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1.
Endoscopy ; 51(7): 684-688, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986867

RESUMO

BACKGROUND: Endoscopic full-thickness transoral outlet reduction (efTOR) is a therapeutic option to reduce a dilated gastrojejunal anastomosis (GJA) after Roux-en-Y gastric bypass (RYGB). Mucosal ablation with argon plasma coagulation (APC) is usually performed to achieve tissue adaptation. However, rupture of sutures before scarring can lead to recurrent dilatation of the GJA. Here, we describe efTOR with a semicircumferential endoscopic submucosal dissection (ESD-efTOR) as an alternative to APC-efTOR. METHODS: We enrolled 41 patients with comparable baseline characteristics (APC-efTOR 26; ESD-efTOR 15). The main objectives were reduction in the GJA diameter and in ruptured sutures. Technical success, complications, total weight loss (TWL), and percentage of total and excess weight loss (%TWL and %EWL) at 3 and 12 months, were assessed. RESULTS: ESD-efTOR resulted in significantly fewer ruptured sutures (20 % vs. 69 %; P = 0.004) and a greater reduction in the GJA (major 20 % vs. 0 %; minor 54 % vs. 37 %; no reduction 13 % vs. 58 %; P = 0.02) after 3 months. Technical efficacy, examination time, and rate of complications were comparable. CONCLUSIONS: ESD-efTOR resulted in a significantly greater reduction in the GJA diameter and a lower risk of ruptured sutures compared with APC-efTOR.


Assuntos
Coagulação com Plasma de Argônio/métodos , Ressecção Endoscópica de Mucosa/métodos , Junção Esofagogástrica/cirurgia , Derivação Gástrica/efeitos adversos , Jejuno/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Estômago/cirurgia , Anastomose Cirúrgica/efeitos adversos , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Junção Esofagogástrica/diagnóstico por imagem , Seguimentos , Boca , Obesidade Mórbida/cirurgia , Reoperação/métodos , Técnicas de Sutura/efeitos adversos , Fatores de Tempo
2.
Z Gastroenterol ; 57(8): 971-976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31398768

RESUMO

BACKGROUND: Neopharyngeal obstruction after therapy of head and neck cancer is a frequent and clinically challenging problem without evidence-based guideline recommendations. CASE: We present two cases of complete esophageal obstruction after treatment for head and neck cancer. Due to complete obstruction of long distance stricture standard dilatation procedures were impossible to perform. In both cases, recanalization was achieved by combining an antegrade with a retrograde maneuver. In one patient endoscopic cutting with a papillotome was needed. CONCLUSION: Even in complex cases of post-therapeutic stenosis an endoscopic approach may offer a feasible alternative to surgical therapy, especially in the subset of frail patients.


Assuntos
Estenose Esofágica/terapia , Esofagoscopia/métodos , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/terapia , Idoso , Dilatação , Estenose Esofágica/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
3.
Z Gastroenterol ; 57(3): 312-316, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30861555

RESUMO

The relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.


Assuntos
Fibrose Cística , Enterocolite Neutropênica , Obstrução Intestinal , Adulto , Fibrose Cística/complicações , Enterocolite Neutropênica/diagnóstico , Enterocolite Neutropênica/etiologia , Enterocolite Neutropênica/cirurgia , Fibrose , Humanos , Masculino
4.
Pancreatology ; 18(5): 477-481, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29884332

RESUMO

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.

