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1.
Gastroenterology ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38795735

RESUMO

BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) is standard therapy for nonpedunculated colorectal polyps ≥20 mm. It has been suggested recently that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AEs), but evidence from a randomized trial is missing. METHODS: In this randomized controlled multicentric trial involving 19 centers, nonpedunculated colorectal polyps ≥20 mm were randomly assigned to cold or hot EMR. The primary outcome was major AE (eg, perforation or postendoscopic bleeding). Among secondary outcomes, major AE subcategories, postpolypectomy syndrome, and residual adenoma were most relevant. RESULTS: Between 2021 and 2023, there were 396 polyps in 363 patients (48.2% were female) enrolled for the intention-to-treat analysis. Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001; odds ratio [OR], 0.12; 95% CI, 0.03-0.54). Rates for perforation and postendoscopic bleeding were significantly lower in the cold group, with 0% vs 3.9% (P = .007) and 1.0% vs 4.4% (P = .040). Postpolypectomy syndrome occurred with similar frequency (3.1% vs 4.4%; P = .490). After cold resection, residual adenoma was found more frequently, with 23.7% vs 13.8% (P = .020; OR, 1.94; 95% CI, 1.12-3.38). In multivariable analysis, lesion diameter of ≥4 cm was an independent predictor for major AEs (OR, 3.37) and residual adenoma (OR, 2.47) and for high-grade dysplasia/cancer for residual adenoma (OR, 2.92). CONCLUSIONS: Cold resection of large, nonpedunculated colorectal polyps appears to be considerably safer than hot EMR; however, at the cost of a higher residual adenoma rate. Further studies have to confirm to what extent polyp size and histology can determine an individualized approach. German Clinical Trials Registry (Deutsches Register Klinischer Studien), Number DRKS00025170.

2.
Visc Med ; 40(2): 53-60, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584859

RESUMO

Introduction: Surgery for perihilar cholangiocarcinoma (pCCA) is associated with high rates of postoperative morbidity and mortality. Extended liver resection (EXT) increases R0 resection rate and survival; however, patients with high perioperative risk are not suitable for extended resection. This study aimed to compare overall survival and surgical morbidity in patients with extended liver resection and parenchyma-preserving hepatectomy (PPH). Methods: Between January 2010 and November 2020, 113 consecutive patients with pCCA underwent surgery at our institution. Eighty-two patients were resected in curative intent. Sixty-four patients received extended liver resection, and 18 patients PPH. Outcomes of resections were evaluated. Results: There was no significant difference in overall survival in patients with PPH compared to extended liver resection (log-rank p = 0.286). Patients with PPH experienced lower rates of postoperative morbidity and mortality. There was no case of in-house mortality in PPH-resected patients compared to 10 cases (16%) in patients that received EXT (p = 0.073). Conclusion: PPH shows similar overall survival with lower rates of postoperative morbidity and mortality. Our findings support the role of a PPH, in selected patients with pCCA, that are not suitable for extended resection due to increased perioperative risk.

3.
Front Oncol ; 14: 1286896, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450189

RESUMO

Background: Cachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is known on the global changes of the overall serum metabolome, which represents a functional readout of the whole-body metabolic state. Here, we aimed to comprehensively characterize serum metabolite alterations and analyze associated pathways in cachectic cancer patients to gain new insights that could help instruct strategies for novel interventions of greater clinical benefit. Methods: Serum was sampled from 120 metastatic cancer patients (stage UICC IV). Patients were grouped as cachectic or non-cachectic according to the criteria for cancer cachexia agreed upon international consensus (main criterium: weight loss adjusted to body mass index). Samples were pooled by cachexia phenotype and assayed using non-targeted gas chromatography-mass spectrometry (GC-MS). Normalized metabolite levels were compared using t-test (p < 0.05, adjusted for false discovery rate) and partial least squares discriminant analysis (PLS-DA). Machine-learning models were applied to identify metabolite signatures for separating cachexia states. Significant metabolites underwent MetaboAnalyst 5.0 pathway analysis. Results: Comparative analyses included 78 cachectic and 42 non-cachectic patients. Cachectic patients exhibited 19 annotable, significantly elevated (including glucose and fructose) or decreased (mostly amino acids) metabolites associating with aminoacyl-tRNA, glutathione and amino acid metabolism pathways. PLS-DA showed distinct clusters (accuracy: 85.6%), and machine-learning models identified metabolic signatures for separating cachectic states (accuracy: 83.2%; area under ROC: 88.0%). We newly identified altered blood levels of erythronic acid and glucuronic acid in human cancer cachexia, potentially linked to pentose-phosphate and detoxification pathways. Conclusion: We found both known and yet unknown serum metabolite and metabolic pathway alterations in cachectic cancer patients that collectively support a whole-body metabolic state with impaired detoxification capability, altered glucose and fructose metabolism, and substrate supply for increased and/or distinct metabolic needs of cachexia-associated tumors. These findings together imply vulnerabilities, dependencies and targets for novel interventions that have potential to make a significant impact on future research in an important field of cancer patient care.

