancreas. This could be objectivized by HU analysis in CT scans. CONCLUSION: Pancreatic metastases occur late after the first diagnosis of renal carcinoma and show an affinity for lipomatous pancreatic tissues. Due to its rarity in occurrence, multicentric studies are highly recommended to further analyze this correlation between fatty pancreas and RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pancreáticas , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Pâncreas/diagnóstico por imagem , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos
4.
BMC Cancer ; 19(1): 979, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640628

RESUMO

BACKGROUND: One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer. METHODS: Pretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared. RESULTS: One hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05). CONCLUSION: Excellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors. TRIAL REGISTRATION: EudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Consenso , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Alemanha , Humanos , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Prospectivos , Cirurgiões/psicologia , Tomografia Computadorizada por Raios X
5.
J Environ Manage ; 241: 427-438, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31072637

RESUMO

Drinking water treatment plants (DWTPs) designed to remove natural organic matter (NOM) are challenged as concentrations of NOM in raw waters are increasing. Here, we assess seasonal differences in NOM quality and quantity, from raw waters to the distribution network, at three large DWTPs in Oslo, Stockholm and Helsinki. Samples, collected during stable stratification in both winter and summer and during the autumnal turnover, were analysed for NOM concentrations and composition. The NOM was characterized by common routine parameters, size and content (TFF, LC-OCD, fluorescence) and biodegradability. The NOM concentration decreased to 2.5 mg/L (55%), 4.0 mg/L (48%) and 5.7 mg/L (76%) at the respective DWTPs in Oslo, Stockholm and Helsinki. The NOM in raw waters were predominantly in the largest size fraction (>50 kDa), in particular from Oslo. High MW fractions >50 kDa and humics remained the largest fractions with minimum 30% and maximum 80% of the total NOM. The BDOC in treated water <0.3 mg/L and the conditions in the distribution network imply low probability for bacteria regrowth. The multi-step treatment consisting of coagulation/flocculation, sedimentation, rapid sand filtration, ozonation and biological activated carbon filtration (BAC) was most effective in removing NOM. Coagulation/flocculation followed by sedimentation and sand filtration were critical, especially for the removal of biopolymers and humics, and somewhat for building blocks. The sand filtration provided up to 25% additional removal of biopolymers and below 7% removal of other fractions. The ozonation and BAC was more effective and removed 11% of biopolymers, and about 35% of building blocks and LMW neutrals.


Assuntos
Água Potável , Purificação da Água , Clima Frio , Filtração , Compostos Orgânicos
7.
Internist (Berl) ; 59(3): 282-287, 2018 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-28864828

RESUMO

Two female patients were admitted due to ketoacidosis. Serum glucose was moderately elevated. The patients exhibited abdominal and neurologic symptoms. Treatment consisted of metformin, insulin glargin and empagliflozin, as well as glimepiride, insulin detemir and empagliflozin, respectively. Treatment with intravenous fluid replacement, insulin, glucose, potassium and buffer solution led to a normalisation of pH and serum glucose levels. Our report describes two cases of atypical ketoacidosis with moderately elevated serum glucose during sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/efeitos adversos , Cetose/induzido quimicamente , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Glicemia/metabolismo , Cuidados Críticos , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Hidratação , Glucosídeos/uso terapêutico , Humanos , Cetose/sangue , Cetose/diagnóstico , Cetose/terapia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
8.
BMC Cancer ; 17(1): 216, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28340556