5.
Support Care Cancer ; 26(6): 1851-1859, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29270828

RESUMO

PURPOSE: We examined whether multi-disciplinary stepped psycho-social care decreases financial problems and improves return-to-work in cancer patients. METHODS: In a university hospital, wards were randomly allocated to either stepped or standard care. Stepped care comprised screening for financial problems, consultation between doctor and patient, and the provision of social service. Outcomes were financial problems at the time of discharge and return-to-work in patients < 65 years old half a year after baseline. The analysis employed mixed-effect multivariate regression modeling. RESULTS: Thirteen wards were randomized and 1012 patients participated (n = 570 in stepped care and n = 442 in standard care). Those who reported financial problems at baseline were less likely to have financial problems at discharge when they had received stepped care (odds ratio (OR) 0.2, 95% confidence interval (CI) 0.1, 0.7; p = 0.01). There was no evidence for an effect of stepped care on financial problems in patients without such problems at baseline (OR 1.1, CI 0.5, 2.6; p = 0.82). There were 399 patients < 65 years old who were not retired at baseline. In this group, there was no evidence for an effect of stepped care on being employed half a year after baseline (OR 0.7, CI 0.3, 2.0; p = 0.52). TRIAL REGISTRATION: NCT01859429 CONCLUSIONS: Financial problems can be avoided more effectively with multi-disciplinary stepped psycho-social care than with standard care in patients who have such problems.


Assuntos
Neoplasias/economia , Retorno ao Trabalho/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Serviço Social , Adulto Jovem
6.
Digestion ; 97(3): 267-274, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29428940

RESUMO

BACKGROUND: Bile duct stones (BDS) are usually removed via endoscopic retrograde cholangiopancreatography (ERCP) or, if ERCP remains unsuccessful, percutaneous transhepatic cholangiodrainage (PTCD). However, PTCD provides limited access to large BDSs. We analyzed a modified approach of PTCD for percutaneous therapy of BDS. METHODS: We used a modified approach of PTCD with a 13-french (Fr) hemostasis introducer for transhepatic access to BDS. Short-wired balloon or basket catheter were applied for safe removal of BDS. Patient characteristics, effectiveness, and complications were analyzed. RESULTS: We identified 11 patients who underwent PTCD with hemostasis introducer. BDSs were either pushed forward to the duodenum (36%) or both partly pushed and extracted via hemostasis introducer (64%). In some cases, mechanical lithotripsy was necessary (45%). Complete removal of BDS was initially achieved in 36% of patients, 45% received additional PTCD, and in 19% stent implantation was performed. Finally, all BDSs could be removed. Laboratory analysis revealed significant reduction of alkaline phosphatase (p = 0.03) and C reactive protein (p = 0.03). Complications occurred only in 1 patient with post-interventional cholangitis. CONCLUSION: Our study showed feasibility and safety of a modified PTCD with hemostasis introducer. In addition, protection of liver tissue from sharp-edged catheters and stones was achieved. Therefore, our modification revealed an innovational approach for transhepatic removal of BDS.


Assuntos
Cateterismo/métodos , Catéteres , Drenagem/métodos , Cálculos Biliares/cirurgia , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/cirurgia , Cateterismo/efeitos adversos , Cateterismo/instrumentação , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Drenagem/instrumentação , Estudos de Viabilidade , Feminino , Cálculos Biliares/diagnóstico por imagem , Humanos , Masculino , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento
7.
Z Gastroenterol ; 56(11): 1365-1368, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30419579

RESUMO

Anastomotic leakage is a frequent complication after gastrointestinal (GI) surgery and is associated with high morbidity and mortality. Endoluminal therapy offers numerous advantages compared to surgical revision. We present the case of a 74-year-old female patient with anastomotic leakage after esophagogastrostomy. The defect was closed using the OverStitch endoscopic suturing system with immediate technical and clinical success. Hereby, an example of the feasibility of this novel technique in a case of anastomotic leakage is presented and provides an outlook for the rising importance of endoscopic therapy.