4.
Endosc Int Open ; 12(1): E36-E42, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38188926

RESUMO

Introduction The anti-cholinergic agent hyoscine-N-butylbromide (HBB) is used in gastrointestinal (GI) endoscopy to decrease motility and facilitate endoscopic procedures. Data from clinical studies to support this practice is limited especially for therapeutic procedures. Likewise, patterns of use among endoscopist are largely unclear. This study sought to assess usage of HBB among German-speaking endoscopists. Material and Methods We conducted an anonymous online survey among endoscopists in German-speaking countries. Results A total of 207 physicians participated in the survey. The majority (76.9%) were experienced endoscopists and 92.3% of respondents use HBB at least occasionally during procedures. The reported median stated frequency of HBB use varied greatly between different types of procedures and increased with the complexity of the procedure being performed. HBB was rarely used in diagnostic esophagogastroduodenoscopies (EGD) (median stated frequency 1% of procedures), while use frequency was significantly higher in EGD with endoscopic mucosal resection (EMR) (10%; p=0.002) and EGD with endoscopic submucosal dissection (ESD) (20%; p<0.001). Similarly, use frequency during diagnostic colonoscopy was lower (5%) compared to colonoscopy with EMR (20%, p=0.005) or ESD (42.5%, p<0.001). The highest use frequency was reported for ERCP (50%). The most frequently stated reason to use HBB was facilitation of the procedure (80.6%) followed by increasing diagnostic yield (58.3%). Conclusion German-speaking endoscopists commonly use HBB, most frequently to facilitate complex therapeutic procedures. Given there is almost no data supporting HBB use in therapeutic endoscopy, we suggest that more research is needed to evaluate benefits and risks of this practice.

5.
Dig Dis Sci ; 68(9): 3614-3624, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37421512

RESUMO

BACKGROUND: For an adequate educational strategy of ESD in non-Asian settings with prevalence-based indication it is essential to define adequate lesions, suitable for the beginner without on-site expert-supervision. AIMS: We analyzed possible predictors for outcome parameters of effectiveness and safety during the initial learning curve. METHODS: The first 120 ESDs of four operators (n = 480), performed between 2007 and 2020 in four tertiary hospitals, were enrolled. Uni-/multivariable regression analysis was done with sex, age, pretreated lesion, lesion size, organ, and organ-based localization as possible independent predictors for en bloc resection (EBR), complication, and resection speed. RESULTS: Rates of EBR, complication, and resection speed were 84.5%, 14.2%, and 6.20 (± 4.45) cm2/h. Independent predictors for EBR were pretreated lesion (OR 0.27 [0.13-0.57], p < 0.001) and non-colonic ESD (OR 2.29 [1.26-4.17] (rectum)/5.72 [2.36-13.89] (stomach)/7.80 [2.60-23.42] (esophagus), p < 0.001), for complication pretreated lesion (OR 3.04 [1.46-6.34], p < 0.001) and lesion size (OR 1.02 [1.004-1.04], p = 0.012) and for resection speed pretreated lesion (RC - 3.10 [- 4.39 to - 1.81], p < 0.001), lesion size (RC 0.13 [0.11-0.16], p < 0.001) and male patient (RC - 1.11 [- 1.85 to - 0.37], p < 0.001). We found no significant difference in the incidence of technically unsuccessful resections in esophageal (1/84), gastric (3/113), rectal (7/181), and colonic (3/101) ESDs (p = 0.76). Technical failure was mainly caused by complication and fibrosis/pretreatment. CONCLUSION: During the initial learning curve of an unsupervised ESD program with prevalence-based indication, pretreated lesions and colonic ESDs should be avoided. In contrast, lesion size and organ-based localizations have less predictive value for the outcome.