RESUMO

BACKGROUND: Former studies already revealed the anti-neoplastic properties of the anti-infective agent Taurolidine (TRD) against many tumor species in vitro and in vivo. Its anti-proliferative and cell death inducing capacity is largely due to its main derivative Taurultam (TRLT). In this study it could be demonstrated, that substance 2250 - a newly defined innovative structural analogue of TRLT - exhibits an anti-neoplastic effect on malignant pancreatic carcinoma in vitro and in vivo. METHODS: The anti-neoplastic potential of substance 2250 as well as its mode of action was demonstrated in extensive in vitro analysis, followed by successful and effective in vivo testings, using xenograft models derived from established pancreatic cancer cell lines as well as patient derived tissue. RESULTS: Our functional analysis regarding the role of oxidative stress (ROS) and caspase activated apoptosis showed, that ROS driven programmed cell death (PCD) is the major mechanisms induced by substance 2250 in pancreatic carcinoma. What is strongly relevant towards clinical practice is especially the observed inhibition of patient derived pancreatic cancer tumor growth in mice treated with this new substance in combination with its sharply higher metabolic stability. CONCLUSION: These encouraging results provide new therapeutical opportunities in pancreatic cancer treatment and build the basis for further functional analysis as well as first clinical studies for this promising agent.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Tiadiazinas/administração & dosagem , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Camundongos , Estrutura Molecular , Neoplasias Pancreáticas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tiadiazinas/química , Tiadiazinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Pancreáticas
9.
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
10.
Zentralbl Chir ; 141(6): 625-629, 2016 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-27501071

RESUMO

Background: Postoperative pancreatic fistulas (POPF) remain a major concern after distal pancreatectomy. Irrespective of the technique to close the pancreatic remnant, pancreatic fistulas will occur in approximately 30 % of patients undergoing distal pancreatectomy. For the first time ever, autologous fibrin sealant (Vivostat®) was used to additionally seal the pancreatic remnant after a distal pancreatectomy. The aim was to analyse whether this changes the postoperative outcome. Patients/Material and Methods: In 2015, a technical case series was performed in 15 patients who underwent distal pancreatectomy. The pancreatic remnant was additionally sealed with autologous fibrin sealant (Vivostat®). Results: A postoperative pancreatic fistula (POPF) occurred in 5/15 patients (33 %). One patient had a POPF grade A (1/15, 6.7 %), whereas a POPF grade B occurred in 4/15 patients (26.7 %). 75 % (3/4) of the patients with a POPF grade B were sufficiently treated with antibiotics, whereas a CT-guided percutaneous drainage had to be placed only in one case. Conclusion: Autologous fibrin sealant is simple to apply and seems to be well tolerated. However, it does not seem to avoid the development of postoperative pancreatic fistulas after distal pancreatectomy.


Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Pancreatectomia/métodos , Fístula Pancreática/prevenção & controle , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/cirurgia , Pancreatite Crônica/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/classificação , Fístula Pancreática/terapia , Resultado do Tratamento
11.
Internist (Berl) ; 57(4): 385-9, 2016 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-26873007

RESUMO

A 64-year-old woman presented with a history of recurrent hypoglycemia. A prolonged fasting test revealed an increased "amended" insulin-glucose ratio. Transabdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI) did not show abnormal results. An insulinoma was suspected based on a contrast-enhanced endoscopic US examination as well as a (68)gallium-DOTA-exendin-4 positron-emission tomography (PET)/CT. The diagnosis of an insulinoma was confirmed histologically after surgical removal of the tumor. Hypoglycemia did not occur during the postoperative period. The prolonged fasting test is the gold standard for the diagnosis of an insulinoma. Novel imaging procedures, such as contrast-enhanced endoscopic US or (68)gallium-DOTA-exendin-4 PET/CT are valuable additions to the diagnostic workup.


Assuntos
Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Insulinoma/complicações , Insulinoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Recidiva
12.
Ann Oncol ; 24(9): 2444-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23704195

RESUMO

BACKGROUND: Information about diagnosis, treatment options and prognosis has been emphasized as a key to empower cancer patients to make treatment decisions reflecting their values. However, surveys indicate that patients' preferences regarding information and treatment decision-making differ. In this qualitative interview study, we explored pancreatic cancer patients' perceptions and preferences on information and treatment decision-making. PATIENTS AND METHODS: Qualitative in-depth interviews with patients with pancreatic cancer. Purposive sampling and qualitative analysis were carried out. RESULTS: We identified two stages of information and treatment decision-making. Patients initially emphasize trust in their physician and indicate rather limited interest in details about surgical and medical treatment. In the latter stage of disease, patients perceive themselves more active regarding information seeking and treatment decision-making. All patients discuss their poor prognosis. Reflecting on their own situation, all patients interviewed pointed out that hope was an important driver to undergo further treatment also in advanced stages of the disease. Interviewees unanimously emphasized the difficulty of anticipating the time at which stopping cancer treatment would be the right decision. CONCLUSIONS: The findings can serve as starting point for reflection on professional decision-making in pancreatic cancer and larger representative surveys on ethical issues in treatment decision-making in pancreatic cancer.