Assuntos
Fístula Anastomótica/cirurgia , Endoscopia , Esofagoscopia , Esofagostomia , Gastroscopia , Gastrostomia , Técnicas de Sutura , Idoso , Esofagoscopia/métodos , Esofagostomia/efeitos adversos , Feminino , Gastroscopia/métodos , Gastrostomia/efeitos adversos , Humanos , Reoperação , Técnicas de Sutura/instrumentação
8.
Am J Gastroenterol ; 112(3): 441-446, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28094314

RESUMO

OBJECTIVES: Our aims were to assess risks of early rebleeding after successful endoscopic hemostasis for Forrest oozing (FIB) peptic ulcer bleeding (PUBs) compared with other stigmata of recent hemorrhage (SRH). METHODS: These were post hoc multivariable analyses of a large, international, double-blind study (NCT00251979) of patients randomized to high-dose intravenous (IV) esomeprazole (PPI) or placebo for 72 h. Rebleeding rates of patients with PUB SRH treated with either PPI or placebo after successful endoscopic hemostasis were also compared. RESULTS: For patients treated with placebo for 72 h after successful endoscopic hemostasis, rebleed rates by SRH were spurting arterial bleeding (FIA) 22.5%, adherent clot (FIIB) 17.6%, non-bleeding visible vessel (FIIA) 11.3%, and oozing bleeding (FIB) 4.9%. Compared with FIB patients, FIA, FIIB, and FIIA had significantly greater risks of rebleeding with odds ratios (95% CI's) from 2.61 (1.05, 6.52) for FIIA to 6.66 (2.19, 20.26) for FIA. After hemostasis, PUB rebleeding rates for FIB patients at 72 h were similar with esomeprazole (5.4%) and placebo (4.9%), whereas rebleed rates for all other major SRH (FIA, FIIA, FIIB) were lower for PPI than placebo, but the treatment by SRH interaction test was not statistically significant. CONCLUSIONS: After successful endoscopic hemostasis, FIB patients had very low PUB rebleeding rates irrespective of PPI or placebo treatment. This implies that after successful endoscopic hemostasis the prognostic classification of FIB ulcers as a high-risk SRH and the recommendation to treat these with high-dose IV PPI's should be re-evaluated.


Assuntos
Eletrocoagulação/métodos , Endoscopia do Sistema Digestório , Epinefrina/uso terapêutico , Hemostasia Cirúrgica/métodos , Úlcera Péptica Hemorrágica/cirurgia , Vasoconstritores/uso terapêutico , Administração Intravenosa , Idoso , Método Duplo-Cego , Esomeprazol/uso terapêutico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Úlcera Péptica/complicações , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica Hemorrágica/etiologia , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Instrumentos Cirúrgicos , Resultado do Tratamento
9.
Psychooncology ; 26(10): 1675-1683, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28665542

RESUMO

OBJECTIVE: Emotional distress in cancer patients often goes unnoticed in daily routine; therefore, distress screening is now recommended in many national guidelines. However, screening alone does not necessarily translate into better well-being. We examined whether stepped psychooncological care improves referral to consultation-liaison (CL) services and improves well-being. METHODS: In a cluster-randomized trial, wards were randomly allocated to stepped versus standard care. Stepped care comprised screening for distress, consultation between doctor and patient about the patient's need for CL services, and provision of CL service. Primary outcomes were referral to psychosocial services and emotional well-being half a year after baseline, measured with the Hospital Anxiety and Depression Scale. A secondary endpoint was uptake of outpatient health care. Analysis employed mixed-effects multivariate regression modeling. RESULTS: Thirteen wards were randomized; 1012 patients participated. With stepped care (N = 570; 7 wards), 22% of the patients were referred to CL services and 3% with standard care (N = 442; 6 wards; odds ratio [OR] 10.0; P < .001). Well-being 6 months after baseline was 9.5 after stepped care (N = 341) and 9.4 after standard care (N = 234, ß -0.3; P = .71). After stepped care, patients with psychiatric comorbidity went more often to psychotherapists (OR 4.0, P = .05) and to psychiatrists (OR 2.3, P = .12), whereas patients without comorbidity used psychiatrists less often (OR 0.4, P = .04) than in standard care. CONCLUSIONS: Stepped care resulted in better referral to CL services. The patients' emotional well-being was not improved, but uptake of outpatient psychiatric help was increased in patients with psychiatric comorbidity and decreased in patients without.