Assuntos
Ressecção Endoscópica de Mucosa , Humanos , Masculino , Ressecção Endoscópica de Mucosa/efeitos adversos , Curva de Aprendizado , Prevalência , Resultado do Tratamento , Colo , Estudos Retrospectivos
6.
Liver Int ; 43(10): 2116-2129, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37366005

RESUMO

BACKGROUND: Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) are a valuable model to investigate host-pathogen interactions of hepatitis viruses in a mature and authentic environment. Here, we investigate the susceptibility of HLCs to the hepatitis delta virus (HDV). METHODS: We differentiated hPSC into HLCs, and inoculated them with infectious HDV produced in Huh7NTCP . HDV infection and cellular response was monitored by RTqPCR and immunostaining. RESULTS: Cells undergoing hepatic differentiation become susceptible to HDV after acquiring expression of the viral receptor Na+ -taurocholate co-transporting polypeptide (NTCP) during hepatic specification. Inoculation of HLCs with HDV leads to detection of intracellular HDV RNA and accumulation of the HDV antigen in the cells. Upon infection, the HLCs mounted an innate immune response based on induction of the interferons IFNB and L, and upregulation of interferon-stimulated genes. The intensity of this immune response positively correlated with the level of viral replication and was dependant on both the JAK/STAT and NFκB pathway activation. Importantly, this innate immune response did not inhibit HDV replication. However, pre-treatment of the HLCs with IFNα2b reduced viral infection, suggesting that ISGs may limit early stages of infection. Myrcludex efficiently abrogated infection and blocked innate immune activation. Lonafarnib treatment of HDV mono infected HLCs on the other hand led to exacerbated viral replication and innate immune response. CONCLUSION: The HDV in vitro mono-infection model represents a new tool to study HDV replication, its host-pathogen interactions and evaluate new antiviral drugs in cells displaying mature hepatic functions.


Assuntos
Hepatite D , Vírus Delta da Hepatite , Humanos , Vírus Delta da Hepatite/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Hepatite D/tratamento farmacológico , Hepatócitos/metabolismo , Imunidade Inata , Interferons/uso terapêutico , Células-Tronco , Replicação Viral , Vírus da Hepatite B/genética
7.
Surg Endosc ; 37(6): 4370-4380, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36759355

RESUMO

BACKGROUND: Iatrogenic colorectal perforation is a rare event with a relevant mortality and the need for surgical therapy in around ¾ of cases. METHODS: In this retrospective multicentric cohort study iatrogenic colorectal perforations from 2004 to 2021 were analyzed. Primary outcome parameters were incidence and clinical success of 1st line endoscopic treatment. Comparative analysis of interventional and non-interventional perforations was performed and predictors for clinical success of endoscopic therapy were identified. RESULTS: From 103,570 colonoscopies 213 (0.2%) iatrogenic perforations were identified. 68.4% were interventional (80 during polypectomy/EMR, 54 during ESD and 11 for other reasons) and 31.6% non-interventional perforations (39 by the tip, 19 by the shaft, 7 by inversion, two by biopsy and one by distension). Incidence of 1st line endoscopic therapy was 61.0% and clinical success 81.5%. Other non-surgical therapies were conducted in 8.9% with clinical success in 94.7% of cases. In interventional perforations both incidence and clinical success of 1st line endoscopic therapy were significantly higher compared to non-interventional perforations [71.7% vs. 38.2% (p < 0.01) resp. 86.5% vs. 61.5% (p < 0.01)]. Mortality was 2.3% and significantly lower in the group of interventional perforations (0.7% vs. 5.9%, p = 0.037). Multivariable analysis revealed perforation size < 5 mm as only independent predictor for clinical success of 1st line endoscopic treatment [OR 14.85 (1.57-140.69), p = 0.019]. CONCLUSIONS: Endoscopic therapy is treatment of choice in the majority of iatrogenic colorectal perforations. In case of interventional perforations it is highly effective but only a minority of non-interventional perforations are good candidates for endoscopic treatment.