Assuntos
Tomada de Decisões , Neoplasias Pancreáticas/terapia , Preferência do Paciente , Relações Médico-Paciente , Confiança , Adulto , Idoso , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Consentimento Livre e Esclarecido , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Satisfação do Paciente , Prognóstico , Inquéritos e Questionários
13.
Zentralbl Chir ; 138 Suppl 2: e55-62, 2013 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-22025359

RESUMO

The surveillance of patients with Barrett mucosa in the distal oesophagus leads to an increase of patients diagnosed with early cancer of the oesophagogastric junction and stomach with only superficial infiltration. Comparable to Asian countries where screening of patients at risk is recommended due to the high incidence of gastric cancer, endoscopic resection of early cancer in the stomach and distal oesophagus is increasing. In spite of the special endoscopic techniques--there are several requirements for the resected specimen which ensure its exact pathohistological evaluation. This is necessary to detect the exact depth of infiltration and the resection margins. To provide an exact pathohistological diagnosis is important for further therapeutic implications and prognosis. Advanced carcinomas of the oesophagus and stomach need multimodal treatment with radiation and chemotherapy. This has a special impact on the tumour which leads to pathohistological detectable changes as estimated in the so-called regression grading.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Esôfago de Barrett/patologia , Esôfago de Barrett/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Esofagoscopia , Terapia Neoadjuvante , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/classificação , Esôfago de Barrett/classificação , Carcinoma de Células Escamosas/classificação , Terapia Combinada , Neoplasias Esofágicas/classificação , Junção Esofagogástrica/patologia , Esôfago/patologia , Mucosa Gástrica/patologia , Humanos , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/classificação , Prognóstico
14.
Environ Technol ; 44(11): 1549-1565, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34839798

RESUMO

Solar radiation experiments showed a shift in the composition of natural organic matter (NOM). Due to irradiation, the concentration of high molecular weight (HMW) molecules decreased, and that of the low molecular weight (LMW) fraction increased. Microbiological analyses showed that biodegradation was neglectable. To assess the consequences for water treatment processes, coagulation jar tests were performed by comparing the removal effectivity for NOM fractions from irradiated and unirradiated raw water. The degree of dissolved organic carbon (DOC) removal by coagulation was lower for irradiated waters. As primarily HMW organic compounds are removed by coagulation, the decrease in coagulation performance is attributed to the increase in the LMW concentration due to photochemical reactions induced by solar radiation. Flocs were about 15% larger for irradiated water. Possibilities to adapt water treatment to respond to changes in DOC composition and concentration are outlined. Ozonation-biofiltration is judged as the most promising treatment process to cope with climate change-related challenges in drinking water treatment.


Assuntos
Água Potável , Purificação da Água , Purificação da Água/métodos , Compostos Orgânicos/análise , Matéria Orgânica Dissolvida , Biodegradação Ambiental
15.
J Cancer Res Clin Oncol ; 149(11): 9071-9083, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37171614

RESUMO

PURPOSE: The Oxathiazinane substance class is characterized by a high diversity of chemical structures yet to be fully investigated. Our research group recently proved that the 1.4.5-oxathiazine-4.4-dioxide, known as substance GP-2250, possesses antineoplastic properties as shown on pancreatic carcinoma. This current study aims to gain insights into the structure and activity relationship of a series of different Oxathiazinanes regarding their antineoplastic activity and the potential correlation with antibacterial activity. We investigated the newly synthesized Oxathiazinane derivatives: 2255, 2256, 2287, 2289, 2293 and 2296 in comparison to GP-2250. METHODS: The antineoplastic effect was evaluated in different cancer entities (breast, skin, pancreas and colon cancer cell lines) by viability, proliferation, and cell migration assays in vitro. Disc diffusion tests were performed on various bacteria strains to examine the antibacterial potential. Additionally, reactive oxygen species (ROS) assays were conducted to investigate mechanistic aspects. RESULTS: The substances GP-2250, 2293, 2289 and 2296 not only showed antineoplastic activity in four different cancer entities but also antibacterial effects, as tested on multiple bacteria strains including MRSA (Methicillin-resistant Staphylococcus aureus). Furthermore, these substances also induced high ROS levels up to 110% in the treated cancer cell lines compared to untreated control cells. These results indicate a correlation between an antineoplastic capacity and antibacterial properties of these derivatives. Both activities appear to be ROS driven. The Oxathiazinane derivatives 2255, 2256 and 2287 lacked both, antineoplastic and antibacterial activity. CONCLUSION: Thus, a comparable structure activity relationship became apparent for both the antineoplastic and antibacterial activity.