Assuntos
Ansiedade/prevenção & controle , Ansiedade/psicologia , Neoplasias/psicologia , Relações Médico-Paciente , Encaminhamento e Consulta , Adulto , Idoso , Ansiedade/etiologia , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Neoplasias/complicações , Participação do Paciente , Médicos , Psicoterapia , Serviço Social em Psiquiatria/métodos
10.
Z Gastroenterol ; 55(4): 375-378, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28427108

RESUMO

Solid pancreatic lesions found on imaging procedures are suspicious for malignancy and, therefore, demand immediate diagnostic evaluation and therapy. In the case of indeterminate histology, a primary resection should be considered in order to preserve the possibility of curative surgery, although rare entities may be initially disregarded. We present here the case of a 48-year-old female patient with a hypoechoic lesion of the pancreatic head, which was clearly delineated from the surrounding pancreatic tissue. The challenging diagnosis of metastatic leiomyosarcoma could only be established by considering the long-term clinical history and former histology specimens.


Assuntos
Cisto Pancreático/diagnóstico por imagem , Ultrassonografia , Feminino , Humanos , Leiomiossarcoma , Pessoa de Meia-Idade
13.
Internist (Berl) ; 62(10): 1005-1006, 2021 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-34586450
14.
Int J Med Microbiol ; 305(1): 148-56, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25547265

RESUMO

Two hundred and twenty-five healthy German volunteers traveling to 53 different countries (mostly in Asia, Africa and South America) were enrolled in a prospective cohort study. Stool samples and data on potential travel-associated risk factors (such as type of travel, nutritional habits, occurrence of gastroenteritis) were collected before and after traveling. Screening for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) and carbapenemase-producing Enterobacteriaceae (CPE) was performed using selective media (CHROMagar™ ESBL/CPE plates). Isolates with confirmed ESBL-phenotype were examined for the presence of blaCTX-M, blaTEM, blaSHV, and blaVIM, blaIMP, blaNDM, blaKPC, blaOXA-48 genes by PCR amplification and sequencing. Antimicrobial susceptibility testing was performed using conventional microbroth dilution. Pre-travel analysis of 205 fully evaluable participants revealed an ESBL-PE prevalence rate of 6.8% (14/205). Among 191 participants that were ESBL-negative before travel, 58 (30.4%) were colonized by ESBL-producing Escherichia coli, and 5 (8.6%) additionally carried ESBL-producing Klebsiella pneumoniae upon return. However, no carbapenem-resistant Enterobacteriaceae were detected. ESBL-genotyping revealed that 52/54 (96.6%) E. coli and 4/4 (100%) K. pneumoniae strains available for sequencing produced CTX-M enzymes, mostly CTX-M-15 (33/56, 58.9%), and 2/54 (3.7%) E. coli strains produced SHV-12 enzymes. Travel to India was associated with the highest ESBL-PE acquisition rate (11/15, 73.3%; p=0.015), followed by South East Asia (22/46, 47.8%; p=0.038). Evaluation of travel-associated risk factors demonstrated significance for the occurrence of gastroenteritis (p=0.011). Strictly practiced hand hygiene and exclusive consumption of packaged beverages showed no protective effect. The ESBL-PE persistence rate after 6 months was 8.6% (3/35). We conclude that global efforts are needed to address the further spread of ESBL-PE in the community. Active surveillance and contact isolation precautions may be recommended at admission to medical facilities especially for patients who traveled to India and South East Asia in the previous 6 months.


Assuntos
Portador Sadio/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Viagem , Resistência beta-Lactâmica , beta-Lactamases/metabolismo , Adolescente , Adulto , Idoso , Técnicas Bacteriológicas , Portador Sadio/microbiologia , Criança , Pré-Escolar , Estudos de Coortes , Meios de Cultura/química , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Feminino , Genes Bacterianos , Alemanha/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Estudos Prospectivos , Análise de Sequência de DNA , Adulto Jovem , beta-Lactamases/genética
15.
Arch Biochem Biophys ; 565: 89-94, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25475530