Assuntos
Neoplasias Colorretais , Perfuração Intestinal , Humanos , Estudos Retrospectivos , Estudos de Coortes , Resultado do Tratamento , Colonoscopia/efeitos adversos , Neoplasias Colorretais/patologia , Doença Iatrogênica , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Perfuração Intestinal/epidemiologia
8.
Surg Endosc ; 37(4): 2574-2586, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36344898

RESUMO

BACKGROUND AND AIMS: As there is still no consensus about the adequate training strategy for ESD in Western countries, we evaluated unsupervised prevalence-based learning curves including detailed organ-specific subgroup analysis. METHODS: The first 120 ESDs of four operators (n = 480) were divided into three groups (1: ESD 1-40, 2: ESD 41-80, 3: ESD 81-120). Outcome parameters were rates of technical success, en bloc and R0 resection, the resection speed, rates of conversion to EMR, curative resection, adverse events, surgery due to adverse events, and recurrence. In addition, we analyzed the achievement of quality benchmarks indicating levels of expertise. RESULTS: After exclusion of pretreated lesions, 438 procedures were enrolled in the final analysis. Technical success rates were > 96% with significant improvements regarding rate of en bloc resection (from 82.6 to 91.2%), resection speed (from 4.54 to 7.63 cm2/h), and rate of conversion to EMR (from 22.0 to 8.1%). No significant differences could be observed for rates of R0 resection (65.9 vs. 69.6%), curative resection (55.8 vs. 55.7%), adverse events (16.3 vs. 11.7%), surgery due to adverse events (1.5 vs. 1.3%), and recurrence (12.5 vs. 4.5%). Subgroup and benchmark analysis revealed an improvement in esophageal, gastric, and rectal ESD with achievement of competence levels for the esophagus and stomach within 80 and most of the benchmarks for proficiency level within 120 procedures. Some of the benchmarks could also be achieved in rectal ESD. CONCLUSIONS: This trial confirms safety and feasibility of unsupervised ESD along the initial learning curve with prevalence-based indication and exclusion of colonic cases.


Assuntos
Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/educação , Curva de Aprendizado , Prevalência , Mucosa Gástrica/cirurgia , Estômago
9.
PLoS One ; 17(10): e0275029, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36302047

RESUMO

BACKGROUND: Endoscopic ultrasound-guided biliary drainage (EUS-BD) was associated with better clinical success and a lower rate of adverse events (AEs) than fluoroscopy-guided percutaneous transhepatic biliary drainage (PTBD) in recent single center studies with mainly retrospective design and small case numbers (< 50). The aim of this prospective European multicenter study is to compare both drainage procedures using ultrasound-guidance and primary metal stent implantation in patients with malignant distal bile duct obstruction (PUMa Trial). METHODS: The study is designed as a non-randomized, controlled, parallel group, non-inferiority trial. Each of the 16 study centers performs the procedure with the best local expertise (PTBD or EUS-BD). In PTBD, bile duct access is performed by ultrasound guidance. EUS-BD is performed as an endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS), EUS-guided choledochoduodenostomy (EUS-CDS) or EUS-guided antegrade stenting (EUS-AGS). Insertion of a metal stent is intended in both procedures in the first session. Primary end point is technical success. Secondary end points are clinical success, duration pf procedure, AEs graded by severity, length of hospital stay, re-intervention rate and survival within 6 months. The target case number is 212 patients (12 calculated dropouts included). DISCUSSION: This study might help to clarify whether PTBD is non-inferior to EUS-BD concerning technical success, and whether one of both interventions is superior in terms of efficacy and safety in one or more secondary endpoints. Randomization is not provided as both procedures are rarely used after failed endoscopic biliary drainage and study centers usually prefer one of both procedures that they can perform best. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03546049 (22.05.2018).