Assuntos
Antineoplásicos , Staphylococcus aureus Resistente à Meticilina , Humanos , Staphylococcus aureus Resistente à Meticilina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , Antineoplásicos/farmacologia , Antineoplásicos/química
16.
Diabetologia ; 55(5): 1346-54, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22286529

RESUMO

AIMS/HYPOTHESIS: Diabetes frequently develops in patients with pancreatic disorders. We aimed to determine the lower threshold of beta cell area for diabetes manifestation as well as the impact of insulin sensitivity on glucose homoeostasis in patients with pancreatic diabetes. METHODS: Eighty-two patients undergoing pancreatic surgery underwent pre-operative oral glucose challenge. Fractional pancreatic beta cell area was determined, and indices of insulin sensitivity and beta cell function were calculated. RESULTS: HbA1c and glucose levels were similar in patients with high and intermediate beta cell area, but were significantly higher in those with the lowest beta cell area (p < 0.0001). Insulin secretion was reduced only in patients with the lowest beta cell area (p < 0.001). The relative beta cell deficits at the onset of diabetes and impaired glucose tolerance were 64% and 21%, respectively, based on 2 h glucose levels. Deteriorating insulin sensitivity was associated with a small increase in the incidence of diabetes. CONCLUSIONS/INTERPRETATION: In conclusion, pancreatic diabetes probably develops after a reduction in beta cell area of ~65%. Post-challenge glucose excursions are much more closely related to pancreatic beta cell area than to fasting glycaemia, thereby underlining the usefulness of the OGTT in patients with pancreatic disorders.


Assuntos
Diabetes Mellitus/patologia , Células Secretoras de Insulina/patologia , Insulina/metabolismo , Pâncreas/patologia , Glicemia/metabolismo , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Humanos , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão
17.
Ann Oncol ; 23(3): 570-576, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21810728

RESUMO

Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.


Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Projetos de Pesquisa , Antineoplásicos/farmacologia , Europa (Continente) , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa/normas , Projetos de Pesquisa/tendências
18.
Langenbecks Arch Surg ; 397(6): 917-25, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22695970

RESUMO

PURPOSE: According to the International Union Against Cancer (UICC), R1 is defined as the microscopic presence of tumor cells at the surface of the resection margin (RM). In contrast, the Royal College of Pathologists (RCP) suggested to declare R1 already when tumor cells are found within 1 mm of the RM. The aim of this study was to determine the significance of the RM concerning the prognosis of pancreatic ductal adenocarcinoma (PDAC). METHODS: From 2007 to 2009, 62 patients underwent a curative operation for PDAC of the pancreatic head. The relevance of R status on cumulative overall survival (OS) was assessed on univariate and multivariate analysis for both the classic R classification (UICC) and the suggestion of the RCP. RESULTS: Following the UICC criteria, a positive RM was detected in 8 %. Along with grading and lymph node ratio, R status revealed a significant impact on OS on univariate and multivariate analysis. Applying the suggestion of the RCP, R1 rate rose to 26 % resulting in no significant impact on OS in univariate analysis. CONCLUSIONS: Our study has shown that the RCP suggestion for R status has no impact on the prognosis of PDAC. In contrast, our data confirmed the UICC R classification of RM as well as N category, grading, and lymph node ratio as significant prognostic factors.