RESUMO

The gene p8 encodes for a small cytoprotective protein with no apparent enzymatic activity being proposed to act as co-transcription factor whose expression is increased during inflammation. Recent data from astrocytes demonstrates that p8 suppression leads to induction of heme oxygenase 1 (HO-1). Here, we assessed the cross-talk between p8 and HO-1 in mouse embryonic fibroblasts (MEF) observing an increased expression of HO-1 in p8-deficient (p8(-/-)) MEFs in non-treated and treated conditions. This effect was independent of the cell cycle. Our findings revealed that generation of reactive oxygen species (ROS) was higher in p8(-/-) MEFs. Mitochondria and NADPH oxidases were not the origin of ROS. This observation was not restricted to MEF as suppression of p8 gene transcription in MiaPaCa-2 cells also led to increased intracellular ROS. Additionally, p8 deficiency did not affect the Rac1 dependant NADPH oxidase complex. Our data shows that p8 deficiency increases ROS and subsequently the expression of anti-oxidative enzymes, such as HO-1, suggesting an involvement in the anti-oxidative defense. Moreover, we suggest that the severity of AP observed in p8(-/-) mice is induced by an impaired anti oxidative capacity of the pancreas, which is caused by increased generation of ROS.


Assuntos
Proteínas de Ligação a DNA/deficiência , Embrião de Mamíferos/metabolismo , Fibroblastos/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas de Neoplasias/deficiência , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Embrião de Mamíferos/patologia , Fibroblastos/patologia , Heme Oxigenase-1/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Mitocôndrias/patologia , Pâncreas/metabolismo , Pâncreas/patologia , Transcrição Gênica/genética
16.
Scand J Gastroenterol ; 50(2): 224-32, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25429378

RESUMO

OBJECTIVE: Liver graft steatosis has not been noninvasively evaluated yet. We therefore characterized liver transplant recipients by transient elastography (TE) and controlled attenuation parameter (CAP) and correlated the results with clinical and genetic risk factors. METHODS: A total of 204 patients (pretransplant disease: n = 102 nonalcoholic etiology, nonalcoholic liver cirrhosis (non-ALC); n = 102 alcoholic liver disease, ALC; 42% female; median age 57.8 years; median time since transplantation 66 months) underwent ultrasound, TE, CAP, and nonalcoholic fatty liver disease (NAFLD) fibrosis score. Recipient DNA samples were genotyped for patatin-like phospholipase domain-containing protein 3 (PNPLA3) (rs738409) and IL28B (rs8099917, rs12979860) polymorphisms. RESULTS: Increased hepatic echogenicity at ultrasound was observed in 36% of patients, CAP values >252 and >300 dB/m indicated steatosis and advanced steatosis in 44% and 24% of individuals. Advanced fibrosis (TE >7.9 kPa) was associated with increased CAP results (266 vs. 229 dB/m, p = 0.012). PNPLA3 G-allele carriers had increased CAP values (257 vs. 222 dB/m, p = 0.032), higher liver stiffness (TE 6.4 vs. 5.5 kPa, p = 0.005), and prevalence of diabetes mellitus (40% vs. 22%, p = 0.016). No such association was observed for IL28B polymorphisms. ALC compared to non-ALC patients had higher body mass index (28.1 vs. 25.5 kg/m², p < 0.001), higher prevalence of diabetes mellitus (41% vs. 25%, p = 0.017), and PNPLA3 CG + GG genotype (73% vs. 47%, p = 0.006), and had elevated TE (6.3 vs. 5.4 kPa, p = 0.022), CAP (266 vs. 221 dB/m, p = 0.001), and NAFLD fibrosis score (score -0.5 vs. -1.3, p < 0.001). CONCLUSION: Modern noninvasive liver graft assessment frequently detects hepatic steatosis, which is associated with graft fibrosis, components of the metabolic syndrome and recipient PNPLA3 rs738409 genotype, especially in ALC patients.