Assuntos
Colestase , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colestase/diagnóstico por imagem , Colestase/cirurgia , Drenagem/efeitos adversos , Drenagem/métodos , Endossonografia/métodos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Estudos Retrospectivos , Stents/efeitos adversos , Ultrassonografia de Intervenção
10.
J Clin Exp Hepatol ; 12(1): 68-79, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35068787

RESUMO

BACKGROUND: Potential indications for surgery frequently arise in patients awaiting liver transplantation. There is a risk of hepatic decompensation and death triggered by surgical trauma, but this has not been studied in detail in this unique population. We aimed to quantify the impact of surgical interventions in patients awaiting liver transplantation on hepatic function and identify risk factors for decompensation. METHODS: All surgeries between 2000 and 2018 in patients awaiting liver transplantation in a highvolume German liver transplant center were analyzed retrospectively. Change in liver function measured as indicated by MELD score was assessed and complication rates recorded. The primary endpoint was a composite of an increase in MELD score by > 5 points or death. A logistic regression model was used for multivariate analysis to identify risk factors. RESULTS: In total, 177 surgical procedures in 148 patients were analyzed. The primary endpoint was reached in 42 cases (23.7%). The overall in-hospital complication rate (including death) was 44.1%. Multivariate analysis identified elevated leukocyte count, perioperative blood transfusion, preoperative presence of ascites, and preoperative circulatory support as independent risk factors for a decline in liver function or death. CONCLUSION: Surgery in patients awaiting liver transplantation carries a relevant risk of hepatic decompensation and death that needs to be considered when deciding whether to perform elective surgery prior to or defer until after liver transplantation.

11.
Cells ; 10(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209751

RESUMO

The HCV replication cycle is tightly associated with host lipid metabolism: Lipoprotein receptors SR-B1 and LDLr promote entry of HCV, replication is associated with the formation of lipid-rich membranous organelles and infectious particle assembly highjacks the very­low-density lipoprotein (VLDL) secretory pathway. Hence, medications that interfere with the lipid metabolism of the cell, such as statins, may affect HCV infection. Here, we study the interplay between lipoprotein receptors, lipid homeostasis, and HCV infection by genetic and pharmacological interventions. We found that individual ablation of the lipoprotein receptors SR­B1 and LDLr did not drastically affect HCV entry, replication, or infection, but double lipoprotein receptor knock-outs significantly reduced HCV infection. Furthermore, we could show that this effect was neither due to altered expression of additional HCV entry factors nor caused by changes in cellular cholesterol content. Strikingly, whereas lipid­lowering drugs such as simvastatin or fenofibrate did not affect HCV entry or infection of immortalized hepatoma cells expressing SR-B1 and/or LDLr or primary human hepatocytes, ablation of these receptors rendered cells more susceptible to these drugs. Finally, we observed no significant differences between statin users and control groups with regards to HCV viral load in a cohort of HCV infected patients before and during HCV antiviral treatment. Interestingly, statin treatment, which blocks the mevalonate pathway leading to decreased cholesterol levels, was associated with mild but appreciable lower levels of liver damage markers before HCV therapy. Overall, our findings confirm the role of lipid homeostasis in HCV infection and highlight the importance of the mevalonate pathway in the HCV replication cycle.


Assuntos
Hepacivirus/patogenicidade , Hipolipemiantes/farmacologia , Receptores de Lipoproteínas/metabolismo , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Linhagem Celular , Células Cultivadas , Colesterol/metabolismo , Estudos de Coortes , Genótipo , Glicoproteínas/metabolismo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/patologia , Hepatite C/virologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Hepatócitos/virologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Receptores de Lipoproteínas/deficiência , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
12.
Visc Med ; 37(1): 1-2, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33718478
14.
United European Gastroenterol J ; 8(6): 716-724, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32366182

RESUMO

BACKGROUND: Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is an emerging disease with grim prognosis. OBJECTIVE: Our aim was the analysis of prognostic factors, long-term outcome and risk of tumour development in SSC-CIP compared with primary sclerosing cholangitis (PSC) patients. METHODS: Retrospective analysis between 2008 and 2018. RESULTS: One hundred and eleven patients with SSC-CIP and 408 PSC patients were identified. Median orthotopic liver transplantation (OLT)-free survival was 16 months for SSC-CIP and 147 months for PSC (p < 0.001). OLT was performed in 18/111 SSC-CIP compared with 166/408 PSC patients (p < 0.001). Malignant tumours were detected in 17.9% of PSC patients (73/408) compared with 2.7% (3/111) in SSC-CIP (p < 0.001). In multivariate Cox regression analysis low levels of C-reactive protein (hazard ratio 4.687 (95% confidence interval (CI) 1.144-19.199, p = 0.032) were significantly associated with a prolonged survival whereas higher age (hazard ratio 0.488 (95% CI 0.23-1.038), p = 0.062) showed a trend for shorter survival in SSC-CIP. For PSC malignancies (hazard ratio 0.42 (95% CI 0.313-0.575), p < 0.001) and higher age (hazard ratio 0.709 (95% CI 0.544-0.922), p = 0.01) were associated with a shorter OLT-free survival. CONCLUSION: SSC-CIP is characterized by acute onset of liver disease and poor prognosis but with lower tumour incidence compared with PSC.