Assuntos
Carcinoma Ductal Pancreático/classificação , Carcinoma Ductal Pancreático/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/classificação , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Análise de Variância , Biópsia por Agulha , Carcinoma Ductal Pancreático/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Pancreatectomia/métodos , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/mortalidade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Sociedades Médicas , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
19.
Ultraschall Med ; 33(7): E196-E201, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21630184

RESUMO

PURPOSE: EUS elastography has been used to facilitate the diagnosis of pancreatic cancer, but as yet the interpretation of this procedure has been largely subjective. The present study has been designed to validate a quantitative approach for the analysis of EUS elastography, and to assess its relationship with pancreatic fibrosis. MATERIALS AND METHODS: 86 patients with malignant pancreatic masses and 28 control subjects without any evidence of pancreatic diseases were examined by EUS elastography. EUS video sequences were subjected to a quantitative analysis based on mean hue histogram analysis. Pancreatic fibrosis was determined by quantitative morphometry in tissue specimens from 36 patients. RESULTS: The mean RGB (red, green, blue) value was significantly higher in the cancer patients compared to the controls (14.0 ± 0.4 vs. 11.5 ± 0.9; p = 0.0085), albeit with significant overlap between the groups. In contrast, a much sharper separation between the groups was obtained based on the individual color values for blue, green and red (p < 0.0001, respectively). By these means, 100 % sensitivity and specificity for the distinction between tumor and normal tissue was obtained for the blue color value, while the red and green color values were less discriminative. The fractional fiber content of the tumors was unrelated to the respective hue histogram color values. CONCLUSION: Quantitative EUS elastography allows for clear differentiation between malignant pancreatic tumors and normal tissue. Using this approach, we demonstrated that the stiffness of pancreatic tumors is largely independent of their fiber content.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Interpretação de Imagem Assistida por Computador/métodos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Idoso , Biópsia por Agulha Fina , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Carcinoma/secundário , Carcinoma/cirurgia , Neoplasias do Ducto Colédoco/diagnóstico por imagem , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/secundário , Neoplasias do Ducto Colédoco/cirurgia , Cistadenoma/diagnóstico por imagem , Cistadenoma/patologia , Cistadenoma/cirurgia , Feminino , Fibrose , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/cirurgia , Pâncreas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/cirurgia , Sensibilidade e Especificidade , Ultrassonografia de Intervenção
20.
Zentralbl Chir ; 137(6): 559-64, 2012 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-23264197

RESUMO

BACKGROUND: After pancreatic head resection the reconstruction of small and fragile bile ducts is technically demanding, resulting in more postoperative bile leaks. One option for the reconstruction is the placement of a T-tube drainage at the site of the anastomosis. MATERIAL AND METHODS: Standard reconstruction after pancreatic head resection was an end-to-side hepaticojejunostomy with PDS 5.0, 15-25 cm distally from the pancreaticojejunostomy. For patients with a small bile duct diameter (≤ 5 mm) or a fragile bile duct wall the reconstruction was performed with PDS 6.0 and a T-tube drainage at the side of the anastomosis. RESULTS: The reconstruction with a T-tube drainage at the site of the anastomosis is technically easy to perform and offers the opportunity for immediate visualisation of the anastomosis in the postoperative period by application of water soluble contrast medium. If a bile leak occurs, biliary deviation through the T-tube drainage can enable a conservative management without revisional laparotomy in selected patients. Whether or not a conservative management of postoperative bile leaks will lead to more bile duct strictures is a subject for further investigations. CONCLUSION: A T-tube drainage at the site of the anastomosis can probably not prevent postoperative bile leaks from a difficult hepaticojejunostomy, but in selected patients it offers the opportunity for a conservative management resulting in less re-operations. Therefore we recommend the augmentation of a difficult hepaticojejunostomy with a T-tube drainage.


Assuntos
Anastomose Cirúrgica/instrumentação , Ductos Biliares Extra-Hepáticos/cirurgia , Fístula Biliar/cirurgia , Colestase Extra-Hepática/cirurgia , Drenagem/instrumentação , Jejunostomia/instrumentação , Pancreatectomia , Complicações Pós-Operatórias/cirurgia , Implantação de Prótese/instrumentação , Fístula Biliar/diagnóstico , Fístula Biliar/prevenção & controle , Colangiopancreatografia por Ressonância Magnética , Colestase Extra-Hepática/diagnóstico , Constrição Patológica/cirurgia , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Desenho de Prótese , Reoperação , Fatores de Risco , Tomografia Computadorizada por Raios X
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