Assuntos
Interleucinas/genética , Lipase/genética , Transplante de Fígado/efeitos adversos , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/genética , Adulto , Idoso , Alelos , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus , Técnicas de Imagem por Elasticidade , Feminino , Genótipo , Humanos , Interferons , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto Jovem
17.
Cochrane Database Syst Rev ; 1: CD006745, 2015 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-25620061

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common global cancer. When HCC is diagnosed early, interventions such as percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), or radiofrequency (thermal) ablation (RF(T)A) may have curative potential and represent less invasive alternatives to surgery. OBJECTIVES: To evaluate the beneficial and harmful effects of PEI or PAI in adults with early HCC defined according to the Milan criteria, that is, one cancer nodule up to 5 cm in diameter or up to three cancer nodules up to 3 cm in diameter compared with no intervention, sham intervention, each other, other percutaneous interventions, or surgery. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1946 to July 2014), EMBASE (1976 to July 2014), and Science Citation Index Expanded (1900 to July 2014). We handsearched meeting abstracts of six oncological and hepatological societies and references of articles to July 2014. We contacted researchers in the field. SELECTION CRITERIA: We considered randomised clinical trials comparing PEI or PAI versus no intervention, sham intervention, each other, other percutaneous interventions, or surgery for the treatment of early HCC regardless of blinding, publication status, or language. We excluded studies comparing RFA or combination of different interventions as such interventions have been or will be addressed in other Cochrane Hepato-Biliary Group systematic reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, and extracted and analysed data. We calculated the hazard ratios (HR) for median overall survival and recurrence-free survival using the Cox regression model with Parmar's method. We reported type and number of adverse events descriptively. We assessed risk of bias by The Cochrane Collaboration domains to reduce systematic errors and risk of play of chance by trial sequential analysis to reduce random errors. We assessed the methodological quality with GRADE. MAIN RESULTS: We identified three randomised trials with 261 participants for inclusion. The risk of bias was low in one and high in two trials.Two of the randomised trials compared PEI versus PAI; we included 185 participants in the analysis. The overall survival (HR 1.47; 95% confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42; 95% CI 0.68 to 2.94) were not statistically significantly different between the intervention groups of the two trials. Trial sequential analysis for the comparison PEI versus PAI including two trials revealed that the number of participants that were included in the trials were insufficient in order to judge a relative risk reduction of 20%. Data on the duration of hospital stay were available from one trial for the comparison PEI versus PAI showing a significantly shorter hospital stay for the participants treated with PEI (mean 1.7 days; range 2 to 3 days) versus PAI (mean 2.2 days; range 2 to 5 days). Quality of life was not reported. There were only mild adverse events in participants treated with either PEI or PAI such as transient fever, flushing, and local pain.One randomised trial compared PEI versus surgery; we included 76 participants in the analyses. There was no significant difference in the overall survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group while three postoperative deaths occurred in the surgery group.In addition to the three randomised trials, we identified one quasi-randomised study comparing PEI versus PAI. Due to methodological flaws of the study, we extracted only the data on adverse events and presented them in a narrative way.We found no randomised trials that compared PEI or PAI versus no intervention, best supportive care, sham intervention, or other percutaneous local ablative therapies excluding RFTA. We found also no randomised clinical trials that compared PAI versus other interventional treatments or surgery. We identified two ongoing randomised clinical trials. One of these two trials compares PEI versus surgery and the other PEI versus transarterial chemoembolization. To date, it is unclear whether the trials will be eligible for inclusion in this meta-analysis as the data are not yet available. This review will not be updated until new randomised clinical trials are published and can be used for analysis. AUTHORS' CONCLUSIONS: PEI versus PAI did not differ significantly regarding benefits and harms in people with early HCC, but the two included trials had only a limited number of participants and one trial was judged a high risk of bias. Thus, the current evidence precludes us from making any firm conclusions.There was also insufficient evidence to determine whether PEI versus surgery (segmental liver resection) was more effective, because conclusions were based on a single randomised trial. While some data from this single trial suggested that PEI was safer, the high risk of bias and the lack of any confirmatory evidence make a reliable assessment impossible.We found no trials assessing PEI or PAI versus no intervention, best supportive care, or sham intervention.There is a need for more randomised clinical trials assessing interventions for people with early stage HCC. Such trials should be conducted with low risks of systematic errors and random errors.