Assuntos
Neoplasias dos Ductos Biliares/epidemiologia , Colangite Esclerosante/mortalidade , Falência Hepática Aguda/mortalidade , Transplante de Fígado/estatística & dados numéricos , Doença Aguda , Adulto , Fatores Etários , Neoplasias dos Ductos Biliares/etiologia , Proteína C-Reativa/análise , Colangite Esclerosante/sangue , Colangite Esclerosante/etiologia , Colangite Esclerosante/cirurgia , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva/estatística & dados numéricos , Falência Hepática Aguda/sangue , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/cirurgia , Testes de Função Hepática , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Chirurg ; 91(9): 769-777, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32025744

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive tumor with a growing socioeconomic burden. International guidelines do not predominantly recommend the pretherapeutic determination of the alpha-fetoprotein (AFP) concentration. Regarding the prognostic value of AFP, the European study data are not sufficiently meaningful. OBJECTIVE: This study aimed to demonstrate possible aspects of the AFP level and to investigate the prognostic value of AFP levels as well as to provide impetus for future prospective studies. MATERIAL AND METHODS: At the time of data retrieval the prospective liver databank showed 1382 entries. All patients with a histologically confirmed HCC were included resulting in 92 final entries. For these patients, information on T, N, M and G stages, R status as well as sex, age and etiology of the HCC were available. For data analysis the patient population was divided into six groups based on three cut-off values. Furthermore, a survival analysis was performed using Kaplan-Meier and a multifactorial analysis of the influencing factors regarding outcome. RESULTS: The AFP serum level showed a statistically significant correlation with the tumor diameter (T1/T2 vs. T3/T4) and grading (G1/G2 vs. G3/G4). The survival prognosis was significantly lower in patients with higher AFP values (p < 0.05). The median survival time for patients with AFP levels >8 µg/l was 35 months, with AFP levels >200 µg/l or >400 µg/l showed a reduced median survival of 15 months and 11 months, respectively. High AFP levels were a significant influencing factor for the outcome independent of the T stage, age and R status of patients in comparison to low AFP levels. CONCLUSION: Taking the present results into consideration, the AFP level can have a therapeutic usefulness. Therapeutic consequences could be derived from the height of the measured AFP concentration, with respect to the treatment strategy. Therefore, preoperative and postoperative determination of the AFP serum level is recommended in all HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Prognóstico , Estudos Prospectivos
16.
Int J Hepatol ; 2019: 4793096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355004

RESUMO

BACKGROUND AND STUDY AIMS: Patients undergoing therapeutic endoscopic retrograde cholangiography (ERC) may require different amounts of sedative agents depending on demographic characteristics, indication of ERC, and/or endoscopic intervention. PATIENTS AND METHODS: We retrospectively analyzed all patients undergoing therapeutic ERC from 2008 - 2014 who received deep sedation with propofol ± midazolam. RESULTS: A total of 2448 ERC procedures were performed in 781 patients. The cumulative per procedure propofol dose in the different groups was as follows: PSC 479 mg (±256), bile duct stones 356 mg (±187), benign stenosis/cholestasis 395 mg (±228), malignant stenosis 401 mg (±283), and postliver transplant complications 391 mg (±223) (p < 0.05). Multivariable analysis showed that dilatation therapy (p = 0.001), age (p = 0.001), duration of the intervention (p = 0.001), BMI (p = 0.001), gender (p = 0.001), platelet count (p = 0.003), and bilirubin (p = 0.043) influence independently the propofol consumption. CONCLUSIONS: Demographic characteristics and endoscopic interventions have a distinct influence on the amount of sedation required for therapeutic ERC. Although the sedation-associated complication rate is low optimization of sedative regimens is a prime goal to further reduce adverse events of therapeutic ERC.

17.
J Hepatol ; 71(2): 301-312, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31100314

RESUMO

BACKGROUND & AIMS: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Although HDV-associated liver disease is considered immune-mediated, adaptive immune responses against HDV are weak. Thus, the role of several other cell-mediated mechanisms such as those driven by mucosa-associated invariant T (MAIT) cells, a group of innate-like T cells highly enriched in the human liver, has not been extensively studied in clinical HDV infection. METHODS: MAIT cells from a sizeable cohort of patients with chronic HDV were analyzed ex vivo and in vitro after stimulation. Results were compared with MAIT cells from hepatitis B virus (HBV) monoinfected patients and healthy controls. RESULTS: Circulating MAIT cells were dramatically decreased in the peripheral blood of HDV-infected patients. Signs of decline were also observed in the liver. In contrast, only a modest decrease of circulating MAIT cells was noted in HBV monoinfection. Unsupervised high-dimensional analysis of residual circulating MAIT cells in chronic HDV infection revealed the appearance of a compound phenotype of CD38hiPD-1hiCD28loCD127loPLZFloEomesloHelioslo cells indicative of activation. Corroborating these results, MAIT cells exhibited a functionally impaired responsiveness. In parallel to MAIT cell loss, HDV-infected patients exhibited signs of monocyte activation and increased levels of proinflammatory cytokines IL-12 and IL-18. In vitro, IL-12 and IL-18 induced an activated MAIT cell phenotype similar to the one observed ex vivo in HDV-infected patients. These cytokines also promoted MAIT cell death, suggesting that they may contribute to MAIT cell activation and subsequent loss during HDV infection. CONCLUSIONS: These results suggest that chronic HDV infection engages the MAIT cell compartment causing activation, functional impairment, and subsequent progressive loss of MAIT cells as the HDV-associated liver disease progresses. LAY SUMMARY: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. We found that in patients with HDV, a subset of innate-like T cells called mucosa-associated invariant T cells (or MAIT cells), which are normally abundant in peripheral blood and the liver, are activated, functionally impaired and severely depleted.


Assuntos
Hepatite D Crônica/imunologia , Vírus Delta da Hepatite/fisiologia , Ativação Linfocitária/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Adulto , Idoso , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Feminino , Células Hep G2 , Hepatite D Crônica/virologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Interleucina-12/sangue , Interleucina-18/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/metabolismo , Fenótipo , Receptores de Antígenos de Linfócitos T/metabolismo , Adulto Jovem
18.
Scand J Gastroenterol ; 54(5): 640-645, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31122083

RESUMO

Background: Endoscopic biliary drainage is the standard of care for patients with cholangiocarcinoma (CCA)-induced, obstructive jaundice. Self-expanding metal stents are supposed to be superior to polyethylene stents in terms of reduction of interventions and costs. So far, there are only few real-life data with respect to stent selection and survival in this patient cohort. Methods: In this study, we retrospectively analyzed patients with CCA treated with endoscopic biliary drainage from 2000 to 2015 at Hannover Medical School, Germany. The aim of this study was to analyze whether metal stenting reduces the frequency of interventions and influences survival in a large, real-life cohort. Results: Overall, 422 patients with CCA were included in this study. Indication for endoscopic biliary drainage was most often obstructive jaundice (n = 397; 94.1%). Among these patients, 20 patients (5%) were initially treated with a metal stent and 38 (9.6%) received a metal stent in the subsequent course. Median number of interventions per month was 2.4-fold reduced following metal stenting. Patients first treated with a metal stent had a more advanced tumor stage and a significantly shorter median overall survival (mOS) compared to patients who received a metal stent subsequently (7.5 months vs. 15.2 months; p=.019). There was no difference in mOS for metal vs. polyethylene stenting following a propensity score match for the confounders curative resection and chemotherapy (13.2 vs. 13.7 months, p=.555). Conclusions: Our data confirm that metal stenting reduces the frequency of interventions, but does not influence OS. Metal stenting should be considered specifically in younger patients who are suitable for chemotherapy.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Drenagem/instrumentação , Icterícia Obstrutiva/terapia , Stents Metálicos Autoexpansíveis , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Feminino , Alemanha/epidemiologia , Humanos , Icterícia Obstrutiva/etiologia , Masculino , Pessoa de Meia-Idade , Polietileno , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
19.
Radiologe ; 59(4): 293-299, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30806734