Assuntos
Ácido Acético/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Etanol/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Ácido Acético/efeitos adversos , Administração Cutânea , Adulto , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Etanol/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Carga Tumoral
19.
Ann Hepatol ; 13(6): 803-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25332267

RESUMO

BACKGROUND: Hepatotoxicity is a major side effect of treatment with bosentan in patients with pulmonary hypertension (PH). Bosentan is metabolized by the cytochrome CYP2C9 and inhibits the bile salt export pump, which is encoded by ABCB11. This suggests that genetic variants of CYP2C9 and/or ABCB11 may predispose patients to bosentan-induced liver injury. MATERIAL AND METHODS: PH patients with (n = 23) or without (n = 25) an increase of alanine aminotransferase (ALT) or aspartate-aminotransferase (AST) during bosentan therapy were included in our analysis. Functionally relevant alleles of CYP2C9 and 16 representative variants of ABCB11 were genotyped. Data were analyzed using logistic regression. RESULTS: Variants of ABCB11 were not associated with bosentan-induced liver injury. In contrast, variant alleles of CYP2C9 were more common in patients with elevated transaminases (allele frequency 52%) compared to controls (allele frequency 24%, P = 0.04, odds ratio 3.5, 95% confidence interval 1.01-11.8). CONCLUSION: Our data indicate hepatotoxicity of bosentan from decreased hepatic metabolism due to common variants of CYP2C9.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Anti-Hipertensivos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/genética , Citocromo P-450 CYP2C9/genética , Hipertensão Pulmonar/tratamento farmacológico , Sulfonamidas/efeitos adversos , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bosentana , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
20.
Gut ; 62(4): 582-92, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22427236

RESUMO

OBJECTIVE: In chronic pancreatitis (CP), alterations in several genes have so far been described, but only small cohorts have been extensively investigated for all predisposing genes. DESIGN: 660 patients with idiopathic or hereditary CP and up to 1758 controls were enrolled. PRSS1, SPINK1 and CTRC were analysed by DNA sequencing, and cystic fibrosis transmembrane conductance regulator (CFTR) by melting curve analysis. RESULTS: Frequencies of CFTR variants p.R75Q, p.I148T, 5T-allele and p.E528E were comparable in patients and controls. We identified 103 CFTR variants, which represents a 2.7-fold risk increase (p<0.0001). Severe cystic fibrosis (CF)-causing variants increased the risk of developing CP 2.9-fold, and mild CF-causing variants 4.5-fold (p<0.0001 for both). Combined CF-causing variants increased CP risk 3.4-fold (p<0.0001), while non-CF-causing variants displayed a 1.5-fold over-representation in patients (p=0.14). CFTR compound heterozygous status with variant classes CF-causing severe and mild represented an OR of 16.1 (p<0.0001). Notably, only 9/660 (1.4%) patients were compound heterozygotes in this category. Trans-heterozygosity increased CP risk, with an OR of 38.7, with 43/660 (6.5%) patients and 3/1667 (0.2%) controls being trans-heterozygous (p<0.0001). CONCLUSIONS: Accumulation of CFTR variants in CP is less pronounced than reported previously, with ORs between 2.7 and 4.5. Only CF-causing variants reached statistical significance. Compound and trans-heterozygosity is an overt risk factor for the development of CP, but the number of CFTR compound heterozygotes in particular is rather low. In summary, the study demonstrates the complexity of genetic interactions in CP and a minor influence of CFTR alterations in CP development.


Assuntos
Proteínas de Transporte/genética , Quimotripsina/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Pancreatite Crônica/genética , Tripsina/genética , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Análise de Sequência de DNA , Inibidor da Tripsina Pancreática de Kazal
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