RESUMO

CLINICAL ISSUE: Biliary diseases require fast and rational use of diagnostic tests by both gastroenterologists and radiologists. STANDARD TREATMENT: Standard diagnostic workup includes transabdominal ultrasound, endoscopic retrograde cholangiography (ERC), endoscopic ultrasound, direct cholangioscopy, magnetic resonance cholangiopancreatography (MRI/MRCP), and computed tomography (CT). TREATMENT INNOVATIONS: Modular cholangioscopy is a novel diagnostic method. DIAGNOSTIC WORK-UP: The goal of diagnostic examinations is the determination of the location of obstructions and differentiation of benign from malignant lesions. ACHIEVEMENTS: Transabdominal ultrasound is risk-free and can show the gallbladder in great detail providing high diagnostic accuracy in most conditions. Endoscopic ultrasound, ERC and/or cholangioscopy are powerful tools to investigate the large bile ducts but are associated with inherent procedural risks. PRACTICAL RECOMMENDATIONS: Gall bladder diseases can often be diagnosed with transabdominal ultrasound alone. Bile duct disease often requires the use of endoscopic ultrasound, ERC and/or cholangioscopy.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Gastroenterologistas , Radiologistas , Imageamento por Ressonância Magnética , Estudos Prospectivos
20.
J Hepatol ; 70(4): 603-614, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30472319

RESUMO

BACKGROUND & AIMS: The lipid-binding protein, SEC14L2, is crucial for the efficient viral replication of clinical hepatitis C virus (HCV) isolates in cell culture. Given the role of SEC14L2 in HCV replication, we aimed to study a large number of HCV positive sera carrying genotypes 1-4, to identify viral factors associated with efficient replication in culture. Additionally, we investigated whether 13 single nucleotide polymorphisms (SNPs) of SEC14L2 have an impact on RNA replication of naturally occurring HCV isolates. METHODS: We generated Huh-7.5 cell lines overexpressing SEC14L2 or 13 coding SNPs and tested 73 different HCV positive sera for in vitro replication. Furthermore, we genotyped a cohort of 262 patients with chronic HCV for the common SNP (rs757660) and investigated its effect on the clinical phenotype. RESULTS: HCV isolates from genotype 1, 2, 3 and 4 replicate in Huh-7.5 cells overexpressing SEC14L2. Interestingly, only subgenomic replicons from genotypes 1 and 3 showed enhanced replication whereas genotypes 2 and 4 remained unaffected. Furthermore, replication was independent of viral load. Importantly, all tested SNPs supported HCV RNA replication in vitro, while 1 SNP was associated with decreased SEC1L2 expression and viral RNA. All SNPs exhibited comparable cellular cholesterol and vitamin E abundance in naïve Huh-7.5 cells. CONCLUSIONS: This large screen of natural HCV isolates of 4 genotypes underscores the relevance of SEC14L2 as an in vitro HCV host factor. Additionally, SEC14L2 variants appear to recapitulate the wild-type enhancement of HCV replication. Variant rs191341134 showed a decreased effect due to lowered stability, whereas variant rs757660, a high prevalence mutant, showed a similar phenotype to the wild-type. LAY SUMMARY: Until the year 2015, consistent replication of patient-derived isolates of hepatitis C virus (HCV) in an in vitro model remained a limitation in HCV research. In 2015 a group of authors identified a protein named SEC14L2 that enabled the replication of HCV isolates in cell culture. We performed a large screen encompassing 73 isolates of 4 different HCV genotypes. Additionally, we replaced the natural SEC14L2 with 13 different mutants to test if the protein variation significantly altered its HCV replication enhancing functions. We showed that different genotypes of HCV react differently to the presence of this protein and the variants of the protein mimic the behavior of the wild-type.


Assuntos
Proteínas de Transporte/metabolismo , Genótipo , Hepacivirus/genética , Hepatite C Crônica/genética , Lipoproteínas/metabolismo , Transativadores/metabolismo , Replicação Viral/genética , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Estudos de Coortes , Citosol/metabolismo , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Lipoproteínas/genética , Proteínas Mutantes/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética , RNA Viral/genética , RNA Viral/isolamento & purificação , Replicon , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transativadores/genética , Transdução Genética